Miracle-dz/UniFAR-FTUs huggingface dataset:
Cloretazine (VNP40101M), a novel sulfonylhydrazine alkylating agent, in patients age 60 years or older with previously untreated acute myeloid leukemia.

PURPOSE Cloretazine (VNP40101M) is a sulfonylhydrazine alkylating agent with significant antileukemia activity. A multicenter phase II study of cloretazine was conducted in patients 60 years of age or older with previously untreated acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS). PATIENTS AND METHODS Cloretazine 600 mg/m2 was administered as a single intravenous infusion. Patients were stratified by age, performance score, cytogenetic risk category, type of AML, and comorbidity. RESULTS One hundred four patients, median age 72 years (range, 60 to 84 years), were treated on study. Performance status was 2 in 31 patients (30%) and no patient had a favorable karyotype. Forty-seven patients (45%) had cardiac disease, 25 patients (24%) had hepatic disease, and 19 patients (18%) had pulmonary disease, defined as per the Hematopoietic Cell Transplantation-Specific Comorbidity Index, at study entry. The overall response rate was 32%, with 29 patients (28%) achieving complete response (CR) and four patients (4%) achieving CR with incomplete platelet recovery. Response rates in 44 de novo AML patients, 45 secondary AML patients, and 15 high-risk MDS patients were 50%, 11%, and 40%, respectively. Response by cytogenetic risk category was 39% in 56 patients with intermediate cytogenetic risk and 24% in 46 patients with unfavorable cytogenetic risk. Nineteen (18%) patients died within 30 days of receiving cloretazine therapy. Median overall survival was 94 days, with a 1-year survival of 14%; the median duration of survival was 147 days, with a 1-year survival of 28% for those who achieved CR. CONCLUSION Cloretazine has significant activity and modest extramedullary toxicity in elderly patients with AML or high-risk MDS. Response rates remain consistent despite increasing age and comorbidity.
Function of bacterial community dynamics in the formation of cadaveric semiochemicals during in situ carcass decomposition

The decomposition of dead mammalian tissue involves a complex temporal succession of epinecrotic bacteria. Microbial activity may release different cadaveric volatile organic compounds which in turn attract other key players of carcass decomposition such as scavenger insects. To elucidate the dynamics and potential functions of epinecrotic bacteria on carcasses, we monitored bacterial communities developing on still-born piglets incubated in different forest ecosystems by combining high-throughput Illumina 16S rRNA sequencing with gas chromatography-mass spectrometry of volatiles. Our results show that the community structure of epinecrotic bacteria and the types of cadaveric volatile compounds released over the time course of decomposition are driven by deterministic rather than stochastic processes. Individual cadaveric volatile organic compounds were correlated with specific taxa during the first stages of decomposition which are dominated by bacteria. Through best-fitting multiple linear regression models, the synthesis of acetic acid, indole and phenol could be linked to the activity of Enterobacteriaceae, Tissierellaceae and Xanthomonadaceae, respectively. These conclusions are also commensurate with the metabolism described for the dominant taxa identified for these families. The predictable nature of in situ synthesis of cadaveric volatile organic compounds by epinecrotic bacteria provides a new basis for future chemical ecology and forensic studies.
Liver pathology and hepatocarcinogenesis in a long‐term mouse model of erythropoietic protoporphyria

Erythropoietic protoporphyria (EPP) is an inherited disease of haem synthesis caused by a mutation in one of the alleles of the enzyme ferrochelatase. This mutation leads to partial deficiency of the enzyme, resulting in increased concentrations of protoporphyrin (PP) in blood, liver, and faeces. Five to ten per cent of patients with EPP develop severe liver disease characterized by the presence of PP deposits. This study used histochemistry and immunohistochemistry to investigate the histopathological features present in the livers of 44 mice with a heterozygous or homozygous point mutation in the ferrochelatase gene (fch/+ and fch/fch mice, respectively). Some fch/+ mouse livers showed mixed steatosis and large cell dysplasia. The livers of fch/fch mice showed periportal or septal fibrosis accompanied by an atypical ductular reaction. These findings suggest that the obstruction and damage of a proportion of large and small bile ducts by PP deposits cause an accumulation of PP in the parenchyma, which leads to damage and loss of hepatocytes due to the toxic effects of PP. The classical stages of hepatocarcinogenesis were observed and hepatic progenitor cells appear to be involved in this process. PP acts as the promoting agent and is probably also the initiating agent. Copyright © 2002 John Wiley & Sons, Ltd.
THz reflection imaging for internal structure analysis of artworks

