Miracle-dz/UniFAR-FTUs huggingface dataset:
High-dose-rate intraluminal brachytherapy during preoperative chemoradiation for locally advanced rectal cancers.

AIM To determine the feasibility and safety of high dose rate intraluminal brachytherapy (HDR-ILBT) boost during preoperative chemoradiation for rectal cancer. METHODS Between 2008 and 2009, thirty-six patients with locally advanced rectal cancer (≥ T3 or N+), were treated initially with concurrent capecitabine (825 mg/m(2) oral twice daily) and pelvic external beam radiotherapy (EBRT) (45 Gy in 25 fractions), then were randomized to group A; HDR-ILBT group (n = 17) to receive 5.5-7 Gy × 2 to gross tumor volume (GTV) and group B; EBRT group (n = 19) to receive 5.4 Gy × 3 fractions to GTV with EBRT. All patients underwent total mesorectal excision. RESULTS Grade 3 acute toxicities were registered in 12 patients (70.6%) in group A and in 8 (42.1%) in group B. Complete pathologic response of T stage (ypT0) in group A was registered in 10 patients (58.8%) and in group B, 3 patients (15.8%) had ypT0 (P < 0.0001). Sphincter preservation was reported in 6/9 patients (66.7%) in group A and in 5/10 patients (50%) in group B (P < 0.01). Overall radiological response was 68.15% and 66.04% in Group A and B, respectively. During a median follow up of 18 mo, late grade 1 and 2 sequelae were registered in 3 patients (17.6%) and 4 patients (21.1%) in the groups A and B, respectively. CONCLUSION HDR-ILBT was found to be effective dose escalation technique in preoperative chemoradiation for rectal cancers, with higher response rates, downstaging and with manageable acute toxicities.
Vigabatrin increases human brain homocarnosine and improves seizure control

Homocarnosine, a dipeptide of γ‐aminobutyric acid (GABA) and histidine, is thought to be an inhibitory neuromodulator synthesized in subclasses of GABAergic neurons. Homocarnosine is present in human brain in greater amounts (0.4–1.0 μmol/g) than in other animals. The antiepileptic drug vigabatrin increases human cerebrospinal fluid homocarnosine linearly with daily dose. By using 1H nuclear magnetic resonance spectroscopy, serial occipital lobe GABA and homocarnosine concentrations were measured in 11 patients started on vigabatrin. Daily low‐dose (2 g) vigabatrin increased both homocarnosine and GABA. Larger doses of vigabatrin (4 g) further increased homocarnosine but changed GABA levels minimally. Seizure control improved with increasing homocarnosine and GABA concentrations. Patients whose seizure control improved with the addition of vigabatrin had higher mean homocarnosine, but the same mean GABA concentrations, than those whose seizure control did not improve. Increased homocarnosine may contribute to improved seizure control.
Intergenic splicing between a HERV-H endogenous retrovirus and two adjacent human genes.

We previously reported that a long terminal repeat (LTR) of a human endogenous retrovirus of the HERV-H family promotes expression of a cellular fusion transcript in teratocarcinoma cell lines. This transcript was termed PLA2L due to two regions of similarity to the secreted form of phospholipase A2. In this study, evidence is presented indicating that this transcript appears to be the result of intergenic splicing between the HERV-H element and two independent downstream genes. The 5' gene has been named HHLA1 (HERV-H LTR-associating 1) and is of unknown function but shows sequence conservation in other mammals. The 3' gene is now known to encode human otoconin-90 (OC90) which, in mice, is a major protein expressed in the fetal inner ear. Evidence for intergenic splicing of these two genes includes: (1) the isolation of LTR-driven HHLA1 transcripts, unspliced to otoconin-90 exons, with variable sites of polyadenylation; (2) the cloning of both the putative human intergenic genomic region and the novel 5' terminus of the mouse otoconin-90 gene; (3) the identification of homologous potential signal sequences in the 5' region of mouse otoconin-90 and in the middle of the PLA2L transcript; and (4) the lack of detectable chromosomal rearrangements involving this region in teratocarcinoma cells. The PLA2L transcript therefore represents a rare example of intergenic splicing of two closely linked genes. We hypothesize that human HHLA1 and OC90 are normally expressed independently from different promoters but are expressed from the LTR promoter and spliced together in teratocarcinoma cells. It is tempting to speculate that the high activity of the LTR promoter in this cell type may induce transcriptional fusion between these two genes.
Insufficiency of ciliary cholesterol in hereditary Zellweger syndrome

