Miracle-dz/UniFAR-FTUs huggingface dataset:
Can increased immunogenicity in chronic myeloid leukemia improve outcomes?

ABSTRACT Introduction: Chronic myeloid leukemia (CML) has long been thought to be the model disease for immunotherapy with its characteristic BCR-ABL fusion protein. Although targeted therapy using tyrosine kinase inhibitors (TKIs) is highly effective at inducing remission, most patients require life-long TKI to decrease the risk of relapse. In recent years, much effort has been devoted to finding ways to eliminate CML stem cells (LSCs); the source of disease persistence. Areas covered: In this review, the authors present recent immunologic findings pertinent to CML, vaccinations targeting leukemia antigens, interferon combination therapies, and other emerging strategies aimed at increasing immunogenicity and improving outcomes in patients with CML. Recent publications and abstracts found in Pubmed and hematology/oncology meetings related to these topics were identified and incorporated into this review. Expert commentary: Further understanding of the immune system and antigenic composition of LSCs has allowed for novel therapeutic development. Immunotherapies are effective at the malignant stem cell level and combining these approaches with TKI is a promising option. Despite ongoing challenges, it is increasingly recognized that a cure may be achievable through immunotherapies.
The evolution of climate tolerance in conifer‐feeding aphids in relation to their host's climatic niche

Abstract Climate adaptation has major consequences in the evolution and ecology of all living organisms. Though phytophagous insects are an important component of Earth's biodiversity, there are few studies investigating the evolution of their climatic preferences. This lack of research is probably because their evolutionary ecology is thought to be primarily driven by their interactions with their host plants. Here, we use a robust phylogenetic framework and species‐level distribution data for the conifer‐feeding aphid genus Cinara to investigate the role of climatic adaptation in the diversity and distribution patterns of these host‐specialized insects. Insect climate niches were reconstructed at a macroevolutionary scale, highlighting that climate niche tolerance is evolutionarily labile, with closely related species exhibiting strong climatic disparities. This result may suggest repeated climate niche differentiation during the evolutionary diversification of Cinara. Alternatively, it may merely reflect the use of host plants that occur in disparate climatic zones, and thus, in reality the aphid species' fundamental climate niches may actually be similar but broad. Comparisons of the aphids' current climate niches with those of their hosts show that most Cinara species occupy the full range of the climatic tolerance exhibited by their set of host plants, corroborating the hypothesis that the observed disparity in Cinara species' climate niches can simply mirror that of their hosts. However, 29% of the studied species only occupy a subset of their hosts' climatic zone, suggesting that some aphid species do indeed have their own climatic limitations. Our results suggest that in host‐specialized phytophagous insects, host associations cannot always adequately describe insect niches and abiotic factors must be taken into account.
Factors Affecting Interprofessional Teamwork in Emergency Department Care of Polytrauma Patients: Results of an Exploratory Study

Considering that traumatic injuries are the leading cause of death among young adults across the globe, emergency department care of polytrauma patients is a crucial aspect of optimized care and premature death prevention. Unfortunately, many studies have highlighted important gaps in collaboration among different trauma team professionals, posing a major quality-of-care challenge. Using the conceptual framework for interprofessional teamwork (IPT) of Reeves, Lewin, Espin, and Zwarenstein (2010), the aim of this qualitative descriptive exploratory study was to better understand IPT from the perspective of health professionals in emergency department care of polytrauma patients, specifically by identifying factors that facilitate and impede IPT. Data were collected from a sample of 7 health professionals involved in the care of polytrauma patients through individual interviews and a focus group. In the second phase, 2 structured observations of polytrauma patient care were conducted. Following a thematic analysis, results revealed multiple factors affecting IPT, which can be divided into 5 broad categories: individual, relational, processual, organizational, and contextual. Individual factors, a category that is not part of the conceptual framework of Reeves et al. (2010), also emerged as playing a major part in IPT.
Applications and efficiency of flow cytometry for leukemia diagnostics

