Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of lineage‐specific chimaerism in patients with acute leukaemia and myelodysplastic syndrome after allogeneic stem cell transplantation before and after relapse

Recently, we have shown that patients with acute leukaemias and myelodysplastic syndromes (MDS), who showed increasing mixed chimaerism (MC) upon serial PCR analysis after transplant, have a significantly increased risk of relapse. To determine whether the increasing MC in these patients is caused by the reappearance of normal recipient haematopoiesis or by the reoccurrence of malignant cells, we purified different leucocyte subpopulations and analysed these subfractions with regard to their donor–recipient ratio by a PCR‐based method for the analysis of minisatellite DNA regions. In 14 patients [eight acute lymphoblastic leukaemia (ALL), three acute myelogenous leukaemia (AML) and three MDS] subfractions were analysed when increasing MC was first noted upon serial analysis of the peripheral blood. In seven of these 14 patients (four ALL, two AML and one MDS), subfractions were characterized at the time of frank haematological relapse. In all 14 patients investigated with increasing MC, recipient cells were detected in different mononuclear cell subpopulations. In patients characterized during frank relapse, two distinct distribution patterns were found. Patients who relapsed before day +300 (one ALL, two AML and one MDS) showed recipient‐derived (normal) cells in addition to blast populations in different mononuclear subsets as well as granulocytes. In patients with acute leukaemias who relapsed after day +300 (two ALL and one AML), only leukaemic cells were found that were of recipient origin, whereas all other haematopoietic cell lines were donor derived.
Diversity of bone cell activity as a histomorphometric feature of idiopathic osteoporosis in men

Although osteoporosis in men is an increasing health problem, studies on osteoporosis in males are still scarce. The aim of our study was to determine the characteristics of bone tissue and bone turnover in men with idiopathic osteoporosis. Transiliac crest bone samples were histomorphometrically analyzed after double tetracycline labeling in 32 men aged 37–65 years who were diagnosed with idiopathic osteoporosis by densitometry of the lumbar spine and hip. Bone volume, osteoid surface, osteoblast surface, eroded surface, osteoid thickness, trabecular thickness, trabecular number, trabecular separation, and mineral apposition rate (MAR) were determined in all trabecular bone specimens. Bone volume and structural parameters indicated trabecular bone loss in most patients. Cellular parameters and MAR indicated variations in bone cell actions. No age-related decrease in histomorphometric parameters was found. After the patients were grouped according to MAR values, osteoblast and eroded surfaces were found to be lower in the group with decreased MAR values and elevated in the group of patients with increased MAR parameter. Trabecular thickness was greater in patients with lower than normal MAR, due to reduced resorption and probably loss of very thin trabeculae. Our results suggest that idiopathic osteoporosis in man resembles many characteristics of postmenopausal osteoporosis in women resulting in impaired trabecular structure due to unbalanced cellular activity and bone turnover rate.
Impact of the severity of acute rejection in the early phase after rat lung transplantation on the effectiveness of mycophenolate mofetil to treat chronic allograft rejection.

OBJECTIVES Prevention and treatment of bronchiolitis obliterans (BO) after lung transplantation (LTX) remains disappointing. The high prevalence and the critical detection of early mild acute lung rejection aggravated optimum immunosuppressive therapy. In this study, two hypotheses were investigated: (i) mycophenolate mofetil (MMF) prevented the development of BO after rat LTX. (ii) The effectiveness of MMF depended on the degree of acute rejection (AR) at the time of drug initiation. METHODS A rat model of left lung allo-transplantation (Fisher 344 to Wistar Kyoto) was used to evaluate the basic effect of MMF (30 mg/kg body weight per day) on the development BO. MMF therapy began on Days 0, 7 and 14 after transplantation characterizing different degree of AR of the allograft at the time of drug initiation and ended on Day 60 after transplantation. Non-treated animals were used as controls. Histopathological alterations were analysed according to the International Society for Heart and Lung Transplantation (ISHLT). RESULTS MMF treatment of allografts with high-grade AR (ISHLT-A3-4/B2R; from Day 14 to 60) failed. All animals developed vascular fibrosis and BO. Promising long-term outcome was shown after treatment of mild to moderate acute rejecting of allografts (MMF from Day 7 to 60). The proportion of animals with high grade acute airway inflammation was significantly reduced (33%; P<0.05). All animals were free of BO and chronic vascular alterations (90%). MMF (Day 0-60) significantly reduced the proportion of animals with severe acute vascular rejection and high grade airway inflammation (17 and 0%, respectively; P<0.05, each). None of the animals treated with MMF from Day 0 to 60 developed chronic rejection (CR). CONCLUSIONS MMF significantly reduced AR and CR after rat LTX. However, only allografts with no or mild AR at the time of drug initiation benefited from MMF treatment. In addition, the appearance of early signs of fibroproliferative alterations in the airway structures might prevent a successful long-term outcome.
Cellular metabolism and activation of retinoids: roles of cellular retinoid‐binding proteins 2

