Simulation study on X-ray phase contrast imaging with dual-phase gratings

Abstract

Purpose

Two phase gratings in an X-ray grating interferometers can solve several technical challenges for clinical use of X-ray phase contrast. In this work, we adapt and evaluate this setup design to clinical X-ray sources and detectors in a simulation study.

Methods

For a given set of gratings, we optimize the remaining parameter space of a dual-phase grating setup using a numerical wave front simulation. The simulation results are validated with experimentally obtained visibility measurements on a setup with a microfocus tube and a clinical X-ray detector. We then confirm by simulation that the Lau condition for the \(G_0\) grating also holds for two phase gratings. Furthermore, we use a \(G_0\) grating with a fixed period to search for periods of matching phase grating configurations.

Results

Simulated and experimental visibilities agree very well. We show that the Lau condition for a dual-phase grating setup requires the interference patterns of the first phase grating to constructively overlay at the second phase grating. Furthermore, a total of three setup variants for given \(G_{0}\) periods were designed with the simulation, resulting in visibilities between 4.5 and 9.1%.

Conclusion

Dual-phase gratings can be used and optimized for a medical X-ray source and detector. The obtained visibilities are somewhat lower than for other Talbot–Lau interferometers and are a tradeoff between setup length and spatial resolution (or additional phase stepping, respectively). However, these disadvantage appears minor compared to the overall better photon statistics, and the fact that dual-phase grating setups can be expected to scale to higher X-ray energies.

Biophysical properties of striae rubra and striae alba in human skin: Comparison with normal skin

Skin Research and Technology, EarlyView.

The role of in vivo reflectance confocal microscopy in assessing the stability of vitiligo vulgaris prior to cellular grafting

Skin Research and Technology, EarlyView.

Micro‐relief analysis with skin capacitive imaging

Skin Research and Technology, EarlyView.

Water adsorption with relative humidity changes for keratin and collagen as studied by infrared (IR) micro‐spectroscopy

Skin Research and Technology, EarlyView.

Want To Keep Your Brain Sharp? Take Care Of Your Eyes And Ears

Two large studies show that age-related memory loss can be slowed significantly when older people promptly address hearing and vision loss.

(Image credit: Leyla B/Getty Images)

Research Letter: Cross reactivity of latex agglutination assay complicates the identification of Burkholderia pseudomallei from soil.

Abstract

The monoclonal antibody—based latex agglutination tests targeting a high molecular weight exopolysaccharide antigen of Burkholderia pseudomallei are commercially available. The tests are primarily used in routine diagnosis of melioidosis in major hospitals in Thailand and some endemic countries. Being a rapid test, this technique was employed as a presumptive test to identify colonies of B. pseudomallei among many others grown from soil specimens collected from southern Thailand. Cross-reactivity of these tests with other soil bacteria was a concern since it complicated the identification of B. pseudomallei. Here, we describe the cross-reactivity of two commercial latex agglutination tests for melioidosis with B. territorii, B. pseudomultivorans, B. multivorans and B. cenocepacia isolates from soil.

Metabolomics approach used for understanding temperature-related pectinase activity in Bacillus licheniformis DY2

Abstract

Pectinases are enzymes that catalyze pectin degradation. There is a global demand for pectinases because of their wide utility and catalytic efficiency. Optimization of the fermentation process to increase the pectolytic enzyme activity is generally practiced to lower process costs, but whether temperature influences the metabolome, enhancing pectinase activity, is not known. Here, we developed a metabolomics approach to explore it. The activity of P-DY2 pectinase produced by Bacillus licheniformis DY2 was higher in cells grown at 30°C than those grown at 37 °C. Differential metabolome analysis revealed fluctuating tricarboxylic acid (TCA) cycle at 30 °C. Consistently, the transcripts of TCA cycle genes and activities of pyruvate dehydrogenase and α-Ketoglutaric dehydrogenase were lower at 30 °C than 37 °C. Furthermore, inhibition of pyruvate dehydrogenase and succinate dehydrogenase enhanced the activity of P-DY2, supporting the conclusion that the inactivated pyruvate metabolism and TCA cycle were required for pectinase activity, and that P-DY2 was TCA cycle-independent. Collectively, these findings indicated that fermentation temperature affected P-DY2 activity by metabolic modulation, with an inactivated TCA cycle as a characteristic feature of high P-DY2 activity. More importantly, the present study highlights an approach of promoting pectinase activity through metabolic modulation by using metabolic pathway inhibitors.

