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Background: This study examined the impact of the COVID-19 lockdown on antiretroviral therapy (ART) prescriptions among persons living with HIV (PWH) in Italy. Methods: Data from the ICONA cohort included ART-naïve individuals who started ART between January 2019 and December 2022, and ART-experienced individuals who started new ART with HIV RNA ≤50 cps/mL from January 2016 to December 2022. The analysis focused on the proportion of PWH starting or switching to dual (2DR) versus triple (3DR) ART regimens. Comparisons were made using Chi-square and Kruskal-Wallis tests, with logistic regression (LR) to assess associations, adjusting for sex and age. Results: Among 2481 ART-naïve PWH, 17% were female, with a median age of 40. Using 2020 as the comparator (the lockdown year), the odds ratio (OR) from fitting a LR showed a reduced probability of prescribing 2DR both before and after 2020. The proportion of PWH starting 2DR was 9% in 2019, 18% in 2020, 13% in 2021, and 10% in 2022. Among 12,335 ART-experienced PWH, 20% were female, with a median age of 47. The proportion switching to 2DR rose from 24% in 2016 to 38% in 2020, 62% in 2021, and 65% in 2022, showing a >3-fold higher probability to be switched to 2DR instead of 3DR in recent years (2021-2022). Conclusions: For ART-naive PWH, 2DR initiation did not decrease during the 2020 lockdown but changed in the following years, possibly indicating shifts in clinical practice or resuming HIV services. For ART-experienced PWH, 2DR prescriptions increased significantly over time, especially for INSTI-based regimens. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells/stromal cells (MSCs)-derived extracellular vesicles (EVs) mediate pro-regenerative effects in damaged ischemic tissues by regulating angiogenesis. MSCs-EVs modulate functions of cells including endogenous mature cells, progenitors and stem cells, resulting in restoration of blood flow. However, the mechanisms underlying such MSC-EV activity still remain poorly understood. The present study analyzes biological effects of bone marrow (BM) MSC-EVs on endothelial cells (ECs) in ischemic tissues both in in vitro and in vivo conditions and elucidates the molecular mechanisms underlying the tissue repair. MSC-EVs were isolated from murine BM-derived MSCs and their morphological, antigenic and molecular composition regarding protein and microRNA levels were evaluated to examine their properties. Global proteomic analysis demonstrated the presence in MSC-EVs of proteins regulating pro-regenerative pathways, including integrin α5 (Itgα5) and neuropilin-1 (NRP1) involved in lymphangiogenesis. MSC-EVs were also enriched in microRNAs regulating angiogenesis, TGF-β signaling and processes guiding cellular adhesion and interactions with extracellular matrix. The functional effects of MSC-EVs on capillary ECs in vitro included the increase of capillary-like tube formation and cytoprotection under normal and inflammatory conditions by inhibiting apoptosis. Notably, MSC-EVs enhanced also capillary-like tube formation of lymphatic ECs, which may be regulated by Itgα5 and NRP1. Moreover, in a mouse model of critical hind limb ischemia, MSC-EVs increased the recovery of blood flow in ischemic muscle tissue, which was accompanied with increased vascular density in vivo. This pro-angiogenic effect was associated with an increase in nitric oxide (NO) production via endothelial NO-synthase activation in ischemic muscles. Interestingly, MSC-EVs enhanced lymphangiogenesis, which has never been reported before. The study provides evidence on pro-angiogenic and novel pro-lymphangiogenic role of MSC-EVs on ECs in ischemic tissue mediated by their protein and miRNA molecular cargos. The results highlight Itgα5 and NRP1 carried by MSC-EVs as potential therapeutic targets to boost lymphangiogenesis. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) significantly reduced Human Immunodeficiency Virus (HIV) morbidity and mortality; nevertheless, stigma still characterises the living with this condition. This study explored patients' coping experience by integrating narrative medicine (NM) in a non-interventional clinical trial. From June 2018 to September 2020 the study involved 18 centres across Italy; enrolled patients were both D/C/F/TAF naïve and previously ART-treated. Narratives were collected at enrolment (V1) and last visit (V4) and then independently analysed by three NM specialist researchers through content analysis. One-hundred and fourteen patients completed both V1 and V4 narratives. Supportive relationships with clinicians and undetectable viral load facilitated coping. Conversely, lack of disclosure of HIV-positive status, HIV metaphors, and unwillingness to narrate the life before the diagnosis indicated internalised stigma. This is the first non-interventional study to include narratives as patient reported outcomes (PROs). Improving HIV awareness and reducing the sense of guilt experienced by patients helps to overcome stigma and foster coping. [ABSTRACT FROM AUTHOR]

• The bivalent booster dose increases neutralizing antibodies against BA.5, BQ.1.1, XBB.1 in people living with HIV (PLWH) • PLWH with a hybrid immunity developed higher and broader neutralization against BA.5 • A cross-neutralization activity was found for BQ.1.1. and XBB.1 • Our data support offering a bivalent messenger RNA vaccine booster to advanced PLWH To investigate immunogenicity of SARS-CoV-2 vaccine third booster dose (3BD; fifth dose) with bivalent vaccine original/BA4/5 vaccine in people living with HIV (PLWH). This is an observational cohort study to evaluate the outcomes of SARS-CoV-2 vaccination (HIV-VAC study). We analyzed microneutralization assay and interferon-γ production in 48 PLWH on antiretroviral therapy with clusters of differentiation (CD4) count <200 cell/mm3 and/or previous AIDS according to immunization status: vaccinated PLWH who had a previous SARS-CoV-2 infection (hybrid immunization, HI) vs those only vaccinated (non-hybrid immunization, nHI) and current CD4 count. After 15 days from its administration (T1), the 3BD bivalent messenger RNA vaccine elicited a statistically significant increase of neutralizing antibodies (nAbs) geometric mean titers from T0 to T1 against W-D614G (fold increase 4.8; P <0.0001), BA.5 (8.6 P <0.0001), BQ.1.1 (6.4, P <0.0001) and XBB.1 (6.5, P <0.0001). When compared to BA.5, nAbs geometric mean titers against BQ.1.1 and XBB.1 decreased by 3.5 and 4.1-fold, respectively. After controlling for age, years from AIDS diagnosis, CD4 count at administration and CD4 count nadir, the fold change reduction in nAbs response to other variants of concerns as compared to BA.1, was larger in participants with HI vs those nHI: 0.59 lower (95% confidence interval 0.36-0.97, P = 0.04) for BQ.1.1 and 0.67 lower (95% confidence interval: 0.47-0.96, P = 0.03) for XBB.1. In contrast, the analysis carried little evidence for an association between current CD4 count and response to the fifth dose of bivalent vaccine. Furthermore, cell-mediated immunity remained stable. Our data support the current recommendation of offering bivalent mRNA vaccine booster doses to PLWH with low CD4 count or previous AIDS at first vaccination, especially in those who never previously acquired SARS-CoV-2 and regardless of current CD4 count. [ABSTRACT FROM AUTHOR]