Terahertz (THz) spectroscopy and THz imaging techniques are expected to have great potential for the noninvasive analysis of works of art. THz waves can penetrate opaque materials and create three-dimensional maps of materials by spectroscopic imaging non-destructively. Satisfactory results using model samples have been obtained by many institutions. In particular, the imaging by using THz pulses in reflection mode make it possible to observe internal structure of works of art non-intensively. The structure reveals the technique which interests art historians as well as conservators. Moreover, detecting hidden defects, such as separation between painting and preparation layers of paintings, helps conservators to plan restoration process.
Induction of anti-recombinant human granulocyte-macrophage colony-stimulating factor (Escherichia coli-derived) antibodies and clinical effects in nonimmunocompromised patients.

The pharmacokinetics of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF), induction of anti-GM-CSF antibodies, and clinical effects related to the induction of the antibodies were analyzed in patients with metastatic colorectal carcinoma (CRC) who were not on chemotherapy (n = 20, nonimmunocompromised patients). rhGM-CSF (250 micrograms/m2/d; Escherichia coli-derived) was administered subcutaneously for 10 days every month for 4 months. Eight patients with multiple myeloma (MM) on intensive chemotherapy followed by rhGM-CSF treatment were also included (immunocompromised patients). After a single injection of GM-CSF at the first cycle in CRC patients, the maximum calculated concentration (Cmax) was 5.24 +/- 0.56 ng/mL; the half life (T1/2) was 2.91 +/- 0.8 hours; and the area under the concentration curve (AUC) was 30.86 +/- 6.03 hours x ng/mL (mean +/- SE). No anti-GM-CSF antibodies were detected. During the subsequent cycles, 95% of the CRC patients developed anti-GM-CSF IgG antibodies, which significantly altered the pharmacokinetics of rhGM-CSF at the third and fourth cycles with decreased Cmax (2.87 +/- 0.57 ng/mL; P < .05), T1/2 (1.57 +/- 0.2 hours; P < .05), and AUC (14.90 +/- 4.10 hours x ng/mL; P < .005). The presence of anti-GM-CSF antibodies significantly reduced the GM-CSF-induced enhancement of granulocytes, and there was a clear tendency for a decreased increment of monocytes. Antibodies diminished systemic side effects of rhGM-CSF. Only 1 of 8 MM patients showed a very low anti-GM-CSF antibody titer after GM-CSF therapy, as shown by enzyme-linked immunosorbent assay and Western blot. Therefore, in nonimmunocompromised patients, exogenous nonglycosylated GM-CSF induced an anti-GM-CSF IgG antibody response in practically all patients, which seemed to be of clinical significance. In immunocompromised patients, virtually no significant antibody response was shown.
T-cell dynamics during acute SIV infection

Objectives: To delineate T-cell dynamics during acute SIV infection, particularly of phenotypically defined memory T cell subsets. Design: T cells are a heterogeneous mix of naive and memory subsets delineated by simultaneously measuring CD4, CD8, CD45RA/RO, CD11a, CD28, and CD27. The effects of SIV infection on these subsets was measured to evaluate the impact of changes in functionally distinct cell types during pathogenesis. Methods: Peripheral blood was obtained from six SIV-infected macaques at multiple times before and after SIV infection and analyzed using 12-color flow cytometry. Results: Acute infection was characterized by an initial lymphopenia caused by a decline in B cells. Total T-cell counts remained steady during the early acute phase; however, CD4 cell counts declined while CD8 T cells increased. The decline in CD4 T cells was a result of a decline in both naive and memory cells. CCR5+ or CD103+ subsets of CD4 T cells were depleted but only partially accounted for the decline of CD4 memory T cells, suggesting that acute infection was associated with a rapid redistribution of T cells from the periphery. Naive CD8 cell counts declined while memory CD8 cell counts increased. The increase coincided with declines in plasma viremia and was made up initially of CD27−CD28− (effector) cells; subsequently, the predominant phenotype became CD27+CD28−, akin to central memory cells. Conclusions: A complete understanding of the T-cell dynamics during acute SIV or HIV infection requires the simultaneous evaluation of a broad spectrum of T-cell subsets. Changes in homeostasis and associated immunopathogenesis can no longer be accurately described simply by measuring naive and memory T-cell subsets.
Construct validity and internal consistency of the neuropsychiatric inventory – nursing home (NPI-NH) in German nursing homes

