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Problem: A threefold higher prevalence of antinuclear antibodies (ANA) has been reported in patients with recurrent pregnancy loss (RPL). Nevertheless, the role of ANA in reproductive failure is still unclear. The aim of this study was to investigate the role of ANA during early pregnancy in vivo., Method of Study: We used pregnant mice treated with immunoglobulin G (IgG) obtained from normal healthy subjects (NHS); ANA(+) sera of patients with RPL; and ANA(+) sera from women with uncomplicated pregnancies (HW). Placental immunohistochemical/immunofluorescence staining was performed to detect complement and immune complex deposition. ELISA was performed to evaluate complement levels., Results: ANA(+) IgG from RPL women significantly increased embryo resorption rate, reduced C3, and increased C3a serum levels compared to NHS IgG or ANA(+) -HW IgG. Increased C3 deposition and increased immune complex staining in placental tissues from mice treated with ANA(+) -RPL IgG fraction compared to NHS- and ANA(+) -HW-IgG-treated mice were found., Conclusion: ANA(+) IgG injection in mice is able to induce fetal resorption and complement activation. The presence on placental tissues of immune complexes and complement fragments suggests the complement activation as a possible mechanism of placental damage., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Problem: To investigate the possibility that antinuclear antibodies (ANA) are involved in recurrent pregnancy loss (RPL)., Methods: Case-control study carried out on 294 women (194 cases and 100 controls) in two University hospitals. The presence, the serum titers and the indirect immunofluorescence (IIF) patterns of ANA were determined in women with RPL and in control women., Results: Antinuclear antibodies at titers ≥ 1:80 were detected in 97 (50%) women with RPL and in 16 (16%) control women. Elevated ANA titers (≥1:180) were detected only in RPL women, whereas all control women had ANA titers no greater than 1:80. No differences could be detected in the IIF patterns between RPL and control women. No differences in ANA positivity could be detected according to the type (primary or secondary) or number (>2 versus ≥3) of losses., Conclusions: ANA could be of some value in identifying women with RPL with potential, although still not fully defined, immune abnormalities., (© 2010 John Wiley & Sons A/S.)

Purpose: The aim of this study was to compare the organ doses assessed through a digital phantom‐based and a patient specific‐based dosimetric tool in adult routine thorax computed tomography (CT) examinations with reference to physical dose measurements performed in anthropomorphic phantoms. Methods: Two Monte Carlo based dose calculation tools were used to assess organ doses in routine adult thorax CT examinations. These were a digital phantom‐based dosimetry tool (NCICT, National Cancer Institute, USA) and a patient‐specific individualized dosimetry tool (ImpactMC, CT Imaging GmbH, Germany). Digital phantoms and patients were classified in four groups according to their water equivalent diameter (Dw). Normalized to volume computed tomography dose index (CTDIvol), organ dose was assessed for lungs, esophagus, heart, breast, active bone marrow, and skin. Organ doses were compared to measurements performed using thermoluminescent detectors (TLDs) in two physical anthropomorphic phantoms that simulate the average adult individual as a male (Alderson Research Labs, USA) and as a female (ATOM Phantoms, USA). Results: The average percent difference of NCICT to TLD and ImpactMC to TLD dose measurements across all organs in both sexes was 13% and 6%, respectively. The average ± 1 standard deviation in dose values across all organs with NCICT, ImpactMC, and TLDs was ± 0.06 (mGy/mGy), ± 0.19 (mGy/mGy), and ± 0.13 (mGy/mGy), respectively. Organ doses decreased with increasing Dw in both NCICT and ImpactMC. Conclusion: Organ doses estimated with ImpactMC were in closer agreement to TLDs compared to NCICT. This may be attributed to the inherent property of ImpactMC methodology to generate phantoms that resemble the realistic anatomy of the examined patient as opposed to NCICT methodology that incorporates an anatomical discrepancy between phantoms and patients. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the operation principles of the automatic tube current modulation (ATCM) of a modern GE healthcare CT scanner, and the impact of related settings on image quality and patient dose. Material & Methods: A dedicated phantom (Mercury 4.0) was scanned using two of the most frequently used clinical scanning protocols (chest and abdomen‐pelvis). The preset protocol settings were used as starting points (reference conditions). Scan direction, scan mode (helical vs. axial), total beam width, tube potential (kVp), and ATCM settings were then modified individually to understand their impact on radiation dose and image quality. Regarding the ATCM settings, the SmartmA minimum and maximum mA limits, and the noise index (NI) values were varied. As surrogates of patient dose, the CTDIvol and DLP values of each scan were used. As surrogates of image quality were used the image noise and the detectability index (d') of five different materials (air, solid water, polystyrene, iodine, and bone) embedded in the Mercury phantom calculated with the ImQuest software. Results: The scanning direction did not have any effect on ATCM curves, unlike what has been observed in CT scanners from other manufacturers. Total beam width does matter, however, the SmartmA limit settings and kVp selection had the greatest impact on image quality and dose. It was seen that improper minimum mA limit settings practically invalidated the ATCM operation. In contrast, when full modulation was allowed without restrictions, noise standard deviation, and detectability index became much more consistent across the wide range of phantom diameters. For lower kVp settings an impressive dose reduction was observed that requires further investigation. Conclusion: SmartmA is a tool that if not properly used may increase the patient doses considerably. Therefore, its settings should be carefully adjusted for each preset different clinical protocol. [ABSTRACT FROM AUTHOR]

Purpose: Optimizing CT protocols is challenging in the presence of automatic dose modulation because the CT dose index (CTDIvol) at different patient sizes is unknown to the operator. The task is more difficult when both the image quality index and iterative reconstruction prospectively affect the dose determination. It is of interest in practice to be informed of the CTDIvol during the protocol initialization and evaluation. It was our objective to obtain a predictive relationship between CTDIvol, the image quality index, and iterative reconstruction strength at various patient sizes. Methods: Dose modulation data were collected on a GE Revolution 256‐slice scanner utilizing a Mercury phantom and selections of the noise index (NI) from 8 to 17, the third generation iterative reconstruction (ASIR‐V) from 0% to 80%, and phantom diameters from 16 to 36 cm. The fixed parameters were 120 kVp, a pitch of.984, and a collimation of 40 mm with a primary slice width of 2.5 mm. The CTDIvol per diameter was based on the average tube current over three adjacent slices (same or similar diameter) multiplied by a conversion factor between the average mA of the series and the reported CTDIvol. The relationship between CTDIvol, NI, and ASIR‐V for each diameter was fitted with a 2nd order polynomial of ASIR‐V multiplied by a power law of NI. Results: The ASIR‐V fit parameters versus diameter followed a Lorentz function while the NI exponent versus diameter followed an exponential growth function. The CTDIvol predictions were accurate within 15% compared to phantom results on a separate GE Revolution. For clinical relevance, the phantom diameter was converted to an abdomen or chest equivalent diameter and was well matched to patient data. Conclusion: The fitted relationship for CTDIvol. for given values of NI and ASIR‐V blending for a range of phantom sizes was a good match to phantom and patient data. The results can be of direct help for selecting adequate parameters in CT protocol development. [ABSTRACT FROM AUTHOR]

