Search

Abstract: Foraminifera are unicellular organisms that inhabit the oceans. They play an important role in the global carbon cycle and record valuable paleoclimate information through the uptake of trace elements such as strontium into their calcitic shells. Understanding how foraminifera control their internal fluid composition to make calcite is important for predicting their response to ocean acidification and for reliably interpreting the chemical and isotopic compositions of their shells. Here, we model foraminiferal calcification and strontium partitioning in the benthic foraminifera Cibicides wuellerstorfi and Cibicidoides mundulus based on insights from inorganic calcite experiments. The numerical model reconciles inter-ocean and taxonomic differences in benthic foraminifer strontium partitioning relationships and enables us to reconstruct the composition of the calcifying fluid. We find that strontium partitioning and mineral growth rates of foraminiferal calcite are not strongly affected by changes in external seawater pH (within 7.8–8.1) and dissolved inorganic carbon (DIC, within 2100–2300 μmol/kg) due to a regulated calcite saturation state at the site of shell formation.

Calcium carbonate (CaCO3) is abundant on Earth, is a major component of marine biominerals and thus of sedimentary and metamorphic rocks and it plays a major role in the global carbon cycle by storing atmospheric CO2 into solid biominerals. Six crystalline polymorphs of CaCO3 are known-3 anhydrous: calcite, aragonite, vaterite, and 3 hydrated: ikaite (CaCO3·6H2O), monohydrocalcite (CaCO3·1H2O, MHC), and calcium carbonate hemihydrate (CaCO3·½H2O, CCHH). CCHH was recently discovered and characterized, but exclusively as a synthetic material, not as a naturally occurring mineral. Here, analyzing 200 million spectra with Myriad Mapping (MM) of nanoscale mineral phases, we find CCHH and MHC, along with amorphous precursors, on freshly deposited coral skeleton and nacre surfaces, but not on sea urchin spines. Thus, biomineralization pathways are more complex and diverse than previously understood, opening new questions on isotopes and climate. Crystalline precursors are more accessible than amorphous ones to other spectroscopies and diffraction, in natural and bio-inspired materials.

Key Clinical Message Gliosarcoma, a rare cerebral neoplasm, has not been linked to hippocampal changes in cats. We report a case of complex partial seizures with orofacial involvement, revealing gliosarcoma concurrent with bilateral hippocampal sclerosis. Abstract A 16‐year‐old neutered female domestic shorthair cat presented with acute inappetence, ataxia, disorientation, and vacant staring. Brain MRI revealed an ill‐defined, round, intra‐axial mass in the right piriform lobe, showing hyperintensity on T2W, T2‐FLAIR, and T2*W, and hypointensity on T1W images. The lesion exhibited mass effect and contrast enhancement in its center. Bilateral hyperintensity on T2‐FLAIR images and contrast enhancement were observed in the hippocampus. Brain histologic and immunohistochemical analysis revealed cerebral gliosarcoma with concurrent hippocampal sclerosis. Feline LGI1‐antibody testing on the serum and/or CSF was not performed due to insufficient biomaterial. Although retrospective testing on brain tissue was considered, it ultimately proved unfeasible, preventing us from ruling out antibody‐associated limbic encephalitis. In conclusion, cerebral gliosarcoma should be included in feline intracranial tumor differentials, warranting brain MRI and feline LGI1‐antibody testing in cats showing complex partial seizures with orofacial involvement. In our case, the prognosis remained poor due to the presence of a high‐grade glioma.

Abstract Calcium carbonate (CaCO3) is abundant on Earth, is a major component of marine biominerals and thus of sedimentary and metamorphic rocks and it plays a major role in the global carbon cycle by storing atmospheric CO2 into solid biominerals. Six crystalline polymorphs of CaCO3 are known—3 anhydrous: calcite, aragonite, vaterite, and 3 hydrated: ikaite (CaCO3·6H2O), monohydrocalcite (CaCO3·1H2O, MHC), and calcium carbonate hemihydrate (CaCO3·½H2O, CCHH). CCHH was recently discovered and characterized, but exclusively as a synthetic material, not as a naturally occurring mineral. Here, analyzing 200 million spectra with Myriad Mapping (MM) of nanoscale mineral phases, we find CCHH and MHC, along with amorphous precursors, on freshly deposited coral skeleton and nacre surfaces, but not on sea urchin spines. Thus, biomineralization pathways are more complex and diverse than previously understood, opening new questions on isotopes and climate. Crystalline precursors are more accessible than amorphous ones to other spectroscopies and diffraction, in natural and bio-inspired materials.

Abstract Foraminifera are unicellular organisms that inhabit the oceans. They play an important role in the global carbon cycle and record valuable paleoclimate information through the uptake of trace elements such as strontium into their calcitic shells. Understanding how foraminifera control their internal fluid composition to make calcite is important for predicting their response to ocean acidification and for reliably interpreting the chemical and isotopic compositions of their shells. Here, we model foraminiferal calcification and strontium partitioning in the benthic foraminifera Cibicides wuellerstorfi and Cibicidoides mundulus based on insights from inorganic calcite experiments. The numerical model reconciles inter-ocean and taxonomic differences in benthic foraminifer strontium partitioning relationships and enables us to reconstruct the composition of the calcifying fluid. We find that strontium partitioning and mineral growth rates of foraminiferal calcite are not strongly affected by changes in external seawater pH (within 7.8–8.1) and dissolved inorganic carbon (DIC, within 2100–2300 μmol/kg) due to a regulated calcite saturation state at the site of shell formation.

Due to scattering, particles in a ring may have large momentum deviations, which will change their dynamics, potentially resulting in particle losses. Optimization of off-momentum nonlinear dynamics is, therefore, important for increasing beam lifetime. When analyzing off-momentum dynamics using the approach of resonance driving terms (RDTs), chromatic RDTs are usually used, which denote the deviations from on-momentum dynamics. In this paper, instead of using chromatic RDTs, we propose using off-momentum RDTs to analyze off-momentum dynamics, which is a more direct way. As in the case of on-momentum dynamics, the nonlinear driving terms for off-momentum particles include off-momentum RDTs and off-momentum amplitude-dependent tune shifts, which are calculated based on off-momentum linear optics. Similar to the analysis of on-momentum dynamics in our previous work [B. Wei et al., Phys. Rev. Accel. Beams 26, 084001 (2023)PRABCJ2469-988810.1103/PhysRevAccelBeams.26.084001], we study the fluctuation or variation of off-momentum RDTs along the longitudinal position, which is very effective for analyzing and optimizing off-momentum dynamic apertures (DAs). Similar results are obtained for the off-momentum case: (i) minimizing the element-by-element average of the RDTs is more effective than minimizing one-turn RDTs in enlarging DAs and (ii) minimizing the average of lower-order RDTs helps reduce higher-order RDTs.

