Design, construction, and functional characterization of a tRNA neochromosome in yeast.

Here, we report the design, construction, and characterization of a tRNA neochromosome, a designer chromosome that functions as an additional, de novo counterpart to the native complement of Saccharomyces cerevisiae. Intending to address one of the central design principles of the Sc2.0 project, the ∼190-kb tRNA neochromosome houses all 275 relocated nuclear tRNA genes. To maximize stability, the design incorporates orthogonal genetic elements from non-S. cerevisiae yeast species. Furthermore, the presence of 283 rox recombination sites enables an orthogonal tRNA SCRaMbLE system. Following construction in yeast, we obtained evidence of a potent selective force, manifesting as a spontaneous doubling in cell ploidy. Furthermore, tRNA sequencing, transcriptomics, proteomics, nucleosome mapping, replication profiling, FISH, and Hi-C were undertaken to investigate questions of tRNA neochromosome behavior and function. Its construction demonstrates the remarkable tractability of the yeast model and opens up opportunities to directly test hypotheses surrounding these essential non-coding RNAs.

Upregulation of the secretory pathway Ca2+/Mn2+-ATPase isoform 1 in LPS-stimulated microglia and its involvement in Mn2+-induced Golgi fragmentation.

Microglia play an important protective role in the healthy nervous tissue, being able to react to a variety of stimuli that induce different intracellular cascades for specific tasks. Ca2+ signaling can modulate these pathways, and we recently reported that microglial functions depend on the endoplasmic reticulum as a Ca2+ store, which involves the Ca2+ transporter SERCA2b. Here, we investigated whether microglial functions may also rely on the Golgi, another intracellular Ca2+ store that depends on the secretory pathway Ca2+/Mn2+-transport ATPase isoform 1 (SPCA1). We found upregulation of SPCA1 upon lipopolysaccharide stimulation of microglia BV2 cells and primary microglia, where alterations of the Golgi ribbon were also observed. Silencing and overexpression experiments revealed that SPCA1 affects cell morphology, Golgi apparatus integrity, and phagocytic functions. Since SPCA1 is also an efficient Mn2+ transporter and considering that Mn2+ excess causes manganism in the brain, we addressed the role of microglial SPCA1 in Mn2+ toxicity. Our results revealed a clear effect of Mn2+ excess on the viability and morphology of microglia. Subcellular analysis showed Golgi fragmentation and subsequent alteration of SPCA1 distribution from early stages of toxicity. Removal of Mn2+ by washing improved the culture viability, although it did not effectively reverse Golgi fragmentation. Interestingly, pretreatment with curcumin maintained microglia cultures viable, prevented Mn2+-induced Golgi fragmentation, and preserved SPCA Ca2+-dependent activity, suggesting curcumin as a potential protective agent against Mn2+-induced Golgi alterations in microglia.

An miR164-resistant mutation in the transcription factor gene CpCUC2B enhances carpel arrest and ectopic boundary specification in Cucurbita pepo flower development.

The sex determination process in cucurbits involves the control of stamen or carpel development during the specification of male or female flowers from a bisexual floral meristem, a function coordinated by ethylene. A gain-of-function mutation in the miR164-binding site of CpCUC2B, ortholog of the Arabidopsis transcription factor gene CUC2, not only produced ectopic floral meristems and organs, but also suppressed the development of carpels and promoted the development of stamens. The cuc2b mutation induced the transcription of CpCUC2B in the apical shoots of plants after female flowering but repressed other CUC genes regulated by miR164, suggesting a conserved functional redundancy of these genes in the development of squash flowers. The synergistic androecious phenotype of the double mutant between cuc2b and etr2b, an ethylene-insensitive mutation that enhances the production of male flowers, demonstrated that CpCUC2B arrests the development of carpels independently of ethylene and CpWIP1B. The transcriptional regulation of CpCUC1, CpCUC2, and ethylene genes in cuc2b and ethylene mutants also confirms this conclusion. However, the epistasis of cuc2b over aco1a, a mutation that suppresses stamen arrest in female flowers, and the down-regulation of CpACS27A in cuc2b female apical shoots, indicated that CpCUC2B promotes stamen development by suppressing the late ethylene production.

Long-term use of mepolizumab in a case of chronic eosinophilic pneumonia: extending interval dosing.

