Low-Divergence hBN Single-Photon Source with a 3D-Printed Low-Fluorescence Elliptical Polymer Microlens.

Efficiently collecting light from single-photon emitters is crucial for photonic quantum technologies. Here, we develop and use an ultralow fluorescence photopolymer to three-dimensionally print micrometer-sized elliptical lenses on individual precharacterized single-photon emitters in hexagonal boron nitride (hBN) nanocrystals, operating in the visible regime. The elliptical lens design beams the light highly efficiently into the far field, rendering bulky objective lenses obsolete. Using back focal plane imaging, we confirm that the emission is collimated to a narrow low-divergence beam with a half width at half-maximum of 2.2°. Using photon correlation measurements, we demonstrate that the single-photon character remains undisturbed by the polymer lens. The strongly directed emission and increased collection efficiency is highly beneficial for quantum optical experiments. Furthermore, our approach paves the way for a highly parallel fiber-based detection of single photons from hBN nanocrystals.

Efficacy and safety of Oleogel-S10 (birch triterpenes) for epidermolysis bullosa: results from the phase III randomized double-blind phase of the EASE study.

BACKGROUND: Epidermolysis bullosa (EB) is a heterogeneous group of rare, difficult-to-treat, inherited multisystem diseases affecting epithelial integrity. Patients with EB are affected by mechanical fragility of epithelial surfaces including the skin and, as a result, extensive recurrent blistering is a characteristic of the condition. Chronic wounds predispose patients with EB to the development of squamous cell carcinoma, which is a major cause of premature death. OBJECTIVES: EASE was a double-blind, randomized, vehicle-controlled, phase III study to determine the efficacy and safety of the topical gel Oleogel-S10 (birch triterpenes) in EB. EASE was funded by Amryt Research Limited. METHODS: Patients with dystrophic EB, junctional EB or Kindler EB and a target partial-thickness wound lasting ≥ 21 days and < 9 months that was 10-50 cm2, were enrolled and randomized via computer-generated allocation tables 1 : 1 to Oleogel-S10 or control gel - both with standard-of-care dressings. Study gel was applied to all wounds at least every 4 days. The primary endpoint was the proportion of patients with first complete closure of target wound within 45 days. RESULTS: A total of 223 patients were enrolled and treated (109 treated with Oleogel-S10, 114 with control gel). The primary endpoint was met; Oleogel-S10 resulted in 41·3% of patients with first complete target wound closure within 45 days, compared with 28·9% in the control gel arm (relative risk 1·44, 95% confidence interval (CI) 1·01-2·05; P = 0·013). Adverse events (AEs) occurred with similar frequency for Oleogel-S10 (81·7%) compared with control gel (80·7%). AEs were predominantly of mild-to-moderate intensity (4·6% were severe). CONCLUSIONS: Oleogel-S10 is the first therapy to demonstrate accelerated wound healing in EB. Oleogel-S10 was well -tolerated.

CSL324, a granulocyte colony-stimulating factor receptor antagonist, blocks neutrophil migration markers that are upregulated in hidradenitis suppurativa.

