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Sarcopenia is the age-related loss of skeletal muscle mass as well as muscle strength and/ or performance.1 Sarcopenia is an important public health issue as it has a significant impact on patient health outcomes, and personal and social economic outcomes. It leads to increased adverse outcomes such as increased risks of falls, fractures, postoperative complications, disability and increased mortality.2 It is associated with many chronic diseases such as heart failure, chronic kidney disease, chronic obstructive pulmonary disease, diabetes and cognitive impairment.2,4 The prevalence of sarcopenia is expected to dramatically increase in the next few decades, especially in ageing populations.6

Background: Patients with Relapsed/Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL) ineligible for Hematopoietic Stem Cell Transplantation (HSCT) may benefit from a second line anticancer drug regimen but real-life outcomes are lacking., Objective: To describe the efficacity of 3 anticancer drug regimens (Gemcitabine and Oxaliplatin GEMOX; Ifosfamide and Etoposide IE; Cyclophosphamide, Etoposide, Procarbazine and Prednisone CEPP) combined with Rituximab (R-) in terms of progression-free (PFS) and overall survival (OS)., Patients: Retrospective study including R/R DLBCL patients HSCT ineligible who received at least one cycle of R-GEMOX, R-IE or R-CEPP between 2010 and 2022. Demographic, clinical, biological and survival data were collected. Univariate and multivariate analysis were performed to identify associated variables with survival outcomes., Results: Sixty-two patients (median age 78 [40-102] with predominantly stage III-IV DLBCL (n = 49, 79%), non-germinal center-B like (n = 27, 44%) were included. Median OS and PFS were 9 (CI95% [3-10]) and 4 months (CI95% [2-13]) for R-GEMOX, 4 (CI95% [2-6]) and 1 month (CI95% [1-4]) for R-IE and 5 (CI95% [3-6]) and 3 months (CI95% [2-15]) for R-CEPP, respectively. Univariate analysis selects ECOG, aa-IPI scores, LDH rate and Ann-Arbor stage with no independently association in multivariate analysis., Conclusion: All three regimens show modest survival benefit especially between last anticancer treatment course and death. Emergence of bispecific antibodies and Cart-cells for which real-life benefits have yet to be demonstrated could be coupled with improved access to early palliative care., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Myotonia is the main feature of both myotonic dystrophy (DM) and non-dystrophic myotonia (NDM). It is felt as stiffness, pain, fatigue, and weakness. In France, mexiletine, a non-selective voltage-gated sodium channel blocker, is approved for the treatment of myotonia in adults with NDM, and it has a temporary recommendation for use in the symptomatic treatment of DM in adults. However, it is not currently licensed for treating myotonia in children due to the lack of studies on its use in pediatrics. This has meant heterogeneous practices in its utilization and has led to prescriber reluctance, which has jeopardized accessibility. We undertook a professional practice survey of French pediatric neuromuscular centers to determine their prescribing habits for mexiletine, assessing indications, doses, efficacy, and tolerance., Methods: One medical pediatric professional from each French pediatric neuromuscular center belonging to the national neuromuscular network (FILNEMUS) was invited to complete an anonymous questionnaire., Results: In total, 34 healthcare professionals responded. Of these, 16 had already treated a child for myotonia with mexiletine. Mexiletine was prescribed in one third of pediatric patients with NDM, but it was used in only 3% of DM type 1 patients and in no DM type 2 patients. Pre-treatment assessment always included a cardiac evaluation; however, the method of introduction (inpatient vs. outpatient basis), dosage adjustment, and efficacy evaluation ranged widely. More than half of the respondents reported a high efficacy of mexiletine in their patients; only three reported moderate adverse events (dyspepsia, loss of appetite, and asthenia)., Conclusion: The findings of this first survey on mexiletine for pediatric myotonia in France lend support for the creation of future national guidelines., Competing Interests: Declaration of competing interest - Christine Barnerias and Arnaud Isapof are investigators in the following clinical study: ClinicalTrials NCT04624750 - Christine Barnerias, Catherine Sarret, Yann Pereon, Karim Wahbi, and Arnaud Isapof have participated in industrial symposia for, or have been on the scientific board of, Lupin Pharmaceuticals., (Copyright © 2025. Published by Elsevier Masson SAS.)

Light sheet fluorescence microscopy (LSFM) has emerged as a transformative imaging technique in the study of drug delivery and embryonic development, offering high-resolution, real-time visualization with minimal phototoxicity. This review examines the application of LSFM in tracking drug pharmacokinetics, tissue-specific targeting, and drug efficacy during critical phases of embryonic development. Recent advancements in fluorescent labeling and machine learning integration have enabled more precise monitoring of drug release, distribution, and interaction with developing tissues. The ability of LSFM to capture long-term dynamics at single-cell resolution has revolutionized drug discovery, especially in nanomedicine and targeted therapies. By integrating LSFM with multimodal imaging and AI-driven data analysis, researchers are now better equipped to explore complex biological processes and optimize drug delivery in a highly controlled, minimally invasive manner. Finally, the review highlights the pivotal role of LSFM in advancing drug delivery research, addressing existing challenges, and unlocking new frontiers in clinical applications., 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 © 2025 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The use of an observer tool (OT) has been shown to improve learning of technical skills through observation in simulation. The objective was to assess the impact of a non-technical OT on anaesthesia residents' learning of non-technical skills (NTS) during simulation., Methods: After consent, residents were randomised into 2 groups: OT+ (with an OT based on NTS to be systematically completed during observation of others) and OT- (without OT). Both groups observed a high-fidelity simulation of crisis management (with or without OT), then were asked to perform actively another simulation. The primary outcome was NTS performance, assessed by an evaluator using the Anaesthesia Non-Technical Skills score (ANTS score out of 16) on video recording. Secondary outcomes were results of score items, satisfaction, team performance, and professional impact., Results: No significant difference was found between OT + group (n = 33) and OT- group (n = 30) for the ANTS score (OT + 12 [9.5-12.5], OT- 10.5 [8.75-12]/16 (p = 0.13)). Among sub-items of the ANTS score, decision-making was significantly better in the OT + group (3 [2-3] versus 2 [2-3], p = 0.01). Satisfaction, team performance and perception of professional impact were not significantly different between groups., Conclusions: This study showed no significant difference in learning of observational anaesthesia resident's NTS whether or not they were provided a non-technical OT during crisis management simulation. Decision-making was better with an OT. Further work is necessary to define the place of OT in observer-based learning., Competing Interests: Declarations. Ethical approval: Approval was obtained from the Research Ethics Committee of the French Society of Anaesthesia and Intensive Care Medicine (SFAR, CERAR: IRB 00010254-2022-068). All participants gave written informed consent. Investigators of the study were not in a position of authority which can significantly affect the career progression of the residents included. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

A ventral hernia involves tissue protrusion through the abdominal wall (AW). It is a common surgical issue with high recurrence rates. Primary stability of hernia meshes is essential to guarantee mesh integration, yet existing meshes often fail to match the AW's complex biomechanics. This study proposes a novel method aiming at understanding post-operative mesh-AW interactions. Three fresh frozen human specimens underwent an open Rives-Stoppa implantation of a synthetic hernia mesh coated with metallic micro-beads. Additional beads were placed into the AW muscle tissue. CT scans were conducted at increasing levels of intra-abdominal pressure to reproduce forced breathing. Beads 3D coordinates were exported from the CT-scans and motion and strain of both the hernia mesh and the AW were calculated. At 30 mmHg, the mesh-muscle motion (or sliding) was 2.3 ± 1.3 mm. Muscle exhibited significantly higher strains (12.9 ± 4.7 %) than the hernia mesh (4.7 ± 1.1 %), most likely due to difference in material properties between the mesh and the AW. A repeatability study was carried out to build confidence in the proposed method. This protocol can bring insights of the hernia mesh use-conditions to improve hernia mesh design requirements and develop safer implants to reduce hernia recurrence., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Guillaume Passot, MD, PhD reports a relationship with Medtronic Inc that includes: consulting or advisory. Pascal Rousset, MD, PhD reports a relationship with Medtronic Inc that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 IPEM. Published by Elsevier Ltd. All rights reserved.)

