Miracle-dz/UniFAR-FTUs huggingface dataset:
Independent clonal origins of distinct tumor foci in multifocal papillary thyroid carcinoma.

BACKGROUND Papillary thyroid carcinoma is frequently multifocal. We investigated whether noncontiguous tumor foci arise from intraglandular metastases from a single primary tumor or originate as unrelated clones derived from independent precursors. METHODS Using a polymerase-chain-reaction assay involving the human androgen receptor gene (HUMARA), we analyzed the patterns of X-chromosome inactivation of multiple distinct foci of well-differentiated multifocal papillary thyroid cancer from 17 women. RESULTS Multiple thyroid tumor foci from 10 of 17 patients yielded DNA of adequate quality and were heterozygous for the HUMARA polymorphism and hence suitable for analysis. A single X chromosome was inactivated in each focus, consistent with its monoclonality. When the specific monoclonal configurations of each patient's discrete tumor foci were compared, discordant patterns indicative of independent origins were observed among the tumors from five patients; results in the remaining five were consistent with either a shared or independent clonal origin. CONCLUSIONS Individual tumor foci in patients with multifocal papillary thyroid cancer often arise as independent tumors.
Robotic Surgery: A Current Perspective

Objective:To review the history, development, and current applications of robotics in surgery. Background:Surgical robotics is a new technology that holds significant promise. Robotic surgery is often heralded as the new revolution, and it is one of the most talked about subjects in surgery today. Up to this point in time, however, the drive to develop and obtain robotic devices has been largely driven by the market. There is no doubt that they will become an important tool in the surgical armamentarium, but the extent of their use is still evolving. Methods:A review of the literature was undertaken using Medline. Articles describing the history and development of surgical robots were identified as were articles reporting data on applications. Results:Several centers are currently using surgical robots and publishing data. Most of these early studies report that robotic surgery is feasible. There is, however, a paucity of data regarding costs and benefits of robotics versus conventional techniques. Conclusions:Robotic surgery is still in its infancy and its niche has not yet been well defined. Its current practical uses are mostly confined to smaller surgical procedures.
Adolescents’ Responses to a School-Based Prevention Program Promoting Healthy Eating at School

Background To improve the effectiveness of school-based programs that aim to promote adolescents’ healthy food choices, it is essential to understand the views and behaviors of the target group. This study aimed to get a better understanding of adolescents’ food and health perceptions and their willingness to be involved in a specific school-based prevention program, i.e., the Dutch “Healthy School Canteen Program. ” Methods This study used a mixed-methods research design. First, seven semi-structured focus groups were conducted using a selective sample of 42 Dutch adolescents (25 girls, 17 boys, aged 13–16 years). Second, an online survey among 133 adolescent respondents (72 girls, 61 boys, aged 12–19 years) using snowball sampling was conducted. Content analysis was performed to make inferences about the focus group discussions, whereas statistical analyses were conducted to analyze the survey data. Results Findings from the group discussions indicated that healthy eating was only an issue of importance when adolescents perceived negative physical changes (e.g., with regard to looks or physical performance). Adolescents also indicated that they clearly wanted to make their own food and beverage choices at school. The quantitative data indicated that taste, price, and variety were seen as the most important aspects of a healthy food assortment (mean scores 8.1, 7.8, and 7.7 on a 10-point scale, respectively). In general, a majority of the adolescents (64%) expressed that students should be involved in the organization of a healthy food environment in schools. At the same time, however, adolescents were not willing to participate themselves. This was mostly because they were skeptical about their ideas being heard and put into action by their schools. Conclusion School-based prevention programs, such as the Healthy School Program, should take into account that adolescents have a low risk perception of unhealthy eating and are seeking food choice autonomy. In addition, schools should not lose sight of product price, taste, and variety to make their food assortment attractive to students. If schools aim to involve adolescents in prevention programs that promote healthy eating, it is essential that they have a formal student involvement process that ensures that adolescents’ suggestions are valued.
Electroconvulsive therapy vs. paroxetine in treatment‐resistant depression — a randomized study

