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Oncostatin M (OSM) is a cytokine with the unique ability to interact with both the OSM receptor (OSMR) and the leukemia inhibitory factor receptor (LIFR). On the other hand, OSMR interacts with IL31RA to form the interleukin-31 receptor. This intricate network of cytokines and receptors makes it difficult to understand the specific function of OSM. While monoallelic loss-of-function (LoF) mutations in OSMR underlie autosomal dominant familial primary localized cutaneous amyloidosis, the in vivo consequences of human OSM deficiency have never been reported so far. Here, we identified three young individuals from a consanguineous family presenting with inherited severe bone marrow failure syndromes (IBMFS) characterized by profound anemia, thrombocytopenia, and neutropenia. Genetic analysis revealed a homozygous one base-pair insertion in the sequence of OSM associated with the disease. Structural and functional analyses showed that this variant causes a frameshift that replaces the C-terminal portion of OSM, which contains the FxxK motif that interacts with both OSMR and LIFR, with a neopeptide. The lack of detection and signaling of the mutant OSM suggests a LoF mutation. Analysis of zebrafish models further supported the role of the OSM/OSMR signaling in erythroid progenitor proliferation and neutrophil differentiation. Our study provides the previously uncharacterized and unexpectedly limited in vivo consequence of OSM deficiency in humans.

The response of ionic solutions to time-varying electric fields, quantified by a frequency-dependent conductivity, is essential in many electrochemical applications. Yet, it constitutes a challenging problem due to the combined effect of Coulombic interactions, hydrodynamics, and thermal fluctuations. Here, we study the frequency-dependent conductivity of ionic solutions using a stochastic density functional theory. In the limit of small concentrations, we recover the classical Debye and Falkenhagen (DF) result, predicting an increase in conductivity with field frequency. At higher concentrations, we use a modified Coulomb interaction potential that accounts for the hard-core repulsion between the ions, which was recently employed in the zero-frequency case. Consequently, we extend the DF result to concentrated electrolytes. We discuss experimental and numerical studies and the complexity of observing the DF effect in such setups., (© 2024 Author(s). All article content, except where otherwise noted, is licensed under a Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).)

When treating anterior and apical prolapse, laparoscopic sacral colpopexy is the gold standard. Currently, it is suggested that the anterior mesh must be the lowest possible to better treat the prolapse and lower the risk of recurrence. The objective of our study was to determine the possibility of using intraoperative transperineal ultrasound measurements during laparoscopic sacral colpopexy in order to better localize the mesh positioning. We conducted a prospective double-blinded single-center study where patients included had intraoperative ultrasounds by an independent ultrasonographer, un-informed of the surgeon's clinical observations. The postoperative measures were performed by another independent ultrasonographer, which was un-informed of the intraoperative measurements. A total of 16 patients were included. The anterior prosthesis was visualized in 81% of patients during laparoscopic sacral colpopexy and in all patients postoperatively. However, intraoperative measures and comparison between intraoperative and postoperative measures significantly varied. None of the patients included had a recurrence of prolapse. LEVEL OF EVIDENCE: 4., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Biological modelling helps understanding complex processes, like energy metabolism, by predicting pathway compensations and equilibrium under given conditions. When deciphering metabolic adaptations, traditional experiments face challenges due to numerous enzymatic activities, needing modelling to anticipate pathway behaviours and orientate research. This paper aims to implement a constraint-based modelling method of muscular energy metabolism, adaptable to individual situations, energy demands, and complex disease-specific metabolic alterations like muscular dystrophy calpainopathy. Our calpainopathy-like model not only confirms the ATP production defect under increasing energy demands, but suggests compensatory mechanisms through anaerobic glycolysis. However, excessive glycolysis indicates a need to enhance mitochondrial respiration, preventing excess lactate production common in several diseases. Our model suggests that moderate-intensity physiotherapy, known to improve aerobic performance and anaerobic buffering, combined with increased carbohydrate and amino acid sources, could be a potent therapeutic approach for calpainopathy., Competing Interests: 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., (© 2024 The Author(s).)

Background: Bereavement following suicide is a risk factor for major depression, post-traumatic stress disorder, suicidal behavior, the emergence of bipolar disorders and prolonged mourning. The scientific literature agrees on the need to deploy support services tailored to the specificities of post-suicide bereavement. Alinéa responds to these specificities with an early and proactive individual postvention program., Method: This article presents the process of co-designing Alinéa by involving participants who have been exposed to suicide either through the loss of a loved one or in the course of their work. This co-design led to the creation of a collaborative system for early, proactive professional intervention. The Alinéa program, design intervention objectives and protocol, are presented in this article., Discussion: The Alinéa system is committed to research and is developing different types of research: evaluative research, fundamental research and action research., 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 © 2024 Coquelin, Kopp-Bigault, Barinoil, Berrouiguet and Guarnaccia.)

