The effect of weight gain and metabolic dysfunction-associated steatotic liver disease on liver fibrosis progression and regression in people with HIV.

OBJECTIVE: People with HIV (PWH) have high risk of liver fibrosis. We investigated the effect of weight gain and metabolic dysfunction-associated steatotic liver disease (MASLD) on liver fibrosis dynamics. DESIGN: Multicenter cohort study. METHODS: Fibrosis progression was defined as development of significant fibrosis (liver stiffness measurement [LSM]≥8 kPa), or transition to cirrhosis (LSM≥13 kPa), for those with significant fibrosis at baseline. Fibrosis regression was defined as transition to LSM<8 kPa, or to LSM<13 kPa for those with cirrhosis at baseline. MASLD was defined as hepatic steatosis (controlled attenuation parameter >248 dB/m) with at least one metabolic abnormality. A continuous-time multi-state Markov model was used to describe transitions across fibrosis states. RESULTS: Among 1183 PWH included from three centres (25.2% with viral hepatitis coinfection), baseline prevalence of significant fibrosis and MASLD was 14.4% and 46.8%, respectively. During a median follow-up of 2.5 years (interquartile range 1.9-3.5) the incidence rate of fibrosis progression and regression was 2.8 (95% CI, 2.3-3.4) and 2.2 (95% CI, 1.9-2.6) per 100 person-years, respectively. In Markov model, weight gain increased the odds of fibrosis progression (odds ratio [OR] 3.11, 95% CI 1.59-6.08), whereas weight gain (OR 0.30, 95% CI 0.10-0.84) and male sex (OR 0.32, 95% CI 0.14-0.75) decreased the odds of fibrosis regression. On multivariable Cox regression analysis, predictors of fibrosis progression were weight gain (adjusted hazard ratio [aHR] 3.12, 95% CI 1.41-6.90) and MASLD (aHR 2.72, 95% CI 1.05-7.02). CONCLUSIONS: Fibrosis transitions are driven by metabolic health variables in PWH, independently of viral hepatitis coinfection and antiretroviral class therapy.

Metabolic dysfunction-associated steatotic liver disease: An opportunity for collaboration between cardiology and hepatology.

Altered metabolic function has many detrimental effects on the body that can manifest as cardiovascular and liver diseases. Traditional approaches to understanding and treating metabolic dysfunction-associated disorders have been organ-centered, leading to silo-type disease care. However, given the broad impact that systemic metabolic dysfunction has on the human body, approaches that simultaneously involve multiple medical specialists need to be developed and encouraged to optimize patient outcomes. In this review, we highlight how several of the treatments developed for cardiac care may have a beneficial effect on the liver and vice versa, suggesting that there is a need to target the disease process, rather than specifically target the cardiovascular or liver specific sequelae of metabolic dysfunction.

Resistive switching in benzylammonium-based Ruddlesden-Popper layered hybrid perovskites for non-volatile memory and neuromorphic computing.

Artificial synapses based on resistive switching have emerged as a promising avenue for brain-inspired computing. Hybrid metal halide perovskites have provided the opportunity to simplify resistive switching device architectures due to their mixed electronic-ionic conduction, yet the instabilities under operating conditions compromise their reliability. We demonstrate reliable resistive switching and synaptic behaviour in layered benzylammonium (BzA) based halide perovskites of (BzA)2PbX4 composition (X = Br, I), showing a transformation of the resistive switching from digital to analog with the change of the halide anion. While (BzA)2PbI4 devices demonstrate gradual set and reset processes with reduced power consumption, the (BzA)2PbBr4 system features a more abrupt switching behaviour. Moreover, the iodide-based system displays excellent retention and endurance, whereas bromide-based devices achieve a superior on/off ratio. The underlying mechanism is attributed to the migration of halide ions and the formation of halide vacancy conductive filaments. As a result, the corresponding devices emulate synaptic characteristics, demonstrating the potential for neuromorphic computing. Such resistive switching and synaptic behaviour highlight (BzA)2PbX4 perovskites as promising candidates for non-volatile memory and neuromorphic computing.

Ageism: the -ism affecting the lives of older people living with HIV.