ABSTRACT Introduction: Multiparametric flow cytometry immunophenotype (MFCI) plays a crucial role in the diagnosis of acute leukemia (AL). Through the comprehensive assessment of surface and intracellular antigens expressed by blasts, MFCI permits to distinguish myeloid or B/T lymphoid AL, or AL of ambiguous lineages. By means of MFCI, the blasts can be characterized in bone marrow, peripheral blood, and body fluids, such as cerebrospinal fluid. Area covered: This review discusses how MFCI is currently applied in the diagnostic evaluation of AL; it also focuses on ‘peculiar’ issues such as the role of MFCI for the diagnosis of central nervous system leukemic involvement. Expert commentary: Despite the improved knowledge about the biology of AL, MFCI remains a fundamental tool to make a prompt and accurate diagnosis. MFCI also provides prognostic information for some antigens are associated with specific cytogenetic/genetic abnormalities and, recently, it became a powerful tool to evaluate the quality and depth of response (the so called ‘measurable residual disease’). Its role as an efficient detector of residual disease paved the way to the investigation of tissues other than bone marrow and peripheral blood, demonstrating that even small amounts of AL appear to have a prognostic impact and may require personalized intervention.
Current challenges: from the path of “original antigenic sin” towards the development of universal flu vaccines

Abstract Annual flu led by influenza viruses is contemplated to be one of the foremost global health challenges due to its rapid spread leading to the life-threatening epidemic or pandemic. An enormous number of people die due to flu and its associated intricacies every year. Annual vaccination is considered to be the gold standard strategy to protect the individual from acquiring infection and further decimation, although recent estimates suggest that overall flu vaccine effectiveness was within 19% to 53% in last five years. A significant weakness of current vaccination is its inability to protect an individual from different or mutant flu strain. Host immune system performs a vital role during natural infection or after vaccination leading to influenza-specific immunities. Previous imprints of common flu or vaccination may alter the outcomes of the current vaccination. Current flu vaccine regime does not consider the host immune status before vaccination. Irrespective of the previous influenza exposure history or prior flu vaccination, individual get flu vaccination based on WHO recommendation with selected strains which may be the reason why induction of broad immunities does not transpire with their testimonial. Over the last few decades, scientific research had identified the role of preexisting immunities on vaccination or natural infection outcome. In this review, we are proposing the concept of personalized flu vaccines depending on individual immune status. We will also discuss why individual was unable to induce broader immunities to protect itself from diverse influenza viruses and how we can accomplish that goal with the current findings.
Optimizing 4D abdominal MRI: image denoising using an iterative back-projection approach

4D-MRI is a promising tool for organ exploration, target delineation and treatment planning. Intra-scan motion artifacts may be greatly reduced by increasing the imaging frame rate. However, poor signal-to-noise ratios (SNR) are observed when increasing spatial and/or frame number per physiological cycle, in particular in the abdomen. In the current work, the proposed 4D-MRI method favored spatial resolution, frame number, isotropic voxels and large field-of-view (FOV) during MR-acquisition. The consequential SNR penalty in the reconstructed data is addressed retrospectively using an iterative back-projection (IBP) algorithm. Practically, after computing individual spatial 3D deformations present in the images using a deformable image registration (DIR) algorithm, each 3D image is individually enhanced by fusing several successive frames in its local temporal neighborood, these latter being likely to cover common independent informations. A tuning parameter allows one to freely readjust the balance between temporal resolution and precision of the 4D-MRI. The benefit of the method was quantitatively evaluated on the thorax of 6 mice under free breathing using a clinically acceptable duration. Improved 4D cardiac imaging was also shown in the heart of 1 mice. Obtained results are compared to theoretical expectations and discussed. The proposed implementation is easily parallelizable and optimized 4D-MRI could thereby be obtained with a clinically acceptable duration.
Recent fluorescence-based optical imaging for video-assisted thoracoscopic surgery segmentectomy.

