Memory for artwork is predictable.

Viewing art is often seen as a highly personal and subjective experience. However, are there universal factors that make a work of art memorable? We conducted three experiments, where we recorded online memory performance for 4,021 paintings from the Art Institute of Chicago, tested in-person memory after an unconstrained visit to the Art Institute, and obtained abstract attribute measures such as beauty and emotional valence for these pieces. Participants showed significant agreement in their memories both online and in-person, suggesting that pieces have an intrinsic "memorability" based solely on their visual properties that is predictive of memory in a naturalistic museum setting. Importantly, ResMem, a deep learning neural network designed to estimate image memorability, could significantly predict memory both online and in-person based on the images alone, and these predictions could not be explained by other low- or high-level attributes like color, content type, aesthetics, and emotion. A regression comprising ResMem and other stimulus factors could predict as much as half of the variance of in-person memory performance. Further, ResMem could predict the fame of a piece, despite having no cultural or historical knowledge. These results suggest that perceptual features of a painting play a major role in influencing its success, both in memory for a museum visit and in cultural memory over generations.

The fragility of artists' reputations from 1795 to 2020.

This study explores the longevity of artistic reputation. We empirically examine whether artists are more- or less-venerated after their death. We construct a massive historical corpus spanning 1795 to 2020 and build separate word-embedding models for each five-year period to examine how the reputations of over 3,300 famous artists-including painters, architects, composers, musicians, and writers-evolve after their death. We find that most artists gain their highest reputation right before their death, after which it declines, losing nearly one SD every century. This posthumous decline applies to artists in all domains, includes those who died young or unexpectedly, and contradicts the popular view that artists' reputations endure. Contrary to the Matthew effect, the reputational decline is the steepest for those who had the highest reputations while alive. Two mechanisms-artists' reduced visibility and the public's changing taste-are associated with much of the posthumous reputational decline. This study underscores the fragility of human reputation and shows how the collective memory of artists unfolds over time.

CRISPR editing of CCR5 and HIV-1 facilitates viral elimination in antiretroviral drug-suppressed virus-infected humanized mice.

Treatment of HIV-1ADA-infected CD34+ NSG-humanized mice with long-acting ester prodrugs of cabotegravir, lamivudine, and abacavir in combination with native rilpivirine was followed by dual CRISPR-Cas9 C-C chemokine receptor type five (CCR5) and HIV-1 proviral DNA gene editing. This led to sequential viral suppression, restoration of absolute human CD4+ T cell numbers, then elimination of replication-competent virus in 58% of infected mice. Dual CRISPR therapies enabled the excision of integrated proviral DNA in infected human cells contained within live infected animals. Highly sensitive nucleic acid nested and droplet digital PCR, RNAscope, and viral outgrowth assays affirmed viral elimination. HIV-1 was not detected in the blood, spleen, lung, kidney, liver, gut, bone marrow, and brain of virus-free animals. Progeny virus from adoptively transferred and CRISPR-treated virus-free mice was neither detected nor recovered. Residual HIV-1 DNA fragments were easily seen in untreated and viral-rebounded animals. No evidence of off-target toxicities was recorded in any of the treated animals. Importantly, the dual CRISPR therapy demonstrated statistically significant improvements in HIV-1 cure percentages compared to single treatments. Taken together, these observations underscore a pivotal role of combinatorial CRISPR gene editing in achieving the elimination of HIV-1 infection.

Molecular animations in genomics education: designing for whom?

Molecular animations can be beneficial as teaching tools for genomics education; however, barriers to their effective implementation remain. This article proposes informed design guidelines from the perspective of the animator that may assist others to effectively communicate scientific concepts to their respective audiences and communities.

Transcriptome analysis reveals that defects in cell cycle regulation contribute to preimplantation embryo arrest.