Objectives: To assess the prevalence of non-utilization of dental care in Lebanon and associated socioeconomic factors and self-care behaviours., Methods: A nationwide, quantitative, survey-based study was conducted by trained interviewers with Lebanese residents aged ≥18 years between July and September 2019. Univariate analyses were performed using Pearson Chi Square test or the Fisher's exact test followed by a binary logistic regression using the SPSS Version 25., Results: Of the 1070 participants, 247 (23.1%) did not utilise any type of healthcare and 144/247 (58.3%) did not utilise dental care. The prevalence of non-utilization of dental care was estimated at 13.5%. Only 4.7% of the respondents consulted their dentist in the past year, among which 53% cited pain/emergencies as the reason for their consultation. Socioeconomic factors associated with the non-utilization of dental care were lack of social medical insurance (OR, 0.49 [95% CI, 0.31 to 0.79]) and long waiting time/patient time restriction (OR, 2.05 [95% CI, 1.26 to 3.35]). On the other hand, facilitators for utilization of dental care included ethical standards/personal qualities of the dentist (OR, 0.53 [95% CI, 0.32 to 0.88]) and convenient cost with respect to the individual's economic status (OR, 0.28 [95% CI, 0.18 to 0.43])., Conclusion: This study suggests that dental care practices in Lebanon, including the non-utilization of dental care, are suboptimal. Measures such as reducing sugar and tobacco consumption, providing information on oral hygiene, and using fluoride products are inexpensive; however, implementing these measures may take substantial time and input by multiple stakeholders., (© 2024 The Author(s). Community Dentistry and Oral Epidemiology published by John Wiley & Sons Ltd.)

Meiotic recombination is a key biological process in plant evolution and breeding, as it generates genetic diversity in each generation through the formation of crossovers (COs). However, due to their importance in genome stability, COs are highly regulated in frequency and distribution. We previously demonstrated that this strict regulation of COs can be modified, both in terms of CO frequency and distribution, in allotriploid Brassica hybrids (2n = 3x = 29; AAC) resulting from a cross between Brassica napus (2n = 4x = 38; AACC) and Brassica rapa (2n = 2x = 20; AA). Using the recently updated B. napus genome now including pericentromeres, we demonstrated that COs occur in these cold regions in allotriploids, as close as 375 kb from the centromere. Reverse transcription quantitative PCR (RT-qPCR) of various meiotic genes indicated that Class I COs are likely involved in the increased recombination frequency observed in allotriploids. We also demonstrated that this modified recombination landscape can be maintained via successive generations of allotriploidy (odd ploidy level). This deregulated meiotic behavior reverts to strict regulation in allotetraploid (even ploidy level) progeny in the second generation. Overall, we provide an easy way to manipulate tight recombination control in a polyploid crop., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Advances in Thyroid Pathology: WHO CLASSIFICATION 2022, BETHESDA SYSTEM 2023, MOLECULAR BIOLOGY AND MOLECULAR TESTING: Thyroid pathology has experienced significant advances with the publication of the 5th edition of the World Health Organization classification of endocrine tumors in 2022 and the third edition of the Bethesda system for thyroid cytopathology in 2023. At the same time, the availability of next-generation sequencing data coupled with numerous translational research projects have considerably increased our knowledge of the genomics and mechanics of thyroid cancers, enabling us to refine prognosis and propose new targeted therapies. In this review, we will take up the main new features of the WHO 2022 and Bethesda 2023 classifications, as well as molecular biology findings, with an emphasis on the practical implications for clinicians., Competing Interests: Liens d’intérêts S. Moog, M. Amine Bani, A. Al Ghuzlan et V. Suciu déclarent ne pas avoir de liens d’intérêts. L. Lamartina déclare des liens d’intérêts pour des financements pour participation à un congrès de la part des laboratoires AAA Novartis et Ipsen; pour participation à des tumor boards de la part des laboratoires Eisai et Ipsen; pour des honoraires perçus de la part des laboratoires Eisai, Lilly et Roche. Cet article fait partie du supplément Prise en charge des cancers thyroïdiens en 2024 : avancées diagnostiques et thérapeutiques réalisé avec le soutien institutionnel de Lilly., (Copyright © 2024 Elsevier Masson SAS. Tous droits réservés. Published by Elsevier Masson SAS. All rights reserved.)

Terminology in schistosomiasis is not harmonised, generating misunderstanding in data interpretation and clinical descriptions. This study aimed to achieve consensus on definitions of clinical aspects of schistosomiasis in migrants and returning travellers. We applied the Delphi method. Experts from institutions affiliated with GeoSentinel and TropNet, identified through clinical and scientific criteria, were invited to participate. Five external reviewers revised and pilot-tested the statements. Statements focusing on the definitions of acute or chronic; possible, probable, or confirmed; active; and complicated schistosomiasis were managed through REDCap and replies managed in a blinded manner. Round 1 mapped the definitions used by experts; subsequent rounds were done to reach consensus, or quantify disagreement, on the proposed statements. Data were analysed with percentages, medians, and IQRs of a 5-point Likert scale. The study was terminated on the basis of consensus or stability-related and time-related criteria. 28 clinicians and scientists met the criteria for experts. 25 (89%) of 28 experts replied to Round 1, 18 (64%) of 28 to Round 2, 19 (68%) of 28 to Round 3, and 21 (75%) of 28 to at least two rounds. High-level consensus (79-100% agreement and IQRs ≤1) was reached for all definitions. Consensus definitions will foster harmonised scientific and clinical communication and support future research and development of management guidelines for schistosomiasis., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Primary open-angle glaucoma (POAG), a leading cause of irreversible vision loss, is closely linked to increased intraocular pressure (IOP), with the trabecular meshwork (TM) playing a critical role in its regulation. The TM, located at the iridocorneal angle, acts as a sieve, filtering the aqueous humor from the eye into the collecting ducts, thus maintaining proper IOP levels. The transforming growth factor-beta 2 (TGF-β2) signaling pathway has been implicated in the pathophysiology of primary open-angle glaucoma POAG particularly, in the dysfunction of the TM. This study utilizes human TM explants to closely mimic in vivo conditions, thereby minimizing transcriptional changes that could arise from cell culture enabling an exploration of the transcriptomic impacts of TGF-β2. Through bulk RNA sequencing and immunohistological analysis, we identified distinct gene expression patterns and morphological changes induced by TGF-β2 exposure (5 ng/ml for 48 h). Bulk RNA sequencing identified significant upregulation in genes linked to extracellular matrix (ECM) regulation and fibrotic signaling. Immunohistological analysis further elucidated the morphological alterations, including cytoskeletal rearrangements and ECM deposition, providing a visual confirmation of the transcriptomic data. Notably, the enrichment analysis unveils TGF-β2's influence on both bone morphogenic protein (BMP) and Wnt signaling pathways, suggesting a complex interplay of molecular mechanisms contributing to TM dysfunction in glaucoma. This characterization of the transcriptomic modifications on an explant model of TM obtained under the effect of this profibrotic cytokine involved in glaucoma is crucial in order to develop and test new molecules that can block their signaling pathways., 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 Elsevier Inc. All rights reserved.)

