Miracle-dz/UniFAR-FTUs huggingface dataset:
Candida albicans Zinc Cluster Protein Upc2p Confers Resistance to Antifungal Drugs and Is an Activator of Ergosterol Biosynthetic Genes

ABSTRACT The human pathogen Candida albicans is responsible for a large proportion of infections in immunocompromised individuals, and the emergence of drug-resistant strains is of medical concern. Resistance to antifungal azole compounds is often due to an increase in drug efflux or an alteration of the pathway for synthesis of ergosterol, an important plasma membrane component in fungi. However, little is known about the transcription factors that mediate drug resistance. In Saccharomyces cerevisiae, two highly related transcriptional activators, Upc2p and Ecm22p, positively regulate the expression of genes involved in ergosterol synthesis (ERG genes). We have identified a homologue in C. albicans of the S. cerevisiae UPC2/ECM22 genes and named it UPC2. Deletion of this gene impaired growth under anaerobic conditions and rendered cells highly susceptible to the antifungal drugs ketoconazole and fluconazole. Conversely, overexpression of Upc2p increased resistance to ketoconazole, fluconazole, and fluphenazine. Azole-induced expression of the ERG genes was abolished in a Δupc2 strain, while basal levels of these mRNAs remained unchanged. Importantly, the purified DNA binding domain of Upc2p bound in vitro to putative sterol response elements in the ERG2 promoter, suggesting that Upc2p increases the expression of the ERG genes by directly binding to their promoters. These results provide an important link between changes in the ergosterol biosynthetic pathway and azole resistance in this opportunistic fungal species.
Topical photodynamic therapy of actinic keratoses with 5-aminolevulinic acid: Randomized controlled trial with six months follow-up

Abstract Background: Topical 5-aminolevulinic acid (ALA) photodynamic therapy (PDT) is an effective treatment for actinic keratosis (AK) with some transient adverse events. Objective: The purpose of the study was to evaluate the efficacy and side effects of two different light doses when treating AKs with ALA-PDT on the face/scalp. Methods: Thirty-eight patients with two histologically confirmed AKs were enrolled in the within-patient comparison study. ALA-PDT was performed twice with two weeks interval for each AK. Patients were randomized to receive a light dose of 70 or 100 J/cm2 as their first split face/scalp treatment. Follow-up examinations were carried out at months 3 and 6. Efficacy end point included clinical/histological AK clearance rate. Results: No significant difference in therapeutic efficacy and adverse events of ALA-PDT was found between the two light doses at both follow-up visits. At months 3 and 6 after PDT the rate of complete remission were respectively 100% and 92.1% for 70 J/cm2, 92.1% and 84.2% for 100 J/cm2. The adverse events of the treatment were rosacea 5/76 (6.58%), hyperpigmentation 4/76 (5.26%), hypopigmentation 4/76 (5.26%), transient milia 3/76 (3.95%). Conclusions: The topical ALA-PDT with the red light dose of 70 J/cm2 is an effective treatment for mild and moderate AKs on the face/scalp with expected adverse events of pigmentation changes, rosacea and transient milia.
Eribulin for heavily pre-treated metastatic breast cancer patients.

AIM To discuss treatment with eribulin in clinical practice outside a clinical trial. METHODS Archives of patients treated for metastatic breast cancer were reviewed and 21 patients treated with the new chemotherapeutic eribulin mesylate, a synthetic analog of a natural marine product, were identified. Information on patients' characteristics and treatment outcomes was extracted. Treatment with eribulin mesylate was initiated at the recommended dose of 1.4 mg/m(2) on days 1 and 8 of a 21-day cycle in 17 patients and at a decreased dose of 1.1 mg/m(2) on days 1 and 8 of a 21-day cycle in 4 patients due to comorbidities and frailty. Efficacy of the drug was evaluated using the revised Response Evaluation Criteria in Solid Tumors criteria. Progression-Free Survival and overall survival (OS) were calculated using the Kaplan-Meier method starting from the date of eribulin therapy initiation to the date of disease progression documentation or death, respectively. RESULTS The median age of patients at the time of eribulin mesylate treatment was 53 years (range 34-75). Sixteen patients had estrogen receptor (ER) and/or partial response (PR) positive disease and 5 had ER/PR negative disease (all triple negative). Eight patients had received 2 or 3 previous lines of chemotherapy for metastatic disease and 13 patients had received 4 or more lines of treatment. The median number of cycles of eribulin received was 3 (range 1-16 years). All patients, except one, discontinued treatment due to progressive disease and one patient due to adverse effects. Six patients had a dose reduction due to side effects. All patients had progressed at the time of the report with a median time to progression of 3 mo (range 1 to 14 mo). Fifteen patients had died with a median OS of 7 mo (range 1-18 mo). Six patients were alive with a median follow-up of 13.5 mo (range 7 to 19 mo). CONCLUSION This series of patients confirms the activity of eribulin in a heavily pre-treated metastatic breast cancer population consistent with phase II and III trials.
Application of Postmortem 3D‐CT Facial Reconstruction for Personal Identification *

