ChemInform Research Articles

Patient-Reported Outcomes 10 Years After Breast-Conserving Surgery for Early-Stage Breast Cancer.

Patient-reported outcomes (PROs) are a critical component of value-based care. Limited data exist describing long-term PROs in patients undergoing breast-conserving surgery (BCS). Patients undergoing surgery for stage 0-III breast cancer at our institution from 2002 to 2012 who agreed to be contacted were invited to participate in a cross-sectional PRO study. Health-related quality of life outcomes using BREAST-Q, EORTC QLQ-C30, and EORTC QLQ-BR45 were collected. Patients reporting chemotherapy within 6 months of receiving the survey were excluded. For this work, we focused on patients who underwent BCS. Multivariable linear regression was performed to identify factors associated with PRO scores, adjusting for age, time since surgery, anatomic stage, molecular subtype, receipt of systemic and/or radiation therapy (RT), locoregional recurrence, or contralateral breast cancer. Among 562 interested and eligible patients, 437 (78%) responded; median time from surgery to survey completion was 10.4 years (interquartile range: 8.0-13.5). Median age at surgery was 53 years (standard deviation 9.8 years), ≥ 90% were white, had upfront surgery for early-stage disease, and completed adjuvant RT. Physical and psychological well-being scores were generally high, with more variation seen for sexual well-being and satisfaction with breasts. This study provides long-term PRO data for patients treated with BCS, demonstrating the ongoing association of breast cancer surgery with quality of life in the survivorship period and highlighting the importance of examining PROs beyond the perioperative period. These data also provide important reference values for the interpretation of PROs among women treated with BCS as we move towards value-based care.

Scoping Review on Transitions in the Context of Pediatric Palliative Care.

Background: Children with complex and chronic conditions receiving palliative care will likely experience many transitions during their life and their treatments. Transition periods for children with life-limiting conditions and their families can be bewildering and highly anxiety-inducing. However, clinical observations seem to point to a more heterogenous care offer, including a lack or discontinuity of services, at the expense of their quality of life. Objective: This paper aims to establish a portrait of the existing literature and identify research gaps on the multiple transitions experienced by this population. Design: A scoping review is provided, following a PRISMA protocol. MEDLINE, PubMed and CINAHL were consulted. The search strategy is based on three key concepts: (1) palliative care/complex condition, (2) child/adolescent, and (3) transition. Articles were screened with the help of Covidence. Results: A total of 72 articles are included for analysis. The aimed population is either identified by age group or by medical status. Respondents are most often parents rather than the children themselves. Transitions include: reaching adulthood, changes in care environment, changes in medical status, and school integration. Conclusion: The discussion notices a definitional murkiness about transitions and highlights the fact that the multifaceted and complex nature of transition over time is largely ignored. New research should involve a diversity of participants and include children's voices. Recommendations include clearer concept definitions, health care policies that adopt an ecosystemic approach, and professional training in the systemic family approach in palliative care.

Assessing disparities through missing race and ethnicity data: results from a juvenile arthritis registry

