Robust SARS-CoV-2-specific T cell immunity is maintained at 6 months following primary infection.

The immune response to SARS-CoV-2 is critical in controlling disease, but there is concern that waning immunity may predispose to reinfection. We analyzed the magnitude and phenotype of the SARS-CoV-2-specific T cell response in 100 donors at 6 months following infection. T cell responses were present by ELISPOT and/or intracellular cytokine staining analysis in all donors and characterized by predominant CD4+ T cell responses with strong interleukin (IL)-2 cytokine expression. Median T cell responses were 50% higher in donors who had experienced a symptomatic infection, indicating that the severity of primary infection establishes a 'set point' for cellular immunity. T cell responses to spike and nucleoprotein/membrane proteins were correlated with peak antibody levels. Furthermore, higher levels of nucleoprotein-specific T cells were associated with preservation of nucleoprotein-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T cell responses are retained at 6 months following infection.

Specialized replication mechanisms maintain genome stability at human centromeres.

The high incidence of whole-arm chromosome aneuploidy and translocations in tumors suggests instability of centromeres, unique loci built on repetitive sequences and essential for chromosome separation. The causes behind this fragility and the mechanisms preserving centromere integrity remain elusive. We show that replication stress, hallmark of pre-cancerous lesions, promotes centromeric breakage in mitosis, due to spindle forces and endonuclease activities. Mechanistically, we unveil unique dynamics of the centromeric replisome distinct from the rest of the genome. Locus-specific proteomics identifies specialized DNA replication and repair proteins at centromeres, highlighting them as difficult-to-replicate regions. The translesion synthesis pathway, along with other factors, acts to sustain centromere replication and integrity. Prolonged stress causes centromeric alterations like ruptures and translocations, as observed in ovarian cancer models experiencing replication stress. This study provides unprecedented insights into centromere replication and integrity, proposing mechanistic insights into the origins of centromere alterations leading to abnormal cancerous karyotypes.

Single-cell analysis reveals the continuum of human lympho-myeloid progenitor cells.

The hierarchy of human hemopoietic progenitor cells that produce lymphoid and granulocytic-monocytic (myeloid) lineages is unclear. Multiple progenitor populations produce lymphoid and myeloid cells, but they remain incompletely characterized. Here we demonstrated that lympho-myeloid progenitor populations in cord blood - lymphoid-primed multi-potential progenitors (LMPPs), granulocyte-macrophage progenitors (GMPs) and multi-lymphoid progenitors (MLPs) - were functionally and transcriptionally distinct and heterogeneous at the clonal level, with progenitors of many different functional potentials present. Although most progenitors had the potential to develop into only one mature cell type ('uni-lineage potential'), bi- and rarer multi-lineage progenitors were present among LMPPs, GMPs and MLPs. Those findings, coupled with single-cell expression analyses, suggest that a continuum of progenitors execute lymphoid and myeloid differentiation, rather than only uni-lineage progenitors' being present downstream of stem cells.

RYBP-PRC1 complexes mediate H2A ubiquitylation at polycomb target sites independently of PRC2 and H3K27me3.

Polycomb-repressive complex 1 (PRC1) has a central role in the regulation of heritable gene silencing during differentiation and development. PRC1 recruitment is generally attributed to interaction of the chromodomain of the core protein Polycomb with trimethyl histone H3K27 (H3K27me3), catalyzed by a second complex, PRC2. Unexpectedly we find that RING1B, the catalytic subunit of PRC1, and associated monoubiquitylation of histone H2A are targeted to closely overlapping sites in wild-type and PRC2-deficient mouse embryonic stem cells (mESCs), demonstrating an H3K27me3-independent pathway for recruitment of PRC1 activity. We show that this pathway is mediated by RYBP-PRC1, a complex comprising catalytic subunits of PRC1 and the protein RYBP. RYBP-PRC1 is recruited to target loci in mESCs and is also involved in Xist RNA-mediated silencing, the latter suggesting a wider role in Polycomb silencing. We discuss the implications of these findings for understanding recruitment and function of Polycomb repressors.

Defining genome architecture at base-pair resolution.

