Miracle-dz/UniFAR-FTUs huggingface dataset:
Psychosocial Stress and Immunity—What Can We Learn From Pig Studies?

Psychosocial stress may impair immune functions and provoke the development of pathologies. The underlying communication between the brain and the immune system is being studied predominantly in rodents. However, pigs offer several advantages as preclinical models for humans because pigs are more similar to humans than rodents in many anatomical and physiological characteristics. Unlike in rodents, the main stress-induced glucocorticoid in humans and pigs is cortisol with a similar circadian rhythm. In this study, we summarize data on short-term and long-term effects of social stress in pigs for their immunity and neuroendocrine regulation with consequences for their health and well-being. As typical social stressors, regrouping, crowding, social isolation, and maternal deprivation have been studied. Psychosocial stress in pigs may affect various reactions of innate and adaptive immunity, such as leukocyte distribution, cytokine secretion, lymphocyte proliferation, and antibody production as well as immune responses to viral infection or vaccination. Furthermore, social stress may induce or promote gastrointestinal diseases through dysregulation of inflammatory processes. In piglets, psychosocial stress may also result in glucocorticoid resistance of lymphocytes, which has been discussed as a cause of allergic asthma in humans. Stress-related neuroendocrine alterations in the cortico-limbic structures, such as the prefrontal cortex, amygdala, hippocampus and hypothalamus, have been demonstrated in pigs at different ages. Based on these data, we propose using pigs as models for psychosocial stress in humans to study the mechanisms of brain-to-immune and immune-to-brain communication from the systemic level down to the cellular and subcellular levels.
The HOVON68 CLL trial revisited: performance status and comorbidity affect survival in elderly patients with chronic lymphocytic leukemia

Abstract In the HOVON68 CLL trial, patients 65 to 75 years of age had no survival benefit from the addition of low-dose alemtuzumab to fludarabine and cyclophosphamide (FC) in contrast to younger patients. The reasons are explored in this 5-year trial update using both survival analysis and competing risk analysis on non-CLL-related mortality. Elderly FCA patients died more frequently from causes not related to CLL, and more often related to comorbidity (mostly cardiovascular) than to infection. In a Cox multivariate analysis, del(17p), performance status >0, and comorbidity were associated with a higher non-CLL-related mortality in the elderly independent of the treatment modality. Thus, while the ‘fit’ elderly with no comorbidity or performance status of 0 might potentially benefit from chemo-immunotherapy with FC, caution is warranted, when considering alemtuzumab treatment in elderly patients with cardiovascular comorbidity.
Inclusion morphology of disabled pipe plate

In order to increase the yield,morphology and character of the inclusion in disabled pipe plate were studied by means of macroscopic and microscopic examinations,electron microscopic scanning and electron beam microanalyzer.The experimental results show that the disabled pipe plate has some flaked inclusionss and cracks with character of hydrogen brittleness.Some main measures preventing the cracks were also put forward.
Pediatric Off-Label and Unlicensed Drug Use and Its Implications.

BACKGROUND Worldwide, in the absence of standard pediatric prescribing information, clinicians often use medicines in children in a dosage form or for an indication that has not been approved for use. Inadequate clinical trials increase exposure to drugs that lack safety-efficacy data in pediatric population. Hence, off-label and unlicensed drug use must be regarded as a patient safety-issue that is known to be associated with increased risks of adverse drug reactions apart from under- or overdosing due to lack of pharmacokinetic data. This review aims to give an overview of the worldwide reported rates of off-label and unlicensed drug use in different patient populations in pediatric settings, with a brief summary of the related adverse drug reactions (ADRs) and a discussion of the existing regulatory provisions and possible solutions for ensuring safe use of medicines in children. METHOD Literature searches were conducted and we included studies that evaluated unlicensed or off-label drug use in various pediatric patient populations. The definition of off-label drug use and unlicensed drug varied between different studies. RESULTS Fourteen studies from different countries were included in the review and were grouped as: studies conducted in the patients admitted in neonatal intensive care units, in pediatric wards, in hospitalized children and in pediatric outpatient settings. The number of patients studied ranged from 34 in neonatal intensive care units to 355 409 hospitalized children. Many studies reported high rates of off-label (9% to 78.7%) and unlicensed (0.3% to 35%) drug use in different pediatric patient settings. CONCLUSION Given the prevalence of unlicensed and off-label drug use, the cooperation of various stakeholders including health professionals, pediatric population and their parents/caregivers, regulatory authorities, and the pharmaceutical industry is integral to instituting individual measures to avoid exposing children to unnecessary risks and avoid depriving them of potentially effective pharmacotherapy. Initiatives to encourage clinical trials for licensing drug use in children by providing market exclusivity and patent extension could aid in bridging the gap between approval and contemporary drug prescribing practices. Enforcement of legislations in the drug development process and subsequent pharmacovigilance could improve the quality of information and accountability of pharmaceutical industry to support and facilitate drug research in children.
FGR in the setting of preterm sterile intra‐uterine milieu is associated with a decrease in RDS

