Miracle-dz/UniFAR-FTUs huggingface dataset:
Optimizing imaging parameters for the separation of multiple labels in a fluorescence image

A theoretical analysis is presented on how to separate the contributions from individual, simultaneously present fluorophores in a spectrally resolved image. Equations are derived that allow the calculation of the signal‐to‐noise ratio of the estimates for such contributions, given the spectral information on the individual fluorophores, the excitation wavelengths and intensities, and the number and widths of the spectral detection channels. We then ask how such imaging parameters have to be chosen for optimal fluorophore separation. We optimize the signal‐to‐noise ratio or optimize a newly defined ‘figure of merit’, which is a measure of efficiency in the use of emitted photons. The influence of photobleaching on the resolution and on the choice of imaging parameters is discussed, as well as the additional resolution gained by including fluorescence lifetime information. A surprisingly small number of spectral channels are required for an almost optimal resolution, if the borders of these channels are optimally selected. The detailed consideration of photobleaching is found to be essential, whenever there is significant bleaching. Consideration of fluorescence lifetime information (in addition to spectral information) improves results, particularly when lifetimes differ by more than a factor of two.
How clinicians talk about the application of goal planning to rehabilitation for people with brain injury–variable interpretations of value and purpose

Primary objective: To explore the way clinicians talk about the value and purpose of goal planning in rehabilitation for people with brain injury Research design: Grounded theory Methods and procedures: Nine clinicians from a range of professional backgrounds were interviewed. The interview data were analysed using the constant comparative method of grounded theory. Main outcomes and results: While the clinicians considered goal planning important, the expressed reasons for valuing goal planning were at times unclear. The term ‘goal’ referred to not one but many concepts within the rehabilitation environment; goal planning was used to serve a range of different purposes. Different reasons for undertaking goal planning were interrelated but at times conflicted, potentially creating tensions within the rehabilitation environment. Conclusions: Discussions around goal planning terminology should progress from service-level agreements towards more evidenced-based international consensus. Individual services might benefit from discussing and agreeing on the purpose for goal planning in their work.
Comparison of visual acuity, refractive outcomes, and satisfaction between LASIK performed with a microkeratome and a femto laser

Purpose To compare refractive outcomes, visual acuities, and satisfaction of patients between those treated with laser-assisted in situ keratomileusis (LASIK) using a Hansatome microkeratome (HM) and femto-assisted laser (FAL). Methods This was a retrospective analysis of 1,366 eyes in 687 patients who underwent LASIK with an HM (n=1,137) and an FAL (n=229) at the two centers of Hashmanis Hospital, Karachi, Pakistan. Refractive outcomes, including sphere, cylinder, and spherical equivalent in diopters (D), and visual acuities were assessed both preoperatively and at 1 month follow-up. Patient satisfaction was gauged by contacting the patient at the time of chart review. Results The postoperative median sphere, cylinder, and spherical equivalent values for those treated with FAL were 0.3±0.7 (−5.5–1.8), −0.5±0.6 (−5.0–1.0), and 0.0±0.7 (−6.0–1.6), respectively. For the HM arm, they were 0.0±1.28 (−10.8–6.8), −0.5±0.5 (−4.5–1.5), and −0.3±1.3 (−11.6–6.8), respectively. All preoperative values were statistically insignificant between the groups, while postoperative values were significant with P-values <0.001. Predictability and efficacy index was higher for the FAL (92.1%, 1.00) than the HM group (82.2%, 0.84). Similarly, patient satisfaction was slightly higher for those treated with FAL (93.3%) than HM (91.4%). Conclusion Our large retrospective analysis of eyes that have undergone LASIK using HM and FAL shows superior refractive outcomes in the latter, with special regard to procedural efficacy and predictability.
IFN-gamma priming of monocytes enhances LPS-induced TNF production by augmenting both transcription and MRNA stability.

