504 results on '"Nicolas E."'
Search Results
2. Long-term homeostasis in microbial consortia via auxotrophic cross-feeding.
- Author
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Grandel NE, Alexander AM, Peng X, Palamountain C, Alnahhas RN, Hirning AJ, Josić K, and Bennett MR
- Abstract
Synthetic microbial consortia are collections of multiple strains or species of engineered organisms living in a shared ecosystem. Because they can separate metabolic tasks among different strains, synthetic microbial consortia have myriad applications in developing biomaterials, biomanufacturing, and biotherapeutics. However, synthetic consortia often require burdensome control mechanisms to ensure that the members of the community remain at the correct proportions. This is especially true in continuous culture systems in which slight differences in growth rates can lead to extinctions. Here, we present a simple method for controlling consortia proportions using cross-feeding in continuous auxotrophic co-culture. We use mutually auxotrophic E. coli with different essential gene deletions and regulate the growth rates of members of the consortium via cross-feeding of the missing nutrients in each strain. We demonstrate precise regulation of the co-culture steady-state ratio by exogenous addition of the missing nutrients. We also model the co-culture's behavior using a system of ordinary differential equations that enable us to predict its response to changes in nutrient concentrations. Our work provides a powerful tool for consortia proportion control with minimal metabolic costs to the constituent strains.
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- 2025
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3. Ultrafast Symmetry Control in Photoexcited Quantum Dots.
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Guzelturk B, Portner J, Ondry J, Ghanbarzadeh S, Tarantola M, Jeong A, Field T, Chandler AM, Wieman E, Hopper TR, Watkins NE, Yu J, Cheng X, Lin MF, Luo D, Kramer PL, Shen X, Reid AH, Borkiewicz O, Ruett U, Zhang X, Lindenberg AM, Ma J, Schaller RD, Talapin DV, and Cotts BL
- Abstract
Symmetry control is essential for realizing unconventional properties, such as ferroelectricity, nonlinear optical responses, and complex topological order, thus it holds promise for the design of emerging quantum and photonic systems. Nevertheless, fast and reversible control of symmetry in materials remains a challenge, especially for nanoscale systems. Here, reversible symmetry changes are unveiled in colloidal lead chalcogenide quantum dots on picosecond timescales. Using a combination of ultrafast electron diffraction and total X-ray scattering, in conjunction with atomic-scale structural modeling and first-principles calculations, it is revealed that symmetry-broken lead sulfide quantum dots restore to a centrosymmetric phase upon photoexcitation. The symmetry restoration is driven by photoexcited electronic carriers, which suppress lead off-centering for about 100 ps. Furthermore, the change in symmetry is closely correlated with the electronic properties, and the bandgap transiently red-shifts in the symmetry-restored quantum dots. Overall, this study elucidates reversible symmetry changes in colloidal quantum dots, and more broadly defines a new methodology to optically control symmetry in nanoscale systems on ultrafast timescales., (© 2024 UChicago Argonne, LLC, Operator of Argonne National Laboratory and The Author(s). Advanced Materials published by Wiley‐VCH GmbH.)
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- 2025
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4. Hydrogenolysis of Haloboranes: from Synthesis of Hydroboranes to Formal Hydroboration Reactions.
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Zwart G, Mifleur A, Durin G, Nicolas E, and Cantat T
- Abstract
Hydroboranes are versatile reagents in synthetic chemistry, but their synthesis relies on energy-intensive processes. Herein, we report a new method for the preparation of hydroboranes from hydrogen and the corresponding haloboranes. Triethylamine (NEt
3 ) form with dialkylchloroboranes a Frustrated Lewis Pair (FLP) able to split H2 and afford the desired hydroborane with ammonium salts. Unreactive haloboranes were unlocked using a catalytic amount of Cy2 BCl, enabling the synthesis of commonly used hydroboranes such as pinacolborane or catecholborane. The mechanisms of these reactions have been examined by DFT studies, highlighting the importance of the base selection. Finally, the system's robustness has been evaluated in one-pot B-Cl hydrogenolysis/hydroboration reactions of C=C unsaturated bonds., (© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH.)- Published
- 2024
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5. Cyclodextrin-Encapsulated NHCs: Increased Selectivity and Reactivity of CO 2 in Amine Formylation.
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Bijouard K, Nicolas E, Anthore-Dalion L, Sollogoub M, and Cantat T
- Abstract
Herein, we describe the confinement of a N-Heterocyclic Carbene (NHC) organocatalyst in the cavity of cyclodextrins (CDs). These confined organocatalysts allow the formylation of amines through CO
2 hydrosilylation. The presence of the cavity of the CDs leads to substrate-selectivity between amines in competition reactions. The use of the smallest α-CD induces the best selectivities but also increased reactivity compared to the bigger β-CD. A careful study conducted by NMR and DFT revealed that in α-CD, the complexed CO2 interacts with the cavity through hydrogen bonds. These H-bonds destabilize the NHC-CO2 adduct and are accountable for the higher reactivity observed using α-CD., (© 2024 The Author(s). Chemistry - A European Journal published by Wiley-VCH GmbH.)- Published
- 2024
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6. Cancer treatments as paradoxical catalysts of tumor awakening in the lung.
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Nicolas E, Kosmider B, Cukierman E, Borghaei H, Golemis EA, and Borriello L
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- Humans, Animals, Neoplasms pathology, Neoplasms metabolism, Neoplasms therapy, Neoplasm Metastasis, Lung Neoplasms pathology, Lung Neoplasms metabolism, Tumor Microenvironment
- Abstract
Much of the fatality of tumors is linked to the growth of metastases, which can emerge months to years after apparently successful treatment of primary tumors. Metastases arise from disseminated tumor cells (DTCs), which disperse through the body in a dormant state to seed distant sites. While some DTCs lodge in pre-metastatic niches (PMNs) and rapidly develop into metastases, other DTCs settle in distinct microenvironments that maintain them in a dormant state. Subsequent awakening, induced by changes in the microenvironment of the DTC, causes outgrowth of metastases. Hence, there has been extensive investigation of the factors causing survival and subsequent awakening of DTCs, with the goal of disrupting these processes to decrease cancer lethality. We here provide a detailed overview of recent developments in understanding of the factors controlling dormancy and awakening in the lung, a common site of metastasis for many solid tumors. These factors include dynamic interactions between DTCs and diverse epithelial, mesenchymal, and immune cell populations resident in the lung. Paradoxically, among key triggers for metastatic outgrowth, lung tissue remodeling arising from damage induced by the treatment of primary tumors play a significant role. In addition, growing evidence emphasizes roles for inflammation and aging in opposing the factors that maintain dormancy. Finally, we discuss strategies being developed or employed to reduce the risk of metastatic recurrence., Competing Interests: Declarations Ethical approval N/A. Informed consent N/A. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)
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- 2024
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7. Exploring bracket torque expression: A comparative in vitro study of new self-ligating bracket designs and archwire geometries.
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Thomas V, Dol G, Tannouri Z, François O, Nicolas E, Soulier-Peigue D, and El Helou M
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- Humans, Models, Dental, Dental Alloys, Dental Stress Analysis, Tooth Movement Techniques instrumentation, In Vitro Techniques, Orthodontic Brackets, Orthodontic Wires, Orthodontic Appliance Design, Torque, Stainless Steel
- Abstract
Objective: This in vitro study aimed to evaluate the torque expression efficiency when it is integrated into the bracket slot versus the bracket base. Additionally, the impact of archwire geometry (rectangular vs. rhomboid) on torque expression has been examined., Material and Methods: The torque expression was evaluated in a full arch printed maxillary model, focusing on tooth #11, which was positioned within an alveolus filled with Typodont wax. Three different types of brackets were utilized: conventional metallic bracket (Minidiamond™), self-ligating bracket with torque in base (Damon Q2™), and a new self-ligating bracket design with torque in slot (Damon Ultima™). Two variations of archwires were used: rectangular and rhomboid stainless steel, measuring 0.019×0.025 inches and 0.019×0.0275 inches, respectively, from ORMCO™. The study included seven groups: six experimental groups and a control group, with 15 measurements in each group, totaling 105 torque measurements. Optical impressions were taken of the tooth's original position and its final position after torque expression. STL files were superimposed using GEOMAGIC software to calculate the percentage of torque expression., Results: The self-ligating bracket with torque in slot (Damon Ultima™) shows significantly higher torque expression than the self-ligating bracket with torque in base (Damon Q2™) with a rectangular stainless steel archwire (P=0.00015). The Ultima™ bracket also demonstrates higher torque expression than both the Q2™ and conventional 22° brackets with a rhomboid stainless steel archwire (P<0.003). No significant difference in torque expression was found between the rectangular and rhomboid stainless steel archwires for any bracket group (P>0.05)., Conclusions: The self-ligating bracket with torque in slot shows comparable torque expression effectiveness to the conventional bracket, outperforming the self-ligating bracket with torque in base. Archwire geometry does not significantly impact torque expression., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)
- Published
- 2024
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8. Changes in Diet During Orthodontic Treatment in Adolescents. A Literature Review
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Tombal É, Nicolas E, Munoz Sanchez ML, Linas N, and El Helou M
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- Adolescent, Humans, Feeding Behavior physiology, Diet methods, Orthodontics, Corrective methods, Orthodontics, Corrective adverse effects
- Abstract
Introduction: Fixed orthodontic treatment, typically initiated during adolescence (a crucial period of growth) raises interest in evaluating dietary modifications resulting from their implementation, providing essential information for formulating appropriate dietary advice. This systematic literature review aims to assess dietary changes in adolescents following orthodontic treatment., Material and Methods: An electronic search was conducted in the PubMed database with no time restrictions, following PRISMA guidelines. A combination of MeSH and non-MeSH terms, with no deadline, was applied, followed by a rigorous assessment of selected articles. The latest search was conducted on September the 20 th, 2023., Results: Among the initially identified 224 articles, only nine studies met the inclusion criteria. All, except one study, reported significant dietary modifications after treatment initiation., Conclusion: The installation of fixed orthodontic treatment in adolescents alters dietary habits, favoring soft foods. Anticipating the consequences on growth and diet habits is crucial, recommending tailored dietary advice before appliance placement. The registration number for this review on PROSPERO is CRD42023454959.