Recent research suggests that infection with Onchocerca volvulus induces neurocognitive decline. This study sought to compare the cognitive outcomes of elderly persons based on onchocerciasis infection status and report the overall prevalence of dementia in the rural Ntui Health District in Cameroon. A community-based approach was used to recruit 103 participants aged ≥60 years. Dementia screening was done using the Community Screening Interview for Dementia (CSID) tool with a cut-off value of ≤29.5. O. volvulus infection was determined via microscopic examination of skin snips and serological testing of Ov16 antibodies using rapid diagnostic tests. Overall, the prevalence of dementia was 10.7%. Among the tested individuals, 17.9% (15/84) and 62.1% (41/66) were positive for O. volvulus and Ov16 antibodies, respectively. A multivariable linear regression model of CSID scores found a significant positive association with education level (8.654; 95% CI: 2.0870 to 15.222). However, having a positive skin snip for O. volvulus (−3.399; 95% CI: −6.805 to 0.007) and inhaling tobacco (−5.441; 95% CI: −9.137 to −1.744) tended to lower the CSID scores. Ongoing onchocerciasis transmission in the Ntui Health District may constitute a risk factor for dementia. Strengthening onchocerciasis elimination and adopting healthier lifestyles would contribute to dementia prevention among the elderly residing in endemic communities.

Key Clinical Message: Gliosarcoma, a rare cerebral neoplasm, has not been linked to hippocampal changes in cats. We report a case of complex partial seizures with orofacial involvement, revealing gliosarcoma concurrent with bilateral hippocampal sclerosis. A 16‐year‐old neutered female domestic shorthair cat presented with acute inappetence, ataxia, disorientation, and vacant staring. Brain MRI revealed an ill‐defined, round, intra‐axial mass in the right piriform lobe, showing hyperintensity on T2W, T2‐FLAIR, and T2*W, and hypointensity on T1W images. The lesion exhibited mass effect and contrast enhancement in its center. Bilateral hyperintensity on T2‐FLAIR images and contrast enhancement were observed in the hippocampus. Brain histologic and immunohistochemical analysis revealed cerebral gliosarcoma with concurrent hippocampal sclerosis. Feline LGI1‐antibody testing on the serum and/or CSF was not performed due to insufficient biomaterial. Although retrospective testing on brain tissue was considered, it ultimately proved unfeasible, preventing us from ruling out antibody‐associated limbic encephalitis. In conclusion, cerebral gliosarcoma should be included in feline intracranial tumor differentials, warranting brain MRI and feline LGI1‐antibody testing in cats showing complex partial seizures with orofacial involvement. In our case, the prognosis remained poor due to the presence of a high‐grade glioma. [ABSTRACT FROM AUTHOR]

Recent research suggests that infection with Onchocerca volvulus induces neurocognitive decline. This study sought to compare the cognitive outcomes of elderly persons based on onchocerciasis infection status and report the overall prevalence of dementia in the rural Ntui Health District in Cameroon. A community-based approach was used to recruit 103 participants aged ≥60 years. Dementia screening was done using the Community Screening Interview for Dementia (CSID) tool with a cut-off value of ≤29.5. O. volvulus infection was determined via microscopic examination of skin snips and serological testing of Ov16 antibodies using rapid diagnostic tests. Overall, the prevalence of dementia was 10.7%. Among the tested individuals, 17.9% (15/84) and 62.1% (41/66) were positive for O. volvulus and Ov16 antibodies, respectively. A multivariable linear regression model of CSID scores found a significant positive association with education level (8.654; 95% CI: 2.0870 to 15.222). However, having a positive skin snip for O. volvulus (−3.399; 95% CI: −6.805 to 0.007) and inhaling tobacco (−5.441; 95% CI: −9.137 to −1.744) tended to lower the CSID scores. Ongoing onchocerciasis transmission in the Ntui Health District may constitute a risk factor for dementia. Strengthening onchocerciasis elimination and adopting healthier lifestyles would contribute to dementia prevention among the elderly residing in endemic communities. [ABSTRACT FROM AUTHOR]

The micro-CT obtain very high-quality of the aortic roots and three-dimensional modeling of aortic leaflets. Different tests (biaxial test) are used to know the biomechanical properties. We propose a new method, which combines pressurization of the aortic root with micro-CT to obtain at the same time, the geometry, and biomechanical properties. The aim is to investigate healthy aorta mechanical property using a micro-CT under pressure and compare them with literature. This study was approved by committee on human research at the French agency of biomedicine (PFFS 20-026). Ten aortic roots were obtained fresh from unused donor hearts with non-cardiac causes of death. We used aortic root under pressure at different pressure level (every 20 mmHg) in order to obtain diameter, geometry, stress-strain curve and Young modulus. All aortic roots (n = 10) obtained a three-dimensional modeling of aortic leaflets with excellent quality. The mean age was 61.2 years [49.5–65.6]. The median of sino-tubular junction diameter was 32.2 mm [29–36] at 80 mmHg. The non-linear stress-strain curves of healthy aortic root were characterized. Young moduli were significantly smaller in low pressure (between 20 and 80 mmHg) 0.6 [0.5–0.8] MPa than high pressure (between 80 and 120 mmHg) 3.2 [2.5–5.6] MPa, P = 0.001 (Fig. 1). Our new method allows a 3D model of the aortic root associated with measurements of biomechanical properties. Our results are found to be consistent with literature data. This new method evaluates the biomechanical properties while keeping the aortic roots intact and maintaining its geometrical complexity for future global aortic root simulation. [ABSTRACT FROM AUTHOR]

Targeted vasopeptide therapies have significantly advanced the management of pulmonary arterial hypertension (PAH). However, due to insufficient preclinical evidence regarding the involvement of the endothelin-1 (ET-1) pathway in chronic thromboembolic pulmonary hypertension (CTEPH) pathophysiology, the potential of ET-1 receptor antagonism in treating CTEPH remains uncertain. In this study, we investigated the role of the ET-1 pathway in CTEPH microvasculopathy using a multifaceted approach. Plasma ET-1 levels were measured in a cohort of 59 CTEPH patients and 41 healthy controls. Additionally, we evaluated the expression of key ET-1 pathway members in pulmonary explants from CTEPH, idiopathic PAH, and control patients. We used an in vitro system to test the hypothesis that the turbulent flow, observed near the vascular obstructions pathognomonic of CTEPH, enhances ET-1 expression. Our findings were further validated in vivo using a CTEPH piglet model that contains distinct regions representing pre- and post-thrombus lung territories. We found a twofold increase in circulating ET-1 levels in CTEPH patients compared to healthy subjects. Pulmonary explants from CTEPH patients exhibited pronounced overexpression of ET-1, endothelin receptor A (ET A ), and phosphorylated myosin light chain (p-MLC) in muscularized pulmonary microvessels, suggesting heightened vascular contraction. In vitro experiments showed that turbulent flow facilitates ET-1 secretion compared to laminar flow regions. Additionally, in the CTEPH piglet model, elevated plasma ET-1 levels were observed compared to controls. Immunofluorescence and confocal microscopy analyses confirmed increased ETA and p-MLC in remodeled arteries from both pulmonary territories. However, ET-1 protein elevation was exclusively observed in the obstructed territory. These findings collectively indicate impaired vascular tone in microvessels of CTEPH patients and the CTEPH piglet model. Furthermore, our data implicates the ET-1 pathway in microvasculopathy, with turbulent flow playing a pathological role. These insights underscore the potential utility of ET-1 receptor antagonists as a promising therapeutic approach for CTEPH treatment., Competing Interests: Declarations Competing interests Over the last three years, C.G. reports grants from Acceleron Pharma (Cambridge, MA, USA), a wholly-owned subsidiary of Merck & Co., Inc. (Rahway, NJ, USA), MSD, Corteria, Structure therapeutics, Diagonal Therapeutics, Gossamer, outside the submitted work. M.H. reports grants and personal fees from Acceleron, Aerovate, Altavant, AOP Orphan, Bayer, Chiesi, Ferrer, Janssen, Merck, MorphogenIX and United Therapeutics, outside the submitted work. All the other authors declare that there is no conflict of interest regarding the publication of this original article., (© 2024. The Author(s).)