Primary cilia are antenna‐like organelles on the surface of most mammalian cells that receive sonic hedgehog (Shh) signaling in embryogenesis and carcinogenesis. Cellular cholesterol functions as a direct activator of a seven‐transmembrane oncoprotein called Smoothened (Smo) and thereby induces Smo accumulation on the ciliary membrane where it transduces the Shh signal. However, how cholesterol is supplied to the ciliary membrane remains unclear. Here, we report that peroxisomes are essential for the transport of cholesterol into the ciliary membrane. Zellweger syndrome (ZS) is a peroxisome‐deficient hereditary disorder with several ciliopathy‐related features and cells from these patients showed a reduced cholesterol level in the ciliary membrane. Reverse genetics approaches revealed that the GTP exchange factor Rabin8, the Rab GTPase Rab10, and the microtubule minus‐end‐directed kinesin KIFC3 form a peroxisome‐associated complex to control the movement of peroxisomes along microtubules, enabling communication between peroxisomes and ciliary pocket membranes. Our findings suggest that insufficient ciliary cholesterol levels may underlie ciliopathies.
Crystal Structure of Staphylococcus aureus Metallopeptidase (Sapep) Reveals Large Domain Motions between the Manganese-bound and Apo-states

Proteases belonging to the M20 family are characterized by diverse substrate specificity and participate in several metabolic pathways. The Staphylococcus aureus metallopeptidase, Sapep, is a member of the aminoacylase-I/M20 protein family. This protein is a Mn2+-dependent dipeptidase. The crystal structure of this protein in the Mn2+-bound form and in the open, metal-free state suggests that large interdomain movements could potentially regulate the activity of this enzyme. We note that the extended inactive conformation is stabilized by a disulfide bond in the vicinity of the active site. Although these cysteines, Cys155 and Cys178, are not active site residues, the reduced form of this enzyme is substantially more active as a dipeptidase. These findings acquire further relevance given a recent observation that this enzyme is only active in methicillin-resistant S. aureus. The structural and biochemical features of this enzyme provide a template for the design of novel methicillin-resistant S. aureus-specific therapeutics.
Enforced expression of HOX11 is associated with an immature phenotype in J2E erythroid cells

Summary. The HOX11 gene encodes a homeodomain transcription factor that is essential for spleen development during embryogenesis. HOX11 is also leukaemogenic, both through its clinical association with childhood T‐cell acute lymphoblastic leukaemia, and its ability to immortalize other haematopoietic cell lineages experimentally. To examine the pathological role of HOX11 in tumorigenesis, we constitutively expressed HOX11 cDNA in J2E murine erythroleukaemic cells, which are capable of terminal differentiation. Enforced HOX11 expression was found to induce a profound alteration in J2E cellular morphology and differentiation status. Our analyses revealed that HOX11 produced clones with a preponderance of less differentiated cells that were highly adherent to plastic. Morphologically, the cells overexpressing HOX11 were larger and had decreased globin levels, as well as a reduction in haemoglobin synthesis in response to erythropoietin (EPO). Immunocytochemical analysis confirmed the immature erythroid phenotype imposed by HOX11, with clones transfected with HOX11 demonstrating expression of the c‐Kit stem cell marker, while retaining EPO receptor expression. Taken together, these results show that HOX11 alters erythroid differentiation, favouring a less mature progenitor‐like stage. This supports the notion that disrupted haematopoietic cell differentiation is responsible for pre‐leukaemic immortalization by the HOX11 oncoprotein.
Rifampin Induces Hydroxyl Radical Formation in Mycobacterium tuberculosis