- Published
- 2024
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9. Real-world Study of Avelumab First-line Maintenance Treatment in Patients with Advanced Urothelial Carcinoma in France: Overall Results from the Noninterventional AVENANCE Study and Analysis of Outcomes by Second-line Treatment.
- Author
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Barthélémy P, Thibault C, Fléchon A, Gross-Goupil M, Voog E, Eymard JC, Abraham C, Chasseray M, Lorgis V, Hilgers W, Gobert A, Le Moulec S, Simon C, Nicolas E, Escande A, Pouessel D, Mouillet G, Josse C, Solbes MN, Lambert P, and Loriot Y
- Abstract
Background: Avelumab first-line maintenance treatment was approved for patients with advanced urothelial carcinoma (aUC) without progression following platinum-based chemotherapy (PBC), based on the results from the JAVELIN Bladder 100 phase 3 trial., Objective: To report the results from AVENANCE, a real-world study of avelumab first-line maintenance treatment., Design, Setting, and Participants: This is a retrospective and prospective, noninterventional study (NCT04822350). Eligible patients with aUC without progression on first-line PBC were enrolled at 82 centers in France between July 2021 and May 2022. The effectiveness population included 595 patients. The median follow-up was 26.3 mo., Intervention: Previous, ongoing, or planned avelumab first-line maintenance treatment., Outcome Measurements and Statistical Analysis: Overall survival (OS) from avelumab initiation (primary endpoint) and safety were evaluated., Results and Limitations: The median age was 73.0 yr, and performance status was 0/1 in 91% of patients and ≥2 in 9.3%. The most common prior first-line chemotherapy regimen was carboplatin plus gemcitabine (61%). At data cutoff (December 7, 2023), the median duration of avelumab treatment was 5.6 mo, 125 patients remained on avelumab, and 55% had received second-line treatment. The median OS from avelumab initiation was 21.3 mo (95% confidence interval [CI], 17.6-24.6), and the median progression-free survival was 5.7 mo (95% CI, 5.2-6.5). In exploratory analyses of this population without disease progression on PBC, the median OS from the start of first-line PBC was 26.5 mo overall, and in subgroups that received second-line enfortumab vedotin (n = 55) or PBC (n = 79), it was 41.5 and 24.5 mo, respectively., Conclusions: Real-world data from AVENANCE confirm the effectiveness and safety of avelumab first-line maintenance treatment in a heterogeneous population, supporting its recommendation for cisplatin-eligible and cisplatin-ineligible patients with aUC who are progression free after first-line PBC. In an exploratory analysis, a small subgroup that received a treatment sequence of first-line PBC without disease progression followed by avelumab first-line maintenance and second-line enfortumab vedotin had a median OS of >3 yr., Patient Summary: A French real-world study, called AVENANCE, looked at avelumab maintenance treatment in people with advanced urothelial cancer whose tumor disappeared, shrank, or stopped growing with chemotherapy. Overall, results were consistent with those seen in a previous clinical trial, and on average, people treated with avelumab maintenance lived for 26.5 mo from the start of chemotherapy. Analyses of different groups of people found that survival varied, with people living for an average of 18-42 mo depending on what treatment they received after they finished avelumab treatment., (Copyright © 2024. Published by Elsevier B.V.)
- Published
- 2024
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10. Can Orthodontic Adhesive Systems Inhibit the Formation and Development of White Spot Lesions During Fixed Orthodontic Treatment? A Systematic Review.
- Author
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El Helou M, Chakar S, Nicolas E, Estephan E, Cuisinier F, and Barthélemi S
- Subjects
- Humans, Orthodontic Appliances, Fixed, Dental Cements chemistry, Dental Caries prevention & control, Dental Bonding
- Abstract
Purpose: This study aims to assess whether orthodontic bonding systems prevent orthodontic-induced white spot lesions (OIWSLs), exploring efficacy and identifying associated factors through a comprehensive systematic review of existing evidence., Materials and Methods: The study complied to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Two evaluators screened records, and data were extracted on orthodontic bonding systems, outcomes, and participant characteristics from PubMed/MEDLINE, Cochrane Library, and EM Premium. The search equation focused on white spot lesions and orthodontic bonding. Only in-vivo studies and clinical trials on humans were included, while in-vitro studies were excluded. The risk of bias was assessed using Cochrane's RoB2 tool for RCTs and ROBINS-I tool for non-randomized studies, evaluating key domains related to bias., Results: The systematic review, including 12 articles with 550 participants and 2,000 teeth, revealed that bonding with nanoparticles of nCaF2-primer and amorphous calcium phosphate-containing adhesives effectively reduced WSLs. In contrast, one-step adhesive without primer (GC Ortho Connect™) was associated with higher and more severe WSLs. Fluoride-releasing primers (Opal Seal™ and Clearfil™) did not exhibit an advantage in demineralization reduction. The inclusion of TiO2 nanoparticles in two studies yielded conflicting results on antibacterial effects., Discussion: Various nanoparticles incorporated into adhesives or primers exhibit promise in preventing white spot lesions in fixed orthodontic treatment. However, the used evaluation methods, such as clinical examinations or advanced imaging, significantly impact result interpretation. The effectiveness of orthodontic adhesives in preventing WSLs should balance between biocompatibility, bond strength and demineralization control tailored to patient-specific needs.
- Published
- 2024
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11. P2X 7 receptors exhibit at least three modes of allosteric antagonism.
- Author
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Oken AC, Ditter IA, Lisi NE, Krishnamurthy I, Godsey MH, and Mansoor SE
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- Animals, Humans, Rats, Adenosine Triphosphate metabolism, Adenosine Triphosphate chemistry, Allosteric Regulation, Ligands, Models, Molecular, Protein Binding, Female, Sf9 Cells, Oocytes, Xenopus laevis, Cryoelectron Microscopy, Purinergic P2X Receptor Antagonists pharmacology, Purinergic P2X Receptor Antagonists chemistry, Receptors, Purinergic P2X7 metabolism, Receptors, Purinergic P2X7 chemistry
- Abstract
P2X receptors are trimeric ion channels activated by adenosine triphosphate (ATP) that contribute to pathophysiological processes ranging from asthma to neuropathic pain and neurodegeneration. A number of small-molecule antagonists have been identified for these important pharmaceutical targets. However, the molecular pharmacology of P2X receptors is poorly understood because of the chemically disparate nature of antagonists and their differential actions on the seven constituent subtypes. Here, we report high-resolution cryo-electron microscopy structures of the homomeric rat P2X
7 receptor bound to five previously known small-molecule allosteric antagonists and a sixth antagonist that we identify. Our structural, biophysical, and electrophysiological data define the molecular determinants of allosteric antagonism in this pharmacologically relevant receptor, revealing three distinct classes of antagonists that we call shallow, deep, and starfish. Starfish binders, exemplified by the previously unidentified antagonist methyl blue, represent a unique class of inhibitors with distinct functional properties that could be exploited to develop potent P2X7 ligands with substantial clinical impact.- Published
- 2024
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12. Cryo-EM structures of the human P2X1 receptor reveal subtype-specific architecture and antagonism by supramolecular ligand-binding.
- Author
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Oken AC, Lisi NE, Ditter IA, Shi H, Nechiporuk NA, and Mansoor SE
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- Humans, Adenosine Triphosphate metabolism, Adenosine Triphosphate chemistry, Benzenesulfonates, Binding Sites, HEK293 Cells, Ligands, Models, Molecular, Protein Binding, Cryoelectron Microscopy, Purinergic P2X Receptor Antagonists pharmacology, Receptors, Purinergic P2X1 chemistry, Receptors, Purinergic P2X1 metabolism, Receptors, Purinergic P2X1 ultrastructure
- Abstract
P2X receptors are a family of seven trimeric non-selective cation channels that are activated by extracellular ATP to play roles in the cardiovascular, neuronal, and immune systems. Although it is known that the P2X1 receptor subtype has increased sensitivity to ATP and fast desensitization kinetics, an underlying molecular explanation for these subtype-selective features is lacking. Here we report high-resolution cryo-EM structures of the human P2X1 receptor in the apo closed, ATP-bound desensitized, and the high-affinity antagonist NF449-bound inhibited states. The apo closed and ATP-bound desensitized state structures of human P2X1 define subtype-specific properties such as distinct pore architecture and ATP-interacting residues. The NF449-bound inhibited state structure of human P2X1 reveals that NF449 has a unique dual-ligand supramolecular binding mode at the interface of neighboring protomers, inhibiting channel activation by overlapping with the canonical P2X receptor ATP-binding site. Altogether, these data define the molecular pharmacology of the human P2X1 receptor laying the foundation for structure-based drug design., (© 2024. The Author(s).)
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- 2024
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13. Impact of the total lesion glycolysis (TLG) in predicting response of follicular lymphoma to rituximab.
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Pignot PE, Bahri H, Malartre S, Morisset S, Lebras L, Guillermin Y, Nicolas E, Rey P, Belhabri A, Jauffret L, Fyot E, Thisse A, Bocquet A, and Michallet AS
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- 2024
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14. High-affinity agonism at the P2X 7 receptor is mediated by three residues outside the orthosteric pocket.
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Oken AC, Lisi NE, Krishnamurthy I, McCarthy AE, Godsey MH, Glasfeld A, and Mansoor SE
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- Animals, Rats, Binding Sites, Sodium metabolism, Humans, Purinergic P2X Receptor Agonists pharmacology, HEK293 Cells, Protein Binding, Models, Molecular, Receptors, Purinergic P2X7 metabolism, Receptors, Purinergic P2X7 genetics, Adenosine Triphosphate metabolism, Adenosine Triphosphate analogs & derivatives, Cryoelectron Microscopy
- Abstract
P2X receptors are trimeric ATP-gated ion channels that activate diverse signaling cascades. Due to its role in apoptotic pathways, selective activation of P2X
7 is a potential experimental tool and therapeutic approach in cancer biology. However, mechanisms of high-affinity P2X7 activation have not been defined. We report high-resolution cryo-EM structures of wild-type rat P2X7 bound to the high-affinity agonist BzATP as well as significantly improved apo receptor structures in the presence and absence of sodium. Apo structures define molecular details of pore architecture and reveal how a partially hydrated Na+ ion interacts with the conductance pathway in the closed state. Structural, electrophysiological, and direct binding data of BzATP reveal that three residues just outside the orthosteric ATP-binding site are responsible for its high-affinity agonism. This work provides insights into high-affinity agonism for any P2X receptor and lays the groundwork for development of subtype-specific agonists applicable to cancer therapeutics., (© 2024. The Author(s).)- Published
- 2024
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15. The vulnerability of sharks, skates, and rays to ocean deoxygenation: Physiological mechanisms, behavioral responses, and ecological impacts.