Vitamin A and related molecules — the retinoids — play essential roles in vision, growth, reproduction, and cellular differentiation beginning in early development. Retinoic acid, a key regulatory retinoid formed intracellularly through the oxidation of retinol, functions as ligand for a family of nuclear retinoic acid receptors that regulate transcription from target genes. Metabolic events are critical to maintaining physiological concentrations of retinoic acid. In the cytoplasm, retinol, retinaldehyde, and retinoic acid are associated with retinoid‐binding proteins, most of which are ~ 15‐kDa proteins belonging to the fatty acid‐binding protein/cellular retinol‐binding protein family. The ligand binding properties and molecular features of these proteins have been well characterized. Recent experiments have highlighted the importance of the cellular retinoid‐binding proteins in controlling the concentration of free retinoids and in directing protein‐bound retinoids to key enzymes responsible for their metabolism. For example, the cellular retinol‐binding protein, CRBP, has been implicated in retinol uptake, retinol esterification, mobilization of retinyl esters, and the initial oxidation of retinol to retinaldehyde. The ligands bound to other retinoid‐binding proteins have also been shown to be available for enzymatic transformation. The new knowledge of the various ways these cytoplasmic proteins buffer the concentration of ligand, control their distribution, and determine their metabolism by specific enzymes is contributing to an improved understanding of the physiological control of retinoid action. — Ross, A. C. Cellular metabolism and activation of retinoids: roles of cellular retinoid‐binding proteins. FASEB J. 7: 317‐327; 1993.
The therapeutic potential of endothelin-1 receptor antagonists and endothelin-converting enzyme inhibitors on the cardiovascular system

Clinical trials have established bosentan, an orally active non-selective endothelin (ET) receptor antagonist, as a beneficial treatment in pulmonary hypertension. Trials have also shown short-term benefits of bosentan in systemic hypertension and congestive heart failure. However, bosentan also increased plasma levels of ET-1, probably by inhibiting the clearance of ET-1 by endothelin type B (ETB) receptors, and this may mean its effectiveness is reduced with long-term clinical use. Preliminary data suggests that selective endothelin type A (ETA) receptor antagonists (BQ-123, sitaxsentan) may be more beneficial than the non-selective ET receptor antagonists in heart failure, especially when the failure is associated with pulmonary hypertension. Experimental evidence in animal disease models suggests that non-selective ET or selective ETA receptor antagonism may have a role in the treatment of atherosclerosis, restenosis, myocarditis, shock and portal hypertension. In animal models of myocardial infarction and/or reperfusion injury, non-selective ET or selective ETA receptor antagonists have beneficial or detrimental effects depending on the conditions and agents used. Thus clinical trials of the non-selective ET or selective ETA receptor antagonists in these conditions are not presently warranted. Several selective endothelin-converting enzyme inhibitors have been synthesised recently, and these are only beginning to be tested in animal models of cardiovascular disease, and thus the clinical potential of these inhibitors is still to be defined.
Not just pushing and shoving: school bullying among African American adolescents.