The measurement of sodium intake may be important for the management of hypertension. Dietary surveys and 24-h urinary collection are often unreliable and/or impractical. We hypothesized that urinary sodium excretion can be accurately estimated through multiple spot urine samples from different days. All enrolled subjects were children of the coauthors of the study. Fifty-two 24-h urinary collections (4 per subject) for measuring sodium excretion and the 297 related urinary samples (1 per voiding) were collected for calculating the urinary sodium/urinary creatinine ratio in 13 children. The mean of 4 measured sodium excretions served as the individual "gold standard". Twenty-four urinary collections were used to generate the equation predicting the mean measured sodium excretion from the mean of 4 urinary sodium/urinary creatinine [= 0.016 × urinary sodium (mmol/L) / urinary creatinine (mmol/L) ratio + 3.3)]; the remaining 28 urinary collections and 153 urinary samples were used for the external validation. All subjects underwent an additional validation procedure involving 12 urinary samples randomly collected on different days 6 months apart. The performance of sodium excretion calculated from a total of over 22,000 possible means of 4 out of all the available urinary samples, randomly taken on different days, was analyzed as to precision (by means of the coefficient of variation) and as to accuracy (by means of the P30). The coefficients of variations of measured vs. calculated sodium excretion were 25.3% vs. 25.8%, and the P30 of calculated sodium excretion was 100%. The excellent performance of calculated sodium excretion was confirmed both by external validation and by samples collected 6 months apart with mean P30s, all between 86 and 100%. Conclusion: In the described experimental conditions, urinary sodium excretion was estimated with equal precision and more accurately (and practically) by the mean of 4 urinary sodium/urinary creatinine ratios from random samples from different days than by a single urinary collection. In real life, with several errors systematically affecting urinary collection, the superiority of calculated sodium excretion is likely to be even greater. What is Known: • The measurement of sodium intake with the current standards of care (dietary survey or 24-h urinary collection) is laborious and can be inaccurate. What is New: • The study provides evidence that sodium intake can be estimated equally precisely, more accurately and more practically with the urinary sodium-to-urinary creatinine ratio from 4 urine samples taken on different days than with a single urinary collection. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) significantly reduced Human Immunodeficiency Virus (HIV) morbidity and mortality; nevertheless, stigma still characterises the living with this condition. This study explored patients’ coping experience by integrating narrative medicine (NM) in a non-interventional clinical trial. From June 2018 to September 2020 the study involved 18 centres across Italy; enrolled patients were both D/C/F/TAF naïve and previously ART-treated. Narratives were collected at enrolment (V1) and last visit (V4) and then independently analysed by three NM specialist researchers through content analysis. One-hundred and fourteen patients completed both V1 and V4 narratives. Supportive relationships with clinicians and undetectable viral load facilitated coping. Conversely, lack of disclosure of HIV-positive status, HIV metaphors, and unwillingness to narrate the life before the diagnosis indicated internalised stigma. This is the first non-interventional study to include narratives as patient reported outcomes (PROs). Improving HIV awareness and reducing the sense of guilt experienced by patients helps to overcome stigma and foster coping. [ABSTRACT FROM AUTHOR]

The Rayleigh–Bénard problem in viscous fluids is one of the most intensely studied problems in fluid mechanics. The literature is rich in studies concerning Navier–Stokes fluids with constant material properties and fluids with variable viscosity and/or thermal conduction, whereas it lacks in results concerning the more realistic case in which all the material properties of the fluid are variable. In this paper, we re-examine the classical problem of the onset of thermal-convection for fluids whose material properties depend on the pressure and temperature by studying the linear stability of the conduction solution. [ABSTRACT FROM AUTHOR]

Benign and malignant lesions in tissues or organs can be detected by elastographic investigations in which pathological regions are spotted from local alterations of the stiffness. As is known, the shear modulus provides a measure of the stiffness of an elastic material. Based on the classical theory of linear elasticity, an elastogram yields estimations of the linear shear modulus from measurements of the speed of small-amplitude transverse waves propagating in the medium tested. In this paper, we show that the estimation of the shear modulus can be improved significantly by employing the fourth-order weakly nonlinear theory of elasticity (FOE), and indicate how the stiffness can be assessed more precisely with the use of FOE. We discuss also why FOE provides more reliable results than the fully nonlinear theory of elasticity. This article is part of the theme issue 'The Ogden model of rubber mechanics: Fifty years of impact on nonlinear elasticity'. [ABSTRACT FROM AUTHOR]

The aim was to measure neutralizing antibody levels against the SARS-CoV-2 Omicron (BA.1) variant in serum samples obtained from vaccinated PLWH and healthcare workers (HCW) and compare them with those against the Wuhan-D614G (W-D614G) strain, before and after the third dose of a mRNA vaccine. We included 106 PLWH and 28 HCWs, for a total of 134 participants. Before the third dose, the proportion of participants with undetectable nAbsT against BA.1 was 88% in the PLWH low CD4 nadir group, 80% in the high nadir group and 100% in the HCW. Before the third dose, the proportion of participants with detectable nAbsT against BA.1 was 12% in the PLWH low nadir group, 20% in the high nadir group and 0% in HCW, respectively. After 2 weeks from the third dose, 89% of the PLWH in the low nadir group, 100% in the high nadir group and 96% of HCW elicited detectable nAbsT against BA.1. After the third dose, the mean log2 nAbsT against BA.1 in the HCW and PLWH with a high nadir group was lower than that seen against W-D614G (6.1 log2 (±1.8) vs. 7.9 (±1.1) and 6.4 (±1.3) vs. 8.6 (±0.8)), respectively. We found no evidence of a different level of nAbsT neutralization by BA.1 vs. W-D614G between PLWH with a high CD4 nadir and HCW (0.40 (−1.64, 2.43); p = 0.703). Interestingly, in PLWH with a low CD4 nadir, the mean log2 difference between nAbsT against BA.1 and W-D614G was smaller in those with current CD4 counts 201–500 vs. those with CD4 counts < 200 cells/mm3 (−0.80 (−1.52, −0.08); p = 0.029), suggesting that in this target population with a low CD4 nadir, current CD4 count might play a role in diversifying the level of SARS-CoV-2 neutralization. [ABSTRACT FROM AUTHOR]

The main aim of this study was to describe the clinical and immunological outcomes, as well as the inflammatory profile, of patients with advanced HIV in an assisted-living facility in which an outbreak of SARS-CoV-2 occurred. SARS-CoV-2 humoral and specific T-cell response were analyzed in patients with HIV infection and COVID-19; as a secondary objective of the analysis, levels of the inflammatory markers (IL-1β, IL-6, IL-8, and TNFα) were tested in the HIV/COVID-19 group, in HIV-positive patients without COVID-19, and in HIV-negative patients with mild/moderate COVID-19. Antibody kinetics and ability to neutralize SARS-CoV-2 were evaluated by ELISA assay, as well as the inflammatory cytokines; SARS-CoV-2 specific T-cell response was quantified by ELISpot assay. Mann–Whitney or Kruskal–Wallis tests were used for comparisons. Thirty patients were included with the following demographics: age, 57 years old (IQR, 53–62); 76% male; median HIV duration of infection, 18 years (15–29); nadir of CD4, 57/mmc (23–100) current CD4 count, 348/mmc (186–565). Furthermore, 83% had at least one comorbidity. The severity of COVID-19 was mild/moderate, and the overall mortality rate was 10% (3/30). Additionally, 90% of patients showed positive antibody titers and neutralizing activity, with a 100% positive SARS-CoV-2 specific T-cell response over time, suggesting the ability to induce an effective specific immunity. Significantly higher levels of IL-6, IL-8, and TNF-α in COVID-19 without HIV vs. HIV/COVID-19 patients (p < 0.05) were observed. HIV infection did not seem to negatively impact COVID-19-related inflammatory state and immunity. Further data are mandatory to evaluate the persistence of these immunity and its ability to expand after exposure and/or vaccination. [ABSTRACT FROM AUTHOR]

