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Wearable augmented reality in neurosurgery offers significant advantages by enabling the visualization of navigation information directly on the patient, seamlessly integrating virtual data with the real surgical field. This ergonomic approach can facilitate a more intuitive understanding of spatial relationships and guidance cues, potentially reducing cognitive load and enhancing the accuracy of surgical gestures by aligning critical information with the actual anatomy in real-time. This study evaluates the benefits of a novel AR platform, VOSTARS, by comparing its targeting accuracy to that of the gold-standard electromagnetic (EM) navigation system, Medtronic StealthStation® S7®. Both systems were evaluated in phantom and human studies. In the phantom study, participants targeted 13 predefined landmarks using identical pointers to isolate system performance. In the human study, three facial landmarks were targeted in nine volunteers post-brain tumor surgery. The performance of the VOSTARS system was superior to that of the standard neuronavigator in both the phantom and human studies. In the phantom study, users achieved a median accuracy of 1.4 mm (IQR: 1.2 mm) with VOSTARS compared to 2.9 mm (IQR: 1.4 mm) with the standard neuronavigator. In the human study, the median targeting accuracy with VOSTARS was significantly better for selected landmarks in the outer eyebrow (3.7 mm vs. 6.6 mm, p = 0.05) and forehead (4.5 mm vs. 6.3 mm, p = 0.021). Although the difference for the pronasal point was not statistically significant (2.7 mm vs. 3.5 mm, p = 0.123), the trend towards improved accuracy with VOSTARS is clear. These findings suggest that the proposed AR technology has the potential to significantly improve surgical outcomes in neurosurgery.

The objective of this study was to evaluate the influence of different light spectra on growth, development indices, survival and color preferences in Macrobrachium rosenbergii larvae. First (trial 1, 25 days), prawns (100 larvae/L) were randomly allocated to 30 cylindrical plastic containers (1 L). This trial was designed with five treatments (light spectra) and six replications: red light, blue light, green light and white light or absence of light (controls) in the 12:12 light:dark (LD) cycle. Next (trial 2), 30 groups of five larvae in two different development stages (VII and XI) were allocated to a system of compartments with different lights: white, red, blue or green. This system was connected by tubes to enable light spectra choices. Final weight, weight gain, consumption and metamorphosis significantly improved under the white light condition versus the other tested groups (p

IntroductionSystemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by microvascular damage, immune system reactivity and progressive fibrosis of skin and internal organs. Interstitial lung disease is the leading cause of death for SSc patients (SSc-ILD), and the process of lung fibrosis involves also circulating monocytes and alveolar macrophages.MethodsCurrent study aimed to identify monocyte/macrophage phenotypes in lung and peripheral blood of SSc-ILD patients by immunostaining and flow cytometry, respectively. Single immunostaining was performed using primary antibodies against CD68 (pan-macrophage marker), CD80, CD86, TLR4 (M1 markers), CD163, CD204, and CD206 (M2 markers). Flow cytometry analysis included the evaluation of CD45, CD14, CD16 (monocyte lineage), CD1c (dendritic lineage), together with M1 and M2 activation markers on circulating monocytes. Protein synthesis of TLR4 and M2 markers was also investigated in cultured monocytes-derived macrophages (MDMs) from SSc-ILD patients by Western Blotting.ResultsLung samples were obtained from 9 SSc-ILD patients (50 ± 9 years old) and 5 control non-SSc patients without lung fibrosis (58 ± 23 years old). Alveolar macrophages (CD68+ cells) showed a significantly higher positivity of M1 and M2 markers in SSc-ILD lung samples than in controls (p