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Waller MJ, Humphries NE, Womersley FC, Loveridge A, Jeffries AL, Watanabe Y, Payne N, Semmens J, Queiroz N, Southall EJ, and Sims DW
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- Animals, Skates, Fish physiology, Oceans and Seas, Elasmobranchii physiology, Climate Change, Oxygen metabolism, Sharks physiology
- Abstract
Levels of dissolved oxygen in open ocean and coastal waters are decreasing (ocean deoxygenation), with poorly understood effects on marine megafauna. All of the more than 1000 species of elasmobranchs (sharks, skates, and rays) are obligate water breathers, with a variety of life-history strategies and oxygen requirements. This review demonstrates that although many elasmobranchs typically avoid hypoxic water, they also appear capable of withstanding mild to moderate hypoxia with changes in activity, ventilatory responses, alterations to circulatory and hematological parameters, and morphological alterations to gill structures. However, such strategies may be insufficient to withstand severe, progressive, or prolonged hypoxia or anoxia where anaerobic metabolic pathways may be used for limited periods. As water temperatures increase with climate warming, ectothermic elasmobranchs will exhibit elevated metabolic rates and are likely to be less able to tolerate the effects of even mild hypoxia associated with deoxygenation. As a result, sustained hypoxic conditions in warmer coastal or surface-pelagic waters are likely to lead to shifts in elasmobranch distributions. Mass mortalities of elasmobranchs linked directly to deoxygenation have only rarely been observed but are likely underreported. One key concern is how reductions in habitat volume as a result of expanding hypoxia resulting from deoxygenation will influence interactions between elasmobranchs and industrial fisheries. Catch per unit of effort of threatened pelagic sharks by longline fisheries, for instance, has been shown to be higher above oxygen minimum zones compared to adjacent, normoxic regions, and attributed to vertical habitat compression of sharks overlapping with increased fishing effort. How a compound stressor such as marine heatwaves alters vulnerability to deoxygenation remains an open question. With over a third of elasmobranch species listed as endangered, a priority for conservation and management now lies in understanding and mitigating ocean deoxygenation effects in addition to population declines already occurring from overfishing., (© 2024 The Author(s). Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of Fisheries Society of the British Isles.)
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- 2024
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16. Disability Caused by Cleft Lip and Palate: A Systematic Review and Critical Valuation Appraisal.
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Blum JD, Benítez DB, Caballero FR, Villavisanis DF, Cho DY, Bartlett SP, Taylor JA, Magee L, Sierra NE, and Swanson JW
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- Humans, Persons with Disabilities, Cleft Lip psychology, Cleft Palate psychology, Disability Evaluation
- Abstract
Objective: Measuring disability as a concept of impaired global function enables beneficiaries of treatment, the impact of treatment, and targets of health system investment to be rigorously assessed. Measures of disability are not well established for cleft lip and palate. This study aims to systematically review disability weight (DW) studies pertaining to orofacial clefts (OFCs) and identify methodological strengths and shortcomings of each approach., Design: Systematic literature review of studies that met the following criteria: (1) peer-reviewed publication, (2) focus on disability valuation, (3) mention orofacial clefts, and (4) publication January 2001-December 2021., Setting: None., Patients/participants: None., Interventions: None., Main Outcome Measure(s): Disability weight method of valuation and the value itself., Results: The final search strategy yielded 1,067 studies. Seven manuscripts were ultimately included for data extraction. The disability weights used in our studies, including those newly generated or taken from the Global Burden of Disease Studies (GBD), ranged widely for isolated cleft lip (0.0-0.100) and cleft palate with or without cleft lip (0.0-0.269). The GBD studies limited their consideration of cleft sequelae informing disability weights to impact on appearance and speech-related concerns, while other studies accounted for comorbidities such as pain and social stigma., Conclusions: Current measures of cleft disability are sparse, inadequately reflect the comprehensive impact of an OFC on function and socialization, and are limited in detail or supporting evidence. Use of a comprehensive health state description in evaluating disability weights offers a realistic means of accurately representing the diverse sequelae of an OFC., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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- 2024
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17. Comparative analyses of time efficiency and cost in fabricating fixed implant-supported prostheses in digital, hybrid, and conventional workflows: A systematic review and meta-analysis.
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Bessadet M, Auduc C, Drancourt N, Nicolas E, and El Osta N
- Abstract
Statement of Problem: Economic considerations affect whether new technologies are adopted in dental practice. Limited evidence exists regarding the time and cost efficiency of different workflows for fabricating implant-supported restorations., Purpose: The purpose of this systematic review and meta-analysis was to compare the time and cost involved in fabricating fixed implant-supported prostheses using digital, hybrid, and conventional methods throughout the entire prosthetic treatment by analyzing both clinical and laboratory steps., Material and Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA)-P 2015 guidelines. The methods and inclusion criteria were specified in a protocol registered with the International Prospective Register of Systematic Reviews (PROSPERO) (registration number CRD42023458734). The databases PubMed, Cochrane, and PROSPERO were searched using keywords: (Prosthodontic OR restorative dentistry OR denture) AND (CAD CAM OR Digital workflow OR Computer Dentistry OR Digital Design) AND (Economic OR cost OR Financial OR time efficiency). Two investigators selected articles independently., Results: A qualitative synthesis of 12 articles published from 2010 to 2023 showed that digital scans took less time than conventional impressions (P<.05) in 7 out of 9 articles. Additionally, 8 articles revealed significant reductions in laboratory working time with digital workflows, intermediate times with hybrid workflows, and longer times with conventional workflows (P<.001). Meta-analysis confirmed the time efficiency of digital scanning over conventional impressions (Hedges g=1.65, 95% CI [0.33, 2.98]) and a substantial reduction in laboratory time with digital workflows compared with other workflows (Hedges g=6.55, 95% CI [2.69; 10.42]). However, no significant difference was found in adjustment time between digital and other workflows (Hedges g=0.91, 95% CI [-0.72; 2.55]). Direct laboratory costs were observed to be higher in conventional workflows compared with hybrid or digital workflows, with hybrid workflows also showing elevated costs compared with digital workflows (P<.05)., Conclusions: The digital workflow demonstrates potential benefits in reducing scan time, laboratory processing time, and direct laboratory costs for implant-supported restorations in partial edentulism. Further research is needed to validate these findings, particularly for long-span implant-supported fixed partial prostheses., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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18. Scalable and adaptable two-ligand co-solvent transfer methodology for gold bipyramids to organic solvents.
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Coplan CD, Watkins NE, Lin XM, and Schaller RD
- Abstract
Large and faceted nanoparticles, such as gold bipyramids, presently require synthesis using alkyl ammonium halide ligands in aqueous conditions to stabilize the structure, which impedes subsequent transfer and suspension of such nanoparticles in low polarity solvents despite success with few nanometer gold nanoparticles of shapes such as spheres. Phase transfer methodologies present a feasible avenue to maintain colloidal stability of suspensions and move high surface energy particles into organic solvent environments. Here, we present a method to yield stable suspensions of gold bipyramids in low-polarity solvents, including methanol, dimethylformamide, chloroform, and toluene, through the requisite combination of two capping agents and the presence of a co-solvent. By utilizing PEG-SH functionalization for stability, dodecanethiol (DDT) as the organic-soluble capping agent, and methanol to aid in the phase transfer, gold bipyramids with a wide-range of aspect ratios and sizes can be transferred between water and chloroform readily and maintain colloidal stability. Subsequent transfer to various organic and low-polarity solvents is then demonstrated for the first time., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)
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- 2024
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19. Intramuscular Myxoma of the Flexor Carpi Ulnaris Causing Cubital Tunnel Syndrome: A Case Report.
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Giusti NE, Somoza AV, and Aziz KT
- Abstract
Introduction: Intramuscular myxomas are rare, benign mesenchymal tumors which commonly arise in muscle of the upper limb, pelvis, abdominal tissue, spine, or facial muscle. There are few case reports of intramuscular myxomas, and none of these describe intramuscular myxoma as a cause of compressive neuropathy., Case Report: We describe the case of a 67-year-old woman who presented to us with a 1-year history of progressive enlargement of a painless right elbow mass. She gradually developed increasing numbness and tingling in her right small finger, which was worse at night. She underwent cubital tunnel release with concurrent right elbow mass excision of the flexor carpi ulnaris muscle. Histology showed intramuscular myxoma. Postoperatively, she had a complete resolution of her symptoms with a good functional outcome., Conclusion: This is the first known case of intramuscular myxoma within the flexor carpi ulnaris causing compressive neuropathy of the ulnar nerve at the elbow., Competing Interests: Conflict of Interest: Nil, (Copyright: © Indian Orthopaedic Research Group.)
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- 2024
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20. A comprehensive supportive care program for fine-tuning cancer immunotherapy.
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de Borms AT, Colard-Thomas J, Laurent PI, Coget E, Carbasse C, Annakib S, Thomas QD, Nicolas E, and Fiteni F
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- Humans, Patient Reported Outcome Measures, Neoplasms therapy, Immunotherapy methods, Immune Checkpoint Inhibitors therapeutic use, Exercise
- Abstract
Supportive care has become a new pilar of modern oncology, and a great deal of research is being conducted in that area, especially on immune checkpoint inhibitors (ICIs), to help fine-tune immunotherapy. Four major areas of supportive care can enhance responsiveness to cancer immunotherapy whilst minimizing adverse effects: diet (indirectly, by modulating the microbiota or directly, by modulating the immune system), physical activity (by modulating the immune system), electronic patient-reported outcomes (ePRO) (by detecting and treating immune-related adverse events early on), and co-medication management (to possibly suppress those drugs that negatively affect the efficacy of ICIs). Therefore, patients treated with ICIs could receive a systematic multimodal supportive care program encompassing regular nutritional counseling, regular physical activity under the supervision of a physical activity professional, ePRO follow-up, and regular pharmaceutical counseling. This type of approach needs to be evaluated in well-conducted randomized clinical trials., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
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- 2024
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21. Immunosuppression-induced Zika virus reactivation causes brain inflammation and behavioral deficits in mice.