ABSTRACT Background: The Neuropsychiatric Inventory (NPI) is one of the most popular and frequently used instruments for assessing so-called challenging behavior in individuals with dementia in research practice. However, no information is available regarding the factor structure of the German version of the Neuropsychiatric Inventory – Nursing Home (NPI-NH). The aim of this study was to evaluate the factor structure (an aspect of construct validity) and internal consistency of the NPI-NH for two different stages of dementia severity in a large German nursing home population. Methods: A total of 784 residents with dementia from 40 nursing homes in three studies was included in a secondary data analysis. Principal component analysis (PCA) using an orthogonal rotational procedure (with varimax rotation) was used to evaluate the factor structure of the NPI. Cronbach's α was used to assess the stability of the scale. Results: The factors agitation & restless behavior, psychosis, and mood were identified (with factor loading > 0.4 explaining 50% of the variance). The factors showed a moderate internal consistency of 0.55 and 0.68 (Cronbach's α). Conclusions: The results show the acceptable factor structure of the NPI for a German population in nursing homes and confirm the results of studies from other countries. The three identified factors appear to be robust over the various stages of dementia severity. The results also support the hypothesis that the NPI-NH can be subdivided into multiple domains.
Fractal properties of the trabecular pattern of the mandible in chronic renal failure.

OBJECTIVES The purpose of this study was to evaluate fractal analysis as a tool to quantitatively determine the mandibular trabecular bone changes in patients with chronic renal failure (CRF). METHODS In the present study, fractal analysis was performed using ImageJ (National Institutes of Health, Bethesda, MD) program with box-counting method over panoramic radiographs of 25 patients (14 females and 11 males) with CRF and 26 healthy individuals (14 females and 12 males) as a control group. The fractal dimension (FD) values of the patients and healthy individuals were compared. In addition, average biochemical parameters [parathyroid hormone (PTH), calcium (Ca), phosphorus (P), product of Ca and P levels (CaxP), alkaline phosphatase (ALP), vitamin D] of the patients with CRF, as measured during the 3 months before the panoramic radiographs, were compared with FD values. RESULTS According to the results, FD values of the patients with CRF were found to be statistically lower than the control group (p < 0.05). The average PTH levels of the patients with CRF were 416.16 ± 310.3 pg ml(-1); average Ca levels were 8.94 ± 1.2 mg dl(-1); average P levels were 5.76 ± 1.7 mg dl(-1); average CaxP values were 51.12 ± 15.03; average ALP levels were 83.44 ± 36.8 U l(-1); and the average vitamin D values were 19.43 ± 9.7 ng ml(-1). In addition, there was no significant correlation between FD values and the biochemical parameters of the patients, and there was no correlation between age, gender and FD. CONCLUSIONS The FD values of the patients with CRF were lower than those of the controls. This finding suggests that FD analysis might be a promising simple and cost-effective tool for evaluating trabecular bone structure.
Are platelet indices useful in the evaluation of type 2 diabetic patients