Failure to respond to adequate pharmacological treatment for major depression is now the most common indication for the use of electroconvulsive therapy (ECT). The advantages of ECT with respect to both speed and quality of response are clinically important issues, but surprisingly few studies have examined the efficacy of ECT in relation to newer antidepressant agents such as selective serotonin reuptake inhibitors (SSRIs). A total of 39 subjects with major depression and with at least two failed antidepressant trials (mean 4.9 trials) were randomized to either paroxetine treatment (n= 18) or right unilateral (RUL) ECT (n=21). Up to the end of the study treatment we found a reduction in the HAMD score of 59% for the ECT group and of 29% for the paroxetine group (P<0.001 paired t‐test). In the ECT group, 71% of subjects fulfilled the response criteria (at least a 50% decrease in total HAMD score). The present study found ECT to be superior to paroxetine in medication‐resistant major depression, in terms of both degree and speed of response.
A 35-GS/s, 4-Bit Flash ADC With Active Data and Clock Distribution Trees

This paper presents a 35-GS/s, 4-bit flash ADC-DAC with active data and clock distribution trees. At mm-wave clock frequencies, skew due to mismatch in the clock and data distribution paths is a significant challenge for both flash and time-interleaved converter architectures. A full-rate front-end track and hold amplifier (THA) may be used to reduce the effect of skew. However, it is found that the THA output must then be distributed to the comparators with a bandwidth greater than the sampling frequency in order to preserve the flat regions of the track and hold waveform. Instead, if the data and clock distribution have very low skew, the THA can be omitted thus obviating the associated nonlinearities and resulting in improved performance. In this work, a tree of fully symmetric and linear BiCMOS buffers, called a ldquodata treerdquo, distributes the input to the comparator bank with a measured 3-dB bandwidth of 16 GHz. The data tree is integrated into a complete 4-bit ADC including a full-rate input THA that can be disabled and a 4-bit thermometer-code DAC for testing purposes. The chip occupies 2.5 mm times 3.2 mm including pads and is implemented in 0.18 mum SiGe BiCMOS technology. The ADC consumes 4.5 W from a 3.3 V supply while the DAC operates from a 5 V supply and consumes 0.5 W. The ADC has 3.7 ENOB with a 3-dB effective resolution bandwidth of 8 GHz and a full-scale differential input range of 0.24 Vpp. With the THA enabled, the performance degrades rapidly beyond 8 GHz to less than 1-bit, but with the THA disabled, the ENOB remains better than 3-bits for inputs up to 11 GHz with an SFDR of better than 26 dB.
Differential Expression of Prognostic Factors and Effect on Survival in Young (≤40) Breast Cancer Patients: A Case-Control Study

The belief that young women develop more aggressive forms of breast cancer than other women is controversial. The purpose of this study was to determine if women 40 years of age and under with breast cancer have more negative prognostic indicators and a higher 5-year mortality than those women over 40 years of age. From January 1998–December 2002, all women with breast cancer were identified from our tumor registry. Women with metastatic disease at presentation were excluded from our study. The women were divided into two groups, women under 40 (cases) and women 40 and over (controls). Seventy-eight cases were identified and matched to 228 controls. These cohorts were matched 3:1 (cases:controls) based on tumor staging. The data collected on each patient included prognostic factors such as tumor size, tumor type, estrogen and progesterone receptors, Her2/neu, and Ki-67. Information on surgical procedure, postoperative therapy, recurrence, and mortality was also gathered. The mean ages for cases and controls were 35 and 59 years, respectively. The rates of modified radical mastectomy were similar in the two groups, but young women were more likely to have breast reconstruction (33.7% vs 9.8%). The rates of breast conservation therapy were actually lower in the group under 40 (32.5% vs 37.6%). Tumors in the 40 and under group were more frequently estrogen receptor negative (33.8% vs 21.9%: P = 0.046) and progesterone receptor negative (50.0% vs 35.5%: P = 0.033). Younger women also experienced a greater prevalence of Ki-67 (P < 0.001) and higher levels of Her2/neu overexpression (P = 0.013). Women over 40 were more likely to receive hormonal therapy (39.7% vs 36.1%). Women over 40 had a lower overall rate of recurrence. A difference in overall survival does exist between these two groups of women, which trends toward significance. The women 40 and under had a lower overall 5-year survival. The reason for this difference remains unclear. Although we demonstrate a higher percentage of younger women with negative biochemical markers, the only factors independently and significantly related to higher mortality were estrogen receptor negativity and tumor stage at presentation.
Analysis by mutagenesis of the ATP binding site of the gamma subunit of skeletal muscle phosphorylase kinase expressed using a baculovirus system.

