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Background and Purpose: This study aimed at training and validating a multi-institutional deep learning (DL) auto segmentation model for nodal clinical target volume (CTVn) in high-risk breast cancer (BC) patients with both training and validation dataset created with multi-institutional participation, with the overall aim of national clinical implementation in Denmark., Materials and Methods: A gold standard (GS) dataset and a high-quality training dataset were created by 21 BC delineation experts from all radiotherapy centres in Denmark. The delineations were created according to ESTRO consensus delineation guidelines. Four models were trained: One per laterality and extension of CTVn internal mammary nodes. The DL models were tested quantitatively in their own test-set and in relation to interobserver variation (IOV) in the GS dataset with geometrical metrics, such as the Dice Similarity Coefficient (DSC). A blinded qualitative evaluation was conducted with a national board, presented to both DL and manual delineations., Results: A median DSC > 0.7 was found for all, except the CTVn interpectoral node in one of the models. In the qualitative evaluation 'no corrections needed' were acquired for 297 (36 %) in the DL structures and 286 (34 %) for manual delineations. A higher rate of 'major corrections' and 'easier to start from scratch' was found in the manual delineations. The models performed within the IOV of an expert group, with two exceptions., Conclusion: DL models were developed on a national consensus cohort and performed on par with the IOV between BC experts and had a comparable or higher clinical acceptance than expert manual delineations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/objective: Information about occurrence and affected groups of symptoms/diagnoses indicative of an HIV infection (so-called HIV indicator conditions; HIV-ICs) is lacking. We analyse HIV-IC incidence, transmission risks and immune status among people living with HIV (PLWH) antiretroviral therapy (ART) naive., Methods: Diagnoses reported for ART-naive PLWH from two multicentre observational, prospective cohort studies between 1999-2023 were analysed. Incidence rates per 1,000 person-years (PYs) were calculated for the overall study period and time periods defined by ART treatment recommendations. For further description, CD4 counts around HIV-IC diagnosis (+ -30 days) and HIV-transmission routes were collected., Results: In total 15,940 diagnoses of 18,534 PLWH in Germany were included. Of those 81% were male (median age: 36 years) and 56% reported being men, who have sex with men as the likely HIV-transmission route. Incidence rates varied between the different HIV-ICs. Syphilis had the highest incidence rate (34 per 1,000 PYs; 95% confidence interval [CI] 29-40) for sexually transmitted infections (STIs), hepatitis B was highest for viral hepatitis diagnoses (18 per 1,000 PYs; 95% CI 17-20); according to CDC-classification herpes zoster for HIV-associated diagnoses (22 per 1,000; 95% CI 20-24) and candidiasis for AIDS-defining diagnoses (30 per 1,000 PYs; 95% CI 29-32). Most PLWH with HIV-ICs (hepatitis, HIV-associated diagnoses and AIDS-defining conditions) had CD4 cell counts < 350., Conclusion: This analysis characterizes HIV-ICs regarding the incidence, HIV-transmission route and patients' immune status. The results underline the importance of HIV-IC-based screening to detect PLWH with already partially impaired immune status and in need of timely ART initiation., (© 2024. The Author(s).)

Background: Mycoplasma genitalium (MG) is an emerging sexually transmitted infection, often harboring resistance-associated mutations to azithromycin (AZM). Global surveillance has been mandated to tackle the burden caused by MG, yet no data are available for Austria. Thus, we aimed to investigate the prevalence of MG, disease characteristics, and treatment outcomes at the largest Austrian HIV-and STI clinic., Methods: All MG test results at the Medical University of Vienna from 02/2019 to 03/2022 were evaluated. Azithromycin resistance testing was implemented in 03/2021., Results: Among 2671 MG tests, 199 distinct and mostly asymptomatic (68%; 135/199) MG infections were identified, affecting 10% (178/1775) of all individuals. This study included 83% (1479/1775) men, 53% (940/1775) men who have sex with men (MSM), 31% (540/1754) HIV+, and 15% (267/1775) who were using HIV pre-exposure prophylaxis (PrEP). In logistic regression analysis, 'MSM' (aOR 2.55 (95% CI 1.65-3.92)), 'use of PrEP' (aOR 2.29 (95% CI 1.58-3.32)), and 'history of syphilis' (aOR 1.57 (95% CI 1.01-2.24) were independent predictors for MG infections. Eighty-nine percent (178/199) received treatment: 11% (21/178) doxycycline (2 weeks), 52% (92/178) AZM (5 days), and 37% ( 65/178) moxifloxacin (7-10 days) and 60% (106/178) had follow-up data available showing negative tests in 63% (5/8), 76% (44/58) and 85% (34/40), respectively. AZM resistance analysis was available for 57% (114/199)) and detected in 68% (78/114). Resistance-guided therapy achieved a cure in 87% (53/61), yet, empiric AZM-treatment (prior to 03/2021) cleared 68% (26/38)., Conclusions: Mycoplasma genitalium was readily detected in this Austrian observational study, affected predominantly MSM and often presented as asymptomatic disease. We observed a worryingly high prevalence of AZM resistance mutations; however, empiric AZM treatment cleared twice as many MG infections as expected., (© 2024. The Author(s).)

Background: Sarcopenia is a progressive and systemic skeletal muscle disorder associated with an increased risk of hospitalization and adverse effects on survival. This study aims to investigate the prevalence and related risk factors of sarcopenia in people living with HIV using the revised European Working Group on Sarcopenia in Older People (EWGSOP2) definition., Methods: This cross-sectional study comprising 379 patients with confirmed HIV infection evaluated the appendicular skeletal muscle mass by employing the bioelectrical impedance analysis method. Muscle strength and functional mobility were analyzed using the five-time sit-to-stand test and the timed "Up and Go" test., Results: The prevalence rates of pre-sarcopenia and sarcopenia among people living with HIV were 3.4 % and 2.1 % according to the revised EWGSOP2 definition. Advanced age (Odds Ratio 1.07, p = .03), lower body mass index (Odds Ratio 0.79, p = .012) and CD4 + T-cell count below 500/μl (Odds Ratio 2.22, p = .007) were identified as significant factors associated with sarcopenia. Sarcopenia was also identified as a significant correlate of frailty ( p < .001)., Conclusion: This is the first study examining the prevalence of sarcopenia in people living with HIV according to the revised EWGSOP2 clinical algorithm. Advanced age, lower body mass index and a poor immune status are determined as promoting factors of sarcopenia. Sarcopenia significantly correlates with frailty. Standardized clinical algorithms are essential for reliable sarcopenia diagnosis in people living with HIV in order to promote intervention strategies and to prevent adverse health outcomes., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Torque teno virus (TTV) is part of the human virome. TTV load was related to the immune status in patients after organ transplantation. We hypothesize that TTV load could be an additional marker for immune function in people living with HIV (PLWH)., Methods: In this analysis, serum samples of PLWH from the RESINA multicenter cohort were reanalyzed for TTV. Investigated clinical and epidemiological parameters included human pegivirus load, patient age and sex, HIV load, CD4+ T-cell count (Centers for Disease Control and Prevention [CDC] stage 1, 2, or 3), and CDC clinical stage (1993 CDC classification system; stage A, B, or C) before initiation of antiretroviral therapy. Regression analysis was used to detect possible associations among parameters., Results: Our analysis confirmed TTV as a strong predictor of CD4+ T-cell count and CDC class 3. This relationship was used to propose a first classification of TTV load with regard to clinical stage. We found no association with clinical CDC stages A-C. The human pegivirus load was inversely correlated with HIV load but not TTV load., Conclusions: TTV load was associated with immunodeficiency in PLWH. Neither TTV nor HIV load were predictive for the clinical categories of HIV infection., Competing Interests: Potential conflicts of interest. B. E. O. J. has received consulting fees from Gilead, ViiV Healthcare (ViiV) and Merck Sharpe and Dohme (MSD). B. E. O. J. has received payment or honoraria for lectures and presentations from Gilead, ViiV and GSK. B. E. O. J. has received support for meetings and travel from Gilead. B. E. O. J. is scientific secretary of the German AIDS Society (unpaid). S. E. has received grants or contracts, support for meetings or travel, and payments or honoraria for lectures or presentations from Gilead, ViiV, MSD and Janssen. S. E. participated on a data safety monitoring board or advisory board for Gilead, ViiV, MSD, Janssen and GSK. S. E. is in a leadership or fiduciary role for the German AIDS Society and the National AIDS Comission NRW. S. E.reveived equipment, materials, drugs, medical writing, gifts or other services from Gilead and GSK. N. L. received consulting fees from ViiV. N. L. received honoraria for lectures from ViiV and MSD. N. L. received support for travel from the Deutsche AIDS Gesellschaft. J. K. R. received consulting fees from Behringer. J. K. R. received payment for lectures or presentations from Gilead, MSD and ViiV. J. K. R. was payed for the particpation on a data safety monitoring board or advisory board for Abivax. J. K. R. is EACS (European AIDS Clinical Society) board member. C. B. received grants or contracts from DZIF (German Center for Infection Research) and DFG (German Research Foundation). C. B. received consulting fees, payment for lectures and presentations, and support for meetings or travel from Abbvie, MSD, Janssen, Gilead and ViiV. C. B. is governing board member of EACS. R. K. received grants from DZIF. R. K. received payment for presentations or lectures from Janssen, Roche, Hologic, Abbvie, Abbott, MSD, ViiV, Gilead and Pfizer. R. K. particpated on a data safety monitoring board or advisory board for ViiV, Gilead, Pfizer, MSD and Janssen. All other authors: No reported conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Introduction: Granulomatosis due to immune reconstitution inflammatory syndrome (IRIS) and disseminated Mycobacterium avium-intracellulare (M. avium) infection may trigger hypercalcemia. Here, we report a rare case of hypercalcemia and acute kidney damage related to IRIS in a person living with Human Immunodeficiency Virus (HIV)., Case Presentation: A 39-year-old male person living with HIV presented with muscle weakness and unwanted weight loss of 8 kg within the last 2 weeks. Laboratory findings included serum hypercalcemia of 3.27 mmol/mL associated with elevated calcitriol and acute kidney damage. Since the first diagnosis of HIV and concomitant disseminated M. avium infection, the patient received antiretroviral therapy (ART), rifabutin, clarithromycin, and ethambutol. 18 Fluoro-D-glucose positron emission computed tomography ( 18 FDG-PET/CT) showed progressive multilocular lymphadenopathy. Biopsy specimen from the duodenum as well as retroperitoneal and mediastinal lymph nodes revealed granulomatous inflammation consistent with IRIS. Treatment with forced diuresis, bisphosphonates, and calcitonin normalized serum calcium and kidney function recovered., Conclusion: Hypercalcemia due to IRIS is a rare differential diagnosis in persons living with HIV and may lead to acute kidney damage, despite sufficient ART and antimycobacterial treatment., (© 2024. The Author(s).)

