Miracle-dz/UniFAR-FTUs huggingface dataset:
Characterization of a Developmentally Early Macrophage Progenitor Found in Normal Mouse Marrow

Summary. In tissue culture high proliferation potential colony forming cells (HPP‐CFC, Bradley & Hodgson, 1979) formed large colonies in which macrophages predominated. Granulocyte/macrophage colony forming cells (GM‐CFC, Bradley & Metcalf, 1966) formed smaller colonies of granulocytes and macrophages. We compared HPP‐CFC from normal adult mouse bone marrow with GM‐CFC from the same source. We found that HPP‐CFC differed from GM‐CFC in the following ways: (1) HPP‐CFC formed larger colonies containing more than 5 × 104 cells. (2) They required spleen conditioned medium (Metcalf & Johnson, 1978) as well as pregnant mouse uterine extract (PMUE, Bradley et al, 1971) as stimulants. (3) Only 9% of HPP‐CFC were killed by the phase specific drug hydroxyurea. 36–55% of GM‐CFC were killed by the same treatment. (4) The modal density of HPP‐CFC was 1·070 g/cm3. That of GM‐CFC was 1·080 g/cm3.
Identification of the amino acids essential for LytSR‐mediated signal transduction in Staphylococcus aureus and their roles in biofilm‐specific gene expression

Recent studies have demonstrated that expression of the Staphylococcus aureus lrgAB operon is specifically localized within tower structures during biofilm development. To gain a better understanding of the mechanisms underlying this spatial control of lrgAB expression, we carried out a detailed analysis of the LytSR two‐component system. Specifically, a conserved aspartic acid (Asp53) of the LytR response regulator was shown to be the target of phosphorylation, which resulted in enhanced binding to the lrgAB promoter and activation of transcription. In addition, we identified His390 of the LytS histidine kinase as the site of autophosphorylation and Asn394 as a critical amino acid involved in phosphatase activity. Interestingly, LytS‐independent activation of LytR was observed during planktonic growth, with acetyl phosphate acting as a phosphodonor to LytR. In contrast, mutations disrupting the function of LytS prevented tower‐specific lrgAB expression, providing insight into the physiologic environment within these structures. In addition, overactivation of LytR led to increased lrgAB promoter activity during planktonic and biofilm growth and a change in biofilm morphology. Overall, the results of this study are the first to define the LytSR signal transduction pathway, as well as determine the metabolic context within biofilm tower structures that triggers these signaling events.
Prevalence of Transmitted HIV-1 Drug Resistance and the Role of Resistance Algorithms: Data From Seroconverters in the CASCADE Collaboration From 1987 to 2003

Objectives:To examine factors influencing the rate of transmitted drug resistance (TDR) among seroconverters, with particular emphasis on 3 widely used genotypic drug resistance algorithms. Methods:The study used data from CASCADE (Concerted Action on Seroconversion to AIDS and Death in Europe), a collaboration of seroconverter cohorts in Europe and Canada. Genotypic resistance data were derived within 18 months of the last seronegative test or date of laboratory evidence of acute infection and before the initiation of antiretroviral therapy. The Stanford algorithm was used to analyze each individual's nucleotide sequence. A multivariate logistic model was used to assess independent relationships between the presence of TDR and exposure category, sex, age at seroconversion, and year of seroconversion. The paper also describes 3 alternative definitions of resistance: the Stanford algorithm, the key resistance mutations defined by the International AIDS Society, and the Agence Nationale de Recherches sur le Sida (ANRS) algorithm. Results:Forty-five of 438 patients (10.3%) seroconverting between 1987 and 2003 were infected with a drug-resistant HIV-1 variant. Forty patients (9.1%) showed resistance mutations to only 1 class of antiretroviral drugs, 2 (0.5%) to 2 classes, and 3 (0.7%) to 3 classes of antiretroviral therapy. It was suggested that individuals seroconverting later in calendar time were more likely to have TDR (relative risk 3.89 and 95% CI: 0.84 to 18.02, and relative risk 4.69 and 95% CI: 1.03 to 21.31, for 1996-1999 and 2000-2003, respectively, compared with pre-1996; P trend = 0.08). This trend was apparent regardless of the definition of TDR used. The total estimated proportion of individuals with TDR varied between 10.3% and 15.5% according to which definition was used. Conclusions:Evidence was found for the rise of TDR over time. A specific definition of what constitutes TDR rather than a simple list of mutations is needed.
The Seasonal Variation of the Chemical Composition of Essential Oils from Porcelia macrocarpa R.E. Fries (Annonaceae) and Their Antimicrobial Activity