IntroductionEnsuring high-quality race and ethnicity data within the electronic health record (EHR) and across linked systems, such as patient registries, is necessary to achieving the goal of inclusion of racial and ethnic minorities in scientific research and detecting disparities associated with race and ethnicity. The project goal was to improve race and ethnicity data completion within the Pediatric Rheumatology Care Outcomes Improvement Network and assess impact of improved data completion on conclusions drawn from the registry.MethodsThis is a mixed-methods quality improvement study that consisted of five parts, as follows: (1) Identifying baseline missing race and ethnicity data, (2) Surveying current collection and entry, (3) Completing data through audit and feedback cycles, (4) Assessing the impact on outcome measures, and (5) Conducting participant interviews and thematic analysis.ResultsAcross six participating centers, 29% of the patients were missing data on race and 31% were missing data on ethnicity. Of patients missing data, most patients were missing both race and ethnicity. Rates of missingness varied by data entry method (electronic vs. manual). Recovered data had a higher percentage of patients with Other race or Hispanic/Latino ethnicity compared with patients with non-missing race and ethnicity data at baseline. Black patients had a significantly higher odds ratio of having a clinical juvenile arthritis disease activity score (cJADAS10) of ≥5 at first follow-up compared with White patients. There was no significant change in odds ratio of cJADAS10 ≥5 for race and ethnicity after data completion. Patients missing race and ethnicity were more likely to be missing cJADAS values, which may affect the ability to detect changes in odds ratio of cJADAS ≥5 after completion.ConclusionsAbout one-third of the patients in a pediatric rheumatology registry were missing race and ethnicity data. After three audit and feedback cycles, centers decreased missing data by 94%, primarily via data recovery from the EHR. In this sample, completion of missing data did not change the findings related to differential outcomes by race. Recovered data were not uniformly distributed compared with those with non-missing race and ethnicity data at baseline, suggesting that differences in outcomes after completing race and ethnicity data may be seen with larger sample sizes.

Patient-reported outcome measures for paediatric gender-affirming care: A systematic review

Patient-reported outcome measures for paediatric gender-affirming care: A systematic review

Do primary care quality improvement frameworks consider equity?

BackgroundQuality improvement (QI) is used by healthcare organisations internationally to improve care. Unless QI explicitly addresses equity, projects that aim to improve care may exacerbate health and care inequalities for...

Reconstruction of Defects After Oral Cancer Surgery With the Superior Thyroid Artery Perforator Flap.

The superior thyroid artery perforator flap (STAPF) was previously presented as a type of locoregional pedicled flap for lateral facial and temple defects. In this study, we aimed to present our clinical experience with this flap for the reconstruction of soft tissue defects after oral cancer surgery. From February 2019 to December 2022, 24 patients with oral cancers at the School and Hospital of Stomatology,Peking University were included. Among these patients, 10 had cancers located in the tongue, five in the cheek inside the oral cavity, three in the lower gingiva, two in the upper gingiva, two in the floor of the mouth, and two in the palate. All patients were treated with extended tumor resection, neck dissection, and STAPFs to reconstruct the soft tissue defects. The details of the flap, including the flap size, venous flow, vascular pedicle length, the attatched muscle, and operation time were evaluated. The dimensions of the flap skin paddle ranged from 3 cm × 5 cm to 6 × 14 cm. Fourteen patients had a closely concomitant superior thyroid vein perforator. Ten patients had non-closely concomitant superior thyroid veins perforators which retrograde external jugular vein. The vascular pedicle length ranged from 5 to 9 cm. The infrahyoid muscle group or sternocleidomastoid muscle was included in the flaps in three patients. A total of 23/24 flaps were successful. The STAPF is a viable reconstructive option for patients with oral cancers. It has the advantages of being robust, being thin, short operation time, and minor donor site complications. 4 Laryngoscope, 2024.

Unraveling the role of computed tomography derived body composition metrics on anastomotic leakages rates in rectal cancer surgery: A protocol for a systematic review and meta-analysis.

Anastomotic leakage is a major concern following total mesorectal excision for rectal cancer, affecting oncological outcomes, morbidity an treatment costs. Body composition has been suggested to influence anastomotic leakage rates. However, literature on how body composition impact anastomotic leakage rates is conflicting. This systematic review aims to evaluate the role of computed tomography derived body composition metrics on anastomotic leakage rates in rectal cancer patients. Databases PubMed/MEDLINE, Cochrane Library, web of science, and EMBASE, will be systematically searched for papers from January 2010 onwards. Study selection, data collection and quality assessment will be independently performed by three research fellows. Outcomes described in three or more studies will be included in the meta-analysis. The Q-test and I2 statistic will be used to assess statistical heterogeneity between studies. Publication bias will be examined by visual inspection of funnel plots and quantified by Egger's test. Sensitivity analyses will be conducted to examine the robustness of the meta-analysis. Reporting of the findings will be in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. This systematic review will synthesize the current evidence and will identify knowledge gaps. Results of the systematic review will aid health care professional in pre-operative decision making and will be distributed through a peer-reviewed publication and presentation of results at international meetings. PROSPERO protocol number: CRD42023471537.