Background: Right ventricle impairment (RVI) is common during acute respiratory distress syndrome (ARDS) in adults and children, possibly mediated by the level of transpulmonary pressure (P L ). We sought to investigate the impact of the level of P L on ARDS-associated right ventricle impairment (RVI)., Methods: Adults and children (> 72 h of life) were included in this two centers prospective study if they were ventilated for a new-onset ARDS or pediatric ARDS, without spontaneous breathing and contra-indication to esophageal catheter. Serial measures of static lung, chest wall, and respiratory mechanics were coupled to critical care echocardiography (CCE) for 3 days. Mixed-effect logistic regression models tested the impact of lung stress (ΔP L ) along with age, lung injury severity, and carbon dioxide partial pressure, on RVI using two definitions: acute cor pulmonale (ACP), and RV dysfunction (RVD). ACP was defined as a dilated RV with septal dyskinesia; RVD was defined as a composite criterion using tricuspid annular plane systolic excursion, S wave velocity, and fractional area change., Results: 46 patients were included (16 children, 30 adults) with 106 CCE (median of 2 CCE/patient). At day one, 19% of adults and 4/7 children > 1 year exhibited ACP, while 59% of adults and 44% of children exhibited RVD. In the entire population, ACP was present on 17/75 (23%) CCE. ACP was associated with an increased lung stress (mean ΔP L of 16.2 ± 6.6 cmH 2 O in ACP vs 11.3 ± 3.6 cmH 2 O, adjusted OR of 1.33, CI95% [1.11-1.59], p = 0.002) and being a child. RVD was present in 59/102 (58%) CCE and associated with lung stress. In children > 1 year, PEEP was significantly lower in case of ACP (9.3 [8.6; 10.0] cmH 2 O in ACP vs 15.0 [11.9; 16.3] cmH 2 O, p = 0.03)., Conclusion: Lung stress was associated with RVI in adults and children with ARDS, children being particularly susceptible to RVI. Trial registration Clinical trials identifier: NCT0418467., (© 2024. The Author(s).)

Background: Spinal manipulation (SM) has been claimed to change anatomy, either in structure or position, and that these changes may be the cause of clinical improvements. The aim of this systematic review was to evaluate and synthesise the peer-reviewed literature on the current evidence of anatomical changes in response to SM., Methods: The review was registered with PROSPERO (CRD42022304971) and reporting was guided by the standards of the PRISMA Statement. We searched Medline, Embase, CINAHL, AMED, Cochrane Library all databases, PEDro, and the Index to Chiropractic Literature from inception to 11 March 2022 and updated on 06 June 2023. Search terms included manipulation, adjustment, chiropractic, osteopathy, spine and spine-related structures. We included primary research studies that compared outcomes with and without SM regardless of study design. Manipulation was defined as high-velocity, low-amplitude thrust delivered by hand to the spine or directly related joints. Included studies objectively measured a potential change in an anatomical structure or in position. We developed a novel list of methodological quality items in addition to a short, customized list of risk of bias (RoB) items. We used quality and RoB items together to determine whether an article was credible or not credible. We sought differences in outcomes between SM and control groups for randomised controlled trials and crossover studies, and between pre- and post-SM outcomes for other study designs. We reported, in narrative form, whether there was a change or not., Results: The search retrieved 19,572 articles and 20 of those were included for review. Study topics included vertebral position (n = 3) facet joint space (n = 5), spinal stiffness (n = 3), resting muscle thickness (n = 6), intervertebral disc pressure (n = 1), myofascial hysteresis (n = 1), and further damage to already damaged arteries (n = 1). Eight articles were considered credible. The credible articles indicated that lumbar facet joint space increased and spinal stiffness decreased but that the resting muscle thickness did not change., Conclusion: We found few studies on this topic. However, there are two promising areas for future study: facet joint space and spinal stiffness. A research strategy should be developed with funding for high quality research centres., (© 2024. The Author(s).)