Patients with preimplantation embryo arrest (PREMBA) often experience assisted reproductive failure primarily due to the lack of transferable embryos, and the molecular mechanisms underlying PREMBA remain unclear. In our study, the embryos from five women with recurrent preimplantation embryo arrest and three women with tubal factor infertility were used for single-embryo transcriptome sequencing. Meanwhile, the transcriptomes of normal human preimplantation embryos obtained from GSE36552 were utilized to perform a comparative analysis with the transcriptomes of PREMBA embryos. Our results showed dysregulation of the cell cycle phase transition might be a potential pathogenic factor contributing to PREMBA. Through integrated analysis of the differentially expressed genes (DEGs) and weighted gene co-expression network analysis (WGCNA), we identified a number of hub genes using the protein-protein interaction network. The top 5 hub genes were as follows: CCNB2, BUB1B, CDC25A, CCNB3, and PLK3. The expression of hub genes was validated in PREMBA embryos and donated embryos using RT-qPCR. The knockdown of Ccnb2 in mouse zygotes led to an increase in embryo fragmentation, a rise in apoptosis, and a reduction in blastocyst formation. Furthermore, silencing the expression of CDC25A in HEK293T cells resulted in a decrease in cell proliferation and an increase in apoptosis, providing further support for our findings. Our findings could predict the development outcomes of preimplantation embryos and be used as potential therapeutic targets to prevent recurrent failures of IVF/ICSI attempts.

Food is Medicine for HIV: Improved health and hospitalizations in the Changing Health through Food Support (CHEFS-HIV) pragmatic randomized trial.

BACKGROUND: Policy support for "Food is Medicine"-medically tailored meals or groceries to improve health-is rapidly growing. No randomized trials have heretofore investigated the benefits of medically tailored food programs for people living with HIV (PLHIV). METHODS: The CHEFS-HIV pragmatic randomized trial included PLHIV who were clients of Project Open Hand (POH), a San Francisco-based nonprofit food organization. The intervention arm (n = 93) received comprehensive medically tailored meals, groceries, and nutritional education. Control participants (n = 98) received less intensive (POH "standard of care") food services. Health, nutrition, and behavioral outcomes were assessed at baseline and 6 months later. Primary outcomes measured were viral non-suppression and health related quality of life. Mixed models estimated treatment effects as differences-in-differences between arms. RESULTS: The intervention arm had lower odds of hospitalization (odds ratio [OR] = 0.11), food insecurity (OR = 0.23), depressive symptoms (OR = 0.32), antiretroviral therapy adherence <90% (OR = 0.18), and unprotected sex (OR = 0.18), and less fatty food consumption (ß= -0.170 servings/day) over 6 months, compared to the control arm. There was no difference between study arms in viral non-suppression and health-related quality of life over 6 months. CONCLUSIONS: A "Food-is-Medicine" intervention reduced hospitalizations and improved mental and physical health among PLHIV, despite no impact on viral suppression. CLINICAL TRIALS REGISTRATION: NCT03191253.

Viral Load Dynamics in Plasma and Semen When Antiretroviral Therapy Is Initiated During Early HIV-1 Infection.

We assessed human immunodeficiency virus (HIV) load in plasma and semen during primary HIV infection using serial samples of semen and plasma during the first 24 weeks after diagnosis in untreated participants and those who started antiretroviral therapy (ART) immediately at diagnosis. In the absence of treatment, semen viral load was >1000 copies/mL in almost all specimens (83%) collected 2-10 weeks after the estimated date of HIV acquisition and remained >1000 copies/mL in 35% of untreated participants at the last observed time point. Thus, in the absence of ART, semen viral load remained at a level consistent with transmissibility throughout primary infection.

In depth analysis of the HIV reservoir confirms effectiveness and safety of DTG/3TC in a phase 4 randomized controlled switch trial (RUMBA).

