Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic workup and costs of a single supplemental molecular breast imaging screen of mammographically dense breasts.

OBJECTIVE The purpose of this study was to examine additional diagnostic workup and costs generated by addition of a single molecular breast imaging (MBI) examination to screening mammography for women with dense breasts. SUBJECTS AND METHODS Women with mammographically dense breasts presenting for screening mammography underwent adjunct MBI performed with 300 MBq (99m)Tc-sestamibi and a direct-conversion cadmium-zinc-telluride dual-head gamma camera. All subsequent imaging tests and biopsies were tracked for a minimum of 1 year. The positive predictive value of biopsies performed (PPV3), benign biopsy rate, cost per patient screened, and cost per cancer detected were determined. RESULTS A total of 1651 women enrolled in the study. Among the 1585 participants with complete reference standard, screening mammography alone prompted diagnostic workup of 175 (11.0%) patients and biopsy of 20 (1.3%) and yielded five malignancies (PPV3, 25%). Results of combined screening mammography plus MBI prompted diagnostic workup of 279 patients (17.6%) and biopsy of 67 (4.2%) and yielded 19 malignancies (PPV3, 28.4%). The benign biopsy rates were 0.9% (15 of 1585) for screening mammography alone and 3.0% (48 of 1585) for the combination (p < 0.001). The addition of MBI increased the cost per patient screened from $176 for mammography alone to $571 for the combination. However, cost per cancer detected was lower for the combination ($47,597) than for mammography alone ($55,851). CONCLUSION The addition of MBI to screening mammography of women with dense breasts increased the overall costs and benign biopsy rate but also increased the cancer detection rate, which resulted in a lower cost per cancer detected than with screening mammography alone.
Physical exercise and health: a review.

BACKGROUND Physical activity results in increased exercise capacity and physical fitness, which may lead to many health benefits. Individuals who are more physically active appear to have lower rates of all-cause mortality, probably due to a decrease in chronic diseases including coronary artery disease (CAD). This may result from an improvement in cardiovascular risk factors in addition to enhanced fibrinolysis, improved endothelial function, decreased sympathetic tone, and other yet undetermined factors. METHODS We reviewed the literature on physical activity and health with particular reference to the benefits derivable by engaging in regular physical activity. The MEDLINE/PUBMED and bibliographic searches for English language studies were used. RESULTS Physical inactivity is now considered a risk factor for Cardiovascular diseases (CVD). Regular exercise results in an increase in exercise capacity and lower myocardial oxygen demand leading to cardiovascular benefits, including lower mortality rates. Physically active individuals suffer from fewer ailments than do less-active individuals. Physical activity reduces cardiovascular risk through lowering of blood pressure, improved glucose tolerance, reduced obesity, improvement in lipid profile, enhanced fibrinolysis, improved endothelial function and enhanced parasympathetic autonomic tone. CONCLUSION Physical exercise has many health benefits and the evidence for this continues to accumulate. Health care professionals should incorporate counselling to patients for physical exercise in their daily clinical practice, while health policy makers and community physicians should see to implementation of this at the community level.
The impact of the death penalty on murder

Both history and daily crime sheets underscore a depressing capacity for human violence and inhumanity. Some scholars feel that eliminating capital punishment would be a step toward reducing the toll of human suffering, whereas others feel that retaining the death penalty will prevent some murders at least. Kovandzic, Vieraitis, and Boots (2009, this issue) provide a comprehensive ordinary least-squares (OLS) state panel data assessment of the most recent postmoratorium data available and reach a strong conclusion that the death penalty does not deter murder. This article is an important piece in the complex jigsaw puzzle that will illuminate which factors can deter which crimes under which circumstances. Commenting on the Kovandzic et al. (2009) article are two scholars who have authored major articles that concern the impact of the death penalty on murder. Richard Berk (2009, this issue) speculates whether the deterrent impact of the death penalty is knowable given current data and methods, whereas Paul Rubin (2009, this issue) argues that “the weight of the evidence as well as the theoretical predictions both argue for deterrence, and econometrically flawed studies such as this article are insufficient to overthrow this presumption. ” With virtually all positions represented by these three documents, I will discuss three recent new studies that I think address some of Berk’s concern and provide strong evidence to support that Kovandzic et al. are right.
Smooth Muscle Autoantibodies in Infectious Mononucleosis

