Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment of choroidal neovascularization using intravitreal bevacizumab.

PURPOSE This study aimed to assess the pharmacodynamic profile of intravitreal bevacizumab in relation to best corrected visual acuity (BCVA), foveal thickness, and other aspects of macular morphology after intravitreal injection of bevacizumab in eyes with subretinal choroidal neovascularization (CNV). METHODS A retrospective observational, uncontrolled case series including 26 eyes in 25 patients followed for up to 6 months after intravitreal injection of bevacizumab 1 mg repeated as deemed necessary after monthly assessments by biomicroscopy, optical coherence tomography, colour fundus photography, fluorescein angiography and BCVA determination. At follow-up, cases were classified by morphological treatment response (reduction or elimination of pathological neovascular leakage, retinal thickening or serous retinal detachment) or absence of response (deterioration or lack of improvement). Primary disease entities included age-related macular degeneration (22 eyes, four of which had evidence of retinal angiomatous proliferation), idiopathic peripapillary neovascularization (one eye), and angioid streaks (three eyes in two patients). RESULTS One month after the first injection, apparent morphological improvement was observed in 24/26 eyes and mean BCVA had improved by 3.1 +/- 7.8 letters (p = 0.05). Of these 24 responders, which included all primary diagnoses, 11 (46%) demonstrated BCVA improvement of >or= 5 letters. The two non-responders (7.7%) had lost > 3 lines of vision at 2 months follow-up. Overall, 18 eyes completed 6 months follow-up, with a mean BCVA improvement of 0.5 +/- 12.7 letters, and 22 eyes completed 3 months follow-up, with a mean BCVA improvement of 2.0 +/- 11.0 letters. Two months after the first injection, 11 (46%) of the 24 responders demonstrated signs of recurrent CNV activity, defined as decreased BCVA and/or increased retinal thickness and/or fluorescein angiographic CNV leakage. No serious drug-related adverse events were observed during the course of the study. CONCLUSIONS Overall mean BCVA remained stable throughout the study. Morphological signs of reduced CNV activity were seen in the majority of eyes at 2-4 weeks after intravitreal bevacizumab injection. Half the responders showed signs of renewed CNV activity at 2 months after their first injection. All first-injection responders were also second-injection responders.
Prospective endoscopic study of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo

Objective: To compare the frequency of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo. Design: Prospective, randomized study. Setting: Intensive care unit in a university hospital. Patients: Twenty‐six adult patients. All patients were mechanically ventilated and were at risk of developing stress ulceration. Interventions: Patients were randomized to receive either sucralfate (2 g every 8 hrs) (group 1) via the nasogastric tube (flushed with 10 mL of sterile water) or 20 mL of sterile water every 8 hrs (group 2) via the nasogastric tube. Measurements and Main Results: At the time of intensive care unit admission, the frequency of stress (acute) erosions (as assessed with the endoscope) was 21.7%. No ulcers were detected. By day 3, the frequency had increased to 37.5% in group 1 and 88.9% in group 2. Mucosal deterioration was more likely in the patients treated with placebo (water) ( p < .05). In total, seven patients developed acute ulceration in group 2 compared with only one patient in group 1 ( p < .05). The frequency of gastric colonization with aerobic Gram‐negative bacilli was 25.6% in group 1 and 28.6% in group 2. Only one retrograde nosocomial pneumonia developed (group 1). Conclusion: Based on our findings, we strongly recommend the adoption of sucralfate as opposed to no prophylaxis in the prevention of acute upper gastrointestinal ulceration. (Crit Care Med 1994; 22:1949–1954)
iRootHair: A Comprehensive Root Hair Genomics Database1[W]