Humans are exposed to toxic methylmercury mainly by consuming marine fish, in particular top predator species like billfishes or tunas. In seafood risk assessments, mercury is assumed to be mostly present as organic methylmercury in predatory fishes; yet high percentages of inorganic mercury were recently reported in marlins, suggesting markedly different methylmercury metabolism across species. We quantified total mercury and methylmercury concentrations in muscle of four billfish species from the Indian and the Pacific oceans to address this knowledge gap. We found low percentages of methylmercury in blue and black marlins (15 ± 7 %) compared to swordfish and striped marlin (89 ± 13 %), with no significant differences among ocean regions. This illustrates that billfishes exhibit species-specific methylmercury bioaccumulation patterns, likely related to unique selenium-dependent in vivo methylmercury demethylation capacities in muscle. Blue and black marlins therefore appeared generally safer for human consumption than swordfish and striped marlin regarding MeHg toxicological effects. Yet, no matter the species, the frequency of recommended weekly billfish meals decreased with increasing fish size, given that mercury naturally accumulates over time. When assessing potential risks of billfish consumption, we therefore recommend measuring methylmercury, rather than total mercury, and relying on a large number of samples to cover a broad range of fish sizes. This study calls for additional characterization of mercury speciation and bioavailability in billfishes to better understand the mechanisms driving species-specific differences of methylmercury detoxification, and to refine dietary advices associated to marine top predators consumption., 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 © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Bluetongue (BT) and Epizootic Hemorrhagic Disease (EHD) are two notifiable animal diseases transmitted to ruminants by small hematophagous midges belonging to the Culicoides genus. The etiological agents, Bluetongue virus (BTV) and Epizootic hemorrhagic disease virus (EHDV), are both members of the Sedoreoviridae family and Orbivirus genus, which include double-stranded (ds) RNA segmented genomes (10 segments). By the end of the summer 2023, first's outbreaks of EHD were reported from the south west of France, concurrently with unexpectedly severe BT cases in Central France and Corsica. Within a few weeks, numerous BT and EHD outbreaks were recorded with significant sanitary and economic impact on cattle and sheep farms (no sanitary impact of EHD for sheep). Using a customized SISPA approach and the nanopore sequencing technology we successfully recovered genomic sequences from viral isolates and blood samples from infected animals from EHD and BT outbreaks. Three different viruses were responsible for these outbreaks: EHDV-8, BTV-8 and BTV-4. The EHDV-8 strain detected in France corresponded to the strain circulating in Tunisia, Sardinia and Spain since 2021 and 2022. A new BTV-8 strain of unknown origin, clearly different from the enzootic strain circulating in France since 2015, was responsible of the BT outbreaks in domestic ruminants in 2023 on both mainland France and Corsica. A second BTV, BTV-4, also involved in BT outbreaks in Corsica, corresponded to a BTV-4 strain occasionally detected on Corsica island since 2016, suggesting either a new introduction of this strain or a silent circulation on the field. The exceptional nature of orbivirus epizootics in France in 2023, including new introduction, emergence or incursions, raises numerous questions regarding BTV and EHDV dynamics and epidemiology and stresses out the need to identify factors involved in these emergences., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

This study investigates the impact of tightening torque (preload) and the friction coefficient on stress generation and fatigue resistance of a Ti-6Al-4V abutment screw with an internal hexagonal connection under dynamic multi-axial masticatory loads in high-cycle fatigue (HCF) conditions. A three-dimensional model of the implant-abutment assembly was simulated using ANSYS Workbench 16.2 computer aided engineering software with chewing forces ranging from 300 N to 1000 N, evaluated over 1.35 × 10 7 cycles, simulating 15 years of service. Results indicate that the healthy range of normal to maximal mastication forces (300-550 N) preserved the screw's structural integrity, while higher loads (≥800 N) exceeded the Ti-6Al-4V alloy's yield strength, indicating a risk of plastic deformation under extreme conditions. Stress peaked near the end of the occluding phase (206.5 ms), marking a critical temporal point for fatigue accumulation. Optimizing the friction coefficient (0.5 µ) and preload management improved stress distribution, minimized fatigue damage, and ensured joint stability. Masticatory forces up to 550 N were well within the abutment screw's capacity to sustain extended service life and maintain its elastic behavior.

Background: Testing and treating symptomatic malaria cases is crucial for case management, but it may also prevent future illness by reducing mean infection duration. Measuring the impact of effective treatment on burden and transmission via field studies or routine surveillance systems is difficult and potentially unethical. This project uses mathematical modeling to explore how increasing treatment of symptomatic cases impacts malaria prevalence and incidence., Methods: Leveraging the OpenMalaria stochastic agent-based transmission model, we first simulated an array of transmission intensities with baseline effective treatment coverages of 28%, 44%, and 54% incorporated to reflect the 2023 coverage distribution across Africa, as estimated by the Malaria Atlas Project. We assessed the impact of increasing coverage to as high as 60%, the highest 2023 estimate on the continent. Subsequently, we performed simulations resembling the specific subnational endemicities of Kenya, Mozambique, and Benin, using the Malaria Atlas Project estimates of intervention coverages to reproduce historical subnational prevalence. We estimated the impact of increasing effective treatment coverage in these example settings in terms of prevalence reduction and clinical cases averted in children under 5 years old and the total population., Results: The most significant prevalence reduction - up to 50% - was observed in young children from lower transmission settings (prevalence below 0.2), alongside a 35% reduction in incidence, when increasing effective treatment from 28% to 60%. A nonlinear relationship between baseline transmission intensity and the impact of treatment was observed. Increasing effective treatment coverage to 60% reduced the risk in high-risk areas (prevalence in children under 5 years old > 0.3), affecting 39% of young children in Benin and 20% in Mozambique previously living in those areas. In Kenya where most of the population lives in areas with prevalence below 0.15, and case management is fairly high (53.9%), 0.39% of children were estimated to transition to lower-risk areas., Conclusions: Improving case management directly reduces the burden of illness, but these results suggest it also reduces transmission, especially for young children. With vector control interventions, enhancing case management can be an important tool for reducing transmission intensity over time., (© 2024. The Author(s).)

Mimicking the multilayered, anisotropic, elastic structure of cardiac tissues for controlled guidiance of 3D cellular orientation is essential in designing bionic scaffolds for cardiac tissue biofabrication. Here, a hierarchically organized, anisotropic, wavy and conductive polycaprolactone/Au scaffold was created in a facile fashion based on mechanical memory during fabrication. The bionic 3D scaffold shows good biocompatibility, excellent biomimetic mechanical properties that guide myoblast alignment, support the hyperelastic behavior observed in native cardiac muscle tissue, and promote myotube maturation, which holds potential for cardiac muscle engineering and the establishment of an in vitro culture platform for drug screening., (Creative Commons Attribution license.)

Background and Research Question: S. maltophilia infections are associated with significant morbidity and mortality. Little is known regarding its presentation, management, and outcome in lung transplant recipients., Study Design and Methods: This retrospective case control study reviewed S. maltophilia respiratory tract infection in lung transplant recipients (01/01/2011-31/01/2020) and described the clinical, microbiological and outcome characteristics matched with lung transplant recipients without respiratory tract infection., Results and Interpretation: We identified 63 S. maltophilia infections in lung transplant recipients. Among them none were colonized before transplantation. Infections occurred a median of 177 (IQR: 45- 681) days post transplantation. Fifty-four (85.7 %) patients received trimethoprim-sulfamethoxazole (400/80 mg three times a week) to prevent Pneumocystis jirovecii pneumonia (PJP). S. maltophilia strains were susceptible to trimethoprim-sulfamethoxazole, levofloxacin, minocycline and ceftazidime in respectively 85.7 %, 82.5 %, 96.8 % and 34.9 % of cases. Median duration of treatment was 9 days (IQR 7-11.5). Clinical and microbiological recurrence were observed in respectively 25.3 % and 39.7 % of cases. Combination therapy was not associated with a decrease in the risk of recurrence and did not prevent the emergence of resistance. S. maltophilia respiratory tract infection was associated with a decline in FEV-1 at one year., Conclusion: S. maltophilia is an important cause of lower respiratory tract infection in lung transplant recipients. Trimethoprim-sulfamethoxazole use as prophylaxis for PJP doesn't prevent S. maltophilia infection among lung transplant recipients. Levofloxacin and trimethoprim-sulfamethoxazole appear to be the two molecules of choice for the treatment of these infections and new antibiotic strategies (cefiderocol, aztreonam/avibactam) are currently being evaluated for multi-resistant S. maltophilia infections., 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 SPLF and Elsevier Masson SAS. All rights reserved.)

