Miracle-dz/UniFAR-FTUs huggingface dataset:
Benzodiazepine receptor occupancy in vivo: correlation with brain concentrations and pharmacodynamic actions.

A tracer radioligand technique employing [3H]Ro 15-1788 was used to measure in vivo benzodiazepine receptor occupancy in mice. Animals were administered clonazepam (CNZ) or lorazepam (LRZ) i.p. or i.v. , followed by [3H]Ro 15-1788. Plasma and cerebral cortical concentrations of the drug and cortical benzodiazepine receptor occupancy were determined at varying doses and times after administration. For both drugs, plasma and brain concentrations decreased in parallel with decreasing doses and with time, and the brain/plasma ratios remained constant. Receptor occupancy was maximal for CNZ and LRZ at doses above 1 and 4 mg/kg, respectively, and decreased with decreasing doses. Comparison of receptor occupancy with brain concentration yielded IC50 values of 21 ng/g for CNZ and 133 ng/g for LRZ. The apparent dissociation constant (Kd) for CNZ was 56 pmol/g and, for LRZ, 372 pmol/g. Hill plots yielded slopes of 1.30 for CNZ and 1.71 for LRZ. Alterations in the nonspecific uptake or elimination of Ro 15-1788 did not explain occupancy changes, inasmuch as brain concentrations of unlabeled Ro 15-1788 (6 mg/kg) were not changed by LRZ administration. The correlation between receptor occupancy and the pharmacodynamic actions of these drugs in blocking pentylenetetrazol seizures and inducing rotarod ataxia indicated that ED50 for these effects occurred at receptor occupancy of 30 to 60% for both drugs.
Racial Diversity in Indie Games: Patterns, Challenges, and Opportunities

Although gamers of color constitute a large part of the digital gaming player base in the US, they are systematically and enormously underrepresented by in-game characters in AAA titles. To extend these findings to indie games, we examine 80 titles and show that the pattern of lack of racial diversity holds. We discuss implications for the industry and players, and present challenges that must be addressed to increase diversity in racial representations of characters in games.
Racial differences in renal kallikrein excretion: effect of the ovulatory cycle.

BACKGROUND Renal kallikrein excretion is diminished in essential hypertension, especially in African-Americans, and evidence exists for a major gene effect on the kallikrein phenotype. In addition, urinary kallikrein excretion differs by gender, with ovulating females having greater kallikrein excretion than males or postmenopausal females. Recent studies have shown that renal kallikrein excretion varies in females during the ovulatory cycle, with levels rising during the luteal phase and returning during the follicular phase to levels that are similar to those of males. In family studies, gender differences in urinary kallikrein excretion were present in white subjects, but not black subjects. We therefore hypothesized dysregulation of kallikrein biosynthetic responses in African-Americans. METHODS We determined urinary kallikrein activity [chromogenic substrate S2266 (D-val-leu-arg-paranitroanilide) assay; in microU/mg creatinine] in white (N = 15) and black (N = 11) ovulating females during the ovulatory cycle. Serum progesterone, estrogen, plasma renin activity as well as urinary aldosterone, and urinary electrolytes were determined to investigate changes between mid-follicular and mid-luteal phases in the two groups. RESULTS White and black groups were matched for age, body mass index, blood pressure, heart rate and renal function. Ovulatory cycle phases were confirmed by serum progesterone determinations, which increased significantly in whites and blacks to a comparable degree [0.84 +/- 0.14 nmol/liter (mid-follicular) to 29.77 +/- 4.70 nmol/liter (mid-luteal) in whites, 0.67 +/- 0.08 nmol/liter (mid-follicular) to 28.62 +/- 5.83 nmol/liter (mid-luteal) in blacks; P < 0.001 for cycle effect, P = NS for race effect and race X cycle interaction]. Urinary kallikrein activity increased from 623 +/- 86 microU/mg creatinine (mid-follicular) to 948 +/- 142 microU/mg creatinine (mid-luteal) in whites, but did not change in blacks during the ovulatory cycle [239 +/- 73 microU/mg creatinine (mid-follicular] to 244 +/- 41 microU/mg creatinine (mid-luteal)]. Two-way ANOVA revealed significant effects on urinary kallikrein for race (P < 0.001), cycle (P < 0.05), and race X cycle interaction (P < 0.05). Thus, white females had higher urinary kallikrein than black females, and demonstrated a significant increase in urinary kallikrein excretion during the ovulatory cycle, whereas no significant change in urinary kallikrein activity was seen in the black group. Enzyme kinetic studies and mixing studies demonstrated that these racial differences in renal kallikrein excretion were quantitative, rather than due to qualitative differences in the renal kallikrein enzyme or due to the presence of a kallikrein inhibitor. CONCLUSIONS These results suggest pronounced blunting of menstrual cycle changes in urinary kallikrein excretion in black females. Blunted urinary kallikrein responses during the ovulatory cycle are consistent with dysregulation of renal kallikrein biosynthetic responses in African-Americans, a group at increased risk for hypertension.
Genetic profiling in acute myeloid leukaemia ─ where are we and what is its role in patient management

