julilili42/papers huggingface dataset:
Chondrification and Character Identification in the Skull Exemplified for the Basicranial Anatomy of Early Squamate Embryos
2017-06-01

ABSTRACT The neurocranium of vertebrates is mainly derived from early cartilaginous anlagen, the so‐called chondrocranium, the base of the future skull. Two initial bar‐shaped and paired chondrifications flank the notochord, the rostral trabecles and the caudal parachordals. In most reptiles, there is an additional component, the transverse acrochordal, which is placed between trabecles and parachordals. All these elements compose the base of the future chondrocranium. There are several drastically different hypotheses concerning the development and interrelationship of these elements. We reexamined the basicranial development in four squamates and found that all species show very similar conditions of early chondrocranial development. The anterior part of the notochord is not embedded into the basal plate as it was previously reported. It remains free. The medial edges of the parachordals form the lateral walls of the basicranial fenestra. Only the posterior portions of the parachordals fuse and form the basal plate. The space in‐between the parachordals is filled with a thin layer of cells, which never chondrify. The anterior tips of the parachordals later fuse with the posterior edge of the acrochordal, which ultimately delimitates, as crista sellaris, the basicranial fenestra anteriorly. We consider the observed processes a common development at least in lizards and review a variety of methodological approaches and differences in data interpretation as reasons for the anatomical differences reported in the literature. Moreover, based on our data we argue that the acrochordal is of mesodermal origin, which coincides with results of fate map experimental studies.
On Proprioception in Action: Multimodality versus Deafferentation
2017-06-01

Abstract Recent research on proprioception reveals that it relies on a systematically distorted model of bodily dimensions. This generates a puzzle about proprioception in action control: action requires accurate bodily parameters. Proprioception is crucial for ordinary action, but if it relies on a systematically distorted body model, then proprioception should contain systematic errors. But we cannot respond by discarding proprioception from motor control, since we know from the severe problems deafferented agents face in acting that ordinary action requires proprioception. The solution is that the possibility of bodily action is provided for by multimodal body representations for action (the ‘body schema’).
Gifted and non-gifted students’ diurnal preference and the relationship between personality, sleep, and sleep quality
2017-06-01

The current study had two main objectives. First, we examined gifted and non-gifted students’ diurnal preferences. Secondly, we examined the relationships among age, gender, personality, sleep quality, and chronotype of gifted students. Data were gathered from 276 gifted students and 1921 non-gifted students whose ages range between 7 and 17 years old, in same three cities in Turkey using the Composite Scale of Morningness (CSM) to assess diurnal preference, the Big Five Inventory (BIG-5) to assess personality and the Pittsburgh Sleep Quality Index (PSQI) to measure sleep quality. The first result indicated that gifted students were more morning-oriented compared to non-gifted students. The other main result was that the conscientiousness was the best predictor of CSM scores in gifted students. Additionally, conscientiousness, age, and global PSQI predicted CSM scores, respectively. Moreover agreeableness, conscientiousness, and emotional stability were positively related to morning orientation, while age, sleep quality, sleep latency, daytime dysfunction, and global PSQI were negatively related with chronotype in gifted students.
RADIOTHERAPY TO BULKY DISEASE PET‐NEGATIVE AFTER IMMUNOCHEMOTHERAPY CAN BE SPARED IN ELDERLY DLBCL PATIENTS: RESULTS OF a PLANNED INTERIM ANALYSIS OF THE FIRST 187 PATIENTS WITH BULKY DISEASE TREATED IN THE OPTIMAL > 60 STUDY OF THE DSHNHL
2017-06-01