Background: Hysterectomy for benign pathologies is one of the most common gynecological surgeries. In recent years, robotic surgery has become an alternative to traditional surgery, but at a higher cost., Objective: Estimate the cost of benign robot-assisted hysterectomy for the purpose of supporting public decision-making, as well as the additional cost per major postoperative complication (ClavienDindo score ≥ 3) avoided one month after surgery robotic versus traditional laparoscopic., Methods: Single-center retrospective study including patients operated on for benign hysterectomy at La Pitié Salpêtrière hospital between January 2016 and December 2019: 99 by robotic approach, and 86 by laparoscopic approach. Comparison of robotic surgery to laparoscopy. Calculation of a cost-effectiveness ratio (ICER). Use of the propensity score inverse weighting method to ensure comparability of groups., Results: Robotic surgery has a total cost of € 6,615 at 1 month per patient compared to € 3,859 for laparoscopic surgery with an additional cost of € 377,534 per major postoperative complication avoided, longer operating time and an absence of significant difference in terms of complications and length of hospitalization., Conclusion: In terms of cost-effectiveness, according to this study, the robot does not appear to be better than laparoscopy. In the years to come, we can expect a development of robotic surgery with rationalization of the practice, with appropriate selection of patients for robotic surgery, development of outpatient surgery and a reduction in the cost of the equipment., Competing Interests: Declaration of competing interest Pr Geoffroy Canlorbe and Dr Jeremy Belghiti are speaker and proctor for Intuitive Surgical. Dr Richard Paul-Dehlinger, Dr Alexandra Vappereau, Dr Alicia Le Bras, Dr Joana Oliveira, Dr Amelia Favier, Pr Catherine Uzan and Pr Isabelle Durand-Zaleski have no conflicts of interest to disclose., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Liquid porosimetry experiments reveal a peculiar trend of the intrusion pressure of water in hydrophobic Cu 2 (3,3',5,5'-tetraethyl-4,4'-bipyrazolate) MOF. At lower temperature (T) range, the intrusion pressure (P i ) increases with T. For higher T values, P i  first reaches a maximum and then decreases. This is at odds with the Young-Laplace law, which for systems showing a continuous decrease of contact angle with T predicts a corresponding reduction of the intrusion pressure. Though the Young-Laplace law is not expected to provide quantitative predictions at the subnanoscale of Cu 2 (tebpz) pores, the physical intuition suggests that to a reduction of their hydrophobicity corresponds a reduction of the P i . Molecular dynamics simulations and sychrothron experiments allowed to clarify the mechanism of the peculiar trend of P i with T. At increasing temperatures the vapor density within the MOF' pores grows significantly, bringing the corresponding partial pressure to ≈5 MPa. This pressure, which is consistent with the shift of P i observed in liquid porosimetry, represents a threshold to be overcame before intrusion takes place. Beyond some value of temperature, the phenomenon of reduction of hydrophobicity (and water surface tension) dominated over the opposite effect of increase of vapor pressure and P i inverts its trend with T., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Background: Heart failure is one of the leading causes of mortality and hospitalization in cardiovascular patients. Guideline-directed medical treatment (GDMT) in the current era includes novel medications such as ARNI and SGLT2 inhibitors, as well as an approach to treatment based on clinical phenotypes. To assess prognostic factors for mortality and hospital readmissions plays a crucial role in patient care., Objectives: This study aimed to determine the rate of 90-day post-discharge events in patients having heart failure with reduced ejection fraction (HFrEF) and investigate the associated clinical factors., Method: A prospective study was conducted on 110 HFrEF patients at the cardiology department of Cho Ray Hospital. The 90-day events included all-cause mortality and rehospitalization due to heart failure., Results: The rate of 90-day events was 45.6%. After multivariable Cox regression analysis, NT-proBNP level ≥ 1858 pg/mL was identified as an independent factor associated with the 90-day events., Conclusion: NT-proBNP cut-off ≥ 1858 pg/mL can be used for the prognosis of 90-day events in HFrEF., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nguyen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The long-term impact of tyrosine kinase inhibitor (TKI) discontinuation on resistance and survival in patients with advanced gastrointestinal stromal tumours (GIST) is unclear. We report the exploratory long-term outcomes of patients with advanced GIST stopping imatinib in the BFR14 trial., Methods: BFR14, an open-label, randomised, phase 3 trial, was done in 17 comprehensive cancer centres or hospitals across France. Patients with advanced GIST aged 18 years or older with an Eastern Cooperative Oncology Group performance status of 0-3, no previous treatment with imatinib, and no previous malignancy were eligible. Patients were treated with oral imatinib 400 mg daily. Patients with a complete or partial response, or stable disease, according to Response Evaluation Criteria in Solid Tumours (1.0) at 1 year, 3 years, and 5 years from the start of treatment were randomly assigned (1:1) to treatment discontinuation until progression (interruption group) or treatment continuation until progression (continuation group). Randomisation was done centrally with computer-generated permuted blocks of two and six patients stratified by participating centre and presence or absence of residual disease on CT scan. The primary endpoint was progression-free survival. Secondary endpoints included time to imatinib resistance and overall survival. Analyses were conducted on an intention-to-treat basis in all randomly assigned patients who were not lost to follow-up. This trial is registered with ClinicalTrial.gov, NCT00367861., Findings: Between May 12, 2003, and March 16, 2004, after 1 year of imatinib, 32 patients were randomly assigned to the interruption group and 26 to the continuation group. Between June 13, 2005, and May 30, 2007, after 3 years of imatinib, 25 patients were randomly assigned to the interruption group and 25 to the continuation group. Between Nov 9, 2007, and July 12, 2010, after 5 years of imatinib, 14 patients were randomly assigned to the interruption group and 13 to the continuation group. Median follow-up was 235·2 months (IQR 128·8-236·6) after the 1-year randomisation, 200·9 months (190·2-208·4) after the 3-year randomisation, and 164·5 months (134·4-176·4) after the 5-year randomisation. Median progression-free survival in the interruption group versus the continuation group after 1 year of imatinib was 6·1 months (95% CI 2·5-10·1) versus 27·8 months (19·5-37·9; hazard ratio [HR] 0·36 [95% CI 0·20-0·64], log-rank p=0·0003), after 3 years of imatinib was 7·0 months (3·5-11·7) versus 67·0 months (48·8-85·6; 0·15 [0·07-0·32], log-rank p<0·0001), and after 5 years of imatinib was 12·0 months (9·0-16·6) versus not reached (NR; NR-NR; 0·13 [0·03-0·58], log-rank p=0·0016). The median time to imatinib resistance after 1 year of imatinib was 28·7 months (95% CI 18·1-39·1) versus 90·6 months (25·3-156·1; HR 0·93 [95% CI 0·51-1·71], log-rank p=0·82), after 3 years was 66·2 months (43·0-89·6) versus 127·3 months (15·0-239·7; 0·35 [0·17-0·72, log-rank p=0·0028), and after 5 years was 58·6 months (0·0-167·4) versus NR (NR-NR; 0·24 [0·05-1·12], log-rank p=0·049). Median overall survival after 1 year of imatinib was 56·0 months (95% CI 30·3-82·9) versus 105·0 months (20·6-189·6; HR 0·84 [95% CI 0·46-1·54], log-rank p=0·57), after 3 years was 104·0 months (90·7-118·7) versus 134·0 months (89·7-178·3; 0·40 [0·20-0·82], log-rank p=0·0096), and after 5 years was NR (NR-NR) versus 110·4 months (82·7-154·1; 1·28 [0·41-3·99]; log-rank p=0·67), INTERPRETATION: Imatinib interruption in patients with GIST without progressive disease is not recommended. Imatinib interruption in non-progressing patients with GIST was associated with rapid progression, faster resistance to imatinib, and shorter overall survival in the long-term follow-up when compared with imatinib continuation in patients after 3 years and 5 years of imatinib., Funding: Centre Léon Bérard, INCa, CONTICANET, Ligue Contre le Cancer, and Novartis., Competing Interests: Declaration of interests J-YB reports grants from NETSARC+, INTERSARC+, and LYRICAN+ from INCA (to the institution), DEpGyn RHU and LYRICAN+ from the Agence Nationale de la Recherche (to the institution), and ERN EURACAN from the EU commission (to the institution); research support from Novartis, Deciphera, and Bayer (to the institution); membership of steering committees for the Intrigue and Motion studies for Deciphera; and membership of the supervisory boards of Transgène and Innate Pharma. IR-C reports research grants from Bristol Myers Squibb (BMS); consulting fees from and participation on data safety boards of Adaptimmune, Agenus, Amgen, AstraZeneca, BMS, Clovis, Daiichi Sankyo, Deciphera, Eisai, EQRX, GSK, MacroGenics, Merck Serono, Mersana, MSD, Novartis, Onxeo, Roche, and Sutro Biopharma. NP reports research grants from Bayer. DP reports travel grants from Roche and Novartis. ALC reports honoraria from Deciphera and Pharmamar. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes 1 . Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome 2 . We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64&#95;65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5' splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide., (© 2024. The Author(s).)