Genetic profiling in acute myeloid leukaemia (AML) is a moving target. Only 4 years ago, AML was re‐classified, based on karyotypic abnormalities. However, numerous important new mutations and other genetic abnormalities that were not considered in this classification have been identified. Current cytogenetic‐based classification is limited by the substantial number of intermediate‐risk patients in whom the preferred therapy is debatable. In addition, the majority of AML patients co‐express multiple mutations and cannot be easily categorized into predefined homogenous groups. The tremendous progress in mass sequencing allows parallel identification of multiple genetic aberrations in large cohorts. Thus, a new concept of genetic profiling has arisen. Genes and proteins biologically interact with each other; therefore, it should not be surprising that mutations in different genes interact. Prognosis is determined by the composition of mutations and aberrations in leukaemic stem cells. As a consequence, clinical decisions no longer rely on scant genetic data and require comprehensive genetic evaluation. Some non‐genetic parameters are also important and should be incorporated into the clinical decision algorithm. Genetic interaction‐based profiles are challenging and recent studies demonstrate an improvement in prognostic predictions with this model. Thus, genetic profiling is likely to have a major therapeutic impact, at least for intermediate‐risk cytogenetics.
SUPRACONDYLAR NAILING FOR SUPRACONDYLAR FEMORAL FRACTURES IN ELDERLY OR INFIRM PATIENTS

We report 33 cases of femoral supracondylar fracture in elderly or debilitated patients treated by Zickel supracondylar nails. Most of the patients were female and their mean age was 79 years. All had concurrent medical problems and only nine could walk unaided. The operating time averaged one hour and mean blood loss was 100 ml. Postoperative management was by mobilisation in a cast brace or plaster. Six patients died before fracture union; all the others achieved union at an average of 12 weeks. The results were excellent in terms ofpain relief, movement and function; there were no infections or nonunions. The locking screws backed out or broke in 26% but this did not prejudice the outcome. Use of the Zickel system is recommended for this group of frail patients.
Early prediction of unexplained syncope by support vector machines

The goal of the present study was to develop and evaluate a new method for the prediction of unexplained syncope occurrences. Diagnosis of syncope is currently based on the reproduction of symptoms in combination with hypotension and bradycardia induced by a 45 min 60–70° head-upright tilt test (HUTT). The main drawback of this widely used test concerns its duration that reaches 55 min if the patient does not faint. Our method is a first step in the avoidance of the HUTT. An electrocardiogram and a transthoracic impedance waveform were recorded for 10 min of supine rest of a HUTT in 128 patients with a history of unexplained recurrent syncope. Seven indices were computed on the transthoracic impedance and its first derivative. The prediction quality of every subset of these variables, mixed with age and sex, has been tested by a support vector machine in a retrospective group of 64 patients (100% of sensitivity and 100% of specificity was reached). The best subset obtained has been evaluated prospectively in a group of 64 patients (94% of sensitivity and 79% of specificity was reached). These results compare very favorably with published results for other unexplained syncope detectors.
A novel rho promoter::Tn10 mutation suppresses and ftsQ1(Ts) missense mutation in an essential Escherichia coli cell division gene by a mechanism not involving polarity suppression

