Miracle-dz/UniFAR-FTUs huggingface dataset:
Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.

BACKGROUND The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). METHODS In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with P<1.29×10-5. RESULTS The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10-6 for superiority). The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P<0.001). Common grade 3 or 4 adverse events that were reported in more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of adverse events were 7.5% and 2.1%, respectively. CONCLUSIONS Among patients receiving initial systemic treatment for HR-positive, HER2-negative advanced breast cancer, the duration of progression-free survival was significantly longer among those receiving ribociclib plus letrozole than among those receiving placebo plus letrozole, with a higher rate of myelosuppression in the ribociclib group. (Funded by Novartis Pharmaceuticals; ClinicalTrials.gov number, NCT01958021 .).
Sickness Absence Trends during and after Long-Term Psychotherapy and Antidepressant Medication among Depressive Employees

130 Favourable short-term outcomes for psychotherapy interventions targeted on depressive patients have been shown [1, 2] , but few studies have examined long-term outcomes in working populations [3] . We used data on recorded sickness absence as an outcome to examine psychotherapy and pharmacotherapy in a large contemporary working population (the 10-Town Study) [4] . The eligible population comprised all 67,106 employees of the local government who had been employed for at least 10 months in 1 year between 1994 and 2002 [5] . We identified three groups: first, those 448 employees who were granted psychotherapy as a treatment for clinically diagnosed depression (ICD-9 codes 296 and 3004; ICD-10 codes F32, F33 and F34) by the Social Insurance Institution of Finland; second, 3,177 employees treated with antidepressants for at least 12 months during the follow-up, and third, Psychother Psychosom 2009;78:130–132
Importance of Adaptive Changes in Vascular Design for Establishment of Primary Hypertension, Studied in Man and in Spontaneously Hypertensive Rats

Experiments are surveyed which deal with the background of the raised resistance in primary hypertension, as studied in man and, particularly, in spontaneously hypertensive rats (SHR). When exposed to frequent neurohormonal pressure rises, resistance vessels adapt structurally within a few weeks with a thickening of the media which encroaches upon the lumen, thus raising the wall/lumen ratio. This structural adaptation, implying both a raised resistance even at complete smooth muscle relaxation and potentiated resistance increases to given smooth muscle activation, appears to be so pronounced in primary hypertension, both in man and SHR, as to account almost alone for the raised “resting” resistance. Concerning hereditary elements, SHR respond to graded environmental stimuli with exaggerated heart rate and pressure rises that are primarily central in origin. These responses, again, serve to trigger a gradual structural adaptation of both the resistance vessels and the left heart which, in turn, seems to be somewhat more pronounced than in controls for a given pressure “load”. Early pharmacological interference in SHR with neurohormonal pressor influences can largely prevent the structural vascular adaptation and, hence, prevent hypertension. Moreover, once established, the structural changes can show considerable and rapid regression if the pressure load is effectively kept lowered by pharmacological means.
Observation of bending wave localization and quasi mobility edge in two dimensions.

Localization of bending waves is observed on a steel plate decorated with Lucite blocks. A significant experimental feature of the localized modes is an exponential decay of the mode intensity from their peaked centers, with a decay length that increases as (f 0 -f 1 ) -1 when the mode frequency f approaches a quasi mobility edge f 0 . Our experimental results, together with finite-element calculations, support the mechanism of strong bending wave scattering by the Lucite block resonances as the source of the localization phenomenon
Role of Bevacizumab as irst-line Therapy for Colon Cancer

The addition of oxaliplatin and irinotecan to the armamentarium for the treatment of colorectal cancer (CRC) has resulted in significant improvements in response rates and survival. Targeted therapies directed at the epidermal growth factor pathway and the vascular endothelial growth factor pathway are beginning to play a role in the treatment of CRC. Bevacizumab is a monoclonal antibody that has been evaluated in randomized studies. In a randomized phase II study, the combination of 5-fluorouracil/leucovorin (5-FU/LV) was compared with 5-FU/LV plus bevacizumab, and a randomized phase III trial evaluated the addition of bevacizumab to the irinotecan/5-FU/LV (IFL) regimen compared with IFL plus placebo. The results of these studies will be reviewed in detail. The role of bevacizumab with other first-line combinations in the treatment of patients with advanced CRC is being evaluated in ongoing clinical trials. Additionally, the activity of bevacizumab is being evaluated for use in the second-line treatment setting for patients with CRC. Semin Oncol 32(suppl9):S43-S47 © 2005 Elsevier Inc. All rights reserved.
Carriage of Staphylococcus aureus among Hajj pilgrims.

