Importin-9 regulates chromosome segregation and packaging in Drosophila germ cells.

Germ cells undergo distinct nuclear processes as they differentiate into gametes. Although these events must be coordinated to ensure proper maturation, the stage-specific transport of proteins in and out of germ cell nuclei remains incompletely understood. Our efforts to genetically characterize Drosophila genes that exhibit enriched expression in germ cells led to the finding that loss of the highly conserved Importin ß/karyopherin family member Importin-9 (Ipo9, herein referring to Ranbp9) results in female and male sterility. Immunofluorescence and fluorescent in situ hybridization revealed that Ipo9KO mutants display chromosome condensation and segregation defects during meiosis. In addition, Ipo9KO mutant males form abnormally structured sperm and fail to properly exchange histones for protamines. Ipo9 physically interacts with proteasome proteins, and Ipo9 mutant males exhibit disruption of the nuclear localization of several proteasome components. Thus, Ipo9 coordinates the nuclear import of functionally related factors necessary for the completion of gametogenesis. This article has an associated First Person interview with the first author of the paper.

Strengthening public health policies for childhood cancer: Peru's achievements through the WHO Global Initiative for Childhood Cancer.

Objective: To report the progress in Peru, since June 2019, in the implementation of the World Health Organization Global Initiative for Childhood Cancer using the CureAll framework, which can be replicated in low- and middle-income countries. Methods: A mixed method was used of participatory and documentary evaluation. The participatory evaluation included stakeholders from various government institutions, nonprofit organizations, and international partners. The documentary aspect consisted of a review of data on the regulatory environment, national projects, and interventions implemented. The Ministry of Health engaged more than 150 participants to form working committees, which have developed policy and regulatory documents to strengthen care services. Results: Achievements include a decrease in the national treatment abandonment rate from 18.6% to 8.5%, the approval of the Childhood Cancer Law, improvements in the management of patients with febrile neutropenia, and a reduction in rates of events of clinical deterioration and mortality of hospitalized patients. The Cure All implementation framework allows local teams to implement specific strategies and monitor early outcomes in pediatric oncology. Conclusions: The results obtained reflect the teamwork, the leadership of the authorities, the technical support of professionals, and the support of involved organizations. Further actions will be needed to guarantee sustainability, and monitoring tools are needed to assure success in the planned activities.

Women's perspectives on the acceptability and feasibility of an HPV screen-and-treat approach to cervical cancer prevention in Iquitos, Peru: a qualitative study.

BACKGROUND: The objective of this study was to explore women's experiences of a screen-and-treat approach with ablative therapy (referred to by the Spanish acronym TVT-TA) as a method of treatment following a positive HPV test in Iquitos, Peru. METHODS: A total of 111 in-depth interviews were conducted with 47 HPV positive women who attended the TVT-TA procedure at a primary-level healthcare facility. Interviews were conducted immediately before, immediately after, and six-weeks after TVT-TA. RESULTS: Most interviewed women reported experiencing moderate pain during ablative therapy and minimal pain immediately after and six weeks after ablative therapy. Women also stated that the pain was less intense than they had expected. The most common physical after-effects of treatment were bleeding and vaginal odor. Women experienced oscillating emotions with fear upon receiving a positive HPV result, calming after hearing about ablative therapy treatment, worry about pain from the treatment itself, relaxation with counseling about the procedure, and relief following treatment. CONCLUSIONS: Nearly all participants emphasized that they were pleased with the TVT-TA process even if they had experienced pain during TVT-TA, recommended that TVT-TA be expanded and available to more women, and stated that TVT-TA was faster and easier than expected. This study found that TVT-TA is a feasible and acceptable means of treating HPV according to the women receiving the treatment.

ONCOPEDS: A mobile application to improve early diagnosis and timely referral in childhood cancer in a low- and middle-income country-A pilot study.