Active gamma subunit of skeletal muscle phosphorylase kinase has been obtained by expression of the rat soleus cDNA in a baculovirus system. The protein exhibited the expected pH 6.8/8.2 activity ratio of 0.6, and its activity was insensitive to Ca2+ addition, indicating that it was free gamma subunit and not a gamma subunit-calmodulin complex. It was stimulated approximately 2-fold by Ca(2+)-calmodulin addition, demonstrating that it had retained high-affinity calmodulin binding. By site-directed mutagenesis, we have examined the role of six of the amino acids that constitute the consensus ATP binding site of the protein kinase, which in the gamma subunit is represented by the sequence 26Gly.Arg. Gly.Val. Ser.Ser. Val.Val33. Changes were evaluated by the kinetic determination of the dissociation constants of gamma-ATP, gamma-ADP, gamma-AMP.PCP, and gamma-phosphorylase and the maximum catalytic activity. The mutants Ser26-gamma, Ser29-gamma, Phe30-gamma, and Gly31-gamma each exhibited an essentially identical dissociation constant for gamma subunit phosphorylase, indicating that these mutations had not caused a global alteration in the protein structure but were limited to changes in the nucleotide binding site domain. Substitution of either Val33 (by Gly) or Gly28 (by Ser), two of the most conserved residues in all protein kinases, resulted in enzyme with marginally detectable activity. In noted contrast, the Ser26 mutant, which substituted the first glycine of the consensus glycine trio motif, and which is also very highly conserved, retained at least 25% of the enzymatic activity. The Gly31 substitution, which restored a glycine to a position characteristic for most protein kinases, had little overall effect upon the maximum rate of catalysis. Restoration of Ser30 to the more typical phenylalanine, which is present in most protein kinases, had minimal effect on catalysis. These data provide the first direct evaluation of the roles that different residues play within this consensus glycine trio/valine motif of the protein kinases, which up to now have only been surmised to be of importance because of their conservation. Two unexpected findings are that for one residue that is very conserved (Gly26) there is some flexibility of substitution not apparent from the evolutionary conservation and that a second quite conserved residue in protein kinases (equivalent to Gly at position 31) does not produce a protein optimized for nucleotide binding.
Quantification of plasma DNA as a screening tool for lung cancer.

BACKGROUND Recent studies suggest that circulating DNA may be a potential tumor marker for lung cancer, but most of these studies are conducted between healthy controls and lung cancer patients, with few or no benign lung disease patients included. The objective of this study was to evaluate the performance of plasma DNA quantification in discriminating lung cancer from the healthy and benign lung disease. METHODS Plasma DNA was extracted with a QIAamp DNA Blood Midi kit and quantified by a PicoGreen dsDNA quantitation kit in 44 healthy individuals, 36 benign lung disease patients and 67 lung cancer patients. Discrimination power was evaluated by the receiver operating characteristic curve. RESULTS Plasma DNA values were significantly increased in lung cancer patients, especially in those with metastases, and in benign lung disease patients compared with that in the healthy individuals (P < 0.001, respectively). The values in lung cancer patients were significantly increased compared with that in the benign lung disease patients (P < 0.001). The area under the curve was 0.96 [95% confidence interval (CI) 0.92 - 0.99] for the healthy versus lung cancer, 0.73 (95% CI 0.64 - 0.83) for lung cancer versus benign lung disease, and 0.86 (95% CI 0.80 - 0.91) for lung cancer versus the healthy and benign lung disease. CONCLUSIONS Plasma DNA quantification has a strong power to discriminate lung cancer from the healthy and from the healthy and benign lung disease, less power to discriminate lung cancer from benign lung disease. Plasma DNA quantification may be useful as a screening tool for lung cancer.
Shape optimization of car body structure based on Uniform Design method