ABSTRACT The antituberculosis (anti-TB) drug rifampin (RIF) binds to the beta subunit of the RNA polymerase (RpoB) of Mycobacterium tuberculosis, but the bactericidal responses triggered after target interaction are not known. To evaluate whether RIF induced an oxidative burst, lysates of RIF-treated M. tuberculosis were tested for determination of reactive oxygen species (ROS) by the electron paramagnetic resonance (EPR) technique using 1-hydroxy-3-carboxy-pyrrolidine (CPH) and 5,5-dimethyl-1-pyrrolidine-N-oxide (DMPO) as spin traps. M. tuberculosis killing by RIF stimulated an increase in the rate of formation of the CPH radical (CP·). Lysate pretreatment with the O2·− and ·OH scavengers superoxide dismutase (SOD) and thiourea (THIO), respectively, or with the metal chelator diethylene triamine pentaacetic acid (DTPA) inhibited CP· formation, arguing in favor of a metal-catalyzed ROS response. Formation of CP· did not increase following treatment of RIF-resistant strains with RIF, indicating that the ROS were induced after RpoB binding. To identify the ROS formed, lysates of RIF-treated bacilli were incubated with DMPO, a spin trap specific for ·OH and O2·−, with or without pretreatment with SOD, catalase, THIO, or DTPA. Superoxide dismutase, catalase, and THIO decreased formation of the DMPO-OH adduct, and SOD plus DTPA completely suppressed it, suggesting that RIF activated metal-dependent O2·−-mediated mechanisms producing ·OH inside tubercle bacilli. The finding that the metal chelator DTPA reduced the bactericidal activity of RIF supported the possibility that ·OH was generated through these mechanisms and that it participated at least in part in M. tuberculosis killing by the drug.
Integrated electrochemical sensor based on electrowetting-on-dielectric microfluidic chip

In this work, we describe the design and study of a novel electrochemical microsensor integrated with electrowetting-on-dielectric (EWOD) microfluidic chip for automatic, rapid and microscale detection. The microsensor was based on the parallel plate EWOD chip. The pretreatment of microliter analyte including dispensing, transporting, mixing and colleting was realized mainly by EWOD electrodes on the bottom plate. The top plate consists of the ground wires for EWOD microfluidics and an on-chip electrochemical cell with gold three-electrode system. The structure and fabrication process were optimized to improve the reliability and stability of integrated chip. The chip can simultaneously realize multifunctional manipulation and online electrochemical detection for reagent droplets. It shows a wide linear range of 10.0 μM-1.0 mM ferrocenemethanol (FcM). The sensitivity of anodic and cathodic peak current was about 5.47 nA/μM (R2=0.99994) and 5.21 nA/μM (R2=0.99904), respectively. This work shows a great promise for microliter biosensing based on smart microfluidic unit and integrated electrochemical cell in the future.
Persistence of ventilatory defect after resolution of pulmonary interstitial emphysema in a preterm baby

Abstract Pulmonary interstitial emphysema is a common complication of mechanical ventilation in preterm babies. We report a case of severe unilateral pulmonary interstitial emphysema in a premature newborn, treated with high-frequency oscillatory ventilation, lateral decubitus positioning and selective intubation. After complete radiological resolution of the pulmonary emphysema in the left lung, the patient was studied by electrical impedance tomography and a marked reduction of ventilation was identified in the left lung despite radiological resolution of the cysts. This finding indicates that functional abnormalities may persist for longer periods after radiologic resolution of such lesions.
A conserved phosphatase cascade that regulates nuclear membrane biogenesis

A newly emerging family of phosphatases that are members of the haloacid dehalogenase superfamily contains the catalytic motif DXDX(T/V). A member of this DXDX(T/V) phosphatase family known as Dullard was recently shown to be a potential regulator of neural tube development in Xenopus [Satow R, Chan TC, Asashima M (2002) Biochem Biophys Res Commun 295:85–91]. Herein, we demonstrate that human Dullard and the yeast protein Nem1p perform similar functions in mammalian cells and yeast cells, respectively. In addition to similarity in primary sequence, Dullard and Nem1p possess similar domains and show similar substrate preferences, and both localize to the nuclear envelope. Additionally, we show that human Dullard can rescue the aberrant nuclear envelope morphology of nem1Δ yeast cells, functionally replacing Nem1p. Finally, Nem1p, has been shown to deposphorylate the yeast phosphatidic acid phosphatase Smp2p [Santos-Rosa H, Leung J, Grimsey N, Peak-Chew S, Siniossoglou S (2005) EMBO J 24:1931–1941], and we show that Dullard dephosphorylates the mammalian phospatidic acid phosphatase, lipin. Therefore, we propose that Dullard participates in a unique phosphatase cascade regulating nuclear membrane biogenesis, and that this cascade is conserved from yeast to mammals.
Fitness of Antibiotic-Resistant Bacteria in the Environment: A Laboratory Activity†