BACKGROUND: Diagnosis delay in children and adolescents with cancer is a public health problem in Peru that leads to high rates of advanced disease and mortality. We aimed to assess the implementation feasibility and potential utility of ONCOpeds®, a mobile application that provides consultations with pediatric oncologists, in reducing the latency to diagnosis (LD) and referral time (RT) among children and adolescents in Peru diagnosed with cancer. MATERIAL AND METHODS: A prospective pilot study was conducted in the region of Callao between November 2017 and April 2018. Primary and secondary care providers were trained on the use of ONCOpeds in five educational sessions. Patients younger than 18 years who resided in Callao and were diagnosed with cancer at four pediatric cancer units in Lima were analyzed by referral type: ONCOpeds facilitated or conventional. RESULTS: ONCOpeds was successfully installed in the smartphones of 78 primary and secondary care providers of Callao. During the study period, 23 new cases of cancer in children and adolescents from the region were diagnosed. Ten patients received ONCOpeds-facilitated referrals and 13 received conventional referrals. The RT decreased among those who received ONCOpeds-facilitated referrals by 66% (P = 0.02); however, the LD did not significantly decrease with the use of ONCOpeds. CONCLUSIONS: The implementation of ONCOpeds was found to be feasible in this pilot study, having a potential utility in improving early diagnosis and referral in children and adolescents newly diagnosed with cancer. Directions for future research include multicenter studies with a larger population to further test the application's effectiveness.

Effect of different cooking methods on sea lettuce (Ulva rigida) volatile compounds and sensory properties.

BACKGROUND: The effect of different cooking methods (boiling, vacuum and steamed cooking) on the volatile compound content and sensory properties of sea lettuce (Ulva rigida) seaweed was assessed. Sea lettuce was cooked at three different temperatures (50, 70 and 100 °C) for three different lengths of time (5, 10 and 15 min). Various statistical techniques were employed in order to establish any possible changes. RESULTS: The different cooking methods modified significantly both the volatile compound content and the sensory properties of sea lettuce seaweed. In general, the cooked samples had lower concentrations of several volatile compounds than the control sample, mainly aldehydes. Regarding sensory analysis, the cooked samples exhibited lower values for various aroma descriptors such as seaside and seaweed, whereas descriptor scores such as cooked fish, salty dry fish and crustacean increased. No clear statistical differences were found between different cooking lengths of time and temperature levels with regard to both volatile compounds and sensory properties. CONCLUSIONS: In the cooking of sea lettuce seaweeds, the main sensory changes and modifications in their volatile content took place during the first minutes of cooking and at medium cooking temperatures. © 2020 Society of Chemical Industry.

Use of Multiflora Bee Pollen as a Flor Velum Yeast Growth Activator in Biological Aging Wines.

Flor velum yeast growth activators during biological aging are currently unknown. In this sense, this research focuses on the use of bee pollen as a flor velum activator. Bee pollen influence on viable yeast development, surface hydrophobicity, and yeast assimilable nitrogen has already been studied. Additionally, bee pollen effects on the main compounds related to flor yeast metabolism and wine sensory characteristics have been evaluated. "Fino" (Sherry) wine was supplemented with bee pollen using six different doses ranging from 0.1 to 20 g/L. Its addition in a dose equal or greater than 0.25 g/L can be an effective flor velum activator, increasing yeast populations and its buoyancy due to its content of yeast assimilable nitrogen and fatty acids. Except for the 20 g/L dose, pollen did not induce any significant effect on flor velum metabolism, physicochemical parameters, organic acids, major volatile compounds, or glycerol. Sensory analysis showed that low bee pollen doses increase wine's biological aging attributes, obtaining the highest score from the tasting panel. Multiflora bee pollen could be a natural oenological tool to enhance flor velum development and wine sensory qualities. This study confirms association between the bee pollen dose applied and the flor velum growth rate. The addition of bee pollen could help winemakers to accelerate or reimplant flor velum in biologically aged wines.

Evolution of volatile compounds and sensory characteristics of edible green seaweed (Ulva rigida) during storage at different temperatures.

BACKGROUND: Edible seaweeds are one of the most important resources that currently exist for their multiple uses and applications. Like other food types, during their storage there are significant changes in sensory characteristics associated with loss of freshness and with production and/or degradation of their volatile compounds. In this study, multiple headspace sorptive extraction (MHSSE) coupled with gas chromatography/mass spectrometry (GC/MS) detection has been applied to an edible green seaweed (Ulva rigida) in order to determine the evolution of volatile compounds during storage for 12 days at 4 or 16 °C. RESULTS: The existing analytical methodology has been updated and validated for 18 additional compounds. At the end, 41 volatile compounds from different chemical families were quantified. Aldehydes, carboxylic acids and esters were the main classes found in U. rigida. Analytical and sensory data were submitted for statistical analysis. During storage, most volatile compounds were only affected by the number of storage days (P < 0.05), with significant decreases as storage time increased. Sensory analysis revealed significant changes in the samples stored for longer times (8, 10 and 12 days), with a clear influence of the boiled vegetable descriptor. CONCLUSION: In order to get a successful preservation of seaweeds and to maintain their marine character during storage, both temperature and time should be carefully controlled. © 2019 Society of Chemical Industry.

