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Leydig cells produce hormones that are required for male development, fertility, and health. Two Leydig cell populations produce these hormones but at different times during development: fetal Leydig cells, which are active during fetal life, and adult Leydig cells, which are functional postnatally. Historically, our ability to understand the origin and function of Leydig cells has been made difficult by the lack of genetic models to exclusively target these cells. Taking advantage of the Leydig cell–exclusive expression pattern of the Insl3 gene, we used a CRISPR/Cas9 gene-editing strategy to knock-in iCre recombinase into the mouse Insl3 locus. To demonstrate the Leydig cell–exclusive nature of our iCre line, lineage-tracing experiments were performed by crossing Insl3 iCre mice with a Rosa26 LoxSTOPLox-TdTomato reporter. iCre activity was restricted to male offspring. TdTomato fluorescence was detected both in fetal and adult Leydig cells and colocalized with CYP17A1, a classic Leydig cell marker. Prior to birth, fluorescence was observed in fetal Leydig cells beginning at embryonic day 13.0. Fluorescence was also detected in adult Leydig cells starting at postnatal day 5 and continuing to the mature testis. Fluorescence was not detected in any other fetal or adult tissue examined, except for the unexpected finding that the adrenal cortex contains some Insl3 -expressing Leydig-like cells. Our Leydig cell–exclusive iCre line therefore constitutes an invaluable new tool to study not only the origin of Leydig cells but also to target genes that have been long-proposed to be important for the development and functioning of these critical endocrine cells. [ABSTRACT FROM AUTHOR]

The early immune kinetics after SARS-CoV-2 vaccination remain poorly understood, particularly among individuals with low-count monoclonal B-cell lymphocytosis (MBLlo). We investigated the cellular and humoral kinetics in the blood of 50 non-MBL healthy donors (HD) vs. 16 MBLlo subjects after SARS-CoV-2 vaccination, who were subclassified according to their history of previous exposure to SARS-CoV-2 into SARS-CoV-2 naïve and previously infected subjects. Overall, we found decreased neutrophil and lymphocyte counts at day +4 following each dose in non-MBL HD, together with an earlier and higher increase in plasma cell (PC) counts and SARS-CoV-2-specific antibody levels after the first vaccine in previously infected non-MBL HD. MBLlo subjects showed a similar profile, except for lower B-cell and higher PC counts after vaccination, and a trend towards a higher (but delayed) antibody response. In summary, we found different cell-kinetic profiles following vaccination in SARS-CoV-2 naïve vs. previously infected non-MBL HD (earlier PC and antibody responses in the latter group); additionally, MBLlo subjects had significantly lower B-cell and higher PC counts after vaccination, and a delayed SARS-CoV-2-specific antibody response. [ABSTRACT FROM AUTHOR]

Hop leaves, a by-product from hop cone harvesting, contain phenolic compounds of potential value for food or beverage applications. However, the abundant phenolics in hop leaves remain largely unquantified. This study quantified phenolics in hop leaves over two crop years, for three commercially significant varieties, at different developmental stages post-flowering. Ethanolic hop extracts were characterised using LC-ESI-qTOF-MS/MS and HPLC-DAD for the annotation and quantification of phenolics and bitter resins. Hop leaf phenolic profile exhibited considerable structural diversity, differing significantly from that of respective cones. Kaempferol/quercetin 3-O-glycosides and chlorogenic acids were the most abundant sub-groups with phenolic acids, procyanidins, prenylflavonoids and bitter resins also present. Phenolic profile was mainly variety-dependent with some crop year and developmental effects. Flavonol 3-O-glycosides were the main compounds driving varietal differences. Findings demonstrate the structural diversity and high concentrations of phenolic compounds in hop leaf extracts and their potential as a source of bioactives for valorisation., 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. Published by Elsevier Ltd.)

Contemporary neuroscience scientists are interested in dyslexia, a complicated brain neurodevelopmental disorder. This condition causes slow and imprecise word comprehension in 5%-17% of the global population across languages and cultures. People with dyslexia often discuss mental health. On the scalp, the EEG signal shows coordinated neural activity that synchronizes. The EEG signal accurately captures these cerebral activity fluctuations due to evolution and mental state. Using statistical approaches, this study will determine if EEG waves indicate sickness. For this, three measures are suggested. The first metric, power spectral density, shows signal frequency and power distribution. The second metric assesses the model's uncertainty or randomness, conveying signal information, using entropy. The third metric, the Kolmogorov-Smirnov Test, uses entropy-based measurements to identify distributions based on Kolmogorov complexity. Applying these measures to the overall EEG signal of the twenty students under study separated the seven students' information from the other thirteen.

Purpose: Although catheter-related infections are the leading cause of bloodstream infections in patients with sickle cell disease (SCD), data are scarce in adult patients. The objectives of the present study were to describe central-venous-catheter-related bloodstream infections in patients with SCD and identify risk factors., Methods: We conducted a retrospective, observational study of adult patients with SCD diagnosed with central-venous-catheter-related bloodstream infections between 2011 and 2023 in two SCD reference centres. Each patient with SCD and a bloodstream infection related to a totally implantable venous access port was matched with two control patients with SCD and an infection-free totally implantable venous access port., Results: Thirty-five (6.6%) of the 534 patients experienced a total of 69 central-venous-catheter-related bloodstream infections. Concomitant vaso-occlusive crises were observed for 81.2% of the infections. The 30-day mortality rate was 2.8%, and the infection recurrence rate was 45.7%. We observed 26 totally implantable venous access port-related bloodstream infections in 19 patients, with an incidence rate of 0.31 per 1000 catheter-days. After adjustment, the frequency of hospital admission for a vaso-occlusive crisis (odds ratio (OR) [95% confidence interval (CI)] = 1.6 [1.2-2.4]) and the presence of a psychiatric comorbidity (19.8 [4.0-148.1]) remained significantly associated with totally implantable venous access port-related bloodstream infections. Suboptimal antibiotic levels were observed in five (39%) of the 13 patients having undergone therapeutic drug monitoring. The treatment failed in four (80%) of the five patients, who presented with glomerular hyperfiltration., Conclusion: A central-venous-catheter-related bloodstream infection is a severe complication in adult patients with SCD and is associated with psychiatric comorbidities and severe SCD., Competing Interests: Declarations. Transparency declarations: None to declare. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: The Birmingham Orthopaedic Oncology Meeting (BOOM), held in January 2024, convened 309 delegates from 53 countries to discuss and refine 21 consensus statements on the optimal management of chondrosarcoma., Methods: With representation from Europe (43%; n = 133), North America (17%; n = 53), South America (16%; n = 49), Asia (13%; n = 40), Australasia (5%; n = 16), the Middle East (4%; n = 12), and Africa (2%; n = 6), the combined experience of treating bone sarcomas among attendees totalled approximately 30,000 cases annually, equivalent to 66 years of experience in the UK alone. The meeting's process began with the formation of a local organizing committee, regional leads, and a scientific committee comprising representatives from 150 specialist units across 47 countries. Supported by major orthopaedic oncology organizations, the meeting used a modified Delphi process to develop consensus statements through online questionnaires, thematic groupings, narrative reviews, and anonymous pre-meeting polling., Results: Strong (> 80%) consensus was achieved on 19 out of 21 statements, reflecting agreement among delegates. Key areas of consensus included the role of radiology in diagnosis and surveillance, the management of locally recurrent disease, and the treatment of dedifferentiated chondrosarcoma. Notably, there was agreement that routine chemotherapy has no role in chondrosarcoma treatment, and radiological surveillance is safe for intraosseous chondrosarcomas. Despite the overall consensus, areas of controversy remain, particularly regarding the treatment of atypical cartilage tumours and surgical margins. These unresolved issues underscore the need for further research and collaboration within the orthopaedic oncology community., Conclusion: BOOM represents the largest global consensus meeting in orthopaedic oncology, providing valuable guidance for clinicians managing chondrosarcoma worldwide. The consensus statements offer a reference for clinical practice, highlight key research priorities, and aim to improve patient outcomes on a global scale., Competing Interests: L. M. Jeys reports royalties or licenses from Implantcast, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Implantcast, Zimmer Biomet, and Stryker, and support for attending meetings and/or travel from Implantcast, all of which are unrelated to this study. G. V. Morris reports consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings and/or travel from Implantcast, all of which are unrelated to this study. E. Botello reports consulting fees, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events, and support for attending meetings and/or travel from Zimmer Biomet, all of which are unrelated to this study. R. A. Boyle reports payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events and support for attending meetings and/or travel from Zimmer Biomet, unrelated to this study. M. T. Houdek reports consulting fees from Link Orthopedics and Stryker, unrelated to this study. A. Puri is a member of the editorial board of The Bone & Joint Journal. P. Ruggieri reports consulting fees from Exactech and royalties or licenses from Stryker, unrelated to this study. M. Laitinen reports support for attending meetings and/or travel from Tree-Step, unrelated to this study., (© 2025 Jeys et al.)

