Miracle-dz/UniFAR-FTUs huggingface dataset:
Reverse Prenyltransferase in the Biosynthesis of Fumigaclavine C in Aspergillus fumigatus: Gene Expression, Purification, and Characterization of Fumigaclavine C Synthase FGAPT1

A putative prenyltransferase gene—fgaPT1—has been identified in the biosynthetic gene cluster of fumigaclavines in Aspergillus fumigatus AF293. The gene was cloned and overexpressed in Escherichia coli, and the His6‐fusion FgaPT1 was purified to near homogeneity and characterized biochemically. The enzyme was found to convert fumigaclavine A into fumigaclavine C by attaching a dimethylallyl moiety to C‐2 of the indole nucleus in a “reverse” manner, that is, by connection of C‐3 of the dimethylallyl moiety to an aromatic nucleus. FgaPT1 is a soluble, dimeric protein with a subunit size of 50 kDa. Km(app) values for fumigaclavine A and dimethylallyl diphosphate were determined to be 6 and 13 μM, respectively, while the turnover number was 0.8 s−1. Metal ions such as Mg2+ and Ca2+ are not essential for the enzymatic activity. FgaPT1 showed relatively strict substrate specificity towards fumigaclavine A, with only dimethylallyl diphosphate being accepted as a donor under our conditions. FgaPT1 is the first reverse prenyltransferase from fungi to have been purified and characterized in homogenous form after heterologous overproduction. Surprisingly, it shows very low sequence similarity to the recently identified prenyltransferase LtxC from cyanobacteria, which also catalyzes the reverse prenylation of an indole nucleus.
Autophagy‐related prognostic signature for breast cancer

Autophagy is a process that degrades intracellular constituents, such as long‐lived or damaged proteins and organelles, to buffer metabolic stress under starvation conditions. Deregulation of autophagy is involved in the progression of cancer. However, the predictive value of autophagy for breast cancer prognosis remains unclear. First, based on gene expression profiling, we found that autophagy genes were implicated in breast cancer. Then, using the Cox proportional hazard regression model, we detected autophagy prognostic signature for breast cancer in a training dataset. We identified a set of eight autophagy genes (BCL2, BIRC5, EIF4EBP1, ERO1L, FOS, GAPDH, ITPR1 and VEGFA) that were significantly associated with overall survival in breast cancer. The eight autophagy genes were assigned as a autophagy‐related prognostic signature for breast cancer. Based on the autophagy‐related signature, the training dataset GSE21653 could be classified into high‐risk and low‐risk subgroups with significantly different survival times (HR = 2.72, 95% CI = (1.91, 3.87); P = 1.37 × 10−5). Inactivation of autophagy was associated with shortened survival of breast cancer patients. The prognostic value of the autophagy‐related signature was confirmed in the testing dataset GSE3494 (HR = 2.12, 95% CI = (1.48, 3.03); P = 1.65 × 10−3) and GSE7390 (HR = 1.76, 95% CI = (1.22, 2.54); P = 9.95 × 10−4). Further analysis revealed that the prognostic value of the autophagy signature was independent of known clinical prognostic factors, including age, tumor size, grade, estrogen receptor status, progesterone receptor status, ERBB2 status, lymph node status and TP53 mutation status. Finally, we demonstrated that the autophagy signature could also predict distant metastasis‐free survival for breast cancer. © 2015 Wiley Periodicals, Inc.
An aseptic meningitis outbreak caused by echovirus 6 in Anhui province, China

An outbreak of aseptic meningitis (AM) occurred in Jinzhai County in Anhui province from April to July in 2005. Totally, 97 children aged 3–15 years were hospitalized. To identify the etiologic agent, 77 cerebrospinal fluid specimens (CSF) and 5 fecal specimens were collected from the patients and cultured by human rhabdomyosarcoma (RD) cell line. Thirty isolates of human echovirus 6 (E6) from 27 CSF and 3 fecal specimens were confirmed by neutralization assay and sequencing analysis of the VP1 gene. The homology of VP1 gene among Anhui isolates was 99.7–100.0% and it indicated that this AM outbreak probable caused by a single transmission link of E6. Phylogenetic analysis based on all the available complete VP1 sequences indicated that E6 could be divided into clusters A, B, and C with at least 15% diversity between clusters and the C cluster could be further divided into C1, C2, C3, and C4. The Anhui isolates most resembled a 2005 strain from Russia (25465 Tambov) and belong to C4. This is the first report that E6 was responsible for an outbreak of AM in China. J. Med. Virol. 82:441–445, 2010. © 2010 Wiley‐Liss, Inc.
CD4+ T lymphocyte modulation of ozone-induced murine pulmonary inflammation.