INTRODUCTION: Mepolizumab, a humanized anti IL-5 monoclonal antibody, has been used off-label for chronic eosinophilic pneumonia (CEP), inducing disease remission and saving systemic corticosteroids. CASE STUDY: We present a case of CEP, requiring long-term corticosteroids therapy due to relapse upon withdrawal. Mepolizumab was started and maintained for 2 years and 6 months. RESULTS: Corticosteroids could be withdrawn and mepolizumab dose interval was spared up to 10 wk with no disease relapse. CONCLUSION: Mepolizumab is shown to be useful for chronic eosinophilic pneumonia, allowing corticosteroid withdrawal. Dose interval may be individualized under close monitoring, for a more efficient treatment, reducing medical costs while improving patients' quality of life.

Analysis of Treatment Discontinuation in Orthokeratology: Studying Efficacy, Safety, and Patient Adherence Over Six Months.

PURPOSE: This study aimed to evaluate the efficacy, safety, and participant compliance of orthokeratology treatment for the correction of myopic refractive errors over a six-month prospective study and to define the potential reasons for early treatment discontinuation. METHODS: A total of 32 participants with low-to-moderate myopia were fitted with the spherical model of corneal refractive therapy (CRT) orthokeratology lenses (Paragon Vision Sciences) and followed over six months, with specific attention to alterations in refractive error, corneal topography, and epithelial thickness. Concurrently, participant feedback and reasons for any treatment discontinuation were documented. RESULTS: Significant changes in refractive error and in corneal topography were observed, with approximately 50% of the refractive error being corrected on the first night of use and 100% by the first two weeks (P<0.001). Central epithelial thickness experienced substantial thinning, reducing to 15.65±4.49 µm (67.38%) (P<0.001) after 6 months of lens use. Six participants withdrew from this study for varied reasons, including unmet visual expectations and difficulty adhering to the lens-wearing regimen. Notably, the dropout group exhibited higher baseline low-order aberrations and less prolate corneas than those who persisted with the treatment (P<0.05). CONCLUSION: Orthokeratology with CRT is efficacious and safe for the correction of low-to-moderate myopia in adults, but a portion of patients discontinue the treatment in the first 6 months of contact lens wear. Special care should be taken when recommending orthokeratology in patients with higher levels of myopia and corneas with less prolate shape, providing more realistic expectations and even changing to dual axis or more sophisticated designs.

Relationship between Body Posture Assessed by Dynamic Baropodometry and Dental Occlusion in Patients with and without Dental Pathology.

Body biomechanics and dental occlusion are related, but this interaction is not fully elucidated. The aim of this study was to investigate the association between body posture and occlusion in patients with and without dental pathology. A cross-sectional study was carried out with 29 patients divided into a control group and a group with pathology (malocclusions). Body posture was evaluated by dynamic baropodometry, analyzing parameters such as the line of gait and the anteroposterior and lateral position of the center of pressure (CoP). Occlusion was classified radiographically according to the sagittal skeletal relationship. Results showed significant differences in mean position phase line between groups (p = 0.01-0.02), with means of 115.85 ± 16.98 mm vs. 95.74 ± 24.47 mm (left side) and 109.03 ± 18.03 mm vs. 91.23 ± 20.80 mm (right side) for controls and pathologies, respectively. The effect size was large (Cohen's d 0.97 and 0.92). There were no differences in the anteroposterior (p = 0.38) or lateral (p = 0.78) position of the CoP. In gait analysis, significant differences were observed in left (548.89 ± 127.50 N vs. 360.15 ± 125.78 N, p < 0.001) and right (535.71 ± 131.57 N vs. 342.70 ± 108.40 N, p < 0.001) maximum heel strength between groups. The results suggest an association between body posture and occlusion, although further studies are needed to confirm this relationship. An integrated postural and occlusal approach could optimize the diagnosis and treatment of dental patients.

Efficacy and safety of biological treatment for inflammatory bowel disease in elderly patients: Results from a GETECCU cohort.