WHO defines ageism as stereotypes, prejudice, and discrimination based on age. Ageism is a multidimensional concept that encompasses multiple components related to the individual, the social group, and the institution in different cultural and environmental settings. In people ageing with HIV these elements include self-stigma, discrimination in society, and experiences in care, many of which are unique to older people. In this Position Paper, we use experience of people with HIV and clinicians taking care of them to explore these issues in high-income countries. The intersectionality of multiple -isms, which affect the lives of older people living with HIV, and ageism enhance several HIV-related issues, including self-inflicted stigma, and loneliness. Research is needed to explore how ageism contributes to worse physical, mental, and social wellbeing outcomes for people with HIV. The model of care for older people living with HIV needs to go beyond virological success by adopting a geriatric mindset, which is attentive to the challenge of ageism and is proactive in promoting a comprehensive approach for the ageing population. All stakeholders and the community should work together to co-create institutional strategies and educational programmes and enable respectful intergenerational dialogue to foster a stigma-free future for older people living with HIV.

Bone Mineral Density and Trabecular Bone Score Changes throughout Menopause in Women with HIV.

OBJECTIVE: The objectives of this study were to describe the trajectories of bone mineral density (BMD) and trabecular bone score (TBS) changes throughout pre-menopause (reproductive phase and menopausal transition) and post-menopause (early and late menopause) in women with HIV (WWH) undergoing different antiretroviral therapies (ARTs) and explore the risk factors associated with those changes. METHODS: This was an observational longitudinal retrospective study in WWH with a minimum of two DEXA evaluations comprising BMD and TBS measurements, both in the pre-menopausal and post-menopausal periods. Menopause was determined according to the STRAW+10 criteria, comprising four periods: the reproductive period, menopausal transition, and early- and late-menopausal periods. Mixed-effects models were fitted to estimate the trajectories of the two outcomes (BMD and TBS) over time. Annualized lumbar BMD and TBS absolute and percentage changes were calculated in each STRAW+10 time window. A backward elimination procedure was applied to obtain the final model, including the predictors that affected the trajectories of BMD or TBS over time. RESULTS: A total of 202 WWH, all Caucasian, were included. In detail, 1954 BMD and 195 TBS data were analyzed. The median number of DEXA evaluations per woman was 10 (IQR: 7, 12). The median observation periods per patient were 12.0 years (IQR = 8.9-14.4) for BMD and 6.0 years (IQR: 4.3, 7.9) for TBS. The prevalence of osteopenia (63% vs. 76%; p < 0.001) and osteoporosis (16% vs. 36%; p < 0.001) increased significantly between the pre-menopausal and post-menopausal periods. Both BMD (1.03 (±0.14) vs. 0.92 (±0.12) g/cm2; p < 0.001) and TBS (1.41 (IQR: 1.35, 1.45) vs. 1.32 (IQR: 1.28, 1.39); p < 0.001) decreased significantly between the two periods. The trend in BMD decreased across the four STRAW+10 periods, with a slight attenuation only in the late-menopausal period when compared with the other intervals. The TBS slope did not significantly change throughout menopause. The delta mean values of TBS in WWH were lower between the menopausal transition and reproductive period compared with the difference between menopause and menopausal transition. CONCLUSIONS: Both BMD and TBS significantly decreased over time. The slope of the change in BMD and TBS significantly decreased in the menopausal transition, suggesting that this period should be considered by clinicians as a key time during which to assess bone health and modifiable risk factors in WWH.

A Machine Learning Approach to Predict Weight Change in ART-Experienced People Living With HIV.

INTRODUCTION: The objective of the study was to develop machine learning (ML) models that predict the percentage weight change in each interval of time in antiretroviral therapy-experienced people living with HIV. METHODS: This was an observational study that comprised consecutive people living with HIV attending Modena HIV Metabolic Clinic with at least 2 visits. Data were partitioned in an 80/20 training/test set to generate 10 progressively parsimonious predictive ML models. Weight gain was defined as any weight change >5%, at the next visit. SHapley Additive exPlanations values were used to quantify the positive or negative impact of any single variable included in each model on the predicted weight changes. RESULTS: A total of 3,321 patients generated 18,322 observations. At the last observation, the median age was 50 years and 69% patients were male. Model 1 (the only 1 including body composition assessed with dual-energy x-ray absorptiometry) had an accuracy greater than 90%. This model could predict weight at the next visit with an error of <5%. CONCLUSIONS: ML models with the inclusion of body composition and metabolic and endocrinological variables had an excellent performance. The parsimonious models available in standard clinical evaluation are insufficient to obtain reliable prediction, but are good enough to predict who will not experience weight gain.