The induction of cytokine expression in monocytes/macrophages by bacterial endotoxin or lipopolysaccharide is a critical, highly regulated host defence response. The augmentation of LPS responses by interferon gamma (IFN-gamma), referred to as priming, is well established. However, the mechanism(s) by which priming occurs is poorly defined. Using tumour necrosis factor (TNF) induction as a model, experiments were designed to analyse in detail the priming effect on the LPS response in human monocytes. Priming by IFN-gamma was primarily manifested at the level of TNF mRNA accumulation. IFN-gamma pre-treatment affected the magnitude rather than the sensitivity of the LPS response. Priming occurred after several hours of treatment, and the primed state was induced by either IFN-gamma or GM-CSF, but not M-CSF. Primed monocytes transcribed TNF mRNA at a higher rate than freshly isolated monocytes upon activation with LPS. The increased transcriptional rate correlated with a marked increase in nuclear factor-kappa B activity in these cells as determined by electrophoretic mobility shift assay using a consensus NF-kappa B oligonucleotide. An additional significant finding was than TNF mRNA induced in primed cells was much more stable than in unprimed cells (T1/2 increased 6-8-fold). Consistent with the increased mRNA stability, the duration of mRNA accumulation was longer following LPS stimulation in primed monocytes, in addition to being of greater magnitude. Finally, primed and unprimed cells possessed a differential sensitivity to the kinase inhibitor H-89. H-89 substantially suppressed LPS-induced TNF mRNA accumulation in unprimed cells, but had no effect on primed monocytes following LPS stimulation. (ABSTRACT TRUNCATED AT 250 WORDS)
Subcutaneous interleukin-2 and interferon alfa administration in patients with metastatic renal cell carcinoma: final results of SCAPP III, a large, multicenter, phase II, nonrandomized study with sequential analysis design--the Subcutaneous Administration Propeukin Program Cooperative Group.

PURPOSE This outpatient multicenter trial tested the hypothesis that subcutaneous administration of an interleukin-2 (IL-2)/interferon alfa (IFN alpha) combination produces a response rate greater than 20% in patients with renal cell carcinoma (RCC). PATIENTS AND METHODS Patients with metastatic RCC received a 12-week induction treatment with subcutaneous IL-2 (5 days/wk, 9 and 18 million U/d)/IFN alpha (3 days/wk, 6 million U/d). After evaluation, patients with objective response or stable disease were randomly assigned to maintenance treatment or short consolidation treatment. RESULTS Lack of benefit was shown at the 12th sequential analysis, and the trial was closed. At the end of the induction period, 26 (21%) of 122 patients had objective responses (including six complete responses). Thirty-three patients (27%) developed severe toxicity requiring dose reductions, delayed treatment, or treatment termination. Survival rates at one, two, and four years were 63%, 38%, and 17%, respectively. Three-year survival was 20% in patients with two poor prognosis factors and 37% in patients with one or no poor prognosis factors (P =.016). Three-year survival was significantly better (P < 10-3) in patients with erythrocyte sedimentation rate less than 35 mm (43%) compared with those with 1-hour sedimentation rate greater than 35 mm (19%). CONCLUSION This study confirms the importance of prognostic factors when initiating cytokine immunotherapy in patients with metastatic RCC and underlines the prognostic value of erythrocyte sedimentation rate before treatment initiation. Nonetheless, this subcutaneous IL-2/IFN alpha combination does not improve response rate or survival compared with subcutaneous IL-2 alone, although a definitive conclusion cannot be drawn in the absence of a randomized study comparing the two treatments.
Identification of a distinctive p‐glycoprotein‐mediated resistance phenotype in human ovarian carcinoma cells after their in vitro exposure to fractionated x‐irradiation

Background. Clinical drug resistance is recognized in patients previously treated with radiotherapy and after chemotherapy. In vitro exposure of mammalian tumor cells to fractionated X‐irradiation also resulted in the expression of drug resistance. Analysis of the resistance phenotype of irradiated Chinese hamster ovary sublines revealed P‐glycoprotein overexpression, without any concomitant increase in P‐glycoprotein messenger RNA, under posttranslational regulation. This study aimed to determine whether this distinctive resistance phenotype could also be identified in irradiated human tumor cells.
Gr-1+ Myeloid Cells Lacking T Cell Protein Tyrosine Phosphatase Inhibit Lymphocyte Proliferation by an IFN-γ- and Nitric Oxide-Dependent Mechanism1