BACKGROUND: Neutrophils have been shown to contribute to the pathophysiology of hidradenitis suppurativa (HS), a chronic, painful and debilitating inflammatory skin disease, yet their exact role remains to be fully defined. Granulocyte colony-stimulating factor (G-CSF), a major regulator of neutrophil development and survival, can be blocked by the novel, fully human anti-G-CSF receptor (G-CSFR) monoclonal antibody CSL324. OBJECTIVES: We investigated the activation and migration of neutrophils in HS and the impact of blocking G-CSFR with CSL324. METHODS: Biopsy and peripheral blood samples were taken from participants of two studies: 2018.206, a noninterventional research study of systemic and dermal neutrophils and inflammatory markers in patients with neutrophilic skin diseases, and CSL324_1001 (ACTRN12616000846426), a single-dose ascending and repeated dose, randomized, double-blind, placebo-controlled study to assess the safety, pharmacokinetics and pharmacodynamics of CSL324 in healthy adult subjects. Ex vivo experiments were performed, including neutrophil enumeration and immunophenotyping, migration, receptor occupancy and transcriptome analysis. RESULTS: The number of cells positive for the neutrophil markers myeloperoxidase (MPO) and neutrophil elastase (NE) was significantly higher in HS lesions compared with biopsies from healthy donors (HDs) (P < 0.0001 and P = 0.0223, respectively). In peripheral blood samples, mean neutrophil counts were significantly higher in patients with HS than in HDs (2.98 vs. 1.60 × 109 L-1, respectively; P = 8.8 × 10-4). Neutrophil migration pathways in peripheral blood were increased in patients with HS and their neutrophils demonstrated an increased migration phenotype, with higher mean CXCR1 on the surface of neutrophils in patients with HS (24453.20 vs. 20798.47 for HD; P = 0.03). G-CSF was a key driver of the transcriptomic changes in the peripheral blood of patients with HS and was elevated in serum from patients with HS compared with HDs (mean 6.61 vs. 3.84 pg mL-1, respectively; P = 0.013). Administration of CSL324 inhibited G-CSF-induced transcriptional changes in HDs, similar to those observed in the HS cohort, as highlighted by expression changes in genes related to neutrophil migratory capacity. CONCLUSIONS: Data suggest that neutrophils contribute to HS pathophysiology and that neutrophils are increased in lesions due to an increase in G-CSF-driven migration. CSL324 counteracted G-CSF-induced transcriptomic changes and blocked neutrophil migration by reducing cell-surface levels of chemokine receptors.

Clinical and dermoscopic features of nail unit melanoma in an Australian nail clinic cohort.

Nail unit melanoma carries diagnostic challenges conferring with its poor prognosis. This audit aims to characterise both clinical and dermoscopic features of nail unit malignant lesions and compare them with biopsied benign lesions. It focuses on informing future practice by aiding in the stratification and recognition of malignant diagnostic patterns in the Australian context.

Clinical and histopathological features of onychopapilloma in an Australian setting: A case series of 50 patients.

Onychopapilloma is an uncommon tumour of the nailbed and the distal nail matrix. To date, only 19 case reports and case series have been reported in the literature. This article includes literature review on all reported cases and provides the first case series of onychopapilloma in an Australian population, evaluating the clinical features and histopathological diagnosis of patients with onychopapilloma in an Australian subspecialty nail clinic.

Intraoral human herpes viruses detectable by PCR in majority of patients.

OBJECTIVES: To identify factors which influence the intraoral prevalence of human herpes viruses (HHVs) using mucosal swabs, saliva samples and qPCR analysis. METHODOLOGY: In this cross-sectional observational study, matched saliva and oral swabs were collected from a total of 115 subjects: 70 immunocompetent subjects with no mucosal abnormalities, 22 with mucosal abnormalities and 23 therapeutically immunocompromised individuals. Extracted DNA was analysed by multiplex qPCR for detection and quantification of HHVs 1-6. RESULTS: At least one human herpes virus was detected in 77.1% of immunocompetent individuals with no mucosal abnormalities, with EBV the most commonly detected at 61.4%. HHV-6 was detected in 17.1%, HSV-1 in 4.3% and CMV in 1.1%. Detection was higher in saliva than in oral swabs. There was no detection of HSV-2 or VZV. Neither presence of oral mucosal abnormality nor therapeutic immunocompromise was related to increased detection of human herpes virus. CONCLUSION: Commensal detection rates of EBV are high, and caution in clinical correlation of positive detection is warranted. Commensal CMV rates are low, and detection is likely to be clinically relevant. This study presents a comprehensive commensal detection rate of HHVs 1-6 by qPCR in saliva and swabs.

A casemix study of patients seen within an urban Aboriginal Health Service dermatology clinic over a five-year period.