The high resolution Rydberg absorption spectrum of 2-butyne C4H6 recorded previously at the SOLEIL synchrotron facility has been interpreted using multichannel quantum defect theory (MQDT). The calculations are based on the continuum scattering calculations of Xu et al., J. Chem. Phys. 136, 154303 (2012) and of Jacovella et al., J. Phys. Chem. A 119, 12339 (2015) pertaining to the dipole-allowed excited state symmetries in absorption from the ground state. In contrast to the traditional approach of calculating low-lying electronic states first and then attempting to extend the calculations to ever higher energy, here the analysis proceeds through the extension of these detailed calculations of the electronic continuum scattering down into the discrete region of the spectrum. The continuum reaction matrices and dipole transition moments are adapted to the discrete Rydberg region via the use of an energy-modified formulation of MQDT theory and associated energy dependences of the quantum defects. The analysis reproduces more than 40 Rydberg states from n ≈ 10 down to the 3d and 4s levels with an rms error of better than 20 cm-1. These belong to five Rydberg series with three different molecular symmetries. While the approach predicts many additional series, most of these are calculated and observed to carry only little oscillator strength. The analysis shows that the Rydberg spectrum is dominated by the excitation of an e″ symmetry electron of fδ and gπ type, in line with what previous studies of the above-threshold shape resonance of 2-butyne have shown. The present study is intended to serve as an example showing how first principles continuum calculations may be useful for the interpretation of highly bound discrete states in a range that poses problems for the standard ab initio techniques. The quantitative treatment of the dipole absorption cross sections is deferred to a future paper., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Background: The plasma concentrations of acyl coenzyme A binding protein (ACBP, also known as diazepam-binding inhibitor, DBI, or 'endozepine') increase with age and obesity, two parameters that are also amongst the most important risk factors for cancer., Methods: We measured ACBP/DBI in the plasma from cancer-free individuals, high-risk patients like the carriers of TP53 or BRCA1/2 mutations, and non-syndromic healthy subjects who later developed cancer. In mice, the neutralization of ACBP/DBI was used in models of non-small cell lung cancer (NSCLC) and breast cancer development and as a combination treatment with chemoimmunotherapy (chemotherapy + PD-1 blockade) in the context of NSCLC and sarcomas. The anticancer T cell response upon ACBP/DBI neutralization was characterized by flow cytometry and single-cell RNA sequencing., Results: Circulating levels of ACBP/DBI were higher in patients with genetic cancer predisposition (BRCA1/2 or TP53 germline mutations) than in matched controls. In non-syndromic cases, high ACBP/DBI levels were predictive of future cancer development, and especially elevated in patients who later developed lung cancer. In preclinical models, ACBP/DBI neutralization slowed down breast cancer and NSCLC development and enhanced the efficacy of chemoimmunotherapy in NSCLC and sarcoma models. When combined with chemoimmunotherapy, the neutralizing monoclonal antibody against ACBP/DBI reduced the frequency of regulatory T cells in the tumor bed, modulated the immune checkpoint profile, and increased activation markers., Conclusion: These findings suggest that ACBP/DBI acts as an endogenous immune suppressor. We conclude that elevation of ACBP/DBI constitutes a risk factor for the development of cancer and that ACBP/DBI is an actionable target for improving cancer immunosurveillance., (© 2024. The Author(s).)

