LLukas22/scidocs huggingface dataset:
Detection of T790M, the Acquired Resistance EGFR Mutation, by Tumor Biopsy versus Noninvasive Blood-Based Analyses.

PURPOSE
The T790M gatekeeper mutation in the EGFR is acquired by some EGFR-mutant non-small cell lung cancers (NSCLC) as they become resistant to selective tyrosine kinase inhibitors (TKI). As third-generation EGFR TKIs that overcome T790M-associated resistance become available, noninvasive approaches to T790M detection will become critical to guide management.


EXPERIMENTAL DESIGN
As part of a multi-institutional Stand-Up-To-Cancer collaboration, we performed an exploratory analysis of 40 patients with EGFR-mutant tumors progressing on EGFR TKI therapy. We compared the T790M genotype from tumor biopsies with analysis of simultaneously collected circulating tumor cells (CTC) and circulating tumor DNA (ctDNA).


RESULTS
T790M genotypes were successfully obtained in 30 (75%) tumor biopsies, 28 (70%) CTC samples, and 32 (80%) ctDNA samples. The resistance-associated mutation was detected in 47% to 50% of patients using each of the genotyping assays, with concordance among them ranging from 57% to 74%. Although CTC- and ctDNA-based genotyping were each unsuccessful in 20% to 30% of cases, the two assays together enabled genotyping in all patients with an available blood sample, and they identified the T790M mutation in 14 (35%) patients in whom the concurrent biopsy was negative or indeterminate.


CONCLUSIONS
Discordant genotypes between tumor biopsy and blood-based analyses may result from technological differences, as well as sampling different tumor cell populations. The use of complementary approaches may provide the most complete assessment of each patient's cancer, which should be validated in predicting response to T790M-targeted inhibitors.
Resolving Quantifier and Number Restriction to Question OWL Ontologies

This paper describes an approach to resolve quantifiers and number restrictions in natural language questions to query ontologies. Incorporating this feature enables natural language query interfaces to capture a wider range of user queries. To deal with quantifiers and number restrictions, we analyzed a corpus of such questions and derived constraints at the syntactic level to recognize and parse them. The approach was implemented and evaluated through a system called ONLI+. Our method has been evaluated by conducting different experiments using the mean reciprocal rank (MRR) measure. Experimental results show that this feature has been incorporated into ONLI+ without degrading its performance in terms of transforming natural language queries into the nRQL queries, but definitely increases the expressivity of the user. To the best of our knowledge no other natural language interface to query ontologies can deal with quantifiers and number restrictions.
Anterior maxilla alveolar ridge dimension and morphology measurement by cone beam computerized tomography (CBCT) for immediate implant treatment planning

BACKGROUND
Implants have been widely used to restore missing teeth. Limited information on applied anatomy at the anterior maxilla compromises the clinical outcome for implant placement in this region. In the current study, Cone Beam Computerized Tomography (CBCT) was used to measure alveolar ridge and buccal undercut dimension at the anterior maxilla to help develop treatment planning for immediate implant placement.


METHODS
CBCT scans were screened to include 51 subjects with full dentition at right maxilla. Measurements were taken at the cross sectional views in the middle of the maxillary right central incisor, lateral incisor, and canine regions. Alveolar height was measured from the alveolar crest to floor of nasal fossa. Alveolar width was measured from the buccal to palatal cortical plate at the coronal, middle, and apical third of the distance from the alveolar crest to floor of the nasal fossa. Buccal undercut location was measured from where the buccal cortical plate started dipping to a line extending at the alveolar crest that was perpendicular to the long axis of the alveolar ridge. The buccal undercut depth was measured from the deepest point of the undercut at the buccal plate to a line tangent to the buccal plate paralleling the long axis of ridge.


RESULTS
Alveolar width increased from coronal to apical direction for each tooth. Mean alveolar widths (mm) were: central incisor, 9.55; lateral incisor, 8.30; canine, 9.62. The lateral incisor had a significantly smaller alveolar width than the other anterior teeth. No significant difference in ridge height was noted among the teeth. Undercut locations from the alveolar crest (mm) were: central incisor, 5.84; lateral incisor, 3.59; canine, 5.11. Undercut depths (mm) were: central incisor, 0.76; lateral incisor, 0.87; canine, 0.73. The percentages of teeth with buccal undercuts were: central incisor, 41%, lateral incisor, 77%, and canine 33%. Male demonstrate significant larger ridge width compared with females for all three teeth.


