Sinecatechins ointment as a potential novel treatment for usual type vulval intraepithelial neoplasia: a single-centre double-blind randomised control study.

OBJECTIVE: To compare the safety and efficacy of 10% sinecatechins (Veregen® ) ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). DESIGN: A Phase II double-blind randomised control trial. SETTING: A tertiary gynaecological oncology referral centre. POPULATION: All women diagnosed with primary and recurrent uVIN. METHODS: Eligible patients were randomised 1:1 to receive either sinecatechins or placebo ointment (applied three times daily for 16 weeks) and were followed up at 2, 4, 8, 16, 32 and 52 weeks. MAIN OUTCOME MEASURES: The primary outcome measure, recorded at 16 and 32 weeks, was histological response (HR). Secondary outcome measures included clinical (CR) response, toxicity, quality of life and pain scores. RESULTS: There was no observed difference in HR between the two arms. However, of the 26 patients who were randomised, all 13 patients who received sinecatechins showed either complete (n = 5) or partial (n = 8) CR, when best CR was evaluated. In placebo group, three patients had complete CR, two had partial CR, six had stable disease and two were lost to follow up. Patients in the sinecatechins group showed a statistically significant improvement in best observed CR as compared with the placebo group (P = 0.002). There was no difference in toxicity reported in either group. CONCLUSION: Although we did not observe a difference in HR between the two treatment arms, we found that 10% sinecatechins application is safe and shows promise in inducing clinical resolution of uVIN lesions and symptom improvement, thus warranting further investigation in a larger multicentre study. TWEETABLE ABSTRACT: A randomised control study indicating that sinecatechins ointment may be a novel treatment for uVIN.

Restoring Superconductivity in the Quantum Metal Phase of NbSe2 Using Dissipative Coupling.

Localization arguments forbid the appearance of a metallic ground state in two dimensions. Yet, a large variety of disordered superconductors are known to manifest an anomalous metal phase in the zero temperature limit. While previous observations were confined to noncrystalline "dirty" superconductors, the recent observation of the so-called Bose metal phase in crystalline thin flakes of NbSe2 has sparked off intense debate. While the exact nature of this phase remains unknown, it is thought that quantum fluctuations play a decisive role in Bose metal physics. In this work, we study the response of the anomalous metal phase in thin flakes of NbSe2 to dissipative coupling. We evince a dramatic quenching of the Bose metal phase when dissipative coupling is strong, fully restoring a zero resistance superconducting state in the entire region of the magnetic field (H)-temperature (T) phase diagram where the Bose metal phase is otherwise observed. The suppression of the Bose metal phase by dissipative coupling is possible only in a quantum system where dissipation can directly affect system thermodynamics. Our observation of a dissipative phase transition in two-dimensional NbSe2 firmly establishes the quantum nature of the anomalous metal phase in this class of "clean" superconductors.

Adjacent Lichen Sclerosis predicts local recurrence and second field tumour in women with vulvar squamous cell carcinoma.

OBJECTIVE: In this study, we investigated if the presence of histologically abnormal epithelium adjacent to the primary tumour influenced the frequency, timing, and topography of local vulvar recurrences (LVR) following treatment for squamous cell carcinoma of the vulva (VSCC). METHODS: The study population comprised a cohort of 201 consecutive cases with incident VSCC. LVR were categorised as local relapses (LR) if they occurred <2cm from the tumour margins, and as second field tumours (SFT) when ≥2cm from these margins. Univariable and multivariable competing risk modelling was performed to identify the prognostic factors associated with local disease recurrence. RESULTS: The characterization of the epithelium adjacent to the invasive component was possible for 199 (99.0%) patients. Of these, 171 (85.9%) were found to have intraepithelial abnormalities found adjacent to the surgical specimen. Multivariable analyses revealed that, following adjustment, Lichen Sclerosis (LS) was associated with an increase in the incidence of LVR, LR and SFT (SHRs: 3.4, 2.7 and 4.4, respectively). Although the incidence of LR and SFT in women with LS associated VSCC was similar, the peak incidence of SFT occurred more than two years before that of LR. CONCLUSIONS: Women with VSCC arising in a field of LS may continue to have an increased risk of developing LR and SFT for many years after resection of their primary tumour. Our study suggests that these women should be followed up more regularly so that LVR can be detected earlier; unless a more robust surveillance programme or chemopreventative treatments become available.