In fact, from their data, it was discovered that low-CD4 + T-cell patients in the HIV group and high-ALT-level patients in the HCV group had a more chaotic fungal community with a possible worse health outcome. HIV co-infections with bacterial, viral, or parasitic microorganisms, on the other hand, may affect the natural history of HIV infection and vice versa. Co-infections are frequent in HIV patients; some of them may be AIDS-defining, while others share the same underlying virus mechanism. [Extracted from the article]

Background: There is conflicting evidence for how HIV influences COVID-19 infection. The aim of this study was to compare characteristics at presentation and the clinical outcomes of people living with HIV (PLWH) versus HIV-negative patients (non-PLWH) hospitalized with COVID-19. Methods: Primary endpoint: time until invasive ventilation/death. Secondary endpoints: time until ventilation/death, time until symptoms resolution. Results: A total of 1647 hospitalized patients were included (43 (2.6%) PLWH, 1604 non-PLWH). PLWH were younger (55 vs. 61 years) and less likely to be with PaO2/FiO2 < 300 mmHg compared with non-PLWH. Among PLWH, nadir of CD4 was 185 (75–322) cells/μL; CD4 at COVID-19 diagnosis was 272 cells/μL (127–468) and 77% of these were virologically suppressed. The cumulative probability of invasive mechanical ventilation/death at day 15 was 4.7% (95%CI 1.2–17.3) in PLWH versus 18.9% (16.9–21.1) in non-PLWH (p = 0.023). The cumulative probability of non-invasive/invasive ventilation/death at day 15 was 20.9% (11.5–36.4) in PLWH versus 37.6% (35.1–40.2) in non-PLWH (p = 0.044). The adjusted hazard ratio (aHR) of invasive mechanical ventilation/death of PLWH was 0.49 (95% CI 0.12–1.96, p = 0.310) versus non-PLWH; similarly, aHR of non-invasive/invasive ventilation/death of PLWH was 1.03 (95% CI 0.53–2.00, p = 0.926). Conclusion: A less-severe presentation of COVID-19 at hospitalization was observed in PLWH compared to non-PLWH; no difference in clinical outcomes could be detected. [ABSTRACT FROM AUTHOR]

Based on the classical theory of simple materials of differential type and the results on the analytical form of constitutive models consistent with the laws of thermodynamics, we introduce a very general response function for the Cauchy stress tensor of a dispersive hyperelastic solid. Next, by focusing on the propagation of localised waves in slightly dispersive quasi incompressible solids, we prove the existence of a rich variety of solitary wave solutions as well as kink wave solutions. Our analysis and results can be easily specialised to shape memory alloys. [Display omitted] • We develop a mathematical model for the stress tensor of dispersive hyperelastic solids within the theory of simple materials of differential type. • We study the wave propagation in dispersive hyperelastic solids. • In the small but finite regime, we find exact solutions representing solitary and kink waves. [ABSTRACT FROM AUTHOR]

• Evidence reassures the safety of COVID-19 vaccination in people with HIV. • Concerns raised on the effects of COVID-19 vaccination on viral load and T cells. • Most of the evidence is anecdotal with conflicting results. • We did not find a detrimental effect of COVID-19 vaccination on viral load and T cells. • We found that vaccination might prime the cluster of differentiation 4 cells independently of antiretroviral therapy. To investigate whether SARS-CoV-2 messenger RNA (mRNA) vaccination has an impact on HIV-related viro-immunological parameters. People with HIV (PWH) in the VAXICONA-ORCHESTRA cohort who received one or more doses of SARS-CoV-2 mRNA vaccine and for whom paired measures of immuno-virological markers (viral load, clusters of differentiation [CD]4, and CD8 count 1 month before and after a vaccine dose [VD]) were available were included. Paired t -test and generalized estimating equation linear regression analyses were used to study changes over ± 1 month around the VD. Subgroup analyses were performed. A total of 510 PWH were enrolled: the median age was 55 years (interquartile range 46-60 years), the CD4 and CD8 count were 489 (287-719) and 790 (59-1104) cells/mm3, respectively, and 81% received three VDs. After a median of 28 (3-53) days from VD, CD4 count increased by +15 cells/mm3 (SD ± 129.7, P = 0.001) and CD8 by +12 (±250.5, P = 0.199) and the viral load decreased by −0.11 log 10 (±0.88, P = 0.001). Similar results were observed after restricting the analysis to viro-suppressed PWH, with CD4 ≤200/mm3, more than 6 months of antiretroviral therapy before VD and after excluding previous COVID-19. A small significant increase in CD4 count and a negligible drop in HIV RNA were observed. Our findings are consistent with the hypothesis that SARS-CoV-2 mRNA vaccine can prime CD4 T spike-specific cells, even in the more immuno-compromised PWH. [ABSTRACT FROM AUTHOR]

• The 1-year incidence estimate of breakthrough infections (BTIs)/hospitalization/death was 24%. • A greater risk of incident BTIs was observed with BA.5 and XBB/EG. • The search for a new prophylaxis is urgently needed. Whether pre-exposure prophylaxis (PrEP) with tixagevimab/cilgavimab 150 mg/150 mg (T/C) in individuals with hematologic disease (HD) may lead to a reduced risk of SARS-CoV-2 breakthrough infection (BTI)/hospitalization, or death in the Omicron era remains to be established. An observational study included participants with HD who received PrEP. BTIs were defined as SARS-CoV-2 positivity by reverse transcription-polymerase chain reaction. The incidence of BTIs (95% CI) and of BTIs/hospitalization/death was calculated using the Kaplan-Meier method and as the number of BTIs per 100 person-years of follow-up according to the circulating variant of concern (VoC). A Poisson regression model was used to evaluate the association between the rate of incidence and circulating VoCs after controlling for demographics and clinical factors. We included 550 HD patients: 71% initiated T/C PrEP when BA.5 was the most prevalent, followed by XBB/EG, BA.2, and BA.1 (19%, 7%, and 3%, respectively). Overall, the 1-year incidence estimate of BTIs/hospitalization/death was 24% (18.7-29.4%). A greater risk of incident infections was observed when BA.5 and XBB/EG sub-lineages circulated (aRR 5.05 [2.17, 11.77]; P <.001 and 3.82 [1.50, 9.7]; P = 0.005, compared to BA.1, respectively). The 1-year incidence of SARS-CoV-2 BTIs/hospitalization/death was 24% which is in line with what was observed in other similar studies. The risk appeared to be higher when more recent Omicron sub-lineages were circulating suggesting a reduction of in vitro neutralization. [ABSTRACT FROM AUTHOR]