The interplay between host factors and viral components impacts viral replication efficiency profoundly. Members of the cellular heterogeneous nuclear ribonucleoprotein family (hnRNPs) have been extensively studied as HIV-1 host dependency factors, but whether they play a role in innate immunity is currently unknown. This study aimed to identify hnRNPA0 as a type I interferon (IFN)-repressed host factor in HIV-1-infected cells. Knockdown of hnRNPA0, a situation that mirrors conditions under IFN stimulation, increased LTR activity, export of unspliced HIV-1 mRNA, viral particle production, and thus, increased infectivity. Conversely, hnRNPA0 overexpression primarily reduced plasmid-driven and integrated HIV-1 long terminal repeat (LTR) activity, significantly decreasing total viral mRNA and protein levels. In addition, high levels of hnRNPA0 significantly reduced the HIV-1 programmed ribosomal frameshifting efficiency, resulting in a shift in the HIV-1 p55/p15 ratio. The HIV-1 alternative splice site usage remained largely unaffected by altered hnRNPA0 levels suggesting that the synergistic inhibition of the LTR activity and viral mRNA transcription, as well as impaired ribosomal frameshifting efficiency, are critical factors for efficient HIV-1 replication regulated by hnRNPA0. The pleiotropic dose-dependent effects under high or low hnRNPA0 levels were further confirmed in HIV-1-infected Jurkat cells. Finally, our study revealed that hnRNPA0 levels in PBMCs were lower in therapy-naive HIV-1-infected individuals compared to healthy controls. Our findings highlight a significant role for hnRNPA0 in HIV-1 replication and suggest that its IFN-I-regulated expression levels are critical for viral fitness allowing replication in an antiviral environment.IMPORTANCERNA-binding proteins, in particular, heterogeneous nuclear ribonucleoproteins (hnRNPs), have been extensively studied. Some act as host dependency factors for HIV-1 since they are involved in multiple cellular gene expression processes. Our study revealed hnRNPA0 as an IFN-regulated host factor, that is differently expressed after IFN-I treatment in HIV-1 target cells and lower expressed in therapy-naïve HIV-1-infected individuals. Our findings demonstrate the significant pleiotropic role of hnRNPA0 in viral replication: In high concentrations, hnRNPA0 limits viral replication by negatively regulating Tat-LTR transcription, retaining unspliced mRNA in the nucleus, and significantly impairing programmed ribosomal frameshifting. Low hnRNPA0 levels as observed in IFN-treated THP-1 cells, particularly facilitate HIV LTR activity and unspliced mRNA export, suggesting a role in innate immunity in favor of HIV replication. Understanding the mode of action between hnRNPA0 and HIV-1 gene expression might help to identify novel therapeutically strategies against HIV-1 and other viruses., Competing Interests: The authors declare no conflict of interest.

While SARS-CoV-2 has transitioned to an endemic phase, infections caused by newly emerged variants continue to result in severe, and sometimes fatal, outcomes or lead to long-term COVID-19 symptoms. Vulnerable populations, such as PLWH, face an elevated risk of severe illness. Emerging variants of SARS-CoV-2, including numerous Omicron subvariants, are increasingly associated with breakthrough infections. Adapting mRNA vaccines to these new variants may offer improved protection against Omicron for vulnerable individuals. In this study, we examined humoral and cellular immune responses before and after administering adapted booster vaccinations to PLWH, alongside a control group of healthy individuals. Four weeks following booster vaccination, both groups exhibited a significant increase in neutralizing antibodies and cellular immune responses. Notably, there was no significant difference in humoral immune response between PLWH and the healthy controls. Immune responses declined rapidly in both groups three months post vaccination. However, PLWH still showed significantly increased neutralizing antibody titers even after three months. These findings demonstrate the efficacy of the adapted vaccination regimen. The results suggest that regular booster immunizations may be necessary to sustain protective immunity.

Background and purpose: Capecitabine can be used as first-line treatment for advanced breast cancer. However, real-world data on efficacy of capecitabine in this setting is sparse. The purpose of the study is to evaluate outcomes of patients with Human Epidermal Growth Factor Receptor (HER2)-normal advanced breast cancer treated with capecitabine monotherapy as first-line treatment., Material and Methods: The study utilized the Danish Breast Cancer Group (DBCG) database and was conducted retrospectively across all Danish oncology departments. Inclusion criteria were female patients, with HER2-normal advanced breast cancer treated with capecitabine monotherapy as the first-line treatment from 2010 to 2020. The primary endpoints were overall survival (OS) and progression-free survival (PFS)., Results: A total of 494 patients were included. Median OS was 16.4 months (95% confidence interval [CI]: 14.5-18.0), and median PFS was 6.0 months (95% CI: 5.3-6.7). Patients with estrogen receptor (ER)-positive disease had significantly longer OS (median: 22.8 vs. 10.5 months, p < 0.001) and PFS (median: 7.4 vs. 4.9 months, p = 0.003), when compared to ER-negative patients. Stratifying by age, patients under 45 years displayed a median PFS of 4.1 months, while those aged 45-70 years and over 70 years had median PFS of 5.7 and 7.2 months, respectively (p = 0.01)., Interpretation:  In this nationwide study, the efficacy of capecitabine as a first-line treatment for HER2-normal advanced breast cancer is consistent with other, mainly retrospective, studies. However, when assessed against contemporary and newer treatments, its effectiveness appears inferior to alternative chemotherapies or targeted therapies.

Background: Initial treatment for advanced ER-positive/HER2-negative breast cancer involves a CDK 4/6 inhibitor (CDK 4/6i). Recent overall survival (OS) analyses led the Danish Medical Council to exclude palbociclib as preferred option. This study aimed to evaluate the real-world effectiveness of abemaciclib, palbociclib, and ribociclib in a Danish context. Additionally, to compare the inhibitors to identify potential endpoint differences., Material and Methods: Patients undergoing first or second line CDK 4/6i treatments from January 1st, 2017, until December 31st, 2021 were included. The primary endpoint was progression free survival (PFS)., Results: Among 2069 Danish patients, 1554 received first line treatment, 515 received second line treatment. In first line, abemaciclib's median PFS was unreached; palbociclib had a median PFS of 32.0 months (95% CI: 28.9-35.3); ribociclib 42.4 months (95% CI: 35.1-52.9). First-line median OS was 37.8 months (95% CI: 32.5-NA); 49.7 months (95% CI: 44.7-54.1); and 54.4 months (95% CI: 47.9-NA) for abemaciclib, palbociclib and ribociclib, respectively. No significant differences in OS were observed, nor in PFS in second line., Conclusion: This study confirms first-line CDK 4/6i effectiveness, with abemaciclib and ribociclib showing prolonged PFS vs. palbociclib. This study could not confirm a ranking of the three CDK 4/6i., (© 2024. The Author(s).)