Objective: To determine if fetal growth restriction (FGR) in the setting of sterile intra‐uterine milieu would be associated with a decrease in respiratory distress syndrome (RDS) of preterm‐neonates. Methods: The relationship between FGR and neonatal RDS was examined in 92 singleton preterm‐neonates (gestational age [GA]: 24.5–33.4 weeks) born to mothers with sterile intra‐uterine milieu, which consisted of both sterile amniotic fluid (AF), and inflammation‐free placenta. Sterile AF was defined in the absence of both infection and inflammation in AF. AF inflammation was defined in the presence of AF MMP‐8 ≥23 ng/ml. FGR was defined in the presence of birth‐weight (BW) below the 5th percentile for GA. Results: FGR was present in 32% and RDS was found in 46% of patients. RDS was less common (24% vs. 56%; P < 0.01) and umbilical arterial pH at birth ≤7.15 was more common (33% vs. 13%; P < 0.05) in preterm‐neonates with FGR than in those without FGR. There is a stepwise increase in RDS with increasing BW (i.e., below the 5th percentile, the 5th ∼10th percentile, and above the 10th percentile for GA) (P < 0.01, linear by linear association). Logistic regression analysis demonstrated that FGR was a better independent predictor of a decrease in RDS (OR = 0.049, 95%CI 0.009–0.259, P < 0.0005) than advanced GA at delivery (OR = 0.584, 95%CI 0.423–0.806, P < 0.005) after adjusting for other confounding variables. Conclusion: FGR in the setting of sterile intra‐uterine milieu is associated with a decrease in RDS of preterm‐neonates. This observation suggests that chronic intra‐uterine hypoxic stress related to FGR may be beneficial to fetal lung maturation. Pediatr Pulmonol. 2016;51:812–819. © 2015 Wiley Periodicals, Inc.
The Temporal Prediction of Stress in Speech and Its Relation to Musical Beat Perception

While rhythmic expectancies are thought to be at the base of beat perception in music, the extent to which stress patterns in speech are similarly represented and predicted during on-line language comprehension is debated. The temporal prediction of stress may be advantageous to speech processing, as stress patterns aid segmentation and mark new information in utterances. However, while linguistic stress patterns may be organized into hierarchical metrical structures similarly to musical meter, they do not typically present the same degree of periodicity. We review the theoretical background for the idea that stress patterns are predicted and address the following questions: First, what is the evidence that listeners can predict the temporal location of stress based on preceding rhythm? If they can, is it thanks to neural entrainment mechanisms similar to those utilized for musical beat perception? And lastly, what linguistic factors other than rhythm may account for the prediction of stress in natural speech? We conclude that while expectancies based on the periodic presentation of stresses are at play in some of the current literature, other processes are likely to affect the prediction of stress in more naturalistic, less isochronous speech. Specifically, aspects of prosody other than amplitude changes (e.g., intonation) as well as lexical, syntactic and information structural constraints on the realization of stress may all contribute to the probabilistic expectation of stress in speech.
Enhanced Application of 18F-FDG PET/CT in Bladder Cancer by Adding Early Dynamic Acquisition to a Standard Delayed PET Protocol

Purpose We investigated the value of early dynamic (ED) PET for the detection and characterization of bladder cancer. Methods Fifty-two bladder cancer patients were prospectively enrolled. The study protocol was composed of ED, whole-body (WB, 60 minutes after injection), and additional delayed (AD, 120 minutes after injection) PET acquisition. Early dynamic PET was acquired for 10 minutes and reconstructed as 5 frames at 2-minute intervals. A focal radiotracer accumulation confined to the bladder wall was considered as PET positive and referred for further quantitative measurement. SUVmax on ED (1fSUVmax, 2fSUVmax, 3fSUVmax, 4fSUVmax, and 5fSUVmax for 5 frames), WB (WBSUVmax), and AD PET (ADSUVmax) were measured. PET results were correlated with bladder cancer pathology variables. Results The sensitivities of ED, WB, and AD PET for bladder cancer were 84.6%, 57.7%, and 61.2%, respectively. The sensitivity of ED PET was significantly higher than that of WB (P = 0.002) and AD PET (P = 0.008). On ED PET, 2fSUVmax was significantly correlated with muscle invasiveness, histological grade, and pathological tumor size (P = 0.018, P = 0.030, and P = 0.030). On WB and AD PET, only pathological tumor size showed significant positive correlation with WBSUVmax and ADSUVmax (P = 0.043 and P = 0.007). Conclusions Early dynamic PET can help to detect and characterize bladder cancer.
Characterization and evaluation of an integrated quality monitoring system for online quality assurance of external beam radiation therapy