Prophylactic low molecular weight heparin (pLMWH) is currently recommended in COVID-19 to reduce the risk of coagulopathy. The aim of this study was to evaluate whether the antinflammatory effects of pLMWH could translate in lower rate of clinical progression in patients with COVID-19 pneumonia. Patients admitted to a COVID-hospital in Rome with SARS-CoV-2 infection and mild/moderate pneumonia were retrospectively evaluated. The primary endpoint was the time from hospital admission to orotracheal intubation/death (OTI/death). A total of 449 patients were included: 39% female, median age 63 (IQR, 50–77) years. The estimated probability of OTI/death for patients receiving pLMWH was: 9.5% (95% CI 3.2–26.4) by day 20 in those not receiving pLMWH vs. 10.4% (6.7–15.9) in those exposed to pLMWH; p-value = 0.144. This risk associated with the use of pLMWH appeared to vary by PaO2/FiO2 ratio: aHR 1.40 (95% CI 0.51–3.79) for patients with an admission PaO2/FiO2 ≤ 300 mmHg and 0.27 (0.03–2.18) for those with PaO2/FiO2 > 300 mmHg; p-value at interaction test 0.16. pLMWH does not seem to reduce the risk of OTI/death mild/moderate COVID-19 pneumonia, especially when respiratory function had already significantly deteriorated. Data from clinical trials comparing the effect of prophylactic vs. therapeutic dosage of LMWH at various stages of COVID-19 disease are needed. [ABSTRACT FROM AUTHOR]

Circulating large extracellular vesicles carrying CA9 in the diagnosis and prognosis of clear-cell renal cell carcinoma The percentage of lEVs expressing CA9 (CA9 SP + sp -lEVs) and t-CA9 levels (Figures 1A and 1B) was significantly higher in plasma from RCC patients compared to those from controls. To further evaluate the prognostic value of CA9 SP + sp -lEVs, RCC patients were divided into high- and low-CA9 groups according to the median value of the numbers of CA9 SP + sp -lEVs. [Extracted from the article]

• The impact of co-infection with SARS-CoV-2 on HIV replication in the central nervous system (CNS) is unknown. • SARS-CoV-2 could alter the permeability of the blood–brain barrier and cause a CNS HIV escape. • The few symptoms during coronavirus disease 2019 (COVID-19) suggest a contained inflammatory response in CNS/plasma. • Poor immunological recovery might contribute to soften immune-pathogenetic processes. We report two cases of HIV positive patients with SARS-CoV-2 infection and a recent diagnosis of opportunistic infections of central nervous system (CNS). We investigated the potential impact of coinfection with SARS-CoV-2 on HIV replication in CNS. [ABSTRACT FROM AUTHOR]

In this article, the attention is focused on a specific battery testing methodology for high-power hybrid electric working vehicle applications. Due to the high power demand, a deep knowledge of the battery behaviour is necessary and requires specific testing procedures, different from the standard activities available in the literature for the automotive field. In this article, the attention focused on the power demand that an energy storage system must satisfy to achieve a certain performance, considering this testing approach closer to the real application. A numerical model of a full electric telescopic handler developed in previous works was used to test a LiFePO4 cell in a hardware-in-the-loop bench test configuration. The output voltage–current characteristic was compared with the same output generated by the numerical model of the considered battery. The same model was then tested according to a handling working cycle proposed by the authors for a telescopic handler derived from the experience of the research group in the field of this type of vehicles. This mission profile was then used to evaluate the performance of the proposed battery pack configuration in a real working scenario and at different SoC levels. [ABSTRACT FROM AUTHOR]

Abstract A vivid research on brain tissue has proven that in simple shear tests the relation between the shear stress and shear strain is linear for strains in a range which is significative in the physiological and pathological regime. Since Mooney–Rivlin materials satisfy this peculiar property when subjected to simple shear deformations, the celebrated mathematical model introduced first by Mooney, and then developed by Rivlin, has been often used to describe the mechanical behaviour of brain tissue. Recently, it has been shown that a most general strain energy density for incompressible isotropic elastic materials exhibiting a linear relationship between shear stress and shear strain in simple shear deformation consists of the sum of the Mooney–Rivlin model and an arbitrary function of the difference of the first two principal invariants of the deformation tensor. For this reason, a strain energy function of this form is called a generalised Mooney–Rivlin model. In this note we design theoretically a procedure aiming at the determination of the generalised Mooney–Rivlin model which fits best the experimental data. Highlights • Pseudo-universal relations for a generalised Mooney–Rivlin (GMR) material. • Small-amplitude wave propagation in a GMR material. • Necessary conditions for an incompressible isotropic elastic material to be modelled as a GMR material. • Acoustic tensor of a GMR material. [ABSTRACT FROM AUTHOR]

Abstract Angiogenesis is a complex process describing the growth of new blood vessels from existing vasculature, and is triggered by local pro-angiogenic factors, such as vascular endothelial growth factor (VEGF), which increase the metabolism of endothelial cells (ECs). Angiogenesis takes part in various physiological conditions such as embryogenesis, placental growth, and in pathological conditions such as tumor growth, diabetic retinopathy, rheumatoid arthritis (RA) and ischemic diseases. Current therapies against excessive angiogenesis target vascular growth signaling. However, tumors often counteract these therapies through adaptive mechanisms, thus novel alternative anti-angiogenic strategies are needed. Targeting metabolism is a new anti-angiogenic paradigm, especially through the inhibition of energy metabolism and glycosylation, with the perspective of maintaining the delicate balance between the beneficial and deleterious effects of excessive angiogenesis in patients. Recent studies described a role for EC glycolysis and its main regulator 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3) in the regulation of angiogenesis, but only few studies are related to the role of the hexosamine biosynthesis pathway during angiogenesis. Glycosylation allows the formation of glycoproteins, glycolipids and proteoglycans and impacts many pathways. The addition of glycans to N-linked proteins is catalyzed by the enzymatic activity of N -acetylglucosaminyltransferases (GnTs), which regulates the glycosylation status of key angiogenic factors such as VEGF receptor 2 (VEGFR2) and Notch. In addition, glycan-galectin (Gal) interactions regulate vascular signaling programs and may contribute to tumor adaptations to anti-angiogenic strategies. Herein, we review novel pharmacological strategies targeting glycosylation, which could be used to decrease excessive angiogenesis in pathological conditions. [ABSTRACT FROM AUTHOR]