Objectives: We aimed to compare clinical spectrum and outcome between adults and children with Takayasu's arteritis (TAK) in a European population., Methods: We made a nationwide retrospective observational study between 1988 and 2019. All adult patients met the ACR diagnostic criteria for TAK and all children met the EULAR/PRINTO/PRES criteria for paediatric TAK., Results: We identified 46 children and 389 adults with TAK. The male to female ratio was 34/46 (0.74) in the paediatric group compared to 241/274 (0.88) in the adult group (P<0.05). Children presented with significantly more systemic symptoms; i.e., fever (P<0.05), fatigue (P<0.001), weight loss (P<0.001), abdominal pain (P<0.05), and myalgia (P<0.05) while adults had more upper limb claudication (P<0.01). Topography of the lesions differed significantly between the two groups: adults had more damage at the cerebral vasculature (P<0.01), upper and lower limbs (P<0.001) while children had more kidney lesions (P<0.05). Children TAK had more frequent (P<0.01) and higher (P<0.001) biological inflammation than adults. Children received higher dose-weight of corticosteroids (P=0.001) and less biotherapy (P<0.010) at diagnosis. Relapses (P<0.05) and death (8.6% vs 4.9%) were more frequent in children TAK than in adults., Conclusion: Paediatric TAK seems more severe than adult TAK. Therefore, paediatrics patients may require closer monitoring and systemic use of biological treatment., (Copyright © 2024 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder affecting motor neurons, with a typical lifespan of 3-5 years. Altered metabolism is a key feature of ALS that strongly influences prognosis, with an increase in whole-body energy expenditure and changes in skeletal muscle metabolism, including greater reliance on fat oxidation. Dyslipidemia has been described in ALS as part of the metabolic dysregulation, but its role in the pathophysiology of the disease remains controversial. Among the lipids, cholesterol is of particular interest as a vital component of cell membranes, playing a key role in signal transduction and mitochondrial function in muscle. The aim of this study was to investigate whether motor dysfunction in ALS might be associated with dysregulation of muscle cholesterol metabolism. We determined cholesterol content and analyzed the expression of key determinants of the cholesterol metabolism pathway in muscle biopsies from thirteen ALS patients and ten asymptomatic ALS-mutation gene carriers compared to sixteen controls. Using human control primary myotubes, we further investigated the potential contribution of cholesterol dyshomeostasis to reliance on mitochondrial fatty acid. We found that cholesterol accumulates in the skeletal muscle of ALS patients and that cholesterol overload significantly correlates with disease severity evaluated by the Revised ALS Functional Rating Scale. These defects are associated with overexpression of the genes of the lysosomal cholesterol transporters Niemann-Pick type C1 (NPC1) and 2 (NPC2), which are required for cholesterol transfer from late endosomes/lysosomes to cellular membranes. Most notably, a significant increase in NPC2 mRNA levels could be detected in muscle samples from asymptomatic ALS-mutation carriers, long before disease onset. We found that filipin-stained unesterified cholesterol accumulated in the lysosomal compartment in ALS muscle samples, suggesting dysfunction of the NPC1/2 system. Accordingly, we report here that experimental NPC1 inhibition or lysosomal pH alteration in human primary myotubes was sufficient to induce the overexpression of NPC1 and NPC2 mRNA. Finally, acute NPC1 inhibition in human control myotubes induced a shift towards a preferential use of fatty acids, thus reproducing the metabolic defect characteristic of ALS muscle. We conclude that cholesterol homeostasis is dysregulated in ALS muscle from the presymptomatic stage. Targeting NPC1/2 dysfunction may be a new therapeutic strategy for ALS to restore muscle energy metabolism and slow motor symptom progression., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Extracellular acyl-coenzyme A binding protein [ACBP encoded by diazepam binding inhibitor (DBI)] is a phylogenetically ancient appetite stimulator that is secreted in a nonconventional, autophagy-dependent fashion. Here, we show that low ACBP/DBI plasma concentrations are associated with poor prognosis in patients with anorexia nervosa, a frequent and often intractable eating disorder. In mice, anorexia induced by chronic restraint stress (CRS) is accompanied by a reduction in circulating ACBP/DBI concentrations. We engineered a chemical-genetic system for the secretion of ACBP/DBI through a biotin-activatable, autophagy-independent pathway. In transgenic mice expressing this system in hepatocytes, biotin-induced elevations in plasma ACBP/DBI concentrations prevented anorexia induced by CRS or chemotherapeutic agents including cisplatin, doxorubicin, and paclitaxel. ACBP/DBI reversed the CRS or cisplatin-induced increase in plasma lipocalin-2 concentrations and the hypothalamic activation of anorexigenic melanocortin 4 receptors, for which lipocalin-2 is an agonist. Daily intravenous injections of recombinant ACBP/DBI protein or subcutaneous implantation of osmotic pumps releasing recombinant ACBP/DBI mimicked the orexigenic effects of the chemical-genetic system. In conclusion, the supplementation of extracellular and peripheral ACBP/DBI might constitute a viable strategy for treating anorexia.

