Controlled Switching of Bistable Nanophase Domains on a Silicon Surface.

Switching the crystalline phase of a material via electrostatic control is a proven strategy for developing memory devices such as memristors that are based on nonvolatile resistance switching phenomena. However, phase switching in atomic-scale systems is often difficult to control and poorly understood. Here, we explore nonvolatile switching of long 2.

Mechanism of Electron-Beam Manipulation of Single-Dopant Atoms in Silicon.

The precise positioning of dopant atoms within bulk crystal lattices could enable novel applications in areas including solid-state sensing and quantum computation. Established scanning probe techniques are capable tools for the manipulation of surface atoms, but at a disadvantage due to their need to bring a physical tip into contact with the sample. This has prompted interest in electron-beam techniques, followed by the first proof-of-principle experiment of bismuth dopant manipulation in crystalline silicon.

Incidence and clearance of penile human papillomavirus infection among circumcised Kenyan men.

Prospective data are limited on human papillomavirus (HPV) acquisition and clearance among circumcised men from resource-limited geographical regions, particularly Africa. The goal of this study was to estimate incidence and clearance of type-specific genital HPV infection in men. Penile exfoliated cell specimens were collected from the glans/coronal sulcus and shaft of 1,037 circumcised Kenyan men at baseline and 6-, 12- and 18-month follow-up visits between 2003-2007.

Performance of human papillomavirus testing on self-collected versus clinician-collected samples for the detection of cervical intraepithelial neoplasia of grade 2 or worse: a randomised, paired screen-positive, non-inferiority trial.

Background: Human papillomavirus (HPV) testing on self-collected samples is a potential alternative to HPV testing on clinician-collected samples, but non-inferiority of its clinical accuracy remains to be assessed in the regular screening population. The IMPROVE study was done to evaluate the clinical accuracy of primary HPV testing on self-collected samples within an organised screening setting.

Methods: In this randomised, non-inferiority trial, women aged 29-61 years were invited to participate in the study as part of their regular screening invitation in the Netherlands.

HPV-based cervical screening: Rationale, expectations and future perspectives of the new Dutch screening programme.

Based on scientific data showing that HPV testing provides better protection against cervical precancer and cancer than cytology, in 2011 the Dutch Health Council advised the Minister of Welfare, Health and Sports to replace cytology by HPV testing in the Dutch population-based screening programme. After a successful evaluation of the feasibility of HPV-based screening in 2014, primary HPV testing for cervical screening was implemented in 2017. The Netherlands has been one of the first countries worldwide to implement nationwide HPV-based screening and its experience with the new programme is therefore followed with great interest.

Management of HPV-positive women in cervical screening using results from two consecutive screening rounds.

We studied whether triage of human papillomavirus (HPV)-positive women participating in an HPV-based screening programme can be improved by including the HPV result at the previous screen in the triage algorithm. We analyzed data of a subgroup of 366 women from the POBASCAM trial, screened by cytology and HPV cotesting. Women were included if they tested HPV-positive in the second HPV-based screening round.

HPV16-Related Cervical Cancers and Precancers Have Increased Levels of Host Cell DNA Methylation in Women Living with HIV.

Data on human papillomavirus (HPV) type-specific cervical cancer risk in women living with human immunodeficiency virus (WLHIV) are needed to understand HPV⁻HIV interaction and to inform prevention programs for this population. We assessed high-risk HPV type-specific prevalence in cervical samples from 463 WLHIV from South Africa with different underlying, histologically confirmed stages of cervical disease. Secondly, we investigated DNA hypermethylation of host cell genes , , and , as markers of advanced cervical disease, in relation to type-specific HPV infection.

Defining hrHPV genotypes in cervical intraepithelial neoplasia by laser capture microdissection supports reflex triage of self-samples using HPV16/18 and FAM19A4/miR124-2 methylation.

Objective: HPV16/18 genotyping and detection of hypermethylation of human cell genes involved in cervical oncogenesis have shown promising results in triage of high-risk HPV (hrHPV)-screen positive women on cervical smears. These tests can be performed on self-samples, which contain cervical and vaginal cells. We studied whether a self-sample represents the hrHPV type causing the worst cervical lesion and whether any differences in hypermethylation of FAM19A4/miR124-2 exist between CIN lesions caused by different hrHPV types.

Publisher Correction: The molecular landscape of head and neck cancer.

The article as originally published contained errors in Figure 3. The direction of the arrows associated with the labels for p53 and RB were incorrect. This has now been corrected in all versions of the article.

Genome-wide microRNA analysis of HPV-positive self-samples yields novel triage markers for early detection of cervical cancer.

