Miracle-dz/UniFAR-FTUs huggingface dataset:
A Pivotal Role for DNase I-Sensitive Regions 3b and/or 4 in the Induction of Somatic Hypermutation of IgH Genes1

Chimeric mice were prepared from embryonic stem cells transfected with IgH genes as transgenes and RAG-2-deficient blastocysts for the purpose of identifying the cis-acting elements responsible for the induction of somatic hypermutation. Among the three transgene constructs used, the VH promoter, the rearranged VH-D-JH, an intron enhancer/matrix attachment region, and human Cμ were common to all, but the 3′-untranslated region in each construct was different. After immunization of mice with a T cell-dependent Ag, the distribution and frequency of hypermutation in transgenes were analyzed. The transgene lacking the 3′ untranslated region showed a marginal degree of hypermutation. Addition of the 3′ enhancer resulted in a slight increase in the number of mutations. However, the transgene containing DNase I-sensitive regions 3b and 4 in addition to the 3′ enhancer showed more than a 10-fold increase in hypermutation, reaching levels comparable to those observed in endogenous VH186.2 genes of C57BL/6 mice.
Randomized, open-label, multicenter, phase III study of eribulin versus dacarbazine in patients (pts) with leiomyosarcoma (LMS) and adipocytic sarcoma (ADI).

LBA10502 Background: In a phase II study of pts with advanced soft tissue sarcoma, 32% and 47% of pts with LMS and ADI respectively, treated with the microtubule dynamics inhibitor eribulin achieved progression-free survival (PFS) at the 12 wk timepoint (Schöffski et al. Lancet Oncol. 2011; NCT00413192). Based on these findings, this phase III study (NCT01327885) compared overall survival (OS) in pts with advanced LMS and ADI treated with eribulin or dacarbazine. METHODS Pts aged ≥ 18 yrs with advanced high/intermediate grade LMS or dedifferentiated, myxoid, round cell or pleomorphic variants of ADI incurable by surgery and/or radiotherapy were enrolled. Pts had ECOG status ≤ 2 and had received ≥ 2 standard systemic treatment regimens including an anthracycline. Pts were randomized 1:1 to eribulin (1.4 mg/m2, IV on D1 and D8) or dacarbazine (850-1200 mg/m2, IV on D1) every 21 days until disease progression. Primary endpoint was OS. Secondary endpoints included PFS, PFS rate at Wk 12 and safety. RESULTS Overall, 452 pts (67% female; 79% < 65 yrs) were randomized (228 eribulin; 224 dacarbazine). Median OS for eribulin and dacarbazine was 13.5 and 11.5 months, respectively (HR = 0.768, 95% CI 0.618-0.954; P= 0.017). PFS was 2.6 months in both arms (HR = 0.877, 95% CI 0.710-1.085; P= 0.229). PFS rate at Wk 12 was 33% and 29% for eribulin and dacarbazine, respectively. In eribulin and dacarbazine arms, respectively, 26% and 14% of pts required dose reductions and 8% and 5% discontinued due to treatment-emergent adverse events (TEAEs). TEAEs were more frequent in eribulin than dacarbazine arm, including neutropenia (44% vs 24%), pyrexia (28% vs 14%), peripheral sensory neuropathy (20% vs 4%) and alopecia (35% vs. 3%); as were TEAEs of grade 3 (63% vs 53%), grade 4 (26% vs 20%), and fatal TEAEs (4% vs 1%). Thrombocytopenia was more frequent in dacarbazine than eribulin arm (28% vs 6%). CONCLUSIONS This phase III trial of eribulin trial met its primary objective of OS benefit in pretreated pts with advanced LMS or ADI. Eribulin had a toxicity profile consistent with prior experience, with no unexpected or new safety findings. FUNDING SOURCE Eisai Inc. CLINICAL TRIAL INFORMATION NCT01327885.
Roentgenographic investigation of frequency and degree of canal curvatures in human permanent teeth.