In the continuity of a previous jet-cooled rovibrational study of trans and cis conformers of 2-furfural in the mid-infrared region (700-1750 cm-1) [Chawananon et al., Molecules 28 (10), 4165 (2023)], the present work investigates the far-infrared spectroscopy of 2-furfural using a long path absorption cell coupled to a high-resolution Fourier transform spectrometer and synchrotron radiation at the AILES beamline of the SOLEIL synchrotron. Guided by anharmonic calculations, vibrational energy levels and excited-state rotational constants are sufficiently predictive for a complete assignment of all fundamental and combination bands up to 700 cm-1, as well as the rovibrational analysis of 4 (1) low-frequency modes of trans-(cis-)2-furfural. A global rovibrational simulation, including far-infrared rovibrational lines and microwave and millimeter-wave rotational lines assigned in a previous study [Motiyenko et al., J. Mol. Spectrosc., 244, 9 (2007)] provides a reliable set of ground- and excited-state rotational parameters involving ring torsion, bending, and ring puckering modes of 2-furfural. In a second step, a rovibrational analysis of several hot band sequences, mainly involving the lowest frequency ring CHO torsion mode, is carried out. Reliable values of some anharmonic coefficients are obtained experimentally and could serve as a benchmark for validating advanced anharmonic calculations related to these large amplitude motions of flexible molecules., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Introduction: The early diagnosis of histological kidney damage after lung transplantation (LT) is of paramount importance given the negative prognostic implications of kidney disease., Methods: Three pathologists analyzed all kidney biopsies (KBs) (N = 100) performed from 2010 to 2021 on lung transplant patients in 4 Paris transplantation centers., Results: The main indication for biopsy was chronic renal dysfunction (72% of patients). Biopsies were performed at a median of 26.3 months after transplantation and 15 months after a decline in estimated glomerular filtration rate (eGFR) or the onset of proteinuria. Biopsies revealed a wide spectrum of chronic lesions involving the glomerular, vascular, and tubulointerstitial compartments. The 4 most frequent final diagnoses, observed in 18% to 49% of biopsies, were arteriosclerosis, acute calcineurin inhibitor (CNI) toxicity, thrombotic microangiopathy (TMA) and acute tubular necrosis (ATN). TMA was significantly associated with a combination of mTOR inhibitors (mTORi) or CNIs with biological signs present in only 50% of patients. The eGFR was poorly correlated with most lesions, particularly percent glomerulosclerosis, and with the risk of end-stage renal disease (ESRD). Thirty-four patients progressed to ESRD at an average of 20.1 months after biopsy. Three factors were independently associated with the risk of ESRD: postoperative dialysis, proteinuria >3 g/g and percent glomerulosclerosis >4%., Conclusion: Given the great diversity of renal lesions observed in lung transplant recipients, early referral to nephrologists for KB should be considered for these patients when they present with signs of kidney disease., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Electrolyte disorders (ED) are common in patients with cancer and in most cases, the etiologies do not differ from the general population. They may also be induced by the cancer, its therapy or paraneoplastic syndromes. ED are associated with poor outcomes, increased morbidity and mortality in this population. Hyponatremia is the most common disorder, often multifactorial, iatrogenic or secondary to the syndrome of inappropriate antidiuretic hormone secretion, usually due to small cell lung cancer. More rarely, hyponatremia may reveal adrenal insufficiency. Hypokalemia is generally multifactorial and associated with other ED. Cisplatin and ifosfamide induce proximal tubulopathies with hypokalemia and/or hypophosphatemia. Hypomagnesemia is often iatrogenic, related to cisplatin or cetuximab, but can be prevented by supplementation. Hypercalcemia can impair life quality and be life-threatening in the most severe cases. Hypocalcemia is less common and often of iatrogenic origin. Finally, the tumor lysis syndrome is a diagnostic and therapeutic emergency that affects the prognosis of patients. Its incidence tends to increase in solid oncology, related to the improvement of therapies. Prevention and early diagnosis of ED are essential to optimize the overall management of patients with underlying cancer and cancer therapy. The aim of this review is to synthesize most frequent ED and their management., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Nephroprotection is a set of recommendations that aim to prevent the risks of acute and/or chronic renal failure and to limit the progression of renal failure towards an end stage. Nephroprotection is not limited to nephrology and applies to all patients at risk of renal failure. Cancer patients are particularly at risk of developing intrinsic and extrinsic renal failure, as well as the toxicity of specific treatments. However, they are poorly included in nephroprotection studies. Thus, current guidelines have not been adapted to these pathologies and oncology-specific comorbidities, such as malnutrition or prognosis, are often not taken into account. In this article, we review the established recommendations by transposing them to the cancer patient as a whole. In addition to the reminder of hygiene and dietary rules to control blood pressure and diabetes, we discuss the importance of therapeutic education, iatrogeny and treatment options to control renal failure in this context. The lack of clearly established data in cancer confirms the needs to strengthen links between oncologists, hematologists and nephrologists and reinforces the emergence of onco-nephrology as a new discipline., (Copyright © 2023 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Background: The therapeutic potential of relaxin for heart failure and renal disease in clinical trials is hampered by the short half-life of serelaxin. Optimization of fatty acid-acetylated single-chain peptide analogues of relaxin culminated in the design and synthesis of R2R01, a potent and selective RXFP1 agonist with subcutaneous bioavailability and extended half-life., Experimental Approach: Cellular assays and pharmacological models of RXFP1 activation were used to validate the potency and selectivity of R2R01. Increased renal blood flow was used as a translational marker of R2R01 activity. Human mastocytes (LAD2 cells) were used to study potential pseudo-allergic reactions and CD4+ T-cells to study immunogenicity. The pharmacokinetics of R2R01 were characterized in rats and minipigs., Key Results: In vitro, R2R01 had comparable potency and efficacy to relaxin as an agonist for human RXFP1. In vivo, subcutaneous administration of R2R01 increased heart rate and renal blood flow in normotensive and hypertensive rat and did not show evidence of tachyphylaxis. R2R01 also increased nipple length in rats, used as a chronic model of RXFP1 engagement. Pharmacokinetic studies showed that R2R01 has a significantly extended terminal half-life. The in vitro assays with LAD2 cells and CD4+ T-cells showed that R2R01 had low potential for pseudo-allergic and immunogenic reactions, respectively., Conclusion and Implications: R2R01 is a potent RXFP1 agonist with an extended half-life that increases renal blood flow in various settings including normotensive and hypertensive conditions. The preclinical efficacy and safety data supported clinical development of R2R01 as a potential new therapy for renal and cardiovascular diseases., (© 2024 British Pharmacological Society.)

Over the past decade our research has implemented a multimodal approach to human lymphopoiesis, combining clonal-scale mapping of lymphoid developmental architecture with the monitoring of dynamic changes in the pattern of lymphocyte generation across ontogeny. We propose that lymphopoiesis stems from founder populations of CD127/interleukin (IL)7R - or CD127/IL7R + early lymphoid progenitors (ELPs) polarized respectively toward the T-natural killer (NK)/innate lymphoid cell (ILC) or B lineages, arising from newly characterized CD117 lo multi-lymphoid progenitors (MLPs). Recent data on the lifelong lymphocyte dynamics of healthy donors suggest that, after birth, lymphopoiesis may become increasingly oriented toward the production of B lymphocytes. Stemming from this, we posit that there are three major developmental transitions, the first occurring during the neonatal period, the next at puberty, and the last during aging., Competing Interests: Declaration of interests The authors have no conflict of interest to declare., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We investigated the viability and influence of NH 4 OH post-synthetic treatment on the pore characteristics of geopolymers. Geopolymers are a class of materials with amorphous aluminosilicate three-dimensional frameworks, regarded as amorphous analogues of zeolites. Similar to zeolites, when geopolymers are used in catalysis or adsorption applications, post-synthetic treatments such as ion exchange with NH 4 + salts ( e.g. , NH 4 Cl and NH 4 NO 3 ) and desilication (using strong bases such as NaOH) are necessary to introduce active sites and modify their pore structure, respectively. Recently, it has been shown that treatment with NH 4 OH combines these two steps, in which acidic sites are introduced and the pore structures of zeolites are modified simultaneously. Considering the increasing interest in geopolymers in catalysis and adsorption applications, understanding the impact of such treatment on the structure of geopolymers is needed. Our diffuse reflectance infrared Fourier-transform spectra show that NH 4 + exchanges Na + in the geopolymer, and laser diffraction with scanning electron microscopy images show that the particle size of the powdered geopolymer decreases after NH 4 OH treatment. N 2 sorption isotherms and 129 Xe and 1 H NMR measurements revealed information about the changes in pore structures: micropores were larger than mesopores and inborn mesopores increased in diameter, thereby reducing the surface area to volume ratio. However, pore accessibility and pore connectivity were not altered by NH 4 OH treatment. Since solid-state NMR and X-ray fluorescence revealed desilication, these changes in particle size and pore characteristics are considered to be due to desilication caused by NH 4 OH treatment., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A simple, low-cost, and efficient device is proposed for the study of porous materials via NMR using small gas probes. Mainly built through additive manufacturing and being equipped with a radiofrequency solenoid microcoil, it only requires tiny quantities of sample and/or gas and is particularly suited for hyperpolarized xenon. The performances of this device have been accessed on a commercial sample of MCM-41 exhibiting multiporosity. Both the delivery mode of hyperpolarized xenon and the stopped-flow system are judged as efficient according to 2D 129 Xe self-diffusion and EXSY experiments.