In this laboratory experiment, we propose an opportunity for students to broaden their understanding of the ecology of antibiotic-resistant and sensitive waterborne bacteria. Antibiotics can be found in rivers or soil as a consequence of agricultural practices or as a result of human use. Concentrations of antibiotics in the environment may range from a few ng to μg L−1. Such concentrations can affect the selection and fitness of resistant bacteria. In this laboratory activity, students learn how to set up a fitness experiment by using an isogenic pair of antibiotic-resistant and sensitive bacteria in the presence or absence of selective pressure. Microcosms were generated by using filtered river water containing populations of resistant and sensitive bacteria. Competition of both populations was measured in the presence or absence of antibiotics. Students appreciated the use of microcosms for in vitro experiments and the extent to which the fitness of resistant and sensitive bacteria changed in the presence and/or absence of a selective pressure in river water. Student learning was measured by using different types of assessments: multiple-choice, true/false, fill in the blanks, laboratory skills observations, and laboratory reports. After the laboratory activity, the percentage of correct answers significantly rose from ~20% to ~85%. Laboratory skills were also evaluated during the exercises, showing no major issues during the experiment. Students showed proficiency in analyzing the complexity of fitness data by reaching a mean of 5.57 (standard error 0.57) over a maximum score of 7 points.
Oxygen modifies artery differentiation and network morphogenesis in the retinal vasculature

The mechanisms that control differentiation of immature blood vessels into either arteries or veins are not well understood. Because oxygen tension in arteries is higher than in veins, oxygen has the potential to be an instructive signal for artery/vein (AV) differentiation. We test this hypothesis by exposing newborn mice to moderate hypoxia (10% atmospheric oxygen) and studying AV differentiation in the developing retinal vasculature. Forming retinal arteries fail to express the artery‐specific markers Delta‐like 4 (Dll4) and EphrinB2 during hypoxia. However, other aspects of AV differentiation are retained such as high levels of alpha smooth muscle actin in arterial mural cells and vein‐specific expression of the msr/apj gene. The capillary network between arteries and veins is denser, and capillaries expressing the venous marker msr/apj are found in territories normally occupied by arterial capillaries. Thus, it appears that high oxygen in arterial blood is required for arterial expression of Dll4 and EphrinB2, which could be involved in cell–cell repulsion pathways that dictate the normal segregation of arteries and veins. Developmental Dynamics 233:822–828, 2005. © 2005 Wiley‐Liss, Inc.
Graphene-Based Conducting Metal Oxide Coated D-Shaped Optical Fiber SPR Sensor

We report a graphene-based indium tin oxide coated surface plasmon resonance sensor built on a D-shaped optical fiber for near infrared. Different parameters of the proposed sensor have been optimized to obtain a maximal phase matching between the core guided mode and the plasmon mode using finite element method. Wavelength sensitivity of the proposed structure is as high as 5700 nm/RIU with a maximum resolution of 1.754 × 10-5 RIU. The proposed sensor can also be used for bio layer thickness monitoring with a maximum resolution of 62.5 pm in wavelength interrogation.
Secure Cooperative Communications Under Secrecy Outage Constraint: A DC Programming Approach

Physical-layer security can offer confidential communications from an information-theoretic viewpoint. This letter focuses on the secrecy rate optimization in presence of an eavesdropper, investigating the cases of direct and cooperative communications. Particularly, the problem of joint power and confusion rate management to provide optimal secrecy rate under admissible information leakage is studied. A secrecy outage constraint and no instantaneous channel state information of eavesdropper's link are assumed. Due to the nonconvexity of the problem, difference of convex functions (DC) programming is employed and a low complexity algorithm is proposed. The performance of the proposed mechanism is evaluated through extended simulations.
Topography of the Human Corpus Callosum Using Diffusion Tensor Tractography