Inhalation of elevated levels of ozone produces a potent inflammatory response in the lung. The magnitude of this response to ozone exposure in mice is inbred strain dependent with the susceptible phenotype being exemplified by the C57BL/6J (B6) strain and the resistant phenotype by the C3H/HeJ (C3) strain. To examine the role of T lymphocytes in the regulation of ozone-induced pulmonary inflammation, mice were pretreated by an intraperitoneal injection of anti-Thy1.2 monoclonal antibody (mAb), anti-CD4+ mAb, or isotype-matched control antibodies (0.5 mg each) and subsequently exposed for 72 h to either filtered air or ozone (0.3 ppm). Immediately after ozone exposure, the cellular profile in the bronchoalveolar lavage fluids (BALF) was assessed. In isotype-treated controls of both strains of mice, ozone exposure induced significant increases in the numbers of macrophages, neutrophils, lymphocytes, and epithelial cells recovered in the BALF; however, the magnitude of each cell type recovered was significantly greater in B6 mice as compared with C3 mice. Both anti-Thy1.2 and anti-CD4+ monoclonal antibody treatments decreased the number of each cell type recovered in the B6 mice and increased the number of cells in the C3 mice. To determine if the CD4+ T-cell-derived cytokine interleukin (IL)-4 was involved in the differential effect of T-cell depletion on the ozone-induced inflammatory responses of C3 and B6 mice, mice were pretreated with either 400 ng of recombinant mouse IL-4 or vehicle, or 5.0 mg anti-IL-4 receptor monoclonal antibody or an isotype-matched antibody before either air or ozone exposure. (ABSTRACT TRUNCATED AT 250 WORDS)
A Vidcasting Project to Promote the Pharmacist's Role in Public Health

Objective. To develop, implement, and assess an Internet-based vidcasting project to promote the pharmacist's role in public health. Design. This was a collaborative effort for 2 different courses taught at 2 different schools of pharmacy. Faculty members created a special instructional design for students to follow in planning, producing, and publishing video public service announcements on the Internet. Assessment. Formative and summative assessments, including course examinations, a grading rubric, student survey, and focus group, were implemented to evaluate student learning and public reaction. Students believed Internet video public service announcements served as a useful reference for patients and professionals, aided in promoting disease prevention and wellness initiatives, positively impacted patient-provider relationships, and increased awareness regarding significance and financial impact of disease burden. Conclusion. Producing a public health information video and vidcasting it on the Internet increased pharmacy students' self-esteem, respect for peers, creative and critical-thinking abilities, and understanding of the need for and importance of pharmacists providing accurate public health information.
Arthroscopic Fragment Resection for Capitellar Osteochondritis Dissecans in Adolescent Athletes: 5- to 12-Year Follow-up

