Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Act or wait-and-see? Adversity, agility, and entrepreneur wellbeing across countries during the Covid-19 pandemic

How can entrepreneurs protect their wellbeing during a crisis? Does engaging agility (namely, opportunity agility and planning agility) in response to adversity help entrepreneurs safeguard their wellbeing? Activated by adversity, agility may function as a specific resilience mechanism enabling positive adaption to crisis. We studied 3,162 entrepreneurs from 20 countries during the COVID-19 pandemic and found that more severe national lockdowns enhanced firm-level adversity for entrepreneurs and diminished their wellbeing. Moreover, entrepreneurs who combined opportunity agility with planning agility experienced higher wellbeing but planning agility alone lowered wellbeing. Entrepreneur agility offers a new agentic perspective to research on entrepreneur wellbeing

Prostate cancer risk regions at 8q24 and 17q24 are differentially associated with somatic TMPRSS2:ERG fusion status.

Molecular and epidemiological differences have been described between TMPRSS2:ERG fusion-positive and fusion-negative prostate cancer (PrCa). Assuming two molecularly distinct subtypes, we have examined 27 common PrCa risk variants, previously identified in genome-wide association studies, for subtype specific associations in a total of 1221 TMPRSS2:ERG phenotyped PrCa cases. In meta-analyses of a discovery set of 552 cases with TMPRSS2:ERG data and 7650 unaffected men from five centers we have found support for the hypothesis that several common risk variants are associated with one particular subtype rather than with PrCa in general. Risk variants were analyzed in case-case comparisons (296 TMPRSS2:ERG fusion-positive versus 256 fusion-negative cases) and an independent set of 669 cases with TMPRSS2:ERG data was established to replicate the top five candidates. Significant differences (P < 0.00185) between the two subtypes were observed for rs16901979 (8q24) and rs1859962 (17q24), which were enriched in TMPRSS2:ERG fusion-negative (OR = 0.53, P = 0.0007) and TMPRSS2:ERG fusion-positive PrCa (OR = 1.30, P = 0.0016), respectively. Expression quantitative trait locus analysis was performed to investigate mechanistic links between risk variants, fusion status and target gene mRNA levels. For rs1859962 at 17q24, genotype dependent expression was observed for the candidate target gene SOX9 in TMPRSS2:ERG fusion-positive PrCa, which was not evident in TMPRSS2:ERG negative tumors. The present study established evidence for the first two common PrCa risk variants differentially associated with TMPRSS2:ERG fusion status. TMPRSS2:ERG phenotyping of larger studies is required to determine comprehensive sets of variants with subtype-specific roles in PrCa.RAE acknowledges support from the NIHR to the Biomedical Research Centre at The Institute of Cancer Research and Royal Marsden NHS Foundation Trust. ML was a fellow of the International Graduate School in Molecular Medicine, Ulm. AER was a fellow of the Heinrich Warner Foundation. The GTEx Consortium is acknowledged for the GTEx data (the full acknowledgement is available in the Supplementary Materials). This work was supported by the following grants for the iCOGS infrastructure: European Community's Seventh Framework Programme under grant agreement n° 223175 [HEALTHF2-2009-223175]; Cancer Research UK [C1287/A10118, C1287/A10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692]; the National Institutes of Health [CA128978] and Post-Cancer GWAS initiative [1U19 CA148537, 1U19 CA148065, 1U19 CA148112 - the GAME-ON initiative]; the Department of Defence [W81XWH-10-1-0341]; the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer; Komen Foundation for the Cure; the Breast Cancer Research Foundation; and the Ovarian Cancer Research Fund. The FHCRC, Tampere, UKGPCS and Ulm groups are part of the ICPCG, supported by the National Institutes of Health [U01 CA089600]. The Molecular Prostate Cancer project of Ulm was funded by the Deutsche Krebshilfe. The Berlin and Ulm collaboration was supported by the Berliner Krebsgesellschaft. The FHCRC studies were supported by the U.S. National Cancer Institute, National Institutes of Health [RO1 CA056678, RO1 CA082664, RO1 CA092579]; with additional support from the Fred Hutchinson Cancer Research Center. Genotyping was supported by the Intramural Program of the National Human Genome Research Institute, National Institutes of Health. The Tampere (Finland) study was supported by the Academy of Finland [116437, 251074, 126714]; the Finnish Cancer Organisations; Sigrid Juselius Foundation; and The Medical Research Fund of Tampere University Hospital [# 9L091]. The PSA screening samples were collected by the Finnish part of ERSPC (European Study of Screening for Prostate Cancer)