Background: Radiotherapy (RT) to bulky sites improves outcome of elderly DLBCL patients [Pfreundschuh et al., Lancet Oncol 2008; 9: 105-116; Held et al., J Clin Oncol 2014; 32:112-1118]. Whether RT can be spared in patients with a PET-negative bulk after R-CHOP was prospectively addressed in OPTIMAL >60. To assure that patients with bulky disease were not put at risk by this PET-based omission of radiotherapy, a planned interim analysis was performed. Patients and Methods: 61 to 80 y-old pts. with untreated DLBCL were randomized to 6xCHOP-14 or 6xCHLIP-14 (liposomal instead of conventional vincristine, 2 mg/m2 [uncapped]) plus 8 x rituximab 375 mg/m2 (R) q 2 wks. or 12xR (days -4,-1,1,4,14,28,42,56,91,126,175, 238). Pts. with bulk (> = 7.5 cm) that remained PET-positive after chemotherapy were assigned to RT (39.6 Gy), while PET-negative bulks were observed. Results: 187/505 (37%) had bulky disease and were compared to 117/306 (38%) RICOVER-60 pts. (38%) who had received 6xCHOP-14 + 8R. OPTIMAL > 60 pts. were older (70 vs. 68 years) and had more IPI = 3 (33% vs. 29%) and IPI = 4,5 (34% vs. 23%) compared to RICOVER-60. PET was performed in 166/187 OPTIMAL > 60 bulk pts. (reasons for no PET: early death: 5; excessive toxicity: 3; protocol violation: 1, non-compliance: 4, change of diagnosis: 6, others: 2). 80/166 (48%) bulks remained PET-positive and 62/80 (78%) were irradiated (reasons for no RT: progression: 8; medical reasons: 9; negative biopsy: 1), reducing RT from 67/117 (57%) in RICOVER-60 by 42% to 62/187 (33%) in OPTIMAL > 60. Despite the unfavorable demographics, outcome of the 187 bulk pts. in OPTIMAL > 60 was non-inferior to RICOVER-60 in an intention-to-treat analysis, not even in the least intensive of the 4 OPTIMAL > 60 treatment arms consisting of 47 pts. who received 6xCHOP-14 + 8R. 2-year PFS and OS in OPTIMAL > 60 was 79% and 88%, respectively, compared to 75% and 78% of the 117 RICOVER-60 pts. In a multivariable analysis adjusting for the IPI risk factors, the hazard ratio of the OPTIMAL > 60 compared to the RICOVER-60 bulk pts. was 0.7 (95% CI: 0.3; 1.5; p = 0.345) for PFS and 0.5 (95% CI: 0.2; 1.3; p = 0.154;p = 0.154) for OS. Conclusion: Radiotherapy can be spared in PET-negative bulks, resulting in a 42% reduction of patients who receive radiotherapy without compromising the outcome of these patients. Supported by Amgen, Roche, Spectrum. Keywords: diffuse large B-cell lymphoma (DLBCL); immunochemotherapy; positron emission tomography (PET).
Variability in and predictors of glycaemic responses after 24 weeks of treatment with exenatide twice daily and exenatide once weekly
2017-06-01

The range of glycated haemoglobin ( HbA1c ) responses and characteristics associated with above‐average response to exenatide twice daily and once weekly were examined. Data were pooled from 8 exenatide‐twice‐daily and 5 exenatide‐once‐weekly studies. A baseline HbA1c ‐corrected measure of change in HbA1c after 24 weeks identified high, average and low responses. Multiple linear regression and multivariate generalized estimating equation models identified factors associated with high response. Among 2355 participants (exenatide twice daily, n = 1414; exenatide once weekly, n = 941), baseline HbA1c correlated with change in HbA1c ( P &lt; .0001). Across baseline HbA1c levels, the 25th to 75th percentile of HbA1c change ranged from −0.3% to −3.2% with exenatide twice daily and from −0.5% to −3.6% with exenatide once weekly. Asian ethnicity and older age were significantly associated with high response to exenatide twice daily; no factors were significantly associated with response to exenatide once weekly. These data provide clinically useful information for estimating the likelihood that, depending on baseline HbA1c , an individual can achieve HbA1c goals. The association between Asian ethnicity, age and high response to exenatide twice daily may relate to the specific effects of exenatide twice daily on postprandial glucose.
Construction, Growth, and Harvesting of Fission Yeast Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) Strains
2017-06-01

Stable isotope labeling by amino acids in cell culture (SILAC) enables the relative quantification of protein amounts and posttranslational modifications in complex biological samples through the use of stable heavy isotope–labeled amino acids. Here we describe methods for the application of SILAC to fission yeast Schizosaccharomyces pombe using either labeled lysine or a combination of labeled lysine and labeled arginine. The latter approach is more complicated than the use of labeled lysine alone but may yield a more comprehensive (phospho)proteomic analysis. The protocol includes methods for construction of SILAC-compatible strains, growth of cultures in labeled medium, cell harvesting, and protein extraction.
Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC) Technology in Fission Yeast
2017-06-01