The cattle tick, Rhipicephalus microplus, causes significant economic losses to the cattle industry. Tick control is predominately achieved via pesticide applications. However, alternative control methods such as vaccines are needed due to the tick's capacity to quickly develop pesticide resistance and to combat tick-borne diseases. We used an in silico reverse vaccinology approach to evaluate and rank open reading frames (ORFs) from the tick's transcriptome for their potential use as anti-R. microplus vaccine antigens. We manually annotated the 200 highest ranked antigens and selected 10 transcript ORFs as vaccine antigen candidates for expression in Pichia pastoris or insect cells. Six of the ten candidate antigens could be successfully expressed and purified in vitro as recombinant proteins with > 1 mg quantity. RT-PCR confirmed the expression of all six transcripts in tick RNA. However, only three of the six transcripts' corresponding ORFs could be confirmed as present in tick tissue protein extracts. Only four of the six vaccine candidate antigens were successfully expressed and purified in sufficient quantity (> 10 mg) for immunogenicity and efficacy trials in cattle. These four were designated BI-TS002, BI-TS004, BI-TS008, and BI-TS009 and sufficient annotation existed that showed sequence similarity to serine‑rich adhesin for platelets, glycine-rich cell wall structural membrane protein, SWM-1 tick serine protease inhibitor, and venom-like dermonecrotic toxins from ticks and spiders, respectively. Cattle immunized with BI-TS004, BI-TS008 and BI-TS009 yielded a statistically significant difference in antibody response post-immunization. This difference was noted on Days 42, 56, 70, and 84 post-immunization for BI-TS008 and BI-TS009, but only on Day 56 for BI-TS004. BI-TS008 and BI-TS009, were formulated with adjuvant and cattle stall tests conducted over a 175 day period to evaluate efficacy against R. microplus infestations. Both an adjuvant only negative control group and a positive control group using the commercially available GAVAC anti-tick vaccine were used. Efficacy was determined by comparing number of engorged adult female ticks, total egg mass weight, and egg hatchability produced from the immunized group to corresponding data from the adjuvant only negative control group. Thus, effects on engorged adult tick number, reproductive capacity, and fertility were measured. Both initial (designated Phase 1 and calculated from tick collections of Days 60–94 days post-first immunization) and long-term (designated Phase 2 and calculated from tick collections of Days 152–175 post-first immunization) efficacies were determined. The overall Phase 1 trial efficacies of BI-TS008, BI-TS009, and GAVAC were 68.3 %, 48.5 %, and 70.7 %, respectively. The overall Phase 2 trial efficacies of BI-TS008, BI-TS009, and GAVAC were 64.4 %, -30.1 %, and 45.1 %, respectively.

RESUMO Uma ‘boa’ relação médico-paciente é fundamental para uma prática clínica efetiva no Sistema Único de Saúde. São comuns, na prática clínica, os problemas de comunicação, o autoritarismo e certa desconsideração da situação existencial e da agenda dos usuários. Paulo Freire tratou de temas similares na educação, sendo menos aproveitado para ensino e prática da condução dos atendimentos médicos. O objetivo deste ensaio foi sintetizar contribuições das ideias freirianas para construção/melhoria da relação médico-paciente em contexto clínico ambulatorial. Metodologicamente, foi realizada uma análise de literatura articulando aspectos da relação médico-paciente e ideias de Freire. A análise consistiu em leitura e síntese livre de obras selecionadas sobre a relação clínica e das ideias contidas nos principais livros de Freire, consideradas pertinentes a essa temática (primeiro e segundo tópicos do artigo). Seguiuse uma síntese das contribuições freirianas, organizadas em cinco temas: reforço ao desafio de desviar da objetificação do usuário; concepção emancipadora, crítica e participativa da relação médico-paciente e dos seus aspectos educativos; importância do mundo da vida dos usuários; importância de abrir e manter o diálogo; ‘bem’ manejar as dinâmicas de poder. As ideias de Freire continuam muito relevantes e contribuem para o ensino e a melhoria da prática clínica ambulatorial.