The specialized root epidermis cells of higher plants produce long, tubular outgrowths called root hairs. Root hairs play an important role in nutrient and water uptake, and they serve as a valuable model in studies of plant cell morphogenesis. More than 1,300 articles that describe the biological processes of these unique cells have been published to date. As new fields of root hair research are emerging, the number of new papers published each year and the volumes of new relevant data are continuously increasing. Therefore, there is a general need to facilitate studies on root hair biology by collecting, presenting, and sharing the available information in a systematic, curated manner. Consequently, in this paper, we present a comprehensive database of root hair genomics, iRootHair, which is accessible as a Web-based service. The current version of the database includes information about 153 root hair-related genes that have been identified to date in dicots and monocots along with their putative orthologs in higher plants with sequenced genomes. In order to facilitate the use of the iRootHair database, it is subdivided into interrelated, searchable sections that describe genes, processes of root hair formation, root hair mutants, and available references. The database integrates bioinformatics tools with a focus on sequence identification and annotation. iRootHair is a unique resource for root hair research that integrates the large volume of data related to root hair genomics in a single, curated, and expandable database that is freely available at www.iroothair. org.
Comparison between reflection-mode photoplethysmography and arterial diameter change detected by ultrasound at the region of radial artery

ObjectiveContinuous monitoring of arterial blood pressure (ABP) can provide vital information on the cardiovascular system in clinical practice and research. To achieve this, methods have been developed to determine ABP continuously and noninvasively, including the wrist volume clamp method, which uses reflection-mode photoplethysmography (PPG) to indicate the volume change of the radial artery. However, this kind of indication is reportedly not accurate enough, and an in-vivo test for its accuracy is still lacking. Our aim was to fix this gap. MethodsAs ultrasound can detect the arterial diameter accurately; we have developed a sensor comprised a PPG sensor and an ultrasound transducer, which can collect reflection-mode PPG and A-mode ultrasound signals, simultaneously. Tests on 15 volunteers were conducted under the similar conditions of using wrist volume clamp method for a comparison between the PPG signal and the radial arterial diameter. ResultsIt was observed that there were obvious differences between the shapes of these two signals, mainly between their drifting trend parts, with the pulsatile components of the signals matching very well. The mean root mean square value of the differences of the trend parts (0.287±0.072) was found to be much larger than that of the pulsatile parts (0.107±0.028). ConclusionThe results indicated that using PPG signal as a reference for ABP measurement at the wrist region might not be accurate enough, and ultrasound has the potential for replacing it in the wrist volume clamp method for more accurate ABP determination.
Efficient calculation of configurational entropy from molecular simulations by combining the mutual‐information expansion and nearest‐neighbor methods

Changes in the configurational entropies of molecules make important contributions to the free energies of reaction for processes such as protein‐folding, noncovalent association, and conformational change. However, obtaining entropy from molecular simulations represents a long‐standing computational challenge. Here, two recently introduced approaches, the nearest‐neighbor (NN) method and the mutual‐information expansion (MIE), are combined to furnish an efficient and accurate method of extracting the configurational entropy from a molecular simulation to a given order of correlations among the internal degrees of freedom. The resulting method takes advantage of the strengths of each approach. The NN method is entirely nonparametric (i.e., it makes no assumptions about the underlying probability distribution), its estimates are asymptotically unbiased and consistent, and it makes optimum use of a limited number of available data samples. The MIE, a systematic expansion of entropy in mutual information terms of increasing order, provides a well‐characterized approximation for lowering the dimensionality of the numerical problem of calculating the entropy of a high‐dimensional system. The combination of these two methods enables obtaining well‐converged estimations of the configurational entropy that capture many‐body correlations of higher order than is possible with the simple histogramming that was used in the MIE method originally. The combined method is tested here on two simple systems: an idealized system represented by an analytical distribution of six circular variables, where the full joint entropy and all the MIE terms are exactly known, and the R,S stereoisomer of tartaric acid, a molecule with seven internal‐rotation degrees of freedom for which the full entropy of internal rotation has been already estimated by the NN method. For these two systems, all the expansion terms of the full MIE of the entropy are estimated by the NN method and, for comparison, the MIE approximations up to third order are also estimated by simple histogramming. The results indicate that the truncation of the MIE at the two‐body level can be an accurate, computationally nondemanding approximation to the configurational entropy of anharmonic internal degrees of freedom. If needed, higher‐order correlations can be estimated reliably by the NN method without excessive demands on the molecular‐simulation sample size and computing time. © 2008 Wiley Periodicals, Inc. J Comput Chem, 2008
Anti‐myelin basic protein and anti‐proteolipid protein specific forms of multiple sclerosis