Introduction: To compare the real-world effectiveness of a third dose of mRNA-1273 versus a third dose of BNT162b2 against breakthrough COVID-19 hospitalizations among adults aged ≥ 65 years who completed a primary series of an mRNA-based COVID-19 vaccine (regardless of which primary series was received)., Materials and Methods: This observational comparative vaccine effectiveness (VE) study was conducted using administrative claims data from the US HealthVerity database (September 22, 2021, to August 31, 2022). A third dose of mRNA-1273 versus BNT162b2 was assessed for preventing COVID-19 hospitalizations and medically attended COVID-19 among adults aged ≥ 65 years. Inverse probability of treatment weighting was applied to balance baseline characteristics between vaccine groups. Incidence rates from patient-level data and hazard ratios (HRs) with 95 % confidence intervals (CIs) using weighted Cox proportional hazards models were calculated to estimate relative VE for each outcome., Results: Overall, 94,587 and 92,377 individuals received a third dose of mRNA-1273 and BNT162b2, respectively. Among the weighted population, the median age was 69 years (interquartile range, 66-74), 53 % were female, and 46 % were commercially insured. COVID-19 hospitalization rates per 1000 person-years (PYs) were 5.61 (95 % CI, 5.13-6.09) for mRNA-1273 and 7.06 (95 % CI, 6.54-7.57) for BNT162b2 (HR, 0.82; 0.69-0.98). Medically attended COVID-19 rates per 1000 PYs (95 % CI) were 95.05 (95 % CI, 93.03-97.06) for mRNA-1273 and 106.55 (95 % CI, 104.53-108.57) for BNT162b2 (HR, 0.93; 0.89-0.98)., Conclusions: Results from this observational comparative VE database study provide evidence that among older adults, a third dose of mRNA-1273 was more effective in preventing breakthrough COVID-19 hospitalization and medically attended COVID-19 infection compared with a third dose of BNT162b2., Competing Interests: Declaration of competing interest EB, LL, SSL, MG, MAM, TS, DBE, DM, and NV are employees of Moderna, Inc., and hold stock/stock options in the company. BK, CB, AT, and KEM are employees of Aetion, Inc., which has been contracted by Moderna, Inc., for the conduct of the present study. BK, CB, and KEM are stock option holders in Aetion, Inc., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Designing iron oxide nanoparticles (IONPs) to effectively combine magnetic hyperthermia (MH) and photothermia (PTT) in one IONP formulation presents a significant challenge to ensure a multimodal therapy allowing the adaptation of the treatment to each patient. Recent research has highlighted the influence of factors such as the size, shape, and amount of defects on both therapeutic approaches. In this study, 20-25 nm spherical IONPs with a spinel composition were synthesized by adapting the protocol of the thermal decomposition method to control the amount of defects. By tuning different synthesis parameters such as the precursor nature, the introduction of a well-known oxidizing agent, dibenzylether (DBE), in the reaction medium, the heating rate and duration and the introduction of a nucleation step, we thus established two different synthesis protocols, one involving the use of a small amount of DBE leading to IONPs with only a few defects and another that took an optimized route to oxidize the wüstite nuclei during the IONP growth and led to IONPs exhibiting more structural and oxygen defects. IONPs exhibiting fewer defects showed enhanced MH and PTT heating values even when immobilized in a matrix, despite a decrease in MH heating values showing that they release mainly heat through the Brownian mechanism. These MH measurements have also confirmed that defects play a key role in enhancing Néel relaxation. PTT measurements demonstrated higher heating values with IONPs with fewer defects and a correlation between Urbach energy and SAR values suggesting an impact of vacancy defects on PTT performances. Therefore, IONPs exhibiting fewer defects under our synthesis conditions appear as suitable IONPs to combine both MH and PTT treatments with high performances. These findings pave the way for promising applications in combined therapies for cancer treatment.