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that commonly results from a high-calorie diet and sedentary lifestyle, leading to insulin resistance and glucose homeostasis perturbation. Physical activity is recommended as one first-line treatment in T2DM, but it leads to contrasted results. We hypothesized that, instead of applying standard exercise protocols, the prescription of personalized exercise programs specifically designed to reverse the potential metabolic alterations in skeletal muscle could result in better results., Methods: To test this hypothesis, we drew the metabolic signature of the fast-twitch quadriceps muscle, based on a combined unbiased NMR spectroscopy and RT-qPCR study, in several T2DM mouse models of different genetic background (129S1/SvImJ, C57Bl/6J), sex and aetiology (high-fat diet (HFD) or HFD/Streptozotocin (STZ) induction or transgenic MKR (FVB-Tg Ckm-IGF1R*K1003R)1Dlr/J) mice. Three selected mouse models with unique muscular metabolic signatures were submitted to three different swimming-based programs, designed to address each metabolic specificity., Results: We found that depending on the genetic background, the sex, and the mode of T2DM induction, specific muscular adaptations occurred, including depressed glycolysis associated with elevated PDK4 expression, shift to β-oxidation, or deregulation of amino-acid homeostasis. Interestingly, dedicated swimming-based exercises designed to restore specific metabolic alterations in muscle were found optimal in improving systemic T2DM hallmarks, including a significant reduction in insulin resistance, the improvement of glucose homeostasis, and a delay in sensorimotor function alterations., Conclusion: The muscle metabolism constitutes an important clue for the design of precision exercises with potential clinical implications for T2DM patients., (© 2024. The Author(s).)

Hot plasma is highly conductive in the direction parallel to a magnetic field. This often means that the electrical potential will be nearly constant along any given field line. When this is the case, the cross-field voltage drops in open-field-line magnetic confinement devices are limited by the tolerances of the solid materials wherever the field lines impinge on the plasma-facing components. To circumvent this voltage limitation, it is proposed to arrange large voltage drops in the interior of a device, but coexist with much smaller drops on the boundaries. To avoid prohibitively large dissipation requires both preventing substantial drift-flow shear within flux surfaces and preventing large parallel electric fields from driving large parallel currents. It is demonstrated here that both requirements can be met simultaneously, which opens up the possibility for magnetized plasma tolerating steady-state voltage drops far larger than what might be tolerated in material media., (© 2024. The Author(s).)

During high-intensity (HI) exercise, metabolic acidosis significantly impairs exercise performance. Increasing the body's buffering capacity through training and exogenous intake of alkalizing supplements may improve high-intensity performance. Manipulating water and diet intake may influence the acid-base balance. The aim of this study was to determine the effects of mineral water rich in bicarbonate ions (STY) or placebo water (PLA) on circulating biomarkers and anaerobic performance and to verify whether alkalizing (ALK) or acidizing (ACI) diet would modulate these effects. Twenty-four athletes, assigned either to ALK (n = 12) or ACI (n = 12) diet for four weeks, completed a 1-min rowing Wingate Test in a double-blind and randomized trial after one week of daily hydration (1.5 to 2L/d) with either STY or PLA. Blood samples were taken before and after each test, and urine samples were collected each week. Chronic consumption of bicarbonate-rich water significantly impacted resting urinary pH irrespective of alkalizing or acidizing dietary intake. STY induced a significant increase in blood pH, lactate, and HCO 3 - ion concentration post-exercise compared to PLA. Similar changes were observed when STY was associated with the ALK diet. In contrast, STY combined with the ACI diet only significantly affected urine pH and peak blood lactate compared to PLA (p < 0.05). No effect of bicarbonate-rich water was reported on anaerobic performance (p > 0.05). Our results suggest that consumption of bicarbonate-rich water alters acid-base balance during a warm-up and after HI exercise, could potentiate beneficial effects of an alkalizing diet on the acid-base balance after HI exercise, and reduces the acid load induced by an acidifying diet., Competing Interests: The authors declare no conflicts of interest, financial or otherwise. The results are presented honestly without fabrications, falsifications, or inappropriate data manipulation., (Copyright: © Academy of Physical Education in Katowice.)