Surgical procedures involving the use of x-rays in the operating room (OR) have increased in recent years, thereby increasing the exposure of OR staff to ionizing radiation. An individual dosimeter makes it possible to record the radiation exposure to which these personnel are exposed, but there is a lack of compliance in the wearing of these dosimeters for several practical reasons. This makes the dose results obtained unreliable. To try to improve the rate of dosimeter wearing in the OR, the Dosibadge project studied the association of the individual dosimeter with the hospital access badge, forming the Dosibadge. Through a study performed at the Tours University Hospital in eight different ORs for two consecutive periods of 3 months. The results show a significant increase in the systematic use of the dosimeter thanks to the Dosibadge, which improves the reliability of the doses obtained on the dosimeters and the monitoring of personnel. The increase is especially marked with clinicians. Following these results and the very positive feedback to this first single-centre study, we are then planning a second multicentre study to validate our proof of concept on different sites, with the three brands of individual dosimeters used in France i.e. dosimeters supplied by Dosilab; Landauer and IRSN., (© 2024 Society for Radiological Protection. Published on behalf of SRP by IOP Publishing Limited. All rights reserved.)

Background: Myositis ossificans (MO) is a rare disease involving the formation of bone outside the musculoskeletal system. While surgical intervention is the main treatment approach, preventing recurrence and standardized rehabilitation are also crucial. Here, we present a surgical strategy to prevent the recurrence of MO., Case Summary: A 28-year-old female patient was admitted for the first time for a comminuted fracture of the left olecranon. However, incorrect postoperative rehabilitation resulted in the development of elbow joint stiffness with ectopic ossification, causing a loss of normal range of motion. The patient was diagnosed with MO based on physical examination, X-ray findings, and clinical presentation. We devised a surgical strategy to remove MO, followed by fixation with an Ilizarov frame, and implemented a scientifically reasonable rehabilitation plan. The surgery lasted for 3 h with an estimated blood loss of 45 mL. A drainage tube was placed after surgery, and fluid was aspirated through ultrasound-guided puncture. The patient experienced a significant reduction in joint stiffness after surgery. In the final follow-up at 9 mouths, there was evident improvement in the range of motion of the elbow joint, and no other symptoms were reported., Conclusion: The Ilizarov frame is an advantageous surgical technique for facilitating rehabilitation after MO removal. It offers benefits such as passive recovery, individualized treatment, and prompt recovery., Competing Interests: Conflict-of-interest statement: All authors have stated that there are no competing interests related to this report., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Objectives: Prophylaxis (P) or pre-emptive strategy (PS) in high-risk liver transplant recipients (LTRs) are either recommended. We compared the results of each strategy., Methods: Two groups of LTR transplanted during two consecutive periods were compared. Only cytomegalovirus (CMV)-mismatched LTR (Donor +/ Recipient -) were included. The primary endpoints were: the onset of polymerase chain reaction-based DNAemia and the proportion of patients with CMV disease. A number of episodes of CMV infection, antiviral therapy, ganciclovir resistance, infectious or immunological complications, cost of both strategies, and survival (1, 5, and 10 years) were also compared., Results: Forty-eight and 60 patients were respectively included in the P and PS groups. Eighteen (38%) in the P group and 56 (93%) in the PS group had CMV DNAemia (p <.0001) with a similar CMV disease rate (16.7% and 15%). Duration of curative therapy was longer in the PS group: 91 days versus 16 (p <.0001). Acute rejection was less frequent (p = .04) and more patients experienced a ganciclovir-resistant CMV infection in the PS group (10% vs. 0, p = .03). The drug-associated cost of PS was higher (10 004 vs. 4804€) and the median number of rehospitalization days tended to be higher (6 vs. 4, p = .06). Survival at any time was similar., Conclusion: We reported more CMV DNAemias and ganciclovir-resistant CMV events with PS. The cost of the PS strategy was higher., (© 2024 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)

The present study provides the first information on the chemical composition and acetylcholinesterase inhibitory activity of the essential oil (EO) from the leaves of Mitrephora poilanei Weeras. & R.M.K.Saunders from Vietnam. Gas chromatography and gas chromatography-mass spectrometry analysis revealed that the main components of the M. poilanei EO were β-caryophyllene (13.2%), α-humulene (10.5%), germacrene D (8.1%), β-elemene (5.2%) and bicyclogermacrene (5.1%). The anti-acetylcholinesterase assay showed that the EO displayed moderate activity with IC 50 value of 31.16 ± 3.06 μg/mL. These findings proposed that the plant can be exploited for its anti-acetylcholinestrate potential.

BACKGROUND Malignant peritoneal mesothelioma is a rare disease with a poor prognosis that often presents with vague symptoms and inconclusive laboratory test results. Causes include industrial pollutants, primarily asbestos, and certain genetic mutations, such as BAP1. Due to the nonspecific symptoms, it is often incidentally diagnosed during or after other surgical procedures. CASE REPORT A 35-year-old healthy woman underwent an uncomplicated laparoscopic left salpingo-oophorectomy for a symptomatic large ovarian mature cystic teratoma. She subsequently presented with late-onset postoperative fever, leukocytosis, and multiple intra-abdominal masses. Following an exploratory laparotomy, extensive infectious disease evaluation, and multiple biopsies requiring interdisciplinary collaboration, malignant peritoneal mesothelioma was diagnosed by positive histologic staining of an omental biopsy for D2-40 and CK5/6. This first specimen was positive for BAP1, with the second, a liver biopsy, testing negative for BAP1. The tumor cell testing was also notable for mutations in NF2, MLL2, and ARID1A, and the hereditary cancer genetic testing was overall unremarkable. Her disease progressed rapidly, and she died 6 months after her initial procedure. CONCLUSIONS This case of rapidly developing malignant peritoneal mesothelioma following surgical management of an ovarian mature teratoma highlights the complexity in diagnosing a rare disease that presents with nonspecific symptoms in an otherwise young and healthy woman. The rapid disease course was likely accelerated by expansive intraperitoneal spread and multiple somatic oncogenic mutations in BAP1, NF2, MLL2, and ARID1A. Gynecologists should keep a broad differential for postoperative complications, as occult malignancies can present with symptoms that mimic postoperative complications.

