Miracle-dz/UniFAR-FTUs huggingface dataset:
A mouse-human phase 1 co-clinical trial of a protease-activated fluorescent probe for imaging cancer

A first-in-human phase 1 clinical trial of the PEGylated protease-activated fluorescent probe, LUM015, enables tumor imaging at a safe and tolerable dose in humans. Protease probe tested in humans Cancer cells secrete more of the protease cathepsin than healthy cells, partly as a way to enzymatically remodel their surroundings for tumor growth and metastasis. Whitley et al. developed an imaging probe that could be activated in the presence of these cathepsins, thus allowing surgeons to distinguish tumor margins intraoperatively. Their probe, called LUM015, was able to signal the presence of cancer in vivo in a mouse sarcoma model, and in a so-called “co-clinical trial” in 15 patients, it was safe and cleaved as expected in different types of tumor tissues. With favorable biodistribution and pharmacokinetics also demonstrated, protease-activated probes are now poised for further adaptation to tumor resections, signaling the presence of residual cancer. Local recurrence is a common cause of treatment failure for patients with solid tumors. Intraoperative detection of microscopic residual cancer in the tumor bed could be used to decrease the risk of a positive surgical margin, reduce rates of reexcision, and tailor adjuvant therapy. We used a protease-activated fluorescent imaging probe, LUM015, to detect cancer in vivo in a mouse model of soft tissue sarcoma (STS) and ex vivo in a first-in-human phase 1 clinical trial. In mice, intravenous injection of LUM015 labeled tumor cells, and residual fluorescence within the tumor bed predicted local recurrence. In 15 patients with STS or breast cancer, intravenous injection of LUM015 before surgery was well tolerated. Imaging of resected human tissues showed that fluorescence from tumor was significantly higher than fluorescence from normal tissues. LUM015 biodistribution, pharmacokinetic profiles, and metabolism were similar in mouse and human subjects. Tissue concentrations of LUM015 and its metabolites, including fluorescently labeled lysine, demonstrated that LUM015 is selectively distributed to tumors where it is activated by proteases. Experiments in mice with a constitutively active PEGylated fluorescent imaging probe support a model where tumor-selective probe distribution is a determinant of increased fluorescence in cancer. These co-clinical studies suggest that the tumor specificity of protease-activated imaging probes, such as LUM015, is dependent on both biodistribution and enzyme activity. Our first-in-human data support future clinical trials of LUM015 and other protease-sensitive probes.
Mineral trioxide aggregate root canal filling of traumatized immature tooth

An 8-year-old female patient reported to the dental clinic seeking a help to save her traumatized maxillary left central incisor. The tooth had been treated with a temporary filling by a general dentist. The coronal tooth structure was intact, discolored, and a temporary filling was placed on the access opening. She gave a history of trauma about 3 years back. An intraoral periapical radiograph revealed an open apex and dentin bridge in the middle of the root canal. The root canal and the access opening were filled with very poor filling. The tooth was managed successfully by conservative means using intracanal calcium hydroxide as an intracanal medicament, followed by mineral trioxide aggregate (MTA) filling. The access opening was filled with glass ionomer and composite resin restoration. One year and 6-month follow-up demonstrated a clinically asymptomatic and adequately functional tooth, with radiological signs of apical regeneration.
Cognitive Impairment and Neurogenotoxic Effects in Rats Exposed to Low-Intensity Microwave Radiation

The health hazard of microwave radiation (MWR) has become a recent subject of interest as a result of the enormous increase in mobile phone usage. The present study aimed to investigate the effects of chronic low-intensity microwave exposure on cognitive function, heat shock protein 70 (HSP70), and DNA damage in rat brain. Experiments were performed on male Fischer rats exposed to MWR for 180 days at 3 different frequencies, namely, 900, 1800 MHz, and 2450 MHz. Animals were divided into 4 groups: group I: sham exposed; group II: exposed to MWR at 900 MHz, specific absorption rate (SAR) 5.953 × 10−4 W/kg; group III: exposed to 1800 MHz, SAR 5.835×10−4 W/kg; and group IV: exposed to 2450 MHz, SAR 6.672 × 10−4 W/kg. All the rats were tested for cognitive function at the end of the exposure period and were subsequently sacrificed to collect brain. Level of HSP70 was estimated by enzyme-linked immunotarget assay and DNA damage was assessed using alkaline comet assay in all the groups. The results showed declined cognitive function, elevated HSP70 level, and DNA damage in the brain of microwave-exposed animals. The results indicated that, chronic low-intensity microwave exposure in the frequency range of 900 to 2450 MHz may cause hazardous effects on the brain.
Selecting Hearing Aid Gain and Frequency Response Characteristics Based on a Comparison of Loudness Judgments and POGO