A Randomized, Controlled Trial Evaluating Perioperative Risk-Stratification and Risk-Based, Protocol-Driven Management After Elective Major Cancer Surgery.

We evaluated the efficacy of risk-based, protocol-driven management versus (vs) usual management after elective major cancer surgery to reduce 30-day rates of postoperative death or serious complications (DSC) . Major cancer surgery is associated with significant perioperative risks which result in worse long-term outcomes. Adults scheduled for elective major cancer surgery were stratified/randomized to risk-based escalating levels of care, monitoring, and co-management vs usual management. The primary study outcome was 30-day rate of DSC. Additional outcomes included complications, adverse events, health care utilization, health-related quality of life (HRQOL), and disease-free and overall survival (DFS and OS). Between August 2014 and June 2020, 1529 patients were enrolled and randomly allocated to the study arms; 738 patients in the Intervention Arm and 732 patients in the Control Arm were eligible for analysis. 30-day rate of DSC with the intervention was 15.0% (95% CI, 12.5-17.6%) vs 14.1%, (95% CI, 11.6-16.6%) with usual management (P=0.65). There were no differences in 30-day rates of complications or adverse events (including return to the operating room); postoperative length of stay; rate of discharge to home; or 30, 60, or 90-day HRQOL or rates of hospital readmission or receipt of anti-neoplastic therapy between the study arms. At median follow-up of 48 months, OS (P=0.57) and DFS (P=0.91) were similar. Risk-based, protocol-driven management did not reduce 30-day rate of DSC after elective major cancer surgery compared to usual management, nor improve postoperative health care utilization, HRQOL, or cancer outcomes. Trials are needed to identify cost-effective, tailored perioperative strategies to optimize outcomes after major cancer surgery.

Biosynthesis of a clickable pyoverdine via in vivo enzyme engineering of an adenylation domain

The engineering of non ribosomal peptide synthetases (NRPS) for new substrate specificity is a potent strategy to incorporate non-canonical amino acids into peptide sequences, thereby creating peptide diversity and broadening applications. The non-ribosomal peptide pyoverdine is the primary siderophore produced by Pseudomonas aeruginosa and holds biomedical promise in diagnosis, bio-imaging and antibiotic vectorization. We engineered the adenylation domain of PvdD, the terminal NRPS in pyoverdine biosynthesis, to accept a functionalized amino acid. Guided by molecular modeling, we rationally designed mutants of P. aeruginosa with mutations at two positions in the active site. A single amino acid change results in the successful incorporation of an azido-l-homoalanine leading to the synthesis of a new pyoverdine analog, functionalized with an azide function. We further demonstrated that copper free click chemistry is efficient on the functionalized pyoverdine and that the conjugated siderophore retains the iron chelation properties and its capacity to be recognized and transported by P. aeruginosa. The production of clickable pyoverdine holds substantial biotechnological significance, paving the way for numerous downstream applications.

Structure-based reshaping of a new ketoreductase from Sphingobacterium siyangense SY1 toward α-haloacetophenones