In higher eukaryotes, many genes are regulated by enhancers that are 104-106 base pairs (bp) away from the promoter. Enhancers contain transcription-factor-binding sites (which are typically around 7-22 bp), and physical contact between the promoters and enhancers is thought to be required to modulate gene expression. Although chromatin architecture has been mapped extensively at resolutions of 1 kilobase and above; it has not been possible to define physical contacts at the scale of the proteins that determine gene expression. Here we define these interactions in detail using a chromosome conformation capture method (Micro-Capture-C) that enables the physical contacts between different classes of regulatory elements to be determined at base-pair resolution. We find that highly punctate contacts occur between enhancers, promoters and CCCTC-binding factor (CTCF) sites and we show that transcription factors have an important role in the maintenance of the contacts between enhancers and promoters. Our data show that interactions between CTCF sites are increased when active promoters and enhancers are located within the intervening chromatin. This supports a model in which chromatin loop extrusion1 is dependent on cohesin loading at active promoters and enhancers, which explains the formation of tissue-specific chromatin domains without changes in CTCF binding.

Hydrogen bonding heterogeneity correlates with protein folding transition state passage time as revealed by data sonification.

Protein-protein and protein-water hydrogen bonding interactions play essential roles in the way a protein passes through the transition state during folding or unfolding, but the large number of these interactions in molecular dynamics (MD) simulations makes them difficult to analyze. Here, we introduce a state space representation and associated "rarity" measure to identify and quantify transition state passage (transit) events. Applying this representation to a long MD simulation trajectory that captured multiple folding and unfolding events of the GTT WW domain, a small protein often used as a model for the folding process, we identified three transition categories: Highway (faster), Meander (slower), and Ambiguous (intermediate). We developed data sonification and visualization tools to analyze hydrogen bond dynamics before, during, and after these transition events. By means of these tools, we were able to identify characteristic hydrogen bonding patterns associated with "Highway" versus "Meander" versus "Ambiguous" transitions and to design algorithms that can identify these same folding pathways and critical protein-water interactions directly from the data. Highly cooperative hydrogen bonding can either slow down or speed up transit. Furthermore, an analysis of protein-water hydrogen bond dynamics at the surface of WW domain shows an increase in hydrogen bond lifetime from folded to unfolded conformations with Ambiguous transitions as an outlier. In summary, hydrogen bond dynamics provide a direct window into the heterogeneity of transits, which can vary widely in duration (by a factor of 10) due to a complex energy landscape.

ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner.

ATRX is an X-linked gene of the SWI/SNF family, mutations in which cause syndromal mental retardation and downregulation of α-globin expression. Here we show that ATRX binds to tandem repeat (TR) sequences in both telomeres and euchromatin. Genes associated with these TRs can be dysregulated when ATRX is mutated, and the change in expression is determined by the size of the TR, producing skewed allelic expression. This reveals the characteristics of the affected genes, explains the variable phenotypes seen with identical ATRX mutations, and illustrates a new mechanism underlying variable penetrance. Many of the TRs are G rich and predicted to form non-B DNA structures (including G-quadruplex) in vivo. We show that ATRX binds G-quadruplex structures in vitro, suggesting a mechanism by which ATRX may play a role in various nuclear processes and how this is perturbed when ATRX is mutated.

Mapping the distance between fire hazard and disaster for communities in Canadian forests.

Communities interspersed throughout the Canadian wildland are threatened by fires that have become bigger and more frequent in some parts of the country in recent decades. Identifying the fireshed (source area) and pathways from which wildland fire may ignite and spread from the landscape to a community is crucial for risk-reduction strategy and planning. We used outputs from a fire simulation model, including fire polygons and rate of spread, to map firesheds, fire pathways and corridors and spread distances for 1980 communities in the forested areas of Canada. We found fireshed sizes are larger in the north, where the mean distances between ecumene and fireshed perimeters were greater than 10 km. The Rayleigh Z test indicated that simulated fires around a large proportion of communities show significant directional trends, and these trends are stronger in the Boreal Plains and Shields than in the Rocky Mountain area. The average distance from which fire, when spreading at the maximum simulated rate, could reach the community perimeter was approximately 5, 12 and 18 km in 1, 2 and 3 days, respectively. The average daily spread distances increased latitudinally, from south to north. Spread distances were the shortest in the Pacific Maritime, Atlantic Maritime and Boreal Plains Ecozones, implying lower rates of spread compared to the rest of the country. The fire corridors generated from random ignitions and from ignitions predicted from local fire history differ, indicating that factors other than fuel (e.g. fire weather, ignition pattern) play a significant role in determining the direction that fires burn into a community.

Efficient Large-Scale, Targeted Gravitational-Wave Probes of Supermassive Black-Hole Binaries.