Background: HIV-positive patients carry an increased risk of HPV infection and associated cancers. Therefore, prevalence and patterns of HPV infection at different anatomical sites, as well as theoretical protection of nonavalent vaccine should be investigated. Aim was to describe prevalence and predictors of oral HPV detection in HIV-positive men, with attention to nonavalent vaccine-targeted HPV types. Further, co-occurrence of HPV DNA at oral cavity and at anal site was assessed.Methods: This cross-sectional, clinic-based study included 305 HIV-positive males (85.9% MSM; median age 44.7 years; IQR: 37.4-51.0), consecutively observed within an anal cancer screening program, after written informed consent. Indication for anal screening was given by the HIV physician during routine clinic visit. Paired oral rinse and anal samples were processed for the all HPV genotypes with QIASYMPHONY and a PCR with MY09/MY11 primers for the L1 region.Results: At the oral cavity, HPV DNA was detected in 64 patients (20.9%), and in 28.1% of these cases multiple HPV infections were found. Prevalence of oral HPV was significantly lower than that observed at the anal site (p < 0.001), where HPV DNA was found in 199 cases (85.2%). Oral HPV tended to be more frequent in patients with detectable anal HPV than in those without (p = 0.08). Out of 265 HPV DNA-positive men regardless anatomic site, 59 cases (19.3%) had detectable HPV at both sites, and 51 of these showed completely different HPV types. At least one nonavalent vaccine-targeted HPV type was found in 17/64 (26.6%) of patients with oral and 199/260 (76.5%) with anal infection. At multivariable analysis, factors associated with positive oral HPV were: CD4 cells <200/μL (versus CD4 cells >200/μL, p = 0.005) and >5 sexual partners in the previous 12 months (versus 0-1 partner, p = 0.008).Conclusions: In this study on Italian HIV-positive men (predominantly MSM), oral HPV DNA was detected in approximately one fifth of tested subjects, but prevalence was significantly lower than that observed at anal site. Low CD4 cell count and increasing number of recent sexual partners significantly increased the odds of positive oral HPV. The absence of co-occurrence at the two anatomical sites may suggest different routes or timing of infection. [ABSTRACT FROM AUTHOR]

Small- and large-amplitude oscillatory shear tests are widely used by experimentalists to measure, respectively, linear and nonlinear properties of viscoelastic materials. These tests are based on the quasi-static approximation according to which the strain varies sinusoidally with time after a number of loading cycles. Despite the extensive use of the quasi-static approximation in solid mechanics, few attempts have been made to justify rigorously such an approximation. The validity of the quasi-static approximation is studied here in the framework of the Mooney-Rivlin Kelvin-Voigt viscoelastic model by solving the equations of motion analytically. For a general nonlinear model, the quasi-static approximation is instead derived by means of a perturbation analysis. [ABSTRACT FROM AUTHOR]

Endothelial progenitor cells (EPCs) and monocytic cells from bone marrow (BM) can be recruited to the injured endothelium and contribute to its regeneration. During metabolic diseases such as obesity and diabetes, progenitor cell function is impaired. Several studies have shown that moderate alcohol consumption prevents the development and progression of atherosclerosis in a variety of animal/mouse models and increases mobilization of progenitor cells. Along with these studies, we identify ethanol at low concentration as therapeutic tool to in vitro expand progenitor cells in order to obtain an adequate number of cells for their use in the treatment of cardiovascular diseases. We evaluated the effects of ethanol on the phenotype of BM-derived cells from mice fed with high-fat diet (HFD). HFD did not induce changes in weight of mice but induced metabolic alterations. HFD feeding increased the differentiation of monocytic progenitors but not EPCs. Whereas ethanol at 0.6% is able to increase monocytic progenitor differentiation, 1% ethanol diminished it. Furthermore, ethanol at 0.6% increased the ability of progenitor cells to promote in vivo angiogenesis as well as secretome of BM-derived cells from mice fed with HFD, but not in mice fed normal diet. In conclusion, ethanol at low concentration is able to increase angiogenic abilities of progenitor cells from animals with early metabolic alterations. [ABSTRACT FROM AUTHOR]

We give conditions on the strain-energy function of nonlinear anisotropic hyperelastic materials that ensure compatibility with the classical linear theories of anisotropic elasticity. We uncover the limitations associated with the volumetric-deviatoric separation of the strain-energy used, for example, in many Finite Element (FE) codes in that it does not fully represent the behavior of anisotropic materials in the linear regime. This limitation has important consequences. We show that, in the small deformation regime, a FE code based on the volumetric-deviatoric separation assumption predicts that a sphere made of a compressible anisotropic material deforms into another sphere under hydrostatic pressure loading, instead of the expected ellipsoid. For finite deformations, the commonly adopted assumption that fibres cannot support compression is incorrectly implemented in current FE codes and leads to the unphysical result that under hydrostatic tension a sphere of compressible anisotropic material deforms into a larger sphere. [ABSTRACT FROM AUTHOR]

Abstract: In this paper we study theoretically the equilibrium configurations of two-dimensional nematic liquid crystals on a cylindrical surface. Configurations are described through a tensor-order parameter that provides information about the tangential optical axis and the dispersion of the molecules around it. Equilibrium equations are obtained by the surface Landau–de Gennes energy recently proposed in Napoli and Vergori [Physical Review E 061701 (2012)]. We show that, whenever free boundary conditions are applied, the extrinsic curvature induces the alignment of the optical axis along the cylinder axis. On the contrary, when strong planar anchoring is imposed on the boundaries, the curvature triggers a sort of Freédricksz-like transition in the alignment. We provide the asymptotic solution of the non-linear problem with strong planar anchoring boundary conditions for elongated cylindrical shells. [Copyright &y& Elsevier]

We propose a continuum model to describe the molecular alignment in thin nematic shells. By contrast with previous accounts, the two-dimensional free energy, aimed at describing the physics of thin films of nematics deposited on curved substrates, is not postulated, but it is deduced from the conventional three-dimensional theories of nematic liquid crystals. Both the director and the order-tensor theories are taken into account. The so-obtained surface energies exhibit extra terms compared to earlier models. These terms reflect the coupling of the shell extrinsic curvature with the nematic order parameters. As expected, the shape of the shell plays a key role in the equilibrium configurations of nematics coating it. [ABSTRACT FROM AUTHOR]

When nematic liquid crystals are constrained to a curved surface, the geometry induces distortions in the molecular orientation. The mechanisms of the geometrical frustration involve the intrinsic as well as the extrinsic geometry of the underlying substrate. We show that the nematic elastic energy promotes the alignment of the flux lines of the nematic director towards geodesies and/or lines of curvature of the surface. As a consequence, the influence of the curvature can be tuned through the Frank elastic moduli. To illustrate this effect, we consider the simple case of nematics lying on a cylindrical shell. By combining the curvature effects with external magnetic fields, the molecular alignment can be reoriented or switched between two stable configurations. This enables the manipulation of nematic alignment for the design of new materials and technological devices. [ABSTRACT FROM AUTHOR]

The paper is concerned with a binary fluid mixture in a porous horizontal layer according to the Brinkman model. The long-time behaviour of the solutions is considered: absorbing sets are shown to exist, and the stability (instability) of the rest state is studied. Following the new approach introduced in Rionero (J. Math. Anal. Appl. 333, 1036–1057 (2007)), the global stability of the rest state is rigorously reduced to the stability of the zero solution of a linear binary system of ODEs. The results obtained are extended to cover the presence of a uniform rotation about a vertical axis. [ABSTRACT FROM AUTHOR]