INTRODUCTION: Biological therapies used for the treatment of inflammatory bowel disease (IBD) have shown to be effective and safe, although these results were obtained from studies involving mostly a young population, who are generally included in clinical trials. The aim of our study was to determine the efficacy and safety of the different biological treatments in the elderly population. METHODS: Multicenter study was carried out in the GETECCU group. Patients diagnosed with IBD and aged over 65 years at the time of initiating biological therapy (infliximab, adalimumab, golimumab, ustekinumab or vedolizumab) were retrospectively included. Among the patients included, clinical response was assessed after drug induction (12 weeks of treatment) and at 52 weeks. Patients' colonoscopy data in week 52 were assessment, where available. Regarding complications, development of oncological events during follow-up and infectious processes occurring during biological treatment were collected (excluding bowel infection by cytomegalovirus). RESULTS: A total of 1090 patients were included. After induction, at approximately 12-14 weeks of treatment, 419 patients (39.6%) were in clinical remission, 502 patients (47.4%) had responded without remission and 137 patients (12.9%) had no response. At 52 weeks of treatment 442 patients (57.1%) had achieved clinical remission, 249 patients had responded without remission (32.2%) and 53 patients had no response to the treatment (6.8%). Before 52 weeks, 129 patients (14.8%) had discontinued treatment due to inefficacy, this being significantly higher (p<0.0001) for Golimumab - 9 patients (37.5%) - compared to the other biological treatments analyzed. With respect to tumor development, an oncological event was observed in 74 patients (6.9%): 30 patients (8%) on infliximab, 23 (7.14%) on adalimumab, 3 (11.1%) on golimumab, 10 (6.4%) on ustekinumab, and 8 (3.8%) on vedolizumab. The incidence was significantly lower (p=0.04) for the vedolizumab group compared to other treatments. As regards infections, these occurred in 160 patients during treatment (14.9%), with no differences between the different biologicals used (p=0.61): 61 patients (19.4%) on infliximab, 39 (12.5%) on adalimumab, 5 (17.8%) on golimumab, 22 (14.1%) on ustekinumab, and 34 (16.5%) on vedolizumab. CONCLUSIONS: Biological drug therapies have response rates in elderly patients similar to those described in the general population, Golimumab was the drug that was discontinued most frequently due to inefficacy. In our experience, tumor development was more frequent in patients who used anti-TNF therapies compared to other targets, although its incidence was generally low and that this is in line with younger patients based on previous literature.

[Challenges and strategies to recover and dynamize primary care: SWOT-CAME analysis in a Health Department]. / Retos y estrategias para recuperar y dinamizar la atención primaria. Metodología DAFO (Debilidades, Amenazas, Fortalezas y Oportunidades)-CAME (Corregir, Afrontar, Mantener y Explotar) en un departamento de salud.

OBJECTIVE: To identify strengths, obstacles, changes in the environment, and capabilities of primary care teams and support units, with the aim of providing high-quality care in an integrated healthcare area. DESIGN: Mixed methods study based on the SWOT matrix and CAME analysis. LOCATION: Primary care, Valencian community. PARTICIPANTS: A total of 271 professionals from different collectives and patient association representatives participated. 99 in the idea generation phase, 154 in the SWOT matrix development phase, and 18 in the CAME analysis development phase. INTERVENTIONS: A SWOT-CAME analysis was conducted, from which action lines were established. Information capture was carried out through nominal groups, and the consensus phase involved integrating all professionals through Delphi and consensus conference techniques. MAIN MEASUREMENTS: Prioritization of proposals to maintain strengths, address threats, exploit opportunities, and correct weaknesses within the framework of an integrated healthcare area action plan. RESULTS: A total of 82 different ideas were proposed (20 strengths; 40 weaknesses; 4 threats; 12 opportunities; 6 threats-opportunities), which, once prioritized, were translated into 7 lines and 33 prioritized actions/interventions (CAME analysis). CONCLUSIONS: Integrated care, seeking collaborative approaches between care levels, redefining roles, digital solutions, staff training, and improvements in equipment and support processes, along with measures to address the aging population and the needs of socio-sanitary centers, constitute the challenges to be addressed.

Role of the Abcg2 Transporter in Secretion into Milk of the Anthelmintic Clorsulon: Interaction with Ivermectin.