Smooth muscle antibodies (S.M.A.) were found in the sera of 81% of 126 patients over 10 years old with seropositive infectious mononucleosis tested within one month of onset. In 27 patients presenting clinically with infectious mononucleosis but having negative Paul-Bunnell tests the incidence of S.M.A. was 44%. In children 10 years of age or less in these two categories S.M.A. were present in 75% and 25% respectively, while in children of similar age not suspected of having infectious mononucleosis the incidence of S.M.A. was 10%. Among 45 adults with past histories of seropositive infectious mononucleosis more than one year before the incidence of S.M.A. was 33%, in contrast to 14% in 98 subjects with a negative history for infectious mononucleosis.
Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer.

PURPOSE Panitumumab is a fully human monoclonal antibody directed against the epidermal growth factor receptor (EGFR). We compared the activity of panitumumab plus best supportive care (BSC) to that of BSC alone in patients with metastatic colorectal cancer who had progressed after standard chemotherapy. PATIENTS AND METHODS We randomly assigned 463 patients with 1% or more EGFR tumor cell membrane staining, measurable disease, and radiologic documentation of disease progression during or within 6 months of most recent chemotherapy to panitumumab 6 mg/kg every 2 weeks plus BSC (n = 231) or BSC alone (n = 232). Tumor assessments by blinded central review were scheduled from week 8 until disease progression. The primary end point was progression-free survival (PFS). Secondary end points included objective response, overall survival (OS), and safety. BSC patients who progressed could receive panitumumab in a cross-over study. RESULTS Panitumumab significantly prolonged PFS (hazard ratio [HR], 0.54; 95% CI, 0.44 to 0.66, [P < .0001]). Median PFS time was 8 weeks (95% CI, 7.9 to 8.4) for panitumumab and 7.3 weeks (95% CI, 7.1 to 7.7) for BSC. Mean (standard error) PFS time was 13.8 (0.8) weeks for panitumumab and 8.5 (0.5) weeks for BSC. Objective response rates also favored panitumumab over BSC; after a 12-month minimum follow-up, response rates were 10% for panitumumab and 0% for BSC (P < .0001). No difference was observed in OS (HR, 1.00; 95% CI, 0.82 to 1.22), which was confounded by similar activity of panitumumab after 76% of BSC patients entered the cross-over study. Panitumumab was well tolerated. Skin toxicities, hypomagnesaemia, and diarrhea were the most common toxicities observed. No patients had grade 3/4 infusion reactions. CONCLUSION Panitumumab significantly improved PFS with manageable toxicity in patients with chemorefractory colorectal cancer.
Long-term neuropsychiatric follow-up in hyperprolinemia type I

The neuropsychiatric phenotype associated with hyperprolinemia type I (HPI) is still under debate. To our knowledge, no long-term follow-up on patients with HPI has been reported so far. We have previously described the clinical, biochemical, and molecular features of four patients with HPI. Here, we report on the neuropsychiatric and genotype features of an expanded sample of 10 patients with HPI with a mean follow-up duration of 11 years. Epileptic manifestations and/or cognitive impairment were prevalent at onset, but they were subsequently replaced by psychiatric disorders. Social behavior and relational skills were considerably impaired in the majority of cases. Learning disability was present in one patient. The complex neurochemical effects of proline on the central nervous system and genotype/phenotype correlations were discussed.
Mutational Alteration of Human Immunodeficiency Virus Type 1 Vif Allows for Functional Interaction with Nonhuman Primate APOBEC3G