Experimental autoimmune encephalomyelitis (EAE) is an animal model of central nervous system (CNS) autoimmunity. It is most commonly used to mimic aspects of multiple sclerosis (MS), a demyelinating disorder of the human brain and spinal cord. The innate immune response displays one of the core pathophysiological features linked to both the acute and chronic stages of MS. Hence, understanding and targeting the innate immune response is essential. Microglia and other CNS resident MUs, as well as infiltrating myeloid cells, diverge substantially in terms of both their biology and their roles in EAE. Recent advances in the field show that antigen presentation, as well as disease‐propagating and regulatory interactions with lymphocytes, can be attributed to specific myeloid cell types and cell states in EAE lesions, following a distinct temporal pattern during disease initiation, propagation and recovery. Furthermore, single‐cell techniques enable the assessment of characteristic proinflammatory as well as beneficial cell states, and identification of potential treatment targets. Here, we discuss the principles of EAE induction and protocols for varying experimental paradigms, the composition of the myeloid compartment of the CNS during health and disease, and systematically review effects on myeloid cells for therapeutic approaches in EAE. [ABSTRACT FROM AUTHOR]

Background: Quantifying radiation burden is necessary for optimizing imaging protocols. The normalized dose coefficient (NDC) is determined from the water‐equivalent diameter (WED) and is used to scale the CTDIvol based on body habitus to determine the size specific dose estimate (SSDE). In this study we determine the SSDE prior to the CT scan and how sensitive the SSDE from WED is to the lifetime attributable risk (LAR) from BEIR VII. Method: For calibration, phantom images are used to relate the mean pixel values along a profile (PPV¯$\overline {{\rm{PPV}}} $) of the CT localizer to the water‐equivalent area (AW) of the CT axial scan at the same z‐location. Images of the CTDIvol phantoms (32 cm, 16 cm, and ∼1 cm) and ACR phantom (Gammex 464) were acquired on four scanners. The relationship between the AW and PPV¯$\overline {{\rm{PPV}}} $ was used to calculate the WED from the CT localizer for patient scans. A total of 790 CT examinations of the chest and abdominopelvic regions were used in this study. The effective diameter (ED) was calculated from the CT localizer. The LAR was calculated based on the patient chest and abdomen using the National Cancer Institute Dosimetry System for Computed Tomography (NCICT). The radiation sensitivity index (RSI) and risk differentiability index (RDI) were calculated for SSDE and CTDIvol. Results: The WED from CT localizers and CT axials scans show good correlation (R2 = 0.96) with the maximum percentage difference being 13.45%. The NDC from WED correlates poorly with LAR for lungs (R2 = 0.18) and stomach (R2 = 0.19), however that is the best correlation. Conclusion: The SSDE can be determined within 20% as recommended by the report of AAPM TG 220. The CTDIvol and SSDE are not good surrogates for radiation risk, however the sensitivity for SSDE improves when using WED instead of ED. [ABSTRACT FROM AUTHOR]

Non‐small cell lung cancer is the most prevalent lung cancer, and almost three‐fourths of patients are diagnosed in the advanced stage directly. In this stage, chemotherapy gives only a 15% 5‐year survival rate. As people have varied symptoms and reactions to a specific cancer type, treatment for the tumor is likely to fall short, complicating cancer therapy. Immunotherapy is a breakthrough treatment involving drugs targeting novel immune checkpoint inhibitors like CTLA‐4 and PD‐1/PD‐L1, along with combination therapies. In addition, the utility of engineered CAR‐T and CAR‐NK cells can be an effective strategy to promote the immune response against tumors. The concept of personalized cancer vaccines with the discovery of neoantigens loaded on dendritic cell vectors can also be an effective approach to cure cancer. Advances in genetic engineering tools like CRISPR/Cas9‐mediated gene editing of T cells to enhance their effector function is another ray of hope. This review aims to provide an overview of recent developments in cancer immunotherapy, which can be used in first‐ and second‐line treatments in the clinical space. Further, the intervention of artificial intelligence to detect cancer tumors at an initial stage with the help of machine learning techniques is also explored. [ABSTRACT FROM AUTHOR]

Cytokine‐induced killer (CIK) cells are a group of highly heterogeneous T cells expressing diverse T‐cell antigen receptors (TCRs), but possessing wide major histocompatibility complex (MHC)‐unrestricted antitumour activity, which have been used in the treatment of many tumours. However, the clonal diversity of different T‐cell subsets and whether there is a certain clonal preference during CIK culture remains to be clarified. We found that the proportion of oligoclones seen in some subfamilies of freshly isolated T cells decreased in varying degrees after culturing. This indicates that the diversity of T‐cell clones had been restored to a certain extent. The diversity differed among different T‐cell subsets, as some TCR subfamily oligoclones mainly appeared in CD3+CD56+ cells, which also indicates the heterogeneity of the CIK cell composition. [ABSTRACT FROM AUTHOR]

Background: Two deep learning image reconstruction (DLIR) techniques from two different computed tomography (CT) vendors have recently been introduced into clinical practice. Purpose: To characterize the noise properties of two DLIR techniques with different training methods, using a phantom containing a simple uniform and a complex non‐uniform region. Methods: A water‐bath phantom with a diameter of 300 mm was used as a base phantom. A textured phantom with a diameter of 128 mm, which was made of two materials, one equivalent to water and the other being 12 mg/ml diluted iodine, irregularly mixed to create a complex texture (non‐uniform region), was placed in the base phantom. Thirty repeated phantom scans were performed using two CT scanners (Revolution CT with Apex Edition, GE Healthcare; Aquilion One PRISM Edition, Canon Medical Systems) at two dose levels (CT dose index: 5 and 15 mGy). Images were reconstructed with each CT system's filtered back projection (FBP) and DLIR [TrueFidelity (TF), GE Healthcare; Advanced intelligent Clear‐IQ Engine Body Sharp (AC), Canon Medical Systems] for three process strengths. For basic characteristics of noise, the standard deviation (SD) and noise power spectrum (NPS) were measured for the uniform (water) region. A noise magnitude map was generated by calculating the inter‐image SD at each pixel position across the 30 images. Then, a noise reduction map (NRM), which visualizes the relative differences in noise magnitude between FBP and DLIR, was calculated. The NRM values ranged from 0.0 to 1.0. A low NRM value represents a less aggressive noise reduction. The histograms of the NRM value were analyzed for the uniform and non‐uniform regions. Results: The reduction in noise magnitude compared with FBP tended to be greater with AC (45%–85%) than with TF (32%–65%). The average NPS frequencies of TF and AC were almost comparable to those of FBP, except for the low‐dose condition and the high noise reduction strength for AC. The NRM values of TF and AC were higher in the uniform region than in the non‐uniform region. In the non‐uniform region, TF's average NRM values (0.21–0.48) tended to be lower than AC's (0.39–0.78). The histograms for TF showed a small overlap between the uniform and the non‐uniform regions; in contrast, those for AC showed a greater overlap. This difference seems to indicate that TF processes the uniform and non‐uniform regions more differently than AC does. Conclusion: This study has revealed a distinct difference in characteristics between the two DLIR techniques: TF tends to offer less aggressive noise reduction in non‐uniform regions and preserve the original signals, whereas AC tends to prioritize noise filtering over edge‐preservation, especially at the low‐dose condition and with the high noise reduction strength. [ABSTRACT FROM AUTHOR]