Abstract Purpose The aim of this work was to comprehensively evaluate a new large field ion chamber transmission detector, Integral Quality Monitor (IQM), for online external photon beam verification and quality assurance. The device is designed to be mounted on the linac accessory tray to measure and verify photon energy, field shape, gantry position, and fluence before and during patient treatment. Methods Our institution evaluated the newly developed ion chamber's effect on photon beam fluence, response to dose, detection of photon fluence modification, and the accuracy of the integrated barometer, thermometer, and inclinometer. The detection of photon fluence modifications was performed by measuring 6 MV with fields of 10 cm × 10 cm and 1 cm × 1 cm “correct” beam, and then altering the beam modifiers to simulate minor and major delivery deviations. The type and magnitude of the deviations selected for evaluation were based on the specifications for photon output and MLC position reported in AAPM Task Group Report 142. Additionally, the change in ion chamber signal caused by a simulated IMRT delivery error is evaluated. Results The device attenuated 6 MV, 10 MV, and 15 MV photon beams by 5.43 ± 0.02%, 4.60 ± 0.02%, and 4.21 ± 0.03%, respectively. Photon beam profiles were altered with the IQM by < 1.5% in the nonpenumbra regions of the beams. The photon beam profile for a 1 cm × 1 cm2 fields were unchanged by the presence of the device. The large area ion chamber measurements were reproducible on the same day with a 0.14% standard deviation and stable over 4 weeks with a 0.47% SD. The ion chamber's dose–response was linear (R2 = 0.99999). The integrated thermometer agreed to a calibrated thermometer to within 1.0 ± 0.7°C. The integrated barometer agreed to a mercury barometer to within 2.3 ± 0.4 mmHg. The integrated inclinometer gantry angle measurement agreed with the spirit level at 0 and 180 degrees within 0.03 ± 0.01 degrees and 0.27 ± 0.03 at 90 and 270 degrees. For the collimator angle measurement, the IQM inclinometer agreed with a plum‐bob within 0.3 ± 0.2 degrees. The simulated IMRT error increased the ion chamber signal by a factor of 11–238 times the baseline measurement for each segment. Conclusions The device signal was dependent on variations in MU delivered, field position, single MLC leaf position, and nominal photon energy for both the 1 cm × 1 cm and 10 cm × 10 cm fields. This detector has demonstrated utility repeated photon beam measurement, including in IMRT and small field applications.
New Perspectives on Diagnosis and Therapy of Malignant Pleural Mesothelioma

Malignant pleural mesothelioma (MPM) is a rare, but severe form of cancer, with an incidence that varies significantly within and among different countries around the world. It develops in about one to two persons per million of the general population, leading to thousands of deaths every year worldwide. To date, the MPM is mostly associated with occupational asbestos exposure. Asbestos represents the predominant etiological factor, with approximately 70% of cases of MPM with well-documented occupational exposure to asbestos, with the exposure time, on average greater than 40 years. Environmental exposure to asbestos is increasingly becoming recognized as a cause of mesothelioma, together with gene mutations. The possible roles of other cofactors, such as viral infection and radiation exposure, are still debated. MPM is a fatal tumor. This cancer arises during its early phase without clinical signs. Consequently, its diagnosis occurs at advanced stages. Standard clinical therapeutic approaches include surgery, chemo- and radiotherapies. Preclinical and clinical researches are making great strides in the field of this deadly disease, identifying new biomarkers and innovative therapeutic approaches. Among the newly identified markers and potential therapeutic targets, circulating microRNAs and the Notch pathway represent promising avenues that could result in the early detection of the tumor and novel therapeutic approaches.
Assessment of interfractional variation of the breast surface following conventional patient positioning for whole‐breast radiotherapy