Ethnopharmacological Relevance: Commiphora kerstingii Engl is a tree which is 20-30 m in height and commonly called "ararrabi" in Hausa. It is found in the Sahelian region (Cameroon, Chad, and Nigeria) where it is utilized for the treatment of several ailments including cancer., Aim of the Study: This study was aimed at investigating the chemical constituents and cytotoxic effect of extracts and isolates from the stem barks and leaves of C. kerstingii., Materials and Methods: Using classical chromatography technique coupled with spectroscopic analysis and literature information, ten (10) compounds were isolated from C. kerstingii stem barks and leaves, out of which two [kerstingilactone (3) and kerstinginone (10)] were new. To evaluate their potential cytotoxic effect, the impact on cell viability, growth, and proliferation was assessed using MTT and CCK-8 assays. Cell death mechanisms were analyzed via flow cytometry, and Western blotting was utilized to examine the expression of specific regulatory proteins. Furthermore, anti-metastatic properties were investigated through assays on cell migration, adhesion, and chemotaxis., Results: Among the tested compounds, 2 (Masticadienonic Acid) and 10 (kerstinginone) exhibited significant dose-dependent inhibition of PC3 and LNCaP cell growth. Compound 2 displayed optimal inhibitory effects within a concentration range of 10-40 μg/mL, while compound 10 demonstrated potent growth inhibition at concentrations of 2.5-10 μg/mL. Both compounds suppressed cell proliferation and the formation of clones. Specifically, compound 2 induced apoptosis solely in the androgen-sensitive LNCaP prostate cancer cells, whereas compound 10 induced a stronger and concentration-dependent apoptotic response in both PC3 and LNCaP cells, resulting in approximately 50-70% apoptotic cells. It also induced potent cell migration/invasion arrest at concentrations ranging from 2.5 to 5 μg/mL and increased cell adhesion to the extracellular matrix., Conclusion: Kerstinginone exhibits potent cytotoxicity and apoptosis-inducing activity, making it a promising lead for discovering a new anticancer drug., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Drug-resistant tuberculosis remains a major obstacle in ending the global tuberculosis epidemic. Deployment of molecular tools for comprehensive drug resistance profiling is imperative for successful detection and characterisation of tuberculosis drug resistance. We aimed to assess the diagnostic accuracy of a new class of molecular diagnostics for drug-resistant tuberculosis., Methods: We conducted a prospective, cross-sectional, multicentre clinical evaluation of the performance of two targeted next-generation sequencing (tNGS) assays for drug-resistant tuberculosis at reference laboratories in three countries (Georgia, India, and South Africa) to assess diagnostic accuracy and index test failure rates. Eligible participants were aged 18 years or older, with molecularly confirmed pulmonary tuberculosis, and at risk for rifampicin-resistant tuberculosis. Sensitivity and specificity for both tNGS index tests (GenoScreen Deeplex Myc-TB and Oxford Nanopore Technologies [ONT] Tuberculosis Drug Resistance Test) were calculated for rifampicin, isoniazid, fluoroquinolones (moxifloxacin, levofloxacin), second line-injectables (amikacin, kanamycin, capreomycin), pyrazinamide, bedaquiline, linezolid, clofazimine, ethambutol, and streptomycin against a composite reference standard of phenotypic drug susceptibility testing and whole-genome sequencing., Findings: Between April 1, 2021, and June 30, 2022, 832 individuals were invited to participate in the study, of whom 720 were included in the final analysis (212, 376, and 132 participants in Georgia, India, and South Africa, respectively). Of 720 clinical sediment samples evaluated, 658 (91%) and 684 (95%) produced complete or partial results on the GenoScreen and ONT tNGS workflows, respectively, with 593 (96%) and 603 (98%) of 616 smear-positive samples producing tNGS sequence data. Both workflows had sensitivities and specificities of more than 95% for rifampicin and isoniazid, and high accuracy for fluoroquinolones (sensitivity approximately ≥94%) and second line-injectables (sensitivity 80%) compared with the composite reference standard. Importantly, these assays also detected mutations associated with resistance to critical new and repurposed drugs (bedaquiline, linezolid) not currently detectable by any other WHO-recommended rapid diagnostics on the market. We note that the current format of assays have low sensitivity (≤50%) for linezolid and more work on mutations associated with drug resistance is needed., Interpretation: This multicentre evaluation demonstrates that culture-free tNGS can provide accurate sequencing results for detection and characterisation of drug resistance from Mycobacterium tuberculosis clinical sediment samples for timely, comprehensive profiling of drug-resistant tuberculosis., Funding: Unitaid., Competing Interests: Declaration of interests TCR, MS, and REC received salary support from FIND through a service contract to UC San Diego. TCR and REC received grant funding from the US National Institutes of Health to develop and evaluate a tNGS solution for drug-resistant tuberculosis (R01AI176401). TCR and REC are co-inventors on a patent associated with the processing of tuberculosis sequencing data (European Patent Application number 14840432.0 and USSN 14/912,918). Both TCR and REC have transferred all rights and present and future interest in and rights to royalties from this patent to UC San Diego and the Translational Genomics Research Institute, respectively. TCR is a co-founder, board member, and unpaid shareholder of Verus Diagnostics, a company that was founded with the intent of developing diagnostic assays. Verus Diagnostics is not pursuing any drug-resistant tuberculosis diagnostics nor any diagnostics related to the technology or approaches discussed or mentioned in this manuscript. Verus Diagnostics was not involved in any way with data collection, analysis, or publication of the results of this manuscript. TCR has not received any financial support from Verus Diagnostics. CR has received honoraria payments from Becton Dickinson and she is on the scientific advisory board for Cepheid and bioMérieux. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Importance: B-cell-targeting monoclonal antibodies have demonstrated safety and efficacy in multiple sclerosis or anti-aquaporin-4 IgG positive neuromyelitis optica spectrum disorder. However, these therapies do not facilitate drug-free remission, which may become possible with cell-based therapies, including chimeric antigen receptor (CAR) T cells. CAR T-cell therapy holds promise for addressing other antibody-mediated CNS disorders, e.g., MOG-associated disease or autoimmune encephalitis., Objective: To provide an overview of the current clinical knowledge on CAR T-cell therapy in central nervous system autoimmunity., Evidence Review: We searched PubMed, Embase, Google Scholar, PsycINFO, and clinicaltrials.gov using the terms 'CAR T cell' and 'multiple sclerosis/MS' or 'neuromyelitis optica/spectrum diseases/NMOSD' or 'MOG-associated disease/MOGAD 'or' autoimmune encephalitis' or 'neuroimmunology'., Findings: An ongoing phase I clinical trial has indicated the safety and benefits of anti-BCMA CAR T cells in 12 patients with AQP4-IgG seropositive neuromyelitis optica spectrum disorder. Case reports involving two individuals with progressive multiple sclerosis and one patient with stiff-person syndrome demonstrated a manageable safety profile following treatment with anti-CD19 CAR T cells. Recruitment has commenced for two larger studies in MS, and a phase I open-label basket study is underway to evaluate BCMA-directed CAR T cells in various antibody-associated inflammatory diseases, including MOG-associated disease. Preclinical research on NMDA receptor antibody autoimmune encephalitis treated with chimeric autoantibody receptor T cells generated promising data., Conclusions and Relevance: There is minimal evidence of the benefits of CAR T-cell therapy in individuals with central nervous system-directed autoimmunity. Nevertheless, multicenter controlled clinical trials with a manageable safety profile appear feasible and are warranted due to very promising case experiences., (© 2024. The Author(s).)

Cancers account for many deaths worldwide and natural compounds and their derivatives are interesting chemotherapeutic agents for cancer drug development. In this study, a natural compound 3,3'4-trimethoxy-4'-rutinosylellagic acid (TR2) and its acetylated derivative 3,3'4-trimethoxy-4'-hexaacetylrutinosylellagic acid (TR22) were evaluated for their antioxidant and anticancer effects against estrogen sensitive (MCF-7) and estrogen non-sensitive (MDA-MB 231) breast adenocarcinoma. In the β-Carotene-linoleic acid assay, DPPH • radical scavenging and CUPRAC assay, the compound TR2 had better activity than the standard α-Tocopherol, while in the ABTS •+ assay, it was more active than both standards α- α-Tocopherol and BHA. Both compounds had good antioxidant effects with TR2 being more active than TR22. Both compounds inhibited growth of breast carcinoma cells when compared to the untreated controls after 72 h. Compound TR22 significantly (p < 0.001) inhibited proliferation of both MCF-7 and MDA-MB 231 breast carcinoma cell lines suggesting that acetylation reaction improves inhibition of breast cancer cells growth. On the contrary, TR2 exhibited better inhibitory effect of clone formation than TR22 suggesting that acetylation reduces the activity in this assay. Both compounds inhibited migration of the cancer cells when compared to the untreated control cells and compound TR2 exhibited greater cellular anti-migration effect than TR22 at the same concentration and after the same period of incubation. Molecular docking studies supplemented the results and revealed that TR2 and TR22 had appreciable interactions with tyrosine kinase with negative binding energies suggesting that they are potent receptor tyrosine kinase inhibitors which can impede on cancer progression., Competing Interests: Declaration of Competing Interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Positron Emission Tomography (PET) is used in oncology for tumor diagnosis, commonly relying on fluorine-18 ( 18 F) emission detection. The conventional method of 18 F incorporation on to probes by covalent bonding is harsh for sensitive biomolecules, which are nonetheless compounds of choice for the development of targeted probes. This study explores gallium- 18 F (Ga 18 F) coordination, a milder alternative method occurring in aqueous media at the final stage of radiosyntheses. Pyclen-based chelating agents were proposed to capture (GaF) species at room temperature and pH≥5 making the radiofluorination process compatible with heat- and acid-sensitive biomolecules. Highly promising results were obtained with the PC2A-based chelating agent LH 2 derived from the new bifunctional PC2A-OAE-NCS compound. The solid-state structure of GaF(L) was elucidated by X-ray diffraction and revealed an unconventional heptacoordination of Ga(III). A high radiochemical conversion (RCC) of 86 % was achieved at room temperature, in water at pH 5 within 20 minutes. Stability studies showed the robustness of the GaF(L) complex in aqueous media for at least one day and at least one hour for the radiolabeled analog Ga 18 F(L). These findings demonstrated that PC2A-based compounds are chelating agents of choice for (Ga 18 F) species, suggesting a real technological breakthrough for PET imaging and precision medicine., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)