Effect on White Grape Must of Multiflora Bee Pollen Addition during the Alcoholic Fermentation Process.

The aim of the present study was to compare and analyze the impact of using bee pollen doses (0.1, 0.25, 1, 5, 10 and 20 g/L) as activator in the alcoholic fermentation process of Palomino fino and Riesling wines. In this regard, its influence on the musts composition, the fermentative kinetics, the evolution of the populations of Saccharomyces cerevisiae, the evolution of yeast-assimilable nitrogen and physico-chemical characteristics of final wines has been analyzed. Bee pollen addition produces significant increases in yeast-assimilable nitrogen and maximum yeasts population and exponential velocity reached during alcoholic fermentation. Bee pollen showed an important effect on yeast survival during the death phase. Final wines showed significantly increase in volatile acidity above doses higher than 10 g/L and Comisión Internacional de L'Eclairage parameters (CIELab), color intensity and Abs 420 nm, from 1 g/L. Therefore, pollen could be used as fermentative activator for the alcoholic fermentation of white wines applying doses below of 1 g/L.

The Wnt pathway limits BMP signaling outside of the germline stem cell niche in Drosophila ovaries.

The mechanisms that modulate and limit the signaling output of adult stem cell niches remain poorly understood. To gain further insights into how these microenvironments are regulated in vivo, we performed a candidate gene screen designed to identify factors that restrict BMP signal production to the cap cells that comprise the germline stem cell (GSC) niche of Drosophila ovaries. Through these efforts, we found that disruption of Wnt4 and components of the canonical Wnt pathway results in a complex germ cell phenotype marked by an expansion of GSC-like cells, pre-cystoblasts and cystoblasts in young females. This phenotype correlates with an increase of decapentaplegic (dpp) mRNA levels within escort cells and varying levels of BMP responsiveness in the germline. Further genetic experiments show that Wnt4, which exhibits graded expression in somatic cells of germaria, activates the Wnt pathway in posteriorly positioned escort cells. The activation of the Wnt pathway appears to be limited by the BMP pathway itself, as loss of Mad in escort cells results in the expansion of Wnt pathway activation. Wnt pathway activity changes within germaria during the course of aging, coincident with changes in dpp production. These data suggest that mutual antagonism between the BMP and Wnt pathways in somatic cells helps to regulate germ cell differentiation.

Lsd1 restricts the number of germline stem cells by regulating multiple targets in escort cells.

Specialized microenvironments called niches regulate tissue homeostasis by controlling the balance between stem cell self-renewal and the differentiation of stem cell daughters. However the mechanisms that govern the formation, size and signaling of in vivo niches remain poorly understood. Loss of the highly conserved histone demethylase Lsd1 in Drosophila escort cells results in increased BMP signaling outside the cap cell niche and an expanded germline stem cell (GSC) phenotype. Here we present evidence that loss of Lsd1 also results in gradual changes in escort cell morphology and their eventual death. To better characterize the function of Lsd1 in different cell populations within the ovary, we performed Chromatin immunoprecipitation coupled with massive parallel sequencing (ChIP-seq). This analysis shows that Lsd1 associates with a surprisingly limited number of sites in escort cells and fewer, and often, different sites in cap cells. These findings indicate that Lsd1 exhibits highly selective binding that depends greatly on specific cellular contexts. Lsd1 does not directly target the dpp locus in escort cells. Instead, Lsd1 regulates engrailed expression and disruption of engrailed and its putative downstream target hedgehog suppress the Lsd1 mutant phenotype. Interestingly, over-expression of engrailed, but not hedgehog, results in an expansion of GSC cells, marked by the expansion of BMP signaling. Knockdown of other potential direct Lsd1 target genes, not obviously linked to BMP signaling, also partially suppresses the Lsd1 mutant phenotype. These results suggest that Lsd1 restricts the number of GSC-like cells by regulating a diverse group of genes and provide further evidence that escort cell function must be carefully controlled during development and adulthood to ensure proper germline differentiation.