Abstract: Postmortem computed tomography (CT) images can show internal findings related to the cause of death, and it can be a useful method for forensic diagnosis. In this study, we scanned a ready‐made box by helical CT on 2‐mm slices in a mobile CT scanner and measured each side of the box to assess whether reconstructed images are useful for superimposition. The mean difference between the actual measurements and the measurements on the three‐dimensional (3D) reconstructed images (3D‐CT images) is 0.9 mm; we regarded it as having no effect on reconstruction for the superimposition method. Furthermore, we could get 3D‐CT images of the skull, which were consistent with the actual skull, indicating that CT images can be applied to superimposition for identification. This study suggested that postmortem CT images can be applied as superimpositions for unidentified cases, and thinner slices or cone beam CT can be a more precise tool.
Persistent Racial/Ethnic Disparities in AIDS Diagnosis Rates among People Who Inject Drugs in U.S. Metropolitan Areas, 1993–2007

Objectives. We estimated race/ethnicity-specific incident AIDS diagnosis rates (IARs) among people who inject drugs (PWID) in U.S. metropolitan statistical areas (MSAs) over time to assess the change in disparities after highly active antiretroviral therapy (HAART) dissemination. Methods. We compared IARs and 95% confidence intervals (CIs) for black/African American and Hispanic/Latino PWID with those of white PWID in 93 of the most populous MSAs. We selected two three-year periods from the years immediately preceding HAART (1993–1995) and the years with the most recent available data (2005–2007). To maximize stability, we aggregated data across three-year periods, and we aggregated data for black/African American and Hispanic/Latino PWID for most comparisons with data for white PWID. We assessed disparities by comparing IAR 95% CIs for overlap. Results. IARs were significantly higher for black/African American and Hispanic/Latino PWID than for white PWID in 81% of MSAs in 1993–1995 and 77% of MSAs in 2005–2007. MSAs where disparities became non-significant over time were concentrated in the West. Significant differences were more frequent in comparisons between black/African American and white PWID (85% of MSAs in 1993–1995, 79% of MSAs in 2005–2007) than in comparisons between Hispanic/Latino and white PWID (53% of MSAs in 1993–1995, 56% of MSAs in 2005–2007). IARs declined modestly across racial/ethnic groups in most MSAs. Conclusions. AIDS diagnosis rates continue to be substantially higher for black/African American and Hispanic/Latino PWID than for white PWID in most large MSAs. This finding suggests a need for increased targeting of prevention and treatment programs, as well as research on MSA-level conditions that may serve to maintain the disparities.
Mini-open vacuum-assisted closure therapy with instillation for debilitated and septic patients with pleural empyema.