Odontonema strictum (Acanthaceae) leave extract was investigated for its flavonoid content. Column chromatography was used for compound isolation and mass spectrometry was performed using electrospray ionization (ESI) in the negative ion mode for compound identification. The full characterization of luteolin 7- O -[β-D-apiofuranosyl-(1 → 2)- O -β-D-ribofuranoside], a flavone glycoside, was achieved using tandem mass spectrometry and high resolution 1D and 2D Nuclear Magnetic Resonance (NMR). Among the 10 flavonoids glycosides detected in the ethanol extract, beside the isolated one, 3 flavone glycosides with luteolin or apigenin aglycone were tentatively identified., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Yvonne L Bonzi Coulibaly reports financial support was provided by International Science Programme (ISP)., (© 2024 The Authors. Published by Elsevier Ltd.)

The phytochemical study of Cordia myxa L. led to the isolation, through chromatographic techniques, of a new triterpenoid saponin, 3- O -[ α - L -rhamnopyranosyl-(1→3)-(6- O -acetyl- β - D -glucopyranosyl)]-22 β -hydroxyolean-12-ene ( 3 ) namely Myxaoside A, together with three known compounds, Soyasaponine I ( 1 ), oleanolic acid ( 2 ), and 3- O -acetyl-oleanolic acid ( 4 ). All structures were established, based on 1 & 2D-NMR spectroscopic analysis and comparison with previous published reports. Compound 1 - 4 were evaluated for their antibacterial activity on various strains of bacteria including Salmonella typhi, Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae and Vibrio cholerae . It appears that compounds 1 and 3 were active on all the tested microbial species, while compounds 2 and 4 , shown no significant effect on S. aureus and K. pneumoniae at low concentrations 6.5 mg/mL and 3.0 mg/mL.

Background: Natalizumab is an effective treatment for relapsing multiple sclerosis (MS). During therapy, individuals are at increased risk of developing progressive multifocal leukoencephalopathy (PML). So far, the relevant reservoir for PML-type JC polyomavirus (JCV) remains elusive. We here tested if the detection of JCV-DNA in stool of persons with MS treated with natalizumab could be a future tool for PML risk assessment., Methods: The presence of JCV-DNA in stool, urine, and whole blood of MS patients treated with natalizumab and known serum anti-JCV antibodies index values (IV) was studied. Different DNA extraction methods, real-time (RT) and droplet digital (dd) PCR techniques were compared. JCV isolates were screened for PML-associated variants by sequencing., Results: Thirty MS patients treated with natalizumab were screened. For 21 patients, blood, stool, and urine samples were available. These patients were stratified according to their serum anti-JCV antibody IV (high (>1.5, n = 12); medium (1.5-0.9, n = 2); low (<0.9, n = 1); negative (n = 6)). JCV-DNA could not be detected in the whole blood or stool samples. Four urine samples had measurable JCV-DNA, ranging from 1.71×10 4 -1.07×10 8 international units (IU)/mL detected by RT-PCR, corresponding to 4.62×10 4 -9.85×10 6 copies/mL measured by ddPCR. All JCV variants were wild-type and derived from patients with high antibody IV., Conclusion: Stool-specific DNA extraction methods provided the highest quality of DNA, while the sensitivity of ddPCR and RT- PCR was comparable. Our findings do not support assessing stool samples for PML risk stratification in persons with MS. Further studies are needed to explore where PML-associated viral variants arise., Competing Interests: Declaration of competing interest C.W. has received institutional honoraria or grant support from Novartis, Sanofi-Genzyme, Alexion, Janssen, Merck, Biogen, Hexal and Roche. S.G. was working for Biogen as a consultant. M.S. received honoraria from Alexion, Argenx, Bayer, Biogen, Datamed, Genzyme, Gilead, Grifols, Merck, Novartis, Roche, Teva. The remaining authors have nothing to declare., (Copyright © 2024. Published by Elsevier B.V.)

How tissue-level information encoded by fields of regulatory gene activity is translated into the patterns of cell polarity and growth that generate the diverse shapes of different species remains poorly understood. Here, we investigate this problem in the case of leaf shape differences between Arabidopsis thaliana , which has simple leaves, and its relative Cardamine hirsuta that has complex leaves divided into leaflets. We show that patterned expression of the transcription factor CUP-SHAPED COTYLEDON1 in C. hirsuta (ChCUC1) is a key determinant of leaf shape differences between the two species. Through inducible genetic perturbations, time-lapse imaging of growth, and computational modeling, we find that ChCUC1 provides instructive input into auxin-based leaf margin patterning. This input arises via transcriptional regulation of multiple auxin homeostasis components, including direct activation of WAG kinases that are known to regulate the polarity of PIN-FORMED auxin transporters. Thus, we have uncovered a mechanism that bridges biological scales by linking spatially distributed and species-specific transcription factor expression to cell-level polarity and growth, to shape diverse leaf forms., Competing Interests: Competing interests statement:The authors declare no competing interest.

Standardizing image datasets is essential for facilitating overall visual comparisons and enhancing compatibility with image-processing workflows. One way to achieve homogeneity for images containing a single object is to align the object to a common orientation. Here, we propose the Virtual Orientation Tools (VOTj): a set of Fiji plugins to center and align an object of interest in images to a vertical or horizontal orientation. To process an image, the plugin requires either a mask outlining the object or a rough annotation of the object directly drawn by the user in the image. The current object orientation is retrieved using Principal Component Analysis (PCA), from which the optimal alignment is derived. The plugins support multi-dimensional images to allow, e.g., aligning individual time points of a time-lapse. The tools can be used for a variety of samples and imaging modalities. Besides, the plugins enable the interactive alignment of a list of images from a directory for batch execution and can be included in custom image-processing workflows using macro-recording., Competing Interests: The authors declare that there are no conflicts of interest present., (Copyright: © 2024 by the authors.)