An extragenic suppressor of the Escherichia coli cell division gene ftsQ1(Ts) was isolated. The suppressor is a Tn10 insertion into the -35 promoter consensus sequence of the rho gene, designated rho promoter::Tn10. The ftsQ1(Ts) mutation was also suppressed by the rho-4 mutant allele. The rho promoter::Tn10 strain does not exhibit rho mutant polarity suppressor phenotypes. In addition, overexpression of the ftsQ1(Ts) mutation does not reverse temperature sensitivity. Furthermore, DNA sequence analysis of the ftsQ1(Ts) allele revealed that the salt-remediable, temperature-sensitive phenotype arose from a single missense mutation. The most striking phenotype of the rho promoter::Tn10 mutant strain is an increase in the level of negative supercoiling. On the basis of these observations, we conclude that the ftsQ1(Ts) mutation may be suppressed by a change in supercoiling.
Regulation of Interleukin‐6 Secretion from Mononuclear Blood Cells by Extracellular Calcium

Interleukin‐6 (IL‐6) is known to enhance osteoclast recruitment, and thereby bone resorption. Thus, IL‐6 has been proposed to mediate hypercalcemia in multiple myeloma and the enhanced osteoclastic activity seen in postmenopausal osteoporosis. We recently reported that the calcium concentration in plasma affects IL‐6 secretion from mononuclear blood cells. To investigate the underlying mechanism, we have studied the effect of calcium on IL‐6 formation in mononuclear blood cells ex vivo and in vitro. Thirteen healthy volunteers were given 1 g of calcium orally after overnight fasting. Plasma levels of ionized calcium (pCa2+) and serum levels of parathyroid hormone (sPTH) were measured after 2 and 4 h, with all subjects still fasting. After 2 h, pCa2+ was increased and sPTH decreased in all 13 persons. IL‐6 secretion ex vivo from mononuclear blood cells drawn 4 h after calcium intake was increased 185% as compared with IL‐6 secretion from cells drawn just before calcium intake. In control experiments without calcium intake, there was no alteration in pCa2+ and no effect on IL‐6 secretion from mononuclear blood cells. In vitro studies revealed that stimulation of isolated mononuclear blood cells with physiological concentrations of calcium dose‐dependently increased IL‐6 secretion with an estimated EC50 at 1.2 mM Ca2+. No effect on the IL‐6 secretion was seen following treatment of the isolated mononuclear blood cells with PTH or calcitonin. These observations demonstrate that the plasma calcium concentration affects IL‐6 secretion from mononuclear blood cells. The in vitro data indicate the involvement of a direct calcium sensing mechanism. These findings might have implications in hypercalcemia and should also be borne in mind when considering the role of cytokines in osteoporosis.
Loxodromics for the cyclic splitting complex and their centralizers

We show that an outer automorphism acts loxodromically on the cyclic splitting complex if and only if it has a filling lamination and no generic leaf of the lamination is carried by a vertex group of a cyclic splitting. This is the analog for the cyclic splitting complex of Handel-Mosher's theorem on loxodromics for the free splitting complex. We also show that such outer automorphisms have virtually cyclic centralizers.
Overcoming the barriers to effective glycaemic control for type 2 diabetes

he rising prevalence of type 2 diabetes will impose an increasing burden of diabetic complications on healthcare systems worldwide. The results of the UK Prospective Diabetes Study (UKPDS), and other studies, confirm the potential of effective glycaemic control to improve and extend the lives of people with type 2 diabetes. However, current management algorithms do not achieve sufficient glycaemic control in most patients to realise these improved clinical outcomes. We need a greater readiness to employ intensification of antidiabetic thera- py earlier and in a manner that supports good compliance if we aim to maintain effective, long-term control of type 2 diabetes.
Toxoplasma Antibodies and Spontaneous Abortion

One hundred and fifty‐two women with spontaneous abortion were investigated by hemagglutination (HA) and immunofluorescence antibody (IFA) tests for toxoplasmosis. In 48 cases, quantitive immunoglobulin (Ig) studies and mouse inoculation with gestational material were performed. Positive toxoplasma antibody titers were observed in 62 cases (40.8%) using HA and in 52 cases (38.2%) using IFA. This prevalence was significantly higher than that observed in 80 normal women who served as controls. Toxoplasma gondii was isolated in two cases. No correlation was found between antibody titers and IgG, IgM or IgA levels. We conclude that toxoplasmosis should be considered as the cause of abortion when a patient's antibody titer exceeds 1:256.
A total motion release warm-up improves dominant arm shoulder internal and external rotation in baseball players.