Background The importance of fluorescence-based optical imaging in various fields of surgery is increasing. This is a prospective cohort study aimed to investigate the feasibility and efficacy of indocyanine-green fluorescence (ICGF)-based navigation for near-infrared (NIR) thoracoscopic segmentectomy. Methods ICGF-based video-assisted thoracoscopic surgery (VATS) segmentectomy was performed in 149 patients. Each patient underwent preoperative evaluation by multidetector-row computed tomography (MDCT), which provided three-dimensional simulations of vascular structures, segmental bronchi, and lung tumor. During the procedure, low-dose ICG (0.25 mg/kg) was injected systemically after the target segmental pulmonary arteries and bronchus were divided. Under NIR-thoracoscopic guidance, an ICG fluorescent line was marked by electric scalpel, followed by division of lung parenchyma along the line by electric scalpel or endoscopic staples. Results An intersegmental line of ICGF was visible in 98% of patients, even with the use of low-dose ICG. Neither ICG-related adverse events nor procedure-related major complications occurred. The 5-year overall (OS) and recurrence-free survival (RFS) rates were 91.8% and 98%, respectively. Localized recurrence at the resected site did not occur in any patient. Conclusions ICGF-based navigation for NIR VATS segmentectomy for patients with lung cancer is feasible and effective.
Community Assessment of Colorectal Cancer Screening Compliance in Northwest Louisiana

Background In the United States, colorectal cancer (CRC) screening rates have steadily increased. The state of Louisiana has persistent lower screening rates compared to the United States and other states, and with African Americans experiencing the highest CRC incidence rates. Aggregate national and state data can be problematic in isolating key health issues and data in rural areas. Study Purpose: At the Louisiana parish-level, which is comparable to county municipalities in other U.S. states, the research study examined endoscopy CRC screening among African American Medicare beneficiaries. Method Using cluster sampling, survey-based data from two neighboring parishes in northwest Louisiana were collected. The survey instrument was adapted from the Medicare Current Beneficiary Survey. Results The key study variables were CRC screening compliance, residence location, self-reported CRC knowledge, and physician recommendation. The findings showed significant differences in CRC screening compliance between the two parishes. Participants with CRC knowledge score of at least 3 out of 5 were more likely to be compliant with CRC screening. The findings demonstrated the importance of isolating geo-specific data, especially in rural areas, to plan effective health education or intervention strategies.
Shear‐thinning behaviour of blood in response to active hyperaemia: Implications for the assessment of arterial shear stress‐mediated dilatation

What is the central question of this study? Quantitative values of shear rate‐specific blood viscosity and shear stress in the human macrovasculature in response to exercise hyperaemia are unknown. What is the main finding and its importance? Using the handgrip exercise model, we showed that an increase in brachial artery shear rate led to a decrease in blood viscosity, despite concomitant haemoconcentration. This shear‐thinning behaviour of blood, secondary to increased erythrocyte deformability, blunted the expected increase in brachial artery shear stress based on shear rate prediction. Our data yield new insights into the magnitude and regulation of macrovascular blood viscosity and shear stress in physiological conditions of elevated metabolic demand and blood flow in humans.
Mitigating Leakage in Secure Cloud-Hosted Data Structures: Volume-Hiding for Multi-Maps via Hashing