BACKGROUND: Reducing the number of active compounds for lifelong HIV treatment is of interest, especially to reduce potential long-term side effects. So far, available data assessing viral control, support the robustness and safety of 2DR (2-drug regimen) ART compared to 3DR. However, further in-depth investigations of the viral reservoirs are mandatory to guarantee long-term safety of these regimens regarding stable intact HIV-1 DNA copies, HIV-1 RNA transcripts and sustained immunological control. METHODS: The Rumba study is the first prospective randomized controlled trial evaluating the impact of switch from 3DR to 2DR on the viral reservoir. Participants on any stable 2nd generation INSTI-based 3DR regimen with HIV-1 RNA<50 copies/ml plasma for at least 3 months were randomized to switch to dolutegravir/lamivudine (DTG/3TC, N=89) or to switch or stay on bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF, N=45). After 48 weeks, virological, immunological and metabolic parameters were evaluated. RESULTS: We did not observe a significant difference in change over time in the mean number of intact HIV-1 DNA copies/million CD4+ T cells with DTG/3TC compared to B/F/TAF. There was no evidence in this study that switching to DTG/3TC increased the active reservoir by HIV-1 transcription. No significant changes in pro-inflammatory cytokines or major immune cell subsets were observed. Changes in exhaustion and activation of specific cellular subsets were small and bidirectional. Metabolic outcomes are similar between the treatment regimens. CONCLUSIONS: This study confirms the safety of DTG/3TC compared to B/F/TAF through viral control after in-depth investigations of the intact HIV-1 reservoir, HIV-1 transcription and inflammatory markers.

Weight Gain After Antiretroviral Therapy Initiation and Subsequent Risk of Metabolic and Cardiovascular Disease.

BACKGROUND: Weight gain following initiation of antiretroviral therapy (ART) is common. We assessed the impact of changes in weight in the year following ART initiation with subsequent cardiometabolic disease among AIDS Clinical Trials Group (ACTG) participants. METHODS: Linear regression models were fit to examine the association between change in weight/waist circumference (WC) in weeks 0-48 and change in metabolic parameters in weeks 0-48 and 48-96. Cox proportional hazard models were fit to examine the association between changes in weight/WC in weeks 0-48 and diabetes mellitus (DM), metabolic syndrome, or cardiometabolic and cardiovascular events after week 48. RESULTS: Participants (N = 2624) were primarily male (81%) and non-White (60%). Mean weight gain from 0-48 weeks was 3.6 kg (SD 7.3); 130 participants developed DM; 360 metabolic syndrome; 424 any cardiometabolic event; 28 any cardiovascular event, over 480 weeks of follow-up. In adjusted models, total cholesterol increased by 0.63 mg/dL (95% confidence interval [CI] [.38, .089]) and LDL by 0.39 mg/dL (0.19, 0.59) per 1 kg increase in weight from weeks 0 to48. Participants who experienced >10% weight gain (vs -5% to 5%) had an increased risk of DM (hazard ratio [HR] 2.01, 95% CI [1.30, 3.08]), metabolic syndrome (HR 2.24, 95% CI [1.55, 2.62]), and cardiometabolic outcomes (HR 1.54, 95% CI [1.22, 1.95]). Participants who lost more than 5% of their baseline weight had a lower risk of incident metabolic syndrome (HR 0.67, 95% CI [0.42, 1.07]). Trends for WC were similar. CONCLUSIONS: Weight and body composition changes in the first year following ART initiation are associated with contemporaneous changes in metabolic parameters and subsequent cardiometabolic disease.

The risk of non-AIDS defining events is lower in ART-naive HIV controllers than in normal progressors on suppressive ART.

BACKGROUND: We aimed to compare the non-AIDS events (nADE) risk between normal progressors using ART (NP-ART) and people with HIV (PWH) that naturally control HIV infection (HIV controllers), as well as the outcomes after ART in HIV controllers on nADE. METHODS: The primary endpoint was major nADE defined as the composite of cardiovascular disease, non-AIDS malignancy or all-cause mortality, whichever came first.. The role of ART in HIV controllers was assessed as a time-varying covariate. RESULTS: We included 1007 ART-naive HIV controllers (of which 60 elite controllers), 1510 Early-ART (<6 months after negative HIV test) and 15437 NP-ART (reference group), contributing 3813, 11,060 and 160,050 years of follow-up, respectively. HIV controllers had lower risk of the primary endpoint (HR 0.55, 95%CI 0.38-0.81, P = 0.0023), all-cause mortality (Adjusted Hazard ratio [aHR]: 0.45, 95% confidence interval [CI] 0.25-0.79, P = 0.0054), cardiovascular disease (aHR 0.47, 95%CI 0.22-0.99, P = 0.046) , but not non-AIDS malignancy (aHR 0.74, 95%CI 0.41-1.35, P = 0.33) than NP-ART. Among HIV controllers, each log10 lower baseline viral load further decreased the risk of nADE (aHR 0.54, 95% CI 0.29-0.99, P = 0.045). ART in HIV controllers did not reduce the risk of any nADE (aHR 1.22, 95% CI 0.66-2.29, P = 0.53). CONCLUSIONS: We found a lower risk of nADE in HIV controllers than NP-ART, especially in those with low plasma viral loads. Initiation of ART did not alter the nADE risk in HIV controllers. Our findings help clinicians to decide on prescribing ART in HIV controllers.