A finite element model for a domestic car-body is built. Based on the stiffness criterion, the stiffness sensitivity of the whole auto-body structure parts are analyzed under torsion and bending loads. Based on the results, the design of the structure and dimension of the body parts is optimized and the stiffness and sensitivity of the whole body is proved to be more reasonable. The Uniform Design method is used to arrange tests. The test results show after appropriate optimization the weight of the vehicle automobile body reduced form 301.5 Kg to 292.6 Kg when the anti-curving and anti-torsional rigidity of the autobody maintained invariable.
Biomarkers of treatment efficacy in patients with chronic spontaneous urticaria.

Summary Background. Currently there are no biomarkers useful to predict the future evolution and the therapeutic response in patients with chronic spontaneous urticaria (CSU). Objective. To review the available information on biomarkers that might be applied for the follow up of the response to guideline recommended therapies for CSU. Methods. A review of the medical literature on CSU potential clinical and laboratory biomarkers in PubMed and MEDLINE including the terms urticaria, chronic urticaria, chronic idiopathic urticaria, chronic spontaneous urticaria, antihistamines (AHs), omalizumab (OMA), cyclosporine (CyA), and treatment. Results. Clinical manifestations that were associated to poor responses to AHs were atopy, asthma, rhinitis / rhinosinusitis, thyroid disease, hypertension, higher disease activity and duration. Laboratory markers of AH resistance that have been reported include Complement C5a fraction, Autologous Serum Skin Test (ASST), Basophil Activation Test (BAT), D-dimer and LCN2 adipokine. Basophil Histamine Release Assay (BHRA), ASST, and basophil CD203c-upregulating activity in the serum correlated with favorable response to OMA, whereas disease duration and severity, BAT, BHRA, and D-dimer levels were associated with better responses to CyA. Conclusion. Some promising biomarkers useful for patient management in CSU, have been identified in the literature. There is, however, an urgent need of new, easy-to-perform markers that can be made widely available for the optimal care of patients suffering CSU.
News Feature: Radiation redux

Could traditional radiation treatments work in concert with immunotherapy to mount a more effective assault on cancer? When Michael Postow started his fellowship training in medical oncology at the Memorial Sloan Kettering Cancer Center (MSKCC) in 2010, he wasn’t familiar with the term “abscopal. ” Coined decades before he was born and then largely forgotten by physicians, it describes a phenomenon in which radiation delivered at one site in the body has an effect on distant tissues that are, literally, “outside” the “scope” of the radiation blast. “It wasn’t something I had ever heard about,” Postow says. That changed when a patient at MSKCC had an unexpected response to radiation therapy. Fig. 1. Researchers are combining radiation therapy, here targeting brain cancer, with immunotherapy in hopes of finding a robust strategy for stymying various cancers. Image courtesy of Shutterstock/John Panella. The young woman had been receiving a then-experimental immunotherapy drug, called ipilimumab, to treat her advanced case of melanoma. The drug, now marketed by Bristol–Myers Squibb as Yervoy, blocks a so-called checkpoint protein that normally blunts immune activation. Ipilimumab, in effect, takes the brakes off the immune system, freeing cancer-killing T cells to mount an attack against the tumor. But this therapeutic strategy only works when there are tumor-targeted T cells in the immune system’s tank, otherwise there’s nothing to rev into action. That seemed to be the case for Postow’s patient. Tumors continued to grow throughout her spleen, in a lymph node in her chest, and near her spine. The pain from the tumor in her back became excruciating. Postow and his colleagues, led by physician-scientist Jedd Wolchok, chief of the melanoma and immunotherapeutics service at MSKCC, arranged for the woman to receive radiation. They expected to shrink the tumor near her spine and offer some relief from the back pain, nothing …
Comparison of short- and long-term function and radiographic osteoarthrosis in dogs after postoperative physical rehabilitation and tibial plateau leveling osteotomy or lateral fabellar suture stabilization.

