Miracle-dz/UniFAR-FTUs huggingface dataset:
Rose Bengal induces dual modes of cell death in melanoma cells and has clinical activity against melanoma

Rose Bengal has been used to assess hepatic function,opthalmic disorders and as a photosensitiser in treatment of skin lesions. In this study RB was tested in-vitro in the absence of light for its effects on melanoma cells and mechanism of its effects. In addition a patient was treated by intralesional injection of a sc metastasis with PV10(RB). Methods A panel of melanoma cells were exposed to RB at different concentrations and for varying periods and effects studied by morphology apoptosis assays and MTT assays Results. RB induced cell death in melanoma cells but not fibroblasts. Death was predominantly due to necrosis but 2 lines also underwent apoptosis that was dependent on activation of caspases. Cell death was not due to release of Reactive oxygen species.RB is taken up into lysosomes and it is probable (but not proven) that cell death results from release of Cathepsins. The patient who had chemotherapy radioresistant recurrent disease in the head and neck area had rapid necrosis of the injected metastasis and this as well as 3 uninjected sc metastases under went complete remission over a period of several months Conclusion Further studies to understand the mechanism of action and its role in clinical management of melanoma are warranted Abstract
Prevalence and Risk Factors Associated With Herpes Simplex Virus-2 Infection in a Contemporary Cohort of HIV-Infected Persons in the United States

Background: We compared the herpes simplex virus type 2 (HSV-2) seroprevalence in a contemporary HIV cohort with the general US population and determined risk factors for HSV-2 infection among HIV-infected persons. Methods: The Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN) Study is a prospective observational cohort of 700 HIV-infected adults enrolled in 4 US cities between 2004 and 2006. At baseline, participants completed a behavioral risk questionnaire and provided specimens for HSV-2 serology. We calculated HSV-2 seroprevalence, standardized by age, gender, and race among HIV-infected persons compared with the general US adult population, using data from the National Health and Nutrition Examination Survey from 2003 to 2006. We examined risk factors associated with HSV-2 infection among HIV-infected persons using multivariate logistic regression. Results: Among 660 (94%) SUN participants with adequate specimens for HSV-2 serologic testing, 548 (83%) were 20 to 49 years old (median age, 39 years; 77% male; 59% non-Hispanic white; median CD4 count, 470 cells/mm3; 74% with HIV RNA viral loads <400 copies/mL). HSV-2 seroprevalence was significantly higher among HIV-infected adults (59.7%, 95% confidence interval: 55.8–63.6) compared with the general US population (19.2%, 95% confidence interval: 17.5–21.1). In multivariate analysis, we found that older age, female gender, black non-Hispanic race/ethnicity, being currently unemployed, high-risk anal HPV infection, and longer duration since HIV diagnosis were associated with significantly higher odds of HSV-2 infection. Conclusion: HSV-2 seroprevalence is 3 times as high among HIV-infected adults as in the general US population. Clinicians should be aware that increased risk for HSV-2 infection was distributed broadly among HIV-infected persons and not limited to those with high-risk sexual behaviors.
Radiofrequency ablation of hepatocellular carcinoma as bridge therapy to liver transplantation: A 10‐year intention‐to‐treat analysis

In a long‐term (10‐year) study of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) as bridging therapy in patients listed for orthotopic liver transplantation (LT), we evaluated the impact of RFA on waiting list dropout rate, post‐LT tumor recurrence, and long‐term intention‐to‐treat, disease‐specific survival (DSS). From March 2004 to October 2014, RFA was performed as the initial stand‐alone bridge therapy to LT for 121 patients (men/women ratio, 83:38; mean age, 60.0 years) with 156 de novo HCCs (mean size, 2.4 cm). Follow‐up period from initial RFA ranged from 1.3 to 128.0 months (median, 42.9 months). We assessed the overall and tumor‐specific waiting list dropout rates, post‐LT tumor recurrence, and 10‐year post‐LT and intention‐to‐treat survival rates. Dropout from the waiting list due to tumor progression occurred in 7.4% of patients. HCC recurrence after LT occurred in 5.6% of patients. The post‐LT overall survival (OS) rate at 5 and 10 years was 75.8% and 42.2%, respectively, and the recurrence‐free survival (RFS) rate was 71.1% and 39.6%, respectively. Intention‐to‐treat OS, RFS, and DSS rates for the entire study population at 5 and 10 years were 63.5% and 41.2%, 60.8% and 37.7%, and 89.5% and 89.5%, respectively. Conclusion: RFA as a first‐line stand‐alone bridge therapy to LT achieves excellent long‐term overall and tumor‐specific survivals, with a low dropout rate from tumor progression despite long wait list times and a sustained low tumor recurrence rate upon post‐LT follow‐up of up to 10 years. (Hepatology 2017;65:1979‐1990)
Conservation of the Ustilago maydis effector See1 in related smuts