Drastic Reduction in Time to Controlled Viral Load in People With Human Immunodeficiency Virus in France, 2009-2019: A Longitudinal Cohort Study.

BACKGROUND: Aspirational targets to end AIDS by 2030 include having 95% of people with human immunodeficiency virus (HIV; PWH) diagnosed, 95% treated, and 95% with controlled viral load (VL). Our objective was to describe, using a large French prospective cohort, the median transition times through the cascade of care between 2009 and 2019. METHODS: We analyzed patients whose first HIV diagnosis was made between 1 January 2009 and 31 December 2019. Using the Kaplan-Meier method, we estimated the time to linkage to care (from HIV diagnosis to first biological assessment), to treatment (date of first antiretroviral therapy [ART] prescription), and to controlled VL (first value <200 copies/mL). Analyses were disaggregated by time periods and patients' characteristics. Censoring date was 31 December 2021. RESULTS: Among the 16 864 patients linked to care since 2009, the median [Q1; Q3] time from HIV diagnosis to controlled VL decreased from 254 [127-745] to 73 [48-132] days in 2009-2011 and 2018-2019, respectively. Transition times from linkage to care to first ART decreased from 67 [17; 414] in 2009-2011 to 13 [5; 26] days in 2018-2019, and from ART to controlled VL from 83 [35; 130] in 2009-2011 to 38 [28; 90] days in 2018-2019. Differences were observed depending on patients' characteristics. CONCLUSIONS: We describe drastic reductions in transition time through the cascade of care, allowing reduction in the transmission period following each new infection. Delayed diagnosis remains the main obstacle to ending AIDS in the next decade.

Risk of tuberculosis after achieving HIV virological suppression on antiretroviral therapy: a Danish nationwide prospective cohort study.

BACKGROUND: In countries with low tuberculosis (TB) burden, the risk of TB in people with HIV (PWH) once HIV virological suppression is achieved is not fully understood. METHODS: In a nationwide cohort, we included all adult PWH from the Danish HIV Cohort initiating antiretroviral therapy (ART) (1995-2017) without prior TB disease. We used Kaplan-Meier estimation and Poisson regression to calculate TB incidence rate (IR) after six months of ART, along with associated risk factors and mortality rates (MR). RESULTS: Among 6,849 PWH initiating ART (median follow-up 7.4 years), 84 developed TB (IR 1.4/1000 person-year [PY]), 54 of them beyond six months of ART initiation, IR 0.97/1000 PY (95%CI:1.17-1.79): 1.95 (95%CI:1.34-2.76) in non-Danish born, 0.36 (95%CI:0.21-0.62) in Danish-born without injection drug use (IDU), and 2.95 (95%CI:1.53-5.66) in Danish-born with IDU. Danish-born with suppressed viremia, and no IDU or known TB exposures had the lowest risk (IR 0.05/1000 PY).In the adjusted analysis, being non-Danish born (aIRR 4.27[95%CI:2.36-7.72]), IDU (aIRR 4.95[95%CI:2.55-9.62]), and previous AIDS-defining events (aIRR 2.05[95%CI:1.06-3.94]) raised TB risk, while suppressed HIV-RNA (aIRR 0.58[95%CI:0.34-0.99]) reduced it. The overall MR for HIV/TB co-infected post- ART was high, at 48.9/1000 PY (95%CI:30.4-78.7). CONCLUSIONS: The TB risk remains elevated in PWH beyond six months of ART initiation, especially among migrants, IDU, those without suppressed HIV-RNA, and individuals exposed to high TB endemic areas or with social risk determinants of health. Conversely, PWH without these risk factors have a TB risk similar to the general population and would not require targeted TB screening strategies.