This is the largest study of Aboriginal and Torres Strait Islander dermatologic presentations to an urban specialist clinic within a community-controlled health organisation. It adds to our understanding of Aboriginal and Torres Strait Islander dermatoepidemiology. Patient files were reviewed over the five-year audit period, with age, gender, Indigenous status, diagnosis, disease category, 'new' or 'review consultation' and 'did not attend' (DNA) data recorded. Our study shows that eczema and benign, pre-malignant or malignant neoplasms are the most common presentations for urban Aboriginal and Torres Strait Islander patients. Lupus erythematosus and cutaneous infections were less prominent in comparison to data from rural and remote populations. Overall, a broad casemix of dermatologic presentations was observed. Similar to other studies, adult male patients were under-represented. Most skin malignancies were diagnosed in this cohort; this, therefore, identifies a possible target for public health intervention. A high ratio of new to review patients is consistent with the clinic offering a consultation model of care facilitated by primary health-care providers' support within Aboriginal Community-Controlled Health Service. DNA rates in this study were lower than hospital outpatient rates in a comparative study and may be attributed to specialist dermatology care being offered in a more culturally sensitive environment. The dermatology clinic at the Victorian Aboriginal Health Services (VAHS) provides a good breadth of specialist dermatology care. The community health-care model could be replicated in centres elsewhere, including interstate, to help overcome barriers to specialist dermatology care experienced by Aboriginal and Torres Strait Islander populations. Additionally, this model improves trainee exposure and understanding of Aboriginal and Torres Strait Islander health.

Successful management of treatment resistant nail psoriasis with tildrakizumab.

Nail psoriasis significantly impacts quality of life and is notoriously difficult to treat. Tildrakizumab, an IL-23 inhibitor, has shown significant clinical improvement in the treatment of moderate-to-severe chronic plaque psoriasis. We report 2 cases of treatment resistant nail psoriasis which showed marked improvement with the use of off-label tildrakizumab. The dosing regimen utilised was consistent with that used to treat chronic plaque psoriasis, with 100 mg subcutaneously at Day 0 and Week 4, and maintenance dosing of 100 mg every 12 weeks thereafter. Significant improvement at 6 and 12 months, as per the modified Nail Psoriasis Severity Index (mNAPSI) and Dermatology Life Quality Index (DLQI), was seen. There have been no tildrakizumab related side effects observed to date. Tildrakizumab appears to be an effective option in managing treatment resistant nail psoriasis.

Comparison of the EUROIMMUN Dermatology Profile ELISA to the novel BIOCHIP Mosaic 7 for the diagnosis of immunobullous skin disease.

BACKGROUND: The BIOCHIP is an indirect immunofluorescence diagnostic investigation which identifies multiple autoantibodies with a mosaic panel of target antigen-specific substrates in a single incubation field. The EUROIMMUN Dermatology Profile ELISA allows simultaneous investigation of the six most important autoantibodies in bullous autoimmune dermatoses. Evaluation of the BIOCHIP Mosaic 7, compared to that of the EUROIMMUN Dermatology Profile ELISA, when used as a diagnostic investigation in pemphigus and pemphigoid, was undertaken in an Australian cohort. METHODS: The serum of 27 patients was analysed including patients with pemphigus vulgaris (n = 10), pemphigus foliaceous (n = 4), bullous pemphigoid (n = 8), mucous membrane pemphigoid (n = 3) and negative controls (n = 2). Results of the BIOCHIP were compared with the EUROIMMUN Dermatology Profile ELISA, as well as with histology, direct immunofluorescence and indirect immunofluorescence. RESULTS: In pemphigus vulgaris, sensitivity & specificity for the BIOCHIP Mosaic 7 were 100% and 94.1%, comparable to that of the EUROIMMUN Dermatology Profile ELISA with 80% sensitivity and 100% specificity. In bullous pemphigoid, sensitivity of the BIOCHIP was 87.5% and sensitivity of the EUROIMMUN Dermatology ELISA profile was 75%, whilst specificities for both diagnostic methods were 100% in our limited cohort. There was substantial or almost perfect concordance between the BIOCHIP Mosaic 7 and EUROIMMUN Dermatology Profile ELISA for pemphigus vulgaris and bullous pemphigoid. CONCLUSION: The BIOCHIP Mosaic 7 is a rapid, reliable diagnostic investigation in pemphigus and bullous pemphigoid. Results indicate it is comparable to the EUROIMMUN Dermatology Profile ELISA, whilst also providing additional testing with salt split skin, on one field.