HIV-Präexpositionsprophylaxe-Versorgung in intersektoraler Zusammenarbeit

$\it Hintergrund$ Zur HIV("human immunodeficiency virus")-Präexpositionsprophylaxe (PrEP) wird am WIR – Walk In Ruhr – Zentrum für Sexuelle Gesundheit und Medizin ein innovatives Modellprojekt zur intersektoralen PrEP-Versorgung durchgeführt. $\it Forschungsziele$ Die vorliegende Studie beschreibt, wer mit der PrEP versorgt wurde und wie sich im Verlauf der PrEP-Einnahme das sexuelle Risikoverhalten änderte sowie welche sexuell übertragbaren Infektionen (STI) und unerwünschte Arzneimittelwirkungen auftraten. $\it Methoden$ In die Studie wurden bisher $\it N$ = 139 Probanden eingeschlossen, die zwischen 10/2017 und 12/2018 mit einer PrEP begonnen haben. Alle PrEP-Nutzer erhielten Fragebögen, zudem wurden Nebenwirkungen, HIV und andere STI mittels klinischer Laborwerte über einen Zeitraum von 13 Monaten erfasst. $\it Ergebnisse$ Die PrEP-Nutzer hatten ein durchschnittliches Alter von 38 Jahren, waren zu 98,6 % Männer, die Sex mit Männern (MSM) hatten, und zeichneten sich durch einen hohen Bildungsstatus und geringe Arbeitslosigkeit aus. Die durchschnittliche Partneranzahl pro Proband innerhalb der letzten 6 Monate stieg im Verlauf signifikant an, während die Kondomnutzung signifikant zurückging. Innerhalb der ersten 4 Monate nach PrEP-Beginn traten 44 STI bei 34 Patienten auf. Es wurde keine HIV-Infektion festgestellt. In den ersten 4 Wochen nach PrEP-Beginn zeigten sich bei 38,8 % der Probanden unerwünschte Arzneimittelwirkungen, hauptsächlich Symptome des Magen-Darm-Trakts. $\it Schlussfolgerung$ Die PrEP-Nutzer hatten einen guten Bildungsstatus und einen festen Arbeitsplatz bzw. eine Ausbildungsstelle. Das sexuelle Risikoverhalten nahm im Verlauf zu, verbunden mit einem gehäuften Auftreten von STI. Unerwünschte Arzneimittelwirkungen zeigten sich insbesondere zu Anfang der PrEP-Einnahme.$\it Background$ HIV pre-exposure prophylaxis (PrEP), a further opportunity to prevent HIV, is available at the WIR—Walk In Ruhr, Centre for Sexual Health and Medicine, as part of an innovative model project for intersectoral PrEP care. $\textit {Research objectives}$ The present study describes the collective of persons provided with PrEP and how PrEP use influences sexual risk behaviour, the incidence of sexually transmitted diseases (STD) and adverse drug reactions. $\it Methods$ A total of 139 men who started PrEP between 10/2017 and 12/2018 have been included in the study. During a period of 13 months of PrEP treatment, all PrEP users received questionnaires; side effects, HIV and other STI were also monitored via clinical laboratory examinations. $\it Results$ The participants’ average age was 38 years and 98.6% of them were men who had sex with men (MSM). Most of them had a high educational background; the unemployment rate was low. The average number of sexual partners within the last 6 months increased significantly, while the use of condoms decreased. In all, 44 STI were found in 34 participants within the first 4 months. No one was infected with HIV. Within the first 4 weeks of PrEP, 38.8% of the participants suffered from side effects, mainly gastrointestinal symptoms. $\it Conclusion$ Most of the participants were working in a job or a vocational training. The sexual risk behaviour increased in the course of using PrEP resulting in a high incidence of STD. Side effects appeared most frequently in the first few weeks after starting PrEP

Sexuelle Gesundheit und Medizin im WIR – Walk In Ruhr: Vorstellung des Zentrums und Ergebnisse der Evaluation