ABSTRACT Human APOBEC3F (hA3F) and APOBEC3G (hA3G) are antiretroviral cytidine deaminases that can be encapsidated during virus assembly to catalyze C→U deamination of the viral reverse transcripts in the next round of infection. Lentiviruses such as human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) have evolved the accessory protein Vif to induce their degradation before packaging. HIV type 1 (HIV-1) Vif counteracts hA3G but not rhesus macaque APOBEC3G (rhA3G) or African green monkey (AGM) APOBEC3G (agmA3G) because of a failure to bind the nonhuman primate proteins. The species specificity of the interaction is controlled by amino acid 128, which is aspartate in hA3G and lysine in rhA3G. With the objective of overcoming this species restriction, mutations were introduced into HIV-1 Vif at amino acid positions that differed in charge between HIV-1 Vif and SIV Vif. The mutant proteins were tested for the ability to counteract hA3G, rhA3G, and agmA3G. Alteration of the conserved sequence at positions 14 to 17 from DRMR to SERQ, which is the sequence in AGM Vif, caused HIV-1 Vif to functionally interact with rhA3G and agmA3G. Mutation of three residues to the sequence SEMQ allowed interaction with rhA3G. SEMQ Vif also counteracted D128K mutant hA3G and wild-type hA3G. Introduction of the sequence into an infectious molecular HIV-1 clone allowed the virus to replicate productively in human cells that expressed rhA3G or hA3G. These findings provide insight into the interaction of Vif with A3G and are a step toward the development of a novel primate model for AIDS.
Heme Oxygenase-1/Carbon Monoxide-regulated Mitochondrial Dynamic Equilibrium Contributes to the Attenuation of Endotoxin-induced Acute Lung Injury in Rats and in Lipopolysaccharide-activated Macrophages

Background:Sepsis-associated acute lung injury remains the major cause of mortality in critically ill patients and is characterized by marked oxidative stress and mitochondrial dysfunction. Mitochondrial dynamics are indispensable for functional integrity. Additionally, heme oxygenase (HO)-1/carbon monoxide conferred cytoprotection against end-organ damage during endotoxic shock. Herein, we tested the hypothesis that HO-1/carbon monoxide played a critical role in maintaining the dynamic process of mitochondrial fusion/fission to mitigate lung injury in Sprague-Dawley rats or RAW 264.7 macrophages exposed to endotoxin. Methods:The production of reactive oxygen species, the respiratory control ratio (RCR), and the expressions of HO-1 and mitochondrial dynamic markers were determined in macrophages. Concurrently, alterations in the pathology of lung tissue, lipid peroxidation, and the expressions of the crucial dynamic proteins were detected in rats. Results:Endotoxin caused a 31% increase in reactive oxygen species and a 41% decrease in RCR levels (n = 5 per group). In parallel, the increased expression of HO-1 was observed in lipopolysaccharide-stimulated macrophages, concomitantly with excessive mitochondrial fission. Furthermore, carbon monoxide-releasing molecule-2 or hemin normalized mitochondrial dynamics, which were abrogated by zinc protoporphyrin IX. Additionally, impaired mitochondrial dynamic balance was shown in Sprague-Dawley rats that received lipopolysaccharide, accompanied by pathologic injury, elevated malondialdehyde contents, decreased manganese superoxide dismutase activities, and lowered RCR levels in rat lung mitochondria. However, the above parameters were augmented by zinc protoporphyrin IX and were in turn reversed by hemin. Conclusions:The HO-1/carbon monoxide system modulated the imbalance of the dynamic mitochondrial fusion/fission process evoked by lipopolysaccharide and efficiently ameliorated endotoxin-induced lung injury in vivo and in vitro.
Aortorenal Arterial Autografts: Long-term Assessment