CONCLUSIONS
At anterior maxilla, the lateral incisor has the thinnest alveolar bone, and most frequently exhibits a buccal undercut which is the closest to alveolar ridge compared with other maxillary anterior teeth.
A review of process fault detection and diagnosis: Part I: Quantitative model-based methods

Fault detection and diagnosis is an important problem in process engineering. It is the central component of abnormal event management (AEM) which has attracted a lot of attention recently. AEM deals with the timely detection, diagnosis and correction of abnormal conditions of faults in a process. Early detection and diagnosis of process faults while the plant is still operating in a controllable region can help avoid abnormal event progression and reduce productivity loss. Since the petrochemical industries lose an estimated 20 billion dollars every year, they have rated AEM as their number one problem that needs to be solved. Hence, there is considerable interest in this field now from industrial practitioners as well as academic researchers, as opposed to a decade or so ago. There is an abundance of literature on process fault diagnosis ranging from analytical methods to artificial intelligence and statistical approaches. From a modelling perspective, there are methods that require accurate process models, semi-quantitative models, or qualitative models. At the other end of the spectrum, there are methods that do not assume any form of model information and rely only on historic process data. In addition, given the process knowledge, there are different search techniques that can be applied to perform diagnosis. Such a collection of bewildering array of methodologies and alternatives often poses a difficult challenge to any aspirant who is not a specialist in these techniques. Some of these ideas seem so far apart from one another that a non-expert researcher or practitioner is often left wondering about the suitability of a method for his or her diagnostic situation. While there have been some excellent reviews in this field in the past, they often focused on a particular branch, such as analytical models, of this broad discipline. The basic aim of this three part series of papers is to provide a systematic and comparative study of various diagnostic methods from different perspectives. We broadly classify fault diagnosis methods into three general categories and review them in three parts. They are quantitative model-based methods, qualitative model-based methods, and process history based methods. In the first part of the series, the problem of fault diagnosis is introduced and approaches based on quantitative models are reviewed. In the remaining two parts, methods based on qualitative models and process history data are reviewed. Furthermore, these disparate methods will be compared and evaluated based on a common set of criteria introduced in the first part of the series. We conclude the series with a discussion on the relationship of fault diagnosis to other process operations and on emerging trends such as hybrid blackboard-based frameworks for fault diagnosis. # 2002 Published by Elsevier Science Ltd.
Adenosine A2A receptor antagonist istradefylline reduces daily OFF time in Parkinson’s disease

BACKGROUND
We evaluated the efficacy and safety of istradefylline, a selective adenosine A2A receptor antagonist administered as adjunctive treatment to levodopa for 12 weeks in a double-blind manner in Parkinson's disease patients with motor complications in Japan.


METHODS
A total of 373 subjects were randomized to receive placebo (n=126), istradefylline 20 mg/day (n=123), or istradefylline 40 mg/day (n=124). The primary efficacy variable was the change in daily OFF time. Other secondary variables were also evaluated.


RESULTS
The change in daily OFF time was significantly reduced in the istradefylline 20 mg/day (-0.99 hours, P=.003) and istradefylline 40 mg/day (-0.96 hours, P=.003) groups compared with the placebo group (-0.23 hours). The most common adverse event was dyskinesia (placebo, 4.0%; istradefylline 20 mg/day, 13.0%; istradefylline 40 mg/day, 12.1%).


CONCLUSIONS
Istradefylline reduced daily OFF time and was well tolerated in Japanese PD patients with motor complications on levodopa treatment.
Integrating the Architecture Tradeoff Analysis Method ( ATAM ) with the Cost Benefit Analysis Method ( CBAM )

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Assessment of atrial conduction in patients with scleroderma by tissue Doppler echocardiography and P wave dispersion.

BACKGROUND
Atrial conduction abnormalities in patients with scleroderma have not been evaluated in terms of P wave duration, P wave dispersion (P(d)) and electromechanical coupling measured by tissue Doppler echocardiography.