Background: Is de novo metastatic breast cancer (dnMBC) the same disease in the elderly as in younger breast cancer remains unclear. This study aimed to determine the metastatic patterns and survival outcomes in dnMBC according to age groups., Methods: We included patients from the Surveillance Epidemiology and End Results program. Chi-square test, multivariate logistic regression analyses, and multivariate Cox regression models were used for statistical analyses., Results: A total of 17719 patients were included. There were 3.6% (n=638), 18.6% (n=3290), 38.0% (n=6725), and 39.9% (n=7066) of patients aged <35, 35-49, 50-64, and ≥65 years, respectively. Older patients had a significantly higher risk of lung metastasis and a significantly lower risk of liver metastasis. There were 19.1%, 25.6%, 30.9%, and 35.7% of patients with lung metastasis in those aged <35, 35-49, 50-64, and ≥65 years, respectively. Moreover, the proportion of liver metastasis was 37.6%, 29.5%, 26.3%, and 19.2%, respectively. Age was the independent prognostic factor associated with breast cancer-specific survival (BCSS) and overall survival (OS). Those aged 50-64 years had significantly inferior BCSS (P<0.001) and OS (P<0.001) than those aged <35 years. Patients aged ≥65 years also had significantly lower BCSS (P<0.001) and OS (P<0.001) than those aged <35 years. However, similar outcomes were found between those aged 35-49 and <35 years., Conclusion: Our study suggests that different age groups may affect the metastatic patterns among patients with dnMBC and the survival of younger patients is more favorable than those of older patients., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Liu, Huang, Chen and Wu.)

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes 1 . Increasingly, large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here, we identify the non-coding RNA RNU4-2 as a novel syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome 2 . We identify an 18 bp region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and Stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 119 individuals with NDD. The vast majority of individuals (77.3%) have the same highly recurrent single base-pair insertion (n.64&#95;65insT). We estimate that variants in this region explain 0.41% of individuals with NDD. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to its contiguous counterpart RNU4-1 and other U4 homologs, supporting RNU4-2 's role as the primary U4 transcript in the brain. Overall, this work underscores the importance of non-coding genes in rare disorders. It will provide a diagnosis to thousands of individuals with NDD worldwide and pave the way for the development of effective treatments for these individuals., Competing Interests: Competing interests NW receives research funding from Novo Nordisk and has consulted for ArgoBio studio. SJS receives research funding from BioMarin Pharmaceutical. AODL is on the scientific advisory board for Congenica, was a paid consultant for Tome Biosciences and Ono Pharma USA Inc., and received reagents from PacBio to support rare disease research. HLR has received support from Illumina and Microsoft to support rare disease gene discovery and diagnosis. MHW has consulted for Illumina and Sanofi and received speaking honoraria from Illumina and GeneDx. SBM is an advisor for BioMarin, Myome and Tenaya Therapeutics. SMS has received honoraria for educational events or advisory boards from Angelini Pharma, Biocodex, Eisai, Zogenix/UCB and institutional contributions for advisory boards, educational events or consultancy work from Eisai, Jazz/GW Pharma, Stoke Therapeutics, Takeda, UCB and Zogenix. The Department of Molecular and Human Genetics at Baylor College of Medicine receives revenue from clinical genetic testing completed at Baylor Genetics Laboratories. JMMH is a full-time employee of Novo Nordisk and holds shares in Novo Nordisk A/S. DGM is a paid consultant for GlaxoSmithKline, Insitro, and Overtone Therapeutics and receives research support from Microsoft.

Anti-infection hydrogels have recently aroused enormous attraction, particularly in the treatment of chronic wounds. Herein, silver nanoparticle@catechol formaldehyde resin microspheres (Ag@CFRs) were fabricated by one-step hydrothermal method and subsequently encapsulated in hydrogels which were developed by Schiff base reaction between aldehyde groups in oxidized hyaluronic acid and amino groups in carboxymethyl chitosan. The developed polysaccharide hydrogel exhibited microporous structure, high swelling capacity, favorable mechanical strength, enhanced tissue adhesion and photothermal activities. Additionally, the hydrogel not only ensured long-term and high-efficiency antibacterial performance (99.9 %) toward E. coli and S. aureus, but also realized superior cytocompatibility in vitro. Moreover, based on the triple antibacterial strategies endowed by chitosan, silver nanoparticles and the photothermal properties of catechol microspheres, the composite hydrogel exhibited excellent anti-infection function, significantly downregulated inflammatory factors (TNF-α and IL-1β) and promoted in vivo infected-wound healing. These results demonstrated that the polysaccharide hydrogel containing Ag@CFRs has great potential for infected-wounds repair., 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 B.V. All rights reserved.)

Background: In patients with pulmonary nodules undergoing computed tomography (CT)-guided localization procedures, a range of liquid-based materials have been employed to date in an effort to guide video-assisted thoracoscopic surgery (VATS) procedures to resect target nodules. However, the relative performance of these different liquid-based localization strategies has yet to be systematically evaluated. Accordingly, this study was developed with the aim of examining the relative safety and efficacy of CT-guided indocyanine green (IG) and blue-stained glue (BSG) PN localization., Methods: Consecutive patients with PNs undergoing CT-guided localization prior to VATS from November 2021 - April 2022 were enrolled in this study. Safety and efficacy outcomes were compared between patients in which different localization materials were used., Results: In total, localization procedures were performed with IG for 121 patients (140 PNs), while BSG was used for localization procedures for 113 patients (153 PNs). Both of these materials achieved 100% technical success rates for localization, with no significant differences between groups with respect to the duration of localization (P = 0.074) or visual analog scale scores (P = 0.787). Pneumothorax affected 8 (6.6%) and 8 (7.1%) patients in the respective IG and BSG groups (P = 0.887), while 12 (9.9%) and 10 (8.8%) patients of these patients experienced pulmonary hemorrhage. IG was less expensive than BSG ($17.2 vs. $165). VATS sublobar resection procedure technical success rates were also 100% in both groups, with no instances of conversion to thoracotomy., Conclusions: IG and BSG both offer similarly high levels of clinical safety and efficacy when applied for preoperative CT-guided PN localization, with IG being less expensive than BSG., 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 Lin, Zhang, Wei, Wu, Wang, Teng, Xian and Han.)

Introduction: Endovascular treatment for acute ischemic stroke patients with large vessel occlusion (LVO) has been established as a promising clinical intervention within a late time window of 6-24 h after symptom onset. Patients with slow progression, however, may still benefit from endovascular treatment beyond the 24-h time window (very late window)., Aim: The aim of this study is to report insight into the potential clinical benefits of endovascular treatment for acute ischemic stroke beyond 24 h from symptom onset., Methods: A retrospective analysis was performed on consecutive patients undergoing endovascular treatment for acute anterior circulation LVO ischemic stroke beyond 24 h. Participants were recruited between July 2019 and November 2020. Patients were selected based on the DAWN/DEFUSE 3 criteria (Perfusion-RAPID, iSchemaView) and patients receiving treatment beyond 24 h were compared to a group of patients receiving endovascular treatment between 6 and 24 h after symptom onset. The primary outcome was the proportion of patients with functional independence at 90 days (modified Rankin Scale score of 0-2). The secondary outcomes were shift modified Rankin Scale (mRS) analysis and successful reperfusion was defined by thrombolysis in cerebral infarction (TICI) 2b-3 on the final procedure. Safety outcomes were symptomatic intracranial hemorrhage and death at the 90-day follow-up. Propensity score (PS)-matched analyses were employed to rectify the imbalanced baseline characteristics between the two groups., Results: A total of 166 patients were recruited with a median age of 63.0 (56.0-69.0) and 28.9% of all patients were females. Patients in the beyond 24-h group had a longer onset-to-groin time (median = 27.2 vs 14.3 h, p < 0.001) than those in the 6- to 24-h group. There were no statistically significant differences between the two groups in National Institutes of Health Stroke Scale (NIHSS) (median = 12.0 vs 15.0, p = 0.37), perfusion imaging characteristics (core: median = 11.0 vs 9.0 mL, p = 0.86; mismatch volume: median = 106.0 vs 96.0, p = 0.44; mismatch ratio = 6.46 vs 7.24, p = 0.91), and perfusion-to-groin time (median = 72.5 vs 76.0 min, p = 0.77). No significant differences were noted among patients between the two groups in the primary endpoint functional independence analysis (50.0% vs 46.6%, p = 0.77) and in the safety endpoint analysis: mortality (15.0% vs 11.0%, p = 0.71) or symptomatic hemorrhage (0% vs 3.42%, p > 0.999). In PS-matched analyses, there were no significant differences among patients between the two groups in functional independence (50.0% vs 54.8%, p = 0.74), mortality (16.7% vs 9.68%, p = 0.50), or symptomatic hemorrhage (0% vs 6.45%, p = 0.53)., Conclusion: Endovascular treatment can be performed safely and effectively in LVO patients beyond 24 h from symptom onset when selected by target mismatch profile. The clinical outcome of these patients was comparable to those treated in the 6- to 24-h window. Larger studies are needed to confirm these findings., 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.