Canal curvatures of 700 permanent human teeth were determined by measuring the angle and the radius of the curvatures and the length of the curved part of the canal. For each type of tooth (except third molars) 50 were selected at random and were investigated. Size 08 silver points were inserted into the canals, and the teeth were radiographed from a facial and proximal view by using a standardized technique. All radiographs were analyzed by a computerized digital image processing system. Of the 1163 root canals examined, 980 (84%) were curved and 65% showed an angle < or = 27 degrees with radii < 40 mm. Thirteen percent displayed angles between 27 degrees and 35 degrees with radii not greater than 15 mm, and 9% of all canals that were investigated had curves > 35 degrees with the greatest radius of 13 mm. The greatest angle of all the teeth was 75 degrees with a radius of 2 mm. To define the canal curvature mathematically and unambiguously, the angle, the radius, and the length of the curve should be given.
Primary immunodeficiency diseases and cancer: The immunodeficiency‐cancer registry

Data from the newly established Immunodeficiency‐Cancer Registry show 151 tumors in 145 patients with primary immunodeficiency syndromes, including: sex‐linked (Bruton's) agammaglobulinemia, 6 patients; severe combined system immunodeficiency, 9 patients; Wiskott‐Aldrich syndrome, 24 patients; ataxia‐telangiectasia, 52 patients; common variable (late onset) immunodeficiency, 41 patients; isolated IgA deficiency, 7 patients; and isolated IgM deficiency, 6 patients. The risk of development of malignancy is from 2–10%, indicating that these individuals have a far greater than chance risk of developing malignancies, in spite of their short life‐spans. Tumors are divided into major histologic types: lymphoreticular, 58% of total; leukemias, 17% of total; epithelial. 18% of total; mesenchymal, 3% of total; and nervous system, 4% of total. Data are reported on 14 families in which 12 siblings had the same tumors and identical primary immunodeficiency diseases. The majority of tumors are lymphoreticular or leukemias: these findings are consistent with the hypothesis that individuals with primary immunodeficiency syndromes have intrinsic abnormalities of the lymphoid system which result in increased frequency of malignant transformation and inability to eliminate transformed cells. Further reporting of tumors is urged.
Factors affecting wettability and bond strength of solder joint couples

Abstract The paper discusses the scientific understanding of the role of interfacial phenomena in joining of dissimilar materials using liquid-phase-assisted processes. From the example of the Sn-alloy/Cu system, it is demonstrated that interaction in the liquid solder/substrate couples is accompanied by a number of complex interfacial reactions leading to significant changes in the structure and chemistry of interfaces (solder/substrate, solder/environment, substrate/environment) and remaining solder layer that finally influence the mechanical properties of solder joints. The experimental data on wetting behavior, interface characterization, and mechanical properties of different solder/metal substrate couples are analyzed in order to display the role of such factors as time and temperature of interaction, environment (protective atmosphere, flux), presence of oxide films on interfaces, alloying additions to a solder, formation of interfacial phases, and porosity.
Effect of Season and Temperature Acclimation on the Function of Crucian Carp (Carassius Carassius) Heart

The temperature dependence of heart rate and isometric contractile properties of cardiac tissue was determined in thermally acclimated crucian carp ( Carassius carassius L.). Fish were adapted for more than 3 weeks to 5 and 15°C during both summer and winter. At all but the lowest experimental temperatures, heart rate ( f H), maximal isometric force ( F max) and pumping capacity were higher in summer fish acclimated to 15°C than in winter fish acclimated to 5°C. Except for f H, similar acclimation effects were observed when comparing cold- and warm-acclimated crucian carp in both seasons. In contrast, the kinetics of isometric contraction was not modified either by seasonal acclimatization or by thermal acclimation within a given season: the temperature dependence of time to peak force (TPT) and time to half-relaxation ( T 1/2R) was independent of the previous thermal history of the fish. The hearts of winter fish were about 10% smaller than those of summer fish. These results show that acclimation to cold does not induce positive compensatory changes in function or size of crucian carp heart, as happens in many other teleost fishes. Instead, an inverse or noncompensatory acclimation was found. Owing to the inverse thermal acclimation, in winter (at 4°C) the contractile performance of the crucian carp heart is less than one-third of that in summer (at 20°C). The low cardiac activity in cold-acclimated crucian carp seems to be associated with its inactive life style, which is necessary during the winter months to minimize energy consumption in a severely hypoxic environment. Note: To whom reprint requests should be addressed.
Can machine learning techniques predict customer dissatisfaction? A feasibility study for the automotive industry