OBJECTIVES This prospective study is an evaluation of the mini-open vacuum-assisted closure with instillation (Mini-VAC-Instill) therapy for the treatment of complicated pleural empyema. METHODS We investigated septic patients in poor general physical condition (Karnofsky index ≤50%) with multimorbidity and/or immunosuppression who were treated by minimally invasive intrathoracic VAC-Instill therapy without the insertion of an open-window thoracostomy (OWT) between December 2012 and November 2014. All patients underwent mini-thoracotomy with position of a tissue retractor, surgical debridement and local decortication. Surgery was followed by intrathoracic vacuum therapy including periodic instillation using antiseptics. The VAC dressings were changed under general anaesthesia and the chest wall was closed during the same hospital stay. All patients received systemic antibiotic therapy. RESULTS Fifteen patients (13 males, median age: 71 years) underwent intrathoracic Mini-VAC-Instill dressings for the management of pleural empyema without bronchopleural fistula. The median length of vacuum therapy was 9 days (5-25 days) and the median number of VAC changes per patient was 1 (1-5). In-hospital mortality was 6.7% (n = 1) and was not related to Mini-VAC-Instill therapy or intrathoracic infection. Control of intrathoracic infection and closure of the chest cavity was achieved in 85.7% of surviving patients (12 of 14). After the follow-up at an average of 13.2 months (range, 3-25 months), we observed recurrence once, 21 days after discharge. Two patients died in the late postoperative period (Day 43 and Day 100 after discharge) of fulminant urosepsis and carcinoma-related multiorgan failure, respectively. Analysis of the follow-up interviews in the outpatient clinic showed a good quality of life and a subjectively good long-term aesthetic result. CONCLUSIONS Mini-VAC-Instill therapy is an upgrade of Mini-VAC, which guarantees the advantage of an open treatment, including flushing but without OWT. This procedure is minimally invasive, highly compatible especially with patients in poor general condition and may be an alternative to the OWT in selected patients. Consequently, a very short course of therapy results in good patient acceptance.
Competitive processivity‐clamp usage by DNA polymerases during DNA replication and repair

Protein clamps are ubiquitous and essential components of DNA metabolic machineries, where they serve as mobile platforms that interact with a large variety of proteins. In this report we identify residues that are required for binding of the β‐clamp to DNA polymerase III of Escherichia coli, a polymerase of the Pol C family. We show that the α polymerase subunit of DNA polymerase III interacts with the β‐clamp via its extreme seven C‐terminal residues, some of which are conserved. Moreover, interaction of Pol III with the clamp takes place at the same site as that of the δ‐subunit of the clamp loader, providing the basis for a switch between the clamp loading machinery and the polymerase itself. Escherichia coli DNA polymerases I, II, IV and V (UmuC) interact with β at the same site. Given the limited amounts of clamps in the cell, these results suggest that clamp binding may be competitive and regulated, and that the different polymerases may use the same clamp sequentially during replication and repair.
Maternal intake of vitamin D during pregnancy and risk of advanced beta cell autoimmunity and type 1 diabetes in offspring

OBJECTIVE: To investigate if maternal diet during pregnancy is associated with occurrence of islet autoimmunity (IA) in the offspring. METHODS: Of 21 700 infants invited to the All Babies in South-east Sweden (ABIS) study, 16 004 screening questionnaires, including a 22-item food frequency questionnaire (FFQ) regarding the mothers' diet during pregnancy, were completed after delivery. Follow-up of the children (questionnaires and blood sampling) was performed at 1, 2.5 and 5 yr of age. IA was defined as being positive (above the 95th percentile for healthy children) in two or more measurements of autoantibodies [glutamic acid decarboxylase (GADA); tyrosine phosphatase (IA-2A), insulin autoantibodies (IAA)] analysed at the three time points or being diagnosed with type 1 diabetes during the 5-yr follow-up period. The 5 724 children in whom we carried out two to three possible blood samplings were included in the study. Logistic regression analysis was used to identify variables predicting IA. RESULTS: Of 5 724 children,191 (3.3%) were considered positive for IA. In a univariate analysis, less than daily consumption of vegetables (3-5 times/week) in the mothers' diet was associated with increased risk of IA (OR 1.71, 95% CI:1.24-2.35, p = 0.001) compared to daily consumption (p for trend = 0.004). The association was strengthened when adjusting for known IA-risk factors (p for trend <0.001). CONCLUSIONS: Daily consumption of vegetables in the mothers' diet during pregnancy was associated with a decreased risk of IA in the offspring. PMID: 19761530 [PubMed in process] Supplemental Content Food Chem Toxicol. 2007 Jan;45(1):64-9. Epub 2006 Aug 7. A two generation reproductive toxicity study with curcumin, turmeric yellow, in Wistar rats. Ganiger S, Malleshappa HN, Krishnappa H, Rajashekhar G, Ramakrishna Rao V, Sullivan F. Toxicology Department, Rallis Research Centre, Rallis India Limited, Post Box No. 5813, Plot Nos. 21 and 22, Peenya II Phase, Bangalore 560 058, India.
Delayed accumulation of activated macrophages and inhibition of remyelination after spinal cord injury in an adult rodent model.