Background: Presurgical computed tomography (CT)-guided localization is frequently employed to reduce the thoracotomy conversion rate, while increasing the rate of successful sublobar resection of ground glass nodules (GGNs) via video-assisted thoracoscopic surgery (VATS). In this study, we compared the clinical efficacies of presurgical CT-guided hook-wire and indocyanine green (IG)-based localization of GGNs., Methods: Between January 2018 and December 2021, we recruited 86 patients who underwent CT-guided hook-wire or IG-based GGN localization before VATS resection in our hospital, and compared the clinical efficiency and safety of both techniques., Results: A total of 38 patients with 39 GGNs were included in the hook-wire group, whereas 48 patients with 50 GGNs were included in the IG group. There were no significant disparities in the baseline data between the two groups of patients. According to our investigation, the technical success rates of CT-based hook-wire- and IG-based localization procedures were 97.4% and 100%, respectively (P = 1.000). Moreover, the significantly longer localization duration (15.3 ± 6.3 min vs. 11.2 ± 5.3 min, P = 0.002) and higher visual analog scale (4.5 ± 0.6 vs. 3.0 ± 0.5, P = 0.001) were observed in the hook-wire patients, than in the IG patients. Occurrence of pneumothorax was significantly higher in hook-wire patients (27.3% vs. 6.3%, P = 0.048). Lung hemorrhage seemed higher in hook-wire patients (28.9% vs. 12.5%, P = 0.057) but did not reach statistical significance. Lastly, the technical success rates of VATS sublobar resection were 97.4% and 100% in hook-wire and IG patients, respectively (P = 1.000)., Conclusions: Both hook-wire- and IG-based localization methods can effectively identified GGNs before VATS resection. Furthermore, IG-based localization resulted in fewer complications, lower pain scores, and a shorter duration of localization., (© 2024. The Author(s).)

Background: To inform the development of an online tool to be potentially used in shared decision-making about breast cancer screening, French women were questioned about participation in breast cancer screening, the health professional's role, and their perceptions of the proposed tool., Methods: We organised focus group discussions with 55 French women. Two different strategies were used to recruit women from high and low socioeconomic backgrounds. We applied both inductive and deductive approaches to conduct a thematic analysis of the discussions. We analysed the responses by using the main determinants from different health behaviour models and compared the two groups., Results: Independently of socioeconomic status, the most important determinant for a woman's participation in breast cancer screening was the perceived severity of breast cancer and the perceived benefits of its early detection by screening. Cues to action reported by both groups were invitation letters; recommendations by health professionals, or group/community activities and public events were reported by women from high and low socioeconomic backgrounds, respectively. Among other positive determinants, women from high socioeconomic backgrounds reported making informed decisions and receiving peer support whereas women from low socioeconomic backgrounds reported community empowerment through group/community events. Fear of cancer was reported as a barrier in both groups. Among other barriers, language issues were reported only by women from low socioeconomic backgrounds; women from high socioeconomic backgrounds reported breast cancer screening-related risks other than overdiagnosis and/or overtreatment. Barriers to accessing the online tool to be developed were mainly reported by women from high socioeconomic backgrounds., Conclusion: Limitations in implementing shared decision-making for women from low socioeconomic backgrounds were highlighted. An online tool that is suitable for all women, regardless of socioeconomic status, would provide "on-demand" reliable and tailored information about breast cancer screening and improve access to health professionals and social exchanges., (© 2024. The Author(s).)

A method for material classification of traditional Chinese medicines based on the physical properties of powder has been established by our research group. This method involves pre-treatment of traditional Chinese medicine decoction pieces, powder preparation, and determination of physical properties, being cumbersome. In this study, the word segmentation logic of semantic analysis was adopted to establish the thesaurus and local standardized semantic word segmentation database with the macroscopic and microscopic characteristics of 36 model traditional Chinese medicines as the basic data. The physical properties of these medicines have been determined and the classification of these medicines is clear in the cluster analysis. A total of 55 keywords for powdery, fibrous, sugary, oily, and brittle materials were screened by association rules and the set inclusion and exclusion criteria, and the weights of the keywords were calculated. Furthermore, the algorithms of the keyword matching scores and the computation rules of the single or multiple material classification were established for building the intelligent model of semantic analysis for the material classification. The semantic classification results of the other 35 TCMs except Pseudostellariae Radix(multi-material medicine) agreed with the clustering results based on the physical properties of the powder, with an agreement rate of 97.22%. In model validation, the prediction results of semantic classification of traditional Chinese medicines were consistent with the clustering results based on the physical properties of powder, with an agreement rate of 83.33%. The results showed that the method of material classification based on semantic analysis was feasible, which laid a foundation for the development of intelligent decision-making technology for personalized traditional Chinese medicine preparations.

This study aims to optimize the composite excipients suitable for the preparation of concentrated water pills of personalized traditional Chinese medicine prescriptions by the extruding-rounding method and investigate the roles of each excipient in the preparation process. The fiber materials and powder materials were taken as the standard materials suitable as excipients in the preparation of personalized concentrated water pills without excipient. Water absorption properties and torque rheology were used as indicators for selecting the materials of composite excipients. The ratio of composite excipients was optimized by D-optimal mixture design. Moreover, to demonstrate the universal applicability of the optimal composite excipients, this study selected three traditional Chinese medicine prescriptions with low, medium, and high extraction rates to verify the optimal ratio. Finally, the effects of each selected excipient on the molding of personalized concentrated water pills were investigated with the four parameters of the pill molding quality as indicators. The optimized composite excipients were dextrin∶microcrystalline cellulose(MCC)∶low-substituted hydroxypropyl cellulose(L-HPC) at a ratio of 1∶2∶4. The composite excipients were used for the preparation of personalized concentrated water pills with stable process, good quality, and a wide range of application. Dextrin acted as a diluent and accelerated the speed of extruding. MCC mainly served as an adhesive, increasing the cohesion and viscosity of the pills. L-HPC as a water absorbent and disintegrating agent can absorb and hold the water of the concentrate and has a strong disintegration effect.

In recent years, as people's living standards continue to improve, and the pace of life accelerates dramatically, the demand and quality of traditional Chinese medicine(TCM) services from patients continue to rise. As an essential supplement to the existing forms of TCM application, such as Chinese patent medicine, decoction, and formulated granules, presonalized TCM preparations is facing an increasing market demand. Currently, manual and semi-mechanized production are the primary production ways in presonalized TCM preparations. However, the production process control level is low, and digitalization and informatization need to be improved, which restricts the automated and intelligent development of presonalized TCM preparations. Presonalized TCM preparations faces a significant opportunity and challenge in integrating with intelligent manufacturing through research and development of intelligent equipment and core technology. This paper overviews the connotation and characteristics of intelligent manufacturing and summarizes the application of intelligent manufacturing technologies such as &quot;Internet of things&quot; &quot;big data&quot;, and &quot;artificial intelligence&quot; in the TCM industry. Based on the innovative research and development model of &quot;intelligent classification of TCM materials, intelligent decision making of prescription and process, and online control and intelligent production&quot; of presonalized TCM preparations, the research practice and achievements from our research group in the field of intelligent manufacturing of presonalized TCM preparations are introduced. Ultimately, the paper proposes the direction for developing intelligent manufacturing of presonalized TCM preparations, which will provide a reference for the research and application of automation and intelligence of presonalized TCM preparations.