Objective: Flow diversion is increasingly used as an endovascular treatment for intracranial aneurysms. FRED-EPI is a prospective, multicenter, French study, conducted to analyze the safety and efficacy of aneurysm treatment with FRED/FRED Jr (Microvention, AlisoViejo, CA, USA) in current clinical practice., Patients and Methods: Patients with intracranial aneurysms treated with FRED and FRED Jr who agreed to participate were prospectively and consecutively included in all French centers using these devices., Results: From June 2020 to January 2022, 135 patients (110 females, 81.5%, and 25 males, 18.5%) with 154 aneurysms were included in 13 French interventional neuroradiology centers. The mean age was 53.9 ± 12.2 years (range: 20 - 77 years). Aneurysm was unruptured in 123 cases (79.9%), ruptured in 4 cases (2.6%), and recanalized in 27 cases (17.5%). Most aneurysms were small (135/154, 87.7%). Aneurysm locations were supraclinoid ICA in 83 (53.9%), cavernous and petrous ICA in 25 (16.2%), anterior cerebral artery or anterior communicating artery in 19 (12.3%), MCA in 7 (4.5%), and posterior circulation in 20 (13.0%). Three patients (2.2%) had hemorrhagic complications (1 delayed aneurysm rupture and 2 delayed remote hematoma) and 3 (2.2%) ischemic complications (2 intrastent thrombosis and 1 stroke related to atherosclerosis) leading to 1-year morbimortality of 4.4%. Complete aneurysm occlusion was reported in 105/139 aneurysms (75.5%)., Conclusions: FRED-EPI confirms good safety of aneurysm treatment with FRED/FRED Jr in current clinical practice with 4.4% 1-year morbimortality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial or personal relationships that could be viewed as influencing the work reported in this paper. The authors declare the following financial or personal relationships that could be viewed as influencing the work reported in this paper:, (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Real-world data regarding patients with non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations receiving mobocertinib are limited. This study describes these patients' characteristics and outcomes., Methods: A chart review was conducted across three countries (Canada, France, and Hong Kong), abstracting data from eligible patients (NCT05207423). The inclusion criteria were: ≥ 18 years old; diagnosis of stage IIIB-IV NSCLC with EGFR ex20ins between January 1, 2017 and November 30, 2021; received mobocertinib. Data on demographics, clinical parameters, treatment patterns, mobocertinib exposure, real-world outcomes, and adverse events (AEs) were collected. Results are also reported by Asian/Non-Asian races., Results: Overall, 105 patients were enrolled (median [IQR] age at initial diagnosis: 64.0 years [56, 71]; women: 62.9%). The most common first-line of therapy (LoT) was chemotherapy; the most common second LoT was EGFR tyrosine kinase inhibitors. Most patients received mobocertinib during LoT two and three (74.3%); the maximum dose was 160 mg/day for 67.6% of the cohort (mean [SD] daily dose: 130.6 mg [36.68]). The median real-world progression-free survival (PFS) on mobocertinib was 4.76 months (95% CI: 3.98, 6.21). The overall response rate and disease control rate were 20.0% and 48.6%, respectively (median duration of response: 8.34 months [95% CI: 3.61, 9.49]). The median overall survival (OS) was 26.28 months (95% CI: 20.21, 36.44). Asian patients had numerically superior PFS and OS compared with non-Asian patients. Regarding safety analysis, 73 patients (69.5%) experienced any AE. The most common AE was diarrhea (any grade) (52 patients; 49.5%)., Conclusions: These data illustrate the real-world effectiveness of mobocertinib., (© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) describes liver diseases caused by the accumulation of triglycerides in hepatocytes (steatosis) as well as the resulting inflammation and fibrosis. Previous studies have demonstrated that accumulation of fat in visceral adipose tissue compartments and the liver is associated with alterations in the circulating levels of some amino acids, notably glutamate. This study aimed to investigate the associations between circulating amino acids, particularly glutamate, and MASLD. In addition, we hypothesized that liver steatosis, concomitant with visceral adiposity, could contribute to the association between circulating glutamate and visceral obesity. We studied a sample of 150 patients living with severe obesity who were non-diabetic and selected to represent a wide range of MASLD severity. Liver histological features were determined by a pathologist from a biopsy sample obtained at the time of bariatric surgery. Bulk RNA sequencing measured the hepatic mRNA expression level of selected genes related to the urea cycle and glutamate metabolism. Fasting plasma amino acid levels were measured by liquid chromatography coupled with tandem mass spectrometry. Patients with more advanced steatosis had larger visceral adipocytes, higher levels of circulating tyrosine, glutamate, and alanine as well as lower levels of serine. MASLD severity was significantly associated with the hepatic mRNA expression of glutamate metabolism genes such as GLS1, GLUL (positively), and NAGS (inversely). In individuals living with obesity, MASLD severity is associated with visceral adipocyte hypertrophy, higher circulating glutamate as well as potential alterations of hepatic amino acid and nitrogen metabolism., (© 2025 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background: Endoscopic submucosal dissection (ESD) is an advanced technique that can provide successful 'en-bloc' and R0 resection rate for large gastrointestinal lesions. To date, several ESD techniques have been proposed, but their comparative efficacy is still unclear., Methods: Major databases were systematically searched for RCTs comparing the efficacy and safety of different ESD techniques for the resection of colonic lesions. The primary outcomes were 'en-bloc' and R0 resection rates. The secondary outcome was the incidence of procedure-related AEs., Results: After selection of studies, 9 RCTs were included in the systematic review. On network meta-analysis for 'en-bloc' resection, pocked with traction ESD (PT-ESD) (RR=1.02; 95%CI=0.96-1.07) and pocket ESD (P-ESD) (RR=1.02; 95%CI=0.98-1.05) showed higher efficacy, whereas hybrid ESD (H-ESD) (RR=0.94; 95%CI=0.87-1.02) lower efficacy compared to conventional ESD (C-ESD). With regard to R0 resection, PT-ESD (RR=1.05; 95%CI=0.96-1.16) showed higher efficacy, and H-ESD (RR=0.97; 95%CI=0.84-1.13) lower efficacy compared to C-ESD. Concerning safety PT-ESD (RR=0.35; 95%CI=0.05-2.48) was associated with lower incidence of AEs, and H-ESD (RR=1.22; 95%CI=0.30-5.01) with higher incidence of AEs, compared to C-ESD., Conclusions: The results of this network meta-analysis show a trend towards greater effectiveness and safety of PT-ESD for the removal of colonic lesions. H-ESD was associated with worse results and should be reserved as a rescue treatment, preferring other techniques., Competing Interests: Conflict-of-interest JJ received consultation fees from Fujifilm, ERBE, Olympus and Pentax; RM received consultation fees from Fujifilm, ERBE, Olympus, Boston Scientific and Pentax; SS received consultation fees from Fujifilm, ERBE, Olympus and Boston Scientific. CH received consultation fees from Fujifilm and Medtronic. AR received consultation fees from Fujifilm, ERBE, Olympus, Boston Scientific and Pentax. RDM received consultation fees from Boston Scientific. All other authors have no proprietary, financial, professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in, or the review of this manuscript., (Copyright © 2025 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Introduction: Recent guidelines recommend the sentinel lymph node (SLN) technique in uterine cancers, as it is associated with lower perioperative complications. 1 Image-guided surgery can address some limitations of SLN procedures, such as low frozen-section accuracy and risk of empty packets, 2-4 by providing real-time lymph node assessment. 5,6 This video describes the surgical procedure of intraoperative robotic ultrasound examination for SLN assessment., Materials and Methods: The Arietta L43K (2-12 MHz, Hitachi, Japan) drop-in robotic ultrasound probe was used to assist with SLN dissection. The procedure was performed on the da Vinci Xi platform. The probe, introduced through an accessory trocar, was manipulated by robotic instruments, providing real-time ultrasound imaging in split-view mode on the surgeon's console. Ultrasound images, captured by the surgeon under the guidance of an experienced ultrasound examiner, were analyzed both in vivo and ex vivo. 7 RESULTS: The procedure involves ten steps, detailed as follows. (1) The procedure begins with the cervical injection of indocyanine green. (2) The pelvic retroperitoneum is opened to allow access to anatomical landmarks. (3) Using near-infrared imaging mode, the lymphatic pathways are highlighted, allowing for the identification of the SLN. (4) Once identified, the drop-in ultrasound probe is introduced. (5) The console is switched to split-view mode, enabling the surgeon to observe ultrasound images alongside the endoscopic view. (6) In vivo imaging is conducted. (7) Both images and videos of the lymph node are captured. (8) The SLN is subsequently dissected. (9) SLN specimens are safely extracted. (10) Ex vivo ultrasound assessment is performed to further evaluate their characteristics., Conclusions: Although its accuracy compared with histology as the gold standard is yet to be demonstrated, image-guided robotic lymph node ultrasound is a feasible and promising procedure for real-time SLN assessment. A prospective study is ongoing (R-LYNUS, NCT06621823) to clinically validate this technique., (© 2025. The Author(s).)