Sentinel lymph node biopsy in vulval cancer: systematic review and meta-analysis.

BACKGROUND: The purpose of this study was to determine the accuracy of sentinel lymph node (SLN) biopsy with technetium 99 (99mTc) and/or blue dye-enhanced lymphoscintigraphy in vulval cancer. METHODS: Sensitive searches of databases were performed upto October 2013. Studies with at least 75% of women with FIGO stage IB or II vulval cancer evaluating SLN biopsy with 99mTc, blue dye or both with reference standard of inguinofemoral lymphadenectomy (IFL) or clinical follow-up were included. Meta-analyses were performed using Meta-Disc version 1.4. RESULTS: Of the 2950 references, 29 studies (1779 women) were included; most of them evaluated 99mTc combined with blue dye. Of these, 24 studies reported results for SLN followed by IFL, and 5 reported clinical follow-up only for SLN negatives. Pooling of all studies was inappropriate because of heterogeneity. Mean SLN detection rates were 94.0% for 99mTc, 68.7% for blue dye and 97.7% for both. SLN biopsy had pooled sensitivity of 95% (95% CI 92-98%) with negative predictive value (NPV) of 97.9% in studies using 99mTc/blue dye, ultrastaging and immunohistochemistry with IFL as reference. Pooled sensitivity for SLN with clinical follow-up for SLN-negatives was 91% (85-95%) with NPV 95.6%. Patients undergoing SLN biopsy experienced less morbidity than those undergoing IFL. CONCLUSIONS: Sentinel lymph node biopsy using 99mTC, blue dye and ultrastaging with immunohistochemistry is highly accurate when restricted to carefully selected patients, within a rigorous protocol, with close follow-up and where sufficient numbers for learning curve optimisation exist. Patients must make an informed choice between the slightly higher groin recurrence rates of SLN biopsy vs the greater morbidity of IFL.

Rapid determination of main constituents of packed juices by reverse phase-high performance liquid chromatography: an insight in to commercial fruit drinks.

The present work reports the compositional analysis of thirteen different packed fruit juices using high performance liquid chromatography (HPLC). Vitamin C, organic acids (citric and malic) and sugars (fructose, glucose and sucrose) were separated, analyzed and quantified using different reverse phase methods. A new rapid reverse phase HPLC method was developed for routine analysis of vitamin C in fruit juices. The precision results of the methods showed that the relative standard deviations of the repeatability and reproducibility were <0.05 and <0.1 respectively. Correlation coefficient of the calibration models developed was found to be higher than 0.99 in each case. It has been found that the content of Vitamin C was less variable amongst different varieties involved in the study. It is also observed that in comparison to fresh juices, the packed juices contain lesser amounts of vitamin C. Citric acid was found as the major organic acids present in packed juices while maximum portion of sugars was of sucrose. Comparison of the amount of vitamin C, organic acids and sugars in same fruit juice of different commercial brands is also reported.

The chromatin landscape of high-grade serous ovarian cancer metastasis identifies regulatory drivers in post-chemotherapy residual tumour cells.