Introduction: Long-term complications of diabetes mellitus are a leading cause of death in people with diabetes. Recent studies suggest that platelets with altered morphology could be associated with an increased risk for developing vascular complications in diabetes. Objective: To evaluate the platelet parameters in diabetic patients and correlate these indices with microvascular and macrovascular complications of the disease. Materials and methods: We analyzed platelet parameters and biochemical data of patients seen in outpatient clinics of a university hospital. Individuals aged between 30 and 60 years were included, 100 patients with type 2 diabetes mellitus (T2DM) (DM group) and 100 non-diabetic patients (control group). Results: We observed increase in plateletcrit (PCT): 0.21 ± 0.054% vs 0.20 ± 0.045% (p = 0.020); in mean platelet volume (MPV): 8.69 ± 1.288 fl vs 8.27 ± 1.244 fl (p = 0.018); and in platelet distribution width (PDW): 17.8 ± 1.06 fl vs 17.5 ± 0.87 fl (p = 0.039) in the DM and control groups, respectively. Values of MPV, PCT, and PDW were higher among patients with complications of T2DM (p < 0.001). In those with macrovascular disease, we observed a correlation between glycated hemoglobin (A1C) and MPV (p = 0.015) and PDW (p = 0.009) levels. Among patients with microvascular complications, there was a correlation between platelet count and MPV with A1C levels (p < 0.001). Conclusion: The study findings point to significant differences in platelet parameters in patients with T2DM, suggesting the presence of more reactive and aggregatable platelets in this group of individuals. These results suggest that platelet evaluation may be useful in the early detection of long-term complications in diabetic patients, considering that it is a simple and low-cost tool.
When does ultrasonography influence management in suspected appendicitis?

Accurate diagnosis of appendicitis is challenging, particularly in children. Moreover, opinion is divided over the role of ultrasonography (US) in its diagnosis and how US may influence management. This study compares the use of US in two tertiary paediatric hospitals and how it influenced the management of suspected appendicitis.
Structural dynamics of myoglobin: spectroscopic and structural characterization of ligand docking sites in myoglobin mutant L29W.

We have studied CO binding to the heme and CO migration among protein internal cavities after photodissociation in sperm whale carbonmonoxy myoglobin (MbCO) mutant L29W using Fourier transform infrared (FTIR) spectroscopy combined with temperature derivative spectroscopy (TDS) and kinetic experiments at cryogenic temperatures. Photoproduct intermediates, characterized by CO at particular locations in the protein, were selectively enhanced by applying special laser illumination protocols. These studies were performed on the L29W mutant protein and a series of double mutants constructed so that bulky amino acid side chains block passageways between cavities or fill these sites. Binding of xenon was also employed as an alternative means of occluding cavities. All mutants exhibit two conformations, A(I) and A(II), with distinctly different photoproduct states and ligand binding properties. These differences arise mainly from different positions of the W29 and H64 side chains in the distal heme pocket [Ostermann, A. , et al. (2000) Nature 404, 205-208]. The detailed knowledge of the interplay between protein structure, protein dynamics, and ligand migration at cryogenic temperatures allowed us to develop a dynamic model that explains the slow CO and O(2) bimolecular association observed after flash photolysis at ambient temperature.
Children with the Le(a+b−) Blood Group Have Increased Susceptibility to Diarrhea Caused by Enterotoxigenic Escherichia coli Expressing Colonization Factor I Group Fimbriae

ABSTRACT Recent studies have shown that children with blood group A have increased susceptibility to enterotoxigenic Escherichia coli (ETEC) diarrhea and that Lewis blood group “a” antigen (Lea) may be a candidate receptor for ETEC colonization factor (CF) antigen I (CFA/I) fimbriae. Based on these findings, we have attempted to determine if children with the Le(a+b−) phenotype may be more susceptible to diarrhea caused by ETEC, in particular ETEC expressing CFA/I and related fimbriae of the CFA/I group, than Le(a−b+) children. To test this hypothesis, we have determined the Lewis antigen expression in 179 Bangladeshi children from a prospective birth cohort study in urban Dhaka in which ETEC expressing major CFs such as CFA/I, CS3, CS5, and CS6 was the most commonly isolated diarrhea pathogen during the first 2 years of life. The Lewis blood group phenotypes were determined by a dot blot immunoassay using saliva samples and by a tube agglutination test using fresh red blood cells. The results indicate that Le(a+b−) children more often had symptomatic than asymptomatic ETEC infections (P < 0.001), whereas symptomatic and asymptomatic ETEC infections were equally frequent in Le(a−b+) children. We also show that children with the Le(a+b−) blood type had significantly higher incidences of diarrhea caused by ETEC expressing fimbriae of the CFA/I group than Le(a−b+) children (P < 0.001). In contrast, we did not find any association between the Lewis blood group phenotype and diarrhea caused by ETEC expressing CS6 or rotavirus.
Accuracy of the Modified Somatic Perception Questionnaire and Pain Disability Index in the Detection of Malingered Pain-Related Disability in Chronic Pain