Human myelin basic protein (hMBP) and proteolipid protein (PLP) were used as antigens in a solid‐phase radioimmunoassay to determine relative frequencies of anti‐MBP and anti‐PLP in cerebrospinal fluid (CSF) of optic neuritis and multiple sclerosis (MS) patients. Forty‐nine of 55 patients with optic neuritis had increased CSF anti‐MBP and the remaining 6 had increased anti‐PLP. Of 385 MS patients, MS relapse: 173 of 180 patients had increased anti‐MBP, 5 of the remaining 7 patients had elevated anti‐PLP, and 2 had neither of these autoantibodies. Progressive MS: 111 of 116 patients had increased anti‐MBP in either free and/or bound form, of the remaining 5 patients 4 had increased anti‐PLP, and 1 had neither anti‐MBP nor anti‐PLP. MS remission: 15 of 87 patients had somewhat increased anti‐MBP, none had anti‐PLP. IgG was purified by affinity chromatography from necropsy central nervous system (CNS) tissue samples of 4 individual patients with clinically definite and neuropathologically confirmed MS. Three of these 4 patients who had increased levels of CSF anti‐MBP also had increased anti‐MBP titers in CNS tissue‐extracted IgG. The fourth patient who had anti‐PLP in CSF also had anti‐PLP in brain tissue IgG. These autoantibodies were not detected simultaneously in any patient. These results suggest that there are at least two immunologically distinct forms of MS, i.e., a common form highly associated with anti‐MBP and more frequent prominent inflammatory characteristics in CSF and CNS, and an infrequent form associated with anti‐PLP in CSF and tissue, and less abundant inflammation. Anti‐MBP purified from CNS tissue IgG by antigen‐specific affinity chromatography was reacted with synthetic peptides of hMBP. The anti‐MBP epitope on the hMBP molecule was restricted between residues 75 and 106. The PLP epitope for anti‐PLP has not as yet been determined. These observations have theoretical implications for anticipated future specific immunotherapy of MS.
Synthesis of Some Benzimidazole-derived Molecules and Their Effects on PARP-1 Activity and MDA-MB-231, MDA-MB-436, MDA-MB-468 Breast Cancer Cell Viability.

BACKGROUND Poly (ADP-ribosyl) polymerase-1 (PARP-1) inhibitors are compounds that are used to treat cancers, which are defective in DNA-repair and DNA Damage-Response (DDR) pathways. OBJECTIVE In this study, a series of potential PARP-1 inhibitor substituted (piperazine-1-carbonyl)phenyl)-1H- benzo[d]imidazole4-carboxamide compounds were synthesised and tested for their PARP-1 inhibitory and anti-cancer activities. METHODS Compounds were tested by cell free colorimetric PARP-1 activity and MTT assay in MDA-MB-231, MDA-MB-436, MDA-MB-468 breast cancer and L929 fibroblast cell lines. RESULTS Our results showed that compound 6a inhibited viability in MDA-MB-231 and MDA-MB-468 cells whereas 8a inhibited viability in MDA-MB-468 cells. Compound 6b significantly inhibited cell viability in tested cancer cells. However, 6b exhibited toxicity in L929 cells whereas 6a and 8a were found to be non-toxic for L929 cells. Compounds 6a, 6b and 8a exhibited significant inhibition of PARP-1 activity. CONCLUSION These three compounds exhibited PARP-1 inhibitory activities and anticancer effects on breast cancer cells and further research will enlighten the underlying mechanisms of their effects.
Genomic imbalances in 61 renal cancers from the proximal tubulus detected by comparative genomic hybridization

