LLukas22/scidocs huggingface dataset:
Phase I clinical and pharmacokinetic study of combination chemotherapy with topotecan and ifosfamide in patients with progressive or relapsed solid tumors.

 Purpose.Topotecan and ifosfamide are effective in the treatment of various solid tumors. Up to the time of this study, the two drugs have been combined just once (Smith et al. 1998). Due to its hematotoxicity, topotecan has been used predominantly within monochemotherapy protocols. However, the combination of topotecan and alkylating agents is supra-additive in many preclinical models. This phase-I trial was primarily performed to evaluate the maximum tolerable dose (MTD) and dose-limiting toxicity (DLT) of a combination chemotherapy with topotecan and ifosfamide using a 5-day schedule. A secondary goal was to estimate the response rate in a group of heavily pretreated patients with advanced solid tumors. Methods.The pharmacokinetics of topotecan were preliminarily determined in some of the patients. A total of 12 patients (three female/nine male), median age 49 years (range 19–69), 11 with prior chemotherapy, received a total of 24 courses of chemotherapy at three dose-levels of topotecan. Ifosfamide was administered by intravenous infusion over 3 h immediately followed by a 30-min infusion of topotecan. Mesna (3×300 mg·m2·day) was given routinely during chemotherapy as a uroprotector. G-CSF (filgrastim) was permitted only in cases of febrile neutropenia (FN). Results.The major toxicity was non-hematologic; severe liver and renal toxicity were observed in three out of 11 patients. Two treatment-related deaths occurred. No clinical remissions occured in 11 evaluable patients. The pharmacokinetics of topotecan were relatively similar in our patients and supported findings in recent literature. The MTD of this combination was defined at dose-level 2 (1.0 mg/m2 of topotecan and 750 mg/m2 of ifosfamide). Conclusions.Further trials should not exceed this dose. The pharmacological causes for the pronounced toxicity have to be clarified.
ARC15105 is a potent antagonist of von Willebrand factor mediated platelet activation and adhesion.

OBJECTIVE
We investigated the stability, pharmacokinetic, and pharmacodynamic profile of the 2(nd) generation anti-von Willeband factor aptamer ARC15105.


METHODS AND RESULTS
Platelet plug formation was measured by collagen/adenosine diphosphate-induced closure time with the platelet function analyzer-100 and platelet aggregation by multiple electrode aggregometry. Platelet adhesion was measured on denuded porcine aortas and in a flow chamber. Aptamer stability was assessed by incubation in nuclease rich human, monkey, and rat serum for up to 72 hours. Pharmacokinetic and pharmacodynamic profiles were tested in cynomolgus monkeys after IV and SC administration. The median IC(100) and IC(50) to prolong collagen/adenosine diphosphate-induced closure timewere 27 nmol/L and 12 nmol/L, respectively. ARC15105 (1.3 μmol/L) completely inhibited ristocetin-induced platelet aggregation in whole blood (P<0.001), but also diminished collagen, ADP, arachidonic acid, and thrombin receptor activating peptide-induced platelet aggregation to some extent (P<0.05). ARC15105 (40 nmol/L) decreased platelet adhesion by >90% on denuded porcine aortas (P<0.001), which was comparable to the degree of inhibition obtained with abciximab. ARC15105 (100 nmol/L) also inhibited platelet adhesion to collagen under arterial shear in a flow chamber by >90% (P<0.001). The IV and SC terminal half-lives in cynomolgus monkeys were 67 and 65 hours, respectively, and the SC bioavailability was ≈98%. Allometric scaling estimates the human T(1/2) would be ≈217 hours. Pharmacodynamic analysis confirms that ARC15105 inhibits von Willeband factor activity >90% in blood samples taken 300 hours after a 20 mg/kg IV or SC dose in monkeys.


CONCLUSIONS
The potency, pharmacokinetic profile, and SC bioavailability of ARC15105 support its clinical investigation for chronic inhibition of von Willeband factor -mediated platelet activation.
A comparison of sleep assessment tools by nurses and patients in critical care.