Binary systems of supermassive black holes are promising sources of low-frequency gravitational waves (GWs) and bright electromagnetic emission. Pulsar timing array GW searches for individual binaries have been limited to only a few candidate systems due to computational demands, which get worse as more pulsars are added. By modeling the GW signal using only components from when the GW passes Earth (rather than also each pulsar), we find constraints on the binary's total mass and GW frequency that are similar to a full signal analysis, yet ∼70 times more efficient.

Exploiting a living biobank to delineate mechanisms underlying disease-specific chromosome instability.

Chromosome instability (CIN) is a cancer hallmark that drives tumour heterogeneity, phenotypic adaptation, drug resistance and poor prognosis. High-grade serous ovarian cancer (HGSOC), one of the most chromosomally unstable tumour types, has a 5-year survival rate of only ~30% - largely due to late diagnosis and rapid development of drug resistance, e.g., via CIN-driven ABCB1 translocations. However, CIN is also a cell cycle vulnerability that can be exploited to specifically target tumour cells, illustrated by the success of PARP inhibitors to target homologous recombination deficiency (HRD). However, a lack of appropriate models with ongoing CIN has been a barrier to fully exploiting disease-specific CIN mechanisms. This barrier is now being overcome with the development of patient-derived cell cultures and organoids. In this review, we describe our progress building a Living Biobank of over 120 patient-derived ovarian cancer models (OCMs), predominantly from HGSOC. OCMs are highly purified tumour fractions with extensive proliferative potential that can be analysed at early passage. OCMs have diverse karyotypes, display intra- and inter-patient heterogeneity and mitotic abnormality rates far higher than established cell lines. OCMs encompass a broad-spectrum of HGSOC hallmarks, including a range of p53 alterations and BRCA1/2 mutations, and display drug resistance mechanisms seen in the clinic, e.g., ABCB1 translocations and BRCA2 reversion. OCMs are amenable to functional analysis, drug-sensitivity profiling, and multi-omics, including single-cell next-generation sequencing, and thus represent a platform for delineating HGSOC-specific CIN mechanisms. In turn, our vision is that this understanding will inform the design of new therapeutic strategies.

Influence of Patient Weight on Prehospital Advanced Airway Procedure Success Rates.

OBJECTIVE: Previous investigations of the relationship between obesity and difficult airway management have provided mixed results. Almost universally, these studies were conducted in the hospital setting, and the influence of patient body weight on successful prehospital airway management remains unclear. Because patient weight could be one readily identifiable risk factor for problematic airway interventions, we sought to evaluate this relationship. METHODS: We conducted a retrospective analysis using the 2020 ESO Data Collaborative dataset. The inclusion criteria consisted of adult patients weighing >30kg with an attempted orotracheal intubation (OTI) and/or blind insertion airway device (BIAD) placement. Separate logistic regression models were developed to determine the influence of weight (dichotomized at 100 kg) on cumulative procedure success for OTI and BIAD, and linear regression models were used to identify trends for each across weight strata. RESULTS: A total of 45,344 patients met inclusionary criteria, among which 40,668(89.7%) suffered from a medical emergency, followed by 3,130(6.9%) with traumatic injuries, and 1,546(3.4%) attributable to a combined medical-trauma etiology. Cardiac arrest occurred either prior to EMS arrival or at some point during EMS care in 38,210(84.3%) patients. OTI was attempted in 18,153(40.0%) patients, while 21,597(47.6%) had a BIAD attempt and 5,594(12.3%) had both airway types attempted. The overall cumulative insertion success rates for OTI and BIAD were 79.5% and 92.7%, respectively. Altogether, 2,711(6.0%) had no advanced airway of any type successfully placed, which represents the overall failed advanced airway rate. After controlling for patient age, sex, minority status, and call type (medical vs. trauma), weight >100kg was associated with decreased likelihood of cumulative OTI success (OR = 0.64, p < 0.001), but higher likelihood of cumulative BIAD success (OR = 1.31, p < 0.001). Cumulative OTI success was associated with a negative 0.6% linear trend per 5 kg of body weight (p < 0.001) while cumulative BIAD success had a 0.2% positive trend (p < 0.001). CONCLUSION: This retrospective analysis of a national EMS database revealed that increasing patient weight was negatively associated with intubation success. A positive, but smaller, linear trend was observed for BIAD placement. Patient weight may be an easily identifiable predictor of difficult oral intubation and may be a consideration when selecting an airway management strategy.

Towards a core outcome set for dysarthria after stroke: What should we measure?