Van-der-Waals magnetic materials can be exfoliated to realize ultrathin sheets or interfaces with highly controllable optical or spintronics responses. In majority, these are collinear ferro-, ferri-, or antiferromagnets, with a particular scarcity of lattice-incommensurate helimagnets of defined left- or right-handed rotation sense, or helicity. Here, we report polarized neutron scattering experiments on DyTe 3 , whose layered structure has highly metallic tellurium layers separated by double-slabs of dysprosium square nets. We reveal cycloidal (conical) magnetic textures, with coupled commensurate and incommensurate order parameters, and probe the evolution of this ground state in a magnetic field. The observations are well explained by a one-dimensional spin model, with an off-diagonal on-site term that is spatially modulated by DyTe 3 's unconventional charge density wave (CDW) order. The CDW-driven term couples to antiferromagnetism, or to the net magnetization in an applied magnetic field, and creates a complex magnetic phase diagram indicative of competing interactions in this easily cleavable van-der-Waals helimagnet., (© 2024. The Author(s).)

We report on time-resolved nonlinear terahertz spectroscopy of a strongly correlated ruthenate, CaRuO&#95;{3}, as a function of temperature, frequency, and terahertz field strength. Third-harmonic radiation for frequencies up to 2.1 THz is observed evidently at low temperatures below 80 K, where the low-frequency linear dynamical response deviates from the Drude model and a coherent heavy quasiparticle band emerges by strong correlations associated with the Hund's coupling. Phenomenologically, by taking an experimentally observed frequency-dependent scattering rate, the deviation of the field driven kinetics from the Drude behavior is reconciled in a time-dependent Boltzmann description, which allows an attribution of the observed third-harmonic generation to the terahertz field driven nonlinear kinetics of the heavy quasiparticles.

Background: The quality of communication in oncology significantly impacts patients' health outcomes, as poor communication increases the risk of unnecessary treatment, inadequate pain relief, higher anxiety levels, and acute hospitalizations. Additionally, ineffective communication skills training (CST) is associated with stress, low job satisfaction, and burnout among doctors working in oncology. While acknowledging the importance of effective communication, the specific features of successful CST remain uncertain. Role-play and recorded consultations with direct feedback appear promising for CST but may be time-consuming and face challenges in transferring acquired skills to clinical contexts. Our aim is to bridge this gap by proposing a novel approach: On-site Supportive Communication Training (On-site SCT). The concept integrates knowledge from previous studies but represents the first randomized controlled trial employing actual doctor-patient interactions during CST., Methods: This randomized multicenter trial is conducted at three departments of oncology in Denmark. Doctors are randomized 1:1 to the intervention and control groups. The intervention group involves participation in three full days of On-site SCT facilitated by a trained psychologist. On-site SCT focuses on imparting communication techniques, establishing a reflective learning environment, and offering emotional support with a compassionate mindset. The primary endpoint is the change in percentage of items rated "excellent" by the patients in the validated 15-item questionnaire Communication Assessment Tool. The secondary endpoints are changes in doctors' ratings of self-efficacy in health communication, burnout, and job satisfaction measured by validated questionnaires. Qualitative interviews will be conducted with the doctors after the intervention to evaluate its relevance, feasibility, and working mechanisms. Doctors have been actively recruited during summer/autumn 2023. Baseline questionnaires from patients have been collected. Recruitment of new patients for evaluation questionnaires is scheduled for Q1-Q2 2024., Discussion: This trial aims to quantify On-site SCT efficacy. If it significantly impacts patients/doctors, it can be a scalable CST concept for clinical practice. Additionally, qualitative interviews will reveal doctors' insight into the most comprehensible curriculum parts., Trial Registration: April 2023 - ClinicalTrials.gov (NCT05842083). April 2023 - The Research Ethics Committee at the University of Southern Denmark (23/19397)., (© 2024. The Author(s).)

Traditional cardiovascular risk scores underestimate the incidence of cardiovascular diseases (CVD) in people living with HIV (PLH). This study compared the effect of HIV-specific cardiovascular risk factors (CRF) with traditional CRF at baseline for their association with incident CVD in PLH. The ongoing, prospective HIV HEART Aging (HIVH) study assesses CVD in PLH in the German Ruhr Area since 2004. PLH from the HIVH study with at least 5 years of follow-up were examined with the help of Cox proportional hazards models using inverse probability-of-censoring weights. The models were adjusted for age and sex. The obtained hazard ratios (HR) and 95% confidence limits (CL) assessed the strength of the associations between CRF and CVD. One thousand two hundred forty-three individuals (male 1,040, female 203; mean age of 43 ± 10 years) with 116 incident CVD events were analyzed. After adjusting for the traditional CRF, the HIV-specific CRF "a history of AIDS" and "higher age at diagnosis of HIV infection" (per 10 years) were associated with an increased CVD risk (HR 1.55, 95% CL: 1.05-2.28 and HR 1.55, 95% CL: 1.09-1.22, respectively). Higher CD4/CD8 ratio (per standard deviation), longer cumulative duration of antiretroviral therapies, and longer duration of HIV infection (per 10 years) showed indications for a decreased CVD risk (HR 0.75, 95% CL: 0.58-0.97, HR 0.71, 95% CL: 0.41-1.23, and HR 0.63, 95% CL: 0.44-0.90, respectively). Out of the traditional CRF, current smoking showed the strongest impact on CVD risk (HR 3.12, 95% CL: 2.06-4.74). In conclusion, HIV-specific factors, such as history of AIDS and CD4/CD8 ratio, were independently associated with an increased cardiovascular risk. Traditional CRF maintained a major effect on CVD. Clinical Trials Number (NCT04330287).

Background: Real-world evidence is an essential component of evidence-based medicine. The aim of the BICSTaR (BICtegravir Single Tablet Regimen) study is to assess effectiveness and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in antiretroviral treatment-naïve (TN) and treatment-experienced (TE) people with HIV., Methods: BICSTaR is a prospective, observational cohort study. Participants (≥18 years) are being followed for 24 months. A pooled analysis is presented at 12 months, with the primary endpoint of effectiveness (HIV-1 RNA <50 copies/mL) and secondary endpoints of safety and tolerability (as per protocol). An exploration of patient-reported outcome measures using standardized questionnaires is included., Results: Between June 2018 and May 2021, 1552 people with HIV were enrolled across 12 countries. The analysed population comprised 1509 individuals (279 TN, 1230 TE); most were white (76%), male (84%) and had one or more comorbid conditions (68%). Median age was 47 years. After 12 months of B/F/TAF treatment, HIV-1 RNA was <50 copies/mL in 94% (221/236) of TN participants and 97% (977/1008) of TE participants. Median CD4 cell count increased by 214 cells/μL (p < 0.001) in TN participants and 13 cells/μL (p = 0.014) in TE participants; median CD4/CD8 ratios increased by 0.30 and 0.03, respectively (both p < 0.001). Persistence was high at 12 months (TN, 97%; TE, 95%). No resistance to B/F/TAF emerged. Study drug-related adverse events occurred in 13% of participants through 12 months, leading to B/F/TAF discontinuation in 6%., Conclusions: The findings of this study provide robust real-world evidence to support the broad use of B/F/TAF in both TN and TE people with HIV., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

The human gut microbiota is influenced by various factors, including health status and environmental conditions, yet considerable inter-individual differences remain unexplained. Previous studies identified that the gut microbiota of men who have sex with men (MSM) is distinct from that of non-MSM. Here, we reveal through species-level microbiota analysis using shotgun metagenomics that the gut microbiota of many MSM with Western origin resembles gut microbial communities of non-Westernized populations. Specifically, MSM gut microbiomes are frequently dominated by members of the Prevotellaceae family, including co-colonization of species from the Segatella copri complex and unknown Prevotellaceae members. Questionnaire-based analysis exploring inter-individual differences in MSM links specific sexual practices to microbiota composition. Moreover, machine learning identifies microbial features associated with sexual activities in MSM. Together, this study shows associations of sexual activities with gut microbiome alterations in MSM, which may have a large impact on population-based microbiota studies., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

A global outbreak of predominantly sexually transmitted mpox infections, outside endemic regions, was reported in May 2022. Thereafter, risk groups were vaccinated against smallpox, a structurally related orthopoxvirus. In the current study, we analyzed T cell responses against peptides derived from orthopoxviruses in 33 HIV-positive patients after two vaccinations against smallpox and in 10 patients after mpox infection. We established an ELISpot assay, detecting either the secretion of the pro-inflammatory cytokine interferon (IFN)-γ or interleukin (IL)-2. After vaccination, 21 out of 33 patients (64%) showed specific IFN-γ secretion and 18 (55%) specific IL-2 secretion, defined as >3-fold higher specific value than negative control and at least 4 spots above the negative control. After mpox infection, all patients showed specific IFN-γ secretion and 7 out of 10 (70%) IL-2 secretion. In vaccinated patients, IFN-γ responses were significantly lower than in patients with mpox infection (median response 4.5 vs. 21.0 spots, p < 0.001). The same trend was observed for IL-2 responses. After mpox infection, IL-2 ELISpot results positively correlated with CD8+ T cells ( p < 0.05). Thus, T cell responses were detectable in two thirds of HIV-positive patients after vaccination and were even more abundant and vigorous after mpox infection.