Disease recurrence following chemotherapy is a major clinical challenge in ovarian cancer (OC), but little is known regarding how the tumour epigenome regulates transcriptional programs underpinning chemoresistance. We determine the single cell chromatin accessibility landscape of omental OC metastasis from treatment-naïve and neoadjuvant chemotherapy-treated patients and define the chromatin accessibility profiles of epithelial, fibroblast, myeloid and lymphoid cells. Epithelial tumour cells display open chromatin regions enriched with motifs for the oncogenic transcription factors MEIS and PBX. Post chemotherapy microenvironments show profound tumour heterogeneity and selection for cells with accessible chromatin enriched for TP53, TP63, TWIST1 and resistance-pathway-activating transcription factor binding motifs. An OC chemoresistant tumour subpopulation known to be present prior to treatment, and characterised by stress-associated gene expression, is enriched post chemotherapy. Nuclear receptors RORa, NR2F6 and HNF4G are uncovered as candidate transcriptional drivers of these cells whilst closure of binding sites for E2F2 and E2F4 indicate post-treated tumour having low proliferative capacity. Delineation of the gene regulatory landscape of ovarian cancer cells surviving chemotherapy treatment therefore reveals potential core transcriptional regulators of chemoresistance, suggesting novel therapeutic targets for improving clinical outcome.

The use of sentinel node sampling in vulval cancer.

Between March 2007 and December 2009, 38 patients underwent sentinel lymph node biopsy (SLNB) sampling, along with vulvectomy, in their management of vulval cancer. A review has been conducted to establish the reliability and accuracy of the new procedure compared with the traditional total inguinofemoral lymphadenectomy. We also aimed to establish both the short- and long-term morbidities of both total inguinofemoral lymphadenectomy and SLNB and to assess the duration of hospital stay in both groups. Our data have shown a reduced short- and long-term morbidity and reduced length of hospital stay for the SLNB procedure. We conclude that it is a reliable and safe procedure, however it should only be conducted in cancer centres.

Correction: Influence of time dependent laser-irradiation for tuning the linear-nonlinear optical response of quaternary Ag10In15S15Se60 films for optoelectronic applications.

[This corrects the article DOI: 10.1039/D2RA07981J.].

Bulk-surface coupling in dual topological insulator Bi1Te1and Sb-doped Bi1Te1single crystals via electron-phonon interaction.

Recently,Bi1Te1has been proved to be a dual topological insulator (TI), a new subclass of symmetry-protected topological phases, and predicted to be higher order topological insulator (HOTI). Being a dual TI (DTI), Bi1Te1is said to host quasi-1D surface states (SSs) due to weak TI phase and topological crystalline insulating SSs at the same time. On the other hand, HOTI supports topologically protected hinge states. So,Bi1Te1is a unique platform to study the electrical signature of topological SS (TSS) of fundamentally different origins. Though there is a report of magneto-transport measurements on large-scale Bi1Te1thin films, the Bi1Te1single crystal is not studied experimentally to date. Even the doping effect in a DTI Bi1Te1is missing in the literature. In this regard, we performed the perpendicular and parallel field magneto-transport measurement on the exfoliated microflake of Bi1Te1and Sb-doped Bi1Te1single crystals, grown by the modified Bridgmann method. Ourmetallicsample shows the weak anti-localization behavior analyzed by the multi-channel Hikami-Larkin-Nagaoka equation. We observed the presence of a pair of decoupled TSS. Further, we extracted the dephasing index (ß) from temperature (T)-dependence of phase coherence length (Lϕ), following the power law equation (Lϕ∝T-ß). The thickness-dependent value ofßindicates the transition in the dephasing mechanism from electron-electron to electron-phonon interaction with the increase in thickness, indicating the enhancement in the strength of bulk-surface coupling. Sb-doped system shows weakened bulk-surface coupling, hinted by the reduced dephasing indices.

Influence of time dependent laser-irradiation for tuning the linear-nonlinear optical response of quaternary Ag10In15S15Se60 films for optoelectronic applications.