Clorsulon is a benzenesulfonamide drug that is effective in treating helminthic zoonoses such as fascioliasis. When used in combination with the macrocyclic lactone ivermectin, it provides high broad-spectrum antiparasitic efficacy. The safety and efficacy of clorsulon should be studied by considering several factors such as drug-drug interactions mediated by ATP-binding cassette (ABC) transporters due to their potential effects on the pharmacokinetics and drug secretion into milk. The aim of this work was to determine the role of ABC transporter G2 (ABCG2) in clorsulon secretion into milk and the effect of ivermectin, a known ABCG2 inhibitor, on this process. Using in vitro transepithelial assays with cells transduced with murine Abcg2 and human ABCG2, we report that clorsulon was transported in vitro by both transporter variants and that ivermectin inhibited its transport mediated by murine Abcg2 and human ABCG2. Wild-type and Abcg2-/- lactating female mice were used to carry out in vivo assays. The milk concentration and the milk-to-plasma ratio were higher in wild-type mice than in Abcg2-/- mice after clorsulon administration, showing that clorsulon is actively secreted into milk by Abcg2. The interaction of ivermectin in this process was shown after the coadministration of clorsulon and ivermectin to wild-type and Abcg2-/- lactating female mice. Treatment with ivermectin had no effect on the plasma concentrations of clorsulon, but the milk concentrations and milk-to-plasma ratios of clorsulon decreased in comparison to those with treatment without ivermectin, only in wild-type animals. Consequently, the coadministration of clorsulon and ivermectin reduces clorsulon secretion into milk due to drug-drug interactions mediated by ABCG2.

FIBER-ML, an Open-Source Supervised Machine Learning Tool for Quantification of Fibrosis in Tissue Sections.

Pathologic fibrosis is a major hallmark of tissue insult in many chronic diseases. Although the amount of fibrosis is recognized as a direct indicator of the extent of disease, there is no consentaneous method for its quantification in tissue sections. This study tested FIBER-ML, a semi-automated, open-source freeware that uses a machine-learning approach to quantify fibrosis automatically after a short user-controlled learning phase. Fibrosis was quantified in sirius red-stained tissue sections from two fibrogenic animal models: acute stress-induced cardiomyopathy in rats (Takotsubo syndrome-like) and HIV-induced nephropathy in mice (chronic kidney disease). The quantitative results of FIBER-ML software version 1.0 were compared with those of ImageJ in Takotsubo syndrome, and with those of inForm in chronic kidney disease. Intra- and inter-operator and inter-software correlation and agreement were assessed. All correlations were excellent (>0.95) in both data sets. The values of discriminatory power between the pathologic and healthy groups were <10-3 for data on Takotsubo syndrome and <10-4 for data on chronic kidney disease. Intra-operator agreement, assessed by intra-class coefficient correlation, was good (>0.8), while inter-operator and inter-software agreement ranged from moderate to good (>0.7). FIBER-ML performed in a fast and user-friendly manner, with reproducible and consistent quantification of fibrosis in tissue sections. It offers an open-source alternative to currently used software, including quality control and file management.

Baricitinib or imatinib in hospitalized COVID-19 patients: Results from COVINIB, an exploratory randomized clinical trial.

Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID-19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients. Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis to identify differences ≥15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered, all-cause mortality, and safety. One hundred and sixty-five patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend toward better results in patients receiving baricitinib was found compared to standard care alone (hazard ratio [HR] for clinical improvement: 1.41, 95% confidence intervals [CI]: 0.96-2.06; HR for discontinuing oxygen: 1.46, 95% CI: 0.94-2.28). No differences were found regarding additional therapies administered or safety. Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial.

3D modelling of cavity-free lasing in nitrogen plasma filaments.

In this article we show results on cavity-free lasing in nitrogen filaments using our 3D, time-dependent Maxwell-Bloch code, Dagon. This code was previously used to model plasma-based soft X-ray lasers and it has been adapted to model lasing in nitrogen plasma filaments. In order to assess the predictive capabilities of the code, we have conducted several benchmarks against experimental and 1D modelling results. Afterwards, we study the amplification of an externally seeded UV beam in nitrogen plasma filaments. Our results show that the phase of the amplified beam carries information about the temporal dynamics of amplification and collisional processes inside the plasma, along with information about the spatial structure of the amplified beam and the active region of the filament. We thus conclude that measuring the phase of an UV probe beam, in combination with 3D Maxwell-Bloch modelling, might be an excellent method for diagnosing electron density value and gradients, mean ionization, density of N2+ ions and the magnitude of collisional processes inside these filaments.

Suppressed-scattering spectral windows for radiative cooling applications.