This study investigates the impact of seasonal variation on the chemical composition of essential oils from the leaves of Porcelia macrocarpa (Annonaceae) obtained over the course of one year (January–December 2011) and the chemical composition of the essential oils obtained from the ripe fruits of the same plant. Furthermore, the essential oils of the leaves were investigated with respect to their antimicrobial activity. The essential oils of the leaves contain a mixture of monoterpenes, one diterpene and several sesquiterpenes. The main components were identified as the sesquiterpenes germacrene D (29%–50%) and bicyclogermacrene (24%–37%). No significant variation was observed for the composition of the essential oil of the leaves over the course ofthe year, except for the month of November, when the ripe fruit were collected. In this month, substantially decreased concentrations of germacrene D (28.8 ± 0.8%) and bicyclogermacrene (23.9 ± 0.6%) were measured and the emergence of spathulenol (10.4 ± 0.2%) was observed. The essential oils extracted from the ripe fruit revealed the presence of a variety of monoterpenes, sesquiterpenes and hydrocarbons. The main constituents of these oils were neryl (8.8 ± 0.2%) and geranyl (27.3 ± 0.7%) formates, γ-muurolene (10.3 ± 0.9%) and dendrolasin (8.23 ± 0.06%). The antimicrobial activity of the essential oil obtained from the leaves of P. macrocarpa towards a range of bacterial and yeast strains was examined. In order to determine the minimum inhibitory concentration (MIC) of essential oils obtained from the January collection of the leaves, broth microdilution assays were carried out, which showed a significant antimicrobial activity towards Cryptococcus neoformans serotypes A and D as well as C. gattii serotypes B and C.
Pharmacokinetic studies of flunixin meglumine and phenylbutazone in plasma, exudate and transudate in sheep.

Flunixin meglumine (FM, 1.1 mg/kg) and phenylbutazone (PBZ, 4.4 mg/kg) were administered intravenously (i.v.) as a single dose to eight sheep prepared with subcutaneous (s.c.) tissue-cages in which an acute inflammatory reaction was stimulated with carrageenan. Pharmacokinetics of FM, PBZ and its active metabolite oxyphenbutazone (OPBZ) in plasma, exudate and transudate were investigated. Plasma kinetics showed that FM had an elimination half-life (t1/2beta) of 2.48 +/- 0.12 h and an area under the concentration - time curve (AUC) of 30.61 +/- 3.41 Lg/mL x h. Elimination of PBZ from plasma was slow (t1/2beta = 17.92 +/- 1.74 h, AUC = 968.04 +/- microg/mL x h). Both FM and PBZ distributed well into exudate and transudate although penetration was slow, indicated by maximal drug concentration (Cmax) for FM of 1.82 +/- 0.22 microg/mL at 5.50 +/- 0.73 h (exudate) and 1.58 +/- 0.30 microg/mL at 8.00 h (transudate), and Cmax for PBZ of 22.32 +/- 1.29 microg/mL at 9.50 +/- 0.73 h (exudate) and 22.07 +/- 1.57 microg/mL at 11.50 +/- 1.92 h (transudate), and a high mean tissue-cage fluids:plasma AUClast ratio obtained in the FM and PBZ groups (80-98%). These values are higher than previous reports in horses and calves using the same or higher dose rates. Elimination of FM and PBZ from exudate and transudate was slower than from plasma. Consequently the drug concentrations in plasma were initially higher and subsequently lower than in exudate and transudate.
Impact of surgical delay on long-term cancer control for clinically localized prostate cancer.