- Author
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Nogueira CO, Lopes da Silva MO, de Lima EV, Christoff RR, Gavino-Leopoldino D, Lemos FS, da Silva NE, Da Poian AT, Assunção-Miranda I, Figueiredo CP, and Clarke JR
- Abstract
Zika virus (ZIKV) is a neurotropic flavivirus that can persist in several tissues. The late consequences of ZIKV persistence and whether new rounds of active replication can occur, remain unaddressed. Here, we investigated whether neonatally ZIKV-infected mice are susceptible to viral reactivation in adulthood. We found that when ZIKV-infected mice are treated with immunosuppressant drugs, they present increased susceptibility to chemically induced seizures. Levels of subgenomic flavivirus RNAs (sfRNAs) were increased, relative to the amounts of genomic RNAs, in the brains of mice following immunosuppression and were associated with changes in cytokine expression. We investigated the impact of immunosuppression on the testicles and found that ZIKV genomic RNA levels are increased in mice following immunosuppression, which also caused significant testicular damage. These findings suggest that ZIKV can establish new rounds of active replication long after acute stages of disease, so exposed patients should be monitored to ensure complete viral eradication., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s).)
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- 2024
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22. Comparative Study of Maxillary Growth in Patients With Unilateral Cleft Treated With and Without Pre-Surgical Orthopedics.
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Agell Sogbe A, Mitiko Aseka Garcia M, Souza Lima Wan-Dall B, Sierra NE, and da Silva Freitas R
- Subjects
- Humans, Female, Prospective Studies, Male, Infant, Treatment Outcome, Cephalometry, Cleft Palate surgery, Maxilla abnormalities, Maxilla growth & development, Maxilla surgery, Cleft Lip surgery
- Abstract
Compare the maxillary growth of patients with Unilateral Cleft treated with pre-surgical Functional Maxillary Orthopedic (FMO) and that of who underwent a surgical procedure with no previous use of appliances., Prospective study, the patients were divided into 2 groups. G1, was composed of 12 patients who received no pre-surgical intervention and cheilorhinoplasty at 6 months of age and G2, included 12 patients treated using Pre-Surgical Funtional Maxilary Orthopedic; they underwent no surgery during the study. Measurements were taken at three times: before the first month of life, at 6 months and between 9-12 months of age. Cleft distance (anterior, medium and posterior), maxillary width (anterior, medium and posterior) and minor and major segment width were analyzed., Alveolar Cleft decrease was 79.82% in G1 and 52% in G2. Posterior Cleft decrease was 24.1% in G1 and 41.77% in G2. Greater Segment Width increase was 24.53% for the patients in G1, and 37.47% for the patients in G2. As for Inter Canine Width, a decrease of 5.16% in G1 and an increase of 9.19% in G2 were found. Medium Arch Width only increased in a statistically significant manner in G2 9.02%., Surgery allowed for the closure of the alveolar cleft. FMO made it possible to close the anterior and the posterior clefts through the growth of the maxillary segments, increased the transverse growth of the maxilla and could prevent maxillary collapse. Each team must individually evaluate whether to indicate or not the use of preoperative orthopedics., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
- Published
- 2024
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23. TDP1 mutation causing SCAN1 neurodegenerative syndrome hampers the repair of transcriptional DNA double-strand breaks.
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Geraud M, Cristini A, Salimbeni S, Bery N, Jouffret V, Russo M, Ajello AC, Fernandez Martinez L, Marinello J, Cordelier P, Trouche D, Favre G, Nicolas E, Capranico G, and Sordet O
- Subjects
- Humans, DNA-Binding Proteins metabolism, DNA-Binding Proteins genetics, DNA Topoisomerases, Type I metabolism, DNA Topoisomerases, Type I genetics, Transcription, Genetic, R-Loop Structures, CRISPR-Cas Systems genetics, DNA Breaks, Double-Stranded, DNA Repair, Phosphoric Diester Hydrolases metabolism, Phosphoric Diester Hydrolases genetics, Neurodegenerative Diseases genetics, Neurodegenerative Diseases metabolism, Neurodegenerative Diseases pathology, Mutation genetics
- Abstract
TDP1 removes transcription-blocking topoisomerase I cleavage complexes (TOP1ccs), and its inactivating H493R mutation causes the neurodegenerative syndrome SCAN1. However, the molecular mechanism underlying the SCAN1 phenotype is unclear. Here, we generate human SCAN1 cell models using CRISPR-Cas9 and show that they accumulate TOP1ccs along with changes in gene expression and genomic distribution of R-loops. SCAN1 cells also accumulate transcriptional DNA double-strand breaks (DSBs) specifically in the G1 cell population due to increased DSB formation and lack of repair, both resulting from abortive removal of transcription-blocking TOP1ccs. Deficient TDP1 activity causes increased DSB production, and the presence of mutated TDP1 protein hampers DSB repair by a TDP2-dependent backup pathway. This study provides powerful models to study TDP1 functions under physiological and pathological conditions and unravels that a gain of function of the mutated TDP1 protein, which prevents DSB repair, rather than a loss of TDP1 activity itself, could contribute to SCAN1 pathogenesis., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2024
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24. Age related impairments in ingestion from a large population based-sample.
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Hennequin M, El Osta N, Munoz-Sanchez ML, Vandenberghe Descamps M, Andreeva VA, Feron G, Nicolas E, Pereira B, Peyron MA, Cousson PY, Sulmont-Rosse C, and Faulks D
- Subjects
- Humans, Adolescent, Adult, Aged, Aged, 80 and over, Oral Health, Mastication, Food, Quality of Life, Xerostomia epidemiology
- Abstract
Objectives: Epidemiological data regarding the evolution of problems related to mastication and swallowing with age are lacking. This study aims to (i) describe changes in oral function with age, using data from a large French population, (ii) validate online, self-report uses of an ICF questionnaire in older persons, and (iii) assess whether impairment is related to avoidance of certain foods, xerostomia, body mass index (BMI) and oral health related quality of life (OHRQoL)., Methods: Volunteers aged ≥18 years with internet access completed a series of questionnaires on sociodemographic, anthropometric and oral health characteristics (oral function, Xerostomia Index (XI), OHRQoL, reasons for avoidance of certain food). Oral function was assessed using items derived from the International Classification of Functioning (ICF). Five ICF items related to ingestion function and six items related to activities and participation were used. A validation study was undertaken to identify those with poor chewing ability and low salivary flow amongst older participants reporting impairment., Findings: 39 597 individuals were included. The prevalence of individuals with impairment for ICF items related to ingestion function and oral activity (eating, drinking and speaking), and the percentage of participants with poor OHRQoL increased significantly with age (p < 0.001). Each ICF item was significantly associated with OHRQoL (p < 0.001), XI (p < 0.001), BMI (p < 0.001) and avoidance of certain food due to chewing or swallowing difficulties., Conclusion: Overall, 21.5% and 13.5% of the study population had chewing and/or biting impairments respectively, which might affect food selection and consumption. These findings raise individual and population-based issues. Further studies are needed to assess whether impairment in oral function might increase frailty in older individuals, and also to compare data with those from other countries., Competing Interests: Declaration of competing interest The authors 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 Ltd.. All rights reserved.)
- Published
- 2024
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25. The macroecology of butyrate-producing bacteria via metagenomic assessment of butyrate production capacity.
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Brame JE, Liddicoat C, Abbott CA, Edwards RA, Robinson JM, Gauthier NE, and Breed MF
- Abstract
Butyrate-producing bacteria are found in many outdoor ecosystems and host organisms, including humans, and are vital to ecosystem functionality and human health. These bacteria ferment organic matter, producing the short-chain fatty acid butyrate. However, the macroecological influences on their biogeographical distribution remain poorly resolved. Here we aimed to characterise their global distribution together with key explanatory climatic, geographical and physicochemical variables. We developed new normalised butyrate production capacity (BPC) indices derived from global metagenomic ( n = 13,078) and Australia-wide soil 16S rRNA ( n = 1331) data, using Geographic Information System (GIS) and modelling techniques to detail their ecological and biogeographical associations. The highest median BPC scores were found in anoxic and fermentative environments, including the human (BPC = 2.99) and non-human animal gut (BPC = 2.91), and in some plant-soil systems (BPC = 2.33). Within plant-soil systems, roots (BPC = 2.50) and rhizospheres (BPC = 2.34) had the highest median BPC scores. Among soil samples, geographical and climatic variables had the strongest overall effects on BPC scores (variable importance score range = 0.30-0.03), with human population density also making a notable contribution (variable importance score = 0.20). Higher BPC scores were in soils from seasonally productive sandy rangelands, temperate rural residential areas and sites with moderate-to-high soil iron concentrations. Abundances of butyrate-producing bacteria in outdoor soils followed complex ecological patterns influenced by geography, climate, soil chemistry and hydrological fluctuations. These new macroecological insights further our understanding of the ecological patterns of outdoor butyrate-producing bacteria, with implications for emerging microbially focused ecological and human health policies., (© 2024 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)
- Published
- 2024
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26. Deep learning-driven imaging of cell division and cell growth across an entire eukaryotic life cycle.