Abstract Recent research studies reported that the employment of wearable augmented reality (AR) systems such as head‐mounted displays for the in situ visualisation of ultrasound (US) images can improve the outcomes of US‐guided biopsies through reduced procedure completion times and improved accuracy. Here, the authors continue in the direction of recent developments and present the first AR system for guiding an in‐depth tumour enucleation procedure under US guidance. The system features an innovative visualisation modality with cutting trajectories that ‘sink’ into the tissue according to the depth reached by the electric scalpel, tracked in real‐time, and a virtual‐to‐virtual alignment between the scalpel's tip and the trajectory. The system has high accuracy in estimating the scalpel's tip position (mean depth error of 0.4 mm and mean radial error of 1.34 mm). Furthermore, we demonstrated with a preliminary user study that our system allowed us to successfully guide an in‐depth tumour enucleation procedure (i.e. preserving the safety margin around the lesion).

In this paper, the recently proposed structural optimization strategy, the Galilei-Optimization (GO), is adapted for improving the toughness response of a holed two-dimensional lattice system made of a network of micro-beams whose geometrical arrangement was prescribed. By taking advantage of the possibility of minimizing stress gradients and stress peaks around the hole via GO, we redesigned the cross sections of the lattice beam elements, equalizing the stresses over the entire domain. Consequently, the resulting optimized microstructure highlighted a significant enhancement of the overall toughness due to a drastic decrease of the stress concentration factor in the hole proximity, preserving the initial stiffness and lowering the total overall weight. To validate the robustness of the procedure and the numerical Finite Element outcomes, two non-optimized and optimized structures were actually built up through 3D printing and tested in the laboratory under the same boundary conditions used for the simulations. This evidence confirmed the effectiveness of the proposed method in obtaining optimized beam-like plates with high toughness, which could pave the way for designing new light materials with extreme mechanical performance well beyond the sole stiffness and strength.

Objectives To investigate pregnancy outcomes in women with autoimmune rheumatic diseases (ARD) in the Italian prospective cohort study P-RHEUM.it.Methods Pregnant women with different ARD were enrolled for up to 20 gestational weeks in 29 Rheumatology Centres for 5 years (2018–2023). Maternal and infant information were collected in a web-based database.Results We analysed 866 pregnancies in 851 patients (systemic lupus erythematosus was the most represented disease, 19.6%). Maternal disease flares were observed in 135 (15.6%) pregnancies. 53 (6.1%) pregnancies were induced by assisted reproduction techniques, 61 (7%) ended in miscarriage and 11 (1.3%) underwent elective termination. Obstetrical complications occurred in 261 (30.1%) pregnancies, including 2.3% pre-eclampsia. Two cases of congenital heart block were observed out of 157 pregnancies (1.3%) with anti-Ro/SSA. Regarding treatments, 244 (28.2%) pregnancies were treated with glucocorticoids, 388 (44.8%) with hydroxychloroquine, 85 (9.8%) with conventional synthetic disease-modifying anti-rheumatic drugs and 122 (14.1%) with biological disease-modifying anti-rheumatic drugs. Live births were 794 (91.7%), mostly at term (84.9%); four perinatal deaths (0.5%) occurred. Among 790 newborns, 31 (3.9%) were small-for-gestational-age and 169 (21.4%) had perinatal complications. Exclusive maternal breast feeding was received by 404 (46.7%) neonates. The Edinburgh Postnatal Depression Scale was compiled by 414 women (52.4%); 89 (21.5%) scored positive for emotional distress.Conclusions Multiple factors including preconception counselling and treat-to-target with pregnancy-compatible medications may have contributed to mitigate disease-related risk factors, yielding limited disease flares, good pregnancy outcomes and frequency of complications which were similar to the Italian general obstetric population. Disease-specific issues need to be further addressed to plan preventative measures.