Background: Capitellar osteochondritis dissecans (OCD) in skeletally immature athletes has often been seen in baseball players and gymnasts. The choice of surgical procedure for unstable lesions in skeletally immature athletes remains controversial. Purpose: To investigate functional outcomes and radiographic changes in the midterm to long-term postoperative period after arthroscopic (AS) resection for small to large capitellar OCD lesions in skeletally immature athletes. Study Design: Case series; Level of evidence, 4. Methods: A total of 38 elbows in 38 patients (33 boys, 5 girls; mean age, 14 years [range, 13-15 years]) with skeletally immature elbows underwent AS resection for capitellar OCD. Patients were observed for at least 5 years (mean, 8 years [range, 5-12 years]). Elbows with a lesion width that did not exceed one-half of the radial head diameter were assigned to group 1 (n = 17 elbows), and larger lesions were assigned to group 2 (n = 21 elbows). Functional scores, patient satisfaction, range of motion (ROM), and osteoarthritis (OA) grades were evaluated between the groups. Results: All patients returned to sports activity. Functional scores at the final follow-up were not significantly different between the groups. Patient satisfaction scores were significantly higher in group 1 than in group 2. There was significant improvement in flexion ROM at the final follow-up compared with preoperative values in group 1 (P = .017), and there was a significant between-group difference (group 1: 141°; group 2: 133°; P = .002). Extension ROM showed significant improvement in both groups (group 1: from –8° to 3°; group 2: from –17° to –1°; P < .001 for both). Group 1 tended to have better extension than group 2, but the difference was not significant. There were no elbows with severe OA in either group, but the OA grade progressed in 5 elbows (29%) in group 1 and 9 elbows (43%) in group 2, and this rate of OA progression was statistically significant between groups (P = .005). Conclusion: Both functional outcomes and radiological findings after AS fragment resection were excellent in elbows with small lesions. Although overall outcomes were acceptable in elbows with larger lesions, flexion ROM and patient satisfaction scores were significantly inferior to those in elbows with smaller lesions.
The Development of 1-D Ice Cloud Microphysics Data Assimilation System (IMDAS) for Cloud Parameter Retrievals by Integrating Satellite Data

Reliable prediction of precipitation by Numerical Weather Prediction (NWP) models depends on the appropriate representation of cloud microphysical processes and accurate initial conditions of observations of atmospheric variables. Therefore, 1D Variational (1D-Var) Ice Cloud Microphysics Data Assimilation System (IMDAS) is developed for retrieving reasonable cloud distributions to improve the predictability of NWP models. The general framework of IMDAS includes the Lin ice cloud microphysics scheme as a model operator, a 4-stream fast microwave radiative transfer model (RTM) in the atmosphere as an observation operator, and a global minimization method known as Shuffled Complex Evolution (SCE). The IMDAS assimilates the satellite microwave radiometer data set of Advanced Microwave Scanning Radiometer (AMSR-E) and retrieves integrated water vapor (IWV) and integrated cloud liquid water content (ICLWC). This new method successfully introduces the heterogeneity into the initial state of the atmosphere, and the modeled microwave brightness temperatures agree well with observations of Wakasa Bay Experiment 2003 in Japan. It has improved the performance of cloud microphysics scheme significantly by the intrusion of heterogeneity into the external Global Reanalysis (GANAL) data, which may improve atmospheric initial conditions.
Magnetic resonance imaging‐based detection of glial brain tumors in mice after antiangiogenic treatment

Proper delineation of gliomas using contrast‐enhanced magnetic resonance imaging (CE‐MRI) poses a problem in neuro‐oncology. The blood brain barrier (BBB) in areas of diffuse‐infiltrative growth may be intact, precluding extravasation and subsequent MR‐based detection of the contrast agent gadolinium diethylenetriaminepenta‐acetic acid (Gd‐DTPA). Treatment with antiangiogenic compounds may further complicate tumor detection as such compounds can restore the BBB in angiogenic regions. The increasing number of clinical trials with antiangiogenic compounds for treatment of gliomas calls for the development of alternative imaging modalities. Here we investigated whether CE‐MRI using ultrasmall particles of iron oxide (USPIO, Sinerem®) as blood pool contrast agent has additional value for detection of glioma in the brain of nude mice. We compared conventional T1‐weighted Gd‐DTPA‐enhanced MRI to T2*‐weighted USPIO‐enhanced MRI in mice carrying orthotopic U87 glioma, which were either or not treated with the antiangiogenic compound vandetanib (ZD6474, ZACTIMA™). In untreated animals, vessel leakage within the tumor and a relatively high tumor blood volume resulted in good MRI visibility with Gd‐DTPA‐ and USPIO‐enhanced MRI, respectively. Consistent with previous findings, vandetanib treatment restored the BBB in the tumor vasculature, resulting in loss of tumor detectability in Gd‐DTPA MRI. However, due to decreased blood volume, treated tumors could be readily detected in USPIO‐enhanced MRI scans. Our findings suggest that Gd‐DTPA MRI results in overestimation of the effect of antiangiogenic therapy of glioma and that USPIO‐MRI provides an important complementary diagnostic tool to evaluate response to antiangiogenic therapy of these tumors. © 2007 Wiley‐Liss, Inc.
Gin‐mediated site‐specific recombination in bacteriophage Mu DNA: overproduction of the protein and inversion in vitro