AIM
The aim of this critical care sleep assessment pilot study was to evaluate the usefulness of three sleep assessment tools to identify which, if any, provided the closest comparison between the nurses' judgement and the patients' experience of their sleep. The study objectives were to: (i) compare patients' and nurses' assessment of sleep using three different rating tools. (ii) Ascertain patients' preferences with non-interventional, user friendly, practical tools in critical care. (iii) Recommend changes and improvements to the way that sleep is assessed and documented.


BACKGROUND
Sleep is important for promoting critical care recovery and sleep disturbance is known to cause irritability, aggression and increased stress levels. The availability and use of valid critical care sleep assessment tools is limited.


DESIGN
A descriptive comparative study using three sleep assessment-rating scales were constructed to provide easy to understand tools for completion by both patients and nurses in critical care.


METHODS
Structured interviews were undertaken with 82 patients and 82 nurses using a convenience sample from four multispecialty critical care units in one large teaching trust. Patients were included in the study if they met a list of pre-defined criteria to obtain responses from lucid orientated patients.


RESULTS
No tool produced a close association between the nurses' assessment of the patients sleep and the patients' assessment of their sleep. Patients found two of the three tools easy to use when rating their sleep. Discussion. Objective invasive measurements of sleep as well as complex subjective tools appear inappropriate to be used as a part of daily critical care practice. The application of simple rating scores has a high degree of error when nurses assess patients' sleep, even though high levels of patient observation and assessment are practiced in critical care.


CONCLUSIONS
More research is needed to examine the assessment of sleep in critical care, particularly linking rating scales to alternative methods of physiological assessment of sleep. Findings indicate nurses are unable to accurately assess critical care patients' sleep using rating assessment tools. However patients were found to prefer two sleep assessment tools, one banded in hours to assess sleep quantity and one as a comparison against normal sleep to assess sleep quality.


RELEVANCE TO CLINICAL PRACTICE
This study reviews the importance of sleep assessment and the diverse methods available for assessing sleep focussing on the critically ill patient. More noteworthy it highlights how nurses sole judgements of patients sleep is not a reliable method in clinical practice, however it provides some indication on the application of 'easy to use' tools to assist in the patients assessments of their sleep.
Randomized trial of fructosamine home monitoring in patients with diabetes.

CONTEXT
Recognition of the importance of glycemic control in type 2 diabetes has generated interest in developing ways to improve such control. Levels of fructosamine, 1-amino-1-deoxyfructose, are highly correlated with those of hemoglobin A1c (HbA1c) and can be monitored in the home.


DESIGN
Randomized trial.


PARTICIPANTS
140 adult patients with HbA1c values of 8% or greater were recruited to the trial through referral from physicians and a direct mailing to potentially eligible persons.


INTERVENTION
Weekly home fructosamine monitoring in addition to daily glucose monitoring. Control patients monitored daily glucose only. Both groups of patients were contacted regularly by telephone and were given the same instructions on diet and exercise.


OUTCOME
Measures of glycemic control 3 and 6 months after randomization.


RESULTS
No significant difference was found between the two groups in the mean absolute decrease of HbA1c levels at 3 months (0.5% in the fructosamine group vs. 0.8% in the control group; P > 0.2), and the difference favored the control group at 6 months (0.7% fructosamine vs. 1.2% control; P = 0.04). Both groups had a statistically significant improvement in glycemic control.


CONCLUSIONS
The addition of home fructosamine monitoring to routine glucose monitoring did not improve glycemic control.
Computer Games: A Double-Edged Sword?

