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In this paper, a novel surrogate model for shape-parametrized vehicle drag force prediction is proposed. It is assumed that only a limited dataset of high-fidelity CFD results is available, typically less than ten high-fidelity CFD solutions for different shape samples. The idea is to take advantage not only of the drag coefficients but also physical fields such as velocity, pressure, and kinetic energy evaluated on a cutting plane in the wake of the vehicle and perpendicular to the road. This additional “augmented” information provides a more accurate and robust prediction of the drag force compared to a standard surface response methodology. As a first step, an original reparametrization of the shape based on combination coefficients of shape principal components is proposed, leading to a low-dimensional representation of the shape space. The second step consists in determining principal components of the x-direction momentum flux through a cutting plane behind the car. The final step is to find the mapping between the reduced shape description and the momentum flux formula to achieve an accurate drag estimation. The resulting surrogate model is a space-parameter separated representation with shape principal component coefficients and spatial modes dedicated to drag-force evaluation. The algorithm can deal with shapes of variable mesh by using an optimal transport procedure that interpolates the fields on a shared reference mesh. The Machine Learning algorithm is challenged on a car concept with a three-dimensional shape design space. With only two well-chosen samples, the numerical algorithm is able to return a drag surrogate model with reasonable uniform error over the validation dataset. An incremental learning approach involving additional high-fidelity computations is also proposed. The leading algorithm is shown to improve the model accuracy. The study also shows the sensitivity of the results with respect to the initial experimental design. As feedback, we discuss and suggest what appear to be the correct choices of experimental designs for the best results.

BackgroundVariants in the MYBPC3 gene are a frequent cause of hypertrophic cardiomyopathy (HCM) but display a large phenotypic heterogeneity. Founder mutations are often believed to be more benign as they prevailed despite potential negative selection pressure. We detected a pathogenic variant in MYBPC3 (del exon 23-26) in several probands. We aimed to assess the presence of a common haplotype and to describe the cardiac characteristics, disease severity and long-term outcome of mutation carriers.MethodsProbands with HCM caused by a pathogenic deletion of exon 23-26 of MYBPC3 were identified through genetic screening using a gene panel encompassing 59 genes associated with cardiomyopathies in a single genetic center in Belgium. Cascade screening of first-degree relatives was performed, and genotype positive relatives were further phenotyped. Clinical characteristics were collected from probands and relatives. Cardiac outcomes included death, heart transplantation, life-threatening arrhythmia, heart failure hospitalization or septal reduction therapy. Haplotype analysis, using microsatellite markers surrounding MYBPC3, was performed in all index patients to identify a common haplotype. The age of the founder variant was estimated based on the size of the shared haplotype using a linkage-disequilibrium based approach.ResultsWe identified 24 probands with HCM harbouring the MYBPC3 exon 23-26 deletion. Probands were on average 51 ± 16 years old at time of clinical HCM diagnosis and 62 ± 10 years old at time of genetic diagnosis. A common haplotype of 1.19 Mb was identified in all 24 probands, with 19 of the probands sharing a 13.8 Mb haplotype. The founder event was estimated to have happened five generations, or 175–200 years ago, around the year 1830 in central Flanders. Through cascade screening, 59 first-degree relatives were genetically tested, of whom 37 (62.7%) were genotype positive (G+) and 22 (37.3%) genotype negative (G-). They were on average 38 ± 19 years old at time of genetic testing. Subsequent clinical assessment revealed a HCM phenotype in 19 (51.4%) G+ relatives. Probands were older (63 ± 10 vs. 42 ± 21 years; p < 0.001) and had more severe phenotypes than G+ family members, presenting with more symptoms (50% vs. 13.5%; p = 0.002), arrhythmia (41.7% vs. 12.9%, p = 0.014), more overt hypertrophy and left ventricular outflow tract obstruction (43.5% vs. 3.0%; p < 0.001). Male G+ relatives more often had a HCM phenotype (78.6% vs. 34.8%; p = 0.010) and were more severely affected than females. At the age of 50, a penetrance of 78.6% was observed, defined as the presence of HCM in 11 of 14 G+ relatives with age ≥50 years. Overall, 20.3% of all variant carriers developed one of the predefined cardiac outcomes after a median follow-up of 5.5 years with an average age of 50 (±21) years.ConclusionA Belgian founder variant, an exon 23-26 deletion in MYBPC3, was identified in 24 probands and 37 family members. The variant is characterized by a high penetrance of 78.6% at the age of 50 years but has variable phenotypic expression. Adverse outcomes were observed in 20.3% of patients during follow-up.