Excited-State Trions in Monolayer WS_{2}.

We discover an excited bound three-particle state, the 2s trion, appearing energetically below the 2s exciton in monolayer WS_{2}, using absorption spectroscopy and ab initio GW and Bethe-Salpeter equation calculations. The measured binding energy of the 2s trion (22 meV) is smaller compared to the 1s intravalley and intervalley trions (37 and 31 meV). With increasing temperature, the 1s and 2s trions transfer their oscillator strengths to the respective neutral excitons, establishing an optical fingerprint of trion-exciton resonance pairs. Our discovery underlines the importance of trions for the entire excitation spectrum of two-dimensional semiconductors.

Esophageal lichen planus: towards diagnosis of an underdiagnosed disease.

Background: Although lichen planus (LP) is a common skin disorder, the prevalence of esophageal involvement (ELP) and its clinical manifestations are poorly defined. We aimed to establish diagnostic criteria and characterize disease outcomes of ELP.Methods: Clinical, endoscopic, histological, and immunofluorescence data from consecutive patients with known LP between 2013 and 2018 were analyzed. We established endoscopic (denudation and tearing of the mucosa, hyperkeratosis and trachealization) and histological criteria (mucosal detachment, T-lymphocytic infiltrate, intraepithelial apoptosis, dyskeratosis, and fibrinogen deposits along the basement membrane) to grade disease severity. Endoscopic findings were correlated with clinical symptoms. Response to medical therapy was monitored.Results: Fifty-two consecutive patients (median age 59.5 years) were analyzed. According to our grading system, 16 patients were considered as severe and 18 as mild ELP. Dysphagia was the only symptom which differentiated patients with severe (14/16) or mild ELP (8/18) from patients without ELP (1/18). Concomitant oral and genital involvement of LP was associated with the presence of ELP, while oral involvement alone was not. Follow-up of 14/16 patients with severe EPL for at least one year revealed that most of these patients responded to topical corticosteroids (budesonide: n = 9/10 or fluticasone n = 2/2). Three budesonide patients experienced a resolution of symptomatic esophageal stenosis.Conclusions: Esophageal involvement of LP is frequent, but may be asymptomatic. ELP can be diagnosed using the diagnostic criteria proposed here. Dysphagia and combined oral and genital manifestation are associated with ELP. Therapy with topical corticosteroids appears to be a prudent therapeutic approach for ELP.

Eosinophilic dermatosis of hematologic malignancy: Correlation of molecular characteristics of skin lesions and extracutaneous manifestations of hematologic malignancy.

BACKGROUND: Skin diseases are frequent in patients with chronic lymphocytic leukemia (CLL) and other hematological neoplasias. Eosinophilic dermatosis (ED) of hematologic malignancy has long been considered a nonspecific cutaneous reaction pattern. Recently neoplastic cells have been shown to be present in ED, thus challenging the classification as a nonspecific dermatosis. METHODS: We report five patients with ED in association with CLL. We further investigated the presence of neoplastic B-cells in the skin infiltrate by immunohistochemistry and immunoglobulin heavy chain rearrangement and compared these to extracutaneous manifestations of CLL. RESULTS: The phenotype of the lymphocytic infiltrate was predominately CD3+ (range: 60%-90%). CD20+ and CD79a+ lymphocytes were less frequent, accounting for up to 15% (range: absent - 15%). CD23+ lymphocytes represented up to 20% (range: absent - 20%) of the infiltrate. The analysis of the immunoglobulin heavy chain rearrangement in the skin specimens showed clonal rearrangements in 4/5 patients and in three of these four patients clones were identical to extracutaneous CLL manifestations. CONCLUSION: Our data show that neoplastic B-cells are very frequently found in ED when systematically evaluated. This findings support the hypothesis that leukemic cells play a pathogenetic role in ED of hematologic malignancy.