Evaluating immunological and inflammatory changes of treatment-experienced people living with HIV switching from first-line triple cART regimens to DTG/3TC vs. B/F/TAF: the DEBATE trial.

Background: The aim of this randomized clinical trial (RCT) was to compare immunological changes in virally suppressed people living with HIV (PLWH) switching from a three-drug regimen (3DR) to a two-drug regimen (2DR). Methods: An open-label, prospective RCT enrolling PLWH receiving a 3DR who switched to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) or dolutegravir/lamivudine (DTG/3TC) was performed. Blood was taken at baseline and months 6 and 12. The primary outcome was the change in CD4+ or CD8+ T-cell counts and CD4/CD8 ratio over time points. The secondary outcomes were the changes in immunological and inflammatory parameters. Parametric mixed-linear models with random intercepts and slopes were fitted separately for each marker after controlling for potential confounders. Results: Between the two arms (33 PLWH each), there was no difference in CD4+ or CD8+ T cells, CD4/CD8 ratio, and IL-6 trajectories. PLWH switching to DTG/3TC had increased levels of both transitional memory and terminally differentiated CD4+ T cells (arm-time interaction p-value = 0.02) and to a lesser extent for the corresponding CD8+ T-cell subsets (p = 0.09). Significantly lower levels of non-classical monocytes were detected in the B/F/TAF arm at T6 (diff = -6.7 cells/mm3; 95% CI; -16, +2.6; p-value for interaction between arm and time = 0.03). All differences were attenuated at T12. Conclusion: No evidence for a difference in absolute CD4+ and CD8+ T-cell counts, CD4/CD8 ratio, and IL-6 trajectories by study arm over 12 months was found. PLWH on DTG/3TC showed higher levels of terminally differentiated and exhausted CD4+ and CD8+ T lymphocytes and non-classical monocytes at T6. Further studies are warranted to better understand the clinical impact of our results. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT04054089.

Can statin preventative treatment inform geroscience-guided therapeutics?

Potential senotherapeutic effect of statins may lead to prevention and reduction of frailty.

Sarcopenic Obesity Phenotypes in Patients With HIV: Implications for Cardiovascular Prevention and Rehabilitation.

BACKGROUND: We aimed to describe prevalence, incidence, and risk factors for sarcopenic obesity (SO) phenotypes in people living with HIV (PWH) and their association with subclinical cardiovascular disease (CVD). METHODS: Observational, longitudinal study of PWH. A minimum of 1 criterion was necessary to diagnose sarcopenia: weak hand grip (HG), low appendicular skeletal muscle index (ASMI), short physical performance battery (SPPB < 11). Obesity was defined as body mass index (BMI) ≥ 30 kg/m2 or visceral adipose tissue (VAT) ≥ 160 cm2. These variables combined generated 5 SO phenotypes: severe SO: low HG + low ASMI + low SPPB + high BMI; SO1: weak HG + high VAT; SO2: weak HG + high BMI; SO3: low ASMI + high VAT; SO4: low ASMI + high BMI. Subclinical CVD was defined as carotid intima-media thickness (IMT) ≥ 1 mm, presence of carotid plaque, or coronary artery calcification (CAC) score > 10. RESULTS: Among 2379 male PWH 72%, median age was 52 years, median HIV vintage 21 years, and median BMI 24 kg/m2. Two PWH had severe SO. The prevalence of SO1-SO4 was 19.7%, 3.6%, 20.8% and 0.8%, respectively. Incidence of SO1-SO4 was 6.90, 1.2, 5.6, and 0.29 × 100 person-years, respectively. SO1 was associated with risk of IMT ≥ 1, and SO3 with risk of CAC score > 10. CONCLUSIONS: There was a large variability in incidence and prevalence of SO phenotypes. The presence of SO may have important implications for cardiovascular prevention and cardiac rehabilitation of PWH who suffered events.

Functional dynamics in framework materials.

Dynamic crystalline materials have emerged as a unique category of condensed phase matter that combines crystalline lattice with components that display dynamic behavior in the solid state. This has involved a range of materials incorporating dynamic functional units in the form of stimuli-responsive molecular switches and machines, among others. In particular, it has been possible by relying on framework materials, such as porous molecular frameworks and other hybrid organic-inorganic systems that demonstrated potential for serving as scaffolds for dynamic molecular functions. As functional dynamics increase the level of complexity, the associated phenomena are often overlooked and need to be explored. In this perspective, we discuss a selection of recent developments of dynamic solid-state materials across material classes, outlining opportunities and fundamental and methodological challenges for their advancement toward innovative functionality and applications.