Richard M. Angelo, Ph.D., CCC-A and G. Donald Miller, Ph.D. CCC-A The prescriptive methods of selecting the hearing aid's frequency and gain characteristics for sensorineural hearing losses have received a great deal of attention from clinicians and researchers. The solution to this problem has been under scrutiny for at least half a century and the answers remain elusive. This is evident in the inconsistencies found among research studies, the lack of agreement on the selection process of an individual hearing aid or the appropriate technique to fit such an aid, and which measures are valid and reliable in this process. The inconsistencies reflect the inherent complexity of the problem and our less than adequate understanding of auditory processes and speech perception. Several variables are involved when choosing the optimum frequency and gain characteristics and successful hearing aid selection depends on consideration of the interaction between these variables. These variables include interactions between the properties of the sound source, the environment, and the receiver, none of which can be held constant in real life. Also, our understanding of the factors governing the speech perception process and the perceptual effects of a sensorineural hearing loss are inadequate. The following two observations emphasize the problem. First, with our current knowledge of hearing impairment, speech perception, and auditory processes, it is impossible to predict the performance of a hearing-impaired person from data of other persons even if the audiometer configurations are similar. Second, speech testing procedures do not provide a suitable basis for hearing aid selection because of their limited ability to discriminate between different frequency and gain characteristics for a listener. In the clinical situation, time constraints reduce reliability and validity of this test stimulus. This limited power stems from such factors as test-retest variability, differential practice effects, and a lack of sensitivity in the stimulus as it relates to differentiation between each aid's clinical or test performance and the aid's performance in real life situations. These factors impose severe limitations on the use of speech in the clinical setting to discrimiBloomsburg University, Department of Communication Disorders and Special Education, Bloomsburg, Pennsylvania
Fast physical-layer unknown tag identification in large-scale RFID systems

Radio Frequency Identification (RFID) technology brings a revolutionary change in warehouse management by automatically monitoring and tracking. Considering the misplaced and newly added tags, fast identifying such unknown tags is of paramount importance, especially in large-scale RFID systems. Unlike existing work, this paper proposes a fast Physical-layer Unknown Tag Identification (PUTI) protocol that gathers intact unknown tag set with high identification efficiency. PUTI utilizes physical layer aggregated signals to separate all unknown tags from known tags and then collects IDs from only the entire unknown tag set. We also optimize the parameter setting and analyze protocol performance in theory. Simulation results show that PUTI outperforms prior unknown tag identification protocols. For example, given a RFID system with 1,000 unknown tags and 10,000 known tags, PUTI represents reduction of 37.7% when compared with the state-of-the-art protocol.
Low Voltage Floating Gate MOS Transistor Based Differential Voltage Squarer

This paper presents novel floating gate MOSFET (FGMOS) based differential voltage squarer using FGMOS characteristics in saturation region. The proposed squarer is constructed by a simple FGMOS based squarer and linear differential voltage attenuator. The squarer part of the proposed circuit uses one of the inputs of two-input FGMOS transistor for threshold voltage cancellation so as to implement a perfect squarer function, and the differential voltage attenuator part acts as input stage so as to generate the differential signals. The proposed circuit provides a current output proportional to the square of the difference of two input voltages. The second order effect caused by parasitic capacitance and mobility degradation is discussed. The circuit has advantages such as low supply voltage, low power consumption, and low transistor count. Performance of the circuit is verified at ±0.75 V in TSMC 0.18 μm CMOS, BSIM3, and Level 49 technology by using Cadence Spectre simulator.
Spatial throughput characterization in cognitive radio networks with primary receiver assisted carrier sensing based opportunistic spectrum access

This paper studies the opportunistic spectrum access (OSA) of secondary users in large-scale overlay cognitive radio (CR) networks. Particularly, a two-phase carrier sensing based protocol, namely the primary receiver assisted carrier sensing (PRA-CS) protocol, is investigated. Under the PRA-CS protocol, a secondary transmitter (ST) is allowed to transmit only if it satisfies the interference constraint at all the active primary receivers (PRs) and has the minimum back-off timer among its secondary contenders. It is worth noting that under the PRA-CS protocol, due to the fact that the activation of STs relies on the spatial realizations of both the primary and secondary networks, even the first order moment measure (average density) of the point process formed by the active STs can not be exactly characterized. To tackle this new difficulty, approximations are made on the conditional distributions of the eligible STs as well as the active STs given a typical primary/secondary receiver (PR/SR) activated at the origin. Based on such approximations, the coverage (transmission non-outage) performance of the primary/secondary network under the proposed PRA-CS protocol is characterized. Simulations are provided to validate our analysis.
Prevention of Ventilator-Associated Pneumonia