The automotive industry is in the strongest competition ever, as this sector gets disrupted by new arising competitors. Providing services to maximum customer satisfaction will be one of the most crucial competitive advantages in the future. Around 1 Terabyte of objective data is created every hour today. This volume will significantly grow in the future by the increasing number of connected services within the automotive industry. However, customer satisfaction determination is solely based on subjective questionnaires today without taking the vast amount of objective sensor and service process data into account. This work presents an industrial application that fills this lack of research and thus provides a solution with a high practical impact to survive in the tough competition of the automotive industry. Therefore, the work addresses these fundamental business questions: 1) Can dissatisfied customers be classified based on data that is produced during every service visit? 2) Can the dissatisfaction indicators be derived from service process data? A machine learning problem is set up that compared 5 classifiers and analyzed data from 19,008 real service visits from an automotive company. The 105 extracted features were drawn from the most significant available sources: warranty, diagnostic, dealer system and general vehicle data. The best result for customer dissatisfaction classification was 88.8% achieved with the SVM classifier (RBF kernel). Furthermore, the 46 most potential indicators for dissatisfaction were identified by the evolutionary feature selection. Our system was capable of classifying customer dissatisfaction solely based on the objective data that is generated by almost every service visit. As the amount of these data is continuously growing, we expect that the presented data-driven approach can achieve even better results in the future with a higher amount of data.
Design and Evaluation of a Fiber-Optic Grip Force Sensor with Compliant 3D-Printable Structure for (f)MRI Applications

Grip force sensors compatible with magnetic resonance imaging (MRI) are used in human motor control and decision-making research, providing objective and sensitive behavioral outcome measures. Commercial sensors are expensive, cover limited force ranges, rely on pneumatic force transmission that cannot detect fast force changes, or are electrically active, which increases the risk of electromagnetic interference. We present the design and evaluation of a low-cost, 3D-printed, inherently MRI-compatible grip force sensor based on a commercial intensity-based fiber-optic sensor. A compliant monobloc structure with flexible hinges transduces grip force to a linear displacement captured by the fiber-optic sensor. The structure can easily be adapted for different force ranges by changing the hinge thickness. A prototype designed for forces up to 800 N was manufactured and showed a highly linear behavior (nonlinearity of 2.37%) and an accuracy of 1.57% in a range between zero and 500 N. It can be printed and assembled within one day and for less than $300. Accurate performance was confirmed, both inside and outside a 3 T MRI scanner within a pilot study. Given its simple design allowing for customization of sensing properties and ergonomics for different applications and requirements, the proposed grip force handle offers researchers a valuable scientific tool.
Extrinsic Activation of Human Coagulation Factors IX and X on the Endothelial Surface

Summary In previous kinetic studies, the catalytic efficiency of the activation of human coagulation factors IX and X by factor VIIa in the presence of purified tissue factor apoprotein was found to be essentially equal. These activation reactions were now studied on the surface of human umbilical vein endothelial cells. The cells were stimulated with endotoxin to express tissue factor. This tissue factor activity was saturable with factor VIIa and could be inhibited by rabbit antibodies against human tissue factor apoprotein. Only stimulated cells supported factor VIIa activity. No difference in the reactivity of factor VII and VIIa was observed in the presence of factor X, due to rapid feedback activation of factor VII by factor Xa. However, the activation of factor IX by factor VII shows a 10 min lag-phase, which reflects that the activation of factor VII by factor IXa is a less efficient process. The kinetic parameters for the factor VIIa dependent activation of factor IX and factor X on the endothelial surface were: Km 0.09 εM, Vmax 0.13 pmol/min, and Km 0.071 εM, Vmax 0.41 pmol/min, respectively. The same ratio between the Vmax for factor X and factor IX activation was observed as in a cell free system. However, the Km of factor IX was 4-fold higher on the endothelial surface than in the cell free system. Together, these kinetic parameters will favour factor X activation 5-fold over factor IX activation at physiological concentrations of these proteins. The activation of factor X by factor VIIa on the endothelial surface was characterized by a short lag-phase, which was absent in factor IX activation. Further, both the activation of factor X and factor IX were down regulated by factor Xa.
Adolescents' music preferences and personality characteristics