Antiretrovirals and Weight Change: Weighing the Evidence.

Body weight is influenced by an interplay of individual and environmental factors. In people with human immunodeficiency virus (HIV), weight is also influenced by disease status with loss accompanying disease progression that is reversed with effective antiretroviral therapy. Weight changes in comparative antiretroviral therapy trials differ by regimen, with greater gains observed with the integrase strand transfer inhibitors dolutegravir and bictegravir, particularly when coadministered with tenofovir alafenamide fumarate, compared with regimens that include agents such as tenofovir disoproxil fumarate that attenuate weight gain. We review weight changes in major randomized trials of preexposure prophylaxis and initial and switch HIV therapy, highlighting the challenges to assessing the role of antiretroviral therapy in weight change. This examination forms the basis for a model that questions assumptions regarding an association between integrase strand transfer inhibitors and tenofovir alafenamide fumarate and excessive weight gain and calls for more careful consideration of these data when making HIV treatment decisions.

A gut check: understanding the interplay of the gastrointestinal microbiome and the developing immune system towards the goal of pediatric HIV remission.

Despite the efficacy of antiretroviral therapy (ART) in reducing the global incidence of vertical HIV transmissions, more than 120,000 children are still infected with the virus each year. Since ART cannot clear the HIV reservoir that is established soon after infection, children living with HIV (CLWH) are forced to rely on therapy for their lives and suffer from long-term drug-related complications. Pediatric HIV infection, like adult infection, is associated with gut microbial dysbiosis, loss of gut epithelial integrity, bacterial translocation, CD4 + T cell depletion, systemic immune activation, and viral reservoir establishment. However, unlike in adults, HIV that is vertically acquired by infants interacts with a gut microbiome that is continuously evolving while concomitantly shaping the infant's immune ontogeny. Therefore, to determine whether there may be interventions that target the HIV reservoir through microbiome-directed approaches, understanding the complex tripartite interactions between the transmitted HIV, the maturing gut microbiome, and the developing immune system during early life is crucial. Importantly, early life is the time when the gut microbiome of an individual is highly dynamic, and this temporal development of the gut microbiome plays a crucial role in educating the maturing immune system of a child. Therefore, manipulation of the gut microbiome of CLWH to a phenotype that can reduce HIV persistence by fostering an antiviral immune system might be an opportune strategy to achieve ART-free viral suppression in CLWH. This review summarizes the current state of knowledge on the vertical transmission of HIV, the developing gut microbiome of CLWH, and the immune landscape of pediatric elite controllers, and explores the prospect of employing microbial modulation as a potential therapeutic approach to achieve ART-free viral suppression in the pediatric population.

Impact of HIV status on prognosis of malignancies among people living with HIV in Japan.

BACKGROUND: Antiretroviral therapy has reduced the incidence and mortality of AIDS-defining malignancies (ADM); however, non-AIDS-defining malignancies (NADM) are a major cause of death among people living with HIV (PLWH) today. Though current guidelines suggest that PLWH should receive the same treatment as the general population, there are limited studies focused on how HIV status affects the prognosis of cancers. The present study aimed to investigate the characteristics and prognosis of malignant diseases among PLWH in Japan. METHODS: Patients with HIV diagnosed with malignant diseases at our institution between 2011 and 2021 were retrospectively reviewed. RESULTS: There were 205 patients who were diagnosed with malignancies. Of these, 87 (42.4%) were diagnosed with ADM and 118 (57.6%) were diagnosed with NADM. Among 69 patients who received chemotherapy for ADM, 24 (34.8%) developed AIDS-defining opportunistic infections during treatment. In contrast, only one (1.8%) of the 56 patients administered chemotherapy for NADM developed AIDS-defining opportunistic infections. Complications of opportunistic infections at diagnosis of malignancies, low CD4+ T-cell count, positive HIV RNA, and nonadministration of antiretroviral therapy were associated with 5-year overall survival among patients with malignant lymphomas. However, the variables associated with HIV did not affect NADM prognosis. CONCLUSIONS: In this analysis, HIV status had a small impact on the prognosis of malignant diseases in PLWH. Few patients with NADM developed AIDS-defining opportunistic infections after receiving chemotherapy.