METHODS
Twenty-four patients with scleroderma and 24 control subjects underwent resting electrocardiogram (ECG), M mode and tissue Doppler echocardiography. The P wave duration was calculated in all leads of the surface ECG. The difference between the maximum (P(max)) and minimum P wave duration was calculated and defined as P(d). Interatrial and intraatrial electromechanical delays were measured with tissue Doppler tissue echocardiography.


RESULTS
The left ventricular dimensions, fractional shortening, and left atrial diameter did not differ between the patients and the controls. P(d) and P(max) were significantly higher in patients with scleroderma compared with controls: 51 +/- 17 versus 28 +/- 7 ms (p < 0.01) and 109 +/- 10 versus 93 +/- 6 ms (p < 0.01), respectively. There was a delay between the onset of the P wave on surface ECG and the onset of the late diastolic wave (A wave; PA) obtained by tissue Doppler echocardiography in patients with scleroderma compared with controls measured at lateral septal annulus (lateral PA; 122 +/- 8 vs. 105 +/- 7 ms, p = 0.001), septal mitral annulus (104 +/- 11 vs. 93 +/- 10 ms, p = 0.01) and tricuspid annulus (right ventricular PA; 71 +/- 9 vs. 64 +/- 7 ms, p = 0.05). Interatrial conduction time (lateral PA - right ventricular PA) was delayed in patients with scleroderma compared with controls (88 +/- 13 vs. 76 +/- 11 ms, p = 0.01). A positive correlation was detected between interatrial electromechanical delay (lateral PA - right ventricular PA) and P(d) (r = 0.5, p = 0.03).


CONCLUSION
Atrial conduction abnormalities as estimated with P(d) and P(max) are significantly higher in patients with scleroderma compared with controls. There is a delay in both intraatrial and interatrial electromechanical coupling intervals in patients with scleroderma.
A phase III study evaluating the safety and efficacy of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting over repeated cycles of chemotherapy

BACKGROUND
Safe, effective and convenient antiemetic regimens that preserve benefit over repeated cycles are needed for optimal supportive care during cancer treatment. NEPA, an oral fixed-dose combination of netupitant, a highly selective NK1 receptor antagonist (RA), and palonosetron (PALO), a distinct 5-HT3 RA, was shown to be superior to PALO in preventing chemotherapy-induced nausea and vomiting after a single cycle of highly (HEC) or moderately (MEC) emetogenic chemotherapy in recent trials. This study was designed primarily to assess the safety but also to evaluate the efficacy of NEPA over multiple cycles of HEC and MEC.


PATIENTS AND METHODS
This multinational, double-blind, randomized phase III study (NCT01376297) in 413 chemotherapy-naïve patients evaluated a single oral dose of NEPA (NETU 300 mg + PALO 0.50 mg) given on day 1 with oral dexamethasone (DEX). An oral 3-day aprepitant (APR) regimen + PALO + DEX was included as a control (3:1 NEPA:APR randomization). In HEC, DEX was administered on days 1-4 and in MEC on day 1. Safety was assessed primarily by adverse events (AEs), including cardiac AEs; efficacy by complete response (CR: no emesis, no rescue).


RESULTS
Patients completed 1961 total chemotherapy cycles (76% MEC, 24% HEC) with 75% completing ≥4 cycles. The incidence/type of AEs was comparable for both groups. Most frequent NEPA-related AEs included constipation (3.6%) and headache (1.0%); there was no indication of increasing AEs over multiple cycles. The majority of AEs were mild/moderate and there were no cardiac safety concerns based on AEs and electrocardiograms. The overall (0-120 h) CR rates in cycle 1 were 81% and 76% for NEPA and APR + PALO, respectively, and antiemetic efficacy was maintained over repeated cycles.