Objective: To create a novel, more advanced in vitro model of human endometrium, using so-called assembloids, looking to explore endometrial receptivity in adenomyosis., Design: Evaluation of assembloid responsiveness to hormonal stimulation by immunohistochemistry, enzyme-linked immunosorbent assay, and scanning electron microscopy., Subjects: Twelve women, six of whom were affected by adenomyosis., Exposure: Organoids (in the form of glandular fragments) and stromal fibroblasts were collected from endometrial biopsies. The two populations were combined inside an extracellular matrix to create 3D assembloids, which were then exposed to hormonal stimulation (β-estradiol for 48 hours, followed by β-estradiol/progesterone/cyclic adenosine monophosphate for 72 hours) to mimic the window of implantation., Main Outcome Measure(s): Glycodelin, leukemia inhibitory factor (LIF), and homeobox A10 (HOXA10) expression, prolactin secretion, and pinopode development., Result(s): Endometrial organoids and stromal cells were successfully isolated from women with and without adenomyosis and combined to generate the assembloid model. On stimulation, assembloids from both groups acquired a more secretory phase-like phenotype, as demonstrated by histology, and were shown to be positive for glycodelin, LIF, and HOXA10 by immunohistochemistry. Adenomyotic assembloids expressed significantly lower levels of LIF and HOXA10 within the stromal compartment after stimulation than did healthy assembloids in the same condition. Enzyme-linked immunosorbent assay revealed prolactin secretion in vitro, showing an upward trend in hormonally treated assembloids from both healthy and affected women. By scanning electron microscopy, fully formed pinopodes were discerned on the epithelial surface of healthy assembloids after stimulation, but they were absent in case of adenomyosis., Conclusion(s): Primary assembloids can be generated from endometrial biopsies from both healthy subjects and women affected by adenomyosis. These assembloids are amenable to hormonal stimulation and mimic secretory phase-specific characteristics of endometrial tissue in vivo, including glycodelin, LIF, and HOXA10 expression, and pinopode formation. Assembloids from adenomyosis appear to be less sensitive to hormonal treatment, showing reduced expression of LIF and HOXA10 in the stromal compartment and failing to form pinopodes. All in all, endometrial assembloids may serve as an advanced preclinical model of adenomyosis-related impaired endometrial receptivity, opening up new horizons in understanding and treating the condition., Competing Interests: Declaration of Interests C.A.S. has nothing to disclose. M.R. has nothing to disclose. C.B. has nothing to disclose. M.Z. has nothing to disclose. A.C. has nothing to disclose. J.D. has nothing to disclose. M.-M.D. has nothing to disclose., (Copyright © 2024 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)

Introduction: This study aimed to evaluate the agreement between the proteinuria/creatinuria (P/C) ratio and the traditional 24-hour proteinuria measurement for proteinuria levels above 3 g/24h in pregnant patients with preeclampsia. Additionally, we assessed whether high levels of each measurement are predictive of adverse maternal and neonatal outcomes., Material and Methods: We conducted a monocentric retrospective study of pregnant patients hospitalized for preeclampsia between January 1, 2019, and November 11, 2020. The primary outcome was a composite measure of adverse maternal outcomes associated with preeclampsia, and the secondary outcome focused on adverse neonatal outcomes. Agreement between high levels of 24-hour proteinuria and the P/C ratio was evaluated using Cohen's Kappa. Maternal and neonatal outcomes were compared across three groups: those with neither, one, or both high proteinuria levels (24-hour proteinuria ≥ 3 g/24h and/or P/C ratio ≥ 300 mg/mmol). Logistic regression, adjusted for confounders, analyzed associations between measures and outcomes, with ROC curves and AUC calculated for predictive models., Results: We found a strong correlation between 24-hour proteinuria and P/C ratio, with 95.1% agreement at the threshold of 3 g/24h and 300 mg/mmol, respectively (Kappa = 0.87, p < 0.01). Both measurements were associated with an increased risk of adverse maternal (aOR 6.78 [2.47-18.63]) and neonatal (aOR 7.00 [1.56-31.31]) outcomes., Discussion: This study demonstrated a strong agreement between the P/C ratio ≥ 300 mg/mmol and 24-hour proteinuria ≥ 3 g/24h, both associated with an increased risk of adverse perinatal outcomes, with the P/C ratio offering a quicker, simpler alternative for managing preeclampsia., Competing Interests: Declaration of competing interest This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., (Copyright © 2024. Published by Elsevier Masson SAS.)

Patients with idiopathic hypersomnia frequently report having unrefreshing naps. However, whether they have abnormal sleep architecture during naps that may explain their unrefreshing aspect is unknown. We compared sleep architecture during short daytime naps in patients with idiopathic hypersomnia reporting unrefreshing and refreshing naps. One-hundred and thirty-four patients tested with one-night polysomnography, followed by an adapted version of the Multiple Sleep Latency Test with four naps, were included. They were asked about the refreshing aspect of their habitual naps during a clinical interview. They were classified as having objective (Multiple Sleep Latency Test ≤ 8 min) or subjective idiopathic hypersomnia (Multiple Sleep Latency Test > 8 min), and as presenting refreshing or unrefreshing naps. We tested Group differences (refreshing versus unrefreshing naps) on nap sleep architecture in the whole sample and for subjective and objective idiopathic hypersomnia subgroups separately using ANCOVAs. No Group effects were observed in the Multiple Sleep Latency Test architecture in the whole sample and in objective and subjective idiopathic hypersomnia subgroups. This study provides preliminary evidence that reporting unrefreshing naps is not associated with clinically significant findings in Multiple Sleep Latency Test sleep architecture in patients with idiopathic hypersomnia. Given that naps taken by patients with idiopathic hypersomnia are typically long, future studies should investigate longer daytime sleep episodes., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Objective: The aim of the study is to investigate the effectiveness of an 8-wk cardiopulmonary rehabilitation program on cardiorespiratory fitness (VO 2 peak) and key cardiopulmonary exercise test measures, quality of life, and symptom burden in individuals with long COVID., Design: Forty individuals with long COVID (mean age 53 ± 11 yrs), were randomized into two groups: (1) rehabilitation group: center-based individualized clinical rehabilitation program (8 wks, 3 sessions per week of aerobic and resistance exercises, and daily inspiratory muscle training) and (2) control group: individuals maintained their daily habits during an 8-wk period., Results: There was a significant difference between groups in mean VO 2 peak improvement ( P = 0.003). VO 2 peak improved significantly in the rehab group (+2.7 mL.kg.min; 95% CI = +1.6 to +3.8; P < 0.001) compared to the control group (+0.3 mL.kg.min; 95% CI = -0.8 to +1.3 P = 0.596), along with VE/VCO 2 slope ( P = 0.032) (-2.4; 95% CI = -4.8 to +0.01; P = 0.049 and +1.3; 95% CI = -1.0 to +3.6; P = 0.272, respectively) and VO 2 at first ventilatory threshold ( P = 0.045). Furthermore, all symptom impact scales improved significantly in the rehabilitation group compared to the control group ( P < 0.05)., Conclusions: An individualized and supervised cardiopulmonary rehabilitation program was effective in improving cardiorespiratory fitness, ventilatory efficiency, and symptom burden in individuals with long COVID. Careful monitoring of symptoms is important to appropriately tailor and adjust rehabilitation sessions., Competing Interests: Financial disclosure statements have been obtained, and no conflicts of interest have been reported by the authors or by any individuals in control of the content of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Rhodolith beds are diverse and globally distributed habitats. Nonetheless, the role of rhodoliths in structuring the associated species community through a hierarchy of positive interactions is yet to be recognised. In this review, we provide evidence that rhodoliths can function as foundation species of multi-level facilitation cascades and, hence, are fundamental for the persistence of hierarchically structured communities within coastal oceans. Rhodoliths generate facilitation cascades by buffering physical stress, reducing consumer pressure and enhancing resource availability. Due to large variations in their shape, size and density, a single rhodolith bed can support multiple taxonomically distant and architecturally distinct habitat-forming species, such as primary producers, sponges or bivalves, thus encompassing a broad range of functional traits and providing a wealth of secondary microhabitat and food resources. In addition, rhodoliths are often mobile, and thus can redistribute associated species, potentially expanding the distribution of species with short-distance dispersal abilities. Key knowledge gaps we have identified include: the experimental assessment of the role of rhodoliths as basal facilitators; the length and temporal stability of facilitation cascades; variations in species interactions within cascades across environmental gradients; and the role of rhodolith beds as climate refugia. Addressing these research priorities will allow the development of evidence-based policy decisions and elevate rhodolith beds within marine conservation strategies., (© 2024 The Author(s). Biological Reviews published by John Wiley & Sons Ltd on behalf of Cambridge Philosophical Society.)