Context: Obesity prevalence is persistently increasing worldwide. Among surgical therapeutic procedures, bypass surgery and sleeve gastrectomy have shown the best results regarding weight loss, prevention, and treatment of secondary complications. However, these surgeries are associated with an increased risk of malabsorption and metabolic changes that could further affect the pharmacokinetics of drugs. On the other hand, patients with a history of such surgeries are more likely to experience pain and request analgesic initiation or adaptation. The question of how to manage pain medication in these patients is challenging due to their narrow therapeutic indexes., Objectives: To summarize the current literature on the impact of bariatric surgery on the subsequent pharmacokinetics of analgesics and propose a multidisciplinary therapeutic attitude to optimize pain management in these patients., Methods: We conducted a systematic review that included all pharmacological studies published after 2000., Results: Unexpectedly, these surgeries seem to increase the bioavailability of drugs by long-term improvement of hepatic function. Yet, the medical community drastically lacks robust guidelines for pain management in those patients. This systematic review aims to bring together pharmacological studies related to the use of pain treatments in patients who underwent bypass surgery or sleeve gastrectomy., Conclusions: Caution should be exercised regarding the risk of overdose in every circumstance: treatment initiation, change of doses, or change of molecule. More prospective trials comparing the pharmacokinetics of medications in obese patients with and without prior bariatric surgery are needed., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: Following the COVID-19 pandemic and ongoing pressures within the National Health Service, there has been an increasing concern about the well-being of junior doctors in the UK. Newly qualified doctors are particularly vulnerable due to the significant shift in responsibility they experience., Objectives: To implement peer-led reflective session for foundation year 1 (FY1) (first-year postgraduation) doctors and to create a dedicated space in which doctors could share difficult or challenging experiences., Methods: In 2021 and 2022, peer-led reflective sessions were held for FY1s in a district general hospital in London, England. Feedback assessing well-being, perceived levels of support, as well as session benefits and areas for improvement, was obtained throughout the year. Qualitative feedback underwent thematic analysis to understand key benefits of the sessions., Results: Feedback collected at the launch of the initiative revealed that over 80% of respondents agreed or strongly agreed that their mental health and well-being had been negatively impacted by work. The majority felt additional support was needed. All attendees found reflective sessions useful. Key benefits were as follows: the provision of a safe psychological space, sharing experiences and reflecting with peers, building relationships with colleagues and the reassurance that others struggled with similar challenges., Conclusion: FY1 doctors reported that starting work negatively affected their well-being and that additional support was needed. Facilitated peer-led reflective sessions were beneficial and offered a supportive environment for FY1s to share and reflect. We propose the initiative can serve members of the wider healthcare team, including doctors of different grades and nurses., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Copepoda is the most abundant taxon in deep-sea hydrothermal vents, where hard substrate is available. Despite the increasing interest in seafloor massive sulphides exploitation, there have been no population genomic studies conducted on vent meiofauna, which are known to contribute over 50% to metazoan biodiversity at vents. To bridge this knowledge gap, restriction-site-associated DNA sequencing, specifically 2b-RADseq, was used to retrieve thousands of genome-wide single-nucleotide polymorphisms (SNPs) from abundant populations of the vent-obligate copepod Stygiopontius lauensis from the Lau Basin. SNPs were used to investigate population structure, demographic histories and genotype-environment associations at a basin scale. Genetic analyses also helped to evaluate the suitability of tailored larval dispersal models and the parameterization of life-history traits that better fit the population patterns observed in the genomic dataset for the target organism. Highly structured populations were observed on both spatial and temporal scales, with divergence of populations between the north, mid, and south of the basin estimated to have occurred after the creation of the major transform fault dividing the Australian and the Niuafo'ou tectonic plate (350 kya), with relatively recent secondary contact events (<20 kya). Larval dispersal models were able to predict the high levels of structure and the highly asymmetric northward low-level gene flow observed in the genomic data. These results differ from most studies conducted on megafauna in the region, elucidating the need to incorporate smaller size when considering site prospecting for deep-sea exploitation of seafloor massive sulphides, and the creation of area-based management tools to protect areas at risk of local extinction, should mining occur., (© 2024 John Wiley & Sons Ltd.)

The mechanisms underpinning the replication of genomic DNA have recently been challenged in Archaea . Indeed, the lack of origin of replication has no deleterious effect on growth, suggesting that replication initiation relies on homologous recombination. Recombination-dependent replication (RDR) appears to be based on the recombinase RadA, which is of absolute requirement when no initiation origins are detected. The origin of this flexibility in the initiation of replication and the extent to which it is used in nature are yet to be understood. Here, we followed the process of DNA replication throughout the growth stages of Thermococcus barophilus . We combined deep sequencing and genetics to elucidate the dynamics of oriC utilization according to growth phases. We discovered that in T. barophilus , the use of oriC diminishes from the lag to the middle of the log phase, and subsequently increases gradually upon entering the stationary phase. Although oriC demonstrates no indispensability, RadA does exhibit essentiality. Notably, a knockdown mutant strain provides confirmation of the pivotal role of RadA in RDR for the first time. Thus, we demonstrate the existence of a tight combination between oriC utilization and homologous recombination to initiate DNA replication along the growth phases. Overall, this study demonstrates how diverse physiological states can influence the initiation of DNA replication, offering insights into how environmental sensing might impact this fundamental mechanism of life., Importance: Replication of DNA is highly important in all organisms. It initiates at a specific locus called ori , which serves as the binding site for scaffold proteins-either Cdc6 or DnaA-depending on the domain of life. However, recent studies have shown that the Archaea , Haloferax volcanii and Thermococcus kodakarensis could subsist without ori . Recombination-dependent replication (RDR), via the recombinase RadA, is the mechanism that uses homologous recombination to initiate DNA replication. The extent to which ori 's use is necessary in natural growth remains to be characterized. In this study, using Thermococcus barophilus , we demonstrated that DNA replication initiation relies on both oriC and RDR throughout its physiological growth, each to varying degrees depending on the phase. Notably, a knockdown RadA mutant confirmed the prominent use of RDR during the log phase. Moreover, the study of ploidy in oriC and radA mutant strains showed that the number of chromosomes per cell is a critical proxy for ensuring proper growth and cell survival., Competing Interests: The authors declare no conflict of interest.

The administration of magnetic resonance imaging (MRI) contrast agents (CAs) has been conducted since 1988 by clinicians to enhance the clarity and interpretability of MR images. CAs based on gadolinium chelates are the clinical standard used worldwide for the diagnosis of various pathologies, such as the detection of brain lesions, the visualization of blood vessels, and the assessment of soft tissue disorders. However, due to ongoing concerns associated with the safety of gadolinium-based contrast agents, considerable efforts have been directed towards developing contrast agents with better relaxivities, reduced toxicity, and eventually combined therapeutic modalities. In this context, grafting (or encapsulating) paramagnetic metals or chelates onto (within) carbon-based nanoparticles is a straightforward approach enabling the production of contrast agents with high relaxivities while providing extensive tuneability regarding the functionalization of the nanoparticles. Here, we provide an overview of the parameters defining the efficacy of lanthanide-based contrast agents and the subsequent developments in the field of nanoparticular-based contrast agents incorporating paramagnetic species.