PURPOSE Radical retropubic prostatectomy (RRP) as definitive management for clinically localized prostate cancer is commonly performed within months of diagnosis. Despite patient anxiety there is little evidence to suggest that a delay of several months from diagnosis to RRP is associated with a worse cancer control rate. However, a recent study cast doubt on the safety of such a delay with respect to cancer control. Therefore, in a contemporary series we determined long-term cancer control in men who underwent RRP for clinically localized prostate cancer with some treated early and others treated after a longer delay. MATERIALS AND METHODS We analyzed data on 926 men who underwent RRP between January 1989 and December 1994. Age, preoperative serum prostate specific antigen (PSA), biopsy Gleason score, clinical and pathological stage, and biochemical recurrence were compared between 162 men who underwent RRP 60 days or less from biopsy and 764 who underwent RRP after a greater delay. Disease-free (PSA less than 0.2 ng/ml) survival rates were compared using Kaplan-Meier analysis. Pathological staging was compared using logistic regression. RESULTS The different groups were well matched for age, serum PSA, pathological stage and followup. However, significantly more men who underwent RRP between 121 and 150 days, and 151 days or greater had T1c disease (48% and 57% vs 35%, p<0.04 and <0.0001, respectively). In addition, significantly more men operated on at 151 days or greater had biopsy Gleason scores 2 to 6 (86% vs 65%, p<0.0001) and significantly fewer had Gleason score 7 disease (13% vs 30%, p<0.002). Men who underwent RRP after 60 or less days had 5 and 10-year biochemical disease-free survival rates comparable to those in men who underwent RRP after 61 to 90, 91 to 120 and 121 to 150 days after diagnosis (82% and 78%, 86% and 78%, 86% and 75%, and 86% and 82%, respectively). Those operated on at 151 days or greater had significantly greater 5 and 10-year biochemical disease-free survival rates (89% and 87%, p<0.04). However, when patients were stratified into different subgroups based on clinical stage, serum PSA and biopsy Gleason score a delay of 150 days or greater no longer impacted differently on long-term cancer control rates. CONCLUSIONS Delays of up to several months from prostate cancer diagnosis to RRP do not appear to impact long-term biochemical cancer control rates. Therefore, patients can be reassured that there is no immediate urgency to perform RRP after prostate cancer diagnosis, especially in those with T1c disease and biopsy Gleason scores less than 7.
Progesterone Promotes Oocyte Maturation, but Not Ovulation, in Nonhuman Primate Follicles Without a Gonadotropin Surge1

Abstract During the periovulatory interval, intrafollicular progesterone (P) prevents follicular atresia and promotes ovulation. Whether P influences oocyte quality or maturation and follicle rupture independent of the midcycle gonadotropin surge was examined. Rhesus monkeys underwent controlled ovarian stimulation with recombinant human gonadotropins followed by a) experiment 1: an ovulatory bolus of hCG alone or with a steroid synthesis inhibitor (trilostane, TRL), or TRL + the progestin R5020; or b) no hCG, but rather sesame oil (vehicle), R5020, or dihydrotestosterone (DHT). In experiment 1, the majority of oocytes remained immature (65% ± 20%) by 12 h post-hCG. However, the percentage of degenerating oocytes increased (P < 0.05) with TRL (42% ± 22% vs. 0% controls), but was reduced (P < 0.05) by progestin replacement (15% ± 7%). By 36 h post-hCG, the majority of oocytes in all three groups reached metaphase II (MI). In experiment 2, no evidence of follicle rupture was observed in the vehicle, R5020, or DHT groups. Despite the absence of hCG, a significant (P < 0.05) percentage of oocytes resumed meiosis to metaphase I in R5020- (41 ± 9) and DHT- (36 ± 15) but not vehicle- (4 ± 4) treated animals. Only oocytes from R5020-treated animals continued meiosis in vivo to MII. More (P < 0.05) oocytes fertilized in vitro with R5020 (40%) than with vehicle (20%) or DHT (22%). Thus, P is unable to elicit ovulation in the absence of an ovulatory gonadotropin surge; however, P and/or androgens may prevent oocyte atresia and promote oocyte nuclear maturation in primate follicles.
Association of Cytidine Deaminase and Xeroderma Pigmentosum Group D Polymorphisms with Response, Toxicity, and Survival in Cisplatin/Gemcitabine-Treated Advanced Non-small Cell Lung Cancer Patients

Background: Selecting patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in non-small cell lung cancer (NSCLC). Genetic variations in drug metabolism may affect the clinical response, toxicity, and prognosis of NSCLC patients treated with cisplatin/gemcitabine-based therapy. Patients and Methods: We evaluated seven single-nucleotide polymorphisms of six genes CDA Lys27Gln (A/C); CDA C435T; ERCC1 C118T; XRCC3 Thr241Met (C/T); XPD Lys751Gln (A/C); P53 Arg72Pro (G/C), and RRM1 C524T in 192 chemotherapy-naive patients with advanced NSCLC treated with cisplatin/gemcitabine-based regimen by TaqMan probe-based assays with 7300 Real-Time PCR System, using genomic DNA extracted from blood samples. Results: The CDA 435 T/T genotype was significantly associated with better response (p = 0.03). The CDA 435 C/T genotype was associated with a significantly increased risk of nonhematological toxicity of grade ≥3 (p = 0.02) after adjusting for performance status, age, and type of treatment regimen. In the multivariate Cox model, the XPD 751 C/C genotype was a significant prognostic factor of longer progression-free survival (p = 0.006). Conclusion: Our data suggest polymorphic variations of drug metabolic gene were associated with response and toxicity of cisplatin/gemcitabine-based therapy and progression-free survival of patients with advanced NSCLC.
Superficial melanoma metastases: appearances on gray-scale and color Doppler sonography.