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Ramakanth S, Kennedy T, Yalcinkaya B, Neupane S, Tadic N, Buchler NE, and Argüello-Miranda O
- Abstract
The life cycle of biomedical and agriculturally relevant eukaryotic microorganisms involves complex transitions between proliferative and non-proliferative states such as dormancy, mating, meiosis, and cell division. New drugs, pesticides, and vaccines can be created by targeting specific life cycle stages of parasites and pathogens. However, defining the structure of a microbial life cycle often relies on partial observations that are theoretically assembled in an ideal life cycle path. To create a more quantitative approach to studying complete eukaryotic life cycles, we generated a deep learning-driven imaging framework to track microorganisms across sexually reproducing generations. Our approach combines microfluidic culturing, life cycle stage-specific segmentation of microscopy images using convolutional neural networks, and a novel cell tracking algorithm, FIEST, based on enhancing the overlap of single cell masks in consecutive images through deep learning video frame interpolation. As proof of principle, we used this approach to quantitatively image and compare cell growth and cell cycle regulation across the sexual life cycle of Saccharomyces cerevisiae . We developed a fluorescent reporter system based on a fluorescently labeled Whi5 protein, the yeast analog of mammalian Rb, and a new High-Cdk1 activity sensor, LiCHI, designed to report during DNA replication, mitosis, meiotic homologous recombination, meiosis I, and meiosis II. We found that cell growth preceded the exit from non-proliferative states such as mitotic G1, pre-meiotic G1, and the G0 spore state during germination. A decrease in the total cell concentration of Whi5 characterized the exit from non-proliferative states, which is consistent with a Whi5 dilution model. The nuclear accumulation of Whi5 was developmentally regulated, being at its highest during meiotic exit and spore formation. The temporal coordination of cell division and growth was not significantly different across three sexually reproducing generations. Our framework could be used to quantitatively characterize other single-cell eukaryotic life cycles that remain incompletely described. An off-the-shelf user interface Yeastvision provides free access to our image processing and single-cell tracking algorithms.
- Published
- 2024
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27. Critical Roles of pH and Activated Carbon on the Speciation and Performance of an Archetypal Organometallic Complex for Aqueous Redox Flow Batteries.
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Burghoff A and Holubowitch NE
- Abstract
A lack of suitable high-potential catholytes hinders the development of aqueous redox flow batteries (RFBs) for large-scale energy storage. Hydrolysis of the charged (oxidized) catholyte typically occurs when its redox potential approaches that of water, with a negative impact on battery performance. Here, we elucidate and address such behavior for a representative iron-based organometallic complex, showing that the associated voltage and capacity losses can be curtailed by several simple means. We discovered that addition of activated carbon cloth (ACC) to the reservoir of low-cost, high-potential [Fe(bpy)
3 ]2+/3+ catholyte-limited aqueous redox flow batteries extends their lifetime and boosts discharge voltage─two typically orthogonal performance metrics. Similar effects are observed when the catholyte's graphite felt electrode is electrochemically oxidized (overcharged) and by modifying the catholyte solution's pH, which was monitored in situ for all flow batteries. Modulation of solution pH alters hydrolytic speciation of the charged catholyte from the typical dimeric species μ-O-[FeIII (bpy)2 (H2 O)]2 4+ , converting it to a higher-potential μ-dihydroxo form, μ-[FeIII (bpy)2 (H2 O)(OH)]2 4+ , at lower pH. The existence of free bpyH2 2+ at low pH is found to strongly correlate with battery degradation. Near-neutral-pH RFBs employing a viologen anolyte, (SPr)2 V, in excess with the [Fe(bpy)3 ]2+/3+ catholyte containing ACC exhibited high-voltage discharge for up to 600 cycles (41 days) with no discernible capacity fade. Correlating pH and voltage data offers powerful fundamental insight into organometallic (electro)chemistry with potential utility beyond battery applications. The findings, with implications toward a host of other "near-neutral" active species, illuminate the critical and underappreciated role of electrolyte pH on intracycle and long-term aqueous flow battery performance.- Published
- 2024
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28. Amplified Spontaneous Emission from Electron-Hole Quantum Droplets in Colloidal CdSe Nanoplatelets.
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Watkins NE, Diroll BT, Williams KR, Liu Y, Greene CL, Wasielewski MR, and Schaller RD
- Abstract
Two-dimensional cadmium selenide nanoplatelets (NPLs) exhibit large absorption cross sections and homogeneously broadened band-edge transitions that offer utility in wide-ranging optoelectronic applications. Here, we examine the temperature-dependence of amplified spontaneous emission (ASE) in 4- and 5-monolayer thick NPLs and show that the threshold for close-packed (neat) films decreases with decreasing temperature by a factor of 2-10 relative to ambient temperature owing to extrinsic (trapping) and intrinsic (phonon-derived line width) factors. Interestingly, for pump intensities that exceed the ASE threshold, we find development of intense emission to lower energy in particular provided that the film temperature is ≤200 K. For NPLs diluted in an inert polymer, both biexcitonic ASE and low-energy emission are suppressed, suggesting that described neat-film observables rely upon high chromophore density and rapid, collective processes. Transient emission spectra reveal ultrafast red-shifting with the time of the lower energy emission. Taken together, these findings indicate a previously unreported process of amplified stimulated emission from polyexciton states that is consistent with quantum droplets and constitutes a form of exciton condensate. For studied samples, quantum droplets form provided that roughly 17 meV or less of thermal energy is available, which we hypothesize relates to polyexciton binding energy. Polyexciton ASE can produce pump-fluence-tunable red-shifted ASE even 120 meV lower in energy than biexciton ASE. Our findings convey the importance of biexciton and polyexciton populations in nanoplatelets and show that quantum droplets can exhibit light amplification at significantly lower photon energies than biexcitonic ASE.
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- 2024
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29. Accuracy of conventional impressions and digital scans for implant-supported fixed prostheses in maxillary free-ended partial edentulism: An in vitro study.
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El Osta N, Drancourt N, Auduc C, Veyrune JL, and Nicolas E
- Subjects
- Humans, Models, Dental, Imaging, Three-Dimensional, Dental Impression Technique, Computer-Aided Design, Dental Implants
- Abstract
Objectives: To evaluate the accuracy of conventional polyether impressions and digital scans produced by five intra-oral scanners (IOSs) in maxillary free-ended partial edentulism for long-span implant-supported prostheses., Methods: This in vitro study involved the impression of a maxillary model with free-end partial edentulism, in which six implants were placed before digitization using a desktop scanner to generate a digital reference model. Conventional impressions (Impregum Penta Soft, 3M) and digital scans with five IOSs (Trios 3 and 4, 3Shape; Primescan, Dentsply-Sirona; CS 3600, Carestream Dental; and i-500, Medit) were obtained. Conventional impressions were digitized using the same desktop scanner. Each digital STL file of conventional or digital impressions was superimposed over the reference STL file to enable comparison. Trueness was assessed by calculating angles and distance deviations. For precision, dispersions of values around their means were also measured., Results: The mean distance deviation was significantly higher for conventional impressions (454.24 ± 334.70 µm) than for IOSs (ranging from 160.98 ± 204.48 µm to 255.56 ± 395.89 µm) (p < 0.001). The mean angular deviation was high with conventional impressions (1.82 ± 1.51°), intermediate with CS 3600 (1.38 ± 1.42°), Primescan (1.37 ± 2.54°) and Trios 4 (1.30 ± 0.64°) scanners, and lower with I500 (0.97 ± 0.75°) and Trios 3 (1.01 ± 0.85°) scanners (p < 0.001). The dispersion of distance values around their means was lowest with Trios 3 and i-500, followed by CS3600, Primescan, and Trios 4, respectively, and higher for conventional impressions (p < 0.001). The dispersion of angular values was smallest with i-500, Trios 3, and Trios 4 compared with other groups and was highest with Primescan (p < 0.001)., Conclusions: Within the limits of the current study, Trios 3 scanner exhibited the highest accuracy, followed by i-500, Trios 4, CS 3600, Primescan, and conventional impressions respectively. IOSs might be reliable for the fabrication of an implant-supported prosthesis. In vivo studies are required to confirm these findings., Clinical Significance: Passive adaptation of the implant-supported framework is a challenge when rehabilitating patients with maxillary free-end partial edentulism. While Conventional impressions remain a reliable and validated technique, but IOSs demonstrated higher accuracy, suitable for the fabrication of long-span implant-supported prostheses in partially edentulous arch., Competing Interests: Declaration of competing interest The authors 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 Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
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30. Evaluation and comparison of the accuracy of three intraoral scanners for replicating a complete denture.
- Author
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Le Texier L, Nicolas E, and Batisse C
- Subjects
- Humans, Dental Impression Technique, Models, Dental, Dental Arch, Denture, Complete, Imaging, Three-Dimensional, Computer-Aided Design
- Abstract
Statement of Problem: Technological advances in digital acquisition tools have increased the scope of intraoral scanners (IOSs), including scanning a removable complete denture (RCD) to replicate it. However, studies assessing the accuracy of IOSs for replicating a maxillary or mandibular RCD are lacking., Purpose: The purpose of this in vitro study was to evaluate the accuracy (trueness and precision) of 3 IOSs while replicating a maxillary and mandibular RCD., Material and Methods: One maxillary and 1 mandibular RCD were scanned with a desktop scanner (D2000) to obtain the reference model. Two operators scanned each RCD 5 times with 3 different IOSs (TRIOS 4, Primescan, and IS3800), following a predefined acquisition protocol. The 60 study models obtained were compared with the reference model using the Geomagic software program. For each comparison, the mean and standard deviation of discrepancy were calculated. Distances were measured on both the reference and the study model, and differences were calculated to assess whether sagittal or transverse deformations were present. The tolerance percentage of the volume of the digital model compared with the volume of the reference model was determined (difference tolerance was set at 0.1 mm). A univariate analysis of variance followed by a post hoc analysis using the Student-Newman-Keuls (α=.05) test was performed to determine the truest and the most precise IOS., Results: The TRIOS 4 and Primescan IOSs had comparable trueness, with mean dimensional variations of 47 ±27 µm and 57 ±8 µm respectively compared with the reference model. The IS3800 had a lower trueness (98 ±35 µm). Primescan was significantly more precise with a mean standard deviation of 64 ±15 µm (P<.05). The TRIOS 4 (141 ±48 µm) and IS3800 (129 ±24 µm) had comparable precision. Primescan showed the least sagittal and transverse deformation., Conclusions: This study determined that an RCD can be replicated using an IOS, although all IOSs did not have equal accuracy. An in vivo study needs to assess whether this procedure is clinically acceptable., (Copyright © 2024 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)
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- 2024
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31. Formoxyboranes as hydroborane surrogates for the catalytic reduction of carbonyls through transfer hydroboration.