Ventilator-associated pneumonia (VAP) is a leading cause of morbidity and mortality in the intensive care unit (ICU). The incidence of VAP varies greatly, ranging from 6 to 52% of intubated patients depending on patient risk factors. The cumulative incidence is approximately 1-3% per day of intubation. Overall, VAP is associated with an attributable mortality of up to 30%. Attributable mortality approaches 50% when VAP is caused by the more virulent organisms that typify late-onset VAP (occurring 4 or more days into mechanical ventilation). The cost per episode of VAP is substantial, although specific data are lacking. The average cost per episode of nosocomial pneumonia is estimated at $3000 to $6000, and the additional length of stay for patients who develop VAP is estimated at 13 days. VAP is typically categorized as either early-onset VAP (occurring in the first 3-4 days of mechanical ventilation) or late-onset VAP. This distinction is important microbiologically. Early-onset VAP is commonly caused by antibiotic-sensitive community-acquired organisms (eg, Streptococcus pneumoniae, Haemophilus influenzae, and Staphylococcus aureus). Lateonset VAP is commonly caused by antibiotic-resistant nosocomial organisms (eg, Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, Acinetobacter species, and Enterobacter species). Most episodes of ventilator-associated pneumonia (VAP) are thought to develop from the aspiration of oropharyngeal secretions containing potentially pathogenic organisms. Aspiration of gastric secretions may also contribute, though likely to a lesser degree. Tracheal intubation interrupts the body’s anatomic and physiologic defenses against aspiration, making mechanical ventilation a major risk factor for VAP. This chapter reviews 4 practices that carry the potential to reduce the incidence of VAP in patients receiving mechanical ventilation. They are: variation in patient positioning, continuous aspiration of subglottic secretions, selective digestive tract decontamination, and the use of sucralfate.
Nonlocal Filtering for Polarimetric SAR Data: A Pretest Approach

A pretest approach based on the complex Wishart distribution in polarimetric synthetic aperture radar (POLSAR) speckle filtering is proposed in this paper. The main principle is to select homogeneous pixels in a large-scale area in the filtering process, which is called pretesting. To preserve details and fine structures while despeckling, the homogeneous pixels are selected by comparing their 3 × 3 neighboring windows. A test statistic based on the complex Wishart distribution is used to decide the selection of homogeneous pixels. Speckle filtering is processed by summing up the homogeneous pixels with weights according to the values of their test statistics. To accelerate the pretest filter, we further propose a refined algorithm, which eliminates redundant operations without deteriorating the performance. We demonstrate the performance of the proposed algorithm by using both simulated and real airborne POLSAR data.
Panchromatic and Multispectral Image Fusion Based on Maximization of Both Spectral and Spatial Similarities

The panchromatic (PAN) sharpening of multispectral (MS) bands can be performed by fusing the PAN and MS images. Measuring similarity criterion computed among input images is one way to synthesize MS images in higher resolution based on either spectral or spatial domains. However, a few methods consider both spectral and spatial similarities. In this paper, the fusion between PAN and MS images is performed by engaging both similarities. We use the spectral histogram, recently introduced to characterize the spectral information of an image in different frequency ranges, as the spectral similarity criterion. This similarity suggests considering a statistical similarity measure between two spectral histograms of two images. Furthermore, we use the fourth-order correlation coefficient as a spatial similarity criterion instead of correlation coefficient. Meanwhile, in the decision level of fusion process, a proper threshold should be selected to determine whether the details should be injected or not. There is no reference to choose it in general cases, and this threshold is calculated for each set of input images separately and is based on intersecting two similarity curves. We do this by first calculating the spatial and spectral similarity criteria for some specific threshold values and then fit two similarity curves on these sample points by the spline interpolation method. Then, after decomposing input images using the nonsubsampled contourlet transform, we inject the PAN details into the MS details considering the selected threshold. The experimental results obtained by applying the proposed image fusion method indicate some improvements in the fusion performance.
Amelioration of sepsis by TIE2 activation–induced vascular protection

Vascular protection through TIE2 activation is a potential treatment strategy to ameliorate sepsis. Antibody TIEs sepsis up in knots Sepsis, or severe systemic inflammation caused by infection, has a high mortality despite the availability of antibiotic treatment, and more specific therapies are urgently needed. One of the difficult-to-treat and potentially life-threatening components of sepsis is vascular disintegration and leakage. Han et al. have discovered an antibody, called ABTAA, which binds to a ligand called angiopoietin 2 (ANG2) in the vasculature, but then activates it instead of blocking its activity like standard antibodies. When ABTAA binds to ANG2, it causes clustering of ANG2 and subsequently its receptor TIE2 at the site, and the resulting signaling cascade protects the vascular walls and blunts the damaging effects of sepsis, greatly increasing survival in mouse models of the disease. Protection of endothelial integrity has been recognized as a frontline approach to alleviating sepsis progression, yet no effective agent for preserving endothelial integrity is available. Using an unusual anti–angiopoietin 2 (ANG2) antibody, ABTAA (ANG2-binding and TIE2-activating antibody), we show that activation of the endothelial receptor TIE2 protects the vasculature from septic damage and provides survival benefit in three sepsis mouse models. Upon binding to ANG2, ABTAA triggers clustering of ANG2, assembling an ABTAA/ANG2 complex that can subsequently bind and activate TIE2. Compared with a conventional ANG2-blocking antibody, ABTAA was highly effective in augmenting survival from sepsis by strengthening the endothelial glycocalyx, reducing cytokine storms, vascular leakage, and rarefaction, and mitigating organ damage. Together, our data advance the role of TIE2 activation in ameliorating sepsis progression and open a potential therapeutic avenue for sepsis to address the lack of sepsis-specific treatment.
Costs of Occupational Injuries and Illnesses