Nanocrystalline Flash Annealed Nickel Oxide for Large Area Perovskite Solar Cells.

The industrialization of perovskite solar cells requires adequate materials and processes to make them economically viable and environmentally sustainable. Despite promising results in terms of power conversion efficiency and operational stability, several hole-transport layers currently in use still need to prove their industrial feasibility. This work demonstrates the use of nanocrystalline nickel oxide produced through flash infrared annealing (FIRA), considerably reducing the materials cost, production time, energy, and the amount of solvents required for the hole transport layer. X-ray photoelectron spectroscopy reveals a better conversion to nickel oxide and a higher oxygen-to-nickel ratio for the FIRA films as compared to control annealing methods, resulting in higher device efficiency and operational stability. Planar inverted solar cells produced with triple cation perovskite absorber result in 16.7% power conversion efficiency for 1 cm2 devices, and 15.9% averaged over an area of 17 cm2 .

Quality of life and intrinsic capacity in patients with post-acute COVID-19 syndrome is in relation to frailty and resilience phenotypes.

The objective of this study was to characterize frailty and resilience in people evaluated for Post-Acute COVID-19 Syndrome (PACS), in relation to quality of life (QoL) and Intrinsic Capacity (IC). This cross-sectional, observational, study included consecutive people previously hospitalized for severe COVID-19 pneumonia attending Modena (Italy) PACS Clinic from July 2020 to April 2021. Four frailty-resilience phenotypes were built: "fit/resilient", "fit/non-resilient", "frail/resilient" and "frail/non-resilient". Frailty and resilience were defined according to frailty phenotype and Connor Davidson resilience scale (CD-RISC-25) respectively. Study outcomes were: QoL assessed by means of Symptoms Short form health survey (SF-36) and health-related quality of life (EQ-5D-5L) and IC by means of a dedicated questionnaire. Their predictors including frailty-resilience phenotypes were explored in logistic regressions. 232 patients were evaluated, median age was 58.0 years. PACS was diagnosed in 173 (74.6%) patients. Scarce resilience was documented in 114 (49.1%) and frailty in 72 (31.0%) individuals. Predictors for SF-36 score < 61.60 were the phenotypes "frail/non-resilient" (OR = 4.69, CI 2.08-10.55), "fit/non-resilient" (OR = 2.79, CI 1.00-7.73). Predictors for EQ-5D-5L < 89.7% were the phenotypes "frail/non-resilient" (OR = 5.93, CI 2.64-13.33) and "frail/resilient" (OR = 5.66, CI 1.93-16.54). Predictors of impaired IC (below the mean score value) were "frail/non-resilient" (OR = 7.39, CI 3.20-17.07), and "fit/non-resilient" (OR = 4.34, CI 2.16-8.71) phenotypes. Resilience and frailty phenotypes may have a different impact on wellness and QoL and may be evaluated in people with PACS to identify vulnerable individuals that require suitable interventions.

The Impact of Spacer Size on Charge Transfer Excitons in Dion-Jacobson and Ruddlesden-Popper Layered Hybrid Perovskites.

Organic materials can tune the optical properties in layered (2D) hybrid perovskites, although their impact on photophysics is often overlooked. Here, we use transient absorption spectroscopy to probe the Dion-Jacobson (DJ) and Ruddlesden-Popper (RP) 2D perovskite phases. We show the formation of charge transfer excitons in DJ phases, resulting in a photoinduced Stark effect which is shown to be dependent on the spacer size. By using electroabsorption spectroscopy, we quantify the strength of the photoinduced electric field, while temperature-dependent measurements demonstrate new features in the transient spectra of RP phases at low temperatures resulting from the quantum-confined Stark effect. This study reveals the impact of spacer size and perovskite phase configuration on charge transfer excitons in 2D perovskites of interest to their advanced material design.

Engaging Early-Career Scientists in Global Policy-Making.