OBJECT Inhibition of remyelination is part of the complex problem of persistent dysfunction after spinal cord injury (SCI), and residual myelin debris may be a factor that inhibits remyelination. Phagocytosis by microglial cells and by macrophages that migrate from blood vessels plays a major role in the clearance of myelin debris. The object of this study was to investigate the mechanisms underlying the failure of significant remyelination after SCI. METHODS The authors investigated macrophage recruitment and related factors in rats by comparing a contusion model (representing contusive SCI with residual myelin debris and failure of remyelination) with a model consisting of chemical demyelination by lysophosphatidylcholine (representing multiple sclerosis with early clearance of myelin debris and remyelination). The origin of infiltrating macrophages was investigated using mice transplanted with bone marrow cells from green fluorescent protein-transfected mice. The changes in levels of residual myelin debris and the infiltration of activated macrophages in demyelinated lesions were investigated by immunostaining at 2, 4, and 7 days postinjury. To investigate various factors that might be involved, the authors also investigated gene expression of macrophage chemotactic factors and adhesion factors. RESULTS Activated macrophages coexpressing green fluorescent protein constituted the major cell population in the lesions, indicating that the macrophages in both models were mainly derived from the bone marrow, and that very few were derived from the intrinsic microglia. Immunostaining showed that in the contusion model, myelin debris persisted for a long period, and the infiltration of macrophages was significantly delayed. Among the chemotactic factors, the levels of monocyte chemoattractant protein-1 and granulocyte-macrophage colony-stimulating factor were lower in the contusion model at 2 and 4 days postinjury. CONCLUSIONS The results suggest that the delayed infiltration of activated macrophages is related to persistence of myelin debris after contusive SCI, resulting in the inhibition of remyelination.
Human immunodeficiency viruses type 1 subtypes circulating in Spain

Genetic subtypes of Human immunodeficiency viruses type 1 (HIV‐1) were investigated in 101 HIV‐1‐infected individuals living in Spain from 1993 to 1998. Samples selected randomly from the HIV clinic population included 29 Spanish native born subjects (28.7%) and 72 foreigners (71.3%). Proviral DNA extracted from peripheral blood mononuclear cells (PBMCs) or viral RNA isolated from plasma was amplified, and endonuclease restriction analysis was carried out on polymerase chain reaction (PCR) products. Restriction fragment length polymorphism (RFLP) analysis on the HIV‐1 protease region enabled the characterisation of the different HIV genotypes infecting these individuals. Overall, 38 subjects (37.6%) carried non‐B subtypes (A in 26, C in 2, D in 1, E in 2, and F in 7), 31 (81.6%) of them being immigrants. Direct sequence analysis of PCR products and/or a specific serological assay confirmed the data obtained by RFLP in most individuals tested. In conclusion, different HIV‐1 subtypes are circulating currently in Spain, with non‐B HIV‐1 subtypes being confined mostly to immigrants. J. Med. Virol. 59:189–193, 1999. © 1999 Wiley‐Liss, Inc.
Clientele recognition of library terms and concepts used by librarians

Using a 30-item multiple-choice type test, this investigation focused on the ability of college students to recognise terms and concepts used by librarians. A total of 447 respondents representing the fields of Education, Nutrition, Food Technology, Tourism and Hotel and Restaurant Management took part in this investigation. Data were gathered through robotfotos and an inventory of commonly used library jargon, duly identified and validated by academic librarians in one of the biggest multi-disciplinary universities in the Philippines. Data were treated in depth through percentage, one-way analysis of variance (ANOVA)t -test and Spearman’s rank correlation. The results showed that respondents’ ability to recognise library terms and concepts posted the highest and lowest ratings of 84 percent and 33 percent, respectively. Further, gender and type of catalogue used (OPAC vs. card catalogue) were found to have a significant relationship with their ability to recognise library terms and concepts. Finally, a moderate positive correlation (rho = 0.58) existed between the respondents’ recognition ability and the librarians’ ranking of frequently asked questions and terms used by the former.
New details of the ultrastructure of the outer segments and ciliary connectives of the rods of human and macaque retinas

Critical examination of the fine structure of the outer segments of human rods shows that the membranes of at least some and probably most of the flattened saccules filling the outer segment are neither connected with the cell membrane nor with that of other saccules. The saccules typically possess a scalloped edge. The nine pairs of filaments in the ciliary connective become nine singlets in the base of the outer segment and lose their precise orientation before terminating somewhere in the length of the outer segment. The centriolar base in the inner segment possesses nine triplets of filaments and irregular numbers of club‐like, fibrous satellites. Rarely tubules insert in the satellite bodies and these may connect to the cell membrane.
Acquisition of secondary structural chromosomal changes in pediatric ewing sarcoma is a probable prognostic factor for tumor response and clinical outcome