Background: Hereditary transthyretin amyloidosis is a life-threatening autosomal dominant systemic disease due to pathogenic TTR variants (ATTRv), mostly affecting the peripheral nerves and heart. The disease is characterised by a combination of symptoms, organ involvement and histological amyloid deposition. The available disease-modifying ATTRv treatments (DMTs) are more effective if initiated early. Pathological nerve conduction studies (NCS) results are the cornerstone of large-fibre polyneuropathy diagnosis, but this anomaly occurs late in the disease. We investigated the utility of a multimodal neurological and cardiac evaluation for detecting early disease onset in ATTRv carriers., Methods: We retrospectively analysed a cohort of ATTRv carriers with normal NCS results regardless of symptoms. Multimodal denervation and infiltration evaluations included a clinical questionnaire (Lauria and New York Heart Association (NYHA)) and examination, intra-epidermal nerve fibre density assessment, autonomic assessment based on heart rate variability, Sudoscan, meta-iodo-benzyl-guanidine scintigraphy, cardiac biomarkers, echocardiography, MRI and searches for amyloidosis on skin biopsy and bone scintigraphy., Results: We included 130 ATTRv carriers (40.8% men, age: 43.6±13.5 years), with 18 amyloidogenic TTR gene mutations, the majority of which was the late-onset Val30Met variant (42.3%). Amyloidosis was detected in 16.9% of mutation carriers, including 9 (6.9%) with overt disease (Lauria>2 or NYHA>1) and 13 asymptomatic carriers (10%) with organ involvement (small-fibre neuropathy or cardiomyopathy). Most of these patients received DMT. Abnormal test results of unknown significance were obtained for 105 carriers (80.8%). Investigations were normal in only three carriers (2.3%)., Conclusions: Multimodal neurological and cardiac investigation of TTRv carriers is crucial for the early detection of ATTRv amyloidosis and initiation of DMT., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

To characterize the neonatal hemodynamic profiles in recipients born after twin-to-twin transfusion syndrome (TTTS) treated with fetoscopic selective laser coagulation (FSLC). Retrospective analysis during the first month of life of recipient twins. Of the 480 newborns born during an 11-year period, 138 recipient twins with prenatal FSLC were classified into four groups: no hemodynamic impairment (NoHI, n = 102, 74%), isolated high blood pressure (HighBP, n = 18, 13%), right ventricular outflow tract obstruction (RVOTO, n = 10, 7%), and cardiac failure (CF, n = 8, 6%). The time (median (IQR)) between FSLC and birth was significantly shorter in the HighBP (36 days (23-54)) and CF (44 days (18-54)) groups than in the RVOTO (91 days (68-112)) and NoHi (82 days (62-104)) groups (p < 0.001).     Conclusion: Four distinct and well-characterized groups of recipients were identified based on their hemodynamics. High blood pressure and heart failure occurred in approximately 20% of the infants and were associated with a time between laser coagulation and birth of less than 2 months. What is Known: • Twin-to-twin transfusion syndrome (TTTS) is characterized by a hemodynamic imbalance that leads to high fetal and neonatal mortality if left untreated. One-third of recipient twins born without prenatal fetoscopic laser coagulation (FSLC) develop a life-threatening cardiac failure. What is New: • Four distinct groups of recipient twins with prenatal FSLC have been identified based on their hemodynamics. High blood pressure and cardiac failure occurred in 20% of the infants and were associated with an interval between FSLC and birth of less than 2 months., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In a recent issue in Nature Cell Biology , Sung Min Son et al. unveil a novel layer in the regulation of the mTORC1/autophagy axis by EP300 which can undergo nucleocytoplasmic shuttling in response to alterations in nutrient availability. The study highlights that, in Hutchinson-Gilford progeria syndrome, overabundant cytoplasmic EP300 results in mTORC1 hyperactivation and impaired autophagy, potentially contributing to premature and accelerated aging., Competing Interests: Conflict of Interest: GK has been holding research contracts with Daiichi Sankyo, Eleor, Kaleido, Lytix Pharma, PharmaMar, Osasuna Therapeutics, Samsara Therapeutics, Sanofi, Tollys, and Vascage. GK is on the Board of Directors of the Bristol Myers Squibb Foundation France. GK is a scientific co-founder of everImmune, Osasuna Therapeutics, Samsara Therapeutics and Therafast Bio. GK is in the scientific advisory boards of Hevolution, Institut Servier, Longevity Vision Funds and Rejuveron Life Sciences. GK is the inventor of patents covering therapeutic targeting of aging, cancer, cystic fibrosis and metabolic disorders. GK's wife, Laurence Zitvogel, has held research contracts with Glaxo Smyth Kline, Incyte, Lytix, Kaleido, Innovate Pharma, Daiichi Sankyo, Pilege, Merus, Transgene, 9 m, Tusk and Roche, was on the on the Board of Directors of Transgene, is a cofounder of everImmune, and holds patents covering the treatment of cancer and the therapeutic manipulation of the microbiota. GK's brother, Romano Kroemer, was an employee of Sanofi and now consults for Boehringer-Ingelheim. The funders had no role in the design of the study; in the writing of the manuscript, or in the decision to publish the results., (Copyright: © 2024 Ferret et al.)