Targeting of Cell Surface Proteolysis of Collagen XVII Impedes Squamous Cell Carcinoma Progression.

Squamous cell carcinoma (SCC) is one of the most common skin cancers and causes significant morbidity. Although the expression of the epithelial adhesion molecule collagen XVII (ColXVII) has been linked to SCC invasion, only little is known about its mechanistic contribution. Here, we demonstrate that ColXVII expression is essential for SCC cell proliferation and motility. Moreover, it revealed that particularly the post-translational modification of ColXVII by ectodomain shedding is the major driver of SCC progression, because ectodomain-selective immunostaining was mainly localized at the invasive front of human cutaneous SCCs, and exclusive expression of a non-sheddable ColXVII mutant in SCC-25 cells inhibits their matrix-independent growth and invasiveness. This cell surface proteolysis, which is strongly elevated during SCC invasion and metastasis, releases soluble ectodomains and membrane-anchored endodomains. Both released ColXVII domains play distinct roles in tumor progression: the endodomain induces proliferation and survival, whereas the ectodomain accelerates invasiveness. Furthermore, specific blockage of shedding by monoclonal ColXVII antibodies repressed matrix-independent growth and invasion of SCC cells in organotypic co-cultures. Thus, selective inhibition of ColXVII shedding may offer a promising therapeutic strategy to prevent SCC progression.

Late-onset malalignment of the great toenails.

Great toenail malalignment is characterised by lateral deviation of the longitudinal axis of the nail plate with respect to the hallux, and is usually post-traumatic, iatrogenic or due to congenital malalignment of the great toenails. We present cases of great toenail malalignment with onset in adolescence or young adulthood without preceding nail surgery or acute trauma. We postulate that this may represent a late-onset presentation of congenital malalignment of the great toenails.

Incorporation of oxygen atoms as a mechanism for photoluminescence enhancement of chemically treated MoS2.

Chemical treatments to enhance photoluminescence (PL) in MoS2 have been explored extensively by experimental means in recent years. However, satisfactory theoretical explanations of the underlying mechanisms remain elusive. In this work, the surface reactions of the superacid bis(trifluoromethane)-sulfonimide (TFSI), hydrogen peroxide (H2O2), molecular oxygen (O2), and sulfuric acid (H2SO4) on a defective MoS2 monolayer have been studied using first principles calculations. An oxygen transfer reaction into a sulfur vacancy with a low activation barrier and thus significant reaction rates already at room temperature has been found. Band structure unfolding techniques show that the incorporation of oxygen atoms into sulfur vacancies restores the band structure of pristine MoS2, which is predicted to have a high PL quantum yield. PL spectroscopy is used to examine the effect of chemical treatment on PL intensity. Our experimental findings support our theoretical predictions, as PL in MoS2 is enhanced by up to a factor 20 after treatment with H2O2 or H2SO4, while the spectral shape is only slightly altered.

On-Chip Waveguide Coupling of a Layered Semiconductor Single-Photon Source.

Fully integrated quantum technology based on photons is in the focus of current research, because of its immense potential concerning performance and scalability. Ideally, the single-photon sources, the processing units, and the photon detectors are all combined on a single chip. Impressive progress has been made for on-chip quantum circuits and on-chip single-photon detection. In contrast, nonclassical light is commonly coupled onto the photonic chip from the outside, because presently only few integrated single-photon sources exist. Here, we present waveguide-coupled single-photon emitters in the layered semiconductor gallium selenide as promising on-chip sources. GaSe crystals with a thickness below 100 nm are placed on Si3N4 rib or slot waveguides, resulting in a modified mode structure efficient for light coupling. Using optical excitation from within the Si3N4 waveguide, we find nonclassicality of generated photons routed on the photonic chip. Thus, our work provides an easy-to-implement and robust light source for integrated quantum technology.