Ustilago maydis is a biotrophic fungus that induces formation of tumors in maize (Zea mays L). In a recent study we identified See1 (Seedling efficient effector 1) as an U. maydis organ-specific effector required for tumor formation in leaves. See1 is required for U. maydis induced reactivation of plant DNA synthesis during leaf tumor progression. The protein is secreted from biotrophic hyphae and localizes to the cytoplasm and nucleus of plant cell. See1 interacts with maize SGT1, a cell cycle and immune regulator, interfering with its MAPK-triggered phosphorylation. Here, we present new data on the conservation of See1 in other closely related smuts and experimental data on the functionality of See1 ortholog in Ustilago hordei, the causal agent of barley covered smut disease.
2D-DIGE-based proteome expression changes in leaves of rice seedlings exposed to low-level gamma radiation at Iitate village, Fukushima

The present study continues our previous research on investigating the biological effects of low-level gamma radiation in rice at the heavily contaminated Iitate village in Fukushima, by extending the experiments to unraveling the leaf proteome. 14-days-old plants of Japonica rice (Oryza sativa L. cv. Nipponbare) were subjected to gamma radiation level of upto 4 µSv/h, for 72 h. Following exposure, leaf samples were taken from the around 190 µSv/3 d exposed seedling and total proteins were extracted. The gamma irradiated leaf and control leaf (harvested at the start of the experiment) protein lysates were used in a 2-D differential gel electrophoresis (2D-DIGE) experiment using CyDye labeling in order to asses which spots were differentially represented, a novelty of the study. 2D-DIGE analysis revealed 91 spots with significantly different expression between samples (60 positive, 31 negative). MALDI-TOF and TOF/TOF mass spectrometry analyses revealed those as comprising of 59 different proteins (50 up-accumulated, 9 down-accumulated). The identified proteins were subdivided into 10 categories, according to their biological function, which indicated that the majority of the differentially expressed proteins consisted of the general (non-energy) metabolism and stress response categories. Proteome-wide data point to some effects of low-level gamma radiation exposure on the metabolism of rice leaves.
Use of Highly Active Antiretroviral Therapy Is Associated With Lower Prevalence of Anal Intraepithelial Neoplastic Lesions and Lower Prevalence of Human Papillomavirus in HIV-Infected Men Who Have Sex With Men

Background: The incidence of anal intraepithelial neoplasia (AIN) and anal cancer is increased in HIV-positive men who have sex with men (MSM). Persistent high-risk human papillomavirus (HPV) infection is an important etiologic agent. Methods: In this study, a group of 250 HIV-positive MSM was included to determine the prevalence of AIN and to investigate the role of highly active antiretroviral therapy (HAART), high-risk HPV, and other risk factors possibly associated with this prevalence. Results: Among patients included, 108 (43.2%) had lesions suspicious for AIN. Histologic analyses showed AIN 1 in 24 patients (22.2%), AIN 2 in 6 patients (5.6%), and AIN 3 in 10 patients (9.3%). In multivariable analyses, the use of HAART was associated with the absence of AIN (P = 0.045). In MSM without HAART, HPV infection was detected significantly more often compared with those who used HAART (P = 0.010). AIN was associated with HPV types 16 and 6. Conclusions: In this cross-sectional study in 250 HIV-positive MSM, the use of HAART was associated with lower prevalence of AIN and a significantly lower prevalence of HPV. This association between the prevalence of AIN and the absence of HAART may contribute to the current debate on when to start HAART in HIV-infected individuals.
Root and root canal morphology of Saudi Arabian permanent dentition