CONTEXT Current literature indicates a correlation between decreased total shoulder range of motion (ROM) and internal rotation (IR) of the dominant arm and increased injury risk in throwers. The optimal method for increasing shoulder ROM, improving performance, and preventing injury is unknown. It is also unknown if treating the non-dominant arm may affect ROM on the dominant side. PURPOSE To explore the effect of the Total Motion Release (TMR®) Trunk Twist (TT) and Arm Raise (AR) on IR and external rotation (ER) of the dominant shoulder in baseball players compared to a traditional dynamic warm-up. DESIGN Cohort study. SETTING University athletic training clinic and baseball field. PARTICIPANTS Pitchers (males, n = 10; age, 18.6 ± 1.3) recruited from local baseball teams were randomly assigned two one of two groups: TMR® treatment group (TMRG; n = 5) or traditional warm-up group (TWG; n = 5). INTERVENTIONS Baseline IR and ER goniometry range of motion (ROM) measurements were recorded. The TMRG then completed the TMR® exercises and post-intervention measurements. The TWG completed a traditional static and dynamic warm-up (e.g., lunges, power skips, sprints, sleeper stretch) and then completed post-intervention measurements. Following the completion of those measurements, the TWG completed the TMR® Trunk Twist and Arm Raise protocol and had post-intervention measurements recorded once more. MAIN OUTCOME MEASURES ROM measures for IR and ER of the dominant shoulder. Alpha level was set at p ≤ 0.05. RESULTS Significant differences were present for IR (p = 0.025) and ER (p = 0.014) between the TMRG and the TWG after initial intervention. Significant differences for IR were present in the TWG between baseline and TMR® intervention and traditional warm-up and TMR® intervention. For the TWG, changes in ER were not statistically significant at baseline, post-warm-up, or post- TMR® intervention. Significant differences were not present for IR (p = 0.44) or ER (p = 0.23) between groups once TMR® had been completed by both groups. CONCLUSIONS TMR® produced larger increases in IR and ER of the throwing shoulder when compared to the TWG. Generalizability is limited, however, by the low number of participants in each group and a potential ceiling effect of attainable ROM gains. Future studies should examine if using a full TMR® treatment process is more beneficial. Additionally, future research should compare TMR® intervention to other warm-up activities or stretching protocols (e.g. resistance tubing, weighted balls) and examine its effect across other variables (e.g., injury rates, throwing velocity). LEVEL OF EVIDENCE Clinical Evidence Based Level 2b.
Examining the safety of dental treatment in pregnant women.

BACKGROUND Although clinicians generally consider it safe to provide dental care for pregnant women, supporting clinical trial evidence is lacking. This study compares safety outcomes from a trial in which pregnant women received scaling and root planing and other dental treatments. METHODS The authors randomly assigned 823 women with periodontitis to receive scaling and root planing, either at 13 to 21 weeks' gestation or up to three months after delivery. They evaluated all subjects for essential dental treatment (EDT) needs, defined as the presence of moderate-to-severe caries or fractured or abscessed teeth; 351 women received complete EDT at 13 to 21 weeks' gestation. The authors used Fisher exact test and a propensity-score adjustment to compare rates of serious adverse events, spontaneous abortions/stillbirths, fetal/congenital anomalies and preterm deliveries (<37 weeks' gestation) between groups, according to the provision of periodontal treatment and EDT. RESULTS Rates of adverse outcomes did not differ significantly (P> .05) between women who received EDT and those who did not require this treatment, or between groups that received both EDT and periodontal treatment, either EDT or periodontal treatment alone, or no treatment. Use of topical or local anesthetics during root planing also was not associated with an increased risk of experiencing adverse outcomes. CONCLUSIONS EDT in pregnant women at 13 to 21 weeks' gestation was not associated with an increased risk of experiencing serious medical adverse events or adverse pregnancy outcomes. Data from larger studies and from groups with other treatment needs are needed to confirm the safety of dental care in pregnant women. CLINICAL IMPLICATIONS This study provides evidence that EDT and use of topical and local anesthetics are safe in pregnant women at 13 to 21 weeks' gestation.
Simulation of Composite Materials by a Network FEM with Error Control