OBJECTIVE: To identify and agree on what outcome domains should be measured in research and clinical practice when working with stroke survivors who have dysarthria. DESIGN: Delphi process, two rounds of an online survey followed by two online consensus meetings. SETTING: UK and Australia. PARTICIPANTS: Stroke survivors with experience of dysarthria, speech and language therapists/pathologists working in stroke and communication researchers. METHODS: Initial list of outcome domains generated from existing literature and with our patient and public involvement group to develop the survey. Participants completed two rounds of this survey to rate importance. Outcomes were identified as 'in', 'unclear' or 'out' from the second survey. All participants were invited to two consensus meetings to discuss these results followed by voting to identify critically important outcome domains for a future Core Outcome Set. All outcomes were voted on in the consensus meetings and included if 70% of meeting participants voted 'yes' for critically important. RESULTS: In total, 148 surveys were fully completed, and 28 participants attended the consensus meetings. A core outcome set for dysarthria after stroke should include four outcome domains: (a) intelligibility of speech, (b) ability to participate in conversations, (c) living well with dysarthria, (d) skills and knowledge of communication partners (where relevant). CONCLUSIONS: We describe the consensus of 'what' speech outcomes after stroke are valued by all stakeholders including those with lived experience. We share these findings to encourage the measurement of these domains in clinical practice and research and for future research to identify 'how' best to measure these outcomes.

Efficacy and Safety of Switching to the 2-Drug Regimen Dolutegravir/Lamivudine Versus Continuing a 3- or 4-Drug Regimen for Maintaining Virologic Suppression in Adults Living With Human Immunodeficiency Virus 1 (HIV-1): Week 48 Results From the Phase 3, Noninferiority SALSA Randomized Trial.

BACKGROUND: In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) demonstrated long-term noninferior efficacy vs continuing tenofovir alafenamide-based regimens in treatment-experienced adults with HIV-1. The phase 3 SALSA study evaluated efficacy and safety of switching to DTG/3TC compared with continuing various 3-/4-drug current antiretroviral regimens (CARs). METHODS: Adults with HIV-1 RNA <50 copies/mL and no previous virologic failure were randomized (1:1, stratified by baseline third agent class) to switch to once-daily fixed-dose combination DTG/3TC or continue CAR (primary endpoint: proportion of participants with HIV-1 RNA ≥50 copies/mL at week 48; Snapshot, intention-to-treat-exposed population, 5% noninferiority margin). RESULTS: Overall, 493 adults (39% women; 39% aged ≥50 years; 19% African American/African heritage; 14% Asian) were randomized to switch to DTG/3TC (n = 246) or continue CAR (n = 247). At week 48, 1 (0.4%) participant in the DTG/3TC group and 3 (1.2%) in the CAR group had HIV-1 RNA ≥50 copies/mL (Snapshot), demonstrating noninferiority (adjusted difference, -0.8%; 95% CI, -2.4%, .8%). Zero participants met confirmed virologic withdrawal criteria; therefore, no resistance testing was performed. Drug-related adverse events were more frequent with DTG/3TC (20%) than CAR (6%) through week 48 but comparable post-week 24 (5% vs 2%, respectively). Proximal tubular renal function and bone turnover biomarkers improved with DTG/3TC. Both groups had generally minimal changes in lipids and inflammatory biomarkers. CONCLUSIONS: Switching to DTG/3TC was noninferior to continuing CAR for maintaining virologic suppression at week 48 with no observed resistance, supporting the efficacy, good safety, and high barrier to resistance of DTG/3TC. CLINICAL TRIALS REGISTRATION: www.clinicaltrials.gov, NCT04021290.

LanceOtron: a deep learning peak caller for genome sequencing experiments.

MOTIVATION: Genome sequencing experiments have revolutionized molecular biology by allowing researchers to identify important DNA-encoded elements genome wide. Regions where these elements are found appear as peaks in the analog signal of an assay's coverage track, and despite the ease with which humans can visually categorize these patterns, the size of many genomes necessitates algorithmic implementations. Commonly used methods focus on statistical tests to classify peaks, discounting that the background signal does not completely follow any known probability distribution and reducing the information-dense peak shapes to simply maximum height. Deep learning has been shown to be highly accurate for many pattern recognition tasks, on par or even exceeding human capabilities, providing an opportunity to reimagine and improve peak calling. RESULTS: We present the peak calling framework LanceOtron, which combines deep learning for recognizing peak shape with multifaceted enrichment calculations for assessing significance. In benchmarking ATAC-seq, ChIP-seq and DNase-seq, LanceOtron outperforms long-standing, gold-standard peak callers through its improved selectivity and near-perfect sensitivity. AVAILABILITY AND IMPLEMENTATION: A fully featured web application is freely available from LanceOtron.molbiol.ox.ac.uk, command line interface via python is pip installable from PyPI at https://pypi.org/project/lanceotron/, and source code and benchmarking tests are available at https://github.com/LHentges/LanceOtron. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

A matched cohort study investigating premature, accentuated, and accelerated aging in people living with HIV.