Efforts to produce adoptive cell therapies in AML have been largely unfruitful, despite the success seen in lymphoid malignancies. Identifying targetable antigens on leukemic cells that are absent on normal progenitor cells remains a major obstacle, as is the hostile tumor microenvironment created by AML blasts. In this review, we summarize the challenges in the development of adoptive cell therapies such as CAR-T, CAR-NK, and TCR-T cells in AML, discussing both autologous and allogeneic therapies. We also discuss methods to address myelotoxicity associated with these therapies, including rapidly switchable CAR platforms and CRISPR-Cas9 genetic engineering of hematopoietic stem cells. Finally, we present the current clinical landscape in these areas, along with future directions in the field.

Objective: Computing the trajectories of mandibular condyles directly from MRI could provide a comprehensive examination, providing both anatomical and kinematic details. This study aimed to investigate the feasibility of extracting 3D condylar trajectories from 2D real-time MRI., Materials and Methods: Twenty healthy subjects underwent real-time MRI while performing jaw opening and closing movements. One axial and two sagittal slices were segmented using a U-Net-based algorithm. After motion compensation, the centers of mass of the resulting masks were projected onto the coordinate system based on anatomical markers and temporally adjusted. The quality of the computed trajectories was evaluated using metrics designed to estimate movement reproducibility, head motion, and slice placement symmetry., Results: The segmentation of the axial slices demonstrated good-to-excellent quality; however, the segmentation of the sagittal slices required some fine-tuning. On average, the intercuspal position shifted by 0.6 mm after an opening-closing cycle. The difference in the superior-inferior coordinate of the condyles in the intercuspal position was 1.5 mm on average. Some subjects demonstrated a significant discrepancy between the axial and the sagittal trajectories., Discussion: Real-time MRI enables the extraction of condylar trajectories for evaluating some clinically relevant parameters. However, attention is required during patient installation and image acquisition., Competing Interests: Declarations. Conflict of interest: The authors have no relevant financial or non-financial interests to disclose. Ethical approval: The data were acquired under two approved ethical protocols: “METHODO” (ClinicalTrials.gov Identifier: NCT02887053, approval: CPP EST-III, 08.10.01) and its successor “EDEN” (ClinicalTrials.gov Identifier: NCT05218460, approval: CPP SUD-EST IV, 26.07.21). This study was performed in line with the principles of the Declaration of Helsinki. The sponsor of this study was the CHRU de Nancy (Department of Methodology, Promotion, Investigation—MPI). Informed consent: All the participants provided written informed consent., (© 2024. The Author(s), under exclusive licence to European Society for Magnetic Resonance in Medicine and Biology (ESMRMB).)

Introduction: Exertional rhabdomyolysis (ER) is the breakdown of muscle cells that occurs after intensive physical activity. Although a cautious and gradual return to physical activity (RTPA) is recommended after an episode of ER, physical sequelae are reported long afterwards., Case Report: We present the case of a 31-year-old untrained amateur runner with no prior medical history who developed heat stroke, ER, and acute kidney failure on the occasion of a half-marathon. Three months later, whereas the patient was symptom-free and CK levels were normal, an MRI revealed typical signs of rhabdomyolysis, which normalized thereafter., Discussion: Given that clinical and biological data inform RTPA decisions, the delay between clinical biological and MRI normalization may cause an RTPA to be initiated prior to full muscle recovery, which could account for the symptoms' prolonged persistence. In sportspeople who have recovered and their CK blood levels are returned to normal, MRI data could defer the RTPA if MRI abnormalities persist or, conversely, give it the green light.

Background: In pancreatic ductal adenocarcinoma (PDAC), the dense stroma rich in cancer-associated fibroblasts (CAFs) and the immunosuppressive microenvironment confer resistance to treatments. To overcome such resistance, we tested the combination of FOLFIRINOX (DNA damage-inducing chemotherapy drugs) with VE-822 (an ataxia-telangiectasia and RAD3-related inhibitor that targets DNA damage repair)., Methods: PDAC spheroid models and organoids were used to assess the combination effects. Tumour growth and the immune and fibrotic microenvironment were evaluated by immunohistochemistry, single-cell analysis and spatial proteomics in patient-derived xenograft (PDX) and orthotopic immunocompetent KPC mouse models., Results: The FOLFIRINOX and VE-822 combination had a strong synergistic effect in several PDAC cell lines, whatever their BRCA1, BRCA2 and ATM mutation status and resistance to standard chemotherapy agents. This was associated with high DNA damage and inhibition of DNA repair signalling pathways, leading to increased apoptosis. In immunocompetent and PDX mouse models of PDAC, the combination inhibited tumour growth more effectively than FOLFIRINOX alone. This was associated with tumour microenvironment remodelling, particularly decreased proportion of fibroblast activated protein-positive CAFs and increased anti-tumorigenic immune cell infiltration and interaction., Conclusion: The FOLFIRINOX and VE-822 combination is a promising strategy to improve FOLFIRINOX efficacy and overcome drug resistance in PDAC., Competing Interests: Competing interests: The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Introduction: Vaginal approaches have become routine in the field of gynecologic surgery, whereas in general surgery vaginal wall transection is an infrequent practice typically reserved for extensive tumor resections. Approximately two decades ago, natural orifice transluminal endoscopic surgery (NOTES) revolutionized conventional boundaries by accessing the peritoneal cavity transorally, transrectally, or transvaginally, enabling general surgery without visible scars. Although transvaginal approaches have been successfully used for various abdominal procedures by general surgeons, a gap remains in comprehensive training to fully exploit the potential of this route., Material and Methods: PubMed, Google Scholar, and Scopus databases were searched to retrieve relevant articles illustrating how general surgeons can adeptly manage vaginal approaches., Results: The article presents a practical framework for general surgeons to execute a complete vaginal approach, addressing the management of vaginal specimen extraction and vaginal cuff closure, even in the absence of an experienced gynecologist., Conclusion: The evolution of abdominal surgery is moving towards less invasive techniques, emphasizing the importance of understanding the nuances and challenges associated with the vaginal route. This approach is linked to minimal oncological, sexual, and infective complications, and to the absence of pregnancy-related complications. Such knowledge becomes increasingly crucial, particularly with the renewed demand for transvaginal access in robot-assisted NOTES procedures.

Significance: Intraoperative optical imaging is a localization technique for the functional areas of the human brain cortex during neurosurgical procedures. These areas can be assessed by monitoring cerebral hemodynamics and metabolism. Robust quantification of these biomarkers is complicated to perform during neurosurgery due to the critical context of the operating room. In actual devices, the inhomogeneities of the optical properties of the exposed brain cortex are poorly taken into consideration, which introduce quantification errors of biomarkers of brain functionality. Moreover, the best choice of spectral configuration is still based on an empirical approach., Aim: We propose a digital instrument simulator to optimize the development of hyperspectral systems for intraoperative brain mapping studies. This simulator can provide realistic modeling of the cerebral cortex and the identification of the optimal wavelengths to monitor cerebral hemodynamics (oxygenated HbO 2 and deoxygenated hemoglobin Hb) and metabolism (oxidized state of cytochromes b and c and cytochrome-c-oxidase oxCytb, oxCytc, and oxCCO)., Approach: The digital instrument simulator is computed with white Monte Carlo simulations of a volume created from a real image of exposed cortex. We developed an optimization procedure based on a genetic algorithm to identify the best wavelength combinations in the visible and near-infrared range to quantify concentration changes in HbO 2 , Hb, oxCCO, and the oxidized state of cytochrome b and c (oxCytb and oxCytc)., Results: The digital instrument allows the modeling of intensity maps collected by a camera sensor as well as images of path length to take into account the inhomogeneities of the optical properties. The optimization procedure helps to identify the best wavelength combination of 18 wavelengths that reduces the quantification errors in HbO 2 , Hb, and oxCCO by 47%, 57%, and 57%, respectively, compared with the gold standard of 121 wavelengths between 780 and 900 nm. The optimization procedure does not help to resolve changes in cytochrome b and c in a significant way but helps to better resolve oxCCO changes., Conclusions: We proposed a digital instrument simulator to optimize the development of hyperspectral systems for intraoperative brain mapping studies. This digital instrument simulator and this optimization framework could be used to optimize the design of hyperspectral imaging devices., (© 2024 The Authors.)