Background!#!Holistic sexual healthcare factors in diversity of social habitat and aims to improvise client outreach for prevention, testing, counseling, and treatment of STIs. Towards this goal, the immunology outpatient clinic, the public health department of Bochum, the AIDS Service Organization Bochum e. v., and other community-driven NGOs mutually cooperate under the umbrella of WIR - Walk In Ruhr, Centre for Sexual Health and Medicine.!##!Objectives!#!WIR is an innovative concept for multi-professional in-house ambulatory healthcare with cross-sectoral and cross-legal reach. It has successfully improved accessibility, testing and treatment rates, and HIV/STI self-assessment. We present the results achieved at WIR.!##!Methods!#!A mixed-method design of qualitative and quantitative surveys.!##!Results!#!The WIR reaches more women (27.7%) and heterosexuals (56.4%) than other counseling/test centers. The rate of positive test results at the WIR increased from 9.3% in 2017 to 12.6% in 2018 and progress from prevention to medical care is a significant aspect of WIR. The Federal Ministry of Health has externally evaluated WIR for over three years.!##!Discussion!#!The integrative care model of WIR allows for early outreach and treatment of individuals with HIV/ST infections. Health advisors remain an important instrument facilitating outreach and psychosocial/psychotherapeutic counseling is administered frequently. Such a multi-layered approach in prevention, testing, and consultation, leads to improvement in both medical outcomes and the self-responsible attitude of patients towards their sexual health. Hence, expansion of integrative care models like WIR on a wider scale could arguably contribute to better health service and sexual health

Changes in the user profiles of HIV pre-exposure prophylaxis (PrEP) before and after PrEP reimbursement.

BACKGROUND: In Germany, oral HIV pre-exposure prophylaxis (PrEP) was licensed in 2016. Health insurances have been covering the costs since 09/2019. This study compares the sociodemographic profiles of PrEP users before and after PrEP re-imbursement. METHODS: Participants were recruited in a cross-sectoral sexual health centre in Germany. baseline data were compared for 139 vs 138 individuals starting PrEP from 10/2017-12/2018 (pre-reimbursement cohort) and 09/2019-3/2020; respectively. The pre-reimbursement cohort was further analysed with respect to sexual behaviour and incident sexually transmitted infections (STIs). RESULTS: There were no significant differences in the sociodemographic characteristics between the two cohorts. Almost all PrEP users were men-who-have-sex-with-men (MSM). Before reimbursement, fewer individuals used PrEP on a daily base, and more had used PrEP prior to enrolment. During follow-up (pre-reimbursement cohort), the number of sexual and condomless intercourse partners increased, so did the proportion engaging in Chemsex. Incidences of infections with C.trachomatis, N.gonorrhoeae, M.genitalium, and T.pallidum were 45.2; 36.8; 30.1; and 9.2, respectively, per 100 person-years. CONCLUSION: The goal to make PrEP available to a broader range of people with the covering of costs was only partially reached. Medically supervised use is important to detect and treat STIs

Sexual behaviour, STI knowledge and Chlamydia trachomatis\textit {Chlamydia trachomatis} (CT) and Neisseria gonorrhoeae\textit {Neisseria gonorrhoeae} (NG) prevalence in an asymptomatic cohort in Ruhr-area, Germany