Predictors of change in CD4 cell count over time for HIV/AIDS patients on ART follow-up in northern Ethiopia: a retrospective longitudinal study.

BACKGROUND: HIV has an effect on lowering CD4 cell count, which lowers the ability to resist contamination. For patients on ART in areas with limited resources, the CD4 cell count assessment is crucial for determining treatment responses and therapeutic decisions. The volatility of CD4 counts following the introduction of ART over time is still largely uncharacterized, and there are few fresh datasets on CD4 cell count progressions. The goal of this study was to identify the key factors that change over time in CD4 cells for HIV/AIDS patients receiving ART follow-up in northern Ethiopia. METHODS: A total of 216 HIV/AIDS patients who initiated ART in the Mekelle General Hospital between 2013 and 2016 were involved using systematic random selection techniques. An examination of exploratory data was used to describe the individual profiles of HIV patients. A multivariable random intercept and slope linear mixed regression analysis regarded predictor variables to be statistically significant if their p-value was less than 0.05. RESULTS: The random intercept and slope linear mixed model result indicated that there were statistically significant predictors of baseline CD4 cell count (ß = 0.0125, P-value = 0.001*) and bedridden functional status (ß = -2.459, p = 0.02*) on the change of CD4 cell count over time in HIV/AIDS patients at the 5% significance level. CONCLUSIONS: Changes in CD4 counts were influenced by the baseline CD4 cell count and the functional status of being bedridden. Because their CD4 cell counts were lower at baseline and they had a functional status of bedridden, the majority of HIV/AIDS patients on ART had substantial predictors on the change of CD4 cell count over time. So, public health service providers should give exceptional guidance and attention is also necessary for those patients who have lower baseline CD4 cell count and bedridden functional status.

Klinefelter syndrome: etiology and clinical considerations in male infertility†.

Klinefelter syndrome (KS) is the most prevalent chromosomal disorder occurring in males. It is defined by an additional X chromosome, 47,XXY, resulting from errors in chromosomal segregation during parental gametogenesis. A major phenotype is impaired reproductive function, in the form of low testosterone and infertility. This review comprehensively examines the genetic and physiological factors contributing to infertility in KS, in addition to emergent assisted reproductive technologies, and the unique ethical challenges KS patients face when seeking infertility treatment. The pathology underlying KS is increased susceptibility for meiotic errors during spermatogenesis, resulting in aneuploid or even polyploid gametes. Specific genetic elements potentiating this susceptibility include polymorphisms in checkpoint genes regulating chromosomal synapsis and segregation. Physiologically, the additional sex chromosome also alters testicular endocrinology and metabolism by dysregulating interstitial and Sertoli cell function, collectively impairing normal sperm development. Additionally, epigenetic modifications like aberrant DNA methylation are being increasingly implicated in these disruptions. We also discuss assisted reproductive approaches leveraged in infertility management for KS patients. Application of assisted reproductive approaches, along with deep comprehension of the meiotic and endocrine disturbances precipitated by supernumerary X chromosomes, shows promise in enabling biological parenthood for KS individuals. This will require continued multidisciplinary collaboration between experts with background of genetics, physiology, ethics, and clinical reproductive medicine.

Transcriptomic Signatures of Human Immunodeficiency Virus Post-Treatment Control.