BACKGROUND The primary purpose of this study was to examine the prevalence of bullying among a sample of African American adolescents and the risk factors associated with odds that a student engages in bullying behavior. METHODS Using a self-report school-based survey, 1542 African American adolescents from a single school district (grades 5-12) living in a midsized, Southern metropolitan region, were asked questions regarding bullying behavior and risk behaviors. A response rate of nearly 80% was obtained. RESULTS Our results indicate that bullying behavior was higher among this group of African American adolescents than reported for other general student populations (8-12%). In addition, age, family violence, negative peer relationships, and behavioral risks all contributed to increased odds of students reporting bullying behavior. CONCLUSIONS Our findings underscore the importance of intervention at an early age. Whether the intervention is in a formal or nonformal setting, specialists along with teachers, parents, and siblings need to begin a multipronged approach (data collection, training/education of school personnel, curriculum development, etc) to address the causes and consequences of bullying among adolescents.
On the Effect of Gaussian Imperfect Channel Estimations on the Performance of Space Modulation Techniques

Space modulation techniques, such as spatial modulation (SM) and space shift keying (SSK), are efficient low complexity implementation of multiple input multiple output (MIMO) systems. In such techniques, a single transmit-antenna is activated during each time instant and the activated antenna index is used to convey information. Due to the novel method of conveying information, a major criticism arises on the practicality of such techniques in the presence of real-time imperfections such as channel estimation errors. Therefore, the aim of this paper is to shed light on this issue. The performance of such systems are analyzed in the presence of Gaussian imperfect channel estimations. More specifically, the performance of SSK system consisting of Nt transmit and Nr receive antennas with maximum-likelihood (ML) detection and imperfect channel state information (CSI) at the receiver is studied. The exact average bit error probability (ABEP) over Rayleigh fading channels is obtained in closed-form for Nt = 2 and arbitrary Nr; while union upper bound is used to compute the ABEP when Nt >; 2 and arbitrary Nr. Furthermore, simple and general asymptotic expression for the ABEP is derived and analyzed. Besides, the effect of imperfect CSI on the performance of SM, Alamouti and SSK schemes considering different number of channel estimation pilots are studied and compared via numerical Monte Carlo simulations. It is shown that, on the contrary to the raised criticism, space modulation techniques are more robust to channel estimation errors than Alamouti since the probability of error is determined by the differences between channels associated with the different transmit antennas rather than the actual channel realization.
Attitudes and Concerns of Diabetic Patients towards Bariatric Surgery as Treatment of Diabetes.

INTRODUCTION Bariatric surgery is increasingly recognised as an effective treatment for type 2 diabetes that significantly improves glycaemic control, even achieving remission. This study examined perceptions and concerns of diabetic patients towards bariatric surgery as a treatment option for diabetes. MATERIALS AND METHODS A total of 150 patients were recruited from a specialised diabetic outpatient clinic and completed a questionnaire (items were rated on a Likert scale from slightly important [lowest score of 1] to extremely important [maximum score of 5]). Logistic regression was performed to identify factors influencing decision for surgery. RESULTS The 74 males and 76 females had mean age of 50 (range 20 to 78) and body mass index (BMI) of 29.6 kg/m2 (range 18.1 to 51); 61% considered surgery favourably. Predictive factors for interest in surgery: higher educational levels (OR = 2.3; 95% CI, 1.2 to 4.4), duration of diabetes (OR = 0.4; 95% CI, 0.2 to 1.0) and use of insulin (OR = 2.1; 95% CI, 1.1 to 4.1). Reasons for surgery: desire for remission (Likert scale 4.7 ± 0.7), to prevent complications (Likert scale 4.5 ± 0.9) and to reduce medications (Likert scale 4.3 ± 1.1). For those not keen on surgery, main reasons were fear of surgery (Likert scale 4 ± 1.5) and satisfaction with current therapy (Likert scale 3.7 ± 1.6). CONCLUSION Many diabetic patients would consider surgery as an option to improve their metabolic disorder (greater interest in patients with higher educational levels, currently using insulin and with shorter duration of diabetes). Surgical complications, length of recovery and duration of benefits were the main concerns.
The "bystander effect": tumor regression when a fraction of the tumor mass is genetically modified.