Shotgun proteomics combined with stable isotope labeling by amino acids in cell culture (SILAC) is a powerful approach to quantify proteins and posttranslational modifications across the entire proteome. SILAC technology in Schizosaccharomyces pombe must cope with the “arginine conversion problem,” in which isotope-labeled arginine is converted to other amino acids. This can be circumvented by either using stable isotope-marked lysine only (as opposed to the more standard lysine/arginine double labeling) or using yeast genetics to create strains that only very inefficiently convert arginine. Both strategies have been used successfully in large-scale (phospho)proteomics projects in S. pombe . Here we introduce methods for performing a typical SILAC-based experiment in fission yeast, including generation of SILAC-compatible strains, sample preparation, and measurement by mass spectrometry.
Stable Isotope Labeling by Amino Acids in Cell Culture (SILAC)-Based Quantitative Proteomics and Phosphoproteomics in Fission Yeast
2017-06-01

Modern mass spectrometry (MS)-based approaches are capable of identifying and quantifying thousands of proteins and phosphorylation events in a single biological experiment. Here we present a (phospho)proteomic workflow based on in-solution proteome digestion of samples labeled by stable isotope labeling by amino acids in cell culture (SILAC) and phosphopeptide enrichment using strong cation exchange (SCX) and TiO 2 chromatographies. These procedures are followed by high-accuracy MS measurement on an Orbitrap mass spectrometer and subsequent bioinformatic processing using MaxQuant software.
650Implanted cardioverter defibrillator (ICD) therapy in patients with suspected myocarditis: time of implantation and occurrence of ventricular arrhythmias
2017-06-01

Background: Sudden cardiac death (SCD) represents the most catastrophic complication of hypertrophic cardiomyopathy (HCM).Despite enormous efforts and development of SCD risk stratification tools (2011 AHA, 2014 ESC) in the context of primary prevention, these have only been partially effective in preventing its occurrence, by means of implantable cardioverter-defibrillators (ICD).Purpose: Electrophysiology study (EPS) has been largely ignored in HCM SCD risk stratification over the last years, despite some promising results.It was thus sought to assess the ability of EPS to improve patient classification regarding risk for serious arrhythmic events.Methods: Two-hundred-and-three consecutive HCM patients risk-stratified for SCD were also submitted to EPS and prospectively followed-up for occurrence of the primary endpoint of SCD or appropriate ICD therapy.The 2011 AHA and 2014 ESC algorithms were also retrospectively applied and evaluated.Results: EPS was feasible in all patients with no major complications.During followup (68.3651.4months) the primary endpoint occurred in 19 patients (1 SCD and 18 appropriate ICD interventions -15 shocks and 3 antitachycardia pacing), yielding an annual incidence of 1.65%.EPS ability to discriminate patients was significant, given that only one of the 124 non-inducible patients reached the primary endpoint (sensitivity 94.7%, specificity 66.8%, PPV 22.8% and NPV 99.2%).Binary logistic regression established inducibility at EPS as the most important factor for endpoint occurrence (O.R. 31.3).An AHA-or ESC-based approach would have miss-classified 3 and 8 endpoint reaching patients respectively into not receiving an ICD.Areas under the curve (AUC) for EPS, 2011 AHA and 2014 ESC were 0.81, 0.5 and 0.67 respectively (p for difference from EPS AUC <0.001 and 0.06).A combinational approach, involving offering ICDs to all either inducible or with a 2014 ESC risk score 6% would have yielded absolute sensitivity and negative predictive value at an acceptable specificity (49.7%).The relevant AUC was 0.75, statistically non-inferior to that of either 2014 ESC or EPS.Survival free from primary endpoint occurrence was significantly better in the non-inducible group (248 vs 142 months, p-logrank <0.001).Finally, 41 patients (20.2%) were diagnosed with impulse production and conduction disorders leading to pacemaker (or ICD, if indicated) implantation.Conclusions: EPS performance in HCM patients is feasible, safe and can improve SCD risk stratification in a primary prevention setting by offering useful clinical information, especially in combination with established guidelines.Moreover, it may allow for detection of bradycardia-related disturbances, amenable to treatment by simple pacemaker implantation.
Die Theologie des Johannesevangeliums
2017-06-01