Purpose: To evaluate the outcomes of resin-based yttrium-90 ( 90 Y) transarterial radioembolization (TARE) for hepatocellular carcinoma (HCC) as a bridging or downstaging therapy to liver transplantation (LT) in terms of safety, tumor response, recurrence, and survival., Materials and Methods: A single-center retrospective analysis of patients with HCC treated with resin-based TARE as bridging or downstaging treatment to LT between January 2006 and April 2021 was performed. TARE-related liver toxicity was assessed. Imaging data were analyzed to assess tumor response. Histopathological analysis of explant livers was performed to assess HCC necrosis. Survival and bridging/downstaging success predictor analysis was performed., Results: Thirty-six patients underwent resin-based TARE with the intention to bridge (33%) or downstage (67%) to LT. Overall, 44% had ≥3 HCC lesions, and 53% had bilobar disease. Median largest tumor diameter was 3.4 cm. TARE was segmental, lobar, and bilobar in 20%, 36%, and 44% of cases, respectively. In total, 17% had Grade 3 bilirubin toxicities. The objective response rate per modified Response Evaluation Criteria in Solid Tumours was 72%. Patients meeting the United Network for Organ Sharing Downstaging criteria had higher chances of successful bridging/downstaging. Twenty-three patients were transplanted. Complete pathological response was noted in 30% of explant livers. Posttransplant tumor recurrence occurred in 26% within a median follow-up period of 1,710 days. Estimated 5-year progression-free, disease-specific, and overall survival rates after LT were 89%, 69%, and 89%, respectively. For the entire patient cohort, these survival rates were 87%, 53%, and 70%, respectively., Conclusions: Resin-based 90 Y TARE can be considered a valuable treatment option for bridging or downstaging patients with HCC to LT, including patients requiring lobar or bilobar TARE for extensive tumoral disease., (Copyright © 2024 SIR. Published by Elsevier Inc. All rights reserved.)

The observation decades ago that inflammatory injuries because of an alloimmune response might be present even in the absence of concomitant clinical impairment in allograft function conduced to the later definition of subclinical rejection. Many studies have investigated the different subclinical rejections defined according to the Banff classification (subclinical T cell-mediated rejection and antibody-mediated rejection), overall concluding that these episodes worsened long-term allograft function and survival. These observations led several transplant teams to perform systematic protocolar biopsies to anticipate treatment of rejection episodes and possibly prevent allograft loss. Paradoxically, the invasive characteristics and associated logistics of such procedures paved the way to investigate noninvasive biomarkers (urine and blood) of subclinical rejection. Among them, several research teams proposed a blood gene signature developed from cohort studies, most of which achieved excellent predictive values for the occurrence of subclinical rejection, mainly antibody-mediated rejection. Interestingly, although all identified genes relate to immune subsets and pathways involved in rejection pathophysiology, very few transcripts are shared among these sets of genes, highlighting the heterogenicity of such episodes and the difficult but mandatory need for external validation of such tools. Beyond this, their application and value in clinical practice remain to be definitively demonstrated in both biopsy avoidance and prevention of clinical rejection episodes. Their combination with other biomarkers, either epidemiological or biological, could contribute to a more accurate picture of a patient's risk of rejection and guide clinicians in the follow-up of kidney transplant recipients., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

The infant flours produced in Burkina Faso are essentially a mixture of cereals and legumes. These raw materials are frequently contaminated with mycotoxins which pose a huge food safety and public health threat. The objective of this study was to determine mycotoxin levels in raw materials and infant flours in Ouagadougou and to investigate the impact of decontamination on the raw materials used in infant flour production. A total of 22 cereals and 17 legumes as raw materials and 26 infant flour samples were analysed for aflatoxins, fumonisin B 1 (FB 1 ), and ochratoxin A (OTA) by liquid chromatography coupled to tandem mass spectrometry, while saline treatment and hand-sorting of grains in mycotoxin reduction were tested. All the samples of raw materials and infant flours were contaminated with aflatoxins, whereas 20.5% and 38.5% of raw materials and 57.7% and 61.5% of infant flours, respectively, were contaminated by FB 1 and OTA. These decontamination assays significantly reduced the levels of mycotoxins. AFB 1 was reduced by 48% after soaking of maize for 6 h in a 6% NaCl solution. Sorting resulted in a 92% reduction in AFB 1 content in peanut. However, soaking in saline solution did not reduce the FB 1 and OTA contents. Sorting did not also reduce FB 1 contents in peanut. Sorting and soaking in 6% saline solution for 6 h are production processes that lead to a reduction in the level of contamination by aflatoxins in maize and peanut used as raw materials for infant flour production., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests., (© 2024. The Author(s) under exclusive licence to Society for Mycotoxin (Research Gesellschaft für Mykotoxinforschung e.V.) and Springer-Verlag GmbH Germany, part of Springer Nature.)

The Ghent Altarpiece, a jewel of Gothic art painted by the van Eyck brothers in the fifteenth century, is particularly noteworthy for its use of an innovative dilution of oil, giving it a realistic scope that is particularly conducive to iconodiagnostic hypotheses. For the first time in the literature, we are taking a medical look at this masterpiece, and more specifically at the representation of its patron, whose identity is well known: Joos Vijd, a powerful notable from the town of Ghent, in modern-day Belgium. A vascular turgidity of the temporal artery, which can be suggestive of temporal arteritis, Hertoghe's sign and a slight ear crease were observed. These signs might be vascular lesions accentuated by Vijd's age and attest to van Eyck's virtuosity and anatomic accuracy., Competing Interests: Declarations. Conflict of interest: No conflict of interest to declare., (© 2024. Fondazione Società Italiana di Neurologia.)

At the beginning of 2020, the entire world was shocked by a global health emergency. According to the literature, fear, high mortality and health restrictions had significant psychological consequences on the population. This study evaluates the French lockdown's impact on the grieving process and how people worked through their grief. Two semi-structured interviews were conducted with 31 participants who had lost a loved one between March 2020, June, and September 2021 (T0) and 6 months later (T1). Subsequently, they were divided into two groups: those who lost someone during the first lockdown (Group 1) and those who lost someone outside the lockdown periods (Group 2). The interviews were analysed using the ALCESTE software, a statistical analysis tool for textual data based on word co-occurrences. This research significantly advances the understanding of bereavement during crises, providing new perspectives and practical insights for policymakers, healthcare professionals and support organisations. Its methodological innovation and detailed analysis contribute to the ongoing discussion on grief and resilience in challenging circumstances. Ultimately, this study lays the foundation for improved support and intervention strategies tailored to the needs of bereaved individuals during crises., (© 2024 The Author(s). International Journal of Psychology published by John Wiley & Sons Ltd on behalf of International Union of Psychological Science.)