Iron is an essential metal critical for normal cellular and biochemical function and it is used as a cofactor in many vital biological pathways within the brain. However, accumulation of excess iron in brain is commonly associated with several neurodegenerative and neurotoxic adverse effects. Chronic exposure of iron leads to an increased risk for several neurodegenerative diseases. The exact mechanism of iron‐induced neurotoxicity is still unclear. Therefore, our study aimed to investigate the mechanism of neurotoxic and neurodegenerative effects through in vitro exposure of ferrous sulphate in rat C6 cell line. The findings of our study have indicated that ferrous sulphate exposure may lead to induction of molecular markers of neuronal inflammation, apoptotic neuronal cell death, amyloid‐beta and hyperphosphorylated tau levels. This study provides a basic mechanistic understanding of signaling pathway and biomarkers involved during iron‐induced neurotoxicity. [ABSTRACT FROM AUTHOR]

Curcumin, isolated from turmeric (Curcuma longa L.) is one of the broadly studied phytomolecule owing to its strong antioxidant and anti‐inflammatory potential and has been considered a promising therapeutic candidate in a wide range of disorders. Considering, its low bioavailability, different curcumin analogs have been developed to afford desired pharmacokinetic profile and therapeutic outcome in varied pathological states. Several preclinical and clinical studies have indicated that curcumin ameliorates mitochondrial dysfunction, inflammation, oxidative stress apoptosis‐mediated neural cell degeneration and could effectively be utilized in the treatment of different neurodegenerative diseases. Hence, in this review, we have summarized key findings of experimental and clinical studies conducted on curcumin and its analogues with special emphasis on molecular pathways, viz. NF‐kB, Nrf2‐ARE, glial activation, apoptosis, angiogenesis, SOCS/JAK/STAT, PI3K/Akt, ERK1/2 /MyD88 /p38 MAPK, JNK, iNOS/NO, and MMP pathways involved in imparting ameliorative effects in the therapy of neurodegenerative disorders and associated conditions. [ABSTRACT FROM AUTHOR]

Purpose: The gold‐standard method for estimation of patient‐specific organ doses in digital tomosynthesis (DT) requires protocol‐specific Monte Carlo (MC) simulations of radiation transport in anatomically accurate computational phantoms. Although accurate, MC simulations are computationally expensive, leading to a turnaround time in the order of core hours for simulating a single exam. This limits their clinical utility. The purpose of this study is to overcome this limitation by utilizing patient‐ and protocol‐specific MC simulations to develop a comprehensive database of air‐kerma‐normalized organ dose coefficients for a virtual population of adult and pediatric patient models over an expanded set of exam protocols in DT for retrospective and prospective estimation of radiation dose in clinical tomosynthesis. Materials and methods: A clinically representative virtual population of 14 patient models was used, with pediatric models (M and F) at ages 1, 5, 10, and 15 and adult patient models (M and F) with body mass index (BMIs) at 10th, 50th, and 90th percentiles of the US population. A graphics processing unit (GPU)‐based MC simulation framework was used to simulate organ doses in the patient models, incorporating the scanner‐specific configuration of a clinical DT system (VolumeRad, GE Healthcare, Waukesha, WI, USA) and an expanded set of exam protocols, including 21 distinct acquisition techniques for imaging a variety of anatomical regions (head and neck, thorax, spine, abdomen, and knee). Organ dose coefficients (hn) were estimated by normalizing organ dose estimates to air kerma at 70 cm (X70cm) from the source in the scout view. The corresponding coefficients for projection radiography were approximated using organ doses estimated for the scout view. The organ dose coefficients were further used to compute air‐kerma‐normalized patient‐specific effective dose coefficients (Kn) for all combinations of patients and protocols, and a comparative analysis examining the variation of radiation burden across sex, age, and exam protocols in DT, and with projection radiography was performed. Results: The database of organ dose coefficients (hn) containing 294 distinct combinations of patients and exam protocols was developed and made publicly available. The values of Kn were observed to produce estimates of effective dose in agreement with prior studies and consistent with magnitudes expected for pediatric and adult patients across the different exam protocols, with head and neck regions exhibiting relatively lower and thorax and C‐spine (apsc, apcs) regions relatively higher magnitudes. The ratios (r = Kn/Kn,rad) quantifying the differences air‐kerma‐normalized patient‐specific effective doses between DT and projection radiography were centered around 1.0 for all exam protocols, with the exception of protocols covering the knee region (pawk, patk). Conclusions: This study developed a database of organ dose coefficients for a virtual population of 14 adult and pediatric XCAT patient models over a set of 21 exam protocols in DT. Using empirical measurements of air kerma in the clinic, these organ dose coefficients enable practical retrospective and prospective patient‐specific radiation dosimetry. The computation of air‐kerma‐normalized patient‐specific effective doses further enables the comparison of radiation burden to the patient populations between protocols and between imaging modalities (e.g., DT and projection radiography), as presented in this study. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the operation principles of the automatic tube current modulation (ATCM) of a CT scanner, using a dedicated phantom and the CT dosimetry index (CTDI) phantom. Material and methods: The Mercury 4.0 phantom and three different configurations of the CTDI dosimetry phantom were employed. A frequently used clinical scanning protocol was employed as a basis for the acquisitions performed with all phantoms, using both scanning directions. Additional acquisitions with different pitch and examination protocols were performed with Mercury phantom, to further explore their effect on ATCM and the resulting image quality. Different software named DICOM Info Extractor, ImageJ, and imQuest, were used to derive CTDIvol and table position, image noise, and water equivalent diameter (WED) of each phantom CT image, respectively. ImQuest was also used to derive the detectability index (d') of five different materials (air, solid water, polystyrene, iodine, and bone) embedded in the Mercury phantom. Results: It was exhibited with all four phantoms that the scanning direction greatly affects the modulation curves. The fitting of the dose modulations curves suggested that for each table position what determines the CTDIvol value is the WED values of the phantom structures laying ahead towards the scanning direction, for a length equal to the effective width of the X‐ray beam. Furthermore, it was also exhibited that ATCM does not fully compensate for larger thicknesses, since images of larger WED phantom sections present more noise (larger SD) in all four phantoms and in Mercury 4.0 phantom smaller detectability (d'). Conclusion: Mercury 4.0 is a dedicated phantom for a complete and in‐depth evaluation of the ATCM operation and the resulting image quality. However, in its absence, different CTDI configurations can be used as an alternative to investigate and comprehend some basic operation principles of the CT scanners' ATCM systems. [ABSTRACT FROM AUTHOR]

Epilepsy affects about 1% of the population and approximately 30% of epileptic patients are resistant to current antiepileptic drugs. As a hallmark in epileptic tissue, many of the epileptic patients show changes in glia morphology and function. There are characteristic changes in different types of glia in different epilepsy models. Some of these changes such as astrogliosis are enough to provoke epileptic seizures. Astrogliosis is well known in mesial temporal lobe epilepsy (MTLE), the most common form of refractory epilepsy. A better understanding of astrocytes alterations could lead to novel and efficient pharmacological approaches for epilepsy. In this review, we present the alterations of astrocyte morphology and function and present some instances of targeting astrocytes in seizure and epilepsy. [ABSTRACT FROM AUTHOR]