The in-operando monitoring of the cell's kinetic thermal and electrochemical processes during operation is a key requirement to understand battery performance, improve safety and to extend battery life. This research presents in-situ measurements of strain and temperature evolution within a graphite electrode during electromechanical lithiation and delithiation. By embedding distributed fibre optics sensor, the frequency shift associated with both temperature and strain are decoupled, allowing the real-time measurement of the solid electrolyte interface formation and the structural deformation within the anode. An in-depth assessment of electrode strain as a function of State of Charge (SoC) and State of Health (SoH) from the formation cycle through to electrical loading allows the assessment of cell performance over its complete life. It is observed that irreversible and non-uniformly distributed anode structural deformation was measured during the formation. The anode reveals an extensive mechanical strain increase with a coefficient of 0.96 με/SoC(%) with respect to the SoC and undergoes a compressive mechanical strain as SoH decreases from 100% to 47%. Collectively, the findings presented provide valuable new information to understand the causes of battery performance degradation as a result of electrode strain and temperature, underpinning new opportunities for battery characterisation and optimal system design. • Novel characterisation of electrode materials. • Distributed fibre sensors embedded in LIBs for thermal and structural monitoring. • Operando tracking of the SEI formation and the irreversible anode strain. • In-depth assessment of anode structural deformation together with SOC and SOH. • To optimise of future battery designs and to promote LIB safety improvement. [ABSTRACT FROM AUTHOR]

Background: With advances in antiretroviral therapy for HIV treatment, newer drug combinations provide improved efficacy, safety, and compliance. This study evaluates switching to a regimen of doravirine (DOR), tenofovir disoproxil fumarate (TDF), and lamivudine (3TC) in a cohort of people living with HIV (PLWH). Methods: this Italian retrospective study included 426 PLWH who switched from rilpivirine (RPV)/TDF/emtricitabine (FTC) to DOR/3TC/TDF. The analysis focused on treatment effectiveness, safety, and metabolic and renal markers. Results: this study reports a treatment failure (defined as virological failure or discontinuation of the regimen) rate of 2.34% (95% confidence interval, 1.28–4.50%), with significant improvement in CD4 counts (+49.93 cells/µL, p < 0.001). Notably, the switch to DOR/3TC/TDF did not result in adverse metabolic effects or significant changes in renal function. Analysis of lipid profiles showed stabilization in the majority of PLWH. Conclusions: this study indicates that switching to a DOR/3TC/TDF from RPV/TDF/FTC is an effective and well-tolerated option for PLWH, with benefits in terms of maintaining viral suppression, CD4 count recovery, and metabolic health, without evidence of renal impairment. These results support the continued use of DOR/3TC/TDF as part of HIV treatment strategies and highlight the need for ongoing research to refine ART regimens for different populations. [ABSTRACT FROM AUTHOR]

Fostering environmentally friendly transport choices lies at the core of the strategies aimed at implementing a sustainable transport system. The discussion on the possible strategies and policies to reach this goal has attracted the attention of both scholars and policy makers. Limited attention appears to have been devoted to the mobility time at tourist destinations by considering environmentally friendly transport options and private motorized ones. This paper fills this gap by performing a beta regression analysis to assess which variables influence the mobility behaviour of tourists at the destination. The main finding of this paper shows that mobility at home, the use of a friendly transport mode to reach the destination and the choice of a static holiday in sea, sun and sand destinations are the most relevant variables that positively influence environmentally friendly mobility. Moreover, improved infrastructures and more appropriate mobility policies and strategies may determine more sustainable transport choices of visitors and residents. • Mobility behaviour at tourist destinations is different with respect to everyday life. • Visitors tend to have a more sustainable travel behaviour when walking is considered. • Appropriate transport policies are crucial for sustainable mobility at destination. [ABSTRACT FROM AUTHOR]

• Switching from tenofovir disoproxil fumarate (TDF)-containing regimens has increased considerably in recent years. • A high proportion of people with a controlled viral load switched from TDF to tenofovir alafenamide (TAF). • Only 3.5% of patients switched from TDF to a dual therapy (DT) regimen. • Low eGFR was associated with a higher risk of switching to DT but not to TAF-based cART. Our aim was to evaluate the association between recent eGFR values and risk of switching from TDF to TAF or dual therapy (DT) in real life. HIV-positive patients achieving HIV-RNA ≤50 copies/mL for the first time after starting a TDF-based regimen were included. Kaplan–Meier (KM) curves and Cox regression models were used to estimate the time from TDF to switch to TAF or DT. 1486 participants were included: median (IQR) age 36 (30–42) years; baseline CKD-EPI eGFR 99.92 (86.47–111.4) mL/min/1.73m2. We observed a consistently higher proportion of people with HIV-RNA ≤50 copies/mL who switched from TDF to TAF rather than to DT. By competing risk analysis, at 2 years from baseline, the probability of switching was 3.5% (95% CI 2.6–4.7%) to DT and 46.7% (42.8–48.5%) to TAF. A significantly higher probability of switching to TAF was found for patients receiving INSTI at baseline versus NNRTIs and PI/b [KM, 65.6% (61.7–69.4%) vs. 4.0% (1.8–6.1%) and 59.9% (52.7–67.2%), respectively; P < 0.0001]. eGFR <60 mL/min/1.73m2 both as time-fixed covariate at baseline or as current value was associated with a higher risk of switching to DT [aHR 6.68 (2.69–16.60) and 8.18 (3.54–18.90); P < 0.001] but not to TAF-based cART [aHR 0.94 (0.39–2.31), P = 0.897; and 1.19 (0.60–2.38), P = 0.617]. Counter to our original hypothesis, current eGFR is used by clinicians to guide switches to DT but does not appear to be a key determinant for switching to TAF. [ABSTRACT FROM AUTHOR]

Signatures of neurodegeneration in clinical samples from a subject with multiple sclerosis (MS) acutely infected with HIV were investigated with single-cell transcriptomics using 10X Chromium technology. Sequencing was carried out on NovaSeq-TM, and the analysis was performed with Cell Ranger software (v 7.1.0) associated with a specifically established bioinformatic pipeline. A total of 1446 single-cell transcriptomes in cerebrospinal fluid (CSF) and 4647 in peripheral blood mononuclear cells (PBMCs) were obtained. In the CSF, many T-cell lymphocytes with an enriched amount of plasma cells and plasmacytoid dendritic (pDC) cells, as compared to the PBMCs, were detected. An unsupervised cluster analysis, putting together our patient transcriptomes with those of a publicly available MS scRNA-seq dataset, showed up-regulated microglial neurodegenerative gene expression in four clusters, two of which included our subject's transcriptomes. A few HIV-1 transcripts were found only in the CD4 central memory T-cells of the CSF compartment, mapping to the gag-pol, vpu, and env regions. Our data, which describe the signs of neurodegenerative gene expression in a very peculiar clinical situation, did not distinguish the cause between multiple sclerosis and HIV infection, but they can give a glimpse of the high degree of resolution that may be obtained by the single-cell transcriptomic approach. [ABSTRACT FROM AUTHOR]