The T cell protein tyrosine phosphatase is involved in the immune system regulation, as evidenced by defective function and development of several hemopoietic cell populations in T cell protein tyrosine phosphatase (TC-PTP)-deficient mice. In particular, B and T cell proliferation is greatly inhibited when total splenocytes are stimulated by LPS or anti-CD3 mAb. To define the functional defect of TC-PTP−/− lymphocytes, we isolated T and B cells from the spleen of TC-PTP−/− mice. We show that the proliferative response of lymphocytes was greatly increased when cultured as a purified population, indicating that an inhibitory population is present in TC-PTP−/− spleen. However, TC-PTP−/− lymphocytes have a 2- to 3-fold lower proliferation rate compared with TC-PTP+/+ lymphocytes, suggesting that, as shown previously in embryonic fibroblasts, TC-PTP is involved in the control of cell cycle in lymphocytes. We have characterized phenotypically and functionally the inhibitory population present in the spleen of TC-PTP−/− mice. We show that a Gr-1+-enriched cell population isolated from TC-PTP−/− mice suppresses the CD3-induced proliferation of T cells in coculture in vitro. The specific inhibition of NO synthesis with NG-monomethyl-l-arginine.monoacetate restored splenocyte responses, and there is a strict correlation between NO levels and the degree of suppression. Neutralization of IFN-γ with specific mAb almost completely abolished the inhibitory activity of Gr-1+ cells and concomitantly high levels of NO secretion. Moreover, inhibition of lymphocyte proliferative responses required cell-cell contact to achieve sufficient levels of NO. These findings demonstrate an important function of TC-PTP in the induction of the NO pathway that mediates inhibition of T cell proliferation.
Idiotype‐induced T cell stimulation requires antigen presentation in association with HLA‐DR molecules

An important and yet unresolved question concerns the mode of T cell recognition of idiotypic epitopes on immunoglobulin molecules in humans. Results from murine and human studies show that some idiotype‐specific T cells recognize conformational epitopes on immunoglobulin, and such T cells are not MHC‐restricted. In the present study T cell stimulation induced by idiotypic determinants on the autologous monoclonal IgG (M‐components) from patients with monoclonal gammopathies was studied. In parallel, T cell stimulation in response to a conventional antigen, purified protein derivative, was also examined. It is shown that, as with conventional antigen, idiotype‐induced T cell stimulation requires the presence of antigen‐presenting cells (APC; monocytes and/or B cells), and is MHC class II (DR)‐restricted. B cells, but not monocytes, can present idiotypic determinants to T cells at very low antigen concentrations, while monocytes do so only when antigen is present at high concentrations. Antigen processing and presentation is abrogated by treatment of APC with chloroquine. In conclusion, our study demonstrates that human idiotype‐specific T cells recognize processed idiotypic determinants presented by MHC class II (HLA‐DR) molecules on APC, and that B cells require about 1000‐fold less antigen than monocytes.
Relationship between raised intraocular pressure and ischemia-modified albumin in serum and humor aqueous: a pilot study in rabbits.

AIM We evaluated the relationship between increased intraocular pressure (IOP), ischemia-modified albumin levels in serum (IMA-s) and in humor aqueous (IMA-HA) in rabbits. METHODS Twenty-five albino New Zealand rabbits weighing between 2.0 and 2.8 kg were used in this pilot study. With permission from Canakkale Onsekiz Mart University Animal Ethics Committee, the IOP of both eyes of each rabbit were recorded with a Tonopen (Tono-Pen XL, Reichart Inc., Depew, NY, USA) after the application of topical proparacaine 0.5% HCl anesthesia. Blood (4 mL) was collected from the marginal ear vein and an intracameral injection of 2.3 mg/mL sodium hyaluronate and subconjunctival dexamethasone was given in the right eye. Anterior chamber aqueous fluid was obtained using a limbal approach with a 27 gauge needle from both eyes. The left eyes were used as controls. IOP was measured on the 1(st), 3(rd) and 10(th) day after the initial injection, with Tonopen, IMA-s levels and IMA-HA examined simultaneously. RESULTS Before the injections, IOP was 11.4±3.0 mm Hg in the right eye and 11.3±3.1 mm Hg in the left eye (P>0.05). There was a statistically significant difference between IMA-s levels before the IOP increase (IMA-s0) and IMA-s levels on the 1(st) and 3(rd) days after the increase in IOP (P=0.012 and P=0.01, respectively). No difference was observed between IMA-s0 and serum IMA levels on the 10(th) day (IMA-s10) after IOP increase (P=0.989). IMA-HA in the right eye in the first day after the injection was positively correlated with IOP (r=0.748; P=0.02). No other correlation is found between any other parameter with IMA-HA levels at any test time. A statistically significant positive correlation was observed between IMA-s values and IOP on the 1(st) and 3(rd) days (r=0.398, P=0.04 and r=0.382, P=0.04, respectively). There was no correlation between IMA-s levels and increased IOP on the 10(th) day after IOP increase (r=0.026, P=0.902). CONCLUSION IMA may be an important indicator of acute damage caused by diseases involving ischemic damage to the eye, especially in case of increased intraocular pressure.
An Absence of Tinnitus