OBJECTIVE To evaluate the prevalence of methicillin resistant Staphylococcus aureus (MRSA) carriage among a cohort of pilgrims during 2004 Hajj season. METHODS Pilgrims attending the 2004 Hajj season were recruited and screened for carriage of MRSA. Standard microbiological techniques were used to screen for the presence of MRSA. RESULTS Out of 411 individuals screened, 85 (20.6%) were positive for Staphylococcus aureus (S. aureus) of which only 6 (1.46 %) were MRSA. Four individuals (4.6%) had the S. aureus organism in both nasal and axillary swabs, while 7 individuals (8%) had the organism in their axillae only. The other 74 individuals (87.1%) had the organism in their nares only. The 6 MRSA isolates were positive for the mecA gene by polymerase chain reaction method. None of the pilgrims examined had any risk factors for community-acquired methicillin resistant S. aureus (CAMRSA). Overall, the prevalence of MRSA in the population of pilgrims examined was found to be low (1.46%) in comparison with most community based studies. CONCLUSION A low rate of MRSA carriage was noticed among the screened cohort. Physicians treating patients suspected of S. aureus infection during the Hajj pilgrimage should bear in mind the possibility of community acquired - MRSA and should obtain appropriate samples for bacterial cultures and susceptibility testing so that antimicrobial agents could be introduced when necessary at a later stage.
Retrograde Amnesia in Free Recall

Supervention of high-priority events in a series of events constituting a free-recall task interferes with postexposure processing of mnemonic information about immediately preceding events, with the result that recall of these preceding events is impaired. Recall of immediately following events is not affected. This retrograde interference is time dependent.
A Secondary Disaster Due To Inhabitant's Action after a Strong Earthquake: A Case Study of the 2008 Sichuan Earthquake

After a strong earthquake occurs, a secondary disaster due to strong aftershocks, flood, landslide or heavy snow can possible to occur and the secondary disaster due to resident’s action also can possible to happen. However, until now seldom researchers have paid attention at it. This paper focused on the Inhabitant’s action after the strong earthquake occurs when a terrible even becomes calm. An inappropriate behavior of people with disadvantaged climate after the worse earthquake can bring a tragedy to their life. Keywords—Sichuan Earthquake, Secondary Disaster, Inhabitant’s Action, inappropriate behavior.
Reply: 'environment' in cancer causation and etiological fraction: limitations and ambiguities (by Boffetta,P. et al. (2007) Carcinogenesis, 28, 913-915).

Dear Sir, ’We derived our pooled risk estimate of mesothelioma from nonoccupational exposure to asbestos from a previous publication authored by some of us, in which the methods for the meta-analysis were described in detail (1). In addition to the summary relative risk, our estimate of the number of non-occupational mesothelioma cases was based on frequencies in the populations experiencing exposures comparable with those in which the relevant epidemiological studies have been carried out. This parameter is subject to great uncertainty, and as a result, we selected it in our commentary as an example of the possible lack of temporal correspondence between risk and exposure data. Mirabelli and Merler suggest a different approach to estimate the number of mesothelioma cases attributable to non-occupational exposure to asbestos, based on the reasonable assumption that all cases with a recorded exposure are attributable to it. Their results of the Italian mesothelioma registry are of interest, and a recent analysis of the same data reported that 4.2% of cases in the registry had environmental asbestos exposure (2). It should be kept in mind that, although all reasonable efforts should be made to reduce and eliminate environmental asbestos exposure, this would have a limited effect on the overall cancer burden. Mesothelioma accounts each year for 1000 cases out of 300 000 total cancer cases (0.3%) in a country such as Italy, and hence 10% of mesothelioma cases represent 0.03% of all cancer cases.
Felsic highland crust on Venus suggested by Galileo Near‐Infrared Mapping Spectrometer data

Received 2 March 2008; revised 29 July 2008; accepted 18 September 2008; published 31 December 2008. [1] We evaluated the spatial variation of Venusian surface emissivity at 1.18 mm wavelength and that of near-surface atmospheric temperature using multispectral images obtained by the Near-Infrared Mapping Spectrometer (NIMS) on board the Galileo spacecraft. The Galileo NIMS observed the nightside thermal emission from the surface and the deep atmosphere of Venus, which is attenuated by scattering from the overlying clouds. To analyze the NIMS data, we used a radiative transfer model based on the adding method. Although there is still an uncertainty in the results owing to the not well known parameters of the atmosphere, our analysis revealed that the horizontal temperature variation in the near-surface atmosphere is no more than ±2 K on the Venusian nightside and also suggests that the majority of lowlands likely has higher emissivity compared to the majority of highlands. One interpretation for the latter result is that highland materials are generally composed of felsic rocks. Since formation of a large body of granitic magmas requires water, the presence of granitic terrains would imply that Venus may have had an ocean and a mechanism to recycle water into the mantle in the past.
The Relation Between Anaerobic Power and Rowing Ergometer Performance of Elite Rowers