Inversion of the G segment in bacteriophage Mu DNA occurs by a site‐specific recombination event and determines the host specificity of Mu phage particles produced. Inversion is mediated by a Mu function (Gin). The gin gene has been placed under control of the inducible λ pL promoter and a synthetic Shine‐Dalgarno linker upstream of the initiation codon. The Gin protein content in induced cells is boosted to ˜10% of total protein. Partially purified extracts from overproducing strains promote efficient inversion of the G DNA segment in vitro which is visualized by agarose gel electrophoresis of the substrate DNA after cutting with appropriate restriction endonucleases. The in vitro reaction requires Mg2+, a super‐coiled DNA substrate and occurs in the absence of exogenous ATP. Inversion from the G(+) to the G(−) orientation is as efficient as the switch from G(−) to G(+).
ACGME case logs: Surgery resident experience in operative trauma for two decades

BACKGROUND Surgery resident education is based on experiential training, which is influenced by changes in clinical management strategies, technical and technologic advances, and administrative regulations. Trauma care has been exposed to each of these factors, prompting concerns about resident experience in operative trauma. The current study analyzed the reported volume of operative trauma for the last two decades; to our knowledge, this is the first evaluation of nationwide trends during such an extended time line. METHODS The Accreditation Council for Graduate Medical Education (ACGME) database of operative logs was queried from academic year (AY) 1989–1990 to 2009–2010 to identify shifts in trauma operative experience. Annual case log data for each cohort of graduating surgery residents were combined into approximately 5-year blocks, designated Period I (AY1989–1990 to AY1993–1994), Period II (AY1994–1995 to AY1998–1999), Period III (AY1999–2000 to AY2002–2003), and Period IV (AY2003–2004 to AY2009–2010). The latter two periods were delineated by the year in which duty hour restrictions were implemented. RESULTS Overall general surgery caseload increased from Period I to Period II (p < 0.001), remained stable from Period II to Period III, and decreased from Period III to Period IV (p < 0.001). However, for ACGME-designated trauma cases, there were significant declines from Period I to Period II (75.5 vs. 54.5 cases, p < 0.001) and Period II to Period III (54.5 vs. 39.3 cases, p < 0.001) but no difference between Period III and Period IV (39.3 vs. 39.4 cases). Graduating residents in Period I performed, on average, 31 intra-abdominal trauma operations, including approximately five spleen and four liver operations. Residents in Period IV performed 17 intra-abdominal trauma operations, including three spleen and approximately two liver operations. CONCLUSION Recent general surgery trainees perform fewer trauma operations than previous trainees. The majority of this decline occurred before implementation of work-hour restrictions. Although these changes reflect concurrent changes in management of trauma, surgical educators must meet the challenge of training residents in procedures less frequently performed. LEVEL OF EVIDENCE Epidemiologic study, level III; therapeutic study, level IV.
Endoscopic ultrasound-guided fine needle aspiration training: evaluation of a new porcine lymphadenopathy model for in vivo hands-on teaching and training, and review of the literature