CONCLUSIONS
NEPA, a convenient single oral dose antiemetic targeting dual pathways, was safe, well tolerated and highly effective over multiple cycles of HEC/MEC.
From Automated Verification to Automated Design

In this talk I will review 50 years of research on the design-synthesis problem and show how the automata-theoretic approach can be used to solve it.
Low-Pass Filtered Volumetric Shadows

We present a novel and efficient method to compute volumetric soft shadows for interactive direct volume visualization to improve the perception of spatial depth. By direct control of the softness of volumetric shadows, disturbing visual patterns due to hard shadows can be avoided and users can adapt the illumination to their personal and application-specific requirements. We compute the shadowing of a point in the data set by employing spatial filtering of the optical depth over a finite area patch pointing toward each light source. Conceptually, the area patch spans a volumetric region that is sampled with shadow rays; afterward, the resulting optical depth values are convolved with a low-pass filter on the patch. In the numerical computation, however, to avoid expensive shadow ray marching, we show how to align and set up summed area tables for both directional and point light sources. Once computed, the summed area tables enable efficient evaluation of soft shadows for each point in constant time without shadow ray marching and the softness of the shadows can be controlled interactively. We integrated our method in a GPU-based volume renderer with ray casting from the camera, which offers interactive control of the transfer function, light source positions, and viewpoint, for both static and time-dependent data sets. Our results demonstrate the benefit of soft shadows for visualization to achieve user-controlled illumination with many-point lighting setups for improved perception combined with high rendering speed.
Prevalence and stability of the DSM-III-R personality disorders in a community-based survey of adolescents.

OBJECTIVE
The purpose of this study was to estimate the prevalence, concurrent validity, and stability of DSM-III-R personality disorders in a large community-based sample of adolescents.


METHOD
A randomly selected community sample of 733 youths ranging in age from 9 to 19 years was followed over a 2-year period. The protocol consisted of structured interviews with the adolescents and their mothers and self-report questionnaires. Algorithms for 10 DSM-III-R axis II disorders were developed to produce diagnoses at two levels of severity; these were validated against multiple indicators of distress and functional impairment.


RESULTS
The overall prevalence of personality disorders peaked at age 12 in boys and at age 13 in girls and declined thereafter. Obsessive-compulsive personality disorder was the most prevalent moderate axis II disorder, narcissistic personality disorder the most prevalent severe disorder, and schizotypal personality disorder the least prevalent axis II disorder, based on both moderate and severe diagnostic thresholds. All moderate axis II disorders were associated with significantly greater odds for at least five of 12 diagnostic validators. Longitudinal follow-up revealed that although most axis II disorders did not persist over a 2-year period, subjects with disorders identified earlier remained at elevated risk for receiving a diagnosis again at follow-up.


CONCLUSIONS
These findings suggest that a substantial minority of adolescents who are not in treatment qualify for DSM-III-R personality disorder diagnoses and that these diagnoses are associated with increased risk of psychological distress and functional impairment.
Long-term outcome of laparoscopic nissen fundoplication compared with laparoscopic thal fundoplication in children: a prospective, randomized study.

BACKGROUND
Laparoscopic fundoplication is increasingly performed in pediatric surgery. Many types of fundoplication are performed, each has advantages and disadvantages. To date there has been no prospective randomized study to determine the optimal laparoscopic technique in children. The aim of the study was to compare the long-term outcomes and control of symptoms after laparoscopic Nissen fundoplication with laparoscopic Thal fundoplication in children.


METHODS
Between July 1998 and April 2007, 175 patients were recruited to this prospective, randomized study. Patients were assessed before the operation and after defined intervals starting at 3 months after surgery. The "absolute" outcome measure for fundoplication failure was recurrence of symptoms that merited a redofundoplication or insertion of a transgastric jejunostomy. "Relative" outcome measures were recurrence of symptoms necessitating reintroduction of antireflux medication (ie, "intention to treat") and postoperative complications (eg, postoperative dysphagia). The median follow-up time was 30 months (range, 1-109). This study has been registered with clinicaltrials.gov (NCT01027975).


RESULTS
Long-term results were available in 167 patients of which 85 underwent a Nissen and 82 a Thal fundoplication. Four patients in the Nissen group (4.7%) and 12 in the Thal group (14.6%) required a redofundoplication. One child in each group developed recurrence of symptoms and had a transgastric jejunostomy performed. The "absolute" failure rate was significant lower in the Nissen group (n = 5; 5.9%) compared with the Thal group (n = 13; 15.9%) (P = 0.038). The vast majority of these patients (17 of 18) had underlying neurological disorders. The "relative" failure rate (ie, "intention to treat") was similar in both groups. Nearly one-quarter of patients developed postoperative dysphagia similarly distributed between both groups. However, severe dysphagia requiring endoscopy +/- dilatation was significantly higher in the Nissen group (n = 10, 11.8%) compared with the Thal group (n = 2; 2.4%) (P = 0.020). One of 31 deaths (0.6%) in this series occurred after surgery, but was not directly related to the fundoplication technique.