• Ninety-four iliac arterial autografts were placed in 86 hypertensive patients (age range, 7 to 57 years) during a 16-year period for renal artery reconstruction of nonatherosclerotic lesions. Ten patients were children, and nine patients had a solitary kidney. Ex vivo repair was used in 21 patients. There were no early postoperative deaths; one patient died three months postoperatively of unrelated disease. Two grafts occluded in the early postoperative period. Follow-up of one to 16 years (mean, 5.6 years) was available in 77 patients (93%). Forty-one patients underwent late arteriography at an average of 5.7 years postoperatively. Fifty-one patients (66%) were regarded as cured of their hypertension, the conditions of 25 patients (32%) improved, and the condition of one patient (1.2%) was unchanged. There were no late autograft occlusions. Atherosclerotic anastomotic stenosis developed in one autograft 13 years postoperatively and was relieved by reoperation. Dilation of one autograft was observed seven years postoperatively but did not increase on subsequent arteriograms. In five children, follow-up angiograms showed that the size of the autograft paralleled that of the contralateral renal artery. These results support the preferential use of an autograft during reconstruction of nonatherosclerotic lesions that cause renovascular hypertension. ( Arch Surg 1981;116:1416-1422)
Exposure‐Response Analysis of Sonidegib (LDE225), an Oral Inhibitor of the Hedgehog Signaling Pathway, for Effectiveness and Safety in Patients With Advanced Solid Tumors

Sonidegib selectively inhibits smoothened protein, suppresses the growth of Hedgehog pathway‐dependent tumors, and has recently been approved in the indication of locally advanced basal cell carcinoma. A comprehensive exposure‐response analysis was conducted to further characterize the relationship of sonidegib exposure to efficacy and safety. Minimum observed plasma concentration at predose (Cmin), peak concentration (Cmax), and area under the curve were used as exposure endpoints. Exposure‐efficacy analyses included data from 190 patients who received sonidegib 200 mg or 800 mg once daily in the primary efficacy study. Objective response rate (ORR) (complete response [CR] or partial response [PR]), progression‐free survival (PFS), and time to tumor response (TTR) were assessed by logistic regression, Cox regression, and Kaplan‐Meier analyses. Exposure‐safety (creatine phosphokinase [CK] elevation) analyses included data from 336 patients pooled from 4 clinical trials and included doses across ranges of 100 to 3000 mg once daily and 250 to 750 mg twice daily. Similar plasma exposure was observed between responders and nonresponders. The logistic regression model of week 5 Cmin vs ORR indicated no relationship between sonidegib exposure resulting from 200 mg or 800 mg doses and the probability of CR or PR. A similar conclusion of no exposure‐efficacy relationship was drawn from the PFS and TTR analyses. Increased exposure was associated with a greater risk of grade 3 or 4 CK elevation, with lower risk in females than in males when Cmin was used in the model. These analyses support the sonidegib dose recommendation for registration and are consistent with clinical observations.
Coping profiles of young Athletes in their everyday life: A three-wave two-month study†

Abstract Young athletes in intensive training settings are confronted with a series of daily stressors although they have a smaller and less flexible coping repertoire than adults. Moreover, previous studies neglected the multivariate nature of coping. Therefore, the purpose of the current study was to first identify coping profiles of young athletes in response to daily stressors related to their competitive sport involvement. Second, the study examined: (a) if such profiles were similar across the three waves, (b) how many participants belonged to the same profile along the three waves, and (c) whether individuals from distinct profiles differed on burnout, stress, and recovery. One hundred and forty-seven young table-tennis players involved in intensive training settings completed the CICS, RESTQ-Sport, and ABQ three times during a 2-month period. Cluster analyses indicated three similar clusters across the three waves: task-oriented coping, distraction- and disengagement-oriented coping, and low coping profiles. The distribution of athletes significantly varied across waves. Burnout, stress, and recovery significantly differed across the coping profiles. Athletes from the task-oriented coping profile were characterized by the best psychological adjustment (high scores of recovery and low scores of stress and burnout). In contrast, athletes from the distraction- and disengagement-oriented coping profile were characterized by the worst psychological adjustment (high scores of stress and burnout and low scores of recovery). These findings highlighted that the coping profiles allow examining coping within a holistic approach, teasing out the complex associations with key outcomes, such as burnout, stress, and recovery.
Just-in-Time or Plenty-of-Time Teaching? Different Electronic Feedback Devices and Their Effect on Student Engagement