The impact of laser irradiation on thin films results in multiple beneficial modifications of their structural, morphological, nonlinear-linear properties for optoelectronics applications. This work deals with the thermally evaporated Ag10In15S15Se60 films and post-laser irradiation to study the variations in structural and optical properties. The current investigation was carried out for different laser irradiation time durations such as 0, 10, 20, 30, and 60 minutes by 532 nm laser (2.34 eV). According to the X-ray diffraction analysis, all thin films have polycrystalline character. The change in the surface morphology after being exposed to the laser has been checked by FESEM, whereas the presence of constitutional elements has been verified by the EDX study. The related changes with laser irradiation in the optical properties, including both linear and nonlinear, were studied using UV-Vis spectroscopy data. The irradiation caused an enhancement in the transmission, and the absorption edge moved towards a lower wavelength, increasing the bandgap energy from 1.71 eV to 1.88 eV. The refractive index reduced as a result of the film's altered structure. The behaviour of the refractive index satisfies Moss's rule (E g n 4 = const). The nonlinear refractive index, first-order and 3rd order nonlinear susceptibility, is found to be decreased with laser irradiation. The dielectric parameters are also observed to be decreased with irradiation. Considering all the alterations in its properties caused by irradiation, the Ag10In15S15Se60 sample could be a favourable material for various photonic devices.

Annealing-induced phase transformation in In10Se70Te20 thin films and its structural, optical and morphological changes for optoelectronic applications.

In2Se3 and In2Te3 have great importance in various device fabrications. The present report is based on the annealing-induced phase formation of both In2Se3 and In2Te3 from In10Se70Te20 thin films at different annealing temperatures as found from the XRD analysis and well supported by the Raman study. The average crystallite size increased with a decrease in the dislocation density. The surface morphology changed with annealing and increased in particle size as noticed from the FESEM images. The uniform distribution and presence of constituent elements in the film were verified using EDX data. The increase in transmittance is accompanied by a decrease in extinction coefficient, optical density and increase in skin depth with annealing. The increase in optical bandgap from 0.418 eV to 0.645 eV upon annealing at 250 °C is associated with a decrease in disorder. The steepness parameter increased and the Se-p value decreased with annealing. The refractive index decreased with an increase in oscillator energy and decrease in dispersion energy. The quality factor, dielectric loss, optical conductivity and electrical susceptibility decreased. The optical electronegativity and plasma frequency increased with annealing. There is a significant change in the non-linear susceptibility and non-linear refractive index with annealing. The observed changes in the film structure and optical behaviour are due to the annealing-induced phase formation from the In10Se70Te20 host matrix upon annealing. Such materials are suitable for optoelectronic and phase change devices.

Correction: In situ laser irradiation: the kinetics of the changes in the nonlinear/linear optical parameters of As50Se40Sb10 thin films for photonic applications.

[This corrects the article DOI: 10.1039/D1RA02368C.].

Probing electron-phonon and phonon-phonon coupling in type-II Dirac semi-metal NiTe2via temperature-dependent Raman spectroscopy.

We report the temperature-dependent structural characterization of type-II Dirac semimetal NiTe2in the form of a bulk single crystal and a nanoflake (200 nm thick). Detailed x-ray diffraction study along with Rietveld refinement analysis reveals superior crystallinity and linear thermal expansion coefficient (αT) of 5.56 × 10-6and 22.5 × 10-6K-1along a or b and c lattice directions, respectively. Temperature evolution of Raman spectra shows non-linear variations in the phonon frequency and full-width half maxima of the out-of-plane A1gand in-plane Egmodes. Raman mode E2g1, corresponding to an in-plane vibration, disappears on decreasing the thickness from bulk to nanoflake. Quantitative analysis with anharmonic model yields dominating electron-phonon interaction over phonon-phonon interaction mediated by three- and four-phonon processes.

Crossover from gapped-to-gapless Dirac surface states in magnetic topologicalinsulator MnBi2Te4.