Benefit of the nutritional and mineral composition of sea lettuce from a traditional salina: Implications for human consumption.

The proximal composition and its seasonal variation of the green seaweed Ulva sp. harvested in a traditional saline (earthen ponds used for marine salt extraction) from Cadiz Bay (Southern Spain) was evaluated. Ulva sp. was also collected in a reference location within the Bay in order to compare and evaluate the effects of the particular characteristics of the saline in the composition of the macroalgae. Moisture, protein, lipid, ash, carbohydrate, fiber and macro- (Na, K, Ca, Mg), micro-mineral contents (Fe, Zn, Cu) and heavy metals (As, Cd, Co, Cr, Hg, Ni, Pb, Sn) of harvested biomass samples as well as environmental parameters of seawater (temperature, salinity, pH, DO, NH4+, NO3-, NO2- and PO43-) were measured. The results showed that Ulva sp. from the earthen ponds in the traditional salina was a better source of proteins, lipids, K and Mg, highlighting in summer with values of 27.54 % versus 6.11 %; 6.71 % versus 3.26 %; 26.60 mg g-1 versus 14.21 mg g-1 and 23.13 mg g-1 versus 17.79 mg g-1, respectively. It also had Na/K and Ca/Mg ratios of less than one, suggesting a healthy food source. Considering the Commission Recommendation (EU) 2018/464 as a working reference, Ulva sp. did not exceed the limit of toxic metals for human consumption.A season and site-season significant interaction on the composition of the seaweeds was observed. The proximal and mineral composition of Ulva sp. was influenced by the special features and environmental conditions of the earthen ponds. Hence, significant differences were observed in the macroalgae collected in the earthen ponds in summer and autumn, in contrast to the winter and spring samples, whose characteristics were similar to those from the inner bay. The closure of the lock-gates in summer to favor the production of salt significantly modified the environmental characteristics of the saline, affecting the physiological capacity of Ulva sp. to assimilate and storage nutrients, and therefore its tissue composition. As a consequence, the highest contents of lipid, ash, Ca, K, Mg and Fe were estimated in the macroalgae.

Uncovering kinesin dynamics in neurites with MINFLUX.

Neurons grow neurites of several tens of micrometers in length, necessitating active transport from the cell body by motor proteins. By tracking fluorophores as minimally invasive labels, MINFLUX is able to quantify the motion of those proteins with nanometer/millisecond resolution. Here we study the substeps of a truncated kinesin-1 mutant in primary rat hippocampal neurons, which have so far been mainly observed on polymerized microtubules deposited onto glass coverslips. A gentle fixation protocol largely maintains the structure and surface modifications of the microtubules in the cell. By analyzing the time between the substeps, we identify the ATP-binding state of kinesin-1 and observe the associated rotation of the kinesin-1 head in neurites. We also observed kinesin-1 switching microtubules mid-walk, highlighting the potential of MINFLUX to study the details of active cellular transport.

The Impact of Sea Urchin as an Ingredient on the Physicochemical, Microbiological, and Sensory Properties of Fish Sauce Fermentation.

The consequences of using 25% whole or shelled sea urchin as an ingredient in anchovy sauce on its fermentation and development of its physicochemical properties after 20 days fermentation was studied. Two varieties of fish and sea urchin sauce were made with or without shell at 1:2:1 ratio (salt:fish:sea urchin) plus a control fish sauce at 1:3 ratio (salt:fish). All sauces were fermented at 40-50 °C for 20 days, where for the first 7 days the preparation remained in a static phase. During their fermentation, pH, salt concentration, aw, TVB-N, TMA, total nitrogen, formaldehyde nitrogen, amino nitrogen, and ammonium nitrogen, as well as aerobic mesophiles and lactic acid bacteria were monitored. The fermentation of the experimental sauces proved to follow an evolution rather similar to the control sauce. The whole and shelled sea urchins provided the necessary microbial and enzymatic load to trigger an adequate hydrolysis of the fish and the production of total nitrogen (16.0-17.6 g/L), formaldehyde nitrogen (15.1-16.0 g/L), and amino nitrogen (0.7-0.8 g/L) of the same order as the control sauce, despite the lower fish content. According to TMA (9.2-13.1 mg N/100 g), VBT (40.0-47.2 mg N/100 g) contents, and pH levels (5.41-5.46), no deviation of the fermentation process was observed under the experimental conditions (salt content, temperature, and agitation after the static phase). Quantitative descriptive analysis (QDA) sensory revealed that the use of sea urchin results in high quality products characterized by their aromas of crustaceans and mollusks. The present study investigates the potential use of shelled and even whole sea urchin as an ingredient for the preparation of high quality fish sauces.