The scattering of light by resonant nanoparticles is a key process for enhancing the solar reflectance in daylight radiative cooling. Here, we investigate the impact of material dispersion on the scattering performance of popular nanoparticles for radiative cooling applications. We show that, due to material dispersion, nanoparticles with a qualitatively similar response at visible frequencies exhibit fundamentally different scattering properties at infrared frequencies. It is found that dispersive nanoparticles exhibit suppressed-scattering windows, allowing for selective thermal emission within a highly reflective sample. The existence of suppressed-scattering windows solely depends on material dispersion, and they appear pinned to the same wavelength even in random composite materials and periodic metasurfaces. Finally, we investigate calcium-silicate-hydrate (CSH), the main phase of concrete, as an example of a dispersive host, illustrating that the co-design of nanoparticles and host allows for tuning of the suppressed-scattering windows. Our results indicate that controlled nanoporosities would enable concrete with daylight passive radiative cooling capabilities.

Synthesis of Mesoporous Silica Particles as Inhibitor Containers for Anticorrosive Applications.

Herein, we introduce an innovative experimental assembly based on a high-speed disperser and a water recirculator connected to a double-wall stainless steel container as a new and effective pathway for an eco-friendly and controlled synthesis of mesoporous silica particles (MSPs). With the setup, we demonstrated a one-pot encapsulation of the particles with an inhibitor benzotriazole (BTA) to produce a smart nano/microcontainer for potential use in anticorrosive coatings. One advantage of the experimental setup is the high volume of reactant solution that can be used, yet with good control of solution temperature and stirring conditions, which increases the yield and saves laboratory time. The results obtained from the modified Stöber method show the successful preparation of near-spherical and "bean-shaped" nanometer-size (∼310 nm) MSPs with high benzotriazole encapsulation capacity (46 wt %). More so, the one-pot BTA encapsulated mesoporous silica approach revealed monodispersed spherical particles at optimal temperature and stirring conditions with a mean diameter of ∼1.1 µm and a BTA encapsulation of 23 wt %. The synthesized particles show pH responsiveness and can be further optimized and applied as nanocarriers in smart anticorrosive coatings. The experimental assembly adopted in this work represents a new, scalable approach for the synthesis of mesoporous silica particles.

Reproducibility and relative validity of a semi-quantitative food and beverage frequency questionnaire for Spanish children aged 3 to 11 years: the COME-Kids F&B-FQ.

A reliable food and beverage frequency questionnaire (F&B-FQ) to measure dietary intakes for children across Spain is currently unavailable. Thus, we designed and assessed the reproducibility and relative validity of a new F&B-FQ in 210 Spanish children aged 3-11 years. COME-Kids F&B-FQ contained 125 items to assess the usual diet intake in the past year among children. To explore the reproducibility, caregivers answered COME-Kids F&B-FQ twice over a 15-day period (± 1 week). To evaluate the relative validity, estimates from a third COME-Kids F&B-FQ administered at 1 year of follow-up were compared with the mean estimates from 3-day dietary records (3d-DR) collected at baseline, 6 months, and after 1 year of follow-up. Reproducibility and relative validity of the COME-Kids F&B-FQ in estimating food groups and nutrients were assessed using Pearson (r) and intra-class (ICC) correlation coefficients. We used the kappa index to evaluate the agreement in repeat administrations or with the 3d-DR. We used Bland-Altman plots to identify bias across levels of intake. A total of 195 children (105 boys, 90 girls) completed the study. The reproducibility of data estimated from COME-Kids F&B-FQ was substantial with mean r and ICC being 0.65 and 0.64 for food groups and 0.63 and 0.62 for nutrients, respectively. Validation assessments comparing the FFQ and 3d-DRs showed r = 0.36 and ICC = 0.30 for food groups and r = 0.29 and ICC = 0.24 for nutrients. The mean agreement for food group reproducibility and relative validity was 86% and 65%, respectively. These estimates were 85% for reproducibility and 64% for relative validity in the case of nutrients. For reproducibility and relative validity, the overall mean kappa index was 63% and 37% for all food groups and 52% and 27% for nutrients, respectively. Bland-Altman plots showed no specific bias relating to the level of intake of nutrients and several food groups. CONCLUSION: COME-Kids F&B-FQ showed substantial reproducibility and acceptable relative validity to assess food and beverage intake in Spanish children aged 3 to 11 years. Most children were correctly classified in relation to the intake of food groups and nutrients, and misclassification was unlikely with reference to 3d-DR. WHAT IS KNOWN: • The estimation of dietary intake in children is complex, especially in large cohorts. • The food frequency questionnaire is a well-recognized and the most frequently used method for assessing food consumption. WHAT IS NEW: • A new food and beverage frequency questionnaire including a beverage section and novel plant-based food items has been validated in Spanish children aged 3-11 years.