Objective: To evaluate the crossing fiber trajectory through the corpus callosum using distortion-corrected diffusion tensor tractography in the human brain. Methods: After correcting distortion associated with large-diffusion gradients, T2-weighted echo planar images (EPIs) acquired from 10 right-handed healthy men were coregistered into T2-weighted fast spin echo images using linear through sixth-order nonlinear, 3-dimensional, polynomial warping functions. The optimal transformation parameters were also applied to the distortion-corrected diffusion-weighted EPIs. Diffusion tensor tractography through the corpus callosum was reconstructed, employing the “1 or 2 regions of interest” method. Results: Compared with the lines through the genu, those through the rostrum ran more inferiorly and seemed to enter the orbital gyrus. Those lines entering posterior temporal white matter (tapetum) crossed through the ventral portion of the splenium and were clearly distinguished from lines that reached parieto-occipital white matter (forceps major). Conclusion: Diffusion tensor tractography is a feasible noninvasive tool to evaluate commissural fiber trajectory.
Detection of SARS Coronavirus in Patients with Severe Acute Respiratory Syndrome by Conventional and Real-Time Quantitative Reverse Transcription-PCR Assays

Abstract Background: A novel coronavirus (CoV) was recently identified as the agent for severe acute respiratory syndrome (SARS). We compared the abilities of conventional and real-time reverse transcription-PCR (RT-PCR) assays to detect SARS CoV in clinical specimens. Methods: RNA samples isolated from nasopharyngeal aspirate (NPA; n = 170) and stool (n = 44) were reverse-transcribed and tested by our in-house conventional RT-PCR assay. We selected 98 NPA and 37 stool samples collected at different times after the onset of disease and tested them in a real-time quantitative RT-PCR specific for the open reading frame (ORF) 1b region of SARS CoV. Detection rates for the conventional and real-time quantitative RT-PCR assays were compared. To investigate the nature of viral RNA molecules in these clinical samples, we determined copy numbers of ORF 1b and nucleocapsid (N) gene sequences of SARS CoV. Results: The quantitative real-time RT-PCR assay was more sensitive than the conventional RT-PCR assay for detecting SARS CoV in samples collected early in the course of the disease. Real-time assays targeted at the ORF 1b region and the N gene revealed that copy numbers of ORF 1b and N gene sequences in clinical samples were similar. Conclusions: NPA and stool samples can be used for early diagnosis of SARS. The real-time quantitative RT-PCR assay for SARS CoV is potentially useful for early detection of SARS CoV. Our results suggest that genomic RNA is the predominant viral RNA species in clinical samples.
Student Molecular Laboratory Performance Outcomes in a Baccalaureate CLS Program

As new molecular assays are developed in research laboratories and approved by the Food and Drug Administration (FDA) for clinical use, molecular diagnostics becomes an integral discipline of clinical laboratory science. Since 2001, guidelines of the National Accreditation Agency for Clinical Laboratory Science (NAACLS) have required that CLS Educational Programs incorporate molecular diagnostics into the curriculum. SETTING: In fall of 2005, CLS faculty/researchers, affiliated with a baccalaureate program in an academic medical university, incorporated molecular diagnostic lecture content with online virtual laboratories into the Clinical Chemistry course. Then beginning in fall of 2006, manual performance of molecular laboratory exercises was introduced. OBJECTIVE: The aim of this study was to assess whether inclusion of hands-on molecular laboratories improved student outcomes on molecular questions during the final course examination. METHOD: CLS faculty evaluated student learning by written examination of lecture and laboratory content. Researchers performed two-sample t-tests to establish if significant differences existed in molecular questions scores achieved by students exposed to virtual and hands-on exercises. RESULTS: The researchers found a statistically significant difference in examination performance between the students that had a hands-on experience and students with virtual laboratory experience only. Further data analysis suggested that hands-on experiential laboratories had the greatest effect on students who performed in the middle percentiles. CONCLUSION: The researchers proposed that in order to improve examination scores of the weakly performing students other interventions may be necessary such as more lecture or laboratory time. This prompted development of a full time clinical molecular methods course, separate from Clinical Chemistry.