We present and discuss a case of lifelong tinnitus in an otolaryngologist (L.D.L.) followed by complete elimination of the tinnitus as a result of a cerebral vascular accident located in the left corona radiata. Pre- and post-CVA audiograms showed no change in hearing. A magnetic resonance imaging study of the brain documents the size and location of the lesion. Discussion looks at recent studies of the central nervous system showing evidence of increased activity related to tinnitus. Our assessment of the lesion and the resulting loss of tinnitus can be explained by the neurophysiological model of tinnitus, which includes plasticity of the central nervous system.
Impalpable pulmonary nodules with ground-glass opacity: Success for making pathologic sections with preoperative marking by lipiodol.

BACKGROUND The developments in high-resolution CT scanning have increased the chance of detecting small bronchioloalveolar carcinoma (BAC) or atypical adenomatous hyperplasia (AAH) that appears as a ground-glass opacity (GGO). However, these lesions are not only difficult to localize during surgery, but they are also hard to make pathologic sections of because they are usually impalpable. Here, we report a method of making pathologic sections for impalpable GGO lesions. METHODS Twenty-nine impalpable GGO lesions < 1 cm in size were marked by 0.4 to 0.5 mL of lipiodol under CT scan before surgery. The lesions were resected under C-arm fluoroscopy. The radiopaque areas marked by lipiodol within the formalin-fixed specimens were cut serially under conventional fluoroscopy for pathologic examinations. RESULTS The mean (+/- SD) size of the lesions was 0.5 +/- 0.2 cm (range, 0.2 to 1 cm), and the mean depth from the pleural surface was 1.6 +/- 1.4 cm (range, 0.2 to 6 cm). The mean number of sections submitted for pathologic examinations was 2.3 +/- 1.7 per lesion (range, 1 to 7 per lesion). While 11 of the 29 lesions (38%) were invisible even on the cut surface of the specimens, all were demonstrated in hematoxylin-eosin sections. The pathologic diagnosis was BAC in 17 lesions, AAH in 10 lesions, and organized pneumonia in 2 lesions. The use of lipiodol did not affect the pathologic findings. CONCLUSIONS The use of fluoroscopy to cut sections from resected specimens after preoperative marking with lipiodol was useful for making pathologic sections of impalpable GGOs < 1 cm in size.
Penetration of projectiles into granular targets

Energetic collisions of subatomic particles with fixed or moving targets have been very valuable to penetrate into the mysteries of nature. But the mysteries are quite intriguing when projectiles and targets are macroscopically immense. We know that countless debris wandering in space impacted (and still do) large asteroids, moons and planets; and that millions of craters on their surfaces are traces of such collisions. By classifying and studying the morphology of such craters, geologists and astrophysicists obtain important clues to understand the origin and evolution of the Solar System. This review surveys knowledge about crater phenomena in the planetary science context, avoiding detailed descriptions already found in excellent papers on the subject. Then, it examines the most important results reported in the literature related to impact and penetration phenomena in granular targets obtained by doing simple experiments. The main goal is to discern whether both schools, one that takes into account the right ingredients (planetary bodies and very high energies) but cannot physically reproduce the collisions, and the other that easily carries out the collisions but uses laboratory ingredients (small projectiles and low energies), can arrive at a synergistic intersection point.
Pathogenic bacteria associated with oysters (Crassostrea brasiliana) and estuarine water along the south coast of Brazil