Intrinsic magnetic topological insulators (MTI) host exotic topological phases such as quantized anomalous Hall insulating phase, arising due to the large magnetic exchange gap. However, the interplay of magnetism and topology in these systems in different temperature regimes remains elusive. In this work, we present the logarithmic temperature-dependence of conductivity for sub-100 nm thick exfoliated flakes of MTI MnBi2Te4 in the presence of out-of-plane magnetic fields and extracted the linear slope, κ. We observed a characteristic change, ∆κ ∼ -0.5 in the low-temperature regime, indicating the gapped Dirac surface state according to Lu-Shen theory. We also report the recovery of topological properties in the system via the weak-antilocalization (WAL) effect in the vicinity of antiferromagnetic to paramagnetic transition and in the paramagnetic regime. Hikami-Larkin-Nagaoka (HLN) analysis suggested the presence of topological surface states. Therefore, our study helps in understanding how intrinsic magnetism masks topological properties in an MTI as long as magnetic ordering persists. .

The impact of fluence dependent proton ion irradiation on the structural and optical properties of Bi5In30Se65 thin films for nonlinear optical devices.

This paper reports the effects of ion irradiation on the structural, linear, and nonlinear optical properties of thermally evaporated Bi5In30Se65 thin films. The prepared films were irradiated with 30 keV proton ions with different fluences, such as 5 × 1015 ions per cm2, 1 × 1016 ions per cm2, and 5 × 1016 ions per cm2. Structural analysis via X-ray diffraction (XRD) confirmed the non-crystalline nature of the film after ion irradiation with different doses. However, after the irradiation dose, the surface morphology changed, as shown by atomic force microscopy (AFM) images and field emission scanning electron microscopy (FESEM) images. The compositions of the films were obtained using energy-dispersive X-ray spectroscopy (EDX). Optical analysis via UV-Visible spectroscopy showed a reduction in the transmittance and an increase in the absorption in the higher wavelength region with irradiation. The optical bandgap and Tauc parameter decreased with an increase in the irradiation fluence, which is due to an increase in the irradiation-induced defects and disorder inside the system. The increases in the third order nonlinear susceptibility and the nonlinear refractive index with ion fluence are useful for nonlinear optical applications. The linear refractive index calculated from the transmittance data increased, satisfying Moss's rule. The optical parameters, such as lattice dielectric constant, optical density, skin depth, optical conductivity, real and imaginary dielectric constants, optical conductivity, loss factor, VELF, and SELF, were calculated using several empirical relationships and showed increasing behavior with the ion irradiation dose. The changes obtained in both the linear and nonlinear parameters will be useful for nonlinear optical device applications.

Differential trends in the rising incidence of endometrial cancer by type: data from a UK population-based registry from 1994 to 2006.

BACKGROUND: Endometrial cancer is the most common gynaecological cancer in the western world, the incidence increasing in the United Kingdom by over 40% since 1993. Two types of endometrial cancer exist - oestrogen-dependent type 1 with good prognosis and non-oestrogen-dependent type 2 with poor prognosis. The histopathological distribution of the increase in endometrial cancer is unknown. This study investigates the observed incidence trends of the two types, the age, stage, and socioeconomic distribution of this increase and survival outcome. METHODS: Data were analysed from 6867 women with endometrial cancer registered between 1994 and 2006, at a UK population-based cancer registry. RESULTS: Increased endometrial cancer incidence is confined to type 1 cancers with a significant increase in age standardised incidence rate (ASR) from 12.0 per 100,000 (confidence interval (CI) 10.7-13.2) in 1994 to 16.3 per 100,000 (CI 14.9-17.7), P<0.001 in 2006, while ASR of type 2 cancer changed from 2.5 per 100,000 (CI 2.0-3.1) in 1994 to 2.2 per 100,000 (CI 1.7-2.7) in 2006, which was not statistically significant P>0.05. Increase in type 1 cancer is most marked in age groups 60-69 years (P<0.001) and 70-79 years (P<0.001) and distributed equally among socioeconomic quintiles. While outcome for type 1 cancer has improved, 1-year survival in type 2 cancer is unchanged from 73.1% in 1994 to 74.3%, P=0.089 and 5-year survival decreased from 55.1% to 40.9%, P=0.001. CONCLUSION: Increased incidence in endometrial cancer is confined to type 1 cancers, seen most in the 60-79 age groups and across all socioeconomic quintiles. Survival in type 2 cancer has decreased significantly. Urgent research is needed to investigate prevention strategies in type 1 and improve therapy in type 2 cancers.