The YAP/Hippo pathway is an organ growth and size regulation rheostat safeguarding multiple tissue stem cell compartments. LATS kinases phosphorylate and thereby inactivate YAP, thus representing a potential direct drug target for promoting tissue regeneration. Here, we report the identification and characterization of the selective small-molecule LATS kinase inhibitor NIBR-LTSi. NIBR-LTSi activates YAP signaling, shows good oral bioavailability, and expands organoids derived from several mouse and human tissues. In tissue stem cells, NIBR-LTSi promotes proliferation, maintains stemness, and blocks differentiation in vitro and in vivo. NIBR-LTSi accelerates liver regeneration following extended hepatectomy in mice. However, increased proliferation and cell dedifferentiation in multiple organs prevent prolonged systemic LATS inhibition, thus limiting potential therapeutic benefit. Together, we report a selective LATS kinase inhibitor agonizing YAP signaling and promoting tissue regeneration in vitro and in vivo, enabling future research on the regenerative potential of the YAP/Hippo pathway., Competing Interests: Declaration of interests All authors except C.B., E.B., K.T.D., W.-Y.L., S.J.F., B.H., M.T.D., P.-A.C., and P.L. are or were employees of Novartis Pharma AG., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A phytochemical study was carried out on stem bark of Combretum fragrans F. Hoffm., a medicinal plant belonging to the Combretaceae family and used traditionally in the treatment of various ailments. Column chromatography separation on silica gel of the crude methanol extract from stem barks of C. fragrans led to the isolation of a new pentacyclic triterpene acid, with a 3,6-epoxide bridge and trivially named as fragransinic acid (1), along with four known compounds: betulin (2), betulinic acid (3), bellericagenin B (4) and a mixture of β -sitosterol (5) and stigmasterol (6). Structures were elucidated by extensive spectroscopic analyses including 1D and 2D NMR, mass spectrometry as well as by comparison with literature data. The above compounds were isolated for the first time from C. adenogonium . Implications for chemosystematics and traditional medicine were briefly discussed.

Vaccine reactogenicity is well documented at the clinical level but the mechanism involved at the local or systemic level are still poorly understood. Muscular tissue where most vaccines are administered is the first place of interaction between the vaccine formulation and the host's immune cells. So far, this site of vaccine administration is not well documented from a mechanistic standpoint. The study of early molecular events at the injection site is crucial to understand the local response to vaccines. In this paper, we report a standardized workflow, from the injection of vaccine formulations in rabbit muscle, to the analysis by desorption electrospray ionization and histology staining to understand the role of lipids involved in the inflammation and its resolution on striated muscular tissue. The analysis of lipid mediators was optimized at the site of needle insertion to allow the spatial comparison of cellular infiltrates at the injection site. We showed that lipids were distributed across the spatial tissue morphology in a time-dependent manner. The MS imaging applied to vaccinology could pave the way to a better understanding of vaccine reactogenicity and mechanism of action., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Emilie Chautard reports a relationship with Sanofi that includes: equity or stocks. Sebastien Laurent reports a relationship with Sanofi-Aventis Research and Development Montpellier that includes: equity or stocks. Patrick Syntin reports a relationship with Sanofi that includes: equity or stocks. Fabienne Piras-Douce reports a relationship with Sanofi that includes: equity or stocks. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Messenger RNA (mRNA) vaccines have demonstrated efficacy against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) in humans. mRNA technology holds tremendous potential for rapid control and prevention of emergencies due to its flexibility with respect to production, application, and design for an efficacious and safe use in humans. We assessed the toxicity and biodistribution of MRT5500, an mRNA vaccine encoding for the full-length of the SARS-CoV-2 spike protein and delivered by lipid nanoparticles (LNPs) containing a novel ionizable lipid, Lipid-1 in preclinical animal models. In the repeated dose toxicity study, rabbits received three intramuscular (IM) injections of MRT5500 at 3-week interval followed by a 4-week observation period. In an exploratory biodistribution study in mice receiving a single IM injection of an mRNA encoding luciferase encapsulated in an LNP containing Lipid-1, the expression of the luciferase protein was monitored in vivo and ex vivo at several time points. In the regulatory biodistribution study in rabbits receiving a single IM injection of MRT5500, the quantification of the mRNA and the ionizable Lipid-1 were monitored in the same organs and time points as in the exploratory biodistribution study. MRT5500 was safe and well-tolerated with a transient acute phase response/inflammation and an expected vaccine-related immunological response, typical of those observed following a vaccine administration. The biodistribution data demonstrated that the mRNA and Lipid-1 components of the vaccine formulations were mainly detected at the injection site and in the draining lymph nodes. These results support the use of MRT5500 and its deployment into clinical trials., (© 2023 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd.)

The elastic properties of conductance arteries are one of the most important hemodynamic functions in the body, and data continue to emerge regarding the importance of their dysfunction in vascular aging and a range of cardiovascular diseases. Here, we provide new insight into the integrative physiology of arterial stiffening and its clinical consequence. We also comprehensively review progress made on pathways/molecules that appear today as important basic determinants of arterial stiffness, particularly those mediating the vascular smooth muscle cell (VSMC) contractility, plasticity and stiffness. We focus on membrane and nuclear mechanotransduction, clearance function of the vascular wall, phenotypic switching of VSMCs, immunoinflammatory stimuli and epigenetic mechanisms. Finally, we discuss the most important advances of the latest clinical studies that revisit the classical therapeutic concepts of arterial stiffness and lead to a patient-by-patient strategy according to cardiovascular risk exposure and underlying disease.