Excessive computer game playing (ECGP) has already become a serious social problem. However, limited data from experimental lab studies are available about the negative consequences of ECGP on players' cognitive characteristics. In the present study, we compared three groups of participants (current ECGP participants, previous ECGP participants, and control participants) on a Multiple Object Tracking (MOT) task. The previous ECGP participants performed significantly better than the control participants, which suggested a facilitation effect of computer games on visuospatial abilities. Moreover, the current ECGP participants performed significantly worse than the previous ECGP participants. This more important finding indicates that ECGP may be related to cognitive deficits. Implications of this study are discussed.
Anticipating Accidents in Dashcam Videos

We propose a Dynamic-Spatial-Attention (DSA) Recurrent Neural Network (RNN) for anticipating accidents in dashcam videos (Fig. 1). Our DSA-RNN learns to (1) distribute soft-attention to candidate objects dynamically to gather subtle cues and (2) model the temporal dependencies of all cues to robustly anticipate an accident. Anticipating accidents is much less addressed than anticipating events such as changing a lane, making a turn, etc., since accidents are rare to be observed and can happen in many different ways mostly in a sudden. To overcome these challenges, we (1) utilize state-of-the-art object detector [3] to detect candidate objects, and (2) incorporate full-frame and object-based appearance and motion features in our model. We also harvest a diverse dataset of 678 dashcam accident videos on the web (Fig. 3). The dataset is unique, since various accidents (e.g., a motorbike hits a car, a car hits another car, etc.) occur in all videos. We manually mark the time-location of accidents and use them as supervision to train and evaluate our method. We show that our method anticipates accidents about 2 seconds before they occur with 80% recall and 56.14% precision. Most importantly, it achieves the highest mean average precision (74.35%) outperforming other baselines without attention or RNN. 2 Fu-Hsiang Chan, Yu-Ting Chen, Yu Xiang, Min Sun
A Plasmodium Calcium-Dependent Protein Kinase Controls Zygote Development and Transmission by Translationally Activating Repressed mRNAs

Calcium-dependent protein kinases (CDPKs) play key regulatory roles in the life cycle of the malaria parasite, but in many cases their precise molecular functions are unknown. Using the rodent malaria parasite Plasmodium berghei, we show that CDPK1, which is known to be essential in the asexual blood stage of the parasite, is expressed in all life stages and is indispensable during the sexual mosquito life-cycle stages. Knockdown of CDPK1 in sexual stages resulted in developmentally arrested parasites and prevented mosquito transmission, and these effects were independent of the previously proposed function for CDPK1 in regulating parasite motility. In-depth translational and transcriptional profiling of arrested parasites revealed that CDPK1 translationally activates mRNA species in the developing zygote that in macrogametes remain repressed via their 3' and 5'UTRs. These findings indicate that CDPK1 is a multifunctional protein that translationally regulates mRNAs to ensure timely and stage-specific protein expression.
High level of plasma remnant-like particle cholesterol may predispose to development of hypertension in normotensive subjects.

BACKGROUND
Remnant-like lipoprotein particle cholesterol (RLP-C) is a highly atherogenic factor. RLP-C induces endothelial dysfunction and is associated with hyperinsulinemia. This study was designed to determine whether high plasma RLP-C levels predispose to the development of hypertension in subjects with normal blood pressure (BP).


METHODS
A total of 1,485 subjects aged >40 years in a Japanese Cohort of the Seven Countries Study received health examinations. We examined BP, anthropometric parameters, and blood chemistries, including fasting RLP-C levels. RLP-C levels were measured by an immune-separation method. We excluded from the analysis 676 subjects who had hypertension (BP ≥ 140/90mm Hg), or were on antihypertensive medication, and/or were on antihyperlipidemic medication at baseline. Ten years later, 681 subjects were re-examined.


RESULTS
Of 681 normotensive subjects at baseline, 303 subjects had developed hypertension 10 years later. Baseline RLP-C level was significantly higher (P < 0.01) in the subjects who developed hypertension than in those who remained normotensive (3.7±1.9 vs. 3.3±1.6mg/dl). Multivariable logistic regression analysis demonstrated that baseline RLP-C was a significant factor for incident hypertension after adjustments for homeostasis model assessment index and other hypertension-related factors (odds ratio = 1.05, 95% CI = 1.00-1.10; P = 0.04).