What Is This Summary About?: This is a summary of an article about an ongoing study called the BICSTaR study.The BICSTaR study includes people with HIV (human immunodeficiency virus) who are taking a medicine called bictegravir/emtricitabine/tenofovir alafenamide (shortened to B/F/TAF). B/F/TAF is a single tablet that contains 3 different drugs for the treatment of HIV. The drugs work together to reduce the levels of HIV so that the virus can no longer be detected by a blood test.People taking part in the study are adults with HIV living in Europe, Canada, Israel, Japan, South Korea, Singapore and Taiwan. People take 1 tablet of B/F/TAF once a day. They are either taking B/F/TAF as their first treatment for HIV, or they have switched to B/F/TAF from another HIV treatment.Researchers looked at how well B/F/TAF worked and how safe it was in people who took B/F/TAF for a year., What Are the Key Takeaways?: Researchers found that B/F/TAF worked well in almost all people in the study by reducing levels of HIV in the blood. The virus could not be found in the blood of more than 9 out of 10 (94%) people who were taking B/F/TAF as their first HIV medicine and more than 9 out of 10 people (97%) who had taken another HIV medicine before starting B/F/TAF. This is known as having an 'undetectable viral load' and is a major goal for HIV treatment success. Researchers did not find any evidence of HIV developing resistance to B/F/TAF, which might stop B/F/TAF from working properly.Around 1 out of 10 people (13%) had side effects (any unwanted sign or symptom that people have when taking a medicine that researchers think might be caused by the medicine) that might have been caused by B/F/TAF. Most of these side effects were not classified as serious. Less than 1 out of 100 (0.1%) people had serious side effects that might have been caused by B/F/TAF. Only 6 out of 100 people stopped taking B/F/TAF due to side effects caused by B/F/TAF. As a result, more than 9 out of 10 people (95%) took B/F/TAF for at least 1 year., What Were the Main Conclusions Reported by the Researchers?: B/F/TAF worked well in people with HIV in this study. Most people (around 9 out of 10) did not have any side effects.

Objective: To understand how mothers use commercial milk formula (CMF) labels to inform their feeding choices and explore mothers' understanding of differences between CMF products., Design: Qualitative study with recruitment via social media. Online semistructured interviews, including a product mapping exercise and thematic analysis., Participants: Mothers (n=25) using CMF for children <3 years living in Great Britain (GB)., Results: Mothers were drawn to brands they recognised from years of exposure to CMF advertising. CMF products were assumed to vary according to brand and stage, but participants found on-pack information did not explain how. This added to anxiety about choosing 'the best one' and mothers would have liked guidance from healthcare professionals (HCPs). Wide availability of CMF for older infants and children, and on-pack messaging suggesting progression from one product to the next, led many to believe these products were necessary. There was confusion over the appropriate use of specialist products. While mothers rarely mentioned on-pack health and nutrition claims, they were attracted to the overall appearance of packs and messaging relating to science, research and nature. References to breast milk and a logo perceived to represent a breastfeeding mother were taken as indicators of closer similarity to breast milk., Conclusions: CMF legislation in GB should be updated to restrict brand advertising and the use of on-pack text and images that mothers perceive as indicating products have a closer similarity to breast milk. Greater input from HCPs was desired by new mothers and would support them to make more informed choices about CMF., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Very limited data on tinea genitalis, a potentially severe dermatophytosis transmitted during sexual intercourse affecting the genital area, suggest its potential to cause outbreaks. Thus, we investigated genital dermatophyte infections at an HIV/sexually transmitted infection clinic and identified 17 men who have sex with men (all people with HIV or pre-exposure prophylaxis users) diagnosed with tinea genitalis., Competing Interests: Potential conflicts of interest. D.C. has served as a speaker and/or advisory board member for Gilead, ViiV Healthcare, and MSD and has received travel support from MSD, ViiV Healthcare, and Gilead. A.M.O. has nothing to disclose. W.M.B. has served as a speaker and/or consultant and/or advisory board member for AbbVie, ViiV Healthcare, and Takeda and has received travel support from AbbVie, MSD, ViiV Healthcare, and Gilead. V.T.R. has nothing to disclose. C.B. has nothing to disclose. S.E. has served as a speaker and/or advisory board member for Gilead, GSK, Janssen, MSD, and ViiV Healthcare and has received travel support from Gilead, Janssen, MSD, and ViiV Healthcare and research grants from Gilead, Janssen, MSD, and ViiV Healthcare. W.W. has served as a speaker, consultant, and/or advisory board member for LEO Pharma, Pfizer, Sanofi Genzyme, Eli Lilly, Novartis, Boehringer Ingelheim, AbbVie, and Janssen. B.W. has served as a speaker for Gilead and an advisory board member for MSD. K.G.P. has served as a speaker and/or consultant and/or advisory board member for ViiV and Gilead and has received travel support from ViiV Healthcare and Gilead., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Human immunodeficiency virus type 1 (HIV-1)-neutralizing antibodies (nAbs) that prevent infection are the main goal of HIV vaccine discovery. But as no nAb-eliciting vaccines are yet available, only data from HIV-1 neutralizers-persons with HIV-1 who naturally develop broad and potent nAbs-can inform about the dynamics and durability of nAb responses in humans, knowledge which is crucial for the design of future HIV-1 vaccine regimens. To address this, we assessed HIV-1-neutralizing immunoglobulin G (IgG) from 2,354 persons with HIV-1 on or off antiretroviral therapy (ART). Infection with non-clade B viruses, CD4 + T cell counts <200 µl -1 , being off ART and a longer time off ART were independent predictors of a more potent and broad neutralization. In longitudinal analyses, we found nAb half-lives of 9.3 and 16.9 years in individuals with no- or low-level viremia, respectively, and 4.0 years in persons who newly initiated ART. Finally, in a potent HIV-1 neutralizer, we identified lower fractions of serum nAbs and of nAb-encoding memory B cells after ART initiation, suggesting that a decreasing neutralizing serum activity after antigen withdrawal is due to lower levels of nAbs. These results collectively show that HIV-1-neutralizing responses can persist for several years, even at low antigen levels, suggesting that an HIV-1 vaccine may elicit a durable nAb response., (© 2023. The Author(s).)