Summary Johannine theology is quite clear and stringent in its conceptuality. This is rooted in the Christocentrism which is characteristic for the Johannine theology as a whole: Jesus Christ is the one and only „subject matter“ which lies in the center of this thinking. All other topics of theology – such as soteriology, eschatology or pneumatology – are unfolded on the basis of Christology and gain their decisive profile from here. Most fundamental for Johannine Christology is the statement that Jesus Christ is the eternal Son of God, who in the same way and with the same seriousness deserves to be called „God“ as the Father. This is the basis for the claim that his death was the saving self-surrender of the Son of God as the true paschal lamb. The salvation, which is enacted in the crucified, is appropriated to the individual through faith in Jesus Christ. This faith is God's work and has its foundation in divine predestination. Johannine eschatology is unique in the New Testament in its strong emphasis on the present reality of salvation: The believer participates in eternal salvation already now in an irreversible and unsurpassable manner; even death cannot threaten and abolish communion with Christ. The gospel of John conceives the Holy Spirit, who completes the salvific work of Christ by giving faith, as a divine person distinct from Father and Son. Thus it is absolutely appropriate to call the Johannine discourse about God trinitarian.
CURRENT THERAPY OF SECONDARY CNS INVOLVEMENT IN MALIGNANT LYMPHOMA: DATA FROM A MULTICENTER PROSPECTIVE INTERNATIONAL REGISTRY
2017-06-01

Introduction: CNS involvement is a rare complication of systemic lymphoma. With conventional therapy, the prognosis of secondary CNS lymphoma is poor with median overall survival (OS) in most series of approx. 6 months. The optimal therapeutic management has not been established thus far. Methods: Since 2011, 181 patients have been included in an ongoing prospective international registry. Here, data of the first 173 patients included until November 2016 is presented. Results: 30 patients had CNS involvement at diagnosis (cohort I) and 143 at progression/relapse (cohort II). The median age was 63 years (26-86). Of 155 patients with complete data available, 122 (79%) had aggressive B-cell lymphoma, 25 (16%) indolent lymphoma, 5 (3%) mantle cell lymphoma and 3 (2%) T-cell lymphoma. Simultaneous systemic involvement was found in 42% of patients in cohort II. Therapy for CNS involvement and outcome was analyzed in 99 patients thus far (16 in cohort I and 83 in cohort II). Systemic therapy alone was given to 48 (49%), systemic + intrathecal therapy to 43 (43%), intrathecal therapy alone to 5 (5%), radiotherapy alone to 2 (2%); one patient did not receive any treatment. Systemic chemotherapy was high-dose methotrexate (HDMTX)-based in 81 (89%) and high-dose cytarabine (HDAraC)-based in 53 (58%); 61 (61% of all) patients received rituximab systemically. Liposomal cytarabine was the most frequent intrathecal therapy given in 30 out of 48 patients (63%). High-dose chemotherapy followed by autologous stem-cell transplantation (HD-ASCT) was performed in 25 (25%) patients. The median progression-free survival (PFS) was 5.9 months (95% CI 3.1-8.7), the median OS 18.6 months (95% CI 10.3-26.9). On univariate analysis, CNS lymphoma at diagnosis, no meningeal involvement, better ECOG performance status, treatment with rituximab, HD-ASCT and response to therapy were associated with better outcome. On multivariate analysis, a prognostic role for CNS involvement at first diagnosis and HD-ASCT (for OS) and no meningeal involvement (for both PFS and OS) was found with response to CNS therapy being the dominating prognostic factor (for both OS and PFS). Conclusions: This is the largest prospective series on SCNSL in the era of modern lymphoma therapies. Our results suggest that with intensive HDMTX- and HDAraC-based chemotherapy, the outcome of secondary CNS lymphoma patients can be improved, particularly if HD-ASCT can be applied. Keywords: autologous stem-cell transplantation (ASCT); extranodal lymphomas; methotrexate (MTX)
ANTI‐INFECTIVE PROPHYLAXIS WITH ACICLOVIR AND COTRIMOXAZOLE SIGNIFICANTLY REDUCES THE RATE OF INFECTIONS AND THERAPY‐ASSOCIATED DEATHS IN ELDERLY PATIENTS WITH DLBCL UNDERGOING R‐CHOP IMMUNOCHEMOTHERAPY
2017-06-01