Achieving and maintaining proper image registration accuracy is an open challenge of image-guided surgery. This work explores and assesses the efficacy of a registration sanity check method for augmented reality-guided navigation (AR-RSC), based on the visual inspection of virtual 3D models of landmarks. We analyze the AR-RSC sensitivity and specificity by recruiting 36 subjects to assess the registration accuracy of a set of 114 AR images generated from camera images acquired during an AR-guided orthognathic intervention. Translational or rotational errors of known magnitude up to ±1.5 mm/±15.5°, were artificially added to the image set in order to simulate different registration errors. This study analyses the performance of AR-RSC when varying (1) the virtual models selected for misalignment evaluation (e. g., the model of brackets, incisor teeth, and gingival margins in our experiment), (2) the type (translation/rotation) of registration error, and (3) the level of user experience in using AR technologies. Results show that: 1) the sensitivity and specificity of the AR-RSC depends on the virtual models (globally, a median true positive rate of up to 79.2% was reached with brackets, and a median true negative rate of up to 64.3% with incisor teeth), 2) there are error components that are more difficult to identify visually, 3) the level of user experience does not affect the method. In conclusion, the proposed AR-RSC, tested also in the operating room, could represent an efficient method to monitor and optimize the registration accuracy during the intervention, but special attention should be paid to the selection of the AR data chosen for the visual inspection of the registration accuracy.

Abstract Background The sand flea Tunga penetrans is one of the agents of tungiasis, an important parasitic skin disease affecting humans and several mammalian species. Tungiasis is mainly observed in disadvantaged rural and peripheral urban communities in Latin America and sub-Saharan Africa. The dog is a major reservoir of Tunga fleas. Hematophagous adult female Tunga spp. embed and grow in their host’s epidermis and cause cutaneous inflammatory disorders. NexGard Spectra® is an orally administered endectocide for dogs, a co-formulation of the isoxazoline afoxolaner and the macrocyclic lactone milbemycin oxime. The objective of this study was to assess the efficacy of this product against canine tungiasis. Methods A blinded, negative-controlled field trial was conducted in a Brazilian community known to be highly endemic for tungiasis. Sixty-six dogs naturally infected with live T. penetrans were randomly allocated to a treated group (44 dogs) and an untreated control group (22 dogs). In a first phase, dogs from the treated group were treated on days 0, 30, and 60. Efficacy was evaluated on the basis of the macroscopic parasitic skin lesions (Fortaleza classification) on days 7, 14, 21, 30, 45, 60, 75, and 90. In a second phase, to evaluate natural reinfections, all dogs were treated on day 90 and evaluated every 2 weeks thereafter until at least 30% of dogs were infected with live sand fleas. Results During the first phase, efficacy (reduction in live sand fleas) of 92.4% was demonstrated on day 7. From day 14 until day 90, the efficacy of NexGard Spectra® was 100%. In the second phase, all dogs were free of live T. penetrans from 15 until 45 days after the day 90 treatment; 60 days post-treatment, 11% of dogs were reinfected, and 75 days post-treatment, 40% of dogs were reinfected. Conclusions NexGard Spectra® was demonstrated to be highly effective against canine tungiasis. In addition to an obvious beneficial effect on the health and welfare of the treated dog, the use of this product may have a one-health benefit on human cases by controlling the main reservoir of sand fleas. Graphical Abstract

Abstract Background Microalgae are emerging hosts for the sustainable production of lutein, a high-value carotenoid; however, to be commercially competitive with existing systems, their capacity for lutein sequestration must be augmented. Previous attempts to boost microalgal lutein production have focussed on upregulating carotenoid biosynthetic enzymes, in part due to a lack of metabolic engineering targets for expanding lutein storage. Results Here, we isolated a lutein hyper-producing mutant of the model green microalga Chlamydomonas reinhardtii and characterized the metabolic mechanisms driving its enhanced lutein accumulation using label-free quantitative proteomics. Norflurazon- and high light-resistant C. reinhardtii mutants were screened to yield four mutant lines that produced significantly more lutein per cell compared to the CC-125 parental strain. Mutant 5 (Mut-5) exhibited a 5.4-fold increase in lutein content per cell, which to our knowledge is the highest fold increase of lutein in C. reinhardtii resulting from mutagenesis or metabolic engineering so far. Comparative proteomics of Mut-5 against its parental strain CC-125 revealed an increased abundance of light-harvesting complex-like proteins involved in photoprotection, among differences in pigment biosynthesis, central carbon metabolism, and translation. Further characterization of Mut-5 under varying light conditions revealed constitutive overexpression of the photoprotective proteins light-harvesting complex stress-related 1 (LHCSR1) and LHCSR3 and PSII subunit S regardless of light intensity, and increased accrual of total chlorophyll and carotenoids as light intensity increased. Although the photosynthetic efficiency of Mut-5 was comparatively lower than CC-125, the amplitude of non-photochemical quenching responses of Mut-5 was 4.5-fold higher than in CC-125 at low irradiance. Conclusions We used C. reinhardtii as a model green alga and identified light-harvesting complex-like proteins (among others) as potential metabolic engineering targets to enhance lutein accumulation in microalgae. These have the added value of imparting resistance to high light, although partially compromising photosynthetic efficiency. Further genetic characterization and engineering of Mut-5 could lead to the discovery of unknown players in photoprotective mechanisms and the development of a potent microalgal lutein production system.