Ketoreductases play an indispensable role in the asymmetric synthesis of chiral drug intermediates, and an in-depth understanding of their substrate selectivity can improve the efficiency of enzyme engineering. In this endeavor, a new short-chain dehydrogenase/reductase (SDR) SsSDR1 identified from Sphingobacterium siyangense SY1 by gene mining method was successfully cloned and functionally expressed in Escherichia coli. Its activity against halogenated acetophenones has been tested and the results illustrated that SsSDR1-WT exhibits high activity for 3,5-bis(trifluoromethyl)acetophenone (1f), an important precursor in the synthesis of aprepitant. In addition, SsSDR1-WT showed obvious substrate preference for acetophenones without α-halogen substitution compared to their α-halogen analogs. To explore the structural basis of substrate selectivity, the X-ray crystal structures of SsSDR1-WT in its apo form and the complex structure with NAD were resolved. Taking 2-chloro-1-(3, 4-difluorophenyl) ethanone (1i) as the representative α-haloacetophenone, the key sites affecting substrate selectivity of SsSDR1-WT were identified and through the rational remodeling of the cavities C1 and C2 of SsSDR1, an excellent mutant I144A/S153L with significantly improved activity against α-halogenated acetophenones was obtained. The asymmetric catalysis of 1f and 1i was performed at the scale of 50 mL, and the space-time yields (STY) of the two were 1200 and 6000 g/L∙d, respectively. This study not only provides valuable biocatalysts for halogenated acetophenones, but also yields insights into the relationship between the substrate-binding pocket and substrate selectivity.

Measuring serum and drainage fluid interleukin-6 and tumor necrosis factor-α levels for early detection of infectious complications after minimally invasive surgery for gastric cancer

ObjectiveInterleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are inflammatory cytokines produced in response to biological invasion or infection. Their levels are elevated in the blood and locally. We examined whether measuring IL-6 and TNF-α levels in serum or drainage fluid on postoperative day (POD) 1 could detect infectious complications after minimally invasive surgery for gastric cancer. MethodsThis cohort study included 205 consecutive patients who underwent laparoscopic or robot-assisted gastrectomy for gastric cancer between November 2020 and July 2023. We measured serum and drainage fluid IL-6 and TNF-α levels on POD 1 after gastrectomy. Receiver operating characteristic (ROC) curves were created to compare the diagnostic values of each cytokine and serum C-reactive protein levels for detecting postoperative infectious complications. ResultsIL-6 and TNF-α levels in the serum or drainage fluid were significantly higher in patients with an infectious complication. In addition, drainage fluid IL-6 levels were significantly different in patients with versus without intra-abdominal abscess. In the ROC curve analysis, serum and drainage fluid IL-6 had the highest AUC values for any infectious complication and intra-abdominal abscess, respectively. POD 1 serum IL-6 level above 47 pg/mL could detect any infectious complication with sensitivity of 74.1% and specificity of 71.8%. POD 1 drainage fluid IL-6 level above 14,750 pg/mL had 100% sensitivity for detecting intra-abdominal abscess with specificity of 56.0%. ConclusionsMeasurement of IL-6 levels in blood and drainage fluid on POD 1 is valuable for early detection of postoperative infectious complications or intra-abdominal abscess after gastric cancer surgery.

Major stoma complications in pediatric patients in a tertiary hospital in a low-middle-income country: a retrospective cohort study.

Intestinal stomas are one of the most common parts of pediatric surgical care,and complications arising from it have significant impact on overall patient outcomes. However, data on major complications in low-middle-income countries remain limited. This pilot retrospective cohort study aimed to investigate the prevalence, types, and management of major stoma complications in pediatric patients at a tertiary government hospital in the Philippines. Medical records of pediatric patients with major stoma complications classified as Clavien-Dindo III-V from June 2018 to June 2023 were reviewed. Patient-related factors (age, sex, diagnosis) and surgery-related factors (stoma type and location, surgeon expertise) were analyzed. Descriptive statistics characterized demographic profiles, while Chi-square and t tests analyzed categorical and continuous variables, respectively. Multivariable logistic regression evaluated independent associations with major stoma complications. Out of 1041 pediatric patients with stomas, 102 cases had major complications, representing a prevalence rate of 9.8%. Mortality directly attributed to stoma complications accounted for 1.3% of the total cases, or 14 deaths in 5years. Neonates comprised a significant portion, primarily diagnosed with congenital conditions like anorectal malformation and Hirschsprung's disease. Ileostomies exhibited a higher incidence of major complications compared to other stoma types. Stomal prolapse and adhesive bowel obstruction are the most common reported stoma complications requiring surgical intervention while stoma revision is the most frequent corrective procedure. The median time from stoma creation to presentation of major complication was 14months, with nearly half of the complications occurring within the first year. Only the presence of ileostomy had significant association with the development of major complications among the risk factors analyzed. This study provides useful insights into stoma complications in pediatric patients in a low-middle income country. Despite the lack of significant associations between the patient-related and surgeon-related factors, and major stoma complications, further investigation into other contributing factors is warranted. Improvements in data collection methods and prospective studies with larger sample sizes are recommended to enhance understanding and optimize care of major stoma complications. Addressing the challenges identified in this study could lead to a comprehensive and tailored approach to pediatric stoma care and their complications.