OBJECTIVES To compare short- and long-term functional and radiographic outcome of cranial cruciate ligament (CrCL) injury in dogs treated with postoperative physical rehabilitation and either tibial plateau leveling osteotomy (TPLO) or lateral fabellar suture stabilization (LFS). STUDY DESIGN Prospective observational clinical study. ANIMALS Medium to large breed dogs with naturally occurring CrCL injury (n=65). METHODS Dogs with CrCL injury were treated with either TPLO or LFS and with identical physical rehabilitation regimes postoperatively. Limb peak vertical force (PVF) was measured preoperatively and at 3, 5, and 7 weeks, and 6 months and 24 months postoperatively. Stifles were radiographically assessed for osteoarthrosis (OA) preoperatively and 24 months postoperatively. RESULTS Thirty-five dogs had LFS and 30 dogs had TPLO. Radiographic OA scores were significantly increased at 24 months compared with preoperative scores in all dogs. Radiographic OA scores preoperatively and at 24 months were not significantly different between treatment groups. PVF was significantly increased from preoperative to 24 months among both treatment groups but not significantly different between treatment groups preoperatively or at 3, 5, 7 weeks, 6, or 24 months. CONCLUSION No significant difference in outcome as determined by ground reaction forces or radiographic OA scores were found between dogs with CrCL injury treated with LFS or TPLO. CLINICAL RELEVANCE LFS and TPLO remain good options for stabilizing stifles with CrCL injury with all dogs showing significant functional improvement. This study does not support the superiority of either surgical technique.
Individually Controlled Aspirin in the Long-Term Treatment of Patients with Chronic Arterial Diseases

A simple method of measuring the biological effect of acetylsalicylic acid (ASA), based on the determination of the disaggregation rate (DR) of plate let aggregation induced by adenosine diphosphate (ADP), is described. The DR was found to correlate with the inhibition of the production of ma londialdehyde (MDA) by platelets (r = 0.66, P < 0.001). Therefore, the DR was used for laboratory monitor ing of the ASA effect. The study in cluded 63 arteriosclerotic patients — patients with ischemic heart disease (IHD), peripheral arterial disease (PAD), or cerebrovascular insuffi ciency (CVI) — who were analyzed before treatment and after receiving ASA in an individually controlled dosage. Before treatment the authors found an increased level of MDA and a longer euglobulin clot lysis time in patients when compared with healthy volunteers (n=16). Extremely differ ent doses of ASA were required to normalize initially elevated MDA lev els in patients. Normalization of the MDA level corresponds to a DR of at least 50% (in comparison with 0-13% without treatment). When judging the ASA dose individually from the 50% DR, the authors demonstrated that there were no differences in the levels of cyclooxygenase- and lipoxy genase-derived eicosanoids between healthy volunteers (n = 16) and arteri osclerotic patients receiving 100-250 mg (n=18), 500 mg (n=17), or 750-1500 mg ASA per day (n=6). Thus, their results support the idea of using individually controlled ASA as the most promising way of resolv ing the "aspirin dilemma" and pro vide a simple and reproducible method of measuring the biological effect of ASA.
Marathon progress: demography, morphology and environment

Abstract As opposed to many other track-and-field events, marathon performances still improve. We choose to better describe the reasons for such a progression. The 100 best marathon runners archived from January 1990 to December 2011 for men and from January 1996 to December 2011 for women were analysed. We determined the impact of historical, demographic, physiological, seasonal and environmental factors. Performances in marathons improve at every level of performance (deciles). In 2011, 94% of the 100 best men athletes were African runners; among women athletes they were 52%. Morphological indicators (stature, body mass and Body Mass Index (BMI)) have decreased. We show a parabolic function between BMI and running speed. The seasonal distribution has two peaks, in spring (weeks 14 to 17) and autumn (weeks 41 to 44). During both periods, the average temperature of the host cities varies close to optimal value for long distance race. African men and women runners are increasingly dominating the marathon and pushing its record, through optimal eco-physiological conditions.