Neurofilament Levels in Dendritic Spines Associate with Synaptic Status.

Neurofilaments are one of the main cytoskeletal components in neurons; they can be found in the form of oligomers at pre- and postsynapses. How their presence is regulated at the postsynapse remains largely unclear. Here we systematically quantified, by immunolabeling, the occurrence of the neurofilament isoform triplet neurofilament light (NFL), medium (NFM), and heavy (NFH) at the postsynapse using STED nanoscopy together with markers of synaptic strength and activity. Our data show that, within dendritic spines, neurofilament isoforms rarely colocalize with each other and that they are present to different extents, with NFL being the most abundant isoform. The amount of the three isoforms correlates with markers of postsynaptic strength and presynaptic activity to varying degrees: NFL shows the highest correlation to both synaptic traits, suggesting its involvement in synaptic response, while NFM exhibits the lowest correlations. By quantifying the presence of neurofilaments at the postsynapse within the context of the synaptic status, this work sheds new light on the regulation of synaptic neurofilaments and their possible contribution to synaptopathies.

Machine Learning to Optimize the Echocardiographic Follow-Up of Aortic Stenosis.

BACKGROUND: Disease progression in patients with mild-to-moderate aortic stenosis is heterogenous and requires periodic echocardiographic examinations to evaluate severity. OBJECTIVES: This study sought to explore the use of machine learning to optimize aortic stenosis echocardiographic surveillance automatically. METHODS: The study investigators trained, validated, and externally applied a machine learning model to predict whether a patient with mild-to-moderate aortic stenosis will develop severe valvular disease at 1, 2, or 3 years. Demographic and echocardiographic patient data to develop the model were obtained from a tertiary hospital consisting of 4,633 echocardiograms from 1,638 consecutive patients. The external cohort was obtained from an independent tertiary hospital, consisting of 4,531 echocardiograms from 1,533 patients. Echocardiographic surveillance timing results were compared with the European and American guidelines echocardiographic follow-up recommendations. RESULTS: In internal validation, the model discriminated severe from nonsevere aortic stenosis development with an area under the receiver-operating characteristic curve (AUC-ROC) of 0.90, 0.92, and 0.92 for the 1-, 2-, or 3-year interval, respectively. In external application, the model showed an AUC-ROC of 0.85, 0.85, and 0.85, for the 1-, 2-, or 3-year interval. A simulated application of the model in the external validation cohort resulted in savings of 49% and 13% of unnecessary echocardiographic examinations per year compared with European and American guideline recommendations, respectively. CONCLUSIONS: Machine learning provides real-time, automated, personalized timing of next echocardiographic follow-up examination for patients with mild-to-moderate aortic stenosis. Compared with European and American guidelines, the model reduces the number of patient examinations.

Effect of lysozyme on "flor" velum yeasts in the biological aging of sherry wines.

Biological aging is a key step in the production of Sherry wine classified as "fine". During this stage, a film of yeast referred to as "flor velum" covers the surface of the wine and substantially alters its characteristics. Other microorganisms may coexist with flor yeasts, such as lactic acid bacteria and non-Saccharomyces yeasts, whose growth may be favored under certain conditions, causing organoleptic deviations and deterioration of the wine. To prevent the development of lactic bacteria, lysozyme usage has been introduced. Lysozyme is a hydrolytic enzyme with muramidase activity that can lyse gram-positive bacteria; its use in winemaking was approved by the OIV in 1997 (resolution OENO 10/97). Thus far, the use of lysozyme during the production of Sherry wines is not widespread despite its effectiveness in controlling lactic acid bacteria. However, there have been no studies on the effect of lysozyme on flor velum. The aim of this study was to determine the influence of lysozyme on yeast growth and the formation, development and metabolism of flor velum during the biological aging process of Sherry wine. The results indicate that lysozyme does not affect the flor yeast during the fermentative stage or biofilm stage. However, if yeast inoculation is carried out under submerged culture conditions during biological aging, low doses of lysozyme (≥12.5 g/hL) affect cell multiplication and the membrane hydrophobicity of the yeast, inhibiting their aggregation and flotation and the subsequent development of flor velum. Thus, the yeast inoculation protocol and the methodology used for the addition of lysozyme influence velum development, its metabolism and the wine characteristics.