OBJECTIVE The purpose of this study was to describe the sonographic appearances of melanoma metastases of the skin, subcutaneous tissues, and superficial lymph nodes. MATERIALS AND METHODS Gray-scale sonography was performed on 31 superficial melanoma metastases in 18 patients. Discreteness of borders, contours, echogenicity, echotexture, and degree of acoustic through-transmission were evaluated for each lesion. Color Doppler sonography was also performed on 25 of the 31 lesions, by which the amount of internal color flow was qualitatively assessed. RESULTS Twenty-eight (90%) of the 31 metastases had well-defined borders. Contours were smooth in 17 (55%), lobulated in 12 (39%), and spiculated in two (6%). Nineteen metastases (61%) were hypoechoic to muscle, 10 (32%) were isoechoic, and two (6%) were hyperechoic. Echotexture was homogeneous in six lesions (19%), mildly heterogeneous in 13 (42%), moderately heterogeneous in 11 (35%), and markedly heterogeneous in one (3%). Twenty-two lesions (71%) showed enhanced acoustic through-transmission. Of the 25 melanoma metastases for which we performed color Doppler sonography, 18 (72%) had internal arterial color flow and seven (28%) did not. The flow was characterized as mild in 13 (72%) of 18, moderate in four (22%), and marked in one (6%). CONCLUSION On sonography, superficial melanoma metastases typically are well-defined hypoechoic lesions with smooth or lobulated contours, mild to moderate heterogeneity, and enhanced acoustic through-transmission. Internal flow revealed by color Doppler sonography is present in many, but not all, superficial melanoma metastases.
Homicides Committed by Youth Assailants: A Retrospective Study

The pediatric population has received considerable attention in the forensic community; the youth assailant of homicide, however, is understudied. The authors retrospectively reviewed all cases referred to the Forensic Pathology Section of the Medical University of South Carolina between January 1991 and May 2006. Cases included in the study were homicides in which 1 or more assailants were 19 years of age or younger. The cases were examined as to the cause and manner of death, victim age, gender, race, incident location, weapon used, assailant-victim relationship, assailant age, gender, race, motive, and postmortem toxicology results. Assailant information was obtained from forensic records at Medical University of South Carolina, police department records, and online search engines of South Carolina State newspaper archives confirmed by law enforcement reports. The youth assailants were predominantly black men, 15 to 19 years of age (range, 4–19 years). Most victims were black male acquaintances, and the motive was most often an argument. The most common cause of death was cerebral laceration because of a gunshot wound. The incident occurred in the home in 41% of cases, followed by the street in 31%. Victim toxicology was frequently positive for cocaine, marijuana, and alcohol.
Toxoplasma gondii infection in workers occupationally exposed to raw meat.

BACKGROUND Raw meat may contain viable Toxoplasma gondii tissue cysts and therefore handling of raw meat may represent a risk for T. gondii infection. AIMS To determine the association of T. gondii infection with occupational exposure to raw meat. METHODS Case-control seroprevalence study design with enzyme-linked immunoassays for the presence and levels of anti-Toxoplasma IgG antibodies and for the presence of anti-Toxoplasma IgM antibodies. Those occupationally exposed to raw meat consisted of butchers working in two abattoirs and 35 butcher's shops in Durango, Mexico. The control group consisted of individuals from the general population from the same region. Socio-demographic, work, clinical and behavioural characteristics from each butcher were obtained. RESULTS One hundred and twenty-four workers occupationally exposed to raw meat and 248 control subjects were examined. Eight (7%) of the butchers and 22 (9%) of the controls were positive for anti-T. gondii IgG antibodies [not statistically significant (NS)]. Anti-T. gondii IgG levels were >150 IU/ml in 7 (6%) butchers and 14 (6%) controls (NS). Anti-T. gondii IgM antibodies were found in five (4%) of the butchers and four (2%) of the controls (NS). None of the factors examined appeared to predict seropositivity although both butchers who reported consuming dried beef were seropositive compared to 6/122 controls (95% CI 0.60-1.29). CONCLUSIONS Occupational exposure to raw meat was not associated with seropositivity for T. gondii infection. Consumption of dried beef may warrant further investigation.
A comparison of oral health in 70-year-old city cohorts in Umeå northern Sweden in 1981 and 1990: oral problems, dental and periodontal status.