The purpose of this study was to quantify the variability of the breast surface position when aligning whole‐breast patients to bony landmarks based on MV portal films or skin marks alone. Surface imaging was used to assess the breast surface position of 11 whole‐breast radiotherapy patients, but was not used for patient positioning. On filmed fractions, AlignRT v5.0 was used to capture the patient's surface after initial positioning based on skin marks (28 “preshifts” surfaces), and after treatment couch shifts based on MV films (41 “postshifts” surfaces). Translations and rotations based on surface captures were recorded, as well as couch shifts based on MV films. For nonfilmed treatments, “daily” surface images were captured following positioning to skin marks alone. Group mean and systematic and random errors were calculated for all datasets. Pearson correlation coefficients, setup margins, and 95% limits of agreement (LOA) were calculated for preshifts translations and MV film shifts. LOA between postshifts surfaces and the filmed treatment positions were also computed. All the surface captures collected were retrospectively compared to both a DICOM reference surface created from the planning CT and to an AlignRT reference surface. All statistical analyses were performed using the DICOM reference surface dataset. AlignRT reference surface data was only used to calculate the LOA with the DICOM reference data. This helped assess any outcome differences between both reference surfaces. Setup margins for preshifts surfaces and MV films range between 8.3–12.0 mm and 5.4–13.4 mm, respectively. The largest margin is along the left–right (LR) direction for preshift surfaces, and along craniocaudal (CC) for films. LOA ranges between the preshifts surfaces and MV film shifts are large (12.6–21.9 mm); these decrease for postshifts surfaces (9.8–18.4 mm), but still show significant disagreements between the two modalities due to their focus on different anatomical landmarks (patient's topography versus bony anatomy). Pearson's correlation coefficients further support this by showing low to moderate correlations in the anterior–posterior (AP) and LR directions (0.47–0.69) and no correlation along CC(<0.15). The use of an AlignRT reference surface compared to the DICOM reference surface does not significantly affect the LOA. Alignment of breast patients based solely on bony alignment may lead to interfractional inconsistencies in the breast surface position. The use of surface imaging tools highlights these discrepancies, and allows the radiation oncology team to better assess the possible effects on treatment quality. PACS number: 87
AJILE Movement Prediction: Multimodal Deep Learning for Natural Human Neural Recordings and Video

Developing useful interfaces between brains and machines is a grand challenge of neuroengineering. An effective interface has the capacity to not only interpret neural signals, but predict the intentions of the human to perform an action in the near future; prediction is made even more challenging outside well-controlled laboratory experiments. This paper describes our approach to detect and to predict natural human arm movements in the future, a key challenge in brain computer interfacing that has never before been attempted. We introduce the novel Annotated Joints in Long-term ECoG (AJILE) dataset; AJILE includes automatically annotated poses of 7 upper body joints for four human subjects over 670 total hours (more than 72 million frames), along with the corresponding simultaneously acquired intracranial neural recordings. The size and scope of AJILE greatly exceeds all previous datasets with movements and electrocorticography (ECoG), making it possible to take a deep learning approach to movement prediction. We propose a multimodal model that combines deep convolutional neural networks (CNN) with long short-term memory (LSTM) blocks, leveraging both ECoG and video modalities. We demonstrate that our models are able to detect movements and predict future movements up to 800 msec before movement initiation. Further, our multimodal movement prediction models exhibit resilience to simulated ablation of input neural signals. We believe a multimodal approach to natural neural decoding that takes context into account is critical in advancing bioelectronic technologies and human neuroscience.
A methodology for direct quantification of over‐ranging length in helical computed tomography with real‐time dosimetry

In helical computed tomography (CT), reconstruction information from volumes adjacent to the clinical volume of interest (VOI) is required for proper reconstruction. Previous studies have relied upon either operator console readings or indirect extrapolation of measurements in order to determine the over‐ranging length of a scan. ( 1 – 5 ) This paper presents a methodology for the direct quantification of over‐ranging dose contributions using real‐time dosimetry. A Siemens SOMATOM Sensation 16 multislice helical CT scanner is used with a novel real‐time “point” fiber‐optic dosimeter system with 10 ms temporal resolution to measure over‐ranging length, which is also expressed in dose‐length‐product (DLP). (6) Film was used to benchmark the exact length of over‐ranging. Over‐ranging length varied from 4.38 cm at pitch of 0.5 to 6.72 cm at a pitch of 1.5, which corresponds to DLP of 131 to 202 mGy‐cm. The dose‐extrapolation method of Van der Molen et al. yielded results within 3%, while the console reading method of Tzedakis et al.( 2 , 4 ) yielded consistently larger over‐ranging lengths. From film measurements, it was determined that Tzedakis et al.( 2 , 4 ) overestimated over‐ranging lengths by one‐half of beam collimation width. Over‐ranging length measured as a function of reconstruction slice thicknesses produced two linear regions similar to previous publications. ( 1 – 4 ) Over‐ranging is quantified with both absolute length and DLP, which contributes about 60 mGy‐cm or about 10% of DLP for a routine abdominal scan. This paper presents a direct physical measurement of over‐ranging length within 10% of previous methodologies. ( 1 – 4 ) Current uncertainties are less than 1%, in comparison with 5% in other methodologies. Clinical implantation can be increased by using only one dosimeter if codependence with console readings is acceptable, with an uncertainty of 1.1% This methodology will be applied to different vendors, models, and postprocessing methods – which have been shown to produce over‐ranging lengths differing by 125%. (4) PACS number: 87.57. qp