The Modified Somatic Perception Questionnaire (MSPQ) and the Pain Disability Index (PDI) are both popular clinical screening instruments in general orthopedic, rheumatologic, and neurosurgical clinics and are useful for identifying pain patients whose physical symptom presentations and disability may be non-organic. Previous studies found both to accurately detect malingered pain presentations; however, the generalizability of these results is not clear. This study used a criterion groups validation design (retrospective cohort of patients with chronic pain, n = 328) with a simulator group (college students, n = 98) to determine the accuracy of the MSPQ and PDI in detecting Malingered Pain Related Disability. Patients were grouped based on independent psychometric evidence of MPRD. Results showed that MSPQ and PDI scores were not associated with objective medical pathology. However, they accurately differentiated Not-MPRD from MPRD cases. Diagnostic statistics associated with a range of scores are presented for application to individual cases. Data from this study can inform the clinical management of chronic pain patients by screening for psychological overlay and malingering, thus alerting clinicians to the possible presence of psychosocial obstacles to effective treatment and triggering further psychological assessment and/or treatment.
Development, Optimization, and Anti-diabetic Activity of Gliclazide-Loaded Alginate–Methyl Cellulose Mucoadhesive Microcapsules

The purpose of this work was to develop and optimize gliclazide-loaded alginate–methyl cellulose mucoadhesive microcapsules by ionotropic gelation using central composite design. The effect of formulation parameters like polymer blend ratio and cross-linker (CaCl2) concentration on properties of gliclazide-loaded alginate–methyl cellulose microcapsules like drug encapsulation efficiency and drug release were optimized. The optimized microcapsules were subjected to swelling, mucoadhesive, and in vivo studies. The observed responses coincided well with the predicted values from the optimization technique. The optimized microcapsules showed high drug encapsulation efficiency (83.57 ± 2.59% to 85.52 ± 3.07%) with low T50% (time for 50% drug release, 5.68 ± 0.09 to 5.83 ± 0.11 h). The in vitro drug release pattern from optimized microcapsules was found to be controlled-release pattern (zero order) with case II transport release mechanism. Particle sizes of these optimized microcapsules were 0.767 ± 0.085 to 0.937 ± 0.086 mm. These microcapsules also exhibited good mucoadhesive properties. The in vivo studies on alloxan-induced diabetic rats indicated the significant hypoglycemic effect that was observed 12 h after oral administration of optimized mucoadhesive microcapsules. The developed and optimized alginate–methyl cellulose microcapsules are suitable for prolonged systemic absorption of gliclazide to maintain lower blood glucose level and improved patient compliance.
Polymorphic Alu insertions in six Brazilian African‐derived populations

At least 25 African‐derived populations (quilombo remnants) are believed to exist in the Ribeira River Valley, located in the southern part of São Paulo State, Brazil. We studied four Alu polymorphic loci (APO, ACE, TPA25, and FXIIIB) in individuals belonging to six quilombo remnants in addition to individuals sampled from the city of São Paulo. The allelic frequencies observed in the quilombo remnants were similar to those previously observed in African‐derived populations from Central and North America. Genetic variability indexes (Fst and Gst values) in our quilombos were higher than the reported values for the majority of other populations analyzed for the same kind of markers, but lower than the variability usually observed in Amerindian groups. The observed high degree of genetic differentiation may be due to genetic drift, especially the founder effect. Our results suggest that these populations behave genetically as semi‐isolates. The degree of genetic variability within populations was larger than among them, a finding described in other studies. In the neighbor‐joining tree, some of the Brazilian quilombos clustered with the African and African‐derived populations (São Pedro and Galvão), others with the Europeans (Pilões, Maria Rosa, and Abobral). Pedro Cubas was placed in an isolated branch. Principal component analysis was also performed and confirmed the trends observed in the neighbor‐joining tree. Overall, the quilombos showed a higher degree of gene flow than average when compared to other worldwide populations, but similar to other African‐derived populations. Am. J. Hum. Biol. 16:264–277, 2004. © 2004 Wiley‐Liss, Inc.