The aims of this paper were to review the studies that investigated the root and root canal morphology of permanent dentition in the Saudi Arabian population and to compare their results with the findings of international morphological studies conducted on other populations. An electronic search using the PubMed and Scopus databases was conducted using combination of the following keywords: "root canal morphology", "root morphology", "dental anomalies", and "Saudi Arabian population". In addition, all issues of the Saudi Dental Journal (since 1989) and Saudi Endodontic Journal (since 2011) were manually searched for relevant articles. Then, the reference lists of the articles were screened to identify further eligible publications. A total of 23 studies met the inclusion criteria and were subjected to data extraction and analysis. Variations from the normal root and canal morphology may occur in all populations including the Saudi Arabian population. Therefore, the clinicians must always take these variations in consideration during root canal treatment to ensure a successful treatment outcome.
DMSA Scintigraphy in Febrile Urinary Tract Infections Could Be Omitted in Children With Low Procalcitonin Levels

Purpose: The objective was to assess procalcitonin (PCT) as a marker of renal involvement in children with urinary tract infections (UTI). Methods: The study included 60 children with UTI, aged (median) 0.6 years (range, 0.1-9.5 years), admitted to a pediatric hospital. White blood cell count, C-reactive protein (CRP), and PCT levels were measured on admission and on the third treatment day, whereas renal involvement was assessed with dimercaptosuccinic acid (DMSA) scintigraphy within 7 days after admission and after 6 months. Results: During febrile UTI, PCT, and CRP levels increased in parallel with the severity of renal lesions in acute DMSA. During repeat DMSA, PCT levels were increased in the group with partially versus totally reversible renal lesions (5.3 μg/L vs 3.0 μg/L; P = 0.005). Procalcitonin and CRP had increased sensitivity (94% and 100%, respectively) and negative predictive values (97% and 100%, respectively), whereas PCT had higher specificity than CRP (100% vs 55%). Conclusions: Procalcitonin is a sensitive marker of the development, severity, and persistence of renal lesions in childhood UTI. Because of the high negative predictive values of PCT, we suggest that, in case of low PCT levels, the possibility of renal involvement is low, and DMSA could be omitted.
Plant endosomal NHX antiporters: Activity and function

ABSTRACT The Arabidopsis NHX antiporter family contains eight members that are divided into three subclasses: vacuolar, endosomal, and plasma membrane. While the plasma membrane and vacuolar NHXs have been studied extensively, the activity and function of the endosomal NHXs are beginning to be discovered. AtNHX5 and AtNHX6 are endosomal Na+,K+/H+ antiporters that share high sequence similarity. They are localized in the Golgi, trans-Golgi network (TGN), and prevacuolear compartment (PVC). Studies have shown that AtNHX5 and AtNHX6 mediate K+ and Na+ transport, and regulate cellular pH homeostasis. Sequence alignment has found that AtNHX5 and AtNHX6 contain four conserved acidic amino acid residues in transmembrane domains that align with yeast and human NHXs. Three of these conserved acidic residues are critical for K+ transport and seedling growth in Arabidopsis. Moreover, studies have shown that the precursors of the seed storage proteins are missorted to the apoplast in the nhx5 nhx6 knockout mutant, suggesting that AtNHX5 and AtNHX6 regulate protein transport into the vacuole. Further analysis found that AtNHX5 and AtNHX6 regulated the binding of VSR to its cargoes. Taken together, AtNHX5 and AtNHX6 play an important role in cellular ion and pH homeostasis, and are essential for protein transport into the vacuole.
Drug rechallenge following drug‐induced liver injury