The Ewing sarcoma (ES) group of tumors commonly have the t(11;22)(q24;q12) or other rearrangements involving 22q12. In addition to these consistent aberrations, both numeric and structural aberrations have been reported: namely gains of chromosomes 8 and 12, the unbalanced translocation t(1;16), and deletions at the short arm of chromosome 1.
Are CIMP and chr16p13.2 copy‐number status independent prognostic markers in Stages II and III colorectal cancer?

Dear Editor, We thank Zanutto et al. for their interest and comments on our recent publication entitled ‘‘Frequent genomic loss at chr16p13.2 is associated with poor prognosis in colorectal cancer. ’’ In this publication, we aimed to identify and characterize recurrent copy-number alterations associated with clinical outcomes of colorectal cancer (CRC). On the basis of a thorough genome-wide analysis of >70 tumors, we found loss of chr16p13.2 to be associated with metastatic recurrence and short recurrence-free survival of Stages II and III microsatellitestable CRC. In their comment to our article, Zanutto et al. reported on the prognostic potential of another type of molecular marker, CpG island methylator phenotype (CIMP). They focused specifically on Stage II tumors (n 1⁄4 42) and provided results indicating that CIMP-high tumors are associated with a favorable outcome. Despite being based on a small number of cases, these results are interesting and in line with previous reports addressing the prognostic potential of CIMP in CRC. Interestingly, another report on CIMP in CRC indicated that CIMP-high tumors were associated with a low number of chromosomal abnormalities. With this information in mind, one may speculate if CIMP status and chr16p13.2 copy number are somehow correlated? A study investigating this possibility would be very interesting and could also address the question as to whether the two molecular markers provide independent prognostic information. If independent, the assays of the two markers, which are both based on PCR analysis of tumor DNA, can be combined possibly yielding an even better prognostic marker. Yours sincerely, Claus Lindbjerg Andersen Philippe Lamy Torben Falck Ørntoft
Isolation, characterization, and mapping of Tn5 insertions into the 140-megadalton invasion plasmid defective in the mouse Sereny test in Shigella flexneri 2a

Using Shigella flexneri 2a YSH6000, we isolated 304 independent Tn5 insertion mutants in the 230-kilobase invasion plasmid, pMYSH6000. The site of each Tn5 insertion was assigned to 23 SalI fragments on the previously made SalI cleavage map of pMYSH6000. Among the 304 insertions, 150 were negative in expression of four phenotypes examined (mouse Sereny test [Ser], invasion into epithelial cells [Inv], Congo red binding [Pcr], and inhibition of bacterial growth [Igr] ): 12 were Ser- Inv+ Pcr+ Igr+, and 142 were positive in all four phenotypes. Tn5 insertions in the avirulent mutants were distributed in two separate SalI fragments, F and G, and in four contiguous SalI fragments, B, P, H, and D. Fragment G contains a novel class of determinant(s) which is required only for Ser+ but not for Inv+, Pcr+, and Igr+. Fragment F contains the previously characterized virF locus. B, P, H, and D each contained both virulent and avirulent Tn5 insertions. This indicates that more than two gene clusters exist within this region. Both are required for expression of all four virulence phenotypes.
Potential uses of carbon nanotubes in the medical field: how worried should patients be?

Carbon nanotubes (CNTs) are cylinders of one or several coaxial graphite layer(s) (single-walled [SW]CNTs or multiwalled [MW]CNTs, respectively) with a catalytic material (iron, nickel or cobalt) often present inside and/or at their extremity, as well as variable amounts of inert synthesis support, depending on the synthesis method [1]. Their diameter is in the order of nanometers (depending on the number of walls) and they can reach several micrometers in length. Owing to their unique electrical properties, unusual strength and particular effectiveness in heat conduction [2], CNTs are particularly promising nanomaterials for industrial use (see [101] for inventory) and, therefore, one can easily imagine that their production will continue to increase in the future. However, the same novel properties that make CNTs interesting raise concerns about their potential adverse effects on biological systems, which could lead to health issues, particularly when thinking of their potential use in the medical field.