Tetraspanin CD151 is a novel prognostic marker in poor outcome endometrial cancer.

BACKGROUND: Type II cancers account for 10% of endometrial cancers but 50% of recurrence. Response rates to chemotherapy at recurrence are poor and better prognostic markers are needed to guide therapy. CD151 is a small transmembrane protein that regulates cell migration and facilitates cancer metastasis. High CD151 expression confers poor prognosis in breast, pancreatic and colorectal cancer. The prognostic significance of tetraspanin CD151 expression in poor outcome endometrial cancers was evaluated, along with oestrogen receptor (ER), progesterone receptor (PR), p53, human epidermal growth factor receptor -2 (HER-2), and CD 151 staining compared with α6ß1, α3ß1 integrins, and E-cadherin. METHODS: Tissue microarray constructed from 156 poor outcome endometrial cancers, tested with immunohistochemistry and staining correlated with clinicopathological data were used. A total of 131 data sets were complete for analysis. RESULTS: Expression of CD151 was significantly higher in uterine papillary serous and clear cell carcinoma than in grade 3 endometrioid carcinoma, sarcoma or carcinosarcoma (P<0.001). In univariate analysis, age, stage, histology type and CD151 were significant for both recurrence free (RFS) and disease specific survival (DSS). In multivariate analyses, CD151 was significant for RFS and DSS (P=0.036 and 0.033, respectively) in triple negative (ER, PR and HER-2 negative) tumours (88/131). The HER-2, p53, ER and PR were not prognostic for survival. There was strong concordance of CD151 with E-cadherin (98%), but not with α6ß1 (35%), α3ß1 staining (60%). CONCLUSION: The CD151 is a novel marker in type 2 cancers that can guide therapeutic decisions. CD151 may have an important role in tumourigenesis in some histology types.

Role of rigidity and temperature in the kinetics of photodarkening in Ge(x)As(45-x)Se55 thin films.

We present insightful results on the kinetics of photodarkening (PD) in Ge(x)As(45-x)Se55 glasses at the ambient and liquid helium temperatures when the network rigidity is increased by varying x from 0 to 16. We observe a many fold change in PD and its kinetics with decreasing network flexibility and temperature. Moreover, temporal evolution of PD shows a dramatic change with increasing x.

In situ laser irradiation: the kinetics of the changes in the nonlinear/linear optical parameters of As50Se40Sb10 thin films for photonic applications.

The photosensitivity of amorphous chalcogenide thin films brings out light-induced changes in the nonlinear and linear optical parameters upon sub-bandgap and bandgap laser irradiation. The present work reports the in situ laser irradiated changes in the optical properties of As50Se40Sb10 thin films. The thermally evaporated film showed an exponential decrease in optical bandgap and increase in Urbach energy. The decay rate of the bandgap was 6.24 min and growth rate of Urbach energy was 6.67 min respectively. The dynamics of photo-induced changes were observed from the changes in linear refractive index and its dependent parameters such as 3rd order nonlinear susceptibility, nonlinear refractive index, dispersion and dielectric parameters. The conversion of heteropolar to homopolar bonds induced the photodarkening mechanism that changed the dispersion parameters. The decrease in E d and E o reduced the oscillator strength along with the zero-frequency dielectric constant. The optical and electrical conductivity changed significantly with time. The changes were saturated with time which brings stability in the film properties that is useful for various optical applications. However, no structural and compositional changes upon laser irradiation were noticed from the X-ray diffraction and EDX studies respectively. The surface homogeneity was checked from the FESEM picture.