INTRODUCTION: The impact of HIV infection on the aging process is disputed and largely unknown. We aimed to identify whether people living with HIV experience premature, accelerated, and/or accentuated aging by investigating the development of four age-related non-communicable diseases in people living with versus without HIV. METHODS: This population-based matched cohort study design used UK-based primary care electronic health records from the IQVIA Medical Research Database. Between January 2000 and January 2020, all people living with and without HIV aged ≥18 years were eligible. Outcomes included cardiovascular disease (CVD), hypertension, type 2 diabetes mellitus (T2DM), and chronic kidney disease (CKD), which were identified by Read codes. We used age at diagnosis to investigate premature aging and age at exit date to investigate accentuation and acceleration. For each outcome, people with and without HIV were excluded if they had the outcome of interest at baseline. Participants were matched based on propensity scores (1:1 ratio). Linear regression was used to report any difference in age at diagnosis between the two groups and to report the prevalence trends for age at exit date. RESULTS: In total, 8880 people living with HIV were matched with 8880 people without HIV and were found to have an earlier onset of CVD (54.5 vs. 56.8; p = 0.002). Similarly, people living with HIV had an earlier onset of hypertension (49.7 vs. 51.4; p = 0.002). No difference was found for T2DM or CKD (53.4 vs. 52.6; p = 0.368 and 57.6 vs. 58.1; p = 0.483, respectively). The burden of CKD increased over time, whereas no difference in the burden was found for the other conditions. CONCLUSION: The earlier development of CVD and hypertension in people living with HIV than in those without HIV indicates premature aging, whereas the increased burden of CKD indicates accelerated aging.

Homologous recombination deficiency in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian cancer: a multi-national observational study.

OBJECTIVE: Olaparib plus bevacizumab maintenance therapy improves survival outcomes in women with newly diagnosed, advanced, high-grade ovarian cancer with a deficiency in homologous recombination. We report data from the first year of routine homologous recombination deficiency testing in the National Health Service (NHS) in England, Wales, and Northern Ireland between April 2021 and April 2022. METHODS: The Myriad myChoice companion diagnostic was used to test DNA extracted from formalin-fixed, paraffin-embedded tumor tissue in women with newly diagnosed International Federation of Gynecology and Obstetrics (FIGO) stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. Tumors with homologous recombination deficiency were those with a BRCA1/2 mutation and/or a Genomic Instability Score (GIS) ≥42. Testing was coordinated by the NHS Genomic Laboratory Hub network. RESULTS: The myChoice assay was performed on 2829 tumors. Of these, 2474 (87%) and 2178 (77%) successfully underwent BRCA1/2 and GIS testing, respectively. All complete and partial assay failures occurred due to low tumor cellularity and/or low tumor DNA yield. 385 tumors (16%) contained a BRCA1/2 mutation and 814 (37%) had a GIS ≥42. Tumors with a GIS ≥42 were more likely to be BRCA1/2 wild-type (n=510) than BRCA1/2 mutant (n=304). The distribution of GIS was bimodal, with BRCA1/2 mutant tumors having a higher mean score than BRCA1/2 wild-type tumors (61 vs 33, respectively, χ2 test p<0.0001). CONCLUSION: This is the largest real-world evaluation of homologous recombination deficiency testing in newly diagnosed FIGO stage III/IV high-grade epithelial ovarian, fallopian tube, or primary peritoneal cancer. It is important to select tumor tissue with adequate tumor content and quality to reduce the risk of assay failure. The rapid uptake of testing across England, Wales, and Northern Ireland demonstrates the power of centralized NHS funding, center specialization, and the NHS Genomic Laboratory Hub network.

Measuring the Effect of Audio Instructions on the Time and Effectiveness of Tourniquet Application by Laypeople.