Introduction: Completion of alcohol and other drug (AOD) treatment is associated with improved health and social outcomes. Previous research has largely focused on individual (e.g. demographic) or service-level (e.g. treatment modality/setting) factors related to treatment completion in isolation. This study investigates the relationship between treatment completion and service-level and substance related factors, after controlling for demographics., Study Design: Retrospective cohort of 53,430 people engaging in government funded specialist AOD treatment across New South Wales, Australia, between 1 January 2015-31 December 2018., Methods: Generalised linear mixed models were used to analyse factors associated with treatment completion, accounting for repeated measures across treatment episodes., Results: Approximately two-thirds (69.8 %, n = 37,330) of the cohort completed treatment at least once during the study period, 42.3 % (22,605) on a single, and 27.5 % (14,725) on multiple occasions. After controlling for demographics, treatment episodes for amphetamines were least likely to be recorded as complete (52.5 %), while those for MDMA were 1.9 (95 % CI: 1.49, 2.45) times more likely (67 %) than amphetamine episodes to be completed. Treatment episodes mandated through criminal justice/child protection agencies were 1.25 (95 % CI: 1.20, 1.30) times more likely to be completed compared to those originating from self-referral. There were no differences in treatment completion between self or health professional referrals (aOR: 0.98, 95 % CI: 0.95, 1.02). Episodes involving involuntary AOD treatment modalities and residential withdrawal were 6.67 times (95% CI: 4.53, 9.81) and 5.02 times (95 % CI: 4.46, 5.64) more likely respectively to be completed compared to those for community rehabilitation. Case management episodes were also more likely (aOR: 2.43, 95 % CI: 2.16, 2.73) to be completed. Episodes of longer treatment duration (≥90 days) were 1.89 times (95 % CI: 1.82, 1.97) more likely to be completed compared to shorter (≤30 days) treatment episodes., Conclusions: Treatment completion was moderated by a range of factors including drug type, treatment modality and duration, and referral source. Low rates of amphetamine treatment completion across treatment modalities confirms the urgent need for further research investigating more effective treatment options for amphetamine use disorders., Competing Interests: Declaration of competing interest None of the authors have any conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: The adoption of colorectal endoscopic submucosal dissection (ESD) is still limited in the West. A recent randomized trial showed that ESD is more effective and only slightly riskier than piecemeal endoscopic mucosal resection; reproducibility outside expert centers was questioned. We evaluated the results according to the annual case volume in a multicentric prospective cohort., Methods: Between September 2019 and September 2022, colorectal ESD was consecutively performed at 13 participating centers classified as low volume (LV), middle volume (MV), and high volume (HV). The main procedural outcomes were assessed. Multivariate and propensity score matching analyses were performed., Results: Three thousand seven hundred seventy ESDs were included. HV centers treated larger and more often colonic lesions than MV and LV centers. En bloc , R0, and curative resection rates were 95.2%, 87.4%, and 83.2%, respectively, and were higher at HV than at MV and LV centers. HV centers also achieved a faster dissection speed. Delayed bleeding and surgery for complications rates were 5.4% and 0.8%, respectively, without significant differences. The perforation rate (overall: 9%) was higher at MV than at LV and HV centers. Lesion characteristics, but not volume center, were independently associated with both R1 resection and perforation. However, after propensity score matching, R0 rates were significantly higher at HV than at LV centers, and perforation rates were significantly higher at MV than at HV centers., Discussion: Colorectal ESD can be successfully implemented in the West, even in nonexpert centers. However, difficult lesions must still be referred to experts., (Copyright © 2024 by The American College of Gastroenterology.)

Background Aims: Despite promising results in pre-clinical studies, mesenchymal stromal cells (MSCs) face significant challenges in clinical translation. A scoping review by our group highlighted two key issues contributing to this gap: (i) lack of a clear and consensus definition for MSCs and (ii) under-reporting of critical parameters in MSC clinical studies. To address these issues, we conducted a modified Delphi study to establish and implement a consensus definition for MSCs and develop reporting guidelines for MSC clinical studies., Methods: A steering committee of 22 international experts, including stakeholders from different MSC research fields, participated in the three Delphi rounds. For the first round, to obtain a broad perspective, additional investigators recommended by the steering committee were invited to participate. The first two rounds consisted of online surveys, whereas the third round took the form of a virtual meeting. Participants were asked to rate a series of potential defining characteristics of MSCs and items for reporting guidelines. Consensus was defined as at least 80% of the participants rating the item in the same category of importance., Results: Eighty-seven international participants participated in the first round survey (spring 2023), 17 participants participated in the second online survey (fall 2023) and 15 participants participated in the final virtual consensus meeting (January 2024). For the MSC definition, 20 items were considered and nine reached consensus. Items included terminology (one item), cell marker expression (five items), tissue origin (one item), stemness (one item) and description of critical quality attributes (one item). For the reporting guidelines, with the 28 initial items and the additional items suggested during round 1, a total of 33 items to report were included. This included items on MSC intervention group and control (e.g., MSC product, dose and administration), MSC characteristics (e.g., MSC provenance, "fitness," viability and immune compatibility) and MSC culture conditions (e.g., oxygen environment, culture medium and use of serum)., Conclusions: By applying a Delphi method to establish a consensus definition for MSCs and reporting guidelines for MSC-based clinical trials, this work represents a significant advance in improving transparency and reproducibility in the conduct and reporting of MSC research., Competing Interests: Declaration of competing interest The authors have no commercial, proprietary or financial interest in the products or companies described in this article., (Copyright © 2024 International Society for Cell & Gene Therapy. All rights reserved.)

Uranium (U) is a non-essential and toxic metal for plants. In Arabidopsis thaliana plants challenged with uranyl nitrate, we showed that U was mostly (64-71% of the total) associated with the root insoluble fraction containing membrane and cell wall proteins. Therefore, to uncover new molecular mechanisms related to U stress, we used label-free quantitative proteomics to analyze the responses of the root membrane- and cell wall-enriched proteome. Of the 2,802 proteins identified, 458 showed differential accumulation (≥1.5-fold change) in response to U. Biological processes affected by U include response to stress, amino acid metabolism, and previously unexplored functions associated with membranes and the cell wall. Indeed, our analysis supports a dynamic and complex reorganization of the cell wall under U stress, including lignin and suberin synthesis, pectin modification, polysaccharide hydrolysis, and Casparian strips formation. Also, the abundance of proteins involved in vesicular trafficking and water flux was significantly altered by U stress. Measurements of root hydraulic conductivity and leaf transpiration indicated that U significantly decreased the plant's water flux. This disruption in water balance is likely due to a decrease in PIP aquaporin levels, which may serve as a protective mechanism to reduce U toxicity. Finally, the abundance of transporters and metal-binding proteins was altered, suggesting that they may be involved in regulating the fate and toxicity of U in Arabidopsis. Overall, this study highlights how U stress impacts the insoluble root proteome, shedding light on the mechanisms used by plants to mitigate U toxicity., 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 Ltd. All rights reserved.)

Background: Hypertension is the most common chronic disease and a major modifiable risk factor for cardio-cerebrovascular and renal diseases. This study estimated the national burden of hypertension, defined as systolic blood pressure ≥140 mm Hg, on morbidity and mortality in 2021 in France., Methods: For all diseases causally associated with hypertension (cardiovascular diseases, chronic kidney diseases, and dementia), the number and proportion of cases attributable to hypertension in adults aged ≥35 years were estimated using population attributable fractions. Age- and sex-specific population attributable fractions were computed using the distribution of hypertension in the French population. These population attributable fractions were applied to nationwide statistics for mortality, hospitalizations, disease prevalence, years of life lost, years of life lived with disability, and disability-adjusted years of life., Results: The largest population attributable fractions were for ischemic heart disease and hemorrhagic stroke, with over 40% of cases attributable to hypertension. Overall, more than 385 000 patients were hospitalized due to hypertension, with 3.7 million hospitalizations and 6.2 million hospital days (all hospitalizations, including 3.4 million for chronic kidney disease) and including 390 000 overnight hospitalization. In 2021, more than 1.15 million individuals lived with ischemic heart disease attributable to hypertension, 1.26 million with chronic kidney diseases, and 358 033 with heart failure. Among 184 059 annual deaths from cardiovascular diseases, dementia, and chronic kidney diseases, 30% (55 280 deaths) were attributable to hypertension. Hypertension accounted for 8.5% of all deaths and 498 052 years of life lost., Conclusions: In France, despite near-universal health coverage and free health care access, the burden attributable to hypertension remains high., Competing Interests: J. Blacher reports, outside the submitted work, personal fees from Abbott, Bayer, Bottu, Egis, Ferring, Steripharma, Kantar, Sanofi, Servier, and Teriak, as well as personal fees and nonfinancial support from Pfizer and Quantum Genomics. P.G. Steg reports, outside the submitted work, receiving research grants from Amarin and Sanofi, working on clinical trials (steering committee, Clinical Events Committee, Data and Safety Monitoring Board) for Amarin, AstraZeneca, Bayer, Bristol-Myers Squibb (BMS), Idorsia, Novartis, Pfizer, Sanofi, and Servier, and consulting or speaking for Amarin, Amgen, BMS/Myokardia, Novo Nordisk, and SFJ. He is a Senior Associate Editor at Circulation. Y. Béjot reports, outside the submitted work, personal fees from BMS, Pfizer, Medtronic, Amgen, Servier, Novo Nordisk, and Novartis. J.M. Halimi reports, outside the submitted work, honoraria from AstraZeneca, Alexion, Bayer, Novo Nordisk, Servier, and Vifor Fresenius. I.D. Zaleski reports, outside the submitted work, fees for consulting and educational programs from Amgen, BMS, Boston Scientific, Medtronic, Merck Sharp & Dohme, and Roche. The other authors report no conflicts.