In the process of preparing presonalized concentrated watered pills, the decoction needs to be concentrated by heat and mixed with medicinal slices or powder to prepare a wet mass. However, some of the traditional Chinese medicine(TCM) components are easily decomposed or transformed by heat. In order to optimize the preparation process of presonalized TCM concentrated watered pills and reduce the loss of heat-unstable components in prescriptions, this study uses five compound TCM prescriptions containing heat-unstable components as model prescriptions, namely the Linggui Zhugan Formula, Xiaochengqi Formula, Sanpian Formula, Xiaoer Qixing Formula, and Xiaoyao Formula. Based on the two kinds of preparation process of presonalized concentrated watered pills previously established by our research group, whole extract concentrated watered pills and concentrated watered pills without excipients are prepared, respectively. Characteristic maps are measured and compared with those of the corresponding decoction. The results show that the characteristic maps of the concentrated watered pills without excipients of the five model prescriptions are very close to those of the decoction, and the number of characteristic peaks and peak areas are higher than those of whole extract concentrated watered pills. In addition, the peak area of some peaks is higher than that of the corresponding decoction. Thus, it is recommended to select the preparation process of prescription-based concentrated watered pills without excipients based on the &quot;unification of medicines and excipients&quot; to preserve those heat-unstable components more effectively when the prescription contains a heat-unstable component of TCM. This study provides a basis for the subsequent reasonable development and application of presonalized TCM pills.

This study aims to optimize the prediction model of personalized water pills that has been established by our research group. Dioscoreae Rhizoma, Leonuri Herba, Codonopsis Radix, Armeniacae Semen Amarum, and calcined Oyster were selected as model medicines of powdery, fibrous, sugary, oily, and brittle materials, respectively. The model prescriptions were obtained by uniform mixing design. With hydroxypropyl methylcellulose E5(HPMC-E5) aqueous solution as the adhesive, personalized water pills were prepared by extrusion and spheronizaition. The evaluation indexes in the pill preparation process and the multi-model statistical analysis were employed to optimize and evaluate the prediction model of personalized water pills. The prediction equation of the adhesive concentration was obtained as follows: Y&#95;1=-4.172+3.63X&#95;A+15.057X&#95;B+1.838X&#95;C-0.997X&#95;D(adhesive concentration of 10% when Y&#95;1&lt;0, and 20% when Y&#95;1&gt;0). The overall accuracy of the prediction model for adhesive concentration was 96.0%. The prediction equation of adhesive dosage was Y&#95;2=6.051+94.944X&#95;A~(1.5)+161.977X&#95;B+70.078X&#95;C~2+12.016X&#95;D~(0.3)+27.493X&#95;E~(0.3)-2.168X&#95;F~(-1)(R~2=0.954, P&lt;0.001). Furthermore, the semantic prediction model for material classification of traditional Chinese medicines was used to classify the materials contained in the prescription, and thus the prediction model of personalized water pills was evaluated. The results showed that the prescriptions for model evaluation can be prepared with one-time molding, and the forming quality was better than that established by the research group earlier. This study has achieved the optimization of the prediction model of personalized water pills.

Computing demands for large scientific experiments, such as the CMS experiment at the CERN LHC, will increase dramatically in the next decades. To complement the future performance increases of software running on central processing units (CPUs), explorations of coprocessor usage in data processing hold great potential and interest. Coprocessors are a class of computer processors that supplement CPUs, often improving the execution of certain functions due to architectural design choices. We explore the approach of Services for Optimized Network Inference on Coprocessors (SONIC) and study the deployment of this as-a-service approach in large-scale data processing. In the studies, we take a data processing workflow of the CMS experiment and run the main workflow on CPUs, while offloading several machine learning (ML) inference tasks onto either remote or local coprocessors, specifically graphics processing units (GPUs). With experiments performed at Google Cloud, the Purdue Tier-2 computing center, and combinations of the two, we demonstrate the acceleration of these ML algorithms individually on coprocessors and the corresponding throughput improvement for the entire workflow. This approach can be easily generalized to different types of coprocessors and deployed on local CPUs without decreasing the throughput performance. We emphasize that the SONIC approach enables high coprocessor usage and enables the portability to run workflows on different types of coprocessors., Competing Interests: Conflict of interestThe authors declare no conflict of interest., (© The Author(s) 2024.)

Objectives: Whether or not a gastric cancer (GC) patient exhibits lymph node metastasis (LNM) is critical to accurately guiding their treatment and prognostic evaluation, necessitating the ability to reliably predict preoperative LNM status. The present meta-analysis sought to examine the diagnostic value of computed tomography (CT)-based predictive models as a tool to gauge the preoperative LNM status of patients with GC., Methods: Relevant articles were identified in the PubMed, Web of Science, and Wanfang databases. These studies were used to conduct pooled analyses examining sensitivity, specificity, positive likelihood ratio (PLR), and negative likelihood ratio (NLR) values, and area under the curve values were computed for summary receiver operating characteristic curves., Results: The final meta-analysis incorporated data from 15 studies, all of which were conducted in China, enrolling 3,817 patients with GC (LNM+: 1790; LNM-: 2027). The developed CT-based predictive model exhibited respective pooled sensitivity, specificity, PLR, and NLR values of 84% (95% confidence interval [CI], 0.79-0.87), 81% (95% CI, 0.76-0.85), 4.39 (95% CI, 3.40-5.67), and 0.20 (95% CI, 0.16-0.26). The identified results were not associated with significant potential for publication bias ( P = 0.071). Similarly, CT-based analyses of LN status exhibited respective pooled sensitivity, specificity, PLR, and NLR values of 62% (95% CI, 0.53-0.70), 77% (95% CI, 0.72-0.81), 2.71 (95% CI, 2.20-3.33), and 0.49 (95% CI, 0.40-0.61), with no significant risk of publication bias ( P = 0.984)., Conclusions: Overall, the present meta-analysis revealed that a CT-based predictive model may outperform CT-based analyses alone when assessing the preoperative LNM status of patients with GC, offering superior diagnostic utility., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Using proton-proton collision data corresponding to an integrated luminosity of 140 fb - 1 collected by the CMS experiment at s = 13 Te V , the Λ b 0 → J / ψ Ξ - K + decay is observed for the first time, with a statistical significance exceeding 5 standard deviations. The relative branching fraction, with respect to the Λ b 0 → ψ ( 2 S ) Λ decay, is measured to be B ( Λ b 0 → J / ψ Ξ - K + ) / B ( Λ b 0 → ψ ( 2 S ) Λ ) = [ 3.38 ± 1.02 ± 0.61 ± 0.03 ] % , where the first uncertainty is statistical, the second is systematic, and the third is related to the uncertainties in B ( ψ ( 2 S ) → J / ψ π + π - ) and B ( Ξ - → Λ π - ) ., Competing Interests: Conflict of interestThe authors declare that they have no Conflict of interest., (© The Author(s) 2024.)

Background: The health crisis related to the COVID-19 pandemic led to an unprecedented situation in France: complete lockdown. The population had to live confined with their families, which often meant that parents telecommuted while caring for their children. However, daily risks remained more than ever at the forefront. The aim of this study was to assess the epidemiology of burns among children during three different periods of family time: school time, vacation, and lockdown., Methods: A single-center retrospective study was conducted at Tours University Hospital. All pediatric surgical emergency room visits recorded from February 10, 2020 to March 31, 2020 were included. The three aforementioned periods were assessed., Results: During lockdown there were significantly more burns compared to other injuries (p = 0.004). Preschool-age children suffered significantly more from burns during the same period (p = 0.029). There were no significant differences for nursery school (p = 0.522), primary school (p = 0.519), middle school (p = 0.613), and high school (p = N) children., Conclusion: This study underlines the need to establish a targeted prevention campaign geared toward a complicated geopolitical situation a pandemic that might occur again., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.)