The evolving landscape of industrial manufacturing is increasingly embracing automation within smart factories. However, the critical role of human operators, particularly in manual assembly and disassembly tasks, remains undiminished. This paper explores the complexities arising from mass customization and remanufacturing, which significantly enhance the intricacy of these manual tasks. Human involvement is essential in these tasks due to their complexity, necessitating a structured learning process to enhance efficiency and mitigate the learning–forgetting cycle. This study focuses on the utilization of virtual reality (VR) as an innovative training tool to address these challenges. By conducting a systematic literature review (SLR) on the impact of VR on training operators for assembly and disassembly tasks, this paper evaluates the current level of VR application, the used technologies, the operator performance, and the VR benefits and limitations. The analysis reveals a limited but promising application of VR in training, highlighting its potential to improve learning outcomes, productivity, and safety while reducing costs. However, the research also identifies gaps in the practical application of VR for training purposes suggesting a future research agenda to explore its full potential.

From sea shores to the abysses of the deep ocean, marine ecosystems have provided humanity with valuable medicinal resources. The use of marine organisms is discussed in ancient pharmacopoeias of different times and geographic regions and is still deeply rooted in traditional medicine. Thanks to present-day, large-scale bioprospecting and rigorous screening for bioactive metabolites, the ocean is coming back as an untapped resource of natural compounds with therapeutic potential. This renewed interest in marine drugs is propelled by a burgeoning research field investigating the molecular mechanisms by which newly identified compounds intervene in the pathophysiology of human diseases. Of great clinical relevance are molecules endowed with anti-inflammatory and immunomodulatory properties with emerging applications in the management of chronic inflammatory disorders, autoimmune diseases, and cancer. Here, we review the historical development of marine pharmacology in the Eastern and Western worlds and describe the status of marine drug discovery. Finally, we discuss the importance of conducting sustainable exploitation of marine resources through biotechnology.

The aim of this retrospective cohort study is to understand if and how much the preventive self-isolation approach might have been a valid model to avoid care-related infection, not only from COVID-19 but also from other non-viral infectious diseases. From March to May 2020, the healthcare and management staff of the Villa Santa Maria long-term care facilities, located in the village of Montenero di Bisaccia (Campobasso, Molise, Italy), decided to carry out a preventive self-isolation plan to safeguard the residents from SARS-CoV-2. The impact on other infectious diseases was evaluated by analyzing the antibiotic therapies prescription trend among the inpatients. Our data showed that although self-isolation protected residents and caregivers from SARS-CoV-2, it can also be associated with mobility reduction, leading to an increase in bedridden pathologies, namely, pressure ulcers and pressure sores. The simultaneous isolation of residents and caregivers in the same location significantly reduced any outside influence as a cause of possible infections.

