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Pure rotational transitions of silicon monosulfide (28Si32S) and its rare isotopic species have been observed in their ground as well as vibrationally excited states by employing Fourier transform microwave (FTMW) spectroscopy of a supersonic molecular beam at centimetre wavelengths (13–37 GHz) and by using long-path absorption spectroscopy at millimetre and submillimetre wavelengths (127–925 GHz). The latter measurements include 91 transition frequencies for 28Si32S, 28Si33S, 28Si34S, 29Si32S and 30Si32S in υ = 0, as well as 5 lines for 28Si32S in υ = 1, with rotational quantum numbers J″≤ 52. The centimetre-wave measurements include more than 300 newly recorded lines. Together with previous data they result in almost 600 transitions (J″ = 0 and 1) from all twelve possible isotopic species, including 29Si36S and 30Si36S, which have fractional abundances of about 7 × 10−6 and 4.5 × 10−6, respectively. Rotational transitions were observed from υ = 0 for the least abundant isotopic species to as high as υ = 51 for the main species. Owing to the high spectral resolution of the FTMW spectrometer, hyperfine structure from the nuclear electric quadrupole moment of 33S was resolved for species containing this isotope, as was much smaller nuclear spin-rotation splitting for isotopic species involving 29Si. By combining the measurements here with previously published microwave and infrared data in one global fit, an improved set of spectroscopic parameters for SiS has been derived which include several terms describing the breakdown of the Born–Oppenheimer approximation. With this parameter set, highly accurate rotational frequencies for this important astronomical molecule can now be predicted well into the terahertz region. [ABSTRACT FROM AUTHOR]

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.

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.)