CONCLUSIONS
In the long-term a laparoscopic Nissen fundoplication had a significantly lower recurrence rate than a Thal fundoplication, particularly in patients with underlying neurological disorders. There was no significant difference between the 2 types of fundoplication in normal children. There was no significant difference between the need for restarting antireflux medication between both groups because of recurrence of moderate symptoms. The incidence of postoperative dysphagia was similar in the 2 groups, however, significantly more patients in the Nissen group required intervention for severe dysphagia. Overall the perioperative death rate was low even in high-risk patients.
Testing static analysis tools using exploitable buffer overflows from open source code

Five modern static analysis tools (ARCHER, BOON, Poly-Space C Verifier, Splint, and UNO) were evaluated using source code examples containing 14 exploitable buffer overflow vulnerabilities found in various versions of Sendmail, BIND, and WU-FTPD. Each code example included a "BAD" case with and a "OK" case without buffer overflows. Buffer overflows varied and included stack, heap, bss and data buffers; access above and below buffer bounds; access using pointers, indices, and functions; and scope differences between buffer creation and use. Detection rates for the "BAD" examples were low except for Poly-Space and Splint which had average detection rates of 87% and 57%, respectively. However, average false alarm rates were high and roughly 50% for these two tools. On patched programs these two tools produce one warning for every 12 to 46 lines of source code and neither tool appears able to accurately distinguished between vulnerable and patched code.
A biomechanical evaluation of three revision screw strategies for failed lateral mass fixation.

STUDY DESIGN
This is a biomechanical study evaluating 3 revision strategies for failed cervical lateral mass screw fixation.


OBJECTIVE
Our primary objective was to compare, following a Magerl trajectory screw failure in the subaxial cervical spine, the pullout strength of (1) a revision screw in the same trajectory, (2) a Roy-Camille trajectory, and (3) pedicle screw fixation. We additionally analyzed the contributions of bone mineral density (BMD) and peak insertional torque to pullout strength.


SUMMARY OF BACKGROUND DATA
Biomechanical studies that have examined revision screw strategies for lateral mass fixation have found either unsatisfactory or highly variable performance.


METHODS
Fresh frozen cervical spinal segments were harvested and BMD testing performed. Bicortical (3.5-mm Vertex) lateral mass screws were placed in a Magerl trajectory in 57 fresh frozen human subaxial cervical vertebrae. All screws were then stripped and revision screws (4.0-mm Vertex) placed using either the same screw path or conversion to a Roy-Camille trajectory. In line pullout testing was performed on each of the revision screws (57 in Magerl revision group, 55 in Roy-Camille). Specimens that had not fractured during testing then had cervical pedicle screws (3.5-mm Vertex) placed and in-line pullout testing repeated (64 pedicles were instrumented) The pullout failure results of the Magerl revision, Roy-Camille revision, and pedicle screw revision groups were compared.


RESULTS
No significant difference was noted in insertional torque (0.28-Nm Magerl, 0.35 Nm Roy-Camille, P > 0.05) or pullout (382-N Magerl, 351 N Roy-Camille, P > 0.05) between the Magerl and Roy-Camille revision groups. Pedicle screw revision had greater pullout strength (566 N) when compared with either the Magerl (382 N) or Roy-Camille (351 N) revision groups (P < 0.01) but also had a 20% pedicle wall breech rate by visual inspection. Insertional torque and pullout strength increased with increased BMD and were significantly correlated in all 3 revision groups (P < 0.05). Similarly, increased BMD was associated with increased pullout strength as demonstrated by the significant positive correlation (P < 0.05).


CONCLUSION
Conversion of a stripped lateral mass screw to an alternate trajectory appears to offer no biomechanical advantage over placement of an increased diameter salvage screw using the same trajectory. Pedicle screw fixation provides superior biomechanical fixation but was associated with a significant breech rate.