Introduction: The use of ionising radiation in medicine accounts for the majority of radiation exposure from artificial sources. Therefore, all measures to safeguard against unnecessary radiation exposure must be taken. As radiographers are central to radiation protection, this study aimed to determine South African radiographers' attitude towards radiation protection, subjective norm and perceived behavioural control concerning radiation protection. Methods: This quantitative cross‐sectional study used an online theory of a planned behaviour radiation protection questionnaire shared through social media platforms from August 2019 to February 2020. Diagnostic radiographers registered with the Health Professions Council of South Africa and employed at radiology departments in South Africa were invited to participate in the study. Results: Four hundred and seventeen radiographers in South Africa responded to the questionnaire. The majority of respondents (90%, n = 376) plan to use radiation protection; however, only 16% continuously used radiation protection in the past. Respondents felt that using radiation protection was extremely good (72.2%), pleasant (47%), beneficial (74.1%), rewarding (55.2%) and worth the time (52.5%); 57% of respondents indicated that using radiation protection takes longer to complete the examination. Respondents report that approval from patients (43.5%), patients' family (32%), radiographer coworkers (31%), radiology managers (47%) and radiologists (43.9%) is very much important to them. Conclusion: The study shows that even though fewer respondents use radiation protection at present, most respondents plan and intend to use radiation protection measures. Respondents felt that radiation protection was good and beneficial, with some respondents feeling that radiation protection is not worth the time, which coincide with lengthening the examination. Overall, South African radiographers' attitudes towards radiation protection, subjective norm, perceived behavioural control and radiation protection intention were high. [ABSTRACT FROM AUTHOR]

Purpose: Estimation of organ doses in digital tomosynthesis (DT) is challenging due to the lack of existing tools that accurately and flexibly model protocol‐ and view‐specific collimations and motion trajectories of the source and detector for a variety of exam protocols, and the computational inefficiencies of conducting MC simulations. The purpose of this study was to overcome these limitations by developing and benchmarking a GPU‐accelerated MC simulation framework compatible with patient‐specific computational phantoms for individualized estimation of organ doses in DT. Materials and methods: The framework for individualized estimation of dose in DT was developed as a two‐step workflow: (1) a custom MATLAB code that accepts a patient‐specific computational phantom and exam description (organ markers for defining the extremities of the anatomical region of interest, tube voltage, source‐to‐image distance, angular sweep range, number of projection views, and the pivot point to image distance ‐ PPID) to compute the field of views (FOVs) for a clinical DT system, and (2) a MC tool (developed using MC‐GPU) modeling the configuration of a clinical DT system to estimate organ doses based on the computed FOVs. Using this framework, we estimated organ doses for 28 radiosensitive organs in an adult reference patient model (M; 30 years) imaged using a commercial DT system (VolumeRad, GE Healthcare, Waukesha, WI). The estimates were benchmarked against values from a comparable organ dose estimation framework (reference dataset developed by the Advanced Laboratory for Radiation Dosimetry Studies at University of Florida) for a posterior–anterior chest exam. The resulting differences were quantified as percent relative errors and analyzed to identify any potential sources of bias and uncertainties. The timing performance (run duration in seconds) of the framework was also quantified for the same simulation to gauge the feasibility of the workflow for time‐constrained clinical applications. Results: The organ dose estimates from the developed framework showed a close agreement with the reference dataset, with percent relative errors ranging from −6.9% to 5.0% and a mean absolute percent difference of 1.7% over all radiosensitive organs, with the exception of testes and eye lens, for which the percent relative errors were higher at −18.9% and −27.6%, respectively, due to their relative positioning outside the primary irradiation field, leading to fewer photons depositing energy and consequently higher errors in estimated organ doses. The run duration for the same simulation was 916.3 s, representing a substantial improvement in performance over existing nonparallelized MC tools. Conclusions: This study successfully developed and benchmarked a GPU‐accelerated framework compatible with patient‐specific anthropomorphic computational phantoms for accurate individualized estimation of organ doses in DT. By enabling patient‐specific estimation of organ doses, this framework can aid clinicians and researchers by providing them with tools essential for tracking the radiation burden to patients for dose monitoring purposes and identifying the trends and relationships in organ doses for a patient population to optimize existing and develop new exam protocols. [ABSTRACT FROM AUTHOR]

Purpose: A Monte Carlo (MC) modeling of single axial and helical CT scan modes has been developed to compute single and accumulated dose distributions. The radiation emission characteristics of an MDCT scanner has been modeled and used to evaluate the dose deposition in infinitely long head and body PMMA phantoms. The simulated accumulated dose distributions determined the approach to equilibrium function, H(L). From these H(L) curves, dose‐related information was calculated for different head and body clinical protocols. Methods: The PENELOPE/penEasy package has been used to model the single axial and helical procedures and the radiation transport of photons and electrons in the phantoms. The bowtie filters, heel effect, focal‐spot angle, and fan‐beam geometry were incorporated. Head and body protocols with different pitch values were modeled for x‐ray spectra corresponding to 80, 100, 120, and 140 kV. The analytical formulation for the single dose distributions and experimental measurements of single and accumulated dose distributions were employed to validate the MC results. The experimental dose distributions were measured with OSLDs and a thimble ion chamber inserted into PMMA phantoms. Also, the experimental values of the CTDI100 along the center and peripheral axes of the CTDI phantom served to calibrate the simulated single and accumulated dose distributions. Results: The match of the simulated dose distributions with the reference data supports the correct modeling of the heel effect and the radiation transport in the phantom material reflected in the tails of the dose distributions. The validation of the x‐ray source model was done comparing the CTDI ratios between simulated, measured and CTDosimetry data. The average difference of these ratios for head and body protocols between the simulated and measured data was in the range of 13–17% and between simulated and CTDosimetry data varied 10–13%. The distributions of simulated doses and those measured with the thimble ion chamber are compatible within 3%. In this study, it was demonstrated that the efficiencies of the CTDI100 measurements in head phantoms with nT = 20 mm and 120 kV are 80.6% and 87.8% at central and peripheral axes, respectively. In the body phantoms with nT= 40 mm and 120 kV, the efficiencies are 56.5% and 86.2% at central and peripheral axes, respectively. In general terms, the clinical parameters such as pitch, beam intensity, and voltage affect the Deq values with the increase of the pitch decreasing the Deq and the beam intensity and the voltage increasing its value. The H(L) function does not change with the pitch values, but depends on the phantom axis (central or peripheral). Conclusions: The computation of the pitch‐equilibrium dose product, D̂eq, evidenced the limitations of the CTDI100 method to determine the dose delivered by a CT scanner. Therefore, quantities derived from the CTDI100 propagate this limitation. The developed MC model shows excellent compatibility with both measurements and literature quantities defined by AAPM Reports 111 and 200. These results demonstrate the robustness and versatility of the proposed modeling method. [ABSTRACT FROM AUTHOR]

B cells have been implicated in the pathology of multiple sclerosis (MS) since initial observations in the 1940s of elevated immunoglobulin concentrations in the cerebrospinal fluid of MS patients. However, the precise mechanism of their involvement has not been elucidated until recently, mainly owing to the technical difficulty of studying this cell population in humans. In this context, experimental autoimmune encephalomyelitis (EAE), a putative animal model of MS, has profoundly contributed to our understanding of B cells in this disease. B cells are now recognized to contribute to MS pathology through the production of autoantibodies, antigen presentation to T cells, secretion of effector cytokines, recognition of microbe‐associated molecules and the induction of ectopic lymphoid follicles in the meninges. All these activities of B cells in MS have been recapitulated in various types of EAE models. Although EAE does not reflect all aspects of MS, it is a useful tool to dissect the complex pathology of this disease if the model selected appropriately reflects the aspect of MS under interest. This is especially true for the study of B cells in MS, as the roles of these cells differ substantially among different EAE models. Even with this limitation, EAE will further enhance our understanding of the role played by B cells in MS. [ABSTRACT FROM AUTHOR]