How is time encoded into organ growth and morphogenesis? We address this question by investigating heteroblasty, where leaf development and form are modified with progressing plant age. By combining morphometric analyses, fate-mapping through live-imaging, computational analyses, and genetics, we identify age-dependent changes in cell-cycle-associated growth and histogenesis that underpin leaf heteroblasty. We show that in juvenile leaves, cell proliferation competence is rapidly released in a "proliferation burst" coupled with fast growth, whereas in adult leaves, proliferative growth is sustained for longer and at a slower rate. These effects are mediated by the SPL9 transcription factor in response to inputs from both shoot age and individual leaf maturation along the proximodistal axis. SPL9 acts by activating CyclinD3 family genes, which are sufficient to bypass the requirement for SPL9 in the control of leaf shape and in heteroblastic reprogramming of cellular growth. In conclusion, we have identified a mechanism that bridges across cell, tissue, and whole-organism scales by linking cell-cycle-associated growth control to age-dependent changes in organ geometry., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: While cochlear implants (CIs) have provided benefits for speech recognition in quiet for subjects with severe-to-profound hearing loss, speech recognition in noise remains challenging. A body of evidence suggests that reducing frequency-to-place mismatch may positively affect speech perception. Thus, a fitting method based on a tonotopic map may improve speech perception results in quiet and noise. The aim of our study was to assess the impact of a tonotopic map on speech perception in noise and quiet in new CI users., Design: A prospective, randomized, double-blind, two-period cross-over study in 26 new CI users was performed over a 6-month period. New CI users older than 18 years with bilateral severe-to-profound sensorineural hearing loss or complete hearing loss for less than 5 years were selected in the University Hospital Centre of Rennes in France. An anatomical tonotopic map was created using postoperative flat-panel computed tomography and a reconstruction software based on the Greenwood function. Each participant was randomized to receive a conventional map followed by a tonotopic map or vice versa. Each setting was maintained for 6 weeks, at the end of which participants performed speech perception tasks. The primary outcome measure was speech recognition in noise. Participants were allocated to sequences by block randomization of size two with a ratio 1:1 (CONSORT Guidelines). Participants and those assessing the outcomes were blinded to the intervention., Results: Thirteen participants were randomized to each sequence. Two of the 26 participants recruited (one in each sequence) had to be excluded due to the COVID-19 pandemic. Twenty-four participants were analyzed. Speech recognition in noise was significantly better with the tonotopic fitting at all signal-to-noise ratio (SNR) levels tested [SNR = +9 dB, p = 0.002, mean effect (ME) = 12.1%, 95% confidence interval (95% CI) = 4.9 to 19.2, standardized effect size (SES) = 0.71; SNR = +6 dB, p < 0.001, ME = 16.3%, 95% CI = 9.8 to 22.7, SES = 1.07; SNR = +3 dB, p < 0.001 ME = 13.8%, 95% CI = 6.9 to 20.6, SES = 0.84; SNR = 0 dB, p = 0.003, ME = 10.8%, 95% CI = 4.1 to 17.6, SES = 0.68]. Neither period nor interaction effects were observed for any signal level. Speech recognition in quiet ( p = 0.66) and tonal audiometry ( p = 0.203) did not significantly differ between the two settings. 92% of the participants kept the tonotopy-based map after the study period. No correlation was found between speech-in-noise perception and age, duration of hearing deprivation, angular insertion depth, or position or width of the frequency filters allocated to the electrodes., Conclusion: For new CI users, tonotopic fitting appears to be more efficient than the default frequency fitting because it allows for better speech recognition in noise without compromising understanding in quiet., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The phenolic composition of Cnicus benedictus roots from four Algerian regions was investigated. Extractions were performed in both hydro-methanolic (30 : 70, v/v) and hydro-ethanolic (30 : 70, v/v) solvents. Their efficiency was determined in terms of the qualitative and quantitative composition in phenolic compounds by HPLC-LC/MS of the different extracts isolated from C. Benedictus roots. Cnicus benedictus roots extract have been characterized by high content of phenolic compounds, where the trans chalcone, 2,3-dihydro flavone, 3-hydroxy flavone and cinnamic acid constitute the major components, in addition to fourteen minor acidic compounds and flavonoids as rutin. The hydro-methanolic extract was the richest in phenolic compounds yield from C benedictus. On the other hand, hydro methanolic (30 : 70, v/v) and hydro ethanolic (30 : 70, v/v) extracts exhibited a high anti-inflammatory activity by in vitro 5-lipoxygenase inhibitory activity (IC 50 : 6.05±94.16 μg/mL) as well as by in silico docking according two methods. Likewise, anti-Alzheimer activity of extracts was confirmed by this last technique taking into account the major compounds identified. Antibacterial tests revealed interesting results compared to amoxicillin for the different regions studied with a high content in trans chalcone and 3-hydroxy Flavone., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Background: Arterial stiffness, as measured by arterial pulse wave velocity (PWV), is an established biomarker for cardiovascular risk and target-organ damage in individuals with hypertension. With the emergence of new devices for assessing PWV, it has become evident that some of these devices yield results that display significant discrepancies compared with previous devices. This discrepancy underscores the importance of comprehensive validation procedures and the need for international recommendations., Methods: A stepwise approach utilizing the modified Delphi technique, with the involvement of key scientific societies dedicated to arterial stiffness research worldwide, was adopted to formulate, through a multidisciplinary vision, a shared approach to the validation of noninvasive arterial PWV measurement devices., Results: A set of recommendations has been developed, which aim to provide guidance to clinicians, researchers, and device manufacturers regarding the validation of new PWV measurement devices. The intention behind these recommendations is to ensure that the validation process can be conducted in a rigorous and consistent manner and to promote standardization and harmonization among PWV devices, thereby facilitating their widespread adoption in clinical practice., Conclusions: It is hoped that these recommendations will encourage both users and developers of PWV measurement devices to critically evaluate and validate their technologies, ultimately leading to improved consistency and comparability of results. This, in turn, will enhance the clinical utility of PWV as a valuable tool for assessing arterial stiffness and informing cardiovascular risk stratification and management in individuals with hypertension., Competing Interests: Disclosures A.P. Avolio is a member of the Scientific Advisory Board of CardieX. P. Boutouyrie has participated in the past in the validation of multiple devices, among them Popmètre and WITHINGS Body Cardio. P. Boutouyrie has research grants with WITHINGS for the development of connected health devices. P. Boutouyrie, P. Segers, and R.M. Bruno are involved as researchers in an H2020 project working on the development of an integrated silicon photonics-based device that aims to measure pulse wave velocity. S. Laurent received research grants and honoraria as a speaker or chairperson and has been on the advisory board of Servier Laboratories, SOM Biotech, and WITHINGS. J. Baulmann has an interest in Redwave Medical GmbH and received equipment and lecture fees from IEM GmbH, BPLab, SMT Medical GmbH & Co, SOT Medical Systems, and Tensiomed. J.A. Chirinos received University of Pennsylvania research grants from the National Institutes of Health, Fukuda-Denshi, Bristol-Myers Squibb, Microsoft, and Abbott. J.A. Chirinos was named inventor in a University of Pennsylvania patent for the use of inorganic nitrates/nitrites for the treatment of heart failure and preserved ejection fraction and patent applications for the use of biomarkers in heart failure. J.A. Chirinos received payments for editorial roles from the American Heart Association, the American College of Cardiology, and Wiley. J.A. Chirinos received research device loans from ATCOR Medical, Fukuda-Denshi, Unex, Uscom, NDD Medical Technologies, Microsoft, and MicroVision Medical. S.S. Daskalopoulou is a cofounder of the start-up PLAKK that aims to identify individual atherosclerotic plaque instability and stroke risk using artificial intelligence methods. C.C. Mayer is an inventor (not holder) of a patent that is partly used in the ARCSolver algorithm in the Mobil-O-Graph 24h PWA Monitor (IEM GmbH). A.E. Schutte received speaker honoraria from Servier, Novartis, Abbott, Sanofi, Omron, Aktiia, and Medtronic. E.M. Urbina was on the Data Safety Monitoring Board of Astellas, Inc, and received an honorarium from Targus Medical, Inc. I. Tan was an employee of ATCOR Medical. E. Bianchini is a cofounder of QUIPU s.r.l., a spin-off company of the Italian National Research Council and the University of Pisa developing software for medical devices.