Offering self-sampling for HPV testing improves the effectiveness of current cervical screening programs by increasing population coverage. Molecular markers directly applicable on self-samples are needed to stratify HPV-positive women at risk of cervical cancer (so-called triage) and to avoid over-referral and overtreatment. Deregulated microRNAs (miRNAs) have been implicated in the development of cervical cancer, and represent potential triage markers.

Virological and Serological Predictors of Anal High-grade Squamous Intraepithelial Lesions Among Human Immunodeficiency Virus-positive Men Who Have Sex With Men.

Background: Our objective was to identify virological and serological predictors of anal high-grade squamous intraepithelial lesions (HSIL) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM).

Methods: HIV-positive MSM were recruited from a longitudinal study during which anal self-swabs and serum were collected at up to 5 bi-annual visits. Swabs were human papillomavirus (HPV) genotyped, and the type-specific HPV viral load in the anal swabs was determined.

HPV E4 expression and DNA hypermethylation of CADM1, MAL, and miR124-2 genes in cervical cancer and precursor lesions.

In this study, we evaluate the expression of human papillomavirus E4 protein (marker for the onset of a productive infection) and hypermethylation of host-cell CADM1, MAL, and miR124-2 genes (marker for an advanced, transforming infection) in cervical intraepithelial neoplasia (CIN) and cancer. A total of 115 cervical lesions were categorized by 3 pathologists into no dysplasia, CIN1, CIN2, CIN3, or cancer by classical histomorphological grading criteria, and by an immunoscore (cumulative value: 0-6) grading system based on Ki-67 (score: 0-3) and p16 (score: 0-3) expression. Lesions were immunostained for E4 protein and analyzed for hypermethylation of CADM1, MAL, or miR124-2 genes.

Detection of hypermethylated genes as markers for cervical screening in women living with HIV.

Introduction: To evaluate the performance of hypermethylation analysis of ASCL1, LHX8 and ST6GALNAC5 in physician-taken cervical scrapes for detection of cervical cancer and cervical intraepithelial neoplasia (CIN) grade 3 in women living with HIV (WLHIV) in South Africa.

Methods: Samples from a prospective observational cohort study were used for these analyses. Two cohorts were included: a cohort of WLHIV who were invited for cervical screening (n = 321) and a gynaecologic outpatient cohort of women referred for evaluation of abnormal cytology or biopsy proven cervical cancer (n = 108, 60% HIV seropositive).

Host-cell DNA methylation patterns during high-risk HPV-induced carcinogenesis reveal a heterogeneous nature of cervical pre-cancer.

Cervical cancer development following a persistent infection with high-risk human papillomavirus (hrHPV) is driven by additional host-cell changes, such as altered DNA methylation. In previous studies, we have identified 12 methylated host genes associated with cervical cancer and pre-cancer (CIN2/3). This study systematically analyzed the onset and DNA methylation pattern of these genes during hrHPV-induced carcinogenesis using a longitudinal in vitro model of hrHPV-transformed cell lines (n = 14) and hrHPV-positive cervical scrapings (n = 113) covering various stages of cervical carcinogenesis.

Molecular heterogeneity in human papillomavirus-dependent and -independent vulvar carcinogenesis.

Vulvar squamous cell carcinoma (VSCC) and precancerous vulvar intraepithelial neoplasia (VIN) can develop through human papillomavirus (HPV)-dependent and -independent pathways, indicating a heterogeneous disease. Only a minority of VIN progress, but current clinicopathological classifications are insufficient to predict the cancer risk. Here we analyzed copy number alterations (CNA) to assess the molecular heterogeneity of vulvar lesions in relation to HPV and cancer risk.

Three-tiered score for Ki-67 and p16 improves accuracy and reproducibility of grading CIN lesions.

Aims: To investigate the accuracy and reproducibility of a scoring system for cervical intraepithelial neoplasia (CIN1-3) based on immunohistochemical (IHC) biomarkers Ki-67 and p16.

Methods: 115 cervical tissue specimens were reviewed by three expert gynaecopathologists and graded according to three strategies: (1) CIN grade based on H&E staining only; (2) immunoscore based on the cumulative score of Ki-67 and p16 only (0-6); and (3) CIN grade based on H&E supported by non-objectified IHC 2 weeks after scoring 1 and 2. The majority consensus diagnosis of the CIN grade based on H&E supported by IHC was used as the .

Triage of high-risk HPV-positive women in population-based screening by miRNA expression analysis in cervical scrapes; a feasibility study.