Ectopic lymphoid follicles (ELFs), resembling germinal centre‐like structures, emerge in a variety of infectious and autoimmune and neoplastic diseases. ELFs can be found in the meninges of around 40% of the investigated progressive multiple sclerosis (MS) post‐mortem brain tissues and are associated with the severity of cortical degeneration and clinical disease progression. Of predominant importance for progressive neuronal damage during the progressive MS phase appears to be meningeal inflammation, comprising diffuse meningeal infiltrates, B‐cell aggregates and compartmentalized ELFs. However, the absence of a uniform definition of ELFs impedes reproducible and comparable neuropathological research in this field. In this review article, we will first highlight historical aspects and milestones around the discovery of ELFs in the meninges of progressive MS patients. In the next step, we discuss how animal models may contribute to an understanding of the mechanisms underlying ELF formation. Finally, we summarize challenges in investigating ELFs and propose potential directions for future research. [ABSTRACT FROM AUTHOR]

Purpose: To compare the impact on CT image quality and dose reduction of two versions of a Deep Learning Image Reconstruction algorithm. Material and methods: Acquisitions on the CT ACR 464 phantom were performed at five dose levels (CTDIvol: 10/7.5/5/2.5/1 mGy) using chest or abdomen pelvis protocol parameters. Raw data were reconstructed using the filtered‐back projection (FBP), the enhanced level of AIDR 3D (AIDR 3De), and the three levels of AiCE (Mild, Standard, and Strong) for the two versions (AiCE V8 vs AiCE V10). The noise power spectrum (NPS) and task‐based transfer function (TTF) for bone (high‐contrast insert) and acrylic (low‐contrast insert) inserts were computed. To quantify the changes of noise magnitude and texture, the square root of the area under the NPS curve and the average spatial frequency (fav) of the NPS curve were measured. The detectability index (d') was computed to model the detectability of either a large mass in the liver or lung, or a small calcification or high contrast tissue boundaries. Results: The noise magnitude was lower with both AiCE versions than with AIDR 3De. The noise magnitude was lower with AiCE V10 than with AiCE V8 (‐4 ± 6% for Mild, ‐13 ± 3% for Standard, and ‐48 ± 0% for Strong levels). fav and TTF50% values for both inserts shifted towards higher frequencies with AiCE than with AIDR 3De. Compared to AiCE V08, fav shifted towards higher frequencies with AiCE V10 (45 ± 4%, 36 ± 3%, and 5 ± 4% for all levels, respectively). The TTF50% values shifted towards higher frequencies with AiCE V10 as compared with AiCE V8 for both inserts, except for the Strong level for the acrylic insert. Whatever the dose and AiCE levels, d' values were higher with AiCE V10 than with AiCE V8 for the small object/calcification and for the large object/lesion. Conclusion: As compared to AIDR 3De, lower noise magnitude and higher spatial resolution and detectability index were found with both versions of AiCE. As compared to AiCE V8, AiCE V10 reduced noise and improved spatial resolution and detectability without changing the noise texture in a simple geometric phantom, except for the Strong level. AiCE V10 seems to have a greater potential for dose reduction than AiCE V8. [ABSTRACT FROM AUTHOR]

Purpose: The global noise (GN) algorithm has been previously introduced as a method for automatic noise measurement in clinical CT images. The accuracy of the GN algorithm has been assessed in abdomen CT examinations, but not in any other body part until now. This work assesses the GN algorithm accuracy in automatic noise measurement in head CT examinations. Methods: A publicly available image dataset of 99 head CT examinations was used to evaluate the accuracy of the GN algorithm in comparison to reference noise values. Reference noise values were acquired using a manual noise measurement procedure. The procedure used a consistent instruction protocol and multiple observers to mitigate the influence of intra‐ and interobserver variation, resulting in precise reference values. Optimal GN algorithm parameter values were determined. The GN algorithm accuracy and the corresponding statistical confidence interval were determined. The GN measurements were compared across the six different scan protocols used in this dataset. The correlation of GN to patient head size was also assessed using a linear regression model, and the CT scanner's X‐ray beam quality was inferred from the model fit parameters. Results: Across all head CT examinations in the dataset, the range of reference noise was 2.9–10.2 HU. A precision of ±0.33 HU was achieved in the reference noise measurements. After optimization, the GN algorithm had a RMS error 0.34 HU corresponding to a percent RMS error of 6.6%. The GN algorithm had a bias of +3.9%. Statistically significant differences in GN were detected in 11 out of the 15 different pairs of scan protocols. The GN measurements were correlated with head size with a statistically significant regression slope parameter (p < 10‒7). The CT scanner X‐ray beam quality estimated from the slope parameter was 3.5 cm water HVL (2.8–4.8 cm 95% CI). Conclusion: The GN algorithm was validated for application in head CT examinations. The GN algorithm was accurate in comparison to reference manual measurement, with errors comparable to interobserver variation in manual measurement. The GN algorithm can detect noise differences in examinations performed on different scanner models or using different scan protocols. The trend in GN across patients of different head sizes closely follows that predicted by a physical model of X‐ray attenuation. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis and periodontitis are chronic inflammatory diseases defined respectively by the destruction of the articular cartilage and tooth-supporting periodontal tissues. Although the epidemiologic evidence for an association between these two diseases is still scarce, there is emerging scientific information linking specific bacterial periodontal pathogens, such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, in the citrullination process, leading to autoantibody formation and compromised immunotolerance of the susceptible patient to rheumatoid arthritis. In this review, we update the existing information on the evidence, not only regarding the epidemiologic association, but also the biologic mechanisms linking these two diseases. Finally, we review information emerging from intervention studies evaluating whether periodontal treatment could influence the initiation and progression of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Gray mold disease caused by the fungus Botrytis cinerea damages many crop hosts worldwide and is responsible for heavy economic losses. Early diagnosis and detection of the disease would allow for more effective crop management practices to prevent outbreaks in field or greenhouse settings. Furthermore, having a simple, non‐invasive way to quantify the extent of gray mold disease is important for plant pathologists interested in measuring infection rates. In this paper, we design and build a bispectral imaging system for discriminating between leaf regions infected with gray mold and those that remain unharmed on a lettuce (Lactuca spp.) host. First, we describe a method to select two optimal (high contrast) spectral bands from continuous hyperspectral imagery (450–800 nm). We then explain the process of building a system based on these two spectral bands, located at 540 and 670 nm. The resultant system uses two cameras, with a narrow band‐pass spectral filter mounted on each, to measure the bispectral reflectance of a lettuce leaf. The two resulting images are combined using a normalized difference calculation that produces a single image with high contrast between the leaves' infected and healthy regions. A classifier was then created based on the thresholding of single pixel values. We demonstrate that this simple classification produces a true‐positive rate of 95.25% with a false‐positive rate of 9.316% in laboratory conditions. [ABSTRACT FROM AUTHOR]