Abstract Background The light-harvesting antennae of photosystem (PS) I and PSII are pigment-protein complexes responsible of the initial steps of sunlight conversion into chemical energy. In natural environments plants are constantly confronted with the variability of the photosynthetically active light spectrum. PSII and PSI operate in series but have different optimal excitation wavelengths. The prompt adjustment of light absorption by photosystems is thus crucial to ensure efficient electron flow needed to sustain downstream carbon fixing reactions. Fast structural rearrangements equilibrate the partition of excitation pressure between PSII and PSI following the enrichment in the red (PSII-favoring) or far-red (PSI-favoring) spectra. Redox imbalances trigger state transitions (ST), a photoacclimation mechanism which involves the reversible phosphorylation/dephosphorylation of light harvesting complex II (LHCII) proteins by the antagonistic activities of the State Transition 7 (STN7) kinase/TAP38 phosphatase enzyme pair. During ST, a mobile PSII antenna pool associates with PSI increasing its absorption cross section. LHCII consists of assorted trimeric assemblies of Lhcb1, Lhcb2 and Lhcb3 protein isoforms (LHCII), several being substrates of STN7. However, the precise roles of Lhcb phosphorylation during ST remain largely elusive. Results We inactivated the complete Lhcb1 and Lhcb2 gene clades in Arabidopsis thaliana and reintroduced either wild type Lhcb1.3 and Lhcb2.1 isoforms, respectively, or versions lacking N-terminal phosphorylatable residues proposed to mediate state transitions. While the substitution of Lhcb2.1 Thr-40 prevented the formation of the PSI-LHCI-LHCII complex, replacement of Lhcb1.3 Thr-38 did not affect the formation of this supercomplex, nor did influence the amplitude or kinetics of PSII fluorescence quenching upon state 1—state 2 transition. Conclusions Phosphorylation of Lhcb2 Thr-40 by STN7 alone accounts for ≈ 60% of PSII fluorescence quenching during state transitions. Instead, the presence of Thr-38 phosphosite in Lhcb1.3 was not required for the formation of the PSI-LHCI-LHCII supercomplex nor for re-equilibration of the plastoquinone redox state. The Lhcb2 phosphomutant was still capable of ≈ 40% residual fluorescence quenching, implying that a yet uncharacterized, STN7-dependent, component of state transitions, which is unrelated to Lhcb2 Thr-40 phosphorylation and to the formation of the PSI-LHCI-LHCII supercomplex, contributes to the equilibration of the PSI/PSII excitation pressure upon plastoquinone over-reduction.

Objectives Glucocorticosteroids (GCs) are the most used anti-inflammatory and immunosuppressive drugs due to their effectiveness in managing pain and disease modification in many immune-inflammatory rheumatic diseases (IRDs). However, their use is limited because of adverse effects (AEs). Material and methods The authors analyzed recent studies, including randomized controlled trials (RCTs), observational, translational studies and systematic reviews, providing an in-depth viewpoint on the benefits and drawbacks of GC use in rheumatology. Results Glucocorticosteroids are essential in managing life-threatening autoimmune diseases and a cornerstone in many IRDs given their swift onset of action, necessary in flares. Several RCTs and meta-analyses have demonstrated that when administered over a long time and on a low-dose basis, GC can slow the radiographic progression in early rheumatoid arthritis (RA) patients by at least 50%, satisfying the conventional definition of a disease-modifying anti-rheumatic drug (DMARD). In the context of RA treatment, the use of modified-release prednisone formulations at night may offer the option of respecting circadian rhythms of both inflammatory response and HPA activation, thereby enabling low-dose GC administration to mitigate nocturnal inflammation and prolonged morning fatigue and joint stiffness. Long-term GC use should be individualized based on patient characteristics and minimized due to their potential AEs. Their chronic use, especially at medium/high dosages, might cause irreversible organ damage due to the burden of metabolic systemic effects and increased risk of infections. Many international guidelines recommend tapering/withdrawal of GCs in sustained remission. Treat-to-target (T2T) strategies are critical in setting targets for disease activity and reducing/discontinuing GCs once control is achieved. Conclusions Glucocorticosteroids’ use in treating IRDs should be judicious, focused on minimizing use, tapering and discontinuing treatment, when possible, to improve long-term safety. Glucocorticosteroids remain part of many therapeutic regimens, particularly at low doses, and elderly RA patients, especially with associated chronic comorbidities, may benefit from long-term low-dose GC treatment. A personalized GC therapy is essential for optimal long-term outcomes.