Robot-assisted versus conventional laparoscopic surgery for rectal cancer.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows: To assess the benefits and harms of robot-assisted surgery for rectal cancer resection.

Postoperative distress and influencing factors in patients with pancreatobiliary cancer

This study aimed to investigate distress levels, using the distress thermometer (DT), and the factors associated with distress in postoperative patients with pancreatobiliary cancer. This study retrospectively investigated 155 patients who underwent surgery for pancreatobiliary cancer between December 1, 2019 and September 30, 2021. The DT and problem list were used to measure distress. Descriptive statistics, t-test, and multivariate logistic regression analysis were used to analyze the data. Of the 155 patients, 16.8% (n = 26) and 83.2% (n = 129) were in the mild-distress and moderate-to-severe distress groups, respectively. The average DT score was 6.21; that for the mild-distress and moderate-to-severe distress groups was 2.46 and 6.97, respectively. More patients in the moderate-to-severe distress group reported having problems of “sadness” (χ2 = 4.538, P < 0.05), “indigestion” (χ2 = 10.128, P < 0.001), “eating” (χ2 = 6.147, P < 0.013), and “getting around” (χ2 = 4.275, P < 0.039) than in the mild-distress group. In addition, occupation status (odds ratio [OR] = 0.342, 95% confidence interval [CI] = 0.133–0.879, P = 0.026) and indigestion (OR = 5.897, 95% CI = 1.647–21.111, P = 0.006) were independent risk factors for the presence of severe distress. Patients with pancreatobiliary cancer demonstrated elevated levels of psychological distress. Healthcare providers should therefore be vigilant when evaluating patients for distress and providing appropriate referrals, particularly those who are unemployed or have indigestion.

Personalized risk prediction for prolonged ileus after minimally invasive colorectal cancer surgery: in-depth risk factor analysis and model development

PurposeDespite the increasing preference for minimally invasive surgery for colorectal cancer (CRC), the incidence of prolonged postoperative ileus (PPOI) remains high. Thus, this study aimed to identify risk factors for PPOI in patients with CRC who underwent minimally invasive surgery (MICRS) and to develop a practical nomogram for predicting individual PPOI risk.MethodsA consecutive series of 2368 patients who underwent MICRS between 2013 and 2023 at two tertiary academic centers were retrospectively studied. Using the data from 1895 patients in the training cohort, a multivariable logistic regression model was employed to select significant variables for the construction of a best-fit nomogram. The nomogram was internally and externally validated.ResultsPPOI occurred in 9.5% of patients. Six independent risk factors were identified to construct a nomogram: advanced age (OR 1.055, P = 0.002), male sex (OR 2.914, P = 0.011), age-adjusted Charlson comorbidity index ≥ 6 (OR 2.643, P = 0.025), preoperative sarcopenia (OR 0.857, P = 0.02), preoperative prognostic nutritional index (OR 2.206, P = 0.047), and intraoperative fluid overload (OR 2.227, P = 0.045). The AUCs of the model for predicting PPOI in the training and external validation cohorts were 0.887 and 0.838, respectively. The calibration curves demonstrated excellent consistency between the nomogram-predicted and observed probabilities in both cohorts. Individuals with a total nomogram score of < 197 or ≥ 197 were considered to be at low or high risk for PPOI, respectively.ConclusionsThe integrated nomogram we developed could provide personalized risk prediction of PPOI after MICRS. This quantification enables surgeons to implement personalized prevention strategies, thereby improving patient outcomes.