Purpose: Assessment of image quality directly in clinical image data is an important quality control objective as phantom‐based testing does not fully represent image quality across patient variation. Computer algorithms for automatically measuring noise in clinical computed tomography (CT) images have been introduced, but the accuracy of these algorithms is unclear. This work benchmarks the accuracy of the global noise (GN) algorithm for automatic noise measurement in contrast‐enhanced abdomen CT exams in comparison to precise reference noise measurements. The GN algorithm was further optimized compared to the previous report in the literature. Methods: Reference values of noise were established in a public image dataset of 82 contrast‐enhanced abdomen CT exams. The reference noise values were obtained by manual regions‐of‐interest measurements of pixel standard deviation in the liver parenchyma according to an instruction protocol. Noise measurements taken by six observers were averaged together to improve reference noise statistical precision. The GN algorithm was used to automatically measure noise in each image set. The accuracy of the GN algorithm was determined in terms of RMS error compared to reference noise. The GN algorithm was optimized by conducting 1000 trials with random algorithm parameter values. The trial with the lowest RMS error was used to select optimum algorithm parameters. Results: The range of noise across CT image sets was 8.8–28.8 HU. Reference noise measurements were made with a precision of ±0.78 HU (95% confidence interval). The RMS error of automatic noise measurement was 0.93 HU (0.77–1.19 HU 95% confidence interval). The automatic noise measurements were equally accurate across image sets of varying noise magnitude. Optimum GN algorithm parameter values were: a kernel size of 7 pixels, and soft tissue lower and upper thresholds of 0 and 170 HU, respectively. Conclusions: The performance of automatic noise measurement was benchmarked in a large clinical CT dataset. The study provides a framework for thorough validation of automatic clinical image quality measurement methods. The GN algorithm was optimized and validated for automatic measurement of soft‐tissue noise in abdomen CT exams. [ABSTRACT FROM AUTHOR]

Sepsis is characterized by dynamic changes of the immune system resulting in deregulated inflammation and failure of homoeostasis and can escalate to septic shock. Circulating monocytes and other innate immune cells are among the first ones to recognize and clear pathogens. Monocytes have an important role in sepsis and septic shock and have been studied as potential diagnostic markers. In total, forty‐two patients with septic shock were recruited and blood samples obtained within first 12 hours of ICU admission. We showed that frequency of classical and intermediate monocytes assessed at the time of admission to the intensive care unit are significantly distinct in patients with septic shock who survived longer that five days from those who died. These parameters correlate significantly with differences in serum levels of inflammatory cytokines MCP‐1, IL‐6, IL‐8, IL‐10, and IL‐18, and with the proportion of helper and cytotoxic T cells. The described changes in frequency of monocyte subsets and their activation status may predict short‐term septic shock survival and help with fast identification of the group of vulnerable patients, who may profit from tailored therapy. [ABSTRACT FROM AUTHOR]

Purpose: To validate a normal‐resolution (NR) simulation (NRsim) algorithm that uses high‐resolution (HR) or super‐high resolution (SHR) acquisitions on a commercial HR computed tomography (CT) scanner by comparing image quality between NRsim‐generated images and actual NR images. NRsim is intended to allow direct comparison between normal‐resolution CT and HR/SHR reconstructions in clinical investigations, without repeating exams. Methods: The Aquilion Precision CT (Canon Medical Systems Corporation) HR CT scanner has three resolution modes resulting from detector binning in the channel (x‐y) and row (z) directions. For NR, each detector element is 0.5 mm × 0.5 mm along the channel and row directions, 0.25 mm × 0.5 mm for HR, and 0.25 mm × 0.25 mm for SHR. The NRsim algorithm simulates NR acquisitions from HR or SHR acquisitions (termed NRHR and NRSHR, respectively) by downsampling the pre‐log raw data in the channel direction for the HR acquisitions and in the channel and row direction for the SHR acquisition. The downsampled data are then reconstructed using the same process as NR. The axial modulation transfer function (MTF), slice sensitivity profile (SSP), and CT number accuracy were measured using the Catphan 600 phantom, and the three‐dimensional noise power spectrum (NPS) was measured in water‐equivalent phantoms for standard protocols across a range of size‐specific dose estimates (SSDE): head (6.2–29.8 mGy), lung (2.2–18.2 mGy), and body (5.6–19.4 mGy). The MTF and NPS measurements were combined to estimate low‐contrast detectability (LCD) using a non‐prewhitening model observer with an eye filter for a 5‐mm disk with 10 HU contrast. All metrics were compared for NR, NRHR, and NRSHR images reconstructed using filtered back projection (FBP) and an iterative reconstruction algorithm (AIDR3D). We chose a 15% error threshold as a reasonable definition of success for NRsim when compared against actual NR based on published studies showing that a just‐noticeable difference in image noise level for human observers is typically <15%. Results: The axial MTF and SSPs for NRsim were in good agreement with NR demonstrated by a maximum difference of 5.1% for the MTF at 10% and 50% across materials (air, Teflon, LDPE, and polystyrene) and a maximum SSP difference of 2.2%. Noise magnitude differences were within 15% across the SSDE levels with the exception of below 4.5 mGy for the lung protocol with FBP. The relative RMSE of normalized NPS comparisons were all <15%. Differences in CT numbers for NRsim reconstructions were within 2 HU of NR. LCD for NRsim was within 15% of NR with the exception of NRSHR for the lung protocol SSDE levels below 3.7 mGy with FBP. Conclusions: NRsim, an algorithm for simulating NR acquisitions using HR and SHR raw data, was introduced and shown to generate images with spatial resolution, noise, HU accuracy, and LCD largely equivalent to scans acquired using an actual NR acquisition. At SSDE levels below ~5 mGy for the lung protocol, differences in noise magnitude and LCD for NRSHR were >15% which defines a region where NRsim degrades due to contributions from electronic noise. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis and chronic periodontitis are both chronic inflammatory diseases characterized by an exacerbated inflammatory reaction that leads to destruction of bone and other connective tissue. Owing to these similarities, the relationship between these two diseases has been investigated for over two decades. In the 2013 proceedings from a workshop jointly held by the European Federation of Periodontology and American Academy of Periodontology in 2012 it was concluded that there was at least minimal evidence of an association between periodontitis and rheumatoid arthritis. In this review, we consider publications in the field over the past 5 years and determine whether the evidence for this relationship has increased. [ABSTRACT FROM AUTHOR]

Purpose: Phantoms are useful tools in diagnostic CT, but practical limitations reduce phantoms to being only a limited patient surrogate. Furthermore, a phantom with a single cross sectional area cannot be used to evaluate scanner performance in modern CT scanners that use dose reduction techniques such as automated tube current modulation (ATCM) and iterative reconstruction (IR) algorithms to adapt x‐ray flux to patient size, reduce radiation dose, and achieve uniform image noise. A new multisized phantom (Mercury Phantom, MP) has been introduced, representing multiple diameters. This work aimed to ascertain if measurements from MP can predict radiation dose and image noise in clinical CT images to prospectively inform protocol design. Methods: The adult MP design included four different physical diameters (18.5, 23.0, 30.0, and 37.0 cm) representing a range of patient sizes. The study included 1457 examinations performed on two scanner models from two vendors, and two clinical protocols (abdominopelvic with and chest without contrast). Attenuating diameter, radiation dose, and noise magnitude (average pixel standard deviation in uniform image) was automatically estimated in patients and in the MP using a previously validated algorithm. An exponential fit of CTDIvol and noise as a function of size was applied to patients and MP data. Lastly, the fit equations from the phantom data were used to fit the patient data. In each patient distribution fit, the normalized root mean square error (nRMSE) values were calculated in the residuals' plots as a metric to indicate how well the phantom data can predict dose and noise in clinical operations as a function of size. Results: For dose across patient size distributions, the difference between nRMSE from patient fit and MP model data prediction ranged between 0.6% and 2.0% (mean 1.2%). For noise across patient size distributions, the nRMSE difference ranged between 0.1% and 4.7% (mean 1.4%). Conclusions: The Mercury Phantom provided a close prediction of radiation dose and image noise in clinical patient images. By assessing dose and image quality in a phantom with multiple sizes, protocol parameters can be designed and optimized per patient size in a highly constrained setup to predict clinical scanner and ATCM system performance. [ABSTRACT FROM AUTHOR]