Tumor cells expressing the herpes simplex virus thymidine kinase (HSV-TK) gene are sensitive to the drug ganciclovir (GCV). We demonstrate here that HSV-TK-positive cells exposed to GCV were lethal to HSV-TK-negative cells as a result of a "bystander effect. " HSV-TK-negative cells were killed in vitro when the population of cultured cells contained only 10% HSV-TK-positive cells. The mechanism of this "bystander effect" on HSV-TK-negative cells appeared to be related to the process of apoptotic cell death when HSV-TK-positive cells were exposed to GCV. Flow cytometric and electron microscopic analyses suggested that apoptotic vesicles generated from the dying gene-modified cells were phagocytized by nearby, unmodified tumor cells. Prevention of apoptotic vesicle transfer prevented the bystander effect. The toxic effect of HSV-TK-positive cells on HSV-TK-negative cells was reproduced in an in vivo model. A mixed population of tumor cells consisting of HSV-TK-positive and HSV-TK-negative cells was inoculated s.c. into mice. Regression of the tumor mass occurred when the inoculum consisted of as few as 10% HSV-TK-expressing tumor cells. The bystander effect was also demonstrated in i.p. tumor studies. Initial experiments demonstrated that prolonged survival (> 70 days) occurred when a mixture containing 50% HSV-TK-positive and 50% HSV-TK-negative cells was injected i.p. followed by GCV treatment. Further, survival was prolonged for mice with a preexisting HSV-TK-negative i.p. tumor burden by injecting HSV-TK-positive cells and GCV. These results suggest that genetic modification of tumor cells may be useful for developing cancer therapies.
Effects of NMDA receptor antagonists with different subtype selectivities on retinal spreading depression

BACKGROUND AND PURPOSE Spreading depression (SD) is a local, temporary disruption of cellular ionic homeostasis that propagates slowly across the cerebral cortex and other neural tissues such as the retina. Spreading depolarization associated with SD occurs in different types of stroke, and this phenomenon correlates also with the initiation of classical migraine aura. The aim of this study was to investigate how NMDA receptor antagonists with different subtype selectivity alter SD.
Morphogenesis of the turtle shell: the development of a novel structure in tetrapod evolution

SUMMARY The turtle shell is an evolutionary novelty that is synapomorphic for chelonians. The carapace is initiated by the entrapment of the ribs by the carapacial ridge (CR), a lateral bulge of the dorsal ectoderm and dermal mesoderm. The mechanisms by which the CR is initiated, the ribs entrapped and the dorsal dermis ossified, remains unknown. Similarly, the formation of the plastron remains unexplained. Here, we present a series of anatomical investigations into plastron and carapace formation in the red‐eared slider, Trachemys scripta, and the snapping turtle, Chelydra serpentina. We document the entrapment of the ribs by the CR and the formation of the plastron and carapacial bones by intramembranous ossification. We note the formation of the ossification centers around each rib, which suggest that the rib is organizing dermal ossification by secreting paracrine factors. The nuchal ossification center is complex and appears to involve multiple bone‐forming regions. Individual ossification centers at the periphery of the carapace form the peripheral and pygial bones. The intramembranous ossification of the plastron proceeds from nine distinct ossification centers, and there appear to be interactions between the spicules of apposing centers as they draw near each other.
Multiparametric Bioinformatics Distinguish the CD4/CD8 Ratio as a Suitable Laboratory Predictor of Combined T Cell Pathogenesis in HIV Infection