Drug‐induced hepatocellular injury is identified internationally by alanine aminotransferase (ALT) levels equal to or exceeding 5× the upper limit of normal (ULN) appearing within 3 months of drug initiation, after alternative causes are excluded. Upon withdrawing the suspect drug, ALT generally decrease by 50% or more. With drug readministration, a positive rechallenge has recently been defined by an ALT level of 3‐5× ULN or greater. Nearly 50 drugs are associated with positive rechallenge after drug‐induced liver injury (DILI): antimicrobials; and central nervous system, cardiovascular and oncology therapeutics. Drugs associated with high rates of positive rechallenge exhibit multiple risk factors: daily dose >50 mg, an increased incidence of ALT elevations in clinical trials, immunoallergic clinical injury, and mitochondrial impairment in vitro. These drug factors interact with personal genetic, immune, and metabolic factors to influence positive rechallenge rates and outcomes. Drug rechallenge following drug‐induced liver injury is associated with up to 13% mortality in prospective series of all prescribed drugs. In recent oncology trials, standardized systems have enabled safer drug rechallenge with weekly liver chemistry monitoring during the high‐risk period and exclusion of patients with hypersensitivity. However, high positive rechallenge rates with other innovative therapeutics suggest that caution should be taken with rechallenge of high‐risk drugs. Conclusion: For critical medicines, drug rechallenge may be appropriate when 1) no safer alternatives are available, 2) the objective benefit exceeds the risk, and 3) patients are fully informed and consent, can adhere to follow‐up, and alert providers to hepatitis symptoms. To better understand rechallenge outcomes and identify key risk factors for positive rechallenge, additional data are needed from controlled clinical trials, prospective registries, and large health care databases. (Hepatology 2017;66:646–654).
A chimeric repressor of petunia PH4 R2R3-MYB family transcription factor generates margined flowers in torenia

ABSTRACT The development of new phenotypes is key to the commercial development of the main floricultural species and cultivars. Important new phenotypes include features such as multiple-flowers, color variations, increased flower size, new petal shapes, variegation and distinctive petal margin colourations. Although their commercial use is not yet common, the transgenic technologies provide a potentially rapid means of generating interesting new phenotypes. In this report, we construct 5 vectors which we expected to change the color of the flower anthocyanins, from purple to blue, regulating vacuolar pH. When these constructs were transformed into purple torenia, we unexpectedly recovered some genotypes having slightly margined petals. These transgenic lines expressed a chimeric repressor of the petunia PhPH4 gene under the control of Cauliflower mosaic virus 35 S RNA promoter. PhPH4 is an R2R3-type MYB transcription factor. The transgenic lines lacked pigmentation in the petal margin cells both on the adaxial and abaxial surfaces. Expressions of Flavanone 3-hydroxylase (F3H), Flavonoid 3′-hydroxylase (F3′H) and Flavonoid 3′5′-hydroxylase (F3′5′H) genes were reduced in the margins of these transgenic lines, suggesting an inhibitory effect of PhPH4 repressor on anthocyanin synthesis.
Nucleotides, micro- and macro-nutrients, limonoids, flavonoids, and hydroxycinnamates composition in the phloem sap of sweet orange

ABSTRACT Currently, the global citrus production is declining due to the spread of Huanglongbing (HLB). HLB, otherwise known as citrus greening, is caused by Candidatus Liberibacter asiaticus (CLas) and is transmitted by the Asian citrus psyllids (ACP), Diaphorina citri Kuwayama. ACP transmits CLas bacterium while feeding on the citrus phloem sap. Multiplication of CLas in the phloem of citrus indicates that the sap contains all the essential nutrients needed for CLas. In this study, we investigated the micro- and macro-nutrients, nucleotides, and others secondary metabolites of phloem sap from pineapple sweet orange. The micro- and macro-nutrients were analyzed using inductively coupled plasma-mass spectroscopy (ICP-MS) and inductively coupled plasma-optical emission spectroscopy (ICP-OES). Nucleotides and other secondary metabolites analysis was accomplished by reversed phase HPLC coupled with UV, fluorescence detection, or negative mode electrospray ionization mass spectrometry (ESI-MS). Calcium (89 mM) was the highest element followed by potassium (38.8 mM) and phosphorous (24 mM). Magnesium and sulfur were also abundant and their concentrations were 15 and 9 mM, respectively. The rest of the elements were found in low amounts (< 2mM). The concentrations of ATP, ADP, and AMP were 16, 31, and 3 µ mole/Kg fwt, respectively. GTP, GMP. NAD, FMN, FAD, and riboflavin were found at concentrations below (3 µ mole/Kg fwt). The phloem was rich in nomilin 124 mM and limonin 176 µ mole/Kg fwt. Hesperidin, vicenin-2, sinensetin, and nobiletin were the most predominant flavonoids. In addition, several hydroxycinnamates were detected. The results of this study will increase our knowledge about the nature and the chemical composition of citrus phloem sap.
Regulation of the WD-repeat/bHLH/MYB complex by gibberellin and jasmonate