- Author
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Durin G, Romero RM, Godou T, Chauvier C, Thuéry P, Nicolas E, and Cantat T
- Abstract
A new class of Lewis base stabilized formoxyboranes demonstrates the feasibility of catalytic transfer hydroboration. In the presence of a ruthenium catalyst, they have shown broad applicability for reducing carbonyl compounds. Various borylated alcohols are obtained in high selectivity and yields up to 99%, tolerating several functional groups. Computational studies enabled to propose a mechanism for this transformation, revealing the role of the ruthenium catalyst and the absence of hydroborane intermediates., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)
- Published
- 2024
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32. Fluorophosphoniums as Lewis acids in organometallic catalysis: application to the carbonylation of β-lactones.
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Pietraru MH, Ponsard L, Lentz N, Thuéry P, Nicolas E, and Cantat T
- Abstract
We describe the synthesis and characterisation of four organic Lewis acids based on fluorophosphoniums, with tetracarbonyl cobaltate as the counter-anion: [R
3 PF]+ [Co(CO)4 ]- (with R = o -Tol, Cy,i Pr, andt Bu). Their catalytic activity was investigated for the carbonylation of β-lactones to succinic anhydrides. In the presence of [t Bu3 PF]+ [Co(CO)4 ]- IV (3 mol%), 90% of succinic anhydride was afforded from β-propiolactone after 16 h at 80 °C, at a very mild pressure of 2 bar of carbon monoxide. Our study sets the first example of the use of a main-group cation as a Lewis acidic partner in the cobalt-catalyzed carbonylation of β-lactones.- Published
- 2024
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33. Highly active fish in low oxygen environments: vertical movements and behavioural responses of bigeye and yellowfin tunas to oxygen minimum zones in the eastern Pacific Ocean.
- Author
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Humphries NE, Fuller DW, Schaefer KM, and Sims DW
- Abstract
Oxygen minimum zones in the open ocean are predicted to significantly increase in volume over the coming decades as a result of anthropogenic climatic warming. The resulting reduction in dissolved oxygen (DO) in the pelagic realm is likely to have detrimental impacts on water-breathing organisms, particularly those with higher metabolic rates, such as billfish, tunas, and sharks. However, little is known about how free-living fish respond to low DO environments, and therefore, the effect increasing OMZs will have cannot be predicted reliably. Here, we compare the responses of two active predators (bigeye tuna Thunnus obesus and yellowfin tuna Thunnus albacares ) to DO at depth throughout the eastern Pacific Ocean. Using time-series data from 267 tagged tunas (59,910 days) and 3D maps of modelled DO, we find that yellowfin tuna respond to low DO at depth by spending more time in shallower, more oxygenated waters. By contrast, bigeye tuna, which forage at deeper depths well below the thermocline, show fewer changes in their use of the water column. However, we find that bigeye tuna increased the frequency of brief upward vertical excursions they performed by four times when DO at depth was lower, but with no concomitant significant difference in temperature, suggesting that this behaviour is driven in part by the need to re-oxygenate following time spent in hypoxic waters. These findings suggest that increasing OMZs will impact the behaviour of these commercially important species, and it is therefore likely that other water-breathing predators with higher metabolic rates will face similar pressures. A more comprehensive understanding of the effect of shoaling OMZs on pelagic fish vertical habitat use, which may increase their vulnerability to surface fisheries, will be important to obtain if these effects are to be mitigated by future management actions., Supplementary Information: The online version contains supplementary material available at 10.1007/s00227-023-04366-2., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial interests to disclose., (© The Author(s) 2024.)
- Published
- 2024
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34. Climate-driven global redistribution of an ocean giant predicts increased threat from shipping.
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Womersley FC, Sousa LL, Humphries NE, Abrantes K, Araujo G, Bach SS, Barnett A, Berumen ML, Lion SB, Braun CD, Clingham E, Cochran JEM, de la Parra R, Diamant S, Dove ADM, Duarte CM, Dudgeon CL, Erdmann MV, Espinoza E, Ferreira LC, Fitzpatrick R, Cano JG, Green JR, Guzman HM, Hardenstine R, Hasan A, Hazin FHV, Hearn AR, Hueter RE, Jaidah MY, Labaja J, Ladino F, Macena BCL, Meekan MG, Morris JJ Jr, Norman BM, Peñaherrera-Palma CR, Pierce SJ, Quintero LM, Ramírez-Macías D, Reynolds SD, Robinson DP, Rohner CA, Rowat DRL, Sequeira AMM, Sheaves M, Shivji MS, Sianipar AB, Skomal GB, Soler G, Syakurachman I, Thorrold SR, Thums M, Tyminski JP, Webb DH, Wetherbee BM, Queiroz N, and Sims DW
- Abstract
Climate change is shifting animal distributions. However, the extent to which future global habitats of threatened marine megafauna will overlap existing human threats remains unresolved. Here we use global climate models and habitat suitability estimated from long-term satellite-tracking data of the world's largest fish, the whale shark, to show that redistributions of present-day habitats are projected to increase the species' co-occurrence with global shipping. Our model projects core habitat area losses of >50% within some national waters by 2100, with geographic shifts of over 1,000 km (∼12 km yr
-1 ). Greater habitat suitability is predicted in current range-edge areas, increasing the co-occurrence of sharks with large ships. This future increase was ∼15,000 times greater under high emissions compared with a sustainable development scenario. Results demonstrate that climate-induced global species redistributions that increase exposure to direct sources of mortality are possible, emphasizing the need for quantitative climate-threat predictions in conservation assessments of endangered marine megafauna., Competing Interests: Competing interestsThe authors declare no competing interests., (© The Author(s) 2024.)- Published
- 2024
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35. Horizontal acquisition of a DNA ligase improves DNA damage tolerance in eukaryotes.
- Author
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Nicolas E, Simion P, Guérineau M, Terwagne M, Colinet M, Virgo J, Lingurski M, Boutsen A, Dieu M, Hallet B, and Van Doninck K
- Subjects
- Animals, Humans, Phylogeny, DNA Ligases genetics, DNA Ligases metabolism, Ligases metabolism, Proteomics, DNA Damage, DNA Ligase ATP genetics, DNA Ligase ATP metabolism, Eukaryota genetics, Rotifera genetics
- Abstract
Bdelloid rotifers are part of the restricted circle of multicellular animals that can withstand a wide range of genotoxic stresses at any stage of their life cycle. In this study, bdelloid rotifer Adineta vaga is used as a model to decipher the molecular basis of their extreme tolerance. Proteomic analysis shows that a specific DNA ligase, different from those usually involved in DNA repair in eukaryotes, is strongly over-represented upon ionizing radiation. A phylogenetic analysis reveals its orthology to prokaryotic DNA ligase E, and its horizontal acquisition by bdelloid rotifers and plausibly other eukaryotes. The fungus Mortierella verticillata, having a single copy of this DNA Ligase E homolog, also exhibits an increased radiation tolerance with an over-expression of this DNA ligase E following X-ray exposure. We also provide evidence that A. vaga ligase E is a major contributor of DNA breaks ligation activity, which is a common step of all important DNA repair pathways. Consistently, its heterologous expression in human cell lines significantly improves their radio-tolerance. Overall, this study highlights the potential of horizontal gene transfers in eukaryotes, and their contribution to the adaptation to extreme conditions., (© 2023. The Author(s).)
- Published
- 2023
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36. Metal-Free Catalytic Hydrogenolysis of Chlorosilanes into Hydrosilanes with "Inverse" Frustrated Lewis Pairs.
- Author
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Durin G, Berthet JC, Thuéry P, Nicolas E, and Cantat T
- Abstract
The challenging metal-free catalytic hydrogenolysis of silyl chlorides to hydrosilanes is unlocked by using an inverse frustrated Lewis pair (FLP), combining a mild Lewis acid (Cy
2 BCl) and a strong phosphazene base (BTPP) in mild conditions (10 bar of H2 , r. t.). In the presence of a stoichiometric amount of the base, the hydrosilanes R3 SiH (R=Me, Et, Ph) are generated in moderate to high yields (up to 95 %) from their chlorinated counterparts. A selective formation of the valuable difunctional monohydride Me2 SiHCl is also obtained from Me2 SiCl2 . A mechanism is proposed based on stoichiometric experiments and DFT calculations; it highlights the critical role of borohydride species generated by the heterolytic splitting of H2 ., (© 2023 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)- Published
- 2023
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37. Local control strategies for management of NSCLC with oligoprogressive disease.
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Mavrikios A, Remon J, Quevrin C, Mercier O, Tselikas L, Botticella A, Nicolas E, Deutsch E, Besse B, Planchard D, Barlesi F, Le Péchoux C, and Levy A
- Subjects
- Humans, Prospective Studies, Retrospective Studies, Disease Progression, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung pathology, Lung Neoplasms drug therapy, Lung Neoplasms pathology, Radiosurgery methods
- Abstract
Progresses of systemic treatments in advanced non-small cell lung cancer (NSCLC), such as immune checkpoint blockers (ICB) and targeted therapies, led to the increased incidence of oligoprogressive disease (OPD). The OPD is a subtype of oligometastatic disease (OMD) defined as a progression of a limited number of lesions during systemic treatment exposure. The hypothesis was formulated that local radical treatments (LRT) could eradicate progressive lesions resulting from resistant clones, ultimately leading to systemic treatment sensitivity restoration. Recently published international consensuses and guidelines aim to obtain a uniform definition of OMD NSCLC, to standardize the inclusion of these patients in future clinical trials, as well as their management in daily practice. Although there is no specific definition of OPD, LRT strategies in OPD are supported after reporting promising results. Both retrospective and preliminary prospective randomized data of LRT for patients with OPD NSCLC are encouraging. More clinical and translational data are needed for selecting best scenarios where LRT should be delivered. In this review, we analyze the current available literature on LRT for patients with OPD in advanced NSCLC and discuss about future trial design and challenges., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: E.D. reports grants and personal fees from Roche-Genentech, grants and personal fees from AstraZeneca, grants and personal fees from Merck Serono, grants and personal fees from Boehringer, grants and personal fees from BMS, and grants and personal fees from MSD. B.B. reports sponsored research at Gustave Roussy Cancer Center by Abbvie, Amgen, AstraZeneca, Chugai Pharmaceutical, Daiichi-Sankyo, Ellipse Pharma, EISAI, Genmab, Genzyme Corporation, Hedera Dx, Inivata, IPSEN, Janssen, MSD, Pharmamar, Roche-Genentech, Sanofi, Socar Research, Tahio Oncology, Turning Point Therapeutics. A.L. reports sponsored research at Gustave Roussy Cancer Center by Amgen, AstraZeneca, Beigene, Roche. The other authors declare that they have no conflicts of interest., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
- Published
- 2023
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38. Direct measurement of cruising and burst swimming speeds of the shortfin mako shark (Isurus oxyrinchus) with estimates of field metabolic rate.