Pressing global challenges, such as climate change, the COVID-19 pandemic, or antibiotic resistance, require coordinated international responses guided by evidence-informed decisions. For this purpose, it is critical that scientists engage in providing insights during the decision-making process. However, the mechanisms for the engagement of scientists in policy-making are complex and vary internationally, which often poses significant challenges to their involvement. Herein, we address some of the mechanisms and barriers for scientists to engage in policy-making with a global perspective by early-career scientists. We highlight the importance of scientific academies, societies, universities, and early-career networks as stakeholders and how they can adapt their structures to actively contribute to shaping global policies, with representative examples from chemistry-related disciplines. We showcase the importance of raising awareness, providing resources and training, and leading discussions about connecting emerging scientists with global decision-makers to address societal challenges through policies.

Prognostic value of non-invasive scores based on liver stiffness measurement, spleen diameter and platelets in HIV-infected patients.

BACKGROUND AND AIMS: People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH. METHODS: We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC). RESULTS: We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis. CONCLUSIONS: Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone.

Evidence gaps on weight gain in people living with HIV: a scoping review to define a research agenda.

BACKGROUND: Combined antiretroviral therapy (cART) dramatically improved survival in people living with HIV (PLWH) but is associated with weight gain (WG), raising concern for a possible obesity epidemic in PLWH. This scoping review aims to identify the gaps in the existing evidence on WG in PLWH and generate a future research agenda. METHODS: This review was conducted according to the methodology for scoping studies and reported according to the PRISMA Extension for Scoping Review checklist. Articles published in English in the last 10 years indexed in Pubmed, WHO Global Index Medicus, or Embase were searched using specific queries focused on WG in PLWH. RESULTS: Following the selection process, 175 included articles were reviewed to search for the available evidence on four specific topics: (I) definition of WG in PLWH, (II) pathogenesis of WG in PLWH, (III) impact of ART on WG, (IV) correlation of WG with clinical outcomes. A summary of the data enabled us to identify gaps and clearly define the following research agenda: (I) develop a data-driven definition of WG in PLWH and define noninvasive assessment methods for body weight and fat composition; (II) further investigate the interaction between HIV/cART and immunity, metabolism, and adipose tissue; (III) establish the specific role of individual drugs on WG; (IV) clarify the independent role of WG, cART, HIV, and metabolic factors on clinical events. CONCLUSIONS: The proposed research agenda may help define future research and fill the knowledge gaps that have emerged from this review.

Fibroscan-Aspartate Aminotransferase Score Predicts Liver-Related Outcomes, but Not Extrahepatic Events, in a Multicenter Cohort of People With Human Immunodeficiency Virus.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is frequent in people with human immunodeficiency virus (PWH). The Fibroscan-aspartate aminotransferase (FAST) score was developed to identify patients with nonalcoholic steatohepatitis (NASH) and significant fibrosis. We investigated prevalence of NASH with fibrosis and the value of FAST score in predicting clinical outcomes in PWH. METHODS: Transient elastography (Fibroscan) was performed in PWH without viral hepatitis coinfection from 4 prospective cohorts. We used FAST >0.35 to diagnose NASH with fibrosis. Incidence and predictors of liver-related outcomes (hepatic decompensation, hepatocellular carcinoma) and extrahepatic events (cancer, cardiovascular disease) were evaluated through survival analysis. RESULTS: Of the 1472 PWH included, 8% had FAST >0.35. Higher body mass index (adjusted odds ratio [aOR], 1.21 [95% confidence interval {CI}, 1.14-1.29]), hypertension (aOR, 2.24 [95% CI, 1.16-4.34]), longer time since HIV diagnosis (aOR, 1.82 [95% CI, 1.20-2.76]), and detectable HIV RNA (aOR, 2.22 [95% CI, 1.02-4.85]) were associated with FAST >0.35. A total of 882 patients were followed for a median of 3.8 years (interquartile range, 2.5-4.2 years). Overall, 2.9% and 11.1% developed liver-related and extrahepatic outcomes, respectively. Incidence of liver-related outcomes was higher in patients with FAST >0.35 versus FAST ≤0.35 (45.1 [95% CI, 26.2-77.7] vs 5.0 [95% CI, 2.9-8.6] per 1000 person-years). FAST >0.35 remained an independent predictor of liver-related outcomes (adjusted hazard ratio, 4.97 [95% CI, 1.97-12.51]). Conversely, FAST did not predict extrahepatic events. CONCLUSIONS: A significant proportion of PWH may have NASH with significant liver fibrosis. FAST score predicts liver-related outcomes and can help management of this high-risk population.