Background: To study if anti-infective prophylaxis with aciclovir and cotrimoxazole is effective in preventing infections in pts. receiving R-CHOP, we compared infections and treatment-related deaths in two prospective DSHNHL trials with different anti-infective strategies. Methods: 61- to 80-year-old pts. in RICOVER-60 study [Pfreundschuh et al; Lancet Oncol 2008; 9:105-116] received 6 or 8 cycles of CHOP-14 with or without 8 applications of rituximab. Anti-infective prophylaxis consisted of ciprofloxazine (500 mg/d) during days of severe leukocytopenia (<1000/mm3). In OPTIMAL > 60, pts. were randomized to 6xCHOP-14 or 6xCHLIP-14 (conventional substituted by liposomal vincristine [2 m/m2, uncapped]) in combination with rituximab, 8 applications q 2 weeks or 12 applications between days -4 and 238 in a 2 × 2 factorial design. In OPTIMAL > 60, anti-infective prophylaxis consisted of cotrimoxazole (2 double-strength doses twice every week p.o.) and aciclovir (4 × 400 mg/d p.o.) in addition to ciprofloxazine. Results: In RICOVER-60, grade 3&4 infections in 232 patients (IPI = 1 and bulky disease or IPI > 1) receiving 6xCHOP-14 + 8R were 6% (76/1200) per cycle and 28% (60/218) per patient. OPTIMAL > 60 pts. were older (70 vs 68 years) and had more IPI = 3 (33% vs 29%) and IPI = 4.5 (34% vs 23%) compared to RICOVER-60. With intensified anti-infective prophylaxis in OPTIMAL > 60, there were no differences with respect to infections between the 4 treatment arms. Despite the considerably less favourable demographics of the OPTIMAL > 60 study, grade 3&4 infections were 4% (83/1987) per cycle and 18% (64/365 pts. with toxicity documentation) per patient, significantly less than in RICOVER-60 (per cycle: p = 0.007; per patient: p = 0.004). Even more importantly, treatment-related deaths (defined as all non-lymphoma associated deaths during and within 2 months after the end of chemotherapy) went down from 15/232 (7%) in RICOVER-60 to 7/385 (2%) in OPTIMAL > 60 (p = 0.003). Conclusion: Anti-infective prophylaxis with cotrimoxazole and aciclovir in addition to ciprofloxazine significantly reduced the rates of severe infections and treatment-related deaths in elderly patients receiving R-CHOP supporting the use of this anti-infective strategy in all DLBCL patients receiving R-CHOP. Keywords: diffuse large B-cell lymphoma (DLBCL); immunochemotherapy; R-CHOP
Hybrid Interventions for Catheter Placement in Pediatric Intestinal Rehabilitation Patients with End-Stage Venous Access
2017-06-01

Introduction: Permanent central venous access is a crucial part of treatment in children with short bowel syndrome and chronic intestinal failure. Catheter infections and venous thromboses are limiting the amount of vessels suitable for catheter placement. End-stage venous access means a serious threat for affected children eventually representing an indication for intestinal transplantation. Thus, catheter placement in these patients is challenging. In our intestinal rehabilitation program we established a combined surgical/interventional approach to maintain or restore central venous access in children with desperate vascular conditions. Aim of this study is to analyze these hybrid interventions. Methods: Data of 14 children (16 interventions) with intestinal failure and end-stage venous access, treated between September 2011 and November 2016, were retrospectively reviewed. Patients underwent hybrid endovascular/open surgical approaches for insertion of central venous catheters. During the complex procedures a large variety of interventional and surgical methods were applied depending on the respective individual conditions. Results: Catheter placement was achieved in all patients. Median age at intervention was 47 months (interquartile range (IQR),29-74). Interventional methods were used as first step of the procedures for example to access small vascular stumps, re-open occluded vessels or prepare collateral vessels that would not have been accessible through surgery alone. Subsequent surgical steps included open access to prepared vessels, seldinger techniques or plain open insertions. Median time for hybrid interventions was 66 minutes (IQR,42-111), contrast medium was used in 8 patients, with a median amount of 10ml (IQR 4–26). Median fluoroscopy time was 198 s (IQR 128–416), median dose of irradiation during angiography was 0.3 Gy*cm2 (IQR,0.1-0.9). No complications occurred during or after interventions. Conclusions: Hybrid endovascular/open surgical procedures can be successfully applied for restoring or maintaining permanent central venous catheters in children with intestinal failure and end-stage venous access. Although extensive in preparation and execution these approaches can be a valuable contribution in intestinal rehabilitation programs, maintaining or resotring venous access in desparate vascular conditions, thereby eventually decreasing the need for intestinal transplantation in affected patients.