$\textbf {Background and objectives}$ STIs present a significant threat to individual and public health, disproportionately affecting youth. The study aimed to evaluate (a) the prevalence of asymptomatic $\textit {Chlamydia trachomatis}$ (CT) and $\textit {Neisseria gonorrhoeae}$ (NG) infections among youth using a rapid assay platform, (b) the participants' sexual behaviour and STI knowledge, (c) the utility of the rapid assay in reducing diagnosis-to-treatment time. $\bf Methods$ In this study, 272 subjects (14–31 years) were included between 12/2016 and 7/2018. A questionnaire was used to collect sociodemographic data, sexual behaviour and STI knowledge. Prevalence of CT and NG infections were tested from oral, vaginal and anal swabs for women and oral, anal swabs and urine for men, using the Cepheid Xpert® CT/NG assay. Time intervals between (i) test to the time the patient were informed of the result (turn around time – TAT) and (ii) test to therapy initiation was documented. $\bf Results$ Of the 272 subjects (48.9% female, 48.9% male, undisclosed 2.2%), 56.6 % reported university education. 46.6% were men who have sex with men (MSM), and 47.4% of women and 63.1% of men had anal intercourse. 59.9% had previously been tested for HIV, while only 39.7% had for CT, 20.6% for NG. Among these asymptomatic youth 7.7% were positive for CT and 5.5% for NG. The localization of CT were 3.7% genital, 5.5% anal and 2.2% oral, while the corresponding localization of NG were 0.4%, 2.9%, 4.4% respectively. 91.8% of the participants were informed of a positive result within 24 h with a median TAT of 03:09 h. 73.3% initiated therapy within 24 h, with a median time from testing to therapy initiation being 06:50 h. $\bf Conclusion$ Asypmtomatic CT and NG infections are common and often not tested in persons at risk. The Cepheid Xpert® CT/NG assay is an effective strategy as it reduces STI diagnosis-to-treatment time to less than a day

Sexuelle Gesundheit und Medizin im WIR – Walk In Ruhr

$\bf Hintergrund:$ Ein ganzheitliches Konzept sexueller Gesundheit und Medizin berücksichtigt die Diversität von Lebenswelten, um Klient*innen für Prävention, Testung, Beratung und Behandlung sexuell übertragbarer Infektionen (STI) zu gewinnen. Mit diesem Verständnis arbeiten die Immunologische Ambulanz, das Gesundheitsamt, die Aidshilfe sowie weitere Selbsthilfeorganisationen im WIR – Walk In Ruhr, Zentrum für Sexuelle Gesundheit und Medizin, in Bochum zusammen. $\textbf {Ziel der Arbeit:}$ Am Beispiel des WIR, das mit seinem innovativen Konzept eines Versorgungszentrums multiprofessionell innerhalb eines Settings sektor- und rechtsformübergreifend arbeitet, wird gezeigt, dass Erreichbarkeit, Test- und Behandlungsquote und HIV/STI-Risiko-Selbsteinschätzung sich verbessern. Das WIR wurde zudem im Auftrag des Bundesministeriums für Gesundheit über 3 Jahre extern evaluiert auch diese Ergebnisse werden dargestellt. $\bf Methode:$ Das Konzept des WIR und die im WIR durchgeführten Studien werden deskriptiv dargestellt. Bei der externen Evaluation wurde ein Mixed-Method-Design aus quantitativen und qualitativen Erhebungen angewandt. $\bf Ergebnis:$ Durch die Kooperation werden häufiger Frauen (27,7 %) und Heterosexuelle (56,4 %) als in der Ambulanz allein erreicht. Die Rate positiver Testergebnisse im WIR stieg von 2017 bis 2018 von 9,3 % auf 12,6 %. $\bf Diskussion:$ Durch das integrative Versorgungskonzept des WIR gelingt es, Menschen mit HIV/STI früh zu erreichen und zu behandeln. Der Übergang von Prävention zu medizinischer Versorgung ist im WIR von zentraler Bedeutung. Gesundheitsberater sind ein wichtiges Instrument für die aufsuchende Arbeit. Psychosoziale sowie psychotherapeutische Beratung werden in hohem Maße genutzt. Durch die vielschichtigen Angebote von Prävention, Test, Beratung werden bessere medizinische Ergebnisse erreicht sowie die Eigenverantwortung für sexuelle Gesundheit gesteigert. Die Übertragung des Konzeptes in die Fläche kann einen Beitrag zur besseren Versorgung zu sexueller Gesundheit leisten.$\bf Background:$ Holistic sexual healthcare factors in diversity of social habitat and aims to improvise client outreach for prevention, testing, counseling, and treatment of STIs. Towards this goal, the immunology outpatient clinic, the public health department of Bochum, the AIDS Service Organization Bochum e. v., and other community-driven NGOs mutually cooperate under the umbrella of WIR – Walk In Ruhr, Centre for Sexual Health and Medicine. $\bf Objectives:$ WIR is an innovative concept for multi-professional in-house ambulatory healthcare with cross-sectoral and cross-legal reach. It has successfully improved accessibility, testing and treatment rates, and HIV/STI self-assessment. We present the results achieved at WIR. $\bf Methods:$ A mixed-method design of qualitative and quantitative surveys. $\bf Results:$ The WIR reaches more women (27.7%) and heterosexuals (56.4%) than other counseling/test centers. The rate of positive test results at the WIR increased from 9.3% in 2017 to 12.6% in 2018 and progress from prevention to medical care is a significant aspect of WIR. The Federal Ministry of Health has externally evaluated WIR for over three years. $\bf Discussion:$ The integrative care model of WIR allows for early outreach and treatment of individuals with HIV/ST infections. Health advisors remain an important instrument facilitating outreach and psychosocial/psychotherapeutic counseling is administered frequently. Such a multi-layered approach in prevention, testing, and consultation, leads to improvement in both medical outcomes and the self-responsible attitude of patients towards their sexual health. Hence, expansion of integrative care models like WIR on a wider scale could arguably contribute to better health service and sexual health