Recently, OTULIN haploinsufficiency was linked to enhanced susceptibility to Staphylococcus aureus infections accompanied by local necrosis and systemic inflammation. The pathogenesis observed in haploinsufficient patients differs from the hyperinflammation seen in classical OTULIN-related autoinflammatory syndrome (ORAS) patients and is characterized by increased susceptibility of dermal fibroblasts to S. aureus alpha toxin-inflicted cytotoxic damage. Immunological abnormalities were not observed in OTULIN haploinsufficient patients, suggesting a non-hematopoietic basis. In this research report, we investigated an Otulin+/− mouse model after in vivo provocation with lipopolysaccharide (LPS) to explore the potential role of hematopoietic-driven inflammation in OTULIN haploinsufficiency. We observed a hyperinflammatory signature in LPS-provoked Otulin+/− mice, which was driven by CD64+ monocytes and macrophages. Bone marrow-derived macrophages (BMDMs) of Otulin+/− mice demonstrated higher proinflammatory cytokine secretion after in vitro stimulation with LPS or polyinosinic:polycytidylic acid (Poly(I:C)). Our experiments in full and mixed bone marrow chimeric mice suggest that, in contrast to humans, the observed inflammation was mainly driven by the hematopoietic compartment with cell-extrinsic effects likely contributing to inflammatory outcomes. Using an OTULIN haploinsufficient mouse model, we validated the role of OTULIN in the regulation of environmentally directed inflammation.

Manufacturing industry faces increasing complexity in the performance of assembly tasks due to escalating demand for complex products with a greater number of variations. Operators require robust assistance systems to enhance productivity, efficiency, and safety. However, existing support services often fall short when operators encounter unstructured open questions and incomplete sentences due to primarily relying on procedural digital work instructions. This draws attention to the need for practical application of natural language processing (NLP) techniques. This study addresses these challenges by introducing a domain-specific dataset tailored to assembly tasks, capturing unique language patterns and linguistic characteristics. We explore strategies to process declarative and imperative sentences, including incomplete ones, effectively. Thorough evaluation of three pre-trained NLP libraries—NLTK, SPACY, and Stanford—is performed to assess their effectiveness in handling assembly-related concepts and ability to address the domain’s distinctive challenges. Our findings demonstrate the efficient performance of these open-source NLP libraries in accurately handling assembly-related concepts. By providing valuable insights, our research contributes to developing intelligent operator assistance systems, bridging the gap between NLP techniques and the assembly domain within manufacturing industry.

Background: To report quantitative and qualitative results on cervical cancer human papillomavirus (HPV)-based screening and treatment algorithms, with/out triage with visual inspection after acetic acid (VIA), followed by ablative treatment (AT). Methods: Women 30 to 54 years old from Durban, South Africa were recruited, regardless of human immunodeficiency virus (HIV) status, randomized into one of two study arms and screened for HPV. VIA triage arm: HPV-positive women were triaged using VIA, biopsied and received AT if VIA positive and eligible; no triage arm: eligible HPV-positive women received AT. Women ineligible for AT were referred to colposcopy. Women were asked about side effects immediately and 1 week after AT. Retention to screening and treatment algorithms was compared between arms. Results: A total of 350 women [275 HIV-uninfected and 75 women living with HIV, (WLWH)] were allocated to receive HPV testing with VIA triage (n = 175) or no triage (n = 175). HPV prevalence was 28% [95% confidence interval (CI) = 23-33]; WLWH: 52% (95% CI = 40-64) versus HIV-uninfected: 21% (95% CI = 17-27; P < 0.05). Among women who underwent VIA triage with histologic diagnosis, 3/17 were VIA negative with cervical intraepithelial neoplasia (CIN)2+; 14/18 were VIA positive with