Comparative genomic hybridization (CGH) has been applied to characterize 61 primary renal cell carcinomas derived histogenetically from the proximal tubulus. The tumor samples comprised 46 clear-cell renal cell carcinomas (ccRCCs) and 15 papillary renal cell carcinomas (pRCCs). Changes in the copy number of entire chromosomes or subregions were detected in 56 tumors (92%). In ccRCCs, losses of chromosome 3 or 3p (63%); 14q (30%); 9 (26%); 1 and 6 or 6q (17% each); 4 and 8 or 8p (15% each); 22 (11%); 2 or 2q and 19 (9% each); 7q, 10, 16, 17p, 18, and Y (7% each); and 5, 11, 13, 15, and 21 (4% each) were detected. Most frequent genomic gains in ccRCC were found on chromosome 5 (63%); 7 (35%); 1 or 1q (33%); 2q (24%); 8 or 8q, 12, and 20 (20% each); 3q (17%); 16 (15%); 19 (13%); 6 and 17 or 17q (11% each); and 4, 10, 11, 21, and Y (9% each). In pRCCs, gains in the copy number of chromosomes 7 and 17 (7/15, each) and 16 and 20 (6/15, each) were frequent. One pRCC showed amplification of subchromosome regions 2q22→q33, 16q, 17q and the entire X chromosome. In pRCC, losses were less frequently seen than gains. Losses of chromosomes 1, 14, 15, and Y (3/15 each) and 2, 4, 6, and 13 (2/15 each) were observed. In ccRCCs, statistical evaluation revealed significant correlations of chromosomal imbalances with tumor stage and grade, i.e., a gain in copy number of chromosome 5 correlated positively with low tumor grade, whereas a gain of chromosomes 10 and 17 correlated positively with high tumor grade. Furthermore, loss of chromosome 4 correlated positively with high tumor stage.
Full and partial posttraumatic stress disorder: findings from a community survey.

OBJECTIVE Full and partial posttraumatic stress disorder (PTSD) following trauma exposure were examined in a community sample in order to determine their prevalence and their relative importance and functional significance. METHOD A standardized telephone interview with a series of trauma probes and a DSM-IV PTSD checklist was administered to a random sample of 1,002 persons in a midsized Midwestern Canadian city. The authors determined current (i.e., 1-months) prevalence rates of full PTSD, i.e., all DSM-IV criteria, and partial PTSD, i.e., fewer than the required number of DSM-IV criterion C symptoms (avoidance/numbing) or criterion D symptoms (increased arousal). Additional questions about interference with functioning were also posed. RESULTS The estimated prevalence of full PTSD was 2.7% for women and 1.2% for men. The prevalence of partial PTSD was 3.4% for women and 0.3% for men. Interference with work or school was significantly more pronounced in persons with full PTSD than in those with only partial symptoms, although the latter were significantly more occupationally impaired than traumatized persons without PTSD. CONCLUSIONS These findings in an epidemiologic sample underscore observations from patient and military groups that many traumatized persons suffer from a subsyndromal form of PTSD. These persons with partial PTSD, although somewhat less impaired than persons with the full syndrome, nonetheless exhibit clinically meaningful levels of functional impairment in association with their symptoms. This subthreshold form of PTSD may be especially prevalent in women. Additional study of partial PTSD is warranted.
Comparison of Accuracy of Whole-Exome Sequencing with Formalin-Fixed Paraffin-Embedded and Fresh Frozen Tissue Samples

Formalin fixing with paraffin embedding (FFPE) has been a standard sample preparation method for decades, and archival FFPE samples are still very useful resources. Nonetheless, the use of FFPE samples in cancer genome analysis using next-generation sequencing, which is a powerful technique for the identification of genomic alterations at the nucleotide level, has been challenging due to poor DNA quality and artificial sequence alterations. In this study, we performed whole-exome sequencing of matched frozen samples and FFPE samples of tissues from 4 cancer patients and compared the next-generation sequencing data obtained from these samples. The major differences between data obtained from the 2 types of sample were the shorter insert size and artificial base alterations in the FFPE samples. A high proportion of short inserts in the FFPE samples resulted in overlapping paired reads, which could lead to overestimation of certain variants; >20% of the inserts in the FFPE samples were double sequenced. A large number of soft clipped reads was found in the sequencing data of the FFPE samples, and about 30% of total bases were soft clipped. The artificial base alterations, C>T and G>A, were observed in FFPE samples only, and the alteration rate ranged from 200 to 1,200 per 1M bases when sequencing errors were removed. Although high-confidence mutation calls in the FFPE samples were compatible to that in the frozen samples, caution should be exercised in terms of the artifacts, especially for low-confidence calls. Despite the clearly observed artifacts, archival FFPE samples can be a good resource for discovery or validation of biomarkers in cancer research based on whole-exome sequencing.
Response and tolerability of a 5-day azacytidine schedule in pateints with myelodysplastic syndromes.