Antiretroviral therapy (ART) transformed HIV from a life-threatening disease to a chronic condition. However, eliminating the virus remains an elusive therapy goal. For several decades, Friend virus (FV) infection serves as a murine model to study retrovirus immunity. Similar to HIV, FV persists at low levels in lymph nodes B cell follicles avoiding elimination by immune cells. Such immune-privileged reservoirs exclude cytotoxic T cells from entry. However, CXCR5+ T cells are permitted to traffic through germinal centers. This marker is predominantly expressed by CD4+ follicular helper T cells (Tfh). Therefore, we explored immunotherapy to induce cytotoxic Tfh, which are rarely found under physiological conditions. The TNF receptor family member CD137 was first identified as a promising target for cancer immunotherapy. We demonstrated that FV-infected mice treatment with αCD137 antibody resulted in an induction of the cytotoxic program in Tfh. The therapy significantly increased numbers of cytotoxic Tfh within B cell follicles and contributed to viral load reduction. Moreover, αCD137 antibody combined with ART delayed virus rebound upon treatment termination without disturbing the lymph node architecture or antibody responses. Thus, αCD137 antibody therapy might be a novel strategy to target the retroviral reservoir and an interesting approach for HIV cure research., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Malyshkina et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Integrase inhibitors have been recently linked to a higher risk for hypertension. In NEAT022 randomized trial, virologically suppressed persons with human immunodeficiency virus (HIV, PWH) with high cardiovascular risk switched from protease inhibitors to dolutegravir either immediately (DTG-I) or after 48 weeks (DTG-D)., Methods: Primary endpoint was incident hypertension at 48 weeks. Secondary endpoints were changes in systolic (SBP) and diastolic (DBP) blood pressure; adverse events and discontinuations associated with high blood pressure; and factors associated with incident hypertension., Results: At baseline, 191 (46.4%) participants had hypertension and 24 persons without hypertension were receiving antihypertensive medications for other reasons. In the 197 PWH (n = 98, DTG-I arm; n = 99, DTG-D arm) without hypertension or antihypertensive agents at baseline, incidence rates per 100 person-years were 40.3 and 36.3 (DTG-I) and 34.7 and 52.0 (DTG-D) at 48 (P = .5755) and 96 (P = .2347) weeks. SBP or DBP changes did not differed between arms. DBP (mean, 95% confidence interval) significantly increased in both DTG-I (+2.78 mmHg [1.07-4.50], P = .0016) and DTG-D (+2.29 mmHg [0.35-4.23], P = .0211) arms in the first 48 weeks of exposure to dolutegravir. Four (3 under dolutegravir, 1 under protease inhibitors) participants discontinued study drugs due to adverse events associated with high blood pressure. Classical factors, but not treatment arm, were independently associated with incident hypertension., Conclusions: PWH at high risk for cardiovascular disease showed high rates of hypertension at baseline and after 96 weeks. Switching to dolutegravir did not negatively impact on the incidence of hypertension or blood pressure changes relative to continuing protease inhibitors., Competing Interests: Potential conflicts of interest. A. G.-C. has received honoraria for lectures (Gilead, Janssen, Merck, Sharp & Dohme [MSD], and ViiV), advisory boards (ViiV) or travel grants (Gilead, MSD, and ViiV) and her institution has received research grants from Gilead, Janssen, MSD, and ViiV; L. W. has received honoraria for lectures and consulting fees (Gilead, MSD, ViiV), advisory boards or travel grants from Gilead, Janssen, MSD, and ViiV; S. R. has received honoraria for lectures, advisory boards or travel grants from Gilead, Janssen, and ViiV. He also reports payment or honoraria from MSD and Theratechnologies; P. D. has received honoraria for lectures or advisory boards and his institution has received research grants from Gilead, Janssen, MSD and ViiV. He also reports consulting fees and payment or honoraria from Gilead Sicences, ViiV Healthcare, Jansen & Cilag, Merck, Sharp & Dohme, Roche, GSK; M. G. has received honoraria for lectures, advisory boards or travel grants from Gilead, MSD, and ViiV; F. R. has received honoraria for lectures (Gilead, Merck, and ViiV), advisory boards (Merck and ViiV) or travel grants (Gilead and ViiV) from Gilead, Janssen, MSD, Theratechnologies, and ViiV. He also reports consulting fees from Gilead, Merck, and ViiV; C. S. has received honoraria for lectures (Gilead and Janssen Cilag), advisory boards or travel grants from Gilead, Janssen, and MSD; M. M. has received honoraria for lectures, advisory boards (Janssen, ViiV, MSD) or travel grants (Janssen and MSD) from ViiV, Janssen, and MSD; J. R. has received honoraria for lectures, advisory boards or travel grants from Abivax, Boehringer (consulting fees), Galapagos, Gilead (honoraria and travel grant), Janssen (honoriaria), Merck (honoraria) Theratechnologies and ViiV (honoraria), and reports a role as GB member of EACS and Co-chair of EuroTEST; C. K. has received honoraria for lectures, advisory boards or travel grants and her institution has received research grants from Gilead (consulting), MSD (consulting, honoraria) and ViiV (consulting, honoraria); G. M. N. B. has received honoraria for lectures, advisory boards or travel grants and his institution has received research grants from Gilead (consulting fees, travel grants, and honoraria), Janssen, MSD (grants, consulting fees, travel grants, honoraria), and ViiV (consulting fees, travel grants, and honoraria), and Theratechnologies (consulting fees and honoraria); G. M. has received honoraria for lectures, advisory boards or travel grants and his institution has received research grants from Gilead, MSD, Theratechnologies, and ViiV; J. F. has received honoraria for lectures, advisory boards or travel grants and consulting fees from Gilead, Janssen, MSD, and ViiV; H. J. S. has received honoraria for lectures (Gilead, ViiV, MSD), advisory boards (Gilead, ViiV, MSD) or travel grants (Gilead) and his institution has received research grants (Gilead, ViiV, MSD, Janssen, GSK, Heidelberg) from Gilead, GSK, Heildelberg Immunotherapeutics, Janssen, MSD, and ViiV, and reports consulting fees from Gilead, ViiV, Janssen & Cilag, and MSD; payment for expert testimony from Gilead; receipt of equipment from Gilead; G. G. has received honoraria for lectures, advisory boards or travel grants and his institution has received research grants from Gilead, MSD, and ViiV; E. F. has received honoraria for lectures (Gilead and ViiV), advisory boards or travel grants from Gilead, Janssen, MSD, and ViiV; S. F. has received honoraria for lectures, advisory boards or travel grants and grants or contracts paid to institution from Gilead, MSD, ViiV, and Janssen; J. M. G. is a full-time employee of and owns stock in ViiV as Senior Global Medical Director since 1 May 2018; A. P. has received honoraria for lectures or advisory boards and consulting fees and his institution has received research grants from Gilead, Janssen, MSD, and ViiV; E. M. has received honoraria for lectures (Gilead, ViiV, MSD) or advisory boards and his institution has received research grants (MSD, ViiV) and consulting fees from Gilead, Janssen, MSD, Theratechnologies, and ViiV. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The ability to anticipate the sensory consequences of our actions (i.e., action-effects) is known to be important for intentional action initiation and control. Learned action-effects can select the responses that previously have been associated with them. What has been largely unexplored is how learned action-effect associations can aid action selection for effects that have not previously associated with an action but are similar to learned effects. In two studies, we aimed to show that when presented new, unknown action-effects, participants select the responses that have previously been associated with similar action-effects. In the first study (n = 27), action-effect similarity was operationalized via stimuli belonging to the same or different categories as the previously learned action-effects. In the second study (n = 31), action-effect similarity was realized via stimuli that require comparable motor responses in real life. Participants first learned that specific responses are followed by specific visual effect stimuli. In the test phase, learned effect stimuli, new but similar effect stimuli and new but dissimilar effect stimuli were presented ahead of the response. The findings revealed that both learned effect stimuli and new similar effect stimuli affected response times, whereas new dissimilar effects did not. When a learned or a new similar effect was followed by a learned response, compared to an unlearned response, the responses were faster. We interpret these findings in terms of action-effect learning. The action-effect once bound to an action is used to select an action if a similar effect for which no action has been learned yet is presented. However, it is noteworthy that, due to our design, other explanations for the found transfer are conceivable. We address these limitations in the General Discussion., (© 2023. The Author(s).)

Background: In the NEAT022 trial, switching from boosted PIs (PI/r) to dolutegravir in people with HIV (PWH) with high cardiovascular risk decreased plasma lipids, soluble CD14 and adiponectin, and showed consistent favourable, although non-significant, effects on carotid intima-media thickness (CIMT) progression at 48 weeks. We hereby communicate planned final 96 week results on biomarker changes and CIMT progression., Methods: PWH on a PI/r-based triple therapy regimen were randomly assigned (1:1) to switch the PI/r component to dolutegravir either immediately (DTG-I group) or after 48 weeks (DTG-D group) and were followed up to 96 weeks. We assessed changes in biomarkers associated with inflammation, endothelial dysfunction, monocyte immune activation, oxidation, insulin resistance, hypercoagulability, heart failure, myocardial injury and glomerular and tubular kidney injury, and right and left CIMT progression at 48 and 96 weeks., Results: Of 415 PWH randomized, 287 (69%) and 143 (34%) contributed to the biomarker and CIMT substudies respectively. There were significant 96 week changes in biomarkers associated with inflammation, immune activation, oxidation, insulin resistance and myocardial injury. Most changes were favourable, except for adiponectin reduction, which may suggest higher insulin resistance. We were unable to detect significant changes in the progression of CIMT between arms or within arms at 96 weeks., Discussion: After 96 weeks, switching from PI/r to dolutegravir in PWH with high cardiovascular risk led to significant changes in several biomarkers associated with cardiovascular disease. Although most changes were favourable, adiponectin reduction was not. There were non-significant changes in CIMT progression., (© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Despite the potentially accompanying negative clinical, epidemiologic, and health economic effects, a large proportion of persons living with the human immunodeficiency virus (HIV) are diagnosed late. Internationally, numerous diseases are known to be HIV indicator diseases. Adequate HIV testing in the presence of HIV indicator diseases could help to diagnose unknown HIV infections earlier. The objective of the HeLP study is to validate published HIV indicator diseases for the German setting and to identify guidelines in terms of these indicator diseases in order to reduce knowledge gaps and increase HIV testing when HIV indicator diseases are diagnosed., Methods: A mixed methods approach is used. In a first step, published HIV indicator diseases will be identified in a systematic literature review and subsequently discussed with clinical experts regarding their relevance for the German setting. For the validation of selected indicator diseases different data sets (two cohort studies, namely HIV-1 seroconverter study & ClinSurv-HIV, and statutory health insurance routine data) will be analyzed. Sensitivity analyses using different time periods will be performed. Guidelines of HIV indicator diseases validated in the HeLP study will be reviewed for mentioning HIV and for HIV testing recommendations. In addition, semi-standardized interviews (followed by a free discussion) with guideline creators will identify reasons why HIV testing recommendations were (not) included. Subsequently, a random sample of physicians in medical practices will be surveyed to identify how familiar physicians are with HIV testing recommendations in guidelines and, if so, which barriers are seen to perform the recommended tests in everyday care., Discussion: The HeLP-study adopts the challenge to validate published HIV indicator diseases for the German setting and has the potential to close a knowledge gap regarding this objective. This has the potential to improve targeted HIV testing for patients with HIV indicator diseases and consequently lead to earlier HIV diagnosis., Trial Registration: DRKS00028743., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Overweight and obesity have increased in people living with HIV (PLH). Our study evaluated weight, body-mass-index (BMI), and waist-to-hip ratio (WHR) change over 5 years of follow-up in PLH compared to the general population., Methods: HIV-positive participants in the HIV Heart Aging (HIVH) study were matched 1:2 by age and sex with HIV-negative controls of the population-based Heinz Nixdorf Recall (HNR) study. Both studies were recruited in the German Ruhr area. The association between HIV and weight, BMI, and WHR changes was examined using linear regression. Regression models were adjusted for parameters potentially affecting weight gain., Results: The matched HIVH and HNR participants (N = 585 and N = 1170, respectively; 14.7% females) had a mean age of 55 years at baseline. Despite the lower baseline weight (- 6 kg, 95% CI - 7.46 to - 4.59), the linear regression showed greater absolute and relative weight and BMI increases after 5 years in HIVH compared to HNR. Adjusting the linear regression models for smoking amplified that HIVH had a higher absolute and relative weight difference of 0.7 kg or ~ 1% compared to HNR after 5 years (95% Cl 0.1 to 1.3 and 0.2 to 1.6, respectively). Adjusting for HDL, LDL, systolic blood pressure, and diabetes mellitus did not affect the results., Conclusions: PLH had lower weight than the general population at baseline and after 5 years, but experienced greater increases in body weight after 5 years. WHR change after 5 years was lower in PLH compared to the general population, despite a higher WHR at baseline., (© 2023. The Author(s).)