Abstract A novel finite element method (FEM) for the computational simulation in particle reinforced composite materials with many inclusions is presented. It is based on a specially designed mesh consisting of triangles and channel-like connections between inclusions which form a network structure. The total number of elements and, hence, the number of degrees of freedom are proportional to the number of inclusions. The error of the method is independent of the possibly tiny distances of neighboring inclusions. We present algorithmic details for the generation of the problem-adapted mesh and derive an efficient residual a posteriori error estimator which enables us to compute reliable upper and lower error bounds. Several numerical examples illustrate the performance of the method and the error estimator. In particular, it is demonstrated that the (common) assumption of a lattice structure of inclusions can easily lead to incorrect predictions about material properties.
Is High Level of Disability an Indication for Spinal Fusion?: Analysis of Long-Term Outcome After Posterior Lumbar Interbody Fusion Using Carbon Fiber Cages

Objective: Posterior lumbar interbody fusion is a recognized procedure for the treatment of back pain associated with degenerative disc disease and segmental instability. It allows decompression of the spinal canal and circumferential fusion through a single posterior incision. Methods: Sixty-five consecutive patients who underwent posterior lumbar interbody fusion using carbon cages and pedicle fixation between 1993 and 2000 were recruited and contacted with a postal survey. Clinical outcome was assessed by the postoperative clinical findings and complications and the fusion rate, which was assessed using the scoring system described by Brantigan and Steffee. Functional outcome was measured by using improvement in the Oswestry Disability Index, return to work, and satisfaction with the surgical outcome. The determinants of functional relief were analyzed against the improvement in disability using multiple regression analysis. Results: The mean postoperative duration at the time of the study was 4.4 years. Overall radiologic fusion rate was 98%. There was a significant improvement in Oswestry Disability Index (P < 0.01). There was 84% satisfaction with the surgical procedure and 61% return to predisease activity level and full employment. We found preoperative level of disability to be the best determinant of functional recovery irrespective of age or the degree of psychological morbidity and litigation (P < 0.01). Conclusion: The combination of posterior lumbar interbody fusion and posterior instrumented fusion is a safe and effective method of achieving circumferential segmental fusion. A direct relationship between preoperative level of disability and functional recovery suggests that disability should be measured preoperatively and spinal fusion should be performed to alleviate disability caused by degenerative spine.
Estrogen receptor-negative, progesterone receptor-positive breast carcinoma: poor clinical outcome.

OBJECTIVE The biological significance of breast carcinomas negative (-) for estrogen receptor (ER), but positive (+) for progesterone receptor (PR) is unclear. It has been proposed that these tumors contain ER whose presence is masked in binding assays by endogenous estrogen. We analyzed the clinical outcome of 17 patients with ER-PR+ tumors. METHODS The disease-free and overall survival of a series of 300 women with invasive breast carcinoma was followed for 7 to 79 (median 41) months. RESULTS The recurrence rate was significantly greater in ER-PR+ tumors (8/17 [47%]) than in ER+PR+ tumors (27/177 [15%]), and it was similar to the high recurrence rate of ER-PR- tumors (21/57 [37%]). The cancer-related death rate was 3 1/2 times higher in the ER-PR+ group than in the ER+PR+ group. A significant association between ER-PR+ tumors and tumor recurrence or cancer-related death persisted even after correction for other variables associated with poor outcome (eg, tumor size and lymph node involvement). CONCLUSIONS Estrogen receptor-negative, progesterone receptor-positive breast carcinomas are biologically different from ER+PR+ tumors and have a poor clinical outcome.
Imitation and Comprehension of Language in Severe Subnormality

The ability of severely retarded children (mean CA 172.6 months, s.d. 11.0; mean Vocabulary Age on the English Picture Vocabulary Test 65.8 months, s.d. 2.95) to both imitate and comprehend language (the latter in the picture-choice situation) was investigated. In addition latencies to response in a picture-choice comprehension situation were analysed. The independent linguistic variable for all tasks was syntactic complexity. The types of error and response latencies suggested that as syntactic complexity increased, both imitation and comprehension became more difficult for the subjects. The usefulness of imitation as a psycholinguistic assessment technique is discussed.