A comparison of oral health in two different samples of 70-year-old men and women living in the city of Umeå in 1981 and 1990 showed that a higher frequency of dental visits among men could be expected in the city population in 1990 (95% CI). The frequency and pattern of reported oral problems was similar in 1981 and 1990. Total edentulousness among men and women in 1981/1990 was 31.3/21.4 and 53.5/35.7% respectively. The lower frequency in 1990 was not statistically significant on the population level. The mean number of teeth was lower in dentated men (12.8 +/- 6.0 V.S. 17.4 +/- 5.4) (p < 0.05) and women (16.9 +/- 6.3 V.S. 13.9 +/- 8.4) (n.s.) in 1990 compared with in 1981 and the functional index according to Eichner showed no difference. Thus, the lower frequency of edentulousness in 1990 mainly seemed to be the result of another distribution of about the same total amount of teeth, on more people. The bleeding index showed values around 30% in both cohorts. Both men and women showed less recurrent caries in 1990 (p < or = 0.05). Men showed a higher number of missing teeth (p < or = 0.01) and of decayed root surfaces (p < or = 0.05) in 1990. The latter might be explained by a larger exposed root surface area which was indicated by a higher frequency (n.s.) of surfaces with an attachment level > 3 mm in the cohort examined in 1990. Although, the compared 70-year-old city cohorts in Umeå examined in 1981 and 199 showed a higher frequency of dental visits and of dentated subjects, no improvement in reported oral health or dental status could be found in the 70-year-old in Umeå in 1990.
The H63D variant in the HFE gene predisposes to arthralgia, chondrocalcinosis and osteoarthritis

Objectives: To investigate the relation between the HFE C282Y and H63D variants with arthralgia and joint pathology in the population-based Rotterdam Study. Methods: From a cohort of 7983 people aged 55 years and over, 2095 randomly drawn subjects were genotyped for C282Y and H63D variants. We compared the frequency of arthralgia, and the presence of chondrocalcinosis, osteophytes, joint space narrowing and radiographic osteoarthritis in hand, hip and knee joints, and Heberden’s nodes in carriers of HFE variants with that in non-carriers. Results: Overall, there was a significantly higher frequency of arthralgia (odds ratio 1.6; 95% CI 1.0 to 2.6), oligoarthralgia (2.3; 1.2 to 4.4) and Heberden’s nodes (2.0; 1.1 to 3.8) in H63D homozygotes compared with non-carriers. In subjects aged 65 years or younger, H63D homozygotes had significantly more often polyarthralgia (3.1; 1.3 to 7.4), chondrocalcinosis in hip or knee joints (4.7; 1.2 to 18.5), and more hand joints with osteophytes (6.1±1.0 vs 4.4±0.3), space narrowing (2.8±0.5 vs 1.0±0.1), radiographic osteoarthritis (4.4±0.7 vs 2.0±0.2) and Heberden’s nodes (3.1; 1.3 to 12.8) than non-carriers. We found no relation of arthralgia or joint pathology to C282Y, but compound heterozygotes had a significantly higher frequency of arthralgia (2.9; 1.0 to 9.3), chondrocalcinosis in hip joints (6.5; 1.8 to 22.3), and an increased number of osteophytes in knee (6.9±1.2, n = 5 vs 2.4±0.1) joints at a later age (>65 years). Conclusions: The HFE H63D variant may explain, at least in part, the prevalence of arthralgia in multiple joints sites, chondrocalcinosis, and hand osteoarthritis in the general population.
Development of a group and family‐based cognitive behavioural therapy program for youth at risk for psychosis

The onset of psychosis typically occurs during adolescence or early adulthood and can have a detrimental impact on social and cognitive development. Cognitive behavioural therapy (CBT) shows promise in reducing the risk of psychosis. Teaching families to apply CBT with their offspring may bolster therapeutic gains made in time‐limited treatment. We developed a comprehensive group‐and‐family‐based CBT (GF‐CBT) program that aims to facilitate psychosocial recovery, decrease symptoms and prevent transition to psychosis in youth at risk. GF‐CBT is grounded in ecological systems and cognitive theories, resilience models and research on information processing in delusions. The theoretical rationale and description of GF‐CBT are presented together with a pilot study that evaluated the program's feasibility and explored participants' outcomes.