- Author
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Waller MJ, Queiroz N, da Costa I, Cidade T, Loureiro B, Womersley FC, Fontes J, Afonso P, Macena BCL, Loveridge A, Humphries NE, Southall EJ, and Sims DW
- Subjects
- Female, Animals, Swimming physiology, Muscles, Temperature, Tuna, Sharks physiology
- Abstract
The shortfin mako shark is a large-bodied pursuit predator thought to be capable of the highest swimming speeds of any elasmobranch and potentially one of the highest energetic demands of any marine fish. Nonetheless, few direct speed measurements have been reported for this species. Here, animal-borne bio-loggers attached to two mako sharks were used to provide direct measurements of swimming speeds, kinematics and thermal physiology. Mean sustained (cruising) speed was 0.90 m s
-1 (±0.07 s.d.) with a mean tail-beat frequency (TBF) of 0.51 Hz (±0.16 s.d.). The maximum burst speed recorded was 5.02 m s-1 (TBFmax = 3.65 Hz) from a 2 m long female. Burst swimming was sustained for 14 s (mean speed = 2.38 m s-1 ), leading to a 0.24°C increase in white muscle temperature in the 12.5 min after the burst. Routine field metabolic rate was estimated at 185.2 mg O2 kg-1 h-1 (at 18°C ambient temperature). Gliding behaviour (zero TBF) was more frequently observed after periods of high activity, especially after capture when internal (white muscle) temperature approached 21°C (ambient temperature: 18.3°C), indicating gliding probably functions as an energy recovery mechanism and limits further metabolic heat production. The results show shortfin mako sharks generally cruise at speeds similar to other endothermic fish - but faster than ectothermic sharks - with the maximum recorded burst speed being among the highest so far directly measured among sharks, tunas and billfishes. This newly recorded high-oxygen-demand performance of mako sharks suggests it may be particularly vulnerable to habitat loss due to climate-driven ocean deoxygenation., (© 2023 The Authors. Journal of Fish Biology published by John Wiley & Sons Ltd on behalf of Fisheries Society of the British Isles.)- Published
- 2023
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39. Implant-supported prostheses in patients with special needs: A systematic literature review of protocols and outcomes.
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Bogner MS, Chambas V, Nicolas E, Faulks D, and Hennequin M
- Abstract
Statement of Problem: Implant-supported prostheses for individuals with special needs have been considered high-risk because of the prevalence of poor oral hygiene and parafunction in this population; however, systematic evidence on protocols and outcomes is scarce., Purpose: The purpose of this systematic review was to summarize implant procedures and outcomes for the special needs population., Material and Methods: A systematic literature review was conducted using PubMed, Embase, and Scopus databases in accordance with the preferred reporting items for systematic reviews and meta-analyses (PRISMA) methodological framework. Data collected included patient information, location and number of implants, surgical and prosthetic procedures, behavior support techniques, postoperative follow-up, complications, and criteria for outcome assessment. Survival rates were pooled for quantitative analysis, and a separate analysis pooling data from groups of special needs patients that present similar risks was undertaken., Results: The qualitative analysis included 79 studies involving 759 patients and 2269 implants. The quantitative analysis included 65 studies concerning 666 patients with special needs and 1886 implants. The overall weighted implant survival rate was 95.4%, with a mean follow-up duration of 40.7 ±29.5 months., Conclusions: In individuals with special needs considered suitable for implant-supported prostheses by their clinician, implant survival rates were similar to those reported in the general population. (J Prosthet Dent xxxx;xxx:xxx-xxx)., (Copyright © 2023 Editorial Council for The Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)
- Published
- 2023
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40. The structural analysis of the periplasmic domain of Sinorhizobium meliloti chemoreceptor McpZ reveals a novel fold and suggests a complex mechanism of transmembrane signaling.
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Salar S, Ball NE, Baaziz H, Nix JC, Sobe RC, Compton KK, Zhulin IB, Brown AM, Scharf BE, and Schubot FD
- Subjects
- Phylogeny, Methyl-Accepting Chemotaxis Proteins chemistry, Methyl-Accepting Chemotaxis Proteins genetics, Methyl-Accepting Chemotaxis Proteins metabolism, Chemotaxis physiology, Bacterial Proteins chemistry, Sinorhizobium meliloti genetics, Sinorhizobium meliloti metabolism
- Abstract
Chemotaxis is a fundamental process whereby bacteria seek out nutrient sources and avoid harmful chemicals. For the symbiotic soil bacterium Sinorhizobium meliloti, the chemotaxis system also plays an essential role in the interaction with its legume host. The chemotactic signaling cascade is initiated through interactions of an attractant or repellent compound with chemoreceptors or methyl-accepting chemotaxis proteins (MCPs). S. meliloti possesses eight chemoreceptors to mediate chemotaxis. Six of these receptors are transmembrane proteins with periplasmic ligand-binding domains (LBDs). The specific functions of McpW and McpZ are still unknown. Here, we report the crystal structure of the periplasmic domain of McpZ (McpZPD) at 2.7 Å resolution. McpZPD assumes a novel fold consisting of three concatenated four-helix bundle modules. Through phylogenetic analyses, we discovered that this helical tri-modular domain fold arose within the Rhizobiaceae family and is still evolving rapidly. The structure, offering a rare view of a ligand-free dimeric MCP-LBD, reveals a novel dimerization interface. Molecular dynamics calculations suggest ligand binding will induce conformational changes that result in large horizontal helix movements within the membrane-proximal domains of the McpZPD dimer that are accompanied by a 5 Å vertical shift of the terminal helix toward the inner cell membrane. These results suggest a mechanism of transmembrane signaling for this family of MCPs that entails both piston-type and scissoring movements. The predicted movements terminate in a conformation that closely mirrors those observed in related ligand-bound MCP-LBDs., (© 2023 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.)
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- 2023
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41. Optimistic narrative future visions: a communication tool for promoting sustainable (plastic) behavior.
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Neef NE, Fußwinkel S, Roos C, Frank L, Shihepo K, and Richter I
- Abstract
Plastic pollution is a pressing global issue, necessitating a focus on consumer behavior to curb this problem at its source. To effectively promote sustainable practices, communication strategies that employ future visions have gained attention. This study examines the effects of a narrative video intervention depicting an optimistic future vision concerning single-use plastic bag consumption in South Africa, compared to a representation of the prevailing status quo . Using a preregistered within-subject design, we assess the psychological and emotional responses to two scenarios of which one is illustrating adaptive behaviors toward reduced plastic bag usage, and the other showcasing current consumption patterns. Parametric analyses revealed a shift in emotional states, characterized by a greater experience of positive emotions and a reduced experience of negative emotions following the exposure to the optimistic future scenario video, as compared to the status quo video. Moreover, engagement with the optimistic future scenario was associated with higher levels of perceived behavioral control and behavioral intentions. No significant changes were found regarding sense of responsibility. These findings point to the potential of optimistic future visions to influence individuals at psychological and emotional levels. This renders optimistic future vision communication as an effective tool for sustainable behavior change, particularly in relation to the sustainable use of plastic shopping bags., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Neef, Fußwinkel, Roos, Frank, Shihepo and Richter.)
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- 2023
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42. Trogocytosis of cancer-associated fibroblasts promotes pancreatic cancer growth and immune suppression via phospholipid scramblase anoctamin 6 (ANO6).
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Ogier C, Solomon AMC, Lu Z, Recoules L, Klochkova A, Gabitova-Cornell L, Bayarmagnai B, Restifo D, Surumbayeva A, Vendramini-Costa DB, Deneka AY, Francescone R, Lilly AC, Sipman A, Gardiner JC, Luong T, Franco-Barraza J, Ibeme N, Cai KQ, Einarson MB, Nicolas E, Efimov A, Megill E, Snyder NW, Bousquet C, Cros J, Zhou Y, Golemis EA, Gligorijevic B, Soboloff J, Fuchs SY, Cukierman E, and Astsaturov I
- Abstract
In pancreatic ductal adenocarcinoma (PDAC), the fibroblastic stroma constitutes most of the tumor mass and is remarkably devoid of functional blood vessels. This raises an unresolved question of how PDAC cells obtain essential metabolites and water-insoluble lipids. We have found a critical role for cancer-associated fibroblasts (CAFs) in obtaining and transferring lipids from blood-borne particles to PDAC cells via trogocytosis of CAF plasma membranes. We have also determined that CAF-expressed phospholipid scramblase anoctamin 6 (ANO6) is an essential CAF trogocytosis regulator required to promote PDAC cell survival. During trogocytosis, cancer cells and CAFs form synapse-like plasma membranes contacts that induce cytosolic calcium influx in CAFs via Orai channels. This influx activates ANO6 and results in phosphatidylserine exposure on CAF plasma membrane initiating trogocytosis and transfer of membrane lipids, including cholesterol, to PDAC cells. Importantly, ANO6-dependent trogocytosis also supports the immunosuppressive function of pancreatic CAFs towards cytotoxic T cells by promoting transfer of excessive amounts of cholesterol. Further, blockade of ANO6 antagonizes tumor growth via disruption of delivery of exogenous cholesterol to cancer cells and reverses immune suppression suggesting a potential new strategy for PDAC therapy.
- Published
- 2023
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43. In Vitro Resistance of Natural Molars vs. Additive-Manufactured Simulators Treated with Pulpotomy and Endocrown.