A Data Transformation Methodology to Create Findable, Accessible, Interoperable, and Reusable Health Data: Software Design, Development, and Evaluation Study.

BACKGROUND: Sharing health data is challenging because of several technical, ethical, and regulatory issues. The Findable, Accessible, Interoperable, and Reusable (FAIR) guiding principles have been conceptualized to enable data interoperability. Many studies provide implementation guidelines, assessment metrics, and software to achieve FAIR-compliant data, especially for health data sets. Health Level 7 (HL7) Fast Healthcare Interoperability Resources (FHIR) is a health data content modeling and exchange standard. OBJECTIVE: Our goal was to devise a new methodology to extract, transform, and load existing health data sets into HL7 FHIR repositories in line with FAIR principles, develop a Data Curation Tool to implement the methodology, and evaluate it on health data sets from 2 different but complementary institutions. We aimed to increase the level of compliance with FAIR principles of existing health data sets through standardization and facilitate health data sharing by eliminating the associated technical barriers. METHODS: Our approach automatically processes the capabilities of a given FHIR end point and directs the user while configuring mappings according to the rules enforced by FHIR profile definitions. Code system mappings can be configured for terminology translations through automatic use of FHIR resources. The validity of the created FHIR resources can be automatically checked, and the software does not allow invalid resources to be persisted. At each stage of our data transformation methodology, we used particular FHIR-based techniques so that the resulting data set could be evaluated as FAIR. We performed a data-centric evaluation of our methodology on health data sets from 2 different institutions. RESULTS: Through an intuitive graphical user interface, users are prompted to configure the mappings into FHIR resource types with respect to the restrictions of selected profiles. Once the mappings are developed, our approach can syntactically and semantically transform existing health data sets into HL7 FHIR without loss of data utility according to our privacy-concerned criteria. In addition to the mapped resource types, behind the scenes, we create additional FHIR resources to satisfy several FAIR criteria. According to the data maturity indicators and evaluation methods of the FAIR Data Maturity Model, we achieved the maximum level (level 5) for being Findable, Accessible, and Interoperable and level 3 for being Reusable. CONCLUSIONS: We developed and extensively evaluated our data transformation approach to unlock the value of existing health data residing in disparate data silos to make them available for sharing according to the FAIR principles. We showed that our method can successfully transform existing health data sets into HL7 FHIR without loss of data utility, and the result is FAIR in terms of the FAIR Data Maturity Model. We support institutional migration to HL7 FHIR, which not only leads to FAIR data sharing but also eases the integration with different research networks.

Health data hubs: an analysis of existing data governance features for research.

BACKGROUND: Digital transformation in healthcare and the growth of health data generation and collection are important challenges for the secondary use of healthcare records in the health research field. Likewise, due to the ethical and legal constraints for using sensitive data, understanding how health data are managed by dedicated infrastructures called data hubs is essential to facilitating data sharing and reuse. METHODS: To capture the different data governance behind health data hubs across Europe, a survey focused on analysing the feasibility of linking individual-level data between data collections and the generation of health data governance patterns was carried out. The target audience of this study was national, European, and global data hubs. In total, the designed survey was sent to a representative list of 99 health data hubs in January 2022. RESULTS: In total, 41 survey responses received until June 2022 were analysed. Stratification methods were performed to cover the different levels of granularity identified in some data hubs' characteristics. Firstly, a general pattern of data governance for data hubs was defined. Afterward, specific profiles were defined, generating specific data governance patterns through the stratifications in terms of the kind of organization (centralized versus decentralized) and role (data controller or data processor) of the health data hub respondents. CONCLUSIONS: The analysis of the responses from health data hub respondents across Europe provided a list of the most frequent aspects, which concluded with a set of specific best practices on data management and governance, taking into account the constraints of sensitive data. In summary, a data hub should work in a centralized way, providing a Data Processing Agreement and a formal procedure to identify data providers, as well as data quality control, data integrity and anonymization methods.