Background: The aim of this study is to determine the relation between anaerobic power outputs and 2000 meter rowing ergometer scores. Method: Randomly selected nine elite youth male rowers participated in the current study. Modified Wingate test and 2000 meter rowing ergometer tests were applied to subjects using Concept II-D rowing ergometer. The results of the study was discussed by the anaerobic power outputs, the time for 500 m intervals at a 2000 m rowing ergometer performance and some anthropometric variables. Results: Data were presented as mean and SD for description porpuse. Variables were analysed and correlation coefficients were calculated by using Sperman’s Corelation. As the result; significant and high negative correlation between 2000 m ergometer performance and mean anaerobic power was found (r = - 0.837; p = 0.005). Conclusion: It has been understood that anaerobic energy system whereby the energy requirements at start and finish stages during 2000-mt performance and aerobic system are important complements of racing performances of rowing athletes.
Exploring energy neutral development for Brainport Eindhoven

Current energy distribution networks are often not equipped for facilitating expected sustainable transitions. Major concerns for future electricity networks are the possibility of peak load increases and the expected growth of decentralized energy generation. In this article, we focus on peak load increases; the effects of possible future developments on peak loads are studied, together with the consequences for the network. The city of Eindhoven (the Netherlands) is used as reference city, for which a scenario is developed in which the assumed future developments adversely influence the maximum peak loads on the network. In this scenario, the total electricity peak load in Eindhoven is expected to increase from 198 MVA in 2009 to 591‐633 MVA in 2040. The necessary investments for facilitating the expected increased peak loads are estimated at 305‐375 million Euros. Based upon these projections, it is advocated that ‐ contrary to current Dutch policy ‐ choices regarding sustainable transitions should be made from the viewpoint of integral energy systems, evaluating economic implications of changes to generation, grid development, and consumption. Recently applied and finished policies on energy demand reduction showed to be effective; however, additional and connecting policies on energy generation and distribution should be considered on short term.
Classification of hand motions in EEG signals using recurrent neural networks

This paper describes hand motion detection and the method for classification of 32-component EEG signals. This method is based on using recurrent convolution neural network as multi-class classifier. In this paper, we propose and empirically evaluate several architectures of recurrent convolutional neural network, and show advantages of using recurrent convolutional neural network for investigating problem. The results prove that this type of classifier can effectively distinguish characteristic features in the initial EEG signals and provide correct values of neural network outputs. Using recurrent convolution layer instead of the standard convolution layer can significantly improve the quality of classification. Adding recurrent connections for convolutional layer neurons increases the depth of the network, maintaining a constant number of parameters by weight sharing between layers.
Cost-effectiveness of the convergent procedure and catheter ablation for non-paroxysmal atrial fibrillation

Abstract Objective: Patients with persistent or longstanding atrial fibrillation have modest success achieving sinus rhythm with catheter ablation or rhythm control medications. Their high risk of stroke, bleed, and heart failure leads to significant morbidity and health care costs. The convergent procedure has been shown to be successful in this population, with 80% of patients in sinus rhythm after 1 year. This study evaluated the cost-effectiveness of the convergent procedure, catheter ablation, and medical management for non-paroxysmal AF patients. Methods: A Markov micro-simulation model was used to estimate costs and effectiveness from a payer perspective. Parameter estimates were from the literature. Three patient cohorts were simulated, representing lower, medium, and higher risks of stroke, bleed, heart failure, and hospitalization. Effects were estimated by quality-adjusted life-years (QALYs). Single-variable sensitivity analysis was performed. Results: After 5 years, convergent procedure patients averaged 1.10 procedures, with 75% of survivors in sinus rhythm; catheter ablation patients had 1.65 procedures, with 49% in sinus rhythm. Compared to medical management, catheter ablation and the convergent procedure were cost-effective for the lower risk (ICER <$35,000) and medium risk (ICER <$15,000) cohorts. The procedures dominated medical management for the higher risk cohort (lower cost and higher QALYs). The convergent procedure dominated catheter ablation for all risk cohorts. Results were subject to simplifying assumptions and limited by uncertain factors such as long-term maintenance of sinus rhythm after successful procedure and incremental AF-associated event rates for AF patients relative to patients in sinus rhythm. In the absence of clinical trial data, convergent procedure efficacy was estimated with observational evidence. Limitations were addressed with sensitivity analyses and a moderate 5 year time horizon. Conclusion: The convergent procedure results in superior maintenance of post-ablation sinus rhythm with fewer repeat ablation procedures compared to catheter ablation, leading to lower cost and higher QALYs after 5 years.
Tachykinin receptor 1 variants associated with aggression in suicidal behavior