As the debate over health care reform continues, costs have become a critical measure in the many plans and proposals to come before us. Knowing costs is important because it allows comparisons across such disparate health conditions as AIDS, Alzheimer's disease, heart disease, and cancer. This book presents the results of a major study estimating the large and largely overlooked costs of occupational injury and illness--costs as large as those for cancer and over four times the costs of AIDS.The incidence and mortality of occupational injury and illness were assessed by reviewing data from national surveys and applied an attributable-risk-proportion method. Costs were assessed using the human capital method that decomposes costs into direct categories such as medical costs and insurance administration expenses, as well as indirect categories such as lost earnings and lost fringe benefits. The total is estimated to be $155 billion and is likely to be low as it does not include costs associated with pain and suffering or of home care provided by family members.Invaluable as an aid in the analysis of policy issues, "Costs of Occupational Injury" "and Illness" will serve as a resource and reference for economists, policy analysts, public health researchers, insurance administrators, labor unions and labor lawyers, benefits managers, and environmental scientists, among others.J. Paul Leigh is Professor in the School of Medicine, Department of Epidemiology and Preventive Medicine, University of California, Davis. Stephen Markowitz, M.D., is Professor in the Department of Community Health and Social Medicine, City University of New York Medical School. Marianne Fahs is Director of the Health Policy Research Center, Milano Graduate School of Management and Urban Policy, New School University. Philip Landrigan, M.D., is Wise Professor and Chair of the Department of Community Medicine, Mount Sinai Medical Center, New York.
IRF7 inhibition prevents destructive innate immunity—A target for nonantibiotic therapy of bacterial infections

Interferon regulatory factor 7 is an innate immune target for non–antibiotic-based immunotherapy for bacterial infection. Beyond antibiotics Antibiotics are the cornerstone of antibacterial therapy; however, the increasing development of resistant bacterial strains stresses the need for alternate approaches. Now, Puthia et al. target bacterial infection by boosting innate immunity. They found that a tight balance between the transcription factor interferon regulatory factor 7 (IRF-7) and its heterodimeric partner IRF-3 is critical for an efficient and self-limiting innate immune response to bacterial infection. Dysregulation of this balance contributed to kidney pathology in infected mice, and IRF7 attenuating polymorphisms associate with recurrent pyelonephritis in human children. Indeed, targeting IRF-7 protected mice against infection and renal tissue damage, suggesting that IRF7 could be a therapeutic target for protection against bacterial infection. Boosting innate immunity represents an important therapeutic alternative to antibiotics. However, the molecular selectivity of this approach is a major concern because innate immune responses often cause collateral tissue damage. We identify the transcription factor interferon regulatory factor 7 (IRF-7), a heterodimer partner of IRF-3, as a target for non–antibiotics-based therapy of bacterial infections. We found that the efficient and self-limiting innate immune response to bacterial infection relies on a tight balance between IRF-3 and IRF-7. Deletion of Irf3 resulted in overexpression of Irf7 and led to an IRF-7–driven hyperinflammatory phenotype, which was entirely prevented if Irf7 was deleted. We then identified a network of strongly up-regulated, IRF-7–dependent genes in Irf3−/− mice with kidney pathology, which was absent in Irf7−/− mice. IRF-3 and IRF-7 from infected kidney cell nuclear extracts were shown to bind OAS1, CCL5, and IFNB1 promoter oligonucleotides. These data are consistent in children with low IRF7 expression in the blood: attenuating IRF7 promoter polymorphisms (rs3758650-T and rs10902179-G) negatively associated with recurrent pyelonephritis. Finally, we identified IRF-7 as a target for immunomodulatory therapy. Administering liposomal Irf7 siRNA to Irf3−/− mice suppressed mucosal IRF-7 expression, and the mice were protected against infection and renal tissue damage. These findings offer a response to the classical but unresolved question of “good versus bad inflammation” and identify IRF7 as a therapeutic target for protection against bacterial infection.