Volume leakage has recently been identified as a major threat to the security of cryptographic cloud-based data structures by Kellaris \em et al. [CCS'16] (see also the attacks in Grubbs \em et al. [CCS'18] and Lacharité \em et al. [S&P'18]). In this work, we focus on volume-hiding implementations of \em encrypted multi-maps as first considered by Kamara and Moataz [Eurocrypt'19]. Encrypted multi-maps consist of outsourcing the storage of a multi-map to an untrusted server, such as a cloud storage system, while maintaining the ability to perform private queries. Volume-hiding encrypted multi-maps ensure that the number of responses (volume) for any query remains hidden from the adversarial server. As a result, volume-hiding schemes can prevent leakage attacks that leverage the adversary's knowledge of the number of query responses to compromise privacy. We present both conceptual and algorithmic contributions towards volume-hiding encrypted multi-maps. We introduce the first formal definition of volume-hiding leakage functions. In terms of design, we present the first volume-hiding encrypted multi-map dprfMM whose storage and query complexity are both asymptotically optimal. Furthermore, we experimentally show that our construction is practically efficient. Our server storage is smaller than the best previous construction while we improve query complexity by a factor of 10-16x. In addition, we introduce the notion of differentially private volume-hiding leakage functions which strikes a better, tunable balance between privacy and efficiency. To accompany our new notion, we present a differentially private volume-hiding encrypted multi-map dpMM whose query complexity is the volume of the queried key plus an additional logarithmic factor. This is a significant improvement compared to all previous volume-hiding schemes whose query overhead was the maximum volume of any key. In natural settings, our construction improves the average query overhead by a factor of 150-240x over the previous best volume-hiding construction even when considering small privacy budget of ε=0.2.
Localization and Tracking of Discrete Mobile Scatterers in Vehicular Environments Using Delay Estimates †

This paper describes an approach to detect, localize, and track moving, non-cooperative objects by exploiting multipath propagation. In a network of spatially distributed transmitting and receiving nodes, moving objects appear as discrete mobile scatterers. Therefore, the localization of mobile scatterers is formulated as a nonlinear optimization problem. An iterative nonlinear least squares algorithm following Levenberg and Marquardt is used for solving the optimization problem initially, and an extended Kalman filter is used for estimating the scatterer location recursively over time. The corresponding performance bounds are derived for both the snapshot based position estimation and the nonlinear sequential Bayesian estimation with the classic and the posterior Cramér–Rao lower bound. Thereby, a comparison of simulation results to the posterior Cramér–Rao lower bound confirms the applicability of the extended Kalman filter. The proposed approach is applied to estimate the position of a walking pedestrian sequentially based on wideband measurement data in an outdoor scenario. The evaluation shows that the pedestrian can be localized throughout the scenario with an accuracy of 0.8 m at 90% confidence.
Acquiring diminutive allomorphs: taking item-specific characteristics into account

Abstract Phonological characteristics and frequencies of stems and allomorphs have been explored as possible factors causing differences in production accuracies between allomorphic forms. However, previous findings are not consistent and the relative contributions of these factors are unclear. This study investigated target and erroneous productions of the Dutch diminutive, which has five allomorphs with varying type frequencies and of which the selection depends on the phonological characteristics of the stems. Typically developing children (N = 115, 5;1–10;3) were tested on their production of real and nonce diminutives. Linear mixed effects modelling was used to analyse the data taking nonverbal IQ into account. Type frequencies of the allomorphs and differences in phonological characteristics of the stems were found to be related to differences in production accuracies between the allomorphs. However, phonological characteristics of the stems appeared to have a bigger impact, mainly due to the phonological complexity of these characteristics.
Nonsteroidal anti-inflammatory drugs and acetaminophen ameliorate muscular mechanical hyperalgesia developed after lengthening contractions via cyclooxygenase-2 independent mechanisms in rats

Nonsteroidal anti-inflammatory drugs and acetaminophen are cyclooxygenase inhibitors commonly used as symptomatic medicines for myofascial pain syndrome. Using the selective inhibitors celecoxib and zaltoprofen, cyclooxygenase-2 has been shown to be involved in the initiation, but not the maintenance, of muscular mechanical hyperalgesia induced by lengthening contractions, which serves as a useful model for the study of myofascial pain syndrome. The effect of other cyclooxygenase-2 inhibitors, such as acetylsalicylic acid, ibuprofen, loxoprofen sodium, and acetaminophen, on muscular mechanical hyperalgesia during maintenance has not been studied. Here, we examined the analgesic effects of the nonsteroidal anti-inflammatory drugs and acetaminophen on the model. Consistent with previous studies, mechanical withdrawal threshold of the muscle was significantly decreased and reached its lowest level 24 h after lengthening contractions. Celecoxib had no effect on muscular mechanical hyperalgesia, when orally administered 24 h after lengthening contractions. In contrast, acetylsalicylic acid, ibuprofen, loxoprofen sodium, and acetaminophen increased the withdrawal threshold, which had decreased by lengthening contractions, in a dose-dependent manner. These results demonstrate the analgesic actions of nonsteroidal anti-inflammatory drugs and acetaminophen in the maintenance process of lengthening contraction-induced muscular mechanical hyperalgesia, which may occur through cyclooxygenase-2 independent mechanisms.
Hypoglycemia and Dementia Risk in Older Patients with Type 2 Diabetes Mellitus: A Propensity-Score Matched Analysis of a Population-Based Cohort Study