Background: OBQ11 was developed in a Swedish context. To evaluate occupational balance, accurate self-rating instruments in the native language are needed., Aim: The aim was to investigate the measurement properties of the Danish version of OBQ11, using the Rasch analysis., Method: Data for the analysis of the Danish version of OBQ11 (OBQ11-DK) was gathered online, and all full data records (n 366) were included in the analysis., Results: Three items showed non-significant marginal under- or overfit, suggesting a degree of misfit between the data and the Rasch model. Unidimensionality was not reached, though, since the proportion of persons with different estimates were more than 5% and thus the OBQ11-DK cannot be said to assess a person's perception of occupational balance., Conclusion: The present version of the OBQ11-DK shows the need for further development and testing and is not tested for test/retest or in clinical samples. The results and small number of items may after modifications and further studies make it feasible to implement OBQ11-DK into settings where the measuring of occupational balance is needed.

We aimed to investigate the neuroprotective effect of rutin on retinal ganglion cells (RGCs) under ischemia-reperfusion (I/R) conditions and the underlying mechanisms involving microglia polarization and JAK/STAT3 signaling. RGCs isolated from C57/Bl6 mice were co-cultured with BV2 microglial cells under normal or in vitro oxygen-glucose deprivation and reoxygenation (OGD/R) conditions. Rutin's effects were evaluated by assessing cell viability, apoptosis rates, cytokine levels, microglial polarization markers and JAK/STAT3 phosphorylation levels. The specific target is confirmed through the inhibitory effect of rutin on the respectively activated signaling factors. Furthermore, molecular docking analyses elucidated rutin-JAK1 interactions. OGD/R conditions significantly reduced RGC viability, exacerbated by BV2 co-culture. However, both 1 μM and 5 μM rutin treatment dose-dependently enhanced RGC viability, reduced apoptosis, and suppressed pro-inflammatory cytokine levels. Western blot analysis indicated that rutin promoted the M2 microglial phenotype and suppressed JAK/STAT3 signaling. Notably, rutin selectively inhibited JAK1 phosphorylation without affecting STAT3. Molecular docking highlighted potential interaction sites between rutin and specific JAK1 pseudokinase domain. Rutin exerts neuroprotective effects against retinal I/R injury by promoting M2 microglial polarization, potentially through the selective inhibition of JAK1 phosphorylation within the JAK/STAT3 signaling pathway. These findings provide a foundation for the therapeutic potential of rutin in retinal I/R injuries.

Vaccines are strongly recommended globally as an effective measure to prevent serious illness from and spread of COVID-19. Concerns about safety following vaccination continue to be the most common reason that people do not accept the vaccine. This retrospective study was carried out on 4341 people who received the first dose of ChAdOx1 nCoV-19, BBIBP-CorV, or mRNA-1273 vaccine at Jio Health Clinic in Ho Chi Minh City, Vietnam. Post-injection side effects were either reported by participants or actively collected by health care staff by means of telemedicine. Local side effects were reported by 35.5% of all individuals, with pain being the most common symptom (33.3%). Systemic side effects were reported by 44.2% of individuals, with fever (25.3%) and fatigue (21.4%) being the most common. Age ≤60 years, female gender, and ChAdOx1 nCoV-19 were significant independent risk factors for both local and systemic side effects, while a history of allergy was significant as a risk factor for local side effects. A total of 43 individuals (1.0%) reported concerning symptoms of rare severe complications, which were addressed and treated by physicians via Jio Health app.

Objectives: Systemic sclerosis (SSc) can cause malnutrition due to frequent gastrointestinal involvement. However, prevalence of malnutrition in SSc is poorly known. The aim of this study was to evaluate the prevalence of malnutrition in SSc and its potential associations with disease features in patients from a tertiary referral center., Methods: All patients meeting American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for SSc followed between January 1, 1985, and January 1, 2019, at the Department of Internal Medicine, Saint Eloi University Hospital, were included. Malnutrition was assessed using the 2020 French recommendations for SSc and the malnutrition universal screening tool score. Severe malnutrition was defined via the French Haute Autorité de Santé (National Health Authority) 2007 criteria., Results: A total of 120 patients were included, with mean age 64 (± 15) y and a female-to-male sex ratio of 5:1. According to 2020 French recommendations, 71 patients (59.2%) were malnourished and 30 (25%) had at least one criterion of severe malnutrition. With the malnutrition universal screening tool score, 41.7%, 20%, and 38.3%, respectively, had low, medium, and high risk of malnutrition. Multivariate analysis revealed the following results: 1) malnutrition was associated with cardiac involvement (P < 0.01); 2) a high malnutrition universal screening tool score was also associated with specific cardiac involvement (P < 0.01); and 3) severe malnutrition was strongly correlated with interincisal distance <35 mm (P = 0.02)., Conclusions: Malnutrition affects more than half of SSc patients and is associated with specific cardiac involvement. Interincisal distance <35 mm could be a red flag for severe malnutrition in SSc., 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 © 2023 Elsevier Inc. All rights reserved.)

Background: Dinutuximab β can be used to treat children with high-risk neuroblastoma (NB). Due to its high price, whether dinutuximab β is cost-effective for the treatment of high-risk NB remains uncertain. Therefore, assessing the cost-effectiveness of dinutuximab β in children with high-risk NB is of high importance., Methods: The health utilities and economic outcomes in children with high-risk NB were projected using a partitioned survival model. The individual patient data (IPD) of add-on treatment with dinutuximab β (GD2 group) were derived from the literature, while the IPD of traditional therapy (TT group) were obtained from retrospective data of Shanghai Children's Medical Center. Treatment costs included drugs, adverse event-related expenses, and medical resource use. Utility values were obtained from the literature. Costs and quality-adjusted life-years (QALYs) were measured over a 10-year time horizon. Deterministic sensitivity analyses (DSA) and probabilistic sensitivity analyses (PSA) were also conducted., Results: Compared with the TT group, QALY increased in the GD2 group by 0.72 with an increased cost of $171,269.70, leading to an incremental cost-effectiveness ratio of 236,462.75$/QALY. DSA showed that the price of dinutuximab β was the main factor on the results than other parameters. Compared with the TT group, the GD2 group could not be cost-effective in the PSA at the $37,920/QALY threshold., Conclusion: Results found that dinutuximab β is not a cost-effective treatment option for children with high-risk NB unless its price is significantly reduced., (© 2023 Wiley Periodicals LLC.)

Deregulation of the Hippo pathway is a driver for cancer progression and treatment resistance. In the context of gastric cancer, YAP1 is a biomarker for poor patient prognosis. Although genomic tumor profiling provides information of Hippo pathway activation, the present study demonstrates that inhibition of Yap1 activity has anti-tumor effects in gastric tumors driven by oncogenic mutations and inflammatory cytokines. We show that Yap1 is a key regulator of cell metabolism, proliferation, and immune responses in normal and neoplastic gastric epithelium. We propose that the Hippo pathway is targetable across gastric cancer subtypes and its therapeutic benefits are likely to be mediated by both cancer cell-intrinsic and -extrinsic mechanisms., (© 2023 Thilakasiri et al.)

Astrocytes are not only the most populous cell type in the human brain, but they also have the most extensive and diverse sets of connections, across synapses, axons, blood vessels, as well as having their own internal network. Unsurprisingly, they are associated with many brain functions; from the synaptic transmission to energy metabolism and fluid homeostasis, and from cerebral blood flow and blood-brain barrier maintenance to neuroprotection, memory, immune defenses and detoxification, sleep, and early development. And yet, notwithstanding these key roles, so many current therapeutic approaches to a range of brain disorders have largely neglected their potential involvement. In this review, we consider the role of astrocytes in three brain therapies; two are emerging treatments (photobiomodulation and ultrasound), while the other is well-established (deep brain stimulation). In essence, we explore the issue of whether external sources, such as light, sound, or electricity, can influence the function of astrocytes, as they do neurons. We find that, when taken all together, each of these external sources can influence many, if not, all of the functions associated with astrocytes. These include influencing neuronal activity, prompting neuroprotection, reducing inflammation (astrogliosis) and potentially increasing cerebral blood flow and stimulating the glymphatic system. We suggest that astrocytes, just like neurons, can respond positively to each of these external applications and that their activation could each impart many beneficial outcomes on brain function; they are likely to be key players underpinning the mechanisms behind many therapeutic strategies., Competing Interests: None