Purpose: Peripartum cardiomyopathy (PPCM) affects women in late pregnancy and postpartum. Cardiovascular magnetic resonance (CMR) can contribute to PPCM diagnosis and management. We explored CMR findings in PPCM, including myocardial strain and late gadolinium enhancement (LGE) patterns. Materials and Methods: This retrospective single-centre study included patients with PPCM who underwent CMR from 2010 to 2018. Exclusions were other cardiomyopathy causes. CMR parameters, including ventricular function, LGE, and myocardial strain, were compared between the PPCM group and healthy controls. Transthoracic echocardiographic data were reviewed to assess functional improvement in PPCM patients. Results: Thirty-two women with PPCM (mean age 42 ± 6 years) and 26 controls (mean age 43 ± 14 years) were included. PPCM patients had significantly lower left ventricular (LV) ejection fractions (median 37.5% vs 60.5%, P < .001), higher LV end-diastolic volumes (median 108 ml/m² vs 76 ml/m², P < .001), and reduced global LV strain compared to controls. Eighteen PPCM patients (58%) had non-ischaemic pattern LGE, with no LGE in controls besides hingepoint LGE (23%). LGE was most prevalent in the basal and mid anteroseptum. LGE patterns included linear mid-wall, subepicardial, and right ventricular side of the septum. Twenty-four patients (92%) showed improvement in LVEF at follow-up echocardiogram (mean LVEF 28% ± 1.9% at diagnosis and 45% ± 3% at follow-up, P < .001). Conclusion: We identified a non-ischaemic pattern LGE that is nonspecific in isolation but could suggest PPCM in the correct clinical context along with abnormal CMR strain values. Future studies should evaluate the clinical application of these findings to facilitate earlier diagnosis and enhance management., 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.

Objectives: To examine if point-of-care (POC) urine tenofovir testing-informed counseling could be used to improve virologic suppression (VS) among participants with virologic failure (VF) after ≥1 prior round of enhanced adherence counseling (EAC)., Methods: Participants were enrolled from 42 clinics across Namibia. At each monthly medication pick-up, participants completed the POC urine test and received EAC informed by this testing (EAC+). If VS was not achieved after 3 months of EAC+, up to 3 additional rounds of EAC+ were provided, with resistance testing at month (M)9., Results: Of 310 potentially eligible participants across 42 clinics in Namibia, we enrolled 211 participants with VF (median age 33 years, 61% female); 195 reached M3 defined as receiving EAC+ and follow-up viral load testing; 169 achieved VS within M3 (87%, P < 0 . 001) and 97% by M9 (181/186) compared to 40% (22/55) prior to the intervention (P < 0.001). Resistance testing was performed in five remaining participants with VF at M9, of whom 1/5 (20%) developed dolutegravir resistance., Conclusion: The urine tenofovir assay when incorporated into adherence counseling has potential to be a cost-effective intervention among participants failing tenofovir-based regimens, increasing VS to 97% in those failing Tenofovir-Lamivudine-Dolutegravir. Encouraging results of this pre-post intervention will be rigorously tested in a randomized trial., Competing Interests: Declarations of competing interest The authors report no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Somatic multigene analysis by next-generation sequencing (NGS) is routinely integrated in medical oncology for clinical decision-making. However, with the fast-growing number of recommended and required genes as well as pan-cancer biomarkers, small panels have become vastly insufficient. Comprehensive genomic profiling (CGP) is, thus, required to screen for clinically relevant markers. In this multicentric study, we report on an extensive analysis across seven centers comparing the results of the novel OncoDEEP CGP assay with the diagnostically validated TruSight Oncology 500 (TSO500) kit on 250 samples. Overall concordance was 90% for clinically relevant gene variants and >96% for more complex biomarkers. Agreement for fusion detection was 94% for the 11 overlapping clinically actionable driver genes. The higher coverage uniformity of OncoDEEP compared to TSO500 allows users to pool more samples per sequencing run. Tertiary data analysis, including reporting, is integrated in the OncoDEEP solution, whereas this is an add-on for TSO500. Finally, we showed that, analytically, the OncoDEEP panel performs well, thereby advocating its use for CGP of solid tumors in diagnostic laboratories, providing an all-in-one solution for optimal patient management., (© 2025 The Author(s). Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Background: The COVID-19 pandemic has impacted the provision and utilisation of health care services with varying magnitude across settings due to spatial temporal variation in the burden of COVID-19 cases and the roll-out of local COVID-19 response policies. This study assesses changes in the provision and utilisation of health care services for three major chronic health conditions (HIV/AIDS, hypertension, and diabetes) over the pre-COVID-19 and COVID-19 pandemic periods in a rural South African sub-district of Agincourt., Methods: Segmented interrupted time series regression models are applied to assess changes in the number of medication collection visits and new diagnoses for HIV/AIDS, hypertension, and diabetes from 1 January 2018 to 30 September 2021 covering the pre- COVID-19 period and the first three waves of the COVID-19 pandemic., Results: The number of medication collection visits for HIV/AIDS, hypertension, and diabetes dropped following the imposition of level 5 lockdown. Despite some improvements over the course of the pandemic, by the end of the third wave in September 2021, visits remained below the pre-COVID-19 era. The number of clinic visits for new diagnoses of HIV/AIDS and hypertension also fell after the introduction of level 5 lockdown. Although the number of new visits for HIV/AIDS bounced back to the pre-COVID-19 trends by the end of the third wave, the number of visits for new hypertension diagnoses remained significantly lower than expected. Referrals for collection of medications from the Central Chronic Medicines Dispensing and Distribution (CCMDD) programme, as an alternative to collection from clinics, increased exponentially over the course of the pandemic., Conclusions: Although the increased adoption of the CCMDD programme can in part account for decreased medication collection visits which persisted well after lockdown measures were lifted, marked reductions in the number of newly diagnosed cases of hypertension warrant concern. A deeper assessment of the appropriateness of referrals to the CCMDD programme as well as the longer-term effects on morbidity and mortality of missed treatment and/or delayed diagnosis is needed for a more granular understanding of the true ramifications of the COVID-19 pandemic and associated lockdown policies in the Agincourt subdistrict and other rural African settings., Competing Interests: Disclosure of interest: The authors completed the ICMJE Disclosure of Interest Form (available upon request from the corresponding author) and disclose no relevant interests., (Copyright © 2025 by the Journal of Global Health. All rights reserved.)

Tumor-induced osteomalacia (TIO) is a rare acquired paraneoplastic syndrome caused by a mesenchymal tumor secreting a phosphaturic hormone called FGF23. Patients present with bone pain, fragility fractures and muscle weakness. Biochemical results show hypophosphatemia, raised serum alkaline phosphatase and reduced calcitriol. We report the case of a 44-year-old man who presented to the Emergency Departement with acute low back pain revealing extensive subchondral fractures between D2 and L5. Investigations showed partial Fanconi syndrome; nevertheless, he had profound hypophosphatemia, low 1,25-OH vitamin D and raised FGF23 levels suggesting a diagnosis of tumor-induced osteomalacia. A subcutaneous lesion was identified in the left leg on a PET-CT initially performed to rule out malignancy in the context of Fanconi syndrome. Tumorectomy enabled complete resolution of the electrolyte disturbances within days of surgery. This case shows that TIO may present as partial Fanconi syndrome, highlighting the importance of testing other electrolytes in cases of hypophosphatemia and the need to look for TIO in cases of partial Fanconi with severe hypophosphatemia., Competing Interests: Declarations. Conflict of interest: None. Informed Consent: Informed consent was obtained from the patients. Human and Animal Rights: Our publication is a case-report; therefore, I do onot know if I need to fill in this section. As it described the clinical case, it did not need ethical approval from the institution. All ethical principles were applied when looking afterthe patient., (© 2025. The Author(s).)