Background: Primary testing for high-risk HPV (hrHPV) is increasingly implemented in cervical cancer screening programs. Many hrHPV-positive women, however, harbor clinically irrelevant infections, demanding additional disease markers to prevent over-referral and over-treatment. Most promising biomarkers reflect molecular events relevant to the disease process that can be measured objectively in small amounts of clinical material, such as miRNAs.

Directed Atom-by-Atom Assembly of Dopants in Silicon.

The ability to controllably position single atoms inside materials is key for the ultimate fabrication of devices with functionalities governed by atomic-scale properties. Single bismuth dopant atoms in silicon provide an ideal case study in view of proposals for single-dopant quantum bits. However, bismuth is the least soluble pnictogen in silicon, meaning that the dopant atoms tend to migrate out of position during sample growth.

Evaluation of human-papillomavirus testing and visual inspection for cervical cancer screening in Rwanda.

Background: A pilot screening campaign in Rwanda, based on careHPV-testing followed by visual inspection with acetic acid triage (careHPV+VIA triage), was evaluated against other WHO-recommended screening options, namely HPV screen-and-treat and VIA screen-and-treat.

Methods: 764 women aged 30-69 underwent at visit 1: i) VIA, and cervical cell collection for ii) careHPV in Rwanda, and iii) liquid-based cytology and GP5+/6+ HR-HPV PCR in The Netherlands. All 177 women positive by VIA, careHPV and/or PCR were recalled, of whom 84% attended.

Cervical cancer risk in HPV-positive women after a negative FAM19A4/mir124-2 methylation test: A post hoc analysis in the POBASCAM trial with 14 year follow-up.

DNA methylation analysis of cervical scrapes using FAM19A4 and mir124-2 genes has shown a good clinical performance in detecting cervical cancer and advanced CIN lesions in need of treatment in HPV-positive women. To date, longitudinal data on the cancer risk of methylation test-negative women are lacking. In our study, we assessed the longitudinal outcome of FAM19A4/mir124-2 methylation analysis in an HPV-positive screening cohort with 14 years of follow-up.

Identification and Validation of a 3-Gene Methylation Classifier for HPV-Based Cervical Screening on Self-Samples.

Offering self-sampling of cervico-vaginal material for high-risk human papillomavirus (hrHPV) testing is an effective method to increase the coverage in cervical screening programs. Molecular triage directly on hrHPV-positive self-samples for colposcopy referral opens the way to full molecular cervical screening. Here, we set out to identify a DNA methylation classifier for detection of cervical precancer (CIN3) and cancer, applicable to lavage and brush self-samples.

Direct atomic fabrication and dopant positioning in Si using electron beams with active real-time image-based feedback.

Semiconductor fabrication is a mainstay of modern civilization, enabling the myriad applications and technologies that underpin everyday life. However, while sub-10 nanometer devices are already entering the mainstream, the end of the Moore's law roadmap still lacks tools capable of bulk semiconductor fabrication on sub-nanometer and atomic levels, with probe-based manipulation being explored as the only known pathway. Here we demonstrate that the atomic-sized focused beam of a scanning transmission electron microscope can be used to manipulate semiconductors such as Si on the atomic level, inducing growth of crystalline Si from the amorphous phase, reentrant amorphization, milling, and dopant front motion.

The molecular landscape of head and neck cancer.

Head and neck squamous cell carcinomas (HNSCCs) arise in the mucosal linings of the upper aerodigestive tract and are unexpectedly heterogeneous in nature. Classical risk factors are smoking and excessive alcohol consumption, and in recent years, the role of human papillomavirus (HPV) has emerged, particularly in oropharyngeal tumours. HPV-induced oropharyngeal tumours are considered a separate disease entity, which recently has manifested in an adapted prognostic staging system while the results of de-intensified treatment trials are awaited.

Eurogin roadmap 2017: Triage strategies for the management of HPV-positive women in cervical screening programs.

Cervical cancer screening will rely, increasingly, on HPV testing as a primary screen. The requirement for triage tests which can delineate clinically significant infection is thus prescient. In this EUROGIN 2017 roadmap, justification behind the most evidenced triages is outlined, as are challenges for implementation.

Realization of a Hole-Doped Mott Insulator on a Triangular Silicon Lattice.

The physics of doped Mott insulators is at the heart of some of the most exotic physical phenomena in materials research including insulator-metal transitions, colossal magnetoresistance, and high-temperature superconductivity in layered perovskite compounds. Advances in this field would greatly benefit from the availability of new material systems with a similar richness of physical phenomena but with fewer chemical and structural complications in comparison to oxides. Using scanning tunneling microscopy and spectroscopy, we show that such a system can be realized on a silicon platform.