CONCLUSIONS
A high level of plasma RLP-C in normotensive subjects may predispose to the development of hypertension in a population of community-dwelling Japanese.
Eminence of scientists in the light of the h-index and other scientometric indicators

Scientometrics cannot offer a simple consistent method for measuring the scientific eminence of individuals. The h-index method introduced by Hirsch was found applicable for evaluating publications of senior scientists with similar publishing features, only. Some simple methods – using the number of citations and journal papers, and the number of citations obtained by the most frequently cited papers – are suggested and tested to demonstrate the advantages and disadvantages of such indexes. The results indicate that calculating scientometric indexes for individuals, self-citations should be excluded and the effect of the different bibliometric features of the field should be taken into account. The correctness of the indexes used for evaluating journal papers of individuals should be investigated also on the individual level.
Face Recognition Using Convolutional Neural Network and Simple Logistic Classifier

In this paper, a hybrid system is presented in whi ch a convolutional neural network (CNN) and a Logistic regression class ifier (LRC) are combined. A CNN is trained to detect and recognize face images , and a LRC is used to classify the features learned by the convolutional network. Applying feature extraction using CNN to normalized data causes the sys tem to cope with faces subject to pose and lighting variations. LRC which is a discriminative classifier is used to classify the extracted features of face images. Discriminant analysis is more efficient when the normality assumptions are s atisfied. The comprehensive experiments completed on Yale face database sh ows improved classification rates in smaller amount of time.
Auricular acupuncture in the treatment of cocaine/crack abuse: a review of the efficacy, the use of the National Acupuncture Detoxification Association protocol, and the selection of sham points.

BACKGROUND
The United Kingdom has had a significant increase in addiction to and use of cocaine among 16-29-year olds from 6% in 1998 to 10% in 2000. In 2000, the United Kingdom had the highest recorded consumption of "recent use" cocaine in Europe, with 3.3% of young adults. Acupuncture is quick, inexpensive, and relatively safe, and may establish itself as an important addiction service in the future.


AIM
To select investigations that meet the inclusion criteria and critically appraise them in order to answer the question: "Is acupuncture effective in the treatment of cocaine addiction?" The focus shall then be directed toward the use of the National Acupuncture Detoxification Association (NADA) protocol as the intervention and the selection of sham points for the control group.


DATA SOURCES
The ARRC database was accessed from Trina Ward (M. Phil. student) at Thames Valley University. AMED, MEDLINE and Embase were also accessed along with "hand" searching methods at the British Library.


INCLUSION AND EXCLUSION CRITERIA
People addicted to either cocaine or crack cocaine as their main addiction, needle-acupuncture, single-double-blinded process, randomized subjects, a reference group incorporating a form of sham points.


EXCLUSION CRITERIA
use of moxibustion, laser acupuncture, transcutaneous electrical nerve stimulation (TENS) electroacupuncture or conditions that did not meet the inclusion criteria.


QUALITY ASSESSMENT
The criteria set by ter Riet, Kleijnen and Knipschild (in 1990); Hammerschlag and Morris (in 1990); Koes, Bouter and van der Heijden (in 1995), were modified into one set of criteria consisting of 27 different values.


RESULTS
Six randomized controlled trials (RCTs) met the inclusion criteria and were included in this review. All studies scored over 60 points indicating a relatively adequate methodology quality. The mean was 75 and the standard deviation was 6.80. A linear regression analysis did not yield a statistically significant association (n = 6, p = 0.11).


CONCLUSIONS
This review could not confirm that acupuncture was an effective treatment for cocaine abuse. The NADA protocol of five treatment points still offers the acupuncturist the best possible combination of acupuncture points based upon Traditional Chinese Medicine. Throughout all the clinical trials reviewed, no side-effects of acupuncture were noted. This paper calls for the full set of 5 treatment points as laid out by the NADA to be included as the treatment intervention. Points on the helix, other than the liver yang points, should be selected as sham points for the control group.
On the Neural Mechanisms Subserving Consciousness and Attention

Consciousness, as described in the experimental literature, is a multi-faceted phenomenon, that impinges on other well-studied concepts such as attention and control. Do consciousness and attention refer to different aspects of the same core phenomenon, or do they correspond to distinct functions? One possibility to address this question is to examine the neural mechanisms underlying consciousness and attention. If consciousness and attention pertain to the same concept, they should rely on shared neural mechanisms. Conversely, if their underlying mechanisms are distinct, then consciousness and attention should be considered as distinct entities. This paper therefore reviews neurophysiological facts arguing in favor or against a tight relationship between consciousness and attention. Three neural mechanisms that have been associated with both attention and consciousness are examined (neural amplification, involvement of the fronto-parietal network, and oscillatory synchrony), to conclude that the commonalities between attention and consciousness at the neural level may have been overestimated. Last but not least, experiments in which both attention and consciousness were probed at the neural level point toward a dissociation between the two concepts. It therefore appears from this review that consciousness and attention rely on distinct neural properties, although they can interact at the behavioral level. It is proposed that a "cumulative influence model," in which attention and consciousness correspond to distinct neural mechanisms feeding a single decisional process leading to behavior, fits best with available neural and behavioral data. In this view, consciousness should not be considered as a top-level executive function but should rather be defined by its experiential properties.
Mining sequential patterns by pattern-growth: the PrefixSpan approach

Sequential pattern mining is an important data mining problem with broad applications. However, it is also a difficult problem since the mining may have to generate or examine a combinatorially explosive number of intermediate subsequences. Most of the previously developed sequential pattern mining methods, such as GSP, explore a candidate generation-and-test approach [R. Agrawal et al. (1994)] to reduce the number of candidates to be examined. However, this approach may not be efficient in mining large sequence databases having numerous patterns and/or long patterns. In this paper, we propose a projection-based, sequential pattern-growth approach for efficient mining of sequential patterns. In this approach, a sequence database is recursively projected into a set of smaller projected databases, and sequential patterns are grown in each projected database by exploring only locally frequent fragments. Based on an initial study of the pattern growth-based sequential pattern mining, FreeSpan [J. Han et al. (2000)], we propose a more efficient method, called PSP, which offers ordered growth and reduced projected databases. To further improve the performance, a pseudoprojection technique is developed in PrefixSpan. A comprehensive performance study shows that PrefixSpan, in most cases, outperforms the a priori-based algorithm GSP, FreeSpan, and SPADE [M. Zaki, (2001)] (a sequential pattern mining algorithm that adopts vertical data format), and PrefixSpan integrated with pseudoprojection is the fastest among all the tested algorithms. Furthermore, this mining methodology can be extended to mining sequential patterns with user-specified constraints. The high promise of the pattern-growth approach may lead to its further extension toward efficient mining of other kinds of frequent patterns, such as frequent substructures.
The cooperative amoeba: Dictyostelium as a model for social evolution.

Social interactions, including cooperation and altruism, are characteristic of numerous species, but many aspects of the evolution, ecology and genetics of social behavior remain unclear. The microbial soil amoeba Dictyostelium discoideum is a model system for the study of social evolution and provides insights into the nature of social cooperation and its genetic basis. This species exhibits altruism during both asexual and sexual cycles of its life history, and recent studies have uncovered several possible genetic mechanisms associated with kin discrimination and cheating behavior during asexual fruiting-body formation. By contrast, the molecular and evolutionary mechanisms that underlie sexual macrocyst formation remain largely enigmatic. D. discoideum, given its utility in molecular genetic studies, should continue to help us address these and other relevant questions in sociobiology, and thereby contribute to a coherent theoretical framework for the nature of social cooperation.