Genome analysis of lactic acid bacterial strains selected as potential starters for traditional Slovakian bryndza cheese

Abstract

Genomes of 21 strains of lactic acid bacteria isolated from Slovakian traditional cheeses were sequenced on an Illumina MiSeq platform. Subsequently, they were analysed regarding taxonomic classification, presence of genes encoding defence systems, antibiotic resistance and production of biogenic amines. Thirteen strains were found to carry genes encoding at least one bacteriocin, 18 carried genes encoding at least one restriction-modification system, all strains carried 1–6 prophages and 9 strains had CRISPR-Cas systems. CRISPR-Cas type II-A was the most common, containing 0–24 spacers. Only 10% spacers were found to be homological to known bacteriophage or plasmid sequences in databases. Two Enterococcus faecium strains and a Lactococcus lactis strain carried antibiotic resistance genes. Genes encoding for ornithine decarboxylase were detected in 4 strains and genes encoding for agmatine deiminase were detected in 4 strains. Lb. paraplantarum 251 L appeared to be the most interesting strain, as it contained genes encoding for two bacteriocins, a restriction-modification system, two CRISPR-Cas systems, four prophages and no genes connected with antibiotic resistance or production of biogenic amines.

Preparation Tips for Academic Interviews

AcademicInterviewQuestionsThirty-oneGlobalUniversities

Epidemiology and Immunopathogenesis of Psoriasis and Its Comorbidities

Abstract

Purpose of Review

While psoriasis has traditionally been considered primarily a skin and joint disorder, there is a new appreciation that psoriasis affects multiple organs. In fact, psoriasis is associated with several comorbidities that also affect the vasculature, guts, lung, kidney, and other tissues. This review aims to summarize the epidemiology and immunopathogenesis of psoriasis and its comorbidities.

Recent Findings

We reviewed the current literature characterizing the epidemiology and immune pathways of psoriasis and its comorbidities and report common inflammatory and immune pathways implicated in the pathogenesis of psoriasis and its comorbidities.

Summary

A variety of diseases are associated with psoriasis, including psoriatic arthritis, metabolic syndrome, atherosclerosis and cardiovascular disease, nonalcoholic fatty liver disease, inflammatory bowel disease, uveitis, and chronic obstructive pulmonary disease. These comorbidities share similar inflammatory and immune pathways with those that are classically implicated in psoriasis: especially the adipokines, TH17, and TNF-α.

Advances in Immune Pathways and Pathogenesis of Atopic Dermatitis

Abstract

Purpose of Review

Atopic dermatitis (AD) is a common chronic skin inflammatory disorder characterized by recurrent eczema accompanied by an intractable itch that leads to an impaired quality of life. This review aims to summarize the advances in immune pathways and pathogenesis of AD.

Recent Findings

We review and summarize the current literature characterizing immune pathways and pathogenesis of AD. The complex interplay among skin barrier deficiency, immunological derangement, microbiome dysbiosis especially Staphylococcus aureus predominance, and pruritus contribute to the development, progression, and chronicity of the disease.

Summary

AD is a complex and multifactorial disease. The skin barrier, dysbiosis of the skin microbiome, immune dysregulation, and severe itch all play a part in the pathogenesis of AD. Based on this progress, better targeted therapies are now emerging.

Sensitive and rapid detection of TERT promoter and IDH mutations in diffuse gliomas

Abstract

Background

Mutations in the promoter of telomerase reverse transcriptase (TERTp) and isocitrate dehydrogenase 1 (IDH1) offer objective markers to assist in classifying diffuse gliomas into genetic subgroups. However, traditional mutation detection techniques lack sensitivity, or have long turnaround times, or high costs. We developed GliomaDx, an allele-specific, locked nucleic acid (LNA)-based qPCR assay to overcome these limitations and sensitively detect TERTp and IDH mutations.

Methods

We evaluated the performance of GliomaDx on cell line DNA and frozen tissue diffuse glioma samples with variable tumor percentage to mimic use in clinical settings and validated low percentage variants using sensitive techniques including droplet digital PCR (ddPCR) and next generation sequencing. We also developed GliomaDx Nest, which incorporates a high-fidelity multiplex pre-amplification step prior to allele-specific PCR for low-input samples such as FFPE.

Results

GliomaDx detects the TERTp and IDH1 alterations at an analytical sensitivity of 0.1% mutant allele fraction (MAF), corresponding to 0.2% tumor cellularity. GliomaDx identified TERTp/IDH1 alterations in a cohort of frozen tissue samples with variable tumor percentage of all major diffuse glioma histologic types. GliomaDx Nest is able to detect these hotspot mutations with similar sensitivity from pre-amplified samples and was successfully tested on a cohort of clinical FFPE samples. Testing of a cohort of previously identified TERTp ^WT-IDH^WT gliomas (by Sanger sequencing) revealed that 26.3% harbored low-percentage mutations. Analysis by ddPCR and whole exome sequencing of these tumors confirmed the low mutant fraction of these alterations and overall mutation-based tumor purity.

Conclusions

Our results show that GliomaDx can rapidly detect TERTp/IDH mutations with high sensitivity, identifying cases that might be missed due to the lack of sensitivity of other techniques. This approach may facilitate more objective classification of diffuse glioma samples in clinical settings such as intraoperative diagnosis or in testing cases with low tumor purity.