The inflammatory disorders collectively termed the seronegative spondyloarthropathies (SpA) include ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, the arthritis associated with inflammatory bowel disease including Crohn's disease and ulcerative colitis, the arthritis related to anterior uveitis, and finally, somewhat controversially Behcet's disease. All of these diseases are associated with SNPs in the IL‐23R or the interleukin‐23 (IL‐23) cytokine itself and related downstream signaling JAK pathway genes and the interleukin‐17 (IL‐17) pathway. In rheumatoid arthritis, the target of the immune response is the synovium but the SpA disorders target the tendon, ligament, and joint capsule skeletal anchorage points that are termed entheses. The discovery that IL‐23R–expressing cells were ensconced in healthy murine enthesis, and other extraskeletal anchorage points including the aortic root and the ciliary body of the eye and that systemic overexpression of IL‐23 resulted in a severe experimental SpA, confirmed a fundamentally different immunobiology to rheumatoid arthritis. Recently, IL‐23R–expressing myeloid cells and various innate and adaptive T cells that produce IL‐17 family cytokines have also been described in the human enthesis. Blockade of IL‐23 pathway with either anti‐p40 or anti‐p19 subunits has resulted in some spectacular therapeutic successes in psoriasis and PsA including improvement in enthesitis in the peripheral skeleton but has failed to demonstrate efficacy in AS that is largely a spinal polyenthesitis. Herein, we discuss the known biology of IL‐23 at the human enthesis and highlight the remarkable emerging story of this unique skeletal tissue. [ABSTRACT FROM AUTHOR]

Peripheral nerve injury elicits spinal microgliosis, contributing to neuropathic pain. The aurora kinases A (AURKA), B (AURKB), and C (AURKC) are potential therapeutic targets in proliferating cells. However, their role has not been clarified in microglia. The aim of this study was to examine the regulation of aurora kinases and their roles and druggability in spinal microgliosis and neuropathic pain. Sprague–Dawley rats received chronic constriction injury (CCI). Gene expression of aurora kinases A‐C was evaluated by quantitative RT‐PCR and western blot, respectively, in spinal cords at 1, 3, 7, and 14 days after CCI. AURKB gene and protein expression was up‐regulated concomitantly with the development of spinal microgliosis and neuropathic pain. Using lentiviral over‐expression and adeno‐associated viral knockdown approaches, the function of AURKB was further investigated by western blot, immunohistochemistry, RNA sequencing, and pain behavior tests. We found that AURKB over‐expression in naive rats caused spinal microgliosis and pain hypersensitivity, whereas AURKB knockdown reduced microgliosis and alleviated CCI‐induced neuropathic pain. Accordingly, RNA sequencing data revealed down‐regulation of genes critically involved in signaling pathways associated with spinal microgliosis and neuropathic pain after AURKB knockdown in CCI rats. To examine its therapeutic potential for treatment of neuropathic pain, animals were treated intrathecally with the pharmacological AURKB inhibitor AZD1152‐HQPA resulting in the alleviation of CCI‐induced pain. Taken together, our findings indicated that AURKB plays a critical role in spinal microgliosis and neuropathic pain. Targeting AURKB may be an efficient method for treatment of neuropathic pain subsequent to peripheral nerve injury. [ABSTRACT FROM AUTHOR]

Colombian forensic investigators required assistance locating clandestine burials of missing persons related to human right atrocities from 14 years ago. Geoscientific search methods were trialled, including a predictive spatial statistical model, using various input and database information, to select the most likely grave locations in difficult mountainous terrain. Groundwork using forensic geomorphology, near‐surface geophysics (ERT) and subsequent probing identified suspect burial positions. One site was in mountainous terrain and the other in former school grounds, both difficult to access and in poor weather conditions. In the mountainous area, a negative resistivity anomaly area was identified and intrusively investigated, found to be a buried rock. In school grounds, after MESP and intelligence were used to identify a burial site, surface depressions were identified, and ERT datasets collected over the highest priority depression; intrusive investigations discovered a hand‐dug pit containing animal bones. This approach is suggested for Latin American searches. [ABSTRACT FROM AUTHOR]

Background: Graft rejection due to alloreactivity is still the main obstacle to successful renal transplantation. Toll‐like receptors (TLRs), which are significantly involved in initiating inflammation, triggering innate immunity, occurrence of ischaemia reperfusion injury (IRI) and subsequent deterioration of allograft function, are of interest in molecular diagnosis of graft rejection. Methods: In present research, we have evaluated the mRNA expressions of TLR‐4, TLR‐2 and myeloid differentiation primary response gene 88 (MyD88) in peripheral blood mononuclear cells (PBMCs) and biopsy samples of 26 stable graft function (SGF), 14 acute T‐cell‐mediated rejection (ACMR), six acute antibody‐mediated rejection (AAMR), 10 chronic T‐cell‐mediated rejection (CCMR) and four chronic antibody‐mediated rejection (CAMR) cases of renal transplant recipients, using TaqMan detector real‐time polymerase chain reaction (RT‐PCR). Results: It was found that TLR4 mRNA level was significantly elevated in PBMCs of both ACMR (P.v: 0.025) and CCMR (P.v: 0.007) cases, while TLR2 gene was upregulated only in PBMCs of ACMR (P.v: 0.024). Moreover, MyD88 expression was increased in biopsy samples of all rejection groups AAMR (P.v: 0.032), ACMR (P.v: 0.002), CAMR (P.v: 0.038) and CCMR (P.v: 0.013) and could distinguish them from stable grafts with AUC (area under curve) of 0.81, 0.80, 0.83 and 0.77, respectively. Conclusion: These data showed that MyD88 gene upregulation in renal tissue could have diagnostic value and increased level of TLR4 mRNA in PBMCs could be suggestive of cell‐mediated rejections. Therefore, monitoring the expression level of inflammatory signalling genes might be useful in predicting allograft rejection. [ABSTRACT FROM AUTHOR]

Type 2 immune response refers to a complicated series of immune responses characterized by Th2 polarization and Th2 cytokines secretion. The IgE secretion, airway hypersensitivity, and effector cell recruitment (eosinophils, mast cells, basophils) in skin lesion and peripheral blood stream could be upregulated during the activation of type 2 immune response. Th1/Th2 ratio, also referred as Th1/Th2 balance, represent the T lymphocytes immune pattern to a certain degree: Th1-dominated responses are often involved in intracellular infections (e.g., mycobacterium tuberculosis) and autoimmune diseases (e.g., Graves' disease) while Th2-dominated responses are involved in allergic conditions (e.g., atopic dermatitis, eczema), IgE mediated diseases (e.g., urticaria), and fibrotic dermatoses (e.g., keloids). Dupilumab, as one of the most widely applied Th2 cytokine inhibitors, could block the bioactivity of IL-14/IL-13 via competitively binding to the common IL-4Rα subunit shared by IL-4 and IL-13 receptors. In addition to the direct inhibition of type 2 response, dupilumab is also effective in autoimmune and some infectious skin diseases through indirect regulation of type 1 immune response. The pathological mechanism of Th2 responses and advanced clinical application of dupilumab in skin diseases will be summarized and discussed in the review., (© 2022 Wiley Periodicals LLC.)