ABSTRACT The phytohormones gibberellin (GA) and jasmonate (JA) regulate various aspects of plant development, growth and defense. Previous studies showed that both DELLA repressors in GA pathway and JA-ZIM domain (JAZ) proteins in JA pathway interact with and repress the WD-repeat/bHLH/MYB transcriptional complex to inhibit trichome initiation, and GA and JA respectively induce DELLAs and JAZs degradation to synergistically enhance trichome formation. In this study, we showed that the DELLA protein RGA and JAZ1 competitively bind to ENHANCER OF GLABRA3 (EGL3), a bHLH component of the WD-repeat/bHLH/MYB complex. GA and JA differently affect the expression and protein stability of the components of the WD-repeat/bHLH/MYB complex, and EGL3 and GL3 repress the expression of JAZ genes as a feedback. The novel findings help to understand the mechanism of the WD-repeat/bHLH/MYB complex in GA/JA-regulated trichome formation.
Various infection status and molecular evidence for horizontal transmission and recombination of Wolbachia and Cardinium among rice planthoppers and related species

Wolbachia and Cardinium are widely distributed and are considered important for their ability to disturb reproduction and affect other fitness‐related traits of their hosts. By using multilocus sequence typing (MLST), RFLP (restriction fragment length polymorphism) and 16S ribosomal DNA gene sequencing methods, we extensively surveyed Wolbachia and Cardinium infection status of four predominant rice planthoppers and one kind of leafhopper in different rice fields. The results demonstrated that Sogatella furcifera (Horváth) and Laodelphax striatellus (Fallén) were infected with the same Wolbachia strain (wStri), while Nilaparvata lugens (Stål) and its closely related species Nilaparvata muiri China were infected with two phylogeneticlly distant strains, wLug and wMui, respectively. Three new Wolbachia strains (provisionally named wMfas1, wMfas2 and wMfas3) were detected in the leafhopper Macrosteles fascifrons (Stål). Only S. furcifera was co‐infected with Cardinium, which indicated that the distribution of Cardinium in these rice planthoppers was narrower than that of Wolbachia. Unambiguous intragenic recombination events among these Wolbachia strains and incongruent phylogenetic relationships show that the connections between different Wolbachia strains and hosts were more complex than we expected. These results suggest that horizontal transmission and host associated specialization are two factors affecting Wolbachia and Cardinium infections among planthoppers and their related species.
Hepatitis C viral load, genotype, and increased risk of developing end‐stage renal disease: REVEAL‐HCV study

The association between hepatitis C virus (HCV) infection and end‐stage renal disease (ESRD) remains controversial without considering the role of HCV viral load and genotype. This study aimed to determine whether HCV RNA level and genotype affect the risk of developing ESRD. Between 1991 and 1992, 19,984 participants aged 30‐65 years were enrolled in a community‐based prospective cohort study in Taiwan. Chronic HCV infection was defined by detectable HCV viral load. ESRD was determined as the need for chronic dialysis or renal transplantation. Conventional Cox proportional hazard and competing risk models were used to determine the hazard ratio (HR) for ESRD. After a median follow‐up of 16.8 years, 204 cases were detected during 319,474 person‐years. The incidence rates of ESRD for nonchronically HCV‐infected and chronically HCV‐infected patients were 60.2 and 194.3 per 100,000 person‐years, respectively. The multivariable HR was 2.33 (95% confidence interval [CI] 1.40‐3.89) when comparing patients with and without chronic HCV infection. Patients with low and high HCV RNA levels were at higher risk of ESRD than those who were nonchronically HCV‐infected (HR, 2.11, 95% CI 1.16‐3.86, and HR, 3.06, 95% CI 1.23‐7.58; Ptrend < 0.001). This association remained robust after taking pre‐ESRD death as a competing event for ESRD. Patients with HCV genotype 1 tended to have a higher risk of developing ESRD (HR, 3.60 95% CI 1.83‐7.07) compared with nonchronically HCV‐infected subjects. Conclusions: This study reveals that chronic HCV infection is associated with an increased risk of developing ESRD and suggests that elevated serum levels of HCV RNA (>167,000 IU/mL) and HCV genotype 1 are strong predictors of ESRD, indicating clinical implications for the management of chronic HCV. (Hepatology 2017;66:784–793).