Background: Several rare surfactant-related gene (SRG) variants associated with interstitial lung disease are suspected to be associated with lung cancer, but data are missing. We aimed to study the epidemiology and phenotype of lung cancer in an international cohort of SRG variant carriers., Methods: We conducted a cross-sectional study of all adults with SRG variants in the OrphaLung network and compared lung cancer risk with telomere-related gene (TRG) variant carriers., Results: We identified 99 SRG adult variant carriers ( SFTPA1 (n=18), SFTPA2 (n=31), SFTPC (n=24), ABCA3 (n=14) and NKX2-1 (n=12)), including 20 (20.2%) with lung cancer ( SFTPA1 (n=7), SFTPA2 (n=8), SFTPC (n=3), NKX2-1 (n=2) and ABCA3 (n=0)). Among SRG variant carriers, the odds of lung cancer was associated with age (OR 1.04, 95% CI 1.01-1.08), smoking (OR 20.7, 95% CI 6.60-76.2) and SFTPA1 / SFTPA2 variants (OR 3.97, 95% CI 1.39-13.2). Adenocarcinoma was the only histological type reported, with programmed death ligand-1 expression ≥1% in tumour cells in three samples. Cancer staging was localised (I/II) in eight (40%) individuals, locally advanced (III) in two (10%) and metastatic (IV) in 10 (50%). We found no somatic variant eligible for targeted therapy. Seven cancers were surgically removed, 10 received systemic therapy, and three received the best supportive care according to their stage and performance status. The median overall survival was 24 months, with stage I/II cancers showing better survival. We identified 233 TRG variant carriers. The comparative risk (subdistribution hazard ratio) for lung cancer in SRG patients versus TRG patients was 18.1 (95% CI 7.1-44.7)., Conclusions: The high risk of lung cancer among SRG variant carriers suggests specific screening and diagnostic and therapeutic challenges. The benefit of regular computed tomography scan follow-up should be evaluated., Competing Interests: Conflict of interest: P. Bonniaud reports grants from AstraZeneca, lecture honoraria from Sanofi and AstraZeneca, travel support from AstraZeneca, Novartis, Sanofi, Boehringer and Stallergenes, and advisory board membership with AstraZeneca, Novartis, Sanofi, GSK and Boehringer. J. Cadranel had a patent planned, received consulting fees and participated on a data safety monitoring board or advisory board for AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, BMS, Daichi, Lilly, Pfizer, Novartis, MSD, Roche and Takeda. A. Cazes reports lecture honoraria and travel support from Boehringer Ingelheim. B. Crestani reports grants from Boehringer Ingelheim, consulting fees from Apellis, BMS, Boehringer Ingelheim and Sanofi, lecture honoraria from Apellis, AstraZeneca, BMS, Boehringer Ingelheim, Novartis and Sanofi, support for attending meetings or travel from AstraZeneca, BMS, Boehringer Ingelheim and Sanofi, participated on a data safety monitoring board or advisory board for Apellis, BMS, Boehringer Ingelheim and Sanofi, and had a leadership role as President of the Board of Trustees of the Fondation du Souffle. R. Epaud reports consulting fees from AstraZeneca, lecture honoraria from GSK, AstraZeneca and Menarini, travel support from GSK and AstraZeneca, and advisory board membership with AstraZeneca and Novartis. M-P. Debray reports lecture honoraria and travel support from Boehringer Ingelheim. E. Manali reports lecture honoraria from Boehringer Ingelheim, CLS Behring and Hoffman-La Roche, support for attending meetings or travel from Boehringer Ingelheim, CLS Behring, Hoffman-La Roche and Elpen, and had a leadership role as a Chair in the ERS Task Force for transition of chILD to adult care. S. Papiris reports lecture honoraria from Boehringer Ingelheim and Hoffmann-La Roche, and travel support from Boehringer Ingelheim and Elpen. N. Nathan reports grants from Legs poix de la Chancellerie des Universités 2022 (number 2022000594). C. Andréjak participated on a data safety monitoring board or advisory board for the EVER-ILD2 study (rituximab in diffuse interstitial pneumonia) and received funding via a grant from the French Research Ministry. S. Jouneau reports grants from AIRB, Boehringer Ingelheim and Roche, lecture honoraria from AIRB, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Chiesi, Genzyme, GSK, LVL, Novartis, Pfizer, Roche and Sanofi, travel support from Boehringer Ingelheim, Roche and AIRB, and advisory board participation for Boehringer Ingelheim, GSK and Sanofi. G. Beltramo reports lecture honoraria from Bristol Myers Squibb, and support for attending meetings or travel from Sanofi Aventis France and Boehringer Ingelheim France. S. Hirschi reports research grants from Agence de la Biomedécine, CSL Behring and Adiral medical assistance, lecture honoraria from Boehringer Ingelheim, travel support from CSL Behring, Boehringer Ingelheim and ISIS Medical, and received medical equipment from ISIS Medical. C. Picard reports lecture honoraria and consulting fees from Boehringer Ingelheim. G. Prévot reports honoraria for presentations and educational event from Boehringer Ingelheim, Sanofi, Jansen and MSD. G. Zalcman reports consulting fees from AstraZeneca, BMS, Pfizer and Sanofi, lecture honoraria from BMS, AstraZeneca and Sanofi, support for attending meetings or travel from AstraZeneca and BMS, and participated on a data safety monitoring board or advisory board for AstraZeneca and BMS. V. Cottin reports grants from Boehringer Ingelheim, consulting fees from AstraZeneca, Boehringer Ingelheim, Celgene/BMS, CSL Behring, Ferrer/United Therapeutics, GSK, Pliant, Pure Tech, RedX, Roche, Sanofi and Shionogi, lecture honoraria from Boehringer Ingelheim, Ferrer/United Therapeutics and Roche, support for attending meetings or travel from Boehringer Ingelheim and Roche, participated on a data safety monitoring board or advisory board for Galapagos, Galecto and GSK, and had a leadership role in an adjudication committee for Fibrogen. R. Borie reports consulting fees from Boehringer Ingelheim, Ferrer and Sanofi, lecture honoraria from Boehringer Ingelheim and Roche, travel support from Boehringer Ingelheim, Roche and Chiesi, and advisory board participation for Savara. The remaining authors have no potential conflicts of interest to disclose., (Copyright ©The authors 2024.)