This study examines how incorporating different electronic feedback devices (i.e., clickers versus web-based polling) may affect specific types of student engagement (i.e., behavioral, emotional, and cognitive engagement), whether students' self-efficacy for learning and performance may differ between courses that have integrated clickers and those that use web-based polling, and whether using web-based polling influences faculty members' instructional practices. The participants included six instructors and 209 students enrolled in classes at a university in the southwestern United States in which the instructors used either clickers or web-based polling. The Plenty-of-Time Teaching (PoTT) and the Just-in-Time Teaching (JiTT) approaches and their implications are presented. The results of this study highlight the benefits of using various types of electronic feedback devices to provide innovative ways to implement JiTT or PoTT, such as gauging students' understanding with pre-class polls, and offer insights that can benefit educators who wish to promote students' emotional and cognitive engagement with various types of feedback devices.
A new high-throughput screening method for the detection of chronic lymphatic leukemia and myelodysplastic syndrome

Abstract Background: The VCS technology of Beckman Coulter differentiates white blood cells based on measures of their volume, conductivity and light scatter. The current study investigated the predictive value of index measures, known as research population data, for the detection of chronic lymphatic leukemia and myelodysplastic syndrome. Methods: Blood cell counts were performed in samples from 44 patients with chronic lymphatic leukemia, 19 patients with myelodysplastic syndrome and 199 healthy blood donors using the Beckman Coulter LH750. Means and standard deviations of volume, conductivity and scatter of lymphocytes and neutrophils were evaluated as predictors for both diseases. Their specificity and selectivity were evaluated by logistic regression and receiver operating characteristic curve analysis. Results: Research population data were significantly different among groups. For chronic lymphatic leukemia, standard deviations of lymphocytes scatter and volume showed most relevant differences in comparison to healthy blood donors (sensitivity 88.6%, specificity 84.4%). For myelodysplastic syndrome, standard deviations of neutrophils conductivity were most predictive (sensitivity 73.7%, specificity 93.0%). Areas under corresponding receiver operating characteristic curves were 0.941 and 0.951, respectively. Conclusions: Based on their high predictive value, research population data could be routinely used to screen for chronic lymphatic leukemia and myelodysplastic syndrome. Clin Chem Lab Med 2008;46:85–8.
The Uncapacitated Facility Location Problem with Client Matching

TheUncapacitated Facility Location Problem with Client Matching (LCM) is an extension of theUncapacitated Facility Location Problem (UFLP), where two clients allocated to a facility can be matched. As in the UFLP, facilities can be opened at any ofm predefined locations with given fixed costs, andn clients have to be allocated to the open facilities. In classical location models, the allocation cost is the distance between a client and an open facility. In the LCM, the allocation cost is either the cost of a return trip between the facility and the client, or the length of a tour containing the facility and two clients. The similarities of the LCM with the classical UFLP and the matching problem are exploited to derive valid inequalities, optimality cuts, and polyhedral results. A greedy heuristic and a branch-and-cut algorithm are developed, and several separation procedures are described. Computational experiments confirm the efficiency of the proposed approach.
Hox Genes of the Direct-type Developing Sea Urchin Peronella japonica

Abstract Peronella japonica is a direct-type developing sea urchin that metamorphoses in 3 days without feeding, providing a good system to analyze developmental mechanisms especially at later larval stages to metamorphosis. We surveyed the Hox genes of P. japonica by PCR and RT-PCR, and isolated 13 Hox-type sequences. Phylogenetic analysis and database searches resulted in identification of all the P. japonica orthologs of the Hox genes that have been reported in other sea urchins, plus 3 Hox-type genes: the Evx-type, the Xlox-type genes, and an additional posterior Hox gene. This is the first report to show the Evx in echinoderms. The present results revealed the putative Hox gene cluster of P. japonica, which contains three anterior, four medial, and four posterior genes plus the Evx. The organization is essentially similar to the vertebrate Hox cluster except for only a single gene for Hox4-5 types. The C-terminal amino acid sequence outside the homeodomain of Hox4/5 suggested that loss of Hox4 might have occurred in the echinoderm lineage.