The influence of socioeconomic disadvantage on short- and long-term outcomes after oesophagectomy for cancer: an Australian multicentre study.

Socioeconomic status (SES) affects outcomes following surgery for various cancers. There are currently no Australian studies that examine the role of socioeconomic disadvantage on outcomes following oesophagectomy for cancer. This study assessed whether SES was associated with short-term perioperative morbidity, long-term survival, and oncological outcomes following oesophagectomy across three tertiary oesophageal cancer centres in Australia. A retrospective cohort study was performed comprising all patients who underwent oesophagectomy for cancer across three Australian centres. Patients were stratified into SES groups using the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD). Outcomes measured included perioperative complication rates, overall survival, and disease-free survival. The study cohort was 462 patients, 205 in the lower SES and 257 in the higher SES groups. The lower SES group presented with more advanced oesophageal cancer stage, a higher rate of T3 (52.6% versus 42.7%, P = 0.038) and N2 disease (19.6% versus 10.5%, P = 0.006), and had a higher rate of readmission within 30 days (11.2% versus 5.4%, P = 0.023). There was no difference in overall survival or disease-free survival between groups. Lower socioeconomic status was associated with more advanced stage and increased risk of early, unplanned readmission following oesophagectomy, but was not associated with a difference in overall or disease-free survival.

Identified Needs in Pediatric Education for Emergency Medicine Physicians: A Qualitative Analysis.

General emergency medicine (EM) physicians provide most pediatric emergency care in the United States, yet EM physicians feel underprepared to manage pediatric emergencies. Pediatric emergency medicine (PEM) education during EM residency is variable, and learner preferences regarding educational experiences have not been widely explored through a qualitative lens. We aimed to better describe EM physicians' PEM educational needs and preferred teaching methods. In 2021, as part of a survey querying senior EM residents and recent graduates from 8 diverse EM programs regarding perceived preparedness for PEM emergencies, educational needs and content delivery methods were assessed using 2 free-text questions. Qualitative analysis included deidentification and iterative coding of the data with double coding of 100% of the comments. We performed conventional content analysis of responses to identify emerging themes. The overall response rate for the survey was 53% (N = 129 out of 242 eligible participants) with 84 distinct free-text responses. Major themes included: 1) desire for education regarding neonates, infants, and critically ill children, especially airway management and 2) need for help translating lessons from PEM rotations to community EM practice. Respondents desired more autonomy during training. Their preferred PEM educational modality was simulation, and they appreciated online clinical pathways for just-in-time decision support. This qualitative study of EM physicians proximal to training adds to a prior needs assessment by describing in detail desired pediatric content and preferred delivery. The findings can be used to better inform the development of PEM curricula for this group of EM physicians.

Intra-articular corticosteroid utilization and characterizations of use in juvenile idiopathic arthritis within the PR-COIN registry.

Intra-articular corticosteroid injections (IACI) have been shown to be effective at improving arthritis across juvenile idiopathic arthritis (JIA) categories. The American College of Rheumatology (ACR) recommends IACI use as primary and adjunctive therapy for JIA patients. However, there remains minimal data describing actual IACI use in North America. The objective of this study was to describe and to evaluate IACI use in JIA, utilizing the Pediatric Rheumatology Care and Outcomes Improvement Network (PR-COIN) registry. Study participants from 13 sites were enrolled in the PR-COIN registry from 2011 to 2015. Demographic and clinical variables were summarized and Chi-squared and t-tests were used to evaluate differences between participants who did or did not receive IACI. Multiple logