Miracle-dz/UniFAR-FTUs huggingface dataset:
New Robust and Reproducible Stereological IHC Ki67 Breast Cancer Proliferative Assessment to Replace Traditional Biased Labeling Index

There is a pressing need for an objective decision tool to guide therapy for breast cancer patients that are estrogen receptor positive and HER2/neu negative. This subset of patients contains a mixture of luminal A and B tumors with good and bad outcomes, respectively. The 2 main current tools are on the basis of immunohistochemistry (IHC) or gene expression, both of which rely on the expression of distinct molecular groups that reflect hormone receptors, HER2/neu status, and most importantly, proliferation. Despite the success of a proprietary molecular test, definitive superiority of any method has not yet been demonstrated. Ki67 IHC scoring assessments have been shown to be poorly reproducible, whereas molecular testing is costly with a longer turnaround time. This work proposes an objective Ki67 index using image analysis that addresses the existing methodological issues of Ki67 quantitation using IHC on paraffin-embedded tissue. Intrinsic bias related to numerical assessment performed on IHC is discussed as well as the sampling issue related to the “peel effect” of tiny objects within a thin section. A new nonbiased stereological parameter (VV) based on the Cavalieri method is suggested for use on a double-stained Ki67/cytokeratin IHC slide. The assessment is performed with open-source ImageJ software with interobserver concordance between 3 pathologists being high at 93.5%. Furthermore, VV was found to be a superior method to predict an outcome in a small subset of breast cancer patients when compared with other image analysis methods being used to determine the Ki67 labeling index. Calibration methodology is also discussed to further this IHC approach.
Chronic-intermittent ethanol exposure during adolescence prevents normal developmental changes in sensitivity to ethanol-induced motor impairments.

BACKGROUND Recent evidence indicates that adolescent and adult rats are differentially sensitive to many of the acute effects of ethanol. Little is known about the neurobehavioral consequences of repeated ethanol exposure during adolescence relative to adulthood. In the present study we examined the impact of repeated ethanol exposure during adolescence and adulthood on subsequent sensitivity to ethanol-induced motor impairments. METHODS The tilting plane test was used to assess the impact of acute ethanol (3.0 g/kg) on motor coordination before (test 1), 2 days after (test 2), and 16 days after (test 3) a 20 day period of chronic-intermittent ethanol (CIE; 5.0 g/kg intraperitoneally every 48 hrs for 20 days) or isovolumetric chronic-intermittent saline (CIS) treatment in adolescent (postnatal (PD) 30) and adult (PD 70) rats. RESULTS Adolescent subjects were less sensitive than adults to the effects of ethanol on motor coordination during test 1. Adolescent CIS-treated subjects exhibited an increase in sensitivity to ethanol-induced motor impairments that reached adult levels by test 2 (PD 51) and remained stable between test 2 and test 3 (PD 65). Adolescent CIE-treated subjects did not exhibit this age-related increase in sensitivity. In this group, the effects of acute ethanol remained unchanged across the three testing days. Adult CIE-treated subjects exhibited a small degree of tolerance between test 1 and test 2 (PD 91) that was no longer evident during test 3 (PD 105). In adult CIS-treated subjects, the effects of acute ethanol remained stable across the three testing days. Blood ethanol concentrations assessed during testing suggest that age-related changes in sensitivity to ethanol-induced motor impairments are not related to changes in ethanol metabolism. CONCLUSIONS The data suggest that CIE exposure during adolescence has a lasting impact on sensitivity to ethanol-induced motor impairments. This effect might stem from a disruption of normal developmental processes.
Classification systems in dynamic environments: an overview

Data mining and machine learning algorithms can be employed to perform a variety of tasks. However, since most of these problems may depend on environments that change over time, performing classification tasks in dynamic environments has been a challenge in data mining research domain in the last decades. Currently, in the literature, the most common strategies used to detect changes are based on accuracy monitoring, which relies on previous knowledge of the data in order to identify whether or not correct classifications are provided. However, such a feedback can be infeasible in practical problems. In this work, we present a comprehensive overview of current machine learning/data mining approaches proposed to deal with dynamic environments problems. The objective is to highlight the main drawbacks and open issues, as well as future directions and problems worthy of investigation. In addition, we provide the definitions of the main terms used to represent this problem in the literature, such as concept drift and novelty detection. WIREs Data Mining Knowl Discov 2016, 6:156–166. doi: 10.1002/widm.1184
Visual Search in Complex Displays: Factors Affecting Conflict Detection by Air Traffic Controllers

Recent free flight proposals to relax airspace constraints and give greater autonomy to aircraft have raised concerns about their impact on controller performance. Relaxing route and altitude restrictions would reduce the regularity of traffic through individual sectors, possibly impairing controller situation awareness. We examined the impact of this reduced regularity in four visual search experiments that tested controllers' detection of traffic conflicts in the four conditions created by factorial manipulation of fixed routes (present vs. absent) and altitude restrictions (present vs. absent). These four conditions were tested under varying levels of traffic load and conflict geometry (conflict time and conflict angle). Traffic load and conflict geometry showed strong and consistent effects in all experiments. Color coding altitude also substantially improved detection times. In contrast, removing altitude restrictions had only a small negative impact, and removing route restrictions had virtually no negative impact. In some cases conflict detection was actually better without fixed routes. The implications and limitations of these results for the feasibility of free flight are discussed. Actual or potential applications include providing guidance in the selection of free flight operational concepts.
Distinct Regions of the Interleukin-7 Receptor Regulate Different Bcl2 Family Members

ABSTRACT The antiapoptotic function of the interleukin-7 (IL-7) receptor is related to regulation of three members of the Bcl2 family: synthesis of Bcl2, phosphorylation of Bad, and cytosolic retention of Bax. Here we show that, in an IL-7-dependent murine T-cell line, different regions of the IL-7 receptor initiate the signal transduction pathways that regulate these proteins. Both Box1 and Y449 are required to signal Bcl2 synthesis and Bax cytosolic retention. This suggests a sequential model in which Jak1, which binds to Box1, is first activated and then phosphorylates Y449, leading to Bcl2 and Bax regulation, accounting for approximately 90% of the survival function. Phosphorylation of Bad required Box1 but not Y449, suggesting that Jak1 also initiates an additional signaling cascade that accounts for approximately 10% of the survival function. Stat5 was activated from the Y449 site but only partially accounted for the survival signal. Proliferation required both Y449 and Box1. Thymocyte development in vivo showed that deletion of Y449 eliminated 90% of αβ T-cell development and completely eliminated γδ T-cell development, whereas deleting Box 1 completely eliminated both αβ and γδ T-cell development. Thus the IL-7 receptor controls at least two distinct pathways, in addition to Stat5, that are required for cell survival.
User-Defined Gestures for Gestural Interaction: Extending from Hands to Other Body Parts

ABSTRACT Most gestural interaction studies on gesture elicitation have focused on hand gestures, and few have considered the involvement of other body parts. Moreover, most of the relevant studies used the frequency of the proposed gesture as the main index, and the participants were not familiar with the design space. In this study, we developed a gesture set that includes hand and non-hand gestures by combining the indices of gesture frequency, subjective ratings, and physiological risk ratings. We first collected candidate gestures in Experiment 1 through a user-defined method by requiring participants to perform gestures of their choice for 15 most commonly used commands, without any body part limitations. In Experiment 2, a new group of participants evaluated the representative gestures obtained in Experiment 1. We finally obtained a gesture set that included gestures made with the hands and other body parts. Three user characteristics were exhibited in this set: a preference for one-handed movements, a preference for gestures with social meaning, and a preference for dynamic gestures over static gestures.
Variation in Macronutrients in Human Bank Milk: Influencing Factors and Implications for Human Milk Banking

Summary: Protein (P), fat (F), and carbohydrate (C) concentration in expressed human bank milk was determined by infrared analysis of 2,554 samples from 224 mothers. The mean contents of P, F, C, and energy (E, calculated from P, F, and C) were 9.0 g/L, 39.0 g/L, 71.9 g/L, and 696 kcal/L, respectively. There was a large variation in the concentration of energy-yielding macronutrients. The contents of P. F, C, and E in the samples with the highest values (97.5 percentile) were 2.3-, 4.8-, 1.2-, and 2.3-fold, respectively, above the contents in the samples with the lowest values (2.5 percentile). The P content decreased exponentially during the 1st 8 months, followed by an increase during the following months. The F content decreased during the 1st 4 months, followed by an almost linear increase. The possible influence of different maternal characteristics on the macronutrient content of the milk was examined. The main results were as follows: the P and F contents increased slightly with increasing body mass index of the mother, the P content decreased with increasing amounts of milk delivered to the milk bank, and the F content was higher in mothers delivering large amounts of milk. By selecting incoming milk with a high P content, we have developed a “high-protein” milk with a P content of about 12 g/L (true protein) and an E content of about 725 kcal/L. Thus, by continuous monitoring of macronutrient content in human bank milk it is possible to develop a “high-protein” milk with sufficient P and E content to cover the needs of preterm infants with very low birth weights (< 1,500 g).
Interactions between Fat and Dachsous and the regulation of planar cell polarity in the Drosophila wing

It was recently suggested that a proximal to distal gradient of the protocadherin Dachsous (Ds) acts as a cue for planar cell polarity (PCP) in the Drosophila wing, orienting cell-cell interactions by inhibiting the activity of the protocadherin Fat (Ft). This Ft-Ds signaling model is based on mutant loss-of-function phenotypes, leaving open the question of whether Ds is instructive or permissive for PCP. We developed tools for misexpressing ds and ft in vitro and in vivo, and have used these to test aspects of the model. First, this model predicts that Ds and Ft can bind. We show that Ft and Ds mediate preferentially heterophilic cell adhesion in vitro, and that each stabilizes the other on the cell surface. Second, the model predicts that artificial gradients of Ds are sufficient to reorient PCP in the wing; our data confirms this prediction. Finally, loss-of-function phenotypes suggest that the gradient of ds expression is necessary for correct PCP throughout the wing. Surprisingly, this is not the case. Uniform levels of ds drive normally oriented PCP and, in all but the most proximal regions of the wing, uniform ds rescues the ds mutant PCP phenotype. Nor are distal PCP defects increased by the loss of spatial information from the distally expressed four-jointed (fj) gene, which encodes putative modulator of Ft-Ds signaling. Thus, while our results support the existence of Ft-Ds binding and show that it is sufficient to alter PCP, ds expression is permissive or redundant with other PCP cues in much of the wing.
Localization of pulmonary nodules before thoracoscopic surgery: value of percutaneous staining with methylene blue.

OBJECTIVE Video-assisted thoracic surgery (VATS) is a new procedure that makes it possible to see the intrathoracic organs and to resect pulmonary nodules without thoracotomy. Preoperative localization of small nodules that may not be visible or palpable during VATS is desirable. Percutaneous placement of spring hookwires is widely used to localize pulmonary nodules before VATS; infrequently, the adjacent lung parenchyma is also stained with methylene blue. The purpose of this study was to evaluate the effectiveness of methylene blue staining of pulmonary nodules without placement of a hookwire. SUBJECTS AND METHODS Fifteen pulmonary nodules in 15 patients were localized preoperatively under CT guidance by using techniques identical to those for CT-guided fine-needle aspiration of pulmonary nodules. Approximately 0.3 ml of methylene blue dye was injected into the nodule with a 22-gauge Chiba needle to stain the nodule, the needle pathway, and the visceral pleura. In two patients, a hookwire also was placed. All patients had solitary nodules in which transbronchial or transthoracic biopsy had been unsuccessful. The mean nodule diameter was 16 mm (range, 8-33 mm), and the mean distance to the nearest pleural surface was 10 mm (range, 0-21 mm). The localization procedure required a mean of 32 min (range, 18-47 min). RESULTS All 15 nodules were stained successfully either in the center or within the margins; the two hookwires were found to be displaced. In three cases, pulmonary hemorrhage occurred as a complication of the percutaneous staining procedure: in one case, subsequent conversion to thoracotomy was necessary owing to pulmonary hemorrhage and additional pleural bleeding during VATS, which resulted from puncture with a trocar directly into the pleural adhesions. Anticipated complications, such as pneumothorax, occurred in five patients; one patient had pleuritic pain, but none required treatment. In one patient, conversion to thoracotomy was done so that an adenocarcinoma could be treated by means of a lobectomy. In two others, thoracotomy was done because of problems with technical devices. CONCLUSIONS Percutaneous staining of pulmonary nodules is an accurate technique for localizing nodules before VATS. The procedure is easily and safely performed, and it obviates wire-related complications, such as severe pleuritic pain.
Malignant transformation of aneurysmal bone cyst, with an analysis of the literature

An 11‐year‐old girl had a lytic, benign‐appearing, expansive lesion of the distal tibia radiologically interpreted as an aneurysmal bone cyst (ABC). Tissue from two extensive curettage procedures was also histologically diagnosed as ABC. Approximately 50 months after the onset of symptoms, and 28 months after her last curettage, a highly pleomorphic osteosarcoma developed. The patient had not received prior radiation therapy. The cases in the literature of possible malignant transformation of ABC are reviewed. The authors separate their case from telangiectatic osteosarcoma, and from “ aneurysmal bone cyst‐like osteosarcoma”.
Two-jet production in hadron collisions at order alpha s3 in QCD.

We calculate the two-jet inclusive cross section at order [alpha][sub [ital s]][sup 3] in QCD. Because the one-loop perturbative corrections are included, there is considerable improvement in theoretical accuracy compared to the Born-level calculation. We compare the predicted dependence of the cross section on the jet-jet scattering angle [eta][sub 1][minus][eta][sub 2] to data from the CDF collaboration. We also discuss the dependence of the cross section on the jet-jet mass.
Experiences on analog circuit technology migration and reuse

This work deals with two aspects of the reuse and redesign of analog circuits. First, a method for technology migration of analog circuits, recently proposed by Galup-Montoro and Schneider (Proc. SBCCI2000, pp. 89-93, 2000), is validated experimentally in the redesign of a Miller OTA from a 2.4 /spl mu/m technology to a 0.8 /spl mu/m technology. In addition, the impact of the method on performance aspects of analog circuits not covered in the original proposal (slew rate and current mirror frequency response) is studied. As a second mechanism for allowing the reuse of analog circuits, the feasibility of the application of the reference bias current as a tuning parameter to customize the performance of an existing design to suit different applications is demonstrated.
An approach to obtain the V-I characteristic of fuel cells by means of DC-DC converters

This paper proposes a new approach to test and evaluate V-I characteristics of fuel cells stacks based on DC-DC converters, which features are simple structure, scalability, fast response and low cost. The measurement of the desired characteristic of fuel cells includes high speed of response, high fidelity and low cost. The obtained results show that all DC-DC topologies are not capable of reproducing this characteristic and that SEPIC (Single-Ended Primary Inductance Converter) converter is optimal for this application. Experimental results show the usefulness of the proposed method.
Concentrations of alprazolam in blood from impaired drivers and forensic autopsies were not much different but showed a high prevalence of co-ingested illicit drugs

Alprazolam is a benzodiazepine anxiolytic widely prescribed for treatment of panic-disorder and social phobias, although this medication is also subject to abuse. In this paper, the concentrations of alprazolam in venous blood samples from impaired drivers were compared with femoral blood samples from forensic autopsies classified as intoxication or other causes of death (e.g. natural, trauma). After liquid–liquid extraction (n-butyl acetate) alprazolam was determined in blood by capillary gas chromatography with a nitrogen–phosphorous detector. The mean (median) and range of alprazolam concentrations in blood from impaired drivers (n = 773) were 0.08 mg/L (0.05 mg/L) and 0.02–3.9 mg/L, respectively. Many traffic offenders had co-ingested ethanol (13%), amphetamine (46%), cannabis (32%), or heroin (14%), as well as other drugs. In deaths attributed to drug intoxication, the mean (median) and range of alprazolam concentrations in blood (n = 438) were 0.10 mg/L (0.06 mg/L) and 0.02–1.6 mg/L, respectively, which were not much different from other causes of death (n = 278); 0.08 mg/L (0.05 mg/L) and 0.02–0.9 mg/L. Median concentrations of alprazolam in blood from living and deceased persons did not seem to depend on the number of co-ingested substances. The result of this pharmacoepidemiological study suggests that alprazolam is a fairly innocent drug when used as monotherapy, but toxicity problems arise when co-ingested with illicit drugs and/or psychoactive medication.
Glucocorticoids Regulate Hippocampal 11β‐Hydroxysteroid Dehydrogenase Activity and Gene Expression in vivo in the Rat

Chronic glucocorticoid excess or deficiency is associated with hippocampal dysfunction and neuronal death. 11β‐hydroxysteroid dehydro‐genase (11β‐OHSD), which catalyses the reversible conversion of corticosterone to inactive 11 ‐dehydrocorticosterone, regulates glucocorticoid access to receptors in the kidney and liver in vivo. The enzyme is also present in the hippocampus where it might modulate glucocorticoid action. We examined the effects of corticosteroid manipulations on hippocampal and peripheral 11β‐OHSD. In the hippocampus, chronic adrenalectomy (10 days) had no effect on 11β‐OHSD activity, compared to sham‐operated controls. Treatment of adrenalectomized animals with dexamethasone (200 μg/kg.day−1), but not aldosterone (20 μg/kg.day−1), for 10 days significantly increased hippocampal 11β‐OHSD activity compared with sham or adrenalectomized rats (22% and 23% rise respectively, P<0.05). These effects reflect changes in transcription of the liver‐type 11β‐OHSD gene, with dexamethasone significantly increasing 11β‐OHSD mRNA expression in the hippocampus compared with sham or adrenalectomized animals (32% and 70% higher respectively, P<0.05). In the liver, adrenalectomy significantly reduced 11β‐OHSD activity (16% lower), which was restored to sham levels by dexamethasone, but not aldosterone. Similar trends were seen in 11β‐OHSD mRNA expression, although these did not reach significance. None of the manipulations altered 11β‐OHSD activity or mRNA expression in the kidney. The hippocampal effects of dexamethasone were similar to those of chronic stress (arthritis) which increased 11β‐OHSD activity (20% rise, P<0.05), although this was not reflected at the level of mRNA. Thus, hippocampal (and hepatic, but not renal) 11β‐OHSD appears to be regulated by chronic glucocorticoid manipulations and stress. Hippocampal 11β‐OHSD may thus ensure optimal long‐term corticosterone exposure of glucocorticoid‐sensitive neurons.
Noncommunicating Cysts and Cerebrospinal Fluid Flow Dynamics in a Patient With a Chiari I Malformation and Syringomyelia—Part II

Cerebrospinal fluid (CSF) flow dynamics are known to be altered in the foramen magnum region in patients with Chiari I malformations. In particular, it has been postulated that the downward tonsillar displacement hinders the rapid bidirectional CSF passage across the foramen magnum, which normally occurs during each cardiac cycle in response to the pulsatile expansion and contraction of the brain. It has been postulated that this creates enlarged cervical subarachnoid pressure waves that compress the spinal cord and forces CSF to penetrate into the spinal cord, propagating syrinx fluid caudally with each heartbeat. However, the incidence of syrinx formation in patients with Chiari I malformations is quite variable, and this is a reflection of the complexity of this problem. It has been reported that 3 types of cavitary patterns can be present in syringomyelia. In particular, it has been determined that the following 3 possibilities exist in these cases: (1) dilatations of the central canal can communicate directly with the fourth ventricle; (2) dilatations of the central canal can occur below a syrinx-free segment of the spinal cord; and (3) extracanalicular syringes can originate in the spinal cord parenchyma and not communicate with the central canal. It is also been suggested that the pathophysiology is different in these 3 conditions. For example, communicating central canal syringes appear to be commonly found in patients with hydrocephalus. Noncommunicating syringes are reported to occur in patients with arachnoiditis. Furthermore, it has also been suggested that different treatment strategies of patients with Chiari I malformations and syringomyelia should be applied based on the type of syrinx that is present. However, it also has been suggested that “noncommunicating” syringomyelia does not really exist, but rather a communication between the syrinx and the fourth ventricle can always be found. There are no descriptions of independent noncommunicating spinal cord syringes, and quantitation of CSF flow through a syrinx before and immediately after surgery has not been studied. We carefully segment the regions of the upper spinal cord in patients with syringomyelia to calculate flow using phase-contrast magnetic resonance imaging (MRI) in the following 3 spaces: subarachnoid space, syrinx cavity, and spinal cord. In this report, we describe a patient with a very unusual syrinx composed of 2 distinct adjacent components that do not communicate.