Objective: To explore on-package formula messaging with reference to legislation and government-issued guidance in Great Britain (GB)., Design: Formula products were identified, pictures of all sides of packs collated and on-package text and images were coded. Compliance with both GB legislation and guidance issued by the Department of Health and Social Care (DHSC) was assessed., Setting: All formula packs that were available for sale over the counter in GB between April and October 2020., Participants: Formula packs ( n 71) including infant formula, follow-on formula, growing-up formula and specialist formula were identified, coded and analysed., Results: In total, 41 % of formula packs included nutrition claims, and 18 % included health claims that may be considered non-permitted, according to DHSC guidance. Additionally, 72 % of products showed images considered 'non-permitted'. Breast Milk Substitute (BMS) legislation states infant and follow-on formula packs should be clearly distinguishable but does not provide criteria to assess similarity. Based on DHSC guidance, 72 % of infant and follow-on formula packs were categorised as showing a high degree of similarity. Marketing practices not covered by current legislation were widespread, such as 94 % of infant formula packs including advertisements for follow-on or growing-up formula., Conclusions: Text and images considered non-permitted according to DHSC guidance for implementing BMS legislation were widespread on formula products available in GB. As terms such as 'similarity' are not defined in BMS legislation, it was unclear if breaches had occurred. Findings support the WHO call for loopholes in domestic legislation to be closed as a matter of urgency.

Acute SARS-CoV-2 infection has been associated with false-positive HIV screening tests. The underlying mechanism is unclear, and for clinical cases, evidence beyond a temporal connection is missing. However, several experimental studies point toward SARS-CoV-2 spike/HIV-1 envelope (Env) cross-reactive antibodies (Abs) as a cause. Here, we present the first case of an individual with convalescent SARS-CoV-2 infection testing false positive in both an HIV screening and confirmatory test. Longitudinal sampling showed that the phenomenon was temporary but lasted for at least 3 months before waning. After excluding a multitude of common determinants for assay interference, we further show by antibody depletion studies that SARS-CoV-2-spike-specific Abs did not cross-react with HIV-1 gp120 in the patient sample. No additional case of HIV test interference was identified in a cohort of 66 individuals who presented to a post-COVID-19 outpatient clinic. We conclude the SARS-CoV-2-associated HIV test interference to be a temporary process capable of disturbing both screening and confirmatory assays. The assay interference is short-lived and/or rare but should be considered by physicians as a possible explanation for unexpected HIV diagnostic results in patients with a recent SARS-CoV-2 infection.

Background: Since May 2022, increasing numbers of monkeypox virus (MPXV) infections have been reported from across Europe and North America. Studies, mainly from Africa, have suggested a higher risk for severe MPXV cases in people living with HIV., Methods: This was a retrospective study of all confirmed MPXV infections observed in the participating centres since 19 May 2022. We conducted a chart review to evaluate clinical characteristics, comorbidities, and coinfections, including HIV, viral hepatitis, and sexually transmitted infections (STIs)., Results: By 30 June 2022, a total of 546 MPXV infections were reported from 42 German centres. All patients were men who have sex with men (MSM), of whom 256 (46.9%) were living with HIV, mostly with a preserved immune system and with viral suppression. In total, 232 (42.5%) MSM were also taking HIV pre-exposure prophylaxis (PrEP) and 58 (10.6%) MSM had no known HIV infection or PrEP use. The median age was 39 years (range 20-67), and comorbidities were rare. However, 52.4% and 29.4% of all patients had been diagnosed with at least one STI within the last 6 months or within the last 4 weeks, respectively. The most frequent localizations of MPXV infection were genital (49.9%) and anal (47.9%), whereas fever (53.2%) and lymphadenopathy (42.6%) were the most frequent general symptoms. The hospitalization rate was low (4.0%), and no fatal course was observed. The clinical picture showed no apparent differences between MSM with or without HIV., Conclusions: In this preliminary cohort analysis from a current large outbreak among MSM in Germany, the clinical picture of MPXV infection did not differ between MSM with and without HIV infection. Severe courses were rare and hospitalization rates were low. However, most patients were relatively healthy, and only a few people living with HIV were viremic or severely immunosuppressed., (© 2022 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: In the NEAT022 trial, virologically suppressed persons with human immunodeficiency virus (HIV) at high cardiovascular risk switching from protease inhibitors to dolutegravir either immediately (DTG-I) or after 48 weeks (DTG-D) showed noninferior virological suppression and significant lipid and cardiovascular disease risk reductions on switching to dolutegravir relative to continuing protease inhibitors., Methods: In post hoc analysis, major endpoints were 48-week and 96-week weight and body mass index (BMI) changes. Factors associated with weight/BMI changes within the first 48 weeks of DTG exposure, proportion of participants by category of percentage weight change, proportions of BMI categories over time, and impact on metabolic outcomes were also assessed., Results: Between May 2014 and November 2015, 204 (DTG-I) and 208 (DTG-D) participants were included. Weight significantly increased (mean, +0.810 kg DTG-I arm, and +0.979 kg DTG-D arm) in the first 48 weeks postswitch, but remained stable from 48 to 96 weeks in DTG-I arm. Switching from darunavir, White race, total to high-density lipoprotein cholesterol ratio <3.7, and normal/underweight BMI were independently associated with higher weight/BMI gains. The proportion of participants with ≥5% weight change increased similarly in both arms over time. The proportions of BMI categories, use of lipid-lowering drugs, diabetes and/or use of antidiabetic agents, and hypertension and/or use of antihypertensive agents did not change within or between arms at 48 and 96 weeks., Conclusions: Switching from protease inhibitors to dolutegravir in persons with HIV with high cardiovascular risk led to modest weight gain limited to the first 48 weeks, which involved preferentially normal-weight or underweight persons and was not associated with negative metabolic outcomes., Clinical Trials Registration: NCT02098837 and EudraCT 2013-003704-39., Competing Interests: Potential conflicts of interest. L. W. has received consulting fees, honoraria for lectures, advisory boards, or travel grants from Gilead, Janssen, MSD, and ViiV. A. G.-C. has received honoraria for lectures, advisory boards, or travel grants and her institution has received research grants from Gilead, Janssen, MSD, and ViiV. S. R. has received grants or contracts, honoraria for lectures, advisory boards, or travel grants from Gilead, Janssen, MSD, Theratechnologies, and ViiV. P. D. has received honoraria for lectures or advisory boards and his institution has received research grants from Gilead, Janssen, MSD, and ViiV Healthcare, and consulting fees from Gilead Sciences, ViiV Healthcare, Janssen-Cilag, and MSD. M. G. has received consulting fees, honoraria for lectures, advisory boards, or travel grants from Gilead, MSD, and ViiV. F. R. has received consulting fees, honoraria for lectures, advisory boards, or travel grants from Gilead, Janssen, MSD, Theratechnologies, and ViiV, and grants or contracts from MSD. C. S. has received consulting fees, honoraria for lectures, advisory boards, or travel grants from Gilead, Janssen, and MSD. M. M. has received consulting fees, honoraria for lectures, advisory boards or travel grants from ViiV, Janssen, and MSD. J. R. has received consulting fees (paid to author) and honoraria for lectures, advisory boards, or travel grants from Abivax, Boehringer, Galapagos, Gilead, Janssen, Merck Theratechnologies, and ViiV, including participation on a data safety monitoring board or advisory board from Abivax and Galapagos (paid to author) and leadership or fiduciary role in other board, society, committee or advocacy group from the European AIDS Clinical Society (EACS) (unpaid participation). C. K. has received consulting fees, honoraria for lectures, advisory boards, or travel grants and her institution has received research grants from Gilead, MSD, and ViiV. G. M. N. B. has received honoraria for lectures, advisory boards, or travel grants and his institution has received research grants from Gilead, Janssen, MSD, and ViiV, including leadership or fiduciary role in other board, society, committee or advocacy group for Chair of the EACS Treatment Recommendations. G. M. has received consulting fees, honoraria for lectures, advisory boards, or travel grants and his institution has received research grants from Gilead, MSD, Theratechnologies, and ViiV. J. F. has received consulting fees, honoraria for lectures, advisory boards, or travel grants from Gilead, Janssen, MSD, and ViiV. H. J. S. has received honoraria for lectures, advisory boards, or travel grants and his institution has received research grants from Gilead, GSK, Heidelberg Immunotherapeutics, Janssen, MSD, and ViiV, including consulting fees from Gilead Sciences, ViiV Health Care, MSD, and Janssen-Cilag (paid to author); participation on a data safety monitoring board or advisory board for Gilead Sciences, ViiV Healthcare, and MSD; leadership or fiduciary role in other board, society, committee, or advocacy group for the EACS guideline working group, German-Austrian guideline working group, and Federal Off-Label Commission German AIDS Society Chairmanship (in the past); and receipt of equipment materials, drugs, medical writing, gifts or other services from Gilead Sciences. G. G. has received honoraria for lectures, advisory boards, or travel grants and participation on a data safety monitoring board or advisory board; his institution has received research grants from Gilead, MSD, and ViiV. E. F. has received honoraria for lectures, advisory boards, or travel grants and received grants or contracts from Gilead, Janssen, MSD, and ViiV (paid to institution). S. E. has received consulting fees, honoraria for lectures, advisory boards, or travel grants and research grants or contracts from Gilead, MSD, and ViiV. J. M. G. is a full-time employee of and owns stock in ViiV as Senior Global Medical Director since 1 May 2018. A. P. has received consulting fees and honoraria for lectures or advisory boards and his institution has received research grants from Gilead, Janssen, MSD, and ViiV. E. M. has received consulting fees and honoraria for lectures or advisory boards and his institution has received research grants from Gilead, Janssen, MSD, Theratechnologies, and ViiV. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2022. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Antibiotic resistant bacteria (ARB) have been detected in remote environments, but the degree to which their presence is due to anthropogenic contamination remains unclear. Here, anthropogenic and ecological determinants of ARB were characterized in remote and highly visited areas of Rocky Mountain National Park in the United States. Soil and water samples were collected from 29 sites once a month for three months and measured for bacteria resistant to seven antibiotics with flow cytometry. A novel index of the likelihood of human presence (HPI) was generated for estimating human impact on ARB abundance. The HPI accounted for 44% of variation in ARB abundance in water samples (p < 0.0001) and 51% of variation in soil samples (p < 0.00001). Human presence index was illustrated as a reliable predictor of ARB abundance despite a tendency to underpredict at higher levels of human impact. Ecological determinants such as temperature, elevation, slope, and aspect were also found to be significantly associated with ARB abundance. These findings suggest that human presence drives the abundance of ARB in Rocky Mountain National Park, but ecological variables play a significant role in their presence and dispersal., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Self-completed 24 h dietary recalls (24-HRs) are increasingly used for research and national dietary surveillance. It is unclear how difficulties with self-completion affect response rates and sample characteristics. This study identified factors associated with being unable to self-complete an online 24-HR but willing to do so with an interviewer. Baseline 24-HRs from the ASCOT Trial were analysed ( n = 1224). Adults who had been diagnosed with cancer in the past seven years and completed treatment, were invited to self-complete 24-HRs online using myfood24 ® . Non-completers were offered an interviewer-administered 24-HR. One third of participants willing to provide dietary data, were unable to self-complete a 24-HR. This was associated with being older, non-white and not educated to degree level. Compared to interviewer-administered 24-HRs, self-completed 24-HRs included 25% fewer items and reported lower intakes of energy, fat, saturated fat and sugar. This study highlights how collection of dietary data via online self-completed 24-HRs, without the provision of an alternative method, contributes to sampling bias. As dietary surveys are used for service and policy planning it is essential to widen inclusion. Optimisation of 24-HR tools might increase usability but interviewer-administered 24-HRs may be the only suitable option for some individuals.