Abstract Oysters and estuarine water samples were collected monthly, from June 1998 to March 1999, in the Cananéia estuary, on the south coast of São Paulo, Brazil, and analyzed for bacterial hazards with and without depuration in filtered estuarine water. Aeromonas spp. , Plesiomonas shigelloides, Vibrio cholerae O1, Vibrio parahaemolyticus, and Vibrio vulnificus were counted in oyster samples using the most probable number (MPN) and their presence verified in the surrounding estuarine water samples. The presence of Salmonella, Shigella, Escherichia coli O157:H7, and fecal coliforms counts were determined in oysters and in water samples too. Sixty percent of water samples contained fecal coliforms ranging from <1 to >200 CFU/100 ml and 100%, 30%, 20% and 10% were positive for V. parahaemolyticus, Salmonella, Aeromonas, and V. vulnificus in 5 l of water samples, respectively. In oyster samples, the fecal coliforms concentration ranged from <3.0 to ≥2.4 × 103 MPN/g in 40% of untreated and from <3.0 to 1.1 × 103 MPN/g in 40% of treated samples. Vibrio parahaemolyticus Kanagawa-negative was detected in all oyster samples and their concentration varied from 3.6 to ≥2.4 × 103 MPN/g. For the untreated oyster samples 80%, 70%, and 10% were positive for V. vulnificus (<3 – 11.0 MPN/g), Aeromonas (<3 – 15 MPN/g), and Salmonella (presence in 25 g), respectively. However, for treated oyster samples 60%, 30%, and 0% of them contained the same bacteria, respectively. Escherichia coli O157:H7, Shigella spp. , P. shigelloides, and V. cholerae O1 were not detected in any of the samples. Fecal indicators did not correlate with Vibrio presence (p>0.05), although the isolation of Aeromonas species had a positive correlation (p = 0.017). The results showed no correlation between temperature, salinity, and bacteria (p > 0.05). The comparison between bacterial concentration in treated and untreated oyster samples, showed that only Aeromonas was higher in untreated oyster samples (p = 0.039). This study contributes toward creating a more global understanding of food-borne bacterial pathogens. The presence and concentration of viable bacterial hazards in oysters and water surrounding areas was determined for the first time on the south coast of São Paulo and it helps to define better the true microbial hazard in the aquatic environment and oysters.
Characterisation of Candida within the Mycobiome/Microbiome of the Lower Respiratory Tract of ICU Patients

Whether the presence of Candida spp. in lower respiratory tract (LRT) secretions is a marker of underlying disease, intensive care unit (ICU) treatment and antibiotic therapy or contributes to poor clinical outcome is unclear. We investigated healthy controls, patients with proposed risk factors for Candida growth in LRT (antibiotic therapy, ICU treatment with and without antibiotic therapy), ICU patients with pneumonia and antibiotic therapy and candidemic patients (for comparison of truly invasive and colonizing Candida spp.). Fungal patterns were determined by conventional culture based microbiology combined with molecular approaches (next generation sequencing, multilocus sequence typing) for description of fungal and concommitant bacterial microbiota in LRT, and host and fungal biomarkes were investigated. Admission to and treatment on ICUs shifted LRT fungal microbiota to Candida spp. dominated fungal profiles but antibiotic therapy did not. Compared to controls, Candida was part of fungal microbiota in LRT of ICU patients without pneumonia with and without antibiotic therapy (63% and 50% of total fungal genera) and of ICU patients with pneumonia with antibiotic therapy (73%) (p<0.05). No case of invasive candidiasis originating from Candida in the LRT was detected. There was no common bacterial microbiota profile associated or dissociated with Candida spp. in LRT. Colonizing and invasive Candida strains (from candidemic patients) did not match to certain clades withdrawing the presence of a particular pathogenic and invasive clade. The presence of Candida spp. in the LRT rather reflected rapidly occurring LRT dysbiosis driven by ICU related factors than was associated with invasive candidiasis.
Expression Profile of Extracellular Matrix and Adhesion Molecules in the Development of Endometriosis in a Mouse Model

Ectopic endometrial tissue induces various reactions in surrounding tissues, such as the surface of the ovary and peritoneal cavity, leading to endometriosis. The aim of this study is to investigate the expression profile of extracellular matrix (ECM) and adhesion molecules in the early steps of development of experimental mouse endometriosis, specifically in peritoneum adjacent to endometrium transplants attached via autotransplantation. The endometriosis model was induced by autotransplantation of endometrium to peritoneal tissue. Peritoneal tissues adjacent to the transplant were obtained at 1, 4, and 7 days posttransplantation. The results showed that messenger RNA expression levels of most of the integrins, collagens, and other ECM reached a peak at 7 days posttransplantation. Uniquely, Lamc2 was significantly increased to its maximum level within 24 hours posttransplantation and may be strongly associated with initiation of the development of endometriosis. These data will be helpful in further investigations of the treatment of endometriosis.