Background Transmitted drug resistance (TDR) is still a critical aspect for the management of individuals living with HIV-1. Thus, its evaluation is crucial to optimize HIV care. Methods Overall, 2386 HIV-1 protease/reverse transcriptase and 1831 integrase sequences from drug-naïve individuals diagnosed in north and central Italy between 2015 and 2021 were analysed. TDR was evaluated over time. Phylogeny was generated by maximum likelihood. Factors associated with TDR were evaluated by logistic regression. Results Individuals were mainly male (79.1%) and Italian (56.2%), with a median (IQR) age of 38 (30–48). Non-B infected individuals accounted for 44.6% (N  = 1065) of the overall population and increased over time (2015–2021, from 42.1% to 51.0%, P  = 0.002). TDR prevalence to any class was 8.0% (B subtype 9.5% versus non-B subtypes 6.1%, P  = 0.002) and remained almost constant over time. Overall, 300 transmission clusters (TCs) involving 1155 (48.4%) individuals were identified, with a similar proportion in B and non-infected individuals (49.7% versus 46.8%, P  = 0.148). A similar prevalence of TDR among individuals in TCs and those out of TCs was found (8.2% versus 7.8%, P  = 0.707). By multivariable analysis, subtypes A, F, and CFR02_AG were negatively associated with TDR. No other factors, including being part of TCs, were significantly associated with TDR. Conclusions Between 2015 and 2021, TDR prevalence in Italy was 8% and remained almost stable over time. Resistant strains were found circulating regardless of being in TCs, but less likely in non-B subtypes. These results highlight the importance of a continuous surveillance of newly diagnosed individuals for evidence of TDR to inform clinical practice. [ABSTRACT FROM AUTHOR]

Progressive Multifocal Leukoencephalopathy (PML) is a demyelinating disease occurring in advanced HIV infection, caused by the reactivation of poliomavirus JC (JCV). The use of pembrolizumab for treatment is based on the inhibition of programmed cell death protein 1 (PD-1), potentially improving the anti JCV-specific response. We used pembrolizumab with combined antiretroviral treatment (cART) on a compassionate-use basis. At each administration, clinical evaluation, MRI and laboratory testing, including CD3, CD4, CD8, PD-1 markers, HIV-RNA and JCV-DNA in cerebrospinal fluid (CSF)/plasma pairs, were performed. The JCV-specific T cell response was analysed by Elispot assay. This study included five HIV patients: four male, median age 43 years (29–52), median CD4 and CD8 count 150 (15–158) and 973 (354–1250) cell/mm3, respectively; median JCV-DNA and HIV-RNA in CSF/plasma pairs 9.540/1.503 cps/mL and 2.230/619 cp/mL, respectively. Overall, patients received between two and seven doses of pembrolizumab. After treatment, we observed JCV-DNA reduction and PD-1 down-regulation both in CSF and in plasma (high in circulating CD4 and CD8 at baseline), which remained stable at low levels in all patients. Three out of five patients showed stability of clinical picture and neuroimaging, while two others died. More data are needed in order to identify predictors of response to therapy. [ABSTRACT FROM AUTHOR]

Objectives To assess the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) among people poorly represented in clinical trials and potentially at higher risk of suboptimal response to ART. Methods Observational cohort study on persons with HIV (PWH) enrolled in ICONA who started BIC/FTC/TAF as initial therapy or as switching regimen while virologically suppressed. Primary endpoint was time to treatment failure (TF): new AIDS/death or virological failure (VF) or discontinuation for toxicity/failure. Secondary endpoints were time to treatment discontinuation for toxicity (TDT) and to VF. Groups of interest were those aged >50 years, female sex, and advanced HIV disease at first ART start. Probability of the events overall and according to groups and adjusted HR for every endpoint were calculated by Kaplan–Meier curves and Cox regression models. Results Nine hundred and thirty-three ART-naive and 1655 ART-experienced PWH initiated BIC/FTC/TAF. Over a median follow-up of 69.8 weeks, 89 (9.6%) PWH at their first regimen experienced TF. PWH aged >50 years had 1.83-fold (95% CI: 1.19–2.83) higher risk of TF; PWH with advanced HIV disease had 2.21-fold (95% CI: 1.53–3.82) higher risk; there were no differences in TF according to sex. Over a median follow-up of 146.3 weeks, 109 (6.6%) out of 1655 switching PWH experienced TF; no differences were found in the risk of TF, TDT and VF according to groups of interest. Conclusions Overall, BIC/FTC/TAF is well tolerated and virologically effective in the real-world scenario for ART-naive and -experienced PWH. Older ART-naive PWH and those with advanced HIV disease may respond less well as the burden of diseases might compromise treatment efficacy. [ABSTRACT FROM AUTHOR]

Nematic films are thin fluid structures, ideally two dimensional, endowed with an in-plane degenerate nematic order. In this paper we examine a generalization of the classical Plateau problem to an axisymmetric nematic film bounded by two coaxial parallel rings. At equilibrium, the shape of the nematic film results from the competition between surface tension, which favors the minimization of the area, and the nematic elasticity, which instead promotes the alignment of the molecules along a common direction. We find two classes of equilibrium solutions in which the molecules are uniformly aligned along the meridians or parallels. Depending on two dimensionless parameters, one related to the geometry of the film and the other to the constitutive moduli, the Gaussian curvature of the equilibrium shape may be everywhere negative, vanishing, or positive. The stability of these equilibrium configurations is investigated. [ABSTRACT FROM AUTHOR]

Objective: This study investigates the effectiveness and tolerability of switching to a darunavir/cobicistat (DRV/c)-based antiretroviral regimen from a ritonavir-boosted protease inhibitor (PI/r)-based regimen in virologically suppressed HIV-positive patients. DRV trough values were also investigated. Setting: Prospective, multicenter, single-country, noninterventional cohort study. Methods: This study included patients on a PI/r-based ART for at least 12 months having plasma HIV-1 RNA, 50 copies/mL since at least 6 months. The primary endpoint, defined as HIV-1 RNA, 50 copies/mL, was measured at 48 6 6 weeks from baseline. A secondary analysis was performed using the time to loss of virological response algorithm. Biochemical parameters, including DRV trough samples, were collected as per clinical practice and measured using high-performance liquid chromatography. Results: Of 336 patients enrolled, 282 completed the study: 70.8% had plasma HIV-1 RNA, 50 copies/mL at 48 weeks; using the time to loss of virological response algorithm, 82.7% maintained virological suppression. Virological failure was observed in 6 patients (1.8%). Adverse event-related discontinuations were 4.5%. After 48 weeks, we found a significant improvement in both triglycerides (median, 130 to 113.5 mg/dL, P = 0.0254) and high-density lipoprotein cholesterol (48 to 49 mg/dL, P, 0.0001) but no change in other biomarkers. DRV trough concentrations in 56 subjects showed a median value of 2862.5 (1469.5-4439) ng/mL, higher in women than in men (4221 vs. 2634 ng/mL, P = 0.046). Conclusions: In stable HIV-1 positive virologically suppressed patients, the switch to DRV/c-based ART was beneficial in terms of low rates of virological failure and adverse events due to its high tolerability and improvement in triglycerides. [ABSTRACT FROM AUTHOR]