Efficient HIV-1 replication depends on balanced levels of host cell components including cellular splicing factors as the family of serine/arginine-rich splicing factors (SRSF, 1-10). Type I interferons (IFN-I) play a crucial role in the innate immunity against HIV-1 by inducing the expression of IFN-stimulated genes (ISGs) including potent host restriction factors. The less well known IFN-repressed genes (IRepGs) might additionally affect viral replication by downregulating host dependency factors that are essential for the viral life cycle; however, so far, the knowledge about IRepGs involved in HIV-1 infection is very limited. In this work, we could demonstrate that HIV-1 infection and the associated ISG induction correlated with low SRSF1 levels in intestinal lamina propria mononuclear cells (LPMCs) and peripheral blood mononuclear cells (PBMCs) during acute and chronic HIV-1 infection. In HIV-1-susceptible cell lines as well as primary monocyte-derived macrophages (MDMs), expression levels of SRSF1 were transiently repressed upon treatment with specific IFNα subtypes in vitro. Mechanically, 4sU labeling of newly transcribed mRNAs revealed that IFN-mediated SRSF1 repression is regulated on early RNA level. SRSF1 knockdown led to an increase in total viral RNA levels, but the relative proportion of the HIV-1 viral infectivity factor (Vif) coding transcripts, which is essential to counteract APOBEC3G-mediated host restriction, was significantly reduced. In the presence of high APOBEC3G levels, however, increased LTR activity upon SRSF1 knockdown facilitated the overall replication, despite decreased vif mRNA levels. In contrast, SRSF1 overexpression significantly impaired HIV-1 post-integration steps including LTR transcription, alternative splice site usage, and virus particle production. Since balanced SRSF1 levels are crucial for efficient viral replication, our data highlight the so far undescribed role of SRSF1 acting as an IFN-modulated cellular dependency factor decisively regulating HIV-1 post-integration steps., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Sertznig, Roesmann, Wilhelm, Heininger, Bleekmann, Elsner, Santiago, Schuhenn, Karakoese, Benatzy, Snodgrass, Esser, Sutter, Dittmer and Widera.)

Some studies in implicit learning investigate the mechanisms by which implicitly acquired knowledge (e.g., learning a sequence of responses) becomes consciously aware. It has been suggested that unexpected changes in the own behavior can trigger search processes, of which the outcome then becomes aware. A consistent empirical finding is that participants who develop explicit knowledge show a sudden decrease in reaction times, when responding to sequential events. This so called RT-drop might indicate the point of time when explicit knowledge occurs. We investigated whether an RT-drop is a precursor for the development of explicit knowledge or the consequence of explicit knowledge. To answer this question, we manipulated in a serial reaction time task the timing of long and short stimulus-onset asynchronies (SOA). For some participants, the different SOAs were presented in blocks of either long or short SOAs, while for others, the SOAs changed randomly. We expected the participants who were given a blocked presentation to express an RT-drop because of the predictable timing. In contrast, randomly changing SOAs should hamper the expression of an RT-drop. We found that more participants in the blocked-SOA condition than in the random-SOA condition showed an RT-drop. Furthermore, the amount of explicit knowledge did not differ between the two conditions. The findings suggest that the RT-drop does not seem to be a presupposition to develop explicit knowledge. Rather, it seems that the RT-drop indicates a behavioral strategy shift as a consequence of explicit knowledge., (© 2021. The Author(s).)

Fluency of processing has shown to influence recognition judgments. Fluency most commonly induces a liberal response bias to judge fluently processed information as well-known because knowledge of a high correlation between the frequency of encounters, memory strength, and thus fluency of processing has been acquired in the past. In this study, we aimed to show that high fluency can increase recognition judgment sensitivity as well if the participants had encountered fluent and non-fluent processing during training. Thirty-three participants have been trained with a 12-element sequence in a serial reaction time task. During training, the response stimulus interval alternated block-wise between constant (fluent) and variable (non-fluent). Participants showed a higher capability of discriminating between old and new test sequences under fluent than under non-fluent test conditions. Furthermore, participants did not show any liberal or conservative bias after they have been trained with alternating fluency., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Esser, Lustig and Haider.)

The expression of type I interferons (IFNs) is one of the immediate host responses during most viral infections. The type I IFN family consists of numerous highly conserved IFNα subtypes, IFNβ, and some others. Although these IFNα subtypes were initially believed to act interchangeably, their discrete biological properties are nowadays widely accepted. Subtype-specific antiviral, immunomodulatory, and anti-proliferative activities were reported explained by differences in receptor affinity, downstream signaling events, and individual IFN-stimulated gene expression patterns. Type I IFNs and increased IFN signatures potentially linked to hyperimmune activation of T cells are critically discussed for chronic HIV (human immunodeficiency virus) infection. Here, we aimed to analyze the broad immunological effects of specific type I IFN subtypes (IFNα2, IFNα14, and IFNβ) on T and NK cell subsets during HIV-1 infection in vitro and ex vivo . Stimulation with IFNα14 and IFNβ significantly increased frequencies of degranulating (CD107a + ) gut-derived CD4 + T cells and blood-derived T and NK cells. However, frequencies of IFNγ-expressing T cells were strongly reduced after stimulation with IFNα14 and IFNβ. Phosphorylation of downstream molecules was not only IFN subtype-specific; also, significant differences in STAT5 phosphorylation were observed in both healthy peripheral blood mononuclear cells (PBMCs) and PBMCs of HIV-infected individuals, but this effect was less pronounced in healthy gut-derived lamina propria mononuclear cells (LPMCs), assuming cell and tissue specific discrepancies. In conclusion, we observed distinct type I IFN subtype-specific potencies in stimulating T and NK cell responses during HIV-1-infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Karakoese, Schwerdtfeger, Karsten, Esser, Dittmer and Sutter.)