16532 Background: Azacitidine (AZA) is a DNA methyltransferase inhibitor with activity in patients with myelodysplastic syndrome (MDS). The current approved schedule of AZA is 75 mg/m2/d for 7 days every 28 days. This schedule is inconvenient for patients and providers because of the need for weekend administration. METHODS The records of 9 patients who received AZA 100 mg/m2/d for 5 days with an anticipated 28 day cycle between 10/04 to 1/06 were reviewed to determine response, duration of response and tolerability. A minimum of two cycles were required for response evaluation (n = 8). All patients were assessed for tolerability. The International Working Group response criteria for MDS was utilized for evaluation. RESULTS Patients had secondary MDS (n = 4), chronic myelomonocytic leukemia (n = 2), refractory anemia (n = 2) and refractory anemia with ringed sideroblasts (n = 1). Of the 8 patients who received at least 2 cycles of therapy, 5 responded: 1 achieved partial response, 3 achieved hematologic improvement in at least one cell line and 1 remained in a stable disease state. The overall response rate was 63%. Average response duration was 6.2 months. The longest response duration was 10 months. Myelosuppression was seen in 2 of the 9 patients treated, one of whom continued treatment with growth factor support; therapy is currently on hold for the other patient. Injection site reaction was seen in 2 patients, resulting in discontinuation of treatment in one. One patient experienced severe malaise after 2 cycles and was given the standard dose for further therapy with a major hematologic improvement. Other isolated events included mouth ulcers, mild nausea and flare of erythema nodosum. Of the 5 responders, 1 later died of disease progression (after 7 cycles), 1 died of a complication of comorbidity (after 5 cycles), 1 is alive with disease progression (after 10 cycles) and 2 are continuing therapy with AZA (after 4 and 5 cycles, respectively). CONCLUSIONS AZA 100 mg/m2/day for 5 days every 28 days seems to be tolerated as well as the 7-day treatment schedule. It also appears to have efficacy similar to the standard dose and schedule. If larger studies are confirmatory, this 5-day schedule may be more convenient for patients and providers. [Table: see text].
Novel approaches for the treatment of psychostimulant and opioid abuse – focus on opioid receptor-based therapies

Introduction: Psychostimulant and opioid addiction are poorly treated. The majority of abstinent users relapse back to drug-taking within a year of abstinence, making ‘anti-relapse’ therapies the focus of much current research. There are two fundamental challenges to developing novel treatments for drug addiction. First, there are three key stimuli that precipitate relapse back to drug-taking: stress, presentation of drug-conditioned cue, taking a small dose of drug. The most successful novel treatment would be effective against all three stimuli. Second, a large number of drug users are poly-drug users: taking more than one drug of abuse at a time. The ideal anti-addiction treatment would, therefore, be effective against all classes of drugs of abuse. Areas covered: In this review, the authors discuss the clinical need and animal models used to uncover potential novel treatments. There is a very broad range of potential treatment approaches and targets currently being examined as potential anti-relapse therapies. These broadly fit into two categories: ‘memory-based’ and ‘receptor-based’ and the authors discuss the key targets here within. Expert opinion: Opioid receptors and ligands have been widely studied, and research into how different opioid subtypes affect behaviours related to addiction (reward, dysphoria, motivation) suggests that they are tractable targets as anti-relapse treatments. Regarding opioid ligands as novel ‘anti-relapse’ medication targets, research suggests that a ‘non-selective’ approach to targeting opioid receptors will be the most effective.