HIV disease progression is characterized by numerous pathological changes of the cellular immune system. Still, the CD4 cell count and viral load represent the laboratory parameters that are most commonly used in the clinic to determine the disease progression. In this study, we conducted an interdisciplinary investigation to determine which laboratory parameters (viral load, CD4 count, CD8 count, CD4 %, CD8 %, CD4/CD8) are most strongly associated with pathological changes of the immune system. Multiparametric flow cytometry was used to assess markers of CD4+ and CD8+ T cell activation (CD38, HLA-DR), exhaustion (PD-1, Tim-3), senescence (CD28, CD57), and memory differentiation (CD45RO, CD27) in a cohort of 47 untreated HIV-infected individuals. Using bioinformatical methods, we identified 139 unique populations, representing the “combined T cell pathogenesis,” which significantly differed between the HIV-infected individuals and healthy control subjects. CD38, HLA-DR, and PD-1 were particularly expressed within these unique T cell populations. The CD4/CD8 ratio was correlated with more pathological T cell populations (n = 10) and had a significantly higher average correlation coefficient than any other laboratory parameters. We also reduced the dimensionalities of the 139-unique populations by Z-transformations and principal component analysis, which still identified the CD4/CD8 ratio as the preeminent surrogate of combined T cell pathogenesis. Importantly, the CD4/CD8 ratio at baseline was shown to be significantly associated with CD4 recovery 2 y after therapy initiation. These results indicate that the CD4/CD8 ratio would be a suitable laboratory predictor in future clinical and therapeutic settings to monitor pathological T cell events in HIV infection.
Candiduria in catheterized intensive care unit patients: emerging microbiological trends.

OBJECTIVES Urinary tract infection (UTI) as a result of Candida spp. is becoming increasingly common in hospitalized setting. Clinicians face dilemma in differentiating colonization from true infection and whether to treat candiduria or not. The objective of the present study was to look into the significance of candiduria in catheterized patients admitted in the ICUs and perform microbiological characterization of yeasts to guide treatment protocols. MATERIALS AND METHODS One hundred consecutive isolates of Candida spp. from the urine sample of 70 catheterized patients admitted in the ICU were collected and stocked for further characterization. A proforma was maintained containing demographic and clinical details. Blood cultures were obtained from all these 70 patients and processed. Species identification of yeasts was done on VITEK. RESULTS Candiduria was more common at extremes of age. The mean duration of catheter days was 11.1 ± 6 days. Other associated risk factors such as diabetes mellitus and antibiotic usage were seen in 38% and 100% of our study group. Concomitant candidemia was seen in 4.3% of cases. Non-albicans Candida spp. (71.4%) emerged as the predominant pathogen causing nosocomial UTI. CONCLUSION The present study reiterates the presence of candiduria in catheterized patients, especially in the presence of diabetes and antibiotic usage. Non-albicans Candida spp. are replacing Candida albicans as the predominant pathogen for nosocomial UTI. Hence, we believe that surveillance for nosocomial candiduria should be carried out in hospitalized patients.
Mechanical properties of various suture materials and placement patterns tested with surrogate in vitro model constructs simulating laryngeal advancement tie-forward procedures in horses.

OBJECTIVE To compare the mechanical properties of laryngeal tie-forward (LTF) surrogate constructs prepared with steel fixtures and No. 5 braided polyester or braided polyethylene by use of a standard or a modified suture placement technique. SAMPLE 32 LTF surrogate constructs. PROCEDURES Surrogate constructs were prepared with steel fixtures and sutures (polyester or polyethylene) by use of a standard or modified suture placement technique. Constructs underwent single-load-to-failure testing. Maximal load at failure, elongation at failure, stiffness, and suture breakage sites were compared among constructs prepared with polyester sutures by means of the standard (n = 10) or modified (10) technique and those prepared with polyethylene sutures with the standard (6) or modified (6) technique. RESULTS Polyethylene suture constructs had higher stiffness, higher load at failure, and lower elongation at failure than did polyester suture constructs. Constructs prepared with the modified technique had higher load at failure than did those prepared with the standard technique for both suture materials. All sutures broke at the knot in constructs prepared with the standard technique. Sutures broke at a location away from the knot in 13 of 16 constructs prepared with the modified technique (3 such constructs with polyethylene sutures broke at the knot). CONCLUSIONS AND CLINICAL RELEVANCE Results suggested LTF surrogate constructs prepared with polyethylene sutures or the modified technique were stronger than those prepared with polyester sutures or the standard technique.