Purpose: Automated assessment of perceptual image quality on clinical Computed Tomography (CT) data by computer algorithms has the potential to greatly facilitate data‐driven monitoring and optimization of CT image acquisition protocols. The application of these techniques in clinical operation requires the knowledge of how the output of the computer algorithms corresponds to clinical expectations. This study addressed the need to validate algorithmic image quality measurements on clinical CT images with preferences of radiologists and determine the clinically acceptable range of algorithmic measurements for abdominal CT examinations. Materials and methods: Algorithmic measurements of image quality metrics (organ HU, noise magnitude, and clarity) were performed on a clinical CT image dataset with supplemental measures of noise power spectrum from phantom images using techniques developed previously. The algorithmic measurements were compared to clinical expectations of image quality in an observer study with seven radiologists. Sets of CT liver images were selected from the dataset where images in the same set varied in terms of one metric at a time. These sets of images were shown via a web interface to one observer at a time. First, the observer rank ordered the CT images in a set according to his/her preference for the varying metric. The observer then selected his/her preferred acceptable range of the metric within the ranked images. The agreement between algorithmic and observer rankings of image quality were investigated and the clinically acceptable image quality in terms of algorithmic measurements were determined. Results: The overall rank‐order agreements between algorithmic and observer assessments were 0.90, 0.98, and 1.00 for noise magnitude, liver parenchyma HU, and clarity, respectively. The results indicate a strong agreement between the algorithmic and observer assessments of image quality. Clinically acceptable thresholds (median) of algorithmic metric values were (17.8, 32.6) HU for noise magnitude, (92.1, 131.9) for liver parenchyma HU, and (0.47, 0.52) for clarity. Conclusions: The observer study results indicated that these algorithms can robustly assess the perceptual quality of clinical CT images in an automated fashion. Clinically acceptable ranges of algorithmic measurements were determined. The correspondence of these image quality assessment algorithms to clinical expectations paves the way toward establishing diagnostic reference levels in terms of clinically acceptable perceptual image quality and data‐driven optimization of CT image acquisition protocols. [ABSTRACT FROM AUTHOR]

Police witness intelligence stated a murdered adult male "Fred" had been vertically buried in wooded hilly terrain 30 years ago in the Midlands, U.K. Conventional search methods were unsuccessful; therefore, the police requested a geophysical investigation to be undertaken to determine whether "Fred" could be detected. A multiphased geophysical approach was conducted, using bulk ground conductivity and metal detectors, then follow‐up magnetics and ground penetrating radar (GPR) survey profiles on electromagnetic (EM) anomalous areas. A tight grid pattern was used to account for the reduced target size. Relatively high‐resolution EM and GPR techniques were determined optimal for this terrain and sandy soil. Geophysical anomalies were identified and the most promising intrusively investigated, and this was found to be a large boulder and tree roots. Study implications suggest careful multiphase geophysical surveys are best practice and give confidence in cold case searches. This study yielded a no‐body result, effectively saving police time and costs from further investigations. [ABSTRACT FROM AUTHOR]

Summary: Background: Nonalcoholic fatty liver disease (NAFLD) is a prevalent disorder associated with obesity and diabetes. Few treatment options are effective for patients with NAFLD, but connections between the gut microbiome and NAFLD and NAFLD‐associated conditions suggest that modulation of the gut microbiota could be a novel therapeutic option. Aim: To examine the effect of the gut microbiota on pathophysiologic causes of NAFLD and assess the potential of microbiota‐targeting therapies for NAFLD. Methods: A PubMed search of the literature was performed; relevant articles were included. Results: The composition of bacteria in the gastrointestinal tract can enhance fat deposition, modulate energy metabolism and alter inflammatory processes. Emerging evidence suggests a role for the gut microbiome in obesity and metabolic syndrome. NAFLD is often considered the hepatic manifestation of metabolic syndrome, and there has been tremendous progress in understanding the association of gut microbiome composition with NAFLD disease severity. We discuss the role of the gut microbiome in NAFLD pathophysiology and whether the microbiome composition can differentiate the two categories of NAFLD: nonalcoholic fatty liver (NAFL, the non‐progressive form) vs nonalcoholic steatohepatitis (NASH, the progressive form). The association between gut microbiome and fibrosis progression in NAFLD is also discussed. Finally, we review whether modulation of the gut microbiome plays a role in improving treatment outcomes for patients with NAFLD. Conclusions: Multiple pathophysiologic pathways connect the gut microbiome with the pathophysiology of NAFLD. Therefore, therapeutics that effectively target the gut microbiome may be beneficial for the treatment of patients with NAFLD. [ABSTRACT FROM AUTHOR]

Aquaporin‐4 (AQP4), the main water‐selective membrane transport protein in the brain, is localized to the astrocyte plasma membrane. Following the establishment of a 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP)‐induced Parkinson's disease (PD) model, AQP4‐deficient (AQP4−/−) mice displayed significantly stronger microglial inflammatory responses and remarkably greater losses of tyrosine hydroxylase (TH+)‐positive neurons than did wild‐type AQP4 (AQP4+/+) controls. Microglia are the most important immune cells that mediate immune inflammation in PD. However, recently, few studies have reported why AQP4 deficiency results in more severe hypermicrogliosis and neuronal damage after MPTP treatment. In this study, transforming growth factor‐β1 (TGF‐β1), a key suppressive cytokine in PD onset and development, failed to increase in the midbrain and peripheral blood of AQP4−/− mice after MPTP treatment. Furthermore, the lower level of TGF‐β1 in AQP4−/− mice partially resulted from impairment of its generation by astrocytes; reduced TGF‐β1 may partially contribute to the uncontrolled microglial inflammatory responses and subsequent severe loss of TH+ neurons in AQP4−/− mice after MPTP treatment. Our study provides not only a better understanding of both aetiological and pathogenical factors implicated in the neurodegenerative mechanism of PD but also a possible approach to developing new treatments for PD via intervention in AQP4‐mediated immune regulation. [ABSTRACT FROM AUTHOR]

This article examines the three production decisions that all business enterprises must face and attempts to incorporate them into a novel decision model. These decisions include designing a production plan that assess how much to produce and the means of production, how to invest capital in order to maintain production and how to finance this investment. The author extends research that has examined portions of these decisions by incorporating them all into one model. The author's model is designed to maximize shareholder value for a single product firm.

According to the US Census Bureau, recent immigrants to the United States are more likely to have a college education than earlier immigrants or the native born.1 In particular, in 2018 13.9% of immigrants ages 25 and older hold a postgraduate degree2 compared to about 13.1% of US adults.1 However, in a highly technological discipline like medical physics, even the highest education needs to be integrated with specific competencies sufficient to practice imaging physics independently.3 To this end, the American Board of Radiology (ABR) provides an alternate pathway to board certification for medical physicists trained in countries other than the United States and Canada.4 To be considered as a candidate for the Alternate Pathway, an applicant must meet several requirements, including completing a Structured Mentorship Program (SMP). The ABR International Medical Graduates Alternate Pathway provided the candidate specific competencies to practice diagnostic imaging physics independently offering alongside opportunities to improve in both clinical and research activities. [Extracted from the article]

A letter to the editor is presented in response to the article "A novel HLA-DRB1*10:01-restricted T cell epitope from citrullinated type II collagen relevant to rheumatoid arthritis" by K. Chemin and colleagues which was published in the previous issue of the journal.