The role of 13 N -ammonia in the differential diagnosis of gliomas and brain inflammatory lesions

Abstract

Objective

To investigate the utility of ¹³N-ammonia PET/CT imaging in the differential diagnosis of gliomas and brain inflammations.

Methods

¹³N-ammonia PET/CT imaging data of 77 patients with gliomas and 34 patients with brain inflammations were retrospectively analyzed. No patients received any treatment before ¹³N-ammonia imaging. All the patients were diagnosed by stereotactic biopsy or clinical follow-up. Visual and semi-quantitative analysis was performed to analyze the results of ¹³N-ammonia imaging. Finally, the uptake ratios of each lesion were calculated and its differences among different groups were tested with one-way ANOVA.

Results

29.4% inflammations, 51.6% low-grade gliomas and 91.3% high-grade gliomas were positive by visual analysis in ¹³N-ammonia imaging. The sensitivity, specificity and accuracy for the diagnosis of gliomas were 75.3%, 55.8% and 67.8%, respectively. As for semi-quantitative analysis, the T/G ratios of inflammatory lesions, low-grade gliomas and high-grade gliomas were 0.88 ± 0.24, 1.04 ± 0.43 and 1.43 ± 0.49, respectively. One-way ANOVA revealed that the T/G ratios of high-grade gliomas were significantly higher than those of low-grade gliomas and inflammations (P < 0.05), but there was no statistical difference between low-grade gliomas and inflammations (P = 0.118). Among the inflammatory lesions, T/G ratios were not statistically different between infectious and demyelinating lesions (P > 0.05). ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing gliomas from inflammations was 1.21 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 52.9%, 94.4%, 65.3%, 95.7% and 45.9%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas was 1.06 with the AUC 0.78. The sensitivity, specificity, accuracy, PPV and NPV were 81.5%, 67.7%, 76.5%, 81.5% and 67.7%, respectively. ROC curve analysis showed that the optimal cut-off value of T/G ratio in distinguishing high-grade gliomas from low-grade gliomas and inflammations was 1.19 with the AUC 0.84. The sensitivity, specificity, accuracy, PPV and NPV were 70.4%, 85.1%, 78.5%, 79.2% and 78.1%, respectively.

Conclusions

¹³N-ammonia imaging is effective in distinguishing high-grade gliomas from low-grade gliomas and inflammations, but its role in the differential diagnosis of low-grade gliomas and brain inflammatory lesions is limited, and the accuracy needs to be improved.

PD‐L1 methylation regulates PD‐L1 expression and is associated with melanoma survival

Pigment Cell &Melanoma Research, Volume 0, Issue ja, -Not available-.

Therapeutic approaches to pyogenic granuloma: an updated review

International Journal of Dermatology, EarlyView.

Pyoderma gangrenosum associated with dulaglutide therapy

International Journal of Dermatology, EarlyView.

Diffuse palmoplantar keratotic papules and melanosis

International Journal of Dermatology, EarlyView.

Mid borderline leprosy in type Bα Blaschko linear pattern: a rare phenomenon

International Journal of Dermatology, EarlyView.

Crisaborole Ointment Improves Quality of Life of Patients with Mild to Moderate Atopic Dermatitis and Their Families

Abstract

Introduction

The impact of crisaborole ointment, a nonsteroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis (AD), on quality of life (QoL) was assessed in two identically designed phase 3 studies (AD-301: NCT02118766; AD-302: NCT02118792, both at http://www.clinicaltrials.gov).

Methods

In both studies, patients aged ≥ 2 years with mild to moderate AD per the Investigator's Static Global Assessment were randomly assigned 2:1 to receive crisaborole or vehicle twice daily for 28 days. QoL was assessed using the Children's Dermatology Life Quality Index (CDLQI) (2–15 years), the Dermatology Life Quality Index (DLQI) (≥ 16 years), and the Dermatitis Family Impact Questionnaire (DFI) (parents/caregivers/family of patients aged 2–17 years). Established QoL score severity bands provided clinical context.

Results

Greater mean improvement in QoL was observed in crisaborole-treated patients than in vehicle-treated patients at day 29 [mean change from baseline (∆BL), CDLQI: − 4.6 vs. − 3.0; P < 0.001; DLQI: − 5.2 vs. − 3.5; P = 0.015]. At baseline, more than half the patients had a "moderate effect" or higher of AD on QoL. At day 29, there was a trend toward more crisaborole- than vehicle-treated patients having "small effect" to "no effect", The QoL of parents/caregivers/family improved more for crisaborole-treated than for vehicle-treated patients (∆BL, DFI: − 3.7 vs. − 2.7; P = 0.003).

Conclusion

Crisaborole treatment results in clinically meaningful improvement in QoL for patients and their parents/caregivers/families.

Trial Registration

AD-301: http://www.clinicaltrials.gov, NCT02118766; AD-302: http://www.clinicaltrials.gov, NCT02118792.

Funding

Anacor Pharmaceuticals, Inc., a wholly owned subsidiary of Pfizer Inc., New York, NY.