This article aims to continue the debate on how explicit, conscious knowledge can arise in an implicit learning situation. We review hitherto existing theoretical views and evaluate their compatibility with two current, successful scientific concepts of consciousness: The Global Workspace Theory and Higher-Order Thought Theories. In this context, we introduce the Unexpected Event Hypothesis (Frensch et al., Attention and implicit learning, John Benjamins Publishing Company, 2003) in an elaborated form and discuss its advantage in explaining the emergence of conscious knowledge in an implicit learning situation., (© 2021. The Author(s).)

Das Kaposi-Sarkom (KS) ist eine seltene, maligne, von lymphatischen Endothelzellen ausgehende, multilokuläre Gefäßerkrankung, die vor allem Haut und Schleimhäute, aber auch das lymphatische System und innere Organe wie den Gastrointestinaltrakt, die Lunge oder die Leber befallen kann. Fünf epidemiologische Subtypen des KS mit variablem klinischem Verlauf und unterschiedlicher Prognose werden unterschieden, die in spezifischen Populationen vermehrt auftreten: (1) klassisches KS, (2) iatrogenes KS bei Immunsuppression, (3) endemisches (afrikanisches) lymphadenopathisches KS, (4) epidemisches, HIV-assoziiertes KS und mit einem Immunrekonstitutions-Inflammations-Syndrom (IRIS) assoziiertes KS und (5) KS bei Männern, die Sex mit Männern haben (MSM) ohne HIV-Infektion. Diese interdisziplinäre Leitlinie fasst aktuelle praxisrelevante Empfehlungen zu Diagnostik und Therapie der verschiedenen Formen des KS zusammen. Die in dieser Kurzleitlinie genannten Empfehlungen werden in der Langfassung der Leitlinie (Online-Version des JDDG) detaillierter ausgeführt., (© 2022 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

Kaposi's sarcoma (KS) is a rare, malignant, multilocular vascular disease originating from lymphatic endothelial cells that can primarily affect the skin and mucous membranes, but also the lymphatic system and internal organs such as the gastrointestinal tract, lungs or liver. Five epidemiological subtypes of KS with variable clinical course and prognosis are distinguished, with increased incidence in specific populations: (1) Classical KS, (2) Iatrogenic KS in immunosuppression, (3) Endemic (African) lymphadenopathic KS, (4) Epidemic, HIV-associated KS and KS associated with immune reconstitution inflammatory syndrome (IRIS), and (5) KS in men who have sex with men (MSM) without HIV infection. This interdisciplinary guideline summarizes current practice-relevant recommendations on diangostics and therapy of the different forms of KS. The recommendations mentioned in this short guideline are elaborated in more detail in the extended version of the guideline (online format of the JDDG)., (© 2022 The Authors. Journal der Deutschen Dermatologischen Gesellschaft published by John Wiley & Sons Ltd on behalf of Deutsche Dermatologische Gesellschaft.)

IntroductionDespite increased use of pre-exposure prophylaxis (PrEP) in Germany, HIV infection rates are not declining and little is known about how this prevention method affects the prevalence of sexually transmitted infections (STI) among men who have sex with men (MSM).AimWe studied, in a large multicentre cohort, STI point prevalence, co-infection rates, anatomical location and influence of PrEP.MethodsThe BRAHMS study was a prospective cohort study conducted at 10 sites in seven major German cities that enrolled MSM reporting increased sexual risk behaviour. At screening visits, MSM were tested for Mycoplasma genitalium (MG), Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Treponema pallidum (TP) , and given a behavioural questionnaire. With binomial regression, we estimated prevalence ratios (PR) and 95% confidence intervals (CI) for the association of PrEP and STI.ResultsWe screened 1,043 MSM in 2018 and 2019, with 53.0% currently using PrEP. At screening, 370 participants (35.5%) had an STI. The most common pathogen was MG in 198 (19.0%) participants, followed by CT (n = 133; 12.8%), NG (n = 105; 10.1%) and TP (n = 37; 3.5%). Among the 370 participants with at least one STI, 14.6% (n = 54) reported STI-related symptoms. Infection prevalence was highest at anorectal site (13.4% MG, 6.5% NG, 10.2% CT). PrEP use was not statistically significant in adjusted models for STI (PR: 1.10; 95% CI: 0.91-1.32), NG/CT, only NG or only CT.ConclusionsPrevalence of asymptomatic STI was high, and PrEP use did not influence STI prevalence in MSM eligible for PrEP according to national guidelines.

Although HIV-specific CD8 T cells are effective in controlling HIV infection, they fail to clear infection even in the presence of antiretroviral therapy (ART) and cure strategies such as "shock-and-kill." Little is known how ART is contributing to HIV-specific CD8 T cell function and the ability to clear HIV infection. Therefore, we first assessed the cytokine polyfunctionality and proliferation of CD8 T cells from ART-treated HIV+ individuals directly ex vivo and observed a decline in the multifunctional response as well as proliferation indices of these cells in individuals treated with integrase inhibitor (INSTI) based ART regimens compared to both protease inhibitor (PI) and nonnucleoside reverse transcriptase inhibitor (NNRTI) based regimens. We next cocultured CD8 T cells with different drugs individually and were able to observe reduced functional properties with significantly decreased ability of CD8 T cells to express IFN-γ, MIP1β and TNF-α only after treatment with INSTI-based regimens. Furthermore, previously activated and INSTI-treated CD8 T cells demonstrated reduced capacity to express perforin and granzyme B compared to PI and NNRTI treated cells. Unexpectedly, CD8 T cells treated with dolutegravir showed a similar killing ability 7 dpi compared to emtricitabine or rilpivirine treated cells. We next used a live cell imaging assay to determine the migratory capacity of CD8 T cells. Only INSTI-treated cells showed less migratory activity after SDF-1α stimulation compared to NRTI regimens. Our data show that the choice of ART can have a significant impact on CD8 T cell effector functions, but the importance for potential eradication attempts is unknown. IMPORTANCE Integrase Strand Transfer Inhibitors (INSTI) are recommended by national and international guidelines as a key component of ART in the treatment of HIV infected patients. In particular, their efficacy, tolerability and low drug-drug interaction profile have made them to the preferred choice as part of the first-line regimen in treatment-naive individuals. Here, we demonstrate that the choice of ART can have a significant impact on function and metabolism of CD8 T cells. In summary, our study provides first evidence on a significant, negative impact on CD8 T cell effector functions in the presence of two INSTIs, dolutegravir and elvitegravir, which may contribute to the limited success of eradicating HIV-infected cells through "shock-and-kill" strategies. Although our findings are coherent with recent studies highlighting a possible role of dolutegravir in weight gain, further investigations are necessary to fully understand the impact of INSTI-based regimens on the health of the individual during antiretroviral therapy.

We report on continuous-wave (cw) laser experiments with a high-quality and large-size Yb:Lu 2 O 3 polycrystalline transparent ceramic in a thin-disk laser oscillator. An output power of up to 1190 W was achieved in multimode operation with an optical efficiency of 60.3%. In fundamental-mode operation, a cw output power of 409 W was extracted with an optical efficiency of 35.6% and a beam propagation factor of M 2  = 1.11.

Background: We sought to identify factors associated with weight gain in randomized clinical trials of antiretroviral therapy (ART) switch., Methods: We explored the effects of demographic factors, clinical characteristics, and ART on weight gain in a pooled analysis of 12 prospective clinical trials, wherein virologically suppressed people living with human immunodeficiency virus (PWH) were randomized to switch or remain on a stable baseline regimen (SBR)., Results: Both PWH randomized to switch ART (n = 4166) and those remaining on SBR (n = 3150) gained weight. Median weight gain was greater in those who switched (1.6 kg, interquartile range [IQR], -.05 to 4.0 vs 0.4 kg, [IQR], -1.8 to 2.4 at 48 weeks, P < .0001), with most weight gain occurring in the first 24 weeks after switch. Among baseline demographic and clinical characteristics, only younger age and lower baseline body mass index were associated with any or ≥10% weight gain. By week 48, 4.6% gained ≥10% weight (6.4% of switch and 2.2% of SBR), the greatest risk was with switch from efavirenz (EFV) to rilpivirine (RPV) or elvitegravir/cobicistat and switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF). Switch from abacavir to TAF was associated with less weight gain than switch from TDF to TAF and was not associated with increased risk for ≥10% weight gain., Conclusions: Moderate weight gain after ART switch was common and usually plateaued by 48 weeks. Baseline ART was a predictor of post-switch weight gain; participants who switched off of EFV and TDF had the greatest weight gain. The biological mechanisms that underlie the differential effects of switching ART agents on weight and associated clinical implications require further study., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)