- Author
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Munoz-Sanchez ML, Gravier A, Francois O, Nicolas E, Hennequin M, and Decerle N
- Abstract
Endocrowns are designed to restore endodontically treated teeth with root canal treatment (Rct). Recently, endocrowns were proposed for teeth treated with full pulpotomy (FP). No data exist on in vitro evaluations for this combination. This study aimed to evaluate the mechanical behavior of pulpotomy-treated teeth with endocrowns according to different protocols for preparation design and materials and to assess whether 3D-printed resin simulators could be a reliable alternative for human teeth during in vitro strength tests. One hundred and ten extracted natural molars were randomized into 11 groups according to the type of endodontic treatment, the material used, and the design of peripheric preparation. One hundred and ten resin simulators were separated similarly. The samples were embedded in epoxy resin blocks before being subjected to oblique compressive load until failure. For natural teeth, the variance analysis separated two homogeneous groups, one regrouping the endodontically treated or pulpotomy-treated teeth without coronal restoration and the other one regrouping all the other samples, i.e., the untreated teeth (positive controls) and the treated and restored teeth. The strength resistance was lower for the resin simulators than for natural teeth in all groups. Within the limit of this study, strength resistance is not the most important criterion for choosing the type of material, preparation, or endodontic treatment for endocrowns. Resin simulators are not efficient for in vitro strength studies.
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- 2023
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44. Loss of Pkd1 limits susceptibility to colitis and colorectal cancer.
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Nikonova AS, Deneka AY, Silva FN, Pirestani S, Tricarico R, Kiseleva AA, Zhou Y, Nicolas E, Flieder DB, Grivennikov SI, and Golemis EA
- Abstract
Colorectal cancer (CRC) is one of the most common cancers, with an annual incidence of ~135,000 in the US, associated with ~50,000 deaths. Autosomal dominant polycystic kidney disease (ADPKD), associated with mutations disabling the PKD1 gene, affects as many as 1 in 1000. Intriguingly, some studies have suggested that individuals with germline mutations in PKD1 have reduced incidence of CRC, suggesting a genetic modifier function. Using mouse models, we here establish that loss of Pkd1 greatly reduces CRC incidence and tumor growth induced by loss of the tumor suppressor Apc. Growth of Pkd1
-/- ;Apc-/- organoids was reduced relative to Apc-/- organoids, indicating a cancer cell-intrinsic activity, even though Pkd1 loss enhanced activity of pro-oncogenic signaling pathways. Notably, Pkd1 loss increased colon barrier function, with Pkd1-deficient animals resistant to DSS-induced colitis, associated with upregulation of claudins that decrease permeability, and reduced T cell infiltration. Notably, Pkd1 loss caused greater sensitivity to activation of CFTR, a tumor suppressor in CRC, paralleling signaling relations in ADPKD. Overall, these data and other data suggest germline and somatic mutations in PKD1 may influence incidence, presentation, and treatment response in human CRC and other pathologies involving the colon., (© 2023. Springer Nature America, Inc.)- Published
- 2023
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45. Usefulness of Doppler Transthoracic Echocardiography for the Diagnosis of Wide-QRS Complex Tachycardia.
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Hamon D, Moulin T, Nicolas E, Labbé JP, Ternacle J, Huguet R, Lim P, Derumeaux G, Teiger E, Miller JM, and Lellouche N
- Subjects
- Humans, Arrhythmias, Cardiac diagnosis, Electrocardiography, Diagnosis, Differential, Tachycardia diagnosis, Echocardiography, Doppler
- Published
- 2023
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46. ThPOK is a critical multifaceted regulator of myeloid lineage development.
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Basu J, Olsson A, Ferchen K, Titerina EK, Chetal K, Nicolas E, Czyzewicz P, Levchenko D, Ge L, Hua X, Grimes HL, Salomonis N, and Kappes DJ
- Subjects
- Animals, Mice, Cell Differentiation, Cell Lineage, DNA-Binding Proteins, Mice, Knockout, RNA, Transcription Factors genetics, CD4 Antigens, Gene Expression Regulation, Thymus Gland
- Abstract
The transcription factor ThPOK (encoded by Zbtb7b) is well known for its role as a master regulator of CD4 lineage commitment in the thymus. Here, we report an unexpected and critical role of ThPOK as a multifaceted regulator of myeloid lineage commitment, differentiation and maturation. Using reporter and knockout mouse models combined with single-cell RNA-sequencing, progenitor transfer and colony assays, we show that ThPOK controls monocyte-dendritic cell versus granulocyte lineage production during homeostatic differentiation, and serves as a brake for neutrophil maturation in granulocyte lineage-specified cells through transcriptional regulation of lineage-specific transcription factors and RNA via altered messenger RNA splicing to reprogram intron retention., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
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- 2023
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47. [Combination strategies for checkpoint inhibition: Current practices and perspectives].
- Author
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Dussart C, Decaux-Tramoni B, Quesada S, Thomas QD, Benzerouale O, Nicolas E, and Fiteni F
- Subjects
- Humans, CTLA-4 Antigen, Immunotherapy methods, Tumor Microenvironment, Programmed Cell Death 1 Receptor, Melanoma drug therapy
- Abstract
T-cell checkpoint blockade therapies have revolutionized treatment protocols and prognosis in patients with cancer. Pointed out by the success of PD-1 (programmed cell death-1) plus CTLA-4 (cytotoxic-T-lymphocyte associated antigen 4) blockade in patients with melanoma, the perspective of new synergistic immunotherapy combinations seems to be an important opportunity to improve outcomes for patients. In this article, we first focus on immunotherapy combinations that have shown their efficiency and that are currently approved in solid tumors. Then, we present a summary of emerging targets with reported pre-clinical efficacy and currently evaluated through ongoing clinical trials and other immunomodulatory molecules in the tumor microenvironment., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
- Published
- 2023
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48. An osmium(II) methane complex: Elucidation of the methane coordination mode.
- Author
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Sempsrott PJ, Trinh BB, Lovitt CF, Capra NE, and Girolami GS
- Subjects
- Ligands, Metals, Osmium, Methane
- Abstract
The activation of inert C─H bonds by transition metals is of considerable industrial and academic interest, but important gaps remain in our understanding of this reaction. We report the first experimental determination of the structure of the simplest hydrocarbon, methane, when bound as a ligand to a homogenous transition metal species. We find that methane binds to the metal center in this system through a single M···H-C bridge; changes in the
1 JCH coupling constants indicate clearly that the structure of the methane ligand is significantly perturbed relative to the free molecule. These results are relevant to the development of better C─H functionalization catalysts.- Published
- 2023
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49. Rho-associated protein kinase 1 inhibition in hepatocytes attenuates nonalcoholic steatohepatitis.
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Dohnalkova E, Bayer RL, Guo Q, Bamidele AO, Kim Lee HS, Valenzuela-Pérez L, Krishnan A, Pavelko KD, Guisot NES, Bunyard P, Kim YB, Ibrahim SH, Gores GJ, and Hirsova P
- Subjects
- Animals, Humans, Mice, Diet, High-Fat adverse effects, Fibrosis, Hepatocytes metabolism, Inflammation drug therapy, Mice, Knockout, Non-alcoholic Fatty Liver Disease drug therapy, Non-alcoholic Fatty Liver Disease enzymology, rho-Associated Kinases antagonists & inhibitors, rho-Associated Kinases genetics
- Abstract
Background: NASH is the progressive form of NAFLD characterized by lipotoxicity, hepatocyte injury, tissue inflammation, and fibrosis. Previously, Rho-associated protein kinase (ROCK) 1 has been implicated in lipotoxic signaling in hepatocytes in vitro and high-fat diet-induced lipogenesis in vivo. However, whether ROCK1 plays a role in liver inflammation and fibrosis during NASH is unclear. Here, we hypothesized that pathogenic activation of ROCK1 promotes murine NASH pathogenesis., Methods and Results: Patients with NASH had increased hepatic ROCK1 expression compared with patients with fatty liver. Similarly, hepatic ROCK1 levels and activity were increased in mice with NASH induced by a western-like diet that is high in fat, fructose, and cholesterol (FFC). Hepatocyte-specific ROCK1 knockout mice on the FFC diet displayed a decrease in liver steatosis, hepatic cell death, liver inflammation, and fibrosis compared with littermate FFC-fed controls. Mechanistically, these effects were associated with a significant attenuation of myeloid cell recruitment. Interestingly, myeloid cell-specific ROCK1 deletion did not affect NASH development in FFC-fed mice. To explore the therapeutic opportunities, mice with established NASH received ROCKi, a novel small molecule kinase inhibitor of ROCK1/2, which preferentially accumulates in liver tissue. ROCK inhibitor treatment ameliorated insulin resistance and decreased liver injury, inflammation, and fibrosis., Conclusions: Genetic or pharmacologic inhibition of ROCK1 activity attenuates murine NASH, suggesting that ROCK1 may be a therapeutic target for treating human NASH., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)
- Published
- 2023
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50. GABA A receptor subunit modulation reversed electrophysiological network alterations after blast exposure in rat organotypic hippocampal slice cultures.
- Author
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Varghese N, Amelinez-Robles NE, and Morrison B 3rd
- Subjects
- Rats, Animals, Receptors, GABA-A, Hippocampus metabolism, Long-Term Potentiation physiology, Neurons metabolism, Brain Injuries, Traumatic metabolism, Blast Injuries complications
- Abstract
Throughout training and deployment, some military service members are frequently exposed to shock waves due to blasts, and some complain of myriad neurological symptoms. In rat organotypic hippocampal slice cultures (OHSCs), blast-induced traumatic brain injury (bTBI) causes deficits in some electrophysiological measures, like long term potentiation, a neuronal correlate for learning and memory. In this study, we further characterized the alterations in the hippocampal network of OHSCs following a single moderate blast exposure. Connectivity and clustering coefficients were reduced across the hippocampal network following bTBI, despite the lack of changes in the firing rate, spike amplitude, spike duration, or inter-spike interval. However, interrogation with the GABA
A receptor antagonist, bicuculline, revealed additional significant differences between injured and control slices in measures of spike amplitude, spike duration, connectivity, and clustering. bTBI also significantly reduced expression of the α1 and α5 GABAA receptor subunits. Treatment with the FDA-approved histone deacetylase inhibitor suberanilohydroxamic acid (SAHA) restored the α1 subunit and attenuated deficits in network measures, like connectivity and clustering coefficients. These findings suggest that GABAA receptors may be implicated in neuronal network changes in OHSCs following bTBI, and their recovery may be a viable therapeutic intervention to mitigate injury-induced neurological symptoms., Competing Interests: Declaration of Competing Interest No competing financial interests exist., (Copyright © 2023 Elsevier Inc. All rights reserved.)- Published
- 2023
- Full Text
- View/download PDF
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