Onco-virotherapy is an emergent treatment for cancer based on viral vectors. The therapeutic activity is based on two different mechanisms including tumor-specific oncolysis and immunostimulatory properties. In this study, we evaluated onco-virotherapy in vitro responses on immunocompetent non-small cell lung cancer (NSCLC) patient-derived tumoroids (PDTs) and healthy organoids. PDTs are accurate tools to predict patient’s clinical responses at the in vitro stage. We showed that onco-virotherapy could exert specific antitumoral effects by producing a higher number of viral particles in PDTs than in healthy organoids. In the present work, we used multiplex protein screening, based on proximity extension assay to highlight different response profiles. Our results pointed to the increase of proteins implied in T cell activation, such as IFN-γ following onco-virotherapy treatment. Based on our observation, oncolytic viruses-based therapy responders are dependent on several factors: a high PD-L1 expression, which is a biomarker of greater immune response under immunotherapies, and the number of viral particles present in tumor tissue, which is dependent to the metabolic state of tumoral cells. Herein, we highlight the use of PDTs as an alternative in vitro model to assess patient-specific responses to onco-virotherapy at the early stage of the preclinical phases.

Combining remote-sensing data with in-situ observations to achieve a comprehensive 3D reconstruction of the ocean state presents significant challenges for traditional interpolation techniques. To address this, we developed the CLuster Optimal Interpolation Neural Network (CLOINet), which combines the robust mathematical framework of the Optimal Interpolation (OI) scheme with a self-supervised clustering approach. CLOINet efficiently segments remote sensing images into clusters to reveal non-local correlations, thereby enhancing fine-scale oceanic reconstructions. We trained our network using outputs from an Ocean General Circulation Model (OGCM), which also facilitated various testing scenarios. Our Observing System Simulation Experiments aimed to reconstruct deep salinity fields using Sea Surface Temperature (SST) or Sea Surface Height (SSH), alongside sparse in-situ salinity observations. The results showcased a significant reduction in reconstruction error up to 40% and the ability to resolve scales 50% smaller compared to baseline OI techniques. Remarkably, even though CLOINet was trained exclusively on simulated data, it accurately reconstructed an unseen SST field using only glider temperature observations and satellite chlorophyll concentration data. This demonstrates how deep learning networks like CLOINet can potentially lead the integration of modeling and observational efforts in developing an ocean digital twin.

Systemic sclerosis (SSc), the most lethal of rheumatologic conditions, is the cause of death in >50% of SSc cases, led by pulmonary fibrosis followed by pulmonary hypertension and then scleroderma renal crisis (SRC). Multiple other preventable and treatable SSc-related vascular, cardiac, gastrointestinal, nutritional and musculoskeletal complications can lead to disability and death. Vascular injury with subsequent inflammation transforming to irreversible fibrosis and permanent damage characterizes SSc. Organ involvement is often present early in the disease course of SSc, but requires careful history-taking and vigilance in screening to detect. Inflammation is potentially reversible provided that treatment intensity quells inflammation and other immune mechanisms. In any SSc phenotype, opportunities for early treatment are prone to be under-utilized, especially in slowly progressive phenotypes that, in contrast to severe progressive ILD, indolently accrue irreversible organ damage resulting in later-stage life-limiting complications such as pulmonary hypertension, cardiac involvement, and malnutrition. A single SSc patient visit often requires much more physician and staff time, organization, vigilance, and direct management for multiple organ systems compared to other rheumatic or pulmonary diseases. Efficiency and efficacy of comprehensive SSc care enlists trending of symptoms and bio-data. Financial sustainability of SSc care benefits from understanding insurance reimbursement and health system allocation policies for complex patients. Sharing care between recognised SSc centers and local cardiology/pulmonary/rheumatology/gastroenterology colleagues may prevent complications and poor outcomes, while providing support to local specialists. As scleroderma specialists, we offer a practical framework with tools to facilitate an optimal, comprehensive and sustainable approach to SSc care. Improved health outcomes in SSc relies upon recogntion, management and, to the extent possible, prevention of SSc and treatment-related complications.