Posttreatment controllers (PTCs) are rare HIV-infected individuals who can limit viral rebound after antiretroviral therapy interruption (ATI), but the mechanisms of this remain unclear. To investigate these mechanisms, we quantified various HIV RNA transcripts (via reverse transcription droplet digital PCR [RT-ddPCR]) and cellular transcriptomes (via RNA-seq) in blood cells from PTCs and noncontrollers (NCs) before and two time points after ATI. HIV transcription initiation did not significantly increase after ATI in PTCs or in NCs, whereas completed HIV transcripts increased at early ATI in both groups and multiply-spliced HIV transcripts increased only in NCs. Compared to NCs, PTCs showed lower levels of HIV DNA, more cell-associated HIV transcripts per total RNA at all times, no increase in multiply-spliced HIV RNA at early or late ATI, and a reduction in the ratio of completed/elongated HIV RNA after early ATI. NCs expressed higher levels of the IL-7 pathway before ATI and expressed higher levels of multiple cytokine, inflammation, HIV transcription, and cell death pathways after ATI. Compared to the baseline, the NCs upregulated interferon and cytokine (especially TNF) pathways during early and late ATI, whereas PTCs upregulated interferon and p53 pathways only at early ATI and downregulated gene translation during early and late ATI. In NCs, viral rebound after ATI is associated with increases in HIV transcriptional completion and splicing, rather than initiation. Differences in HIV and cellular transcription may contribute to posttreatment control, including an early limitation of spliced HIV RNA, a delayed reduction in completed HIV transcripts, and the differential expression of the IL-7, p53, and TNF pathways. IMPORTANCE The findings presented here provide new insights into how HIV and cellular gene expression change after stopping ART in both noncontrollers and posttreatment controllers. Posttreatment control is associated with an early ability to limit increases in multiply-spliced HIV RNA, a delayed (and presumably immune-mediated) ability to reverse an initial rise in processive/completed HIV transcripts, and multiple differences in cellular gene expression pathways. These differences may represent correlates or mechanisms of posttreatment control and may provide insight into the development and/or monitoring of therapeutic strategies that are aimed at a functional HIV cure.

In vivo effect of vaginal seminal plasma application on the human endometrial transcriptome: a randomized controlled trial.

Studies in humans and animals suggest that seminal plasma, the acellular seminal fluid component, stimulates the endometrium to promote immune tolerance and facilitate implantation. We designed a randomized, double-blinded, placebo-controlled trial to investigate changes in the endometrial transcriptomic profile after vaginal application of seminal plasma. The study participants were randomized into two groups. Five women received a vaginal application of seminal plasma, and four received a placebo application with saline solution. The application was performed 2 days after HCG-triggered ovulation in an unstimulated cycle. After 5-8 days, an endometrial biopsy was collected to analyze differences in the endometrial transcriptomic profile using microarray analyses. A differential gene expression analysis and a gene set analysis were performed. The gene set enrichment analysis showed a positive enrichment of pathways associated with the immune response, cell viability, proliferation, and cellular movement. Moreover, pathways involved in implantation, embryo development, oocyte maturation, and angiogenesis were positively enriched. The differential gene expression analysis, after adjusting for multiple testing, showed no significantly differentially expressed genes between the two groups. A comparative analysis was also performed with similar studies conducted in other animals or in vitro using human endometrial cells. The comparative analysis showed that the effect of seminal plasma effect on the endometrium is similar in pigs, mice, and in vitro human endometrial cells. The present study provides evidence that seminal plasma might impact the endometrium during the implantation window, with potential to affect endometrial receptivity and embryo development.

Updates to Male Infertility: AUA/ASRM Guideline (2024).

PURPOSE: In 2023 the American Urological Association (AUA) requested an Update Literature Review (ULR) to incorporate new evidence generated since the 2020 publication of this Guideline. The resulting 2024 Guideline Amendment addresses updated recommendations to provide guidance on the appropriate evaluation and management of the male partner in an infertile couple. MATERIALS AND METHODS: In 2023, the Male Infertility Guideline was updated through the AUA amendment process in which newly published literature is reviewed and integrated into previously published guidelines. An updated literature search identified 4093 new abstracts. Following initial abstract screening, 125 eligible study abstracts met inclusion criteria. On data extraction, 22 studies of interest were included in the final evidence base to inform the Guideline amendment. RESULTS: The Panel developed evidence- and consensus-based statements based on an updated review to provide guidance on evaluation and management of male infertility. These updates are detailed herein. CONCLUSIONS: This update provides several new insights, including revised thresholds for Y-chromosome microdeletion testing, indications for pelvic MRI imaging in infertile males, and guidance regarding the use of testicular sperm in nonazoospermic males. This Guideline will require further review as the diagnostic and treatment options in this space continue to evolve.