The present paper examined the structure of Dutch adolescents' music preferences, the stability of music preferences and the relations between Big‐Five personality characteristics and (changes in) music preferences. Exploratory and confirmatory factor analyses of music‐preference data from 2334 adolescents aged 12–19 revealed four clearly interpretable music‐preference dimensions: Rock, Elite, Urban and Pop/Dance. One thousand and forty‐four randomly selected adolescents from the original sample filled out questionnaires on music preferences and personality at three follow‐up measurements. In addition to being relatively stable over 1, 2 and 3‐year intervals, music preferences were found to be consistently related to personality characteristics, generally confirming prior research in the United States. Personality characteristics were also found to predict changes in music preferences over a 3‐year interval. Copyright © 2007 John Wiley & Sons, Ltd.
Relative effects of wound healing and mechanical stimulus on early bone response to porous‐coated implants

We hypothesized that early bone adaptation to well fixed porous‐coated implants is influenced more by wound healing than by mechanical loading. To test this hypothesis, two groups of dogs with identical, hydraulically controlled porous‐coated implants interference fit within distal femoral trabecular bone were used. One group had no load; the other had 35 N of load applied to the implants. At 5 weeks after surgery, the resulting adaptation of bone around the implants was quantified on a cellular basis by cytochemical analysis of type‐I procollagen synthesis and on a structural basis using three‐dimensional micro‐computed tomography imaging. The percentage of trabecular surfaces covered by osteoblasts expressing type‐I procollagen was significantly increased in bone surrounding the implant in both groups compared with contralateral control bone tissue. There was no difference between the groups with no load or 35 N of load. In addition, measures of trabecular bone structure did not differ significantly between the load and no‐load groups. Taken together, these results suggest that wound healing plays a much greater role in the early response of bone to well fixed porous‐coated implants than does mechanical stimulus.
Safety of artemisinins during early pregnancy, assessed in 62 Sudanese women

Abstract Between June 2006 and October 2008, the safety of artemisinins during early human pregnancy was assessed in central–eastern Sudan. Pregnant women in the first or second trimester who were attending antenatal-care clinics at the Wad Medani, Gadarif and New Halfa hospitals were interviewed. Each was asked if they had had malaria in the first trimester of the index pregnancy and, if so, what treatment they had received. The women who had received artemisinins were then followed-up until delivery and their babies were followed-up until they were 1-year-olds. Overall, 62 of the pregnant women reported receiving artemisinins — artemether injections (48), artesunate plus sulfadoxine–pyrimethamine (11) or artemether plus lumefantrine (three) — during the first trimester. Medical records were available for 51 (82%) of these 62 women, and, in each case, these records showed the reported treatment and that malaria had been confirmed. Only nine (15%) of the 62 women given artemisinins had not known that they were pregnant when treated. Two of the treated women (both given artemether injections in the first trimester) had miscarriages, one at 20 weeks of gestation and the other at 22 weeks, each while receiving quinine infusions for a second attack of malaria. The other 60 women who had received artemisinins delivered apparently healthy babies at full term. No congenital malformations were detected, there was no preterm labour, no maternal deaths were recorded during the follow-up, and none of the babies died during their first year of life. It therefore appears that artemisinins may be safe to use during early pregnancy, although further study is clearly needed.
Clinical subtypes of dementia of the Alzheimer type