We study the propagation of linearly polarized transverse waves in a pre-strained incompressible isotropic elastic solid. Both finite and small-butfinite amplitude waves are examined. Irrespective of the magnitude of the wave amplitude, these waves may propagate only if the (unit) normal to the plane spanned by the directions of propagation and polarization is a principal direction of the left Cauchy-Green deformation tensor associated with the pre-strained state. A rigorous asymptotic analysis of the equations governing the propagation of waves of small but finite amplitude reveals that the time scale over which the nonlinear effects become significant depends on the direction along which the wave travels. Moreover, we design theoretically an experimental procedure to determine the Landau constants of the fourth-order weakly nonlinear theory of elasticity. [ABSTRACT FROM AUTHOR]

We derive the hydrodynamic equations for nematic liquid crystals lying on curved substrates. We invoke the Lagrange-Rayleigh variational principle to adapt the Ericksen-Leslie theory to two-dimensional nematics in which a degenerate anchoring of the molecules on the substrate is enforced. The only constitutive assumptions in this scheme concern the free-energy density, given by the two-dimensional Frank potential, and the density of dissipation which is required to satisfy appropriate invariance requirements. The resulting equations of motion couple the velocity field, the director alignment, and the curvature of the shell. To illustrate our findings, we consider the effect of a simple shear flow on the alignment of a nematic lying on a cylindrical shell. [ABSTRACT FROM AUTHOR]

A 59-year-old treatment-naive patient with advanced HIV infection presented with a severe and protracted course of mpox (formerly known as monkeypox) that did not respond to the current mpox treatment options. The patient worsened clinically, and developed new mucocutaneous lesions and necrotic evolution of pre-existing ones, along with multiple bilateral lung nodules and the appearance of a tracheal necrotic lesion. Although severe forms of mpox have been observed in people with severe immune system deficiency, including those with advanced HIV presentation, the immunological mechanisms underlying this observation have not yet been fully explained. To our knowledge, this is the first account of a necrotising mpox in a person living with HIV, with viral shedding for more than 11 months and a comprehensive immunological description. Moreover, we documented the virus' persistence by detecting mpox virus DNA from multiple sites and quantified anti-monkeypox virus IgA, IgM, IgG, and neutralising antibodies in serum samples. The severe HIV-driven immune depression and the presence of other co-infections might skew and impair immune responses, thus contributing to the persistence of monkeypox virus infection. Further investigations of immune responses to monkeypox virus infection in people with severe immunosuppression are required to improve management and prevention. [ABSTRACT FROM AUTHOR]

Due to their intrinsic complexity, it is not easy to model the mechanical behaviour of biomaterials. Despite the challenges they faced, some researchers have presented mathematical models to describe some aspects of the mechanical response of soft tissues. Since most of the materials of biological interest are composites made of different constituents reinforced by collagen and/or elastin fibres, material dispersion and anisotropy are non-negligible. Within the theory of elasticity, several models for anisotropic materials have been developed. The same cannot be said for anisotropic dispersive materials. The models available in the literature that account for material dispersion are valid only for isotropic materials. This paper aims at introducing a very general model for anisotropic dispersion in transversely isotropic bodies within the theory of simple materials of differential type. Our model has the potential to represent a first step towards a better understanding of the mechanical response of fibre-reinforced soft materials. [ABSTRACT FROM AUTHOR]

Objectives: Only a few studies have addressed liver stiffness dynamics after hepatitis C virus (HCV) treatment in patients with HIV/HCV coinfection. The aim was to evaluate the variation in liver stiffness and in serum liver fibrosis scores in HIV/HCV‐coinfected patients before and after treatment with direct‐acting antivirals (DAAs). Methods: Liver stiffness measured using transient elastography as well as serum liver fibrosis scores [fibrosis‐4 (FIB‐4) score and the aspartate aminotransferase to platelet ratio index (APRI)] were evaluated before and at 6–12 months after DAA treatment. Variation in the outcome variables was evaluated using the Wilcoxon nonparametric test. Univariate analysis and multivariate regression models were used. Results: A total of 78 HIV/HCV‐coinfected subjects were included in the study. Median values of hepatic stiffness significantly decreased after DAA treatment compared with baseline [16.8 (interquartile range (IQR) 10.2–27.0) kPa at baseline vs. 9.4 (IQR 6.7–15.0) kPa after DAA treatment; P < 0.01). Further, a decrease in median FIB‐4 score [2.8 (IQR 1.5–4.8) vs. 2.0 (IQR 1.3–3.2), respectively; P < 0.01] and APRI [0.9 (IQR 0.5–2.2) vs. 0.4 (IQR 0.2–0.7), respectively; P < 0.01] was found. In univariate analysis, liver stiffness decrease was associated with increasing age, ‘other’ HCV genotype (vs. G1), the presence of cirrhosis, higher pre‐DAA liver stiffness, sofosbuvir‐based regimens and longer DAA treatment (all P < 0.05). Multivariate regression confirmed the significance of the association only with higher baseline liver stiffness (P < 0.01). Greater FIB‐4 and APRI reductions were associated with higher respective baseline values, while the presence of hepatic steatosis correlated with lower score reduction after DAA. Conclusions: A reduction in liver stiffness and an improvement in fibrosis scores were observed in HIV/HCV‐coinfected patients soon after DAA treatment. The clinical implications of these observations need to be evaluated in larger populations with longer follow‐up. [ABSTRACT FROM AUTHOR]

A nonlinear elastodynamic system is investigated which is descriptive of transverse wave propagation in an isotropic, incompressible, hyperelastic material subject to body forces associated with a nonlinear substrate potential. Notably, by introducing an appropriate ansatz, both cnoidal and gausson-type exact solutions are isolated. [ABSTRACT FROM AUTHOR]

We study what is clearly one of the most common modes of deformation found in nature, science and engineering, namely the large elastic bending of curved structures, as well as its inverse, unbending, which can be brought beyond complete straightening to turn into eversion. We find that the suggested mathematical solution to these problems always exists and is unique when the solid is modelled as a homogeneous, isotropic, incompressible hyperelastic material with a strain-energy satisfying the strong ellipticity condition. We also provide explicit asymptotic solutions for thin sectors. When the deformations are severe enough, the compressed side of the elastic material may buckle and wrinkles could then develop. We analyse, in detail, the onset of this instability for the Mooney-Rivlin strain energy, which covers the cases of the neo-Hookean model in exact nonlinear elasticity and of third-order elastic materials in weakly nonlinear elasticity. In particular, the associated theoretical and numerical treatment allows us to predict the number and wavelength of the wrinkles. Guided by experimental observations, we finally look at the development of creases, which we simulate through advanced finite-element computations. In some cases, the linearized analysis allows us to predict correctly the number and the wavelength of the creases, which turn out to occur only a few per cent of strain earlier than the wrinkles. [ABSTRACT FROM AUTHOR]