Substance P is involved in the modulation of depression, anxiety, and suicidal‐related behaviors. We studied gene variants of Tachykinin Receptor 1 (TACR1—rs3771810, rs3771825, rs726506, rs1477157) in 167 German suicide attempters (affective spectrum n = 107, schizophrenia spectrum n = 35, borderline personality disorder n = 25), 92 Caucasian individuals who committed suicide and 312 German healthy subjects. Single markers and haplotype analysis in relation to suicidal behaviors (suicide attempters/completers) did not reveal any significant association. The rarest rs3771825 T allele however showed a marginal association with higher Reactive Aggression scores on the Questionnaire for Measuring Factors of Aggression (FAF) (F = 9.86, df = 1; P = 0.0017). Haplotype analyses confirmed the finding. Violence or impulsivity of suicide attempt and State‐Trait Anger Expression Inventory (STAXI) scores were not associated with gene variants. In conclusion, our study suggests that TACR1 gene variants have no major influence on suicidal behavior but may modulate aggression features. © 2007 Wiley‐Liss, Inc.
Influence of antigenic drift on the intensity of influenza outbreaks: Upper respiratory tract infections of military conscripts in Finland

A total of 102,600 upper respiratory infections (URI) were recorded among young military conscripts in the Finnish Defence Forces during the study period from October 1991 to March 1994. This period covered three outbreaks caused by H3N2‐subtype influenza A virus and one outbreak of influenza B. During the 1991/92 outbreak caused by A/Beijing/353/89‐like virus, the calculated influenza A incidence was 2,206/10,000 men. During the 1992/93 outbreak when influenza B was the predominant virus, a new drift variant of influenza A that belonged to the lineage of A/Beijing/32/92‐like and A/Shangdong/9/93‐like viruses circulated but the incidence of influenza A was not more than 1,044/10,000. A higher incidence, 2,810/10,000, was recorded during the 1993/94 outbreak, when the circulating virus was similar to the 1992/93 virus antigenically and with regard to haemagglutinin and neuraminidase (NA) gene sequences. Crossreactive haemagglutination‐inhibition antibodies induced in 1991/92 probably were sufficient to restrict the epidemic activity in 1992/93 but no longer in 1993/94. Furthermore, during the 1991/92 outbreak, some of the A/Beijing/353/89‐like viruses already had shared the NA sequence markers characteristic of the viruses in 1992/93 and 1993/94, which may also have strengthened protection in 1992/93. J. Med. Virol. 72:275–280, 2004. © 2004 Wiley‐Liss, Inc.
Sequential Proteolytic Processing of the Triggering Receptor Expressed on Myeloid Cells-2 (TREM2) Protein by Ectodomain Shedding and γ-Secretase-dependent Intramembranous Cleavage*

Background: TREM2 is a microglial receptor, recently identified as a genetic risk factor for late onset AD. Results: Sequential proteolytic processing of TREM2 involves ectodomain shedding and intramembranous cleavage by γ-secretase and affects signaling via its adaptor protein DAP12. Conclusion: γ-Secretase-mediated intramembranous proteolysis modulates TREM2 signaling. Significance: Inhibition of γ-secretase could impair TREM2 function in neuroinflammation. Triggering receptor expressed on myeloid cells-2 (TREM2) and its signaling adaptor protein TYROBP/DAP12 play important roles in signal transduction in dendritic cells, osteoclasts, tissue macrophages, and microglia. Recently, TREM2 variants have been shown to be linked to late onset Alzheimer disease. Here, we demonstrate that TREM2 undergoes sequential proteolytic processing by ectodomain shedding and intramembrane proteolysis. The C-terminal fragment (CTF) of TREM2 generated by ectodomain shedding is cleaved by γ-secretase. Importantly, pharmacologic and genetic γ-secretase inhibition resulted in accumulation of TREM2 CTF at the plasma membrane that also interacts with the signaling adaptor protein DAP12. Thus, the accumulated TREM2 CTF thereby might limit the interaction of DAP12 with the functional full-length receptor, resulting in decreased DAP12 phosphorylation and impaired metabolism of phosphatidylinositol 4,5-bisphosphate. Together, these data demonstrate γ-secretase-mediated intramembranous proteolysis of TREM2 and functionally link two Alzheimer disease-associated proteins in one signaling pathway.