Background and study aims: Adequate training is required to achieve successful endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS – FNA). Of the variety of training models currently available, none offers verisimilitude to the tactile feel of puncturing a human lymph node. The aim of the current study was to evaluate a new porcine lymph node model for EUS – FNA training and to evaluate its impact on trainees’ performance in patients compared with the literature of other models available. Methods: Two trainees each performed EUS – FNA of 96 lymph nodes in 18 animals with induced lymphadenopathy (mean 1.6 cm [range 0.9 – 3.5 cm]). Accuracy, speed, adequacy of sampling, and trainees’ performance pre- and post-training were measured. Using a questionnaire, data were gathered regarding the effect of training and comfort level in patients. Results were compared with those in the literature. Results: Trainees progressed from hands-on assistance to occasional verbal guidance toward the end of animal training. There was good correlation between puncture time and number of EUS – FNA procedures performed in all but the subcarinal location (r = – 0.17). Comparison of trainee performance in patients before and after training showed a reduction in puncture time (P = 0.0014). Questionnaire analysis revealed increased confidence in echoendoscope- and needle-handling. Comparison with other published models supports these results. Conclusion: Results from the literature and the current study showed that animal training improves trainee performance, confidence, and procedural comfort when returning to patient examinations. The new model produces a realistic response that is similar to EUS – FNA in patients; this experience provides a benefit to endoscopists in terms of improved performance in patients and could be considered for use in accreditation. Due to the small numbers of trainees, larger experiences are needed to confirm training efficacy.
Patient position and hypoxemia during propofol sedation for colonoscopy: a randomized trial

Aim: To evaluate the benefits of the left lateral position in avoiding hypoxemic events in patients undergoing colonoscopy. Methods: We conducted a randomized, prospective, controlled trial at two study sites in Germany. Patients undergoing colonoscopy under propofol sedation were randomized to either the supine or left lateral position. The primary outcome was oxygen desaturation (SaO2 < 90 %). Secondary outcome measures were apneic events, hypotension, patient satisfaction, propofol dosage, cecal intubation time, and adenoma detection. Results: A total of 412 patients were randomized 1:1 to undergo colonoscopy in the supine or left lateral position. No severe adverse events were observed in either group. Intention-to-treat analysis revealed no significant difference in the frequency of desaturation in the left lateral arm compared with the supine arm (6.8 % vs. 12.1 %; P = 0.064). Patients in the left lateral arm showed lower apnea rates (9.4 % vs. 16.2 %; P = 0.040), but had more episodes of hypotension (12.3 % vs. 2.9 %; P < 0.001). The frequency of repositioning was higher in the left lateral group. No significant differences were observed in patient satisfaction and cooperation, propofol dosage, or adenoma detection rate. Patients who were repositioned to facilitate endoscope passage were excluded from per-protocol analysis. The incidence of hypoxemia was lower for the left lateral than for the supine group in per-protocol analysis (1.8 % vs. 11.2 %; P = 0.003). Conclusion: The positioning of patients in the left lateral position during propofol sedation for colonoscopy results in lower desaturation rates provided the position can be maintained throughout endoscopy. ClinicalTrials.gov NCT02001792.
Symptomatic Congenital Cytomegalovirus Infection in Infants Born to Mothers With Preexisting Immunity to Cytomegalovirus

Objectives. To determine the frequency of symptomatic congenital cytomegalovirus (CMV) infection in the offspring of women with a recurrent maternal CMV infection and to characterize the demographic and newborn findings. Methods. Study subjects consisted of infants with symptomatic congenital CMV infection identified by a newborn virologic screening program at the University of Alabama Hospital between 1991 and 1997 and were enrolled in a long-term follow-up study. Maternal infections were categorized by an analysis of archival serum specimens collected before pregnancy and at the time of delivery. Demographic data and clinical findings at birth were collected from maternal and newborn hospital records and from parents at the time of initial evaluation. Results. Of the 47 infants with symptomatic congenital CMV infection identified during the study period, 8 were born to mothers with a confirmed nonprimary or recurrent CMV infection. The type of maternal infection could be ascertained in only ∼43% (20/47) of the children with symptomatic congenital CMV infection born at the University of Alabama Hospital during the study period. There were no significant differences in demographic characteristics of the recurrent infection group and the infants who were born to mothers with either primary CMV infection during pregnancy or unclassified maternal infection. Similarly, the range of severity of clinical abnormalities during the newborn period did not differ in the two groups of children. Furthermore, there were no significant differences in the incidence of sequelae at long-term follow-up in the two groups of children. Conclusions. Symptomatic congenital CMV infection can occur after a nonprimary or recurrent maternal infection. However, the exact incidence of symptomatic congenital CMV infection among children born to women with preexisting immunity remains to be defined.