Volatile Composition and Sensory Characterization of Dry White Wines Made with Overripe Grapes by Means of Two Different Techniques.

Grape over-ripening is a technique that has historically been used for the production of white wines in southern Spain. However, this technique is still widely used for the production of sweet wines. In this study and after recently proving the feasibility of making dry white wines from overripe grapes with and without the presence of grape skin in a warm climate zone, the sensory characterization and analysis of the major and minor volatile compounds in dry white wines made from overripe grapes are presented for the first time. Two over-ripening techniques (sun-drying and climatic chamber drying) were studied for two different periods of time (48 and 96 h), as has the presence of grape skins during alcoholic fermentation. Grape over-ripening implies modifications in the composition of both the major and minor volatile compounds in wines. In terms of sensory analysis, wines with a similar profile were obtained year-on-year. The results of the preference test show that the wines made from grapes that had been over-ripened in the sun for 96 h were preferred by the tasting panel for both vintages. Thus, grape over-ripening under the sun could be considered as a resilience and adaptation technique for increased temperature conditions during the ripening season caused by the effects of climate change.

Serum hemato-immunological biomarkers associated with increased COVID-19 mortality in the Latino population.

Introduction: COVID-19 hospitalizations and deaths have raised the need of identifying prognostic factors for medical decision-making. Methods: Observational, retrospective study analyzing 191 COVID-19 patients' serum inflammatory biomarkers. Results: The median age was 48.7 ± 12.7 years, 75.9% being men. Overweight/obesity was the most common comorbidity in 83.8% of patients. 44.5% had moderate disease followed by 43.5% with severe disease. The mean percentage of pulmonary damage was 53.4% ± 28.7. Serum leukocyte-to-lymphocyte ratio >7.7, neutrophil-to-lymphocyte ratio >10, platelet-to-lymphocyte ratio ≥250 and nutritional index <362 all were independent mortality predictors for COVID-19. Conclusions: A leukocyte-to-lymphocyte ratio >7.7 as well as a nutritional index <362 at hospitalization were independently associated with an increased mortality.

Outcome Analysis in Elective Electrical Cardioversion of Atrial Fibrillation Patients: Development and Validation of a Machine Learning Prognostic Model.

Background: The integrated approach to electrical cardioversion (EC) in atrial fibrillation (AF) is complex; candidates can resolve spontaneously while waiting for EC, and post-cardioversion recurrence is high. Thus, it is especially interesting to avoid the programming of EC in patients who would restore sinus rhythm (SR) spontaneously or present early recurrence. We have analyzed the whole elective EC of the AF process using machine-learning (ML) in order to enable a more realistic and detailed simulation of the patient flow for decision making purposes. Methods: The dataset consisted of electronic health records (EHRs) from 429 consecutive AF patients referred for EC. For analysis of the patient outcome, we considered five pathways according to restoring and maintaining SR: (i) spontaneous SR restoration, (ii) pharmacologic-cardioversion, (iii) direct-current cardioversion, (iv) 6-month AF recurrence, and (v) 6-month rhythm control. We applied ML classifiers for predicting outcomes at each pathway and compared them with the CHA2DS2-VASc and HATCH scores. Results: With the exception of pathway (iii), all ML models achieved improvements in comparison with CHA2DS2-VASc or HATCH scores (p < 0.01). Compared to the most competitive score, the area under the ROC curve (AUC-ROC) was: 0.80 vs. 0.66 for predicting (i); 0.71 vs. 0.55 for (ii); 0.64 vs. 0.52 for (iv); and 0.66 vs. 0.51 for (v). For a threshold considered optimal, the empirical net reclassification index was: +7.8%, +47.2%, +28.2%, and +34.3% in favor of our ML models for predicting outcomes for pathways (i), (ii), (iv), and (v), respectively. As an example tool of generalizability of ML models, we deployed our algorithms in an open-source calculator, where the model would personalize predictions. Conclusions: An ML model improves the accuracy of restoring and maintaining SR predictions over current discriminators. The proposed approach enables a detailed simulation of the patient flow through personalized predictions.