OBJECTIVE: The "Stop the Bleed" campaign was created to educate laypeople about bleeding control and make bleeding control kits available in public locations. Unfortunately, previous research has indicated that up to half of all laypeople cannot effectively apply a tourniquet. The purpose of this study was to determine if laypeople could apply tourniquets more effectively with just-in-time training using combined audio-written instructions versus written-only instructions. METHODS: We conducted a prospective randomized study comparing the application of a tourniquet using a simulated bleeding arm. Participants were laypeople 18 years and older and excluded those with any previous tourniquet experience or training. Participants were randomized to just-in-time training using either audio-written or written-only instructions. Time in seconds to tourniquet application and the effectiveness of the tourniquet application was recorded. Effective application was defined as stopping the flow or significantly slowing the flow to a slow drip. Ineffective tourniquet placement was defined as not significantly changing the flow. Statistical analysis was performed using Fisher's exact, t-test, and linear regression. RESULTS: Eighty-two participants were included; 40 were in the audio-written instructions group, and 58.5% were male. The audio-written group's effective application rate was 92.5% and that of the written-only group was 76.2%. A significantly higher rate of ineffective tourniquet application was noted for the written-only group (23.8%), versus the audio-written group (7.5%), p = .04. Regardless of the type of instructions used, time to effective application of the tourniquet decreased as participant age increased (p = 0.02, 95%CI (-1.24, -0.13). There was no relationship between age and effective tourniquet application (p = 0.06). Time for tourniquet placement was not different between the audio-written (mean 100.4 seconds) and written-only (mean 106.1 seconds) groups (p = 0.58). CONCLUSION: This study suggests that combined audio-written instructions decrease the rate of ineffective tourniquet application by laypeople compared with written-only instructions. Further studies are needed to assess if audio instructions and just-in-time training can further maximize effective tourniquet application.

Traditional Uses, Pharmacological Activities, and Phytochemical Analysis of Diospyros mespiliformis Hochst. ex. A. DC (Ebenaceae): A Review.

Diospyros mespiliformis Hochst. ex. A. DC is widely distributed throughout Africa and around the world. It is utilized ethnobotanically to treat fevers, wounds, malaria, diabetes mellitus, and other diseases. This review aims to provide an exhaustive overview of the traditional uses, pharmacology, and phytochemical analysis of D. mespiliformis, with the objective of identifying its therapeutic potential for further research. Scientific resources, including Google Scholar, Science Direct, Web of Science, Pub Med, and Scopus, were used to find pertinent data on D. mespiliformis. Secondary metabolites tentatively identified from this species were primarily terpenoids, naphthoquinones, phenolics, and coumarins. D. mespiliformis has been reported to demonstrate pharmacological activities, including antimicrobial, antiproliferative, antiparasitic, antioxidant, anti-inflammatory, antiviral, anti-hypersensitivity, and antidiabetic properties. The phytochemicals and extracts from D. mespiliformis have been reported to have some pharmacological effects in in vivo studies and were not toxic to the animal models that were utilized. The D. mespiliformis information reported in this review provides researchers with a comprehensive summary of the current research status of this medicinal plant and a guide for further investigation.

Incidence of Cardiometabolic Diseases in People With and Without Human Immunodeficiency Virus in the United Kingdom: A Population-Based Matched Cohort Study.

BACKGROUND: Evidence on the risk of cardiovascular disease (CVD) and CVD risk factors in people with human immunodeficiency virus (PWH) is limited. We aimed to identify the risk of composite CVD, individual CVD events, and common risk factors. METHODS: This was a nationwide, population-based, cohort study comparing adult (≥18 years old) PWH with people without human immunodeficiency virus (HIV) matched on age, sex, ethnicity, and location. The primary outcome was composite CVD comprising stroke, myocardial infarction, peripheral vascular disease, ischemic heart disease, and heart failure. The secondary outcomes were individual CVD events, hypertension, diabetes, chronic kidney disease (CKD), and all-cause mortality. Cox proportional hazard regression models were used to examine the risk of each outcome. RESULTS: We identified 9233 PWH and matched them with 35 721 HIV-negative individuals. An increased risk was found for composite CVD (adjusted hazard ratio [aHR], 1.50; 95% confidence interval [CI], 1.28-1.77), stroke (aHR, 1.42; 95% CI, 1.08-1.86), ischemic heart disease (aHR, 1.55; 95% CI, 1.24-1.94), hypertension (aHR, 1.37; 95% CI, 1.23-1.53), type 2 diabetes (aHR, 1.28; 95% CI, 1.09-1.50), CKD (aHR, 2.42; 95% CI, 1.98-2.94), and all-cause mortality (aHR, 2.84; 95% CI, 2.48-3.25). CONCLUSIONS: PWH have a heightened risk for CVD and common CVD risk factors, reinforcing the importance for regular screening for such conditions.