Modeling and Prediction of the Immediate and Short-Term Effect of Myopic Orthokeratology.

PURPOSE: To characterize the clinical changes occurring in the initial phase of the orthokeratology (OK) treatment for myopia correction, developing a model of prediction of the refractive changes in such phase. METHODS: Prospective study enrolling 64 eyes of 32 patients (range, 20-40 years) undergoing myopic OK treatment with the reverse geometry contact lens CRT (Paragon Vision Science). Changes in uncorrected visual acuity (UCVA) and best-corrected visual acuity (BCVA), refraction, corneal topography, ocular aberrations, and corneal epithelial thickness were evaluated during the first hour of OK lens wear and after 1 week of OK treatment. Multiple linear regression analysis was used to obtain a model to predict the short-term refractive effect of OK. RESULTS: The UCVA improved at each visit, reaching normal visual acuity values after a week (P<0.001) of OK treatment, which was consistent with the significant spherical equivalent (SE) reduction and central flattening (P<0.001). Multiple linear regression analysis revealed that one night change in refraction (ΔR×1N) could be predicted according to the following expression (P<0.001, R2=0.686): ΔR×1N=1.042+0.028×Age+1.014×BCET (baseline central epithelium thickness)-0.752×BKm (baseline mean keratometry)-1.405×BSE (baseline SE)+1.032×ΔR×1 h (change in SE after 1 hr of OK lens use). Similarly, a statistically relevant linear relationship was obtained for predicting the refractive change after 1 week (ΔR×1W) of OK use (P<0.001, R2=0.928): ΔR×1W=3.470-1.046×BSE-1.552×BBCVA (baseline BCVA)-0.391×BKm+0.450×ΔR×1 h. CONCLUSIONS: The immediate and short-term refractive effects of myopic OK with the reverse geometry contact lens CRT can be predicted with enough accuracy from baseline and first trial visits data.

Comparative RNA-Seq Analysis between Monoecious and Androecious Plants Reveals Regulatory Mechanisms Controlling Female Flowering in Cucurbita pepo.

In the monoecious Cucurbita pepo, the transition to female flowering is the time at which the plant starts the production of female flowers after an initial male phase of development. Ethylene plays an essential role in this process since some ethylene deficient and ethylene-insensitive mutants are androecious and only produce male flowers. To gain insight into the molecular mechanisms regulating the specification and early development of female flowers, we have compared the transcriptomic changes occurring in the shoot apices of WT and androecious ethylene-insensitive etr1b mutant plants upon female flowering transition. There were 1160 female flowering-specific DEGs identified in WT plants upon female flowering, and 284 of them were found to be modulated by the ethylene-insensitive etr1b mutation. The function of these DEGs indicated that female flower specification depends on the adoption of a transcriptional program that includes previously identified sex-determining genes in the ethylene pathway, but also genes controlling the biosynthesis and signaling pathways of other phytohormones, and those encoding for many different transcription factors. The transcriptomic changes suggested that gibberellins play a negative role in female flowering, while ethylene, auxins, ABA and cytokinins are positive regulators. Transcription factors from 34 families, including NAC, ERF, bHLH, bZIP, MYB and C2H2/CH3, were found to be regulating female flowering in an ethylene-dependent or -independent manner. Our data open a new perspective of the molecular mechanisms that control the specification and development of female flowers in C. pepo.

Info-NAS: A Computer Program for the Calculation of Intensive Care Unit Nurse Workload.

The purpose of this study was to design an algorithm that allows automatic calculation of nursing workload in intensive care units, based on the Nursing Activities Score scale, through a computer program. Three methodological steps were used: (1) Delphi method (group of experts); (2) identification of the correspondence: Nursing Activities Score items-variables in the EHR, namely, standardized terminology, laboratory values, and prescriptions; and (3) weighting of variables independently by a group of experts. Finally, the algorithm of the computer program was tested. The results showed an algorithm that calculates the nursing workload in an ICU. The calculation is objective and automatic through the EHRs. This study shows the feasibility of the algorithm as a rapid and objective strategy to quantify adequate nurse staffing in intensive care units. Moreover, it provides nurses with a practical resource for the correct completion of records and is thus an incentive to maintain or improve their quality.