Background AI-systems in endoscopy are predominantly developed and tested using high-quality imagery from expert centers. Their performance may be different when applied on heterogeneous imagery in clinical practice. This is partially caused by the diversity in post-processing enhancement settings used in endoscopy units. We evaluated the impact of post-processing enhancement settings on AI performance and tested specific data augmentation strategies to mitigate performance loss. Methods We used a computer-aided detection (CADe) system for Barrett's neoplasia (6,223 images, 906 patients) and a computer-aided diagnosis (CADx) system for colorectal polyps (3,288 images, 969 patients), both trained on datasets acquired with Olympus equipment. First, systems were trained using their original datasets, which were acquired with limited variability in enhancement settings. These CAD systems were then tested across a wide range of test sets, which comprised the same images, but displayed with different enhancement settings. Then, both CAD systems were retrained using image enhancement-based data augmentation. The performance of these adjusted CAD systems was then evaluated on the same array of test sets. Results When trained on their original training set and tested over a range of enhancement settings, both systems displayed substantial performance variability: 83-92% sensitivity and 84-91% specificity for CADe; 78-85% sensitivity and 45-63% specificity for CADx. After retraining CAD systems using image enhancement-based data augmentation, variability in sensitivity and specificity was reduced to 2% (p>0.001) and 1% (p=0.003) for CADe and 2% (p=0.029) and 8% (p=0.190) for CADx. Conclusion This retrospective study indicates that performance of current endoscopic AI systems can substantially vary depending on the post-processing enhancement settings of the endoscopy unit. Specific data augmentation can mitigate this performance loss., Competing Interests: JJB reports financial support for IRB approved research from, Medtronic, Olympus, Castle Sciences, CDx Diagnostics, Cyted, Lucid, Fractyl Inc, Endogenex, Digma Medical and Aqua Medical and consultancies for Olympus, Fractyl, and Endogenex. ED as endoscopic equipment on loan from FujiFilm; has received a research grant from FujiFilm; has received honoraria for consultancy from Olympus, Fujifilm, Ambu, InterVenn, and Exact Sciences; has received speakers’ fees from Olympus, GI Supply, Norgine,IPSEN, PAION and FujiFilm; and is a supervisory board member of the eNose Company. MV has received an honorarium for educational courses from Tillotts. PHW received financial support for IRB approved research from Olympus., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Background: Radiotherapy as a complement or an alternative to neurosurgery has a central role in the treatment of skull base grade I-II meningiomas. Radiotherapy techniques have improved considerably over the last two decades, becoming more effective and sparing more and more the healthy tissue surrounding the tumour. Currently, hypo-fractionated stereotactic radiotherapy (SRT) for small tumours and normo-fractionated intensity-modulated radiotherapy (IMRT) or proton-therapy (PT) for larger tumours are the most widely used techniques. It is expected a decrease of the risk of cognitive impairment with these modern techniques. However prospective data about cognitive long-term consequences of partial brain irradiation with SRT, PT, or IMRT remain very scarce to date., Methods: CANCER COG is one of the first multicentric study in the world to prospectively assess the cognitive performances of patients following different modalities of cerebral radiotherapy (stereotactic radiotherapy, proton therapy, intensity modulated radiotherapy) for the treatment of grade I-II skull base meningioma, up to at least 10 years after the end of radiotherapy. This longitudinal study includes the follow-up of 3 cohorts, including: patients treated with PRT, IMRT, and SRT. An additionally control group will be formed. The primary objective is to report long-term cognitive deterioration in each cohort until 10 years after the end of irradiation. The rate of clinical symptomatology improvement over time after irradiation, the evolution of health-related quality-of-life, anxiety/depression, fatigue, over time after irradiation, the tumoral local control after irradiation, the progression-free survival (PFS), the professional reintegration for working-age patients will also be assessed. CANCER COG aims to help clinicians to choose the best irradiation techniques with the best benefit/risk ratio. Inclusions started on september 2023., Trial Registration: The study was registered on clinicaltrials.gov with the following number: NCT06036706., Competing Interests: Declarations. Ethics approval and consent to participate: This study has received ethical approval from the Comité de protection des personnes Ouest VI. All patients will give their written informed consent before any study relative assessment start. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Purpose: Prelingual deaf children with cochlear implants show lower digit span test scores compared to normal-hearing peers, suggesting a working memory impairment. To pinpoint more precisely the subprocesses responsible for this impairment, we designed a sequence reproduction task with varying length (two to six stimuli), modality (auditory or visual), and compressibility (sequences with more or less regular patterns). Results on 22 school-age children with cochlear implants and 21 normal-hearing children revealed a deficit of children with cochlear implants only in the auditory modality. We observed no deficit in the visual modality and no deficit in the ability to detect and use regular patterns to improve memorization., Conclusion: These results suggest that the working memory deficit of children with cochlear implants is explained by an impairment in the processing, encoding, and/or storage of the auditory and lexical information, as opposed to a global storage deficit or an inability to use compressibility strategies to improve memorization., Supplemental Material: https://doi.org/10.23641/asha.28216088.

It is well-known that the use of vocabulary in phenotype treatments is often inconsistent. An earlier survey of biologists who create or use phenotypic characters revealed that this lack of standardization leads to ambiguities, frustrating both the consumers and producers of phenotypic data. Such ambiguities are challenging for biologists, and more so for Artificial Intelligence, to resolve. That survey also indicated a strong interest in a new authoring workflow supported by ontologies to ensure published phenotype data are FAIR (Findable, Accessible, Interoperable, and Reusable) and suitable for large-scale computational analyses. In this article, we introduce a prototype software system designed for authors to produce computational phenotype data. This platform includes a web-based, ontology-enhanced editor for taxonomic characters (Character Recorder), an Ontology Backend holding standardized vocabulary (the Cared Ontology), and a mobile application for resolving ontological conflicts (Conflict Resolver). We present two formal user evaluations of Character Recorder, the main interface authors would interact with to produce FAIR data. The evaluations were conducted with undergraduate biology students and Carex experts. We evaluated Character Recorder against Microsoft Excel on their effectiveness, efficiency, and the cognitive demands of the users in producing computable taxon-by-character matrices. The evaluations showed that Character Recorder is quickly learnable for both student and professional participants, with its cognitive demand comparable to Excel's. Participants agreed that the quality of the data Character Recorder yielded was superior. Students praised Character Recorder's educational value, while Carex experts were keen to recommend it and help evolve it from a prototype into a comprehensive tool. Feature improvements recommended by expert participants have been implemented after the evaluation., (© The Author(s) 2025. Published by Oxford University Press.)

Background: Multidisciplinary tumor boards (MTBs) have been established in most countries to allow experts collaboratively determine the best treatment decisions for cancer patients. However, MTBs often face challenges such as case overload, which can compromise MTB decision quality. Clinical decision support systems (CDSSs) have been introduced to assist clinicians in this process. Despite their potential, CDSSs are still underutilized in routine practice. The emergence of large language models (LLMs), such as ChatGPT, offers new opportunities to improve the efficiency and usability of traditional clinical decision support systems (CDSSs)., Objectives: OncoDoc2 is a guideline-based CDSS developed using a documentary approach and applied to breast cancer management. This study aims to evaluate the potential of LLMs, used as question-answering (QA) systems, to improve the usability of OncoDoc2 across different prompt engineering techniques (PETs)., Methods: Data extracted from breast cancer patient summaries (BCPSs), together with questions formulated by OncoDoc2, were used to create prompts for various LLMs, and several PETs were designed and tested. Using a sample of 200 randomized BCPSs, LLMs and PETs were initially compared on their responses to OncoDoc2 questions using classic metrics (accuracy, precision, recall, and F1 score). Best performing LLMs and PETs were further assessed by comparing the therapeutic recommendations generated by OncoDoc2, based on LLM inputs, to those provided by MTB clinicians using OncoDoc2. Finally, the best performing method was validated using a new sample of 30 randomized BCPSs., Results: The combination of Mistral and OpenChat models under the enhanced zero-shot PET showed the best performance as a question-answering system. This approach gets a precision of 60.16%, a recall of 54.18%, an F1 Score of 56.59%, and an accuracy of 75.57% on the validation set of 30 BCPSs. However, this approach yielded poor results as a CDSS, with only 16.67% of the recommendations generated by OncoDoc2 based on LLM inputs matching the gold standard., Conclusions: All the criteria in the OncoDoc2 decision tree are crucial for capturing the uniqueness of each patient. Any deviation from a criterion alters the recommendations generated. Despite a good accuracy rate of 75.57% was achieved, LLMs still face challenges in reliably understanding complex medical contexts and be effective as CDSSs., Competing Interests: The authors declare that they have no conflict of interest., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/).)

Through the analysis of notable studies from 2024, this article offers an overview of key advances in internal medicine with a selection of essential themes. The topics covered include advances in common internal medicine conditions such as cardiovascular diseases, pulmonary disorders, antibiotic use, and fever of unknown origin. This article provides a practical summary to help clinicians stay informed about the latest diagnostic and therapeutic developments., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.