Clinical subtypes of dementia of the Alzheimer type were evaluated by comparing age at onset, aphasia, family history, and motor disorder in 146 individuals with progressive dementia. Early onset was significantly associated with more prevalent and more severe language disorder. Forty-five percent of all probands had familial history of dementia, but we could not differentiate relative familial risk based on age at onset or aphasia. Independent of duration of illness, myoclonus and noniatrogenic extrapyramidal disorder were associated with greater severity of dementia.
A Comparison between Measured and Calculated Changes in the Lung Function after Operation for Pulmonary Cancer

Eighteen patients operated on for pulmonary cancer, the procedure varying from the removal of two segments to pneumonectomy, were subjected to measurement of the spirometric values VC, FEV1, FRC and RV preoperatively and 2–3 months postoperatively. The possibility of predicting the post‐operative values from the number of segments removed was studied, partly with standard percentages (5.26%) per segment (method I), and partly with a percentage per segment in the affected area, calculated from the preoperative regional lung function tests using 133xenon. This latter test was carried out with a mobile apparatus using four detectors with tubular colimators and from the anterior surface of the thorax. Both methods of calculation gave, for the material as a whole, good agreement between the postoperative (measured) and the calculated values. However, with regard to certain patients, the regional lung function tests gave important information on preoperative reduced function in the affected area. In these patients, method No. II was by far the best for prediction of the postoperative values.
Personal fear of death affects the proper process of breaking bad news

Introduction Breaking bad news may be affected not only by insufficient knowledge of a physician, but also by his attitude, religious beliefs, fears, lack of experience, etc. This survey was aimed to test the relation between physicians’ fear of own death and philosophy of life and their inclination to break bad news. Material and methods One hundred seventy students of the last year of medical faculty filled in a 4-item questionnaire created by the authors. The participants were asked on their opinion on whether to inform patients on upcoming death, as well as fear of their own death and willingness to receive bad news. The last question was aimed to distinguish the respondents based on their determination in philosophy of life. Results Ninety-three percent of respondents think that patients should be informed about unfavorable prognosis but only 86% would like to be informed about their own upcoming death. There is a negative correlation between determination of philosophy of life and fear of own death (p = 0.024), but no correlation between fear of own death and the degree of religiousness (Fisher’s accurate p = 0.18). Persons determined to receive information on their own upcoming death are more prone to inform patients about their upcoming death (ρ = 0.31; p < 0.0001). Conclusions Personal fear of own death and low level of determination of philosophy of life may restrain medical professionals from breaking bad news to patients. Not only knowledge of the principles, but also personal attitude should be addressed in the curriculum of physician-patient communication education.
Free Flap Reconstruction in the Head and Neck Region following Radiotherapy: A Cohort Study Identifying Negative Outcome Predictors

Background: With the increased use of radiotherapy in the treatment of head and neck cancers, free tissue transfer in an irradiated field is now common. Reported outcomes with free tissue transfer reconstructions in irradiated areas are often unclear and contradictory. This is attributable in part to small sample size and heterogeneity in patients and procedures. The goals of this study were, first, to determine the outcome of head and neck reconstructions in an irradiated field using a large retrospective cohort and, second, to identify negative outcome predictors that could potentially be modified to reduce the morbidity in these procedures. Methods: Patients undergoing free flap reconstruction in irradiated head and neck regions between July of 2005 and July of 2007 were identified. Charts, including operative and radiotherapy records, were reviewed. Multiple logistic regressions were performed to identify negative outcome predictors. Results: During the study period at the authors' institution, 984 patients underwent head and neck free flap reconstruction. Of these, 137 had free tissue transferred to irradiated fields. Patients received an average radiotherapy dose of 64.5 Gy. The overall flap success rate was 96.4 percent. The postoperative complication rate was 47 percent. There was an overall 22 percent reoperation rate and a 28 percent infection rate. Segmental mandibulectomy, larger flap size, and infection were found to be significant negative outcome predictors. Conclusions: This study confirms that free flap transfer to previously irradiated head and neck areas has a success rate comparable to that of transfer to nonirradiated zones. However, previously irradiated patients have a high risk of complications. Infection, as a modifiable risk factor, should be treated aggressively.