Background Type 2 diabetes mellitus (T2DM) is associated with an increased risk for dementia. The effects of hypoglycemia on dementia are controversial. Thus, we evaluated whether hypoglycemia increases the risk for dementia in senior patients with T2DM. Methods We used the Korean National Health Insurance Service Senior cohort, which includes >10% of the entire senior population of South Korea. In total, 5,966 patients who had ever experienced at least one episode of hypoglycemia were matched with those who had not, using propensity score matching. The risk of dementia was assessed through a survival analysis of matched pairs. Results Patients with underlying hypoglycemic events had an increased risk for all-cause dementia, Alzheimer's dementia (AD), and vascular dementia (VaD) compared with those who had not experienced a hypoglycemic event (hazard ratio [HR], 1.254; 95% confidence interval [CI], 1.166 to 1.349; P<0.001 for all-cause dementia; HR, 1.264; 95% CI, 1.162 to 1.375; P<0.001 for AD; HR, 1.286; 95% CI, 1.110 to 1.490; P<0.001 for VaD). According to number of hypoglycemic episodes, the HRs of dementia were 1.170, 1.201, and 1.358 in patients with one hypoglycemic episode, two or three episodes, and more than three episodes, respectively. In the subgroup analysis, hypoglycemia was associated with an increased risk for dementia in both sexes with or without T2DM microvascular or macrovascular complications. Conclusion Our findings suggest that patients with a history of hypoglycemia have a higher risk for dementia. This trend was similar for AD and VaD, the two most important subtypes of dementia.
Development and Use of the Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy Axicabtagene Ciloleucel in Large B-Cell Lymphoma: A Review.

Importance Axicabtagene ciloleucel, an anti-CD19-CD28-CD3ζ chimeric antigen receptor T-cell therapy, was the first US Food and Drug Administration-approved, genetically engineered T-cell therapy for adults with relapsed or refractory large B-cell lymphoma (LBCL) after 2 or more lines of systemic therapy. There has not been a US Food and Drug Administration-approved product for these cancers in more than 4 decades. Observations Unlike traditional anticancer therapies, axicabtagene ciloleucel is a patient-specific, live-cell product that has unique requirements for manufacturing, shipping, and storage, as well as for its administration and management of its adverse events. In addition, axicabtagene ciloleucel has demonstrated efficacy in patients with refractory LBCL. This review presents a timeline of the rapid clinical development of axicabtagene ciloleucel from bench to bedside, highlights how axicabtagene ciloleucel satisfies an unmet medical need for treatment of refractory LBCL, outlines the logistics of the production process and administration of axicabtagene ciloleucel, describes its mechanism of action, and summarizes the results of the pivotal study. This review also provides a survey of adverse events, with attention to the kinetics of their clinical presentation; discusses the management of adverse events; and offers suggestions for appropriate patient selection for safe administration of axicabtagene ciloleucel. Conclusions and Relevance The integration of axicabtagene ciloleucel therapy into standard-of-care practice for relapsed/refractory LBCL is the beginning of a paradigm shift in the treatment of patients with LBCL and is likely to lead to improvements in their survival and curability. Timely referral to centers offering the therapy is necessary for optimal patient outcomes.