Sexualverhalten und Prävention sexuell übertragbarer Infektionen unter Berücksichtigung der SARS-CoV-2-Pandemie. Daten aus einem Versorgungszentrum für sexuelle Gesundheit und Medizin – WIR

Background!#!Application-based data regarding sexual health and sexual behavior in various sexually active populations are scarce but at the same time relevant with regards to prevention and healthcare supply strategies. Given the structure of its attendees, the Walk In Ruhr (WIR) Center for Sexual Health and Medicine is able to obtain data from diverse living environments.!##!Objectives!#!Based on the online HIV/STI risk test, questionnaires, and attendee data from the WIR, this study aims to deduce population-related findings with regards to age, gender, sexual orientation, and sexual and risk behavior as well as the respective needs for prevention. The influence of the SARS-CoV-19 pandemic on sexual behavior is examined by comparing various phases.!##!Methods!#!The analyzed data sources are the online HIV/STI risk test, the COWIR, and the PrEP study as well as the immunological outpatient clinic and the public health department at the WIR.!##!Results!#!Notwithstanding contact restrictions, sexually transmitted infections (STIs) have increased from 2019 to 2020. Apart from men having sex with men and females having sex with females, young people also have an increased risk of STIs based on sexual practices and the number of sexual contacts. A large number of bisexual and transsexual contacts was found. SARS-CoV‑2 led to a decrease in sexual contacts; sexual practices continued. There was a growing proportion of STI tests and the treatment rate including partner treatment rose.!##!Discussion!#!Data from the WIR center show that young attendees with an active sexual life are being reached. The results from questionnaires and the online HIV/STI risk test are mirrored in increased positive STI test results. These results vary depending on sexual behavior and sexual preferences such that specific strategies for sexual education, prevention, testing, and therapy are required

HIV pre-exposure prophylaxis during the SARS-CoV-2 pandemic

$\bf Aims:$ Since 2017, HIV pre-exposure prophylaxis (PrEP) care has been provided through an intersectoral collaboration at WIR (Walk-in-Ruhr, Center for Sexual Health and Medicine, Bochum, Germany). The aim of this study was to establish possible impact of COVID-restrictions on the sexual behavior of PrEP users in North Rhine-Westphalia. $\bf Methods:$ The current PrEP study collected data of individuals using PrEP, their sexual behavior and sexually transmitted infections (STIs) before (each quarter of year 2018) and during the COVID-19 pandemic (each quarter of year 2020). $\bf Results:$ During the first lockdown in Germany from mid-March until May 2020, PrEP-care appointments at WIR were postponed or canceled. Almost a third of PrEP users had discontinued their PrEP intake in the $2^{nd}$ quarter of 2020 due to alteration of their sexual behavior. The number of sexual partners decreased from a median of 14 partners in the previous 6 months in $1^{st}$ quarter of 2020, to 7 partners in $4^{th}$ quarter of 2020. Despite such a significant reduction in partner number during the pandemic in comparison to the pre-pandemic period, a steady rate of STIs was observed among PrEP users in 2020. \(\bf Conclusion:\9 The SARS-CoV-2-pandemic has impacted PrEP-using MSM in North Rhine-Westphalia with respect to their PrEP intake regimen and sexual behavior in 2020. Our study revealed a steady rate of STI among PrEP users even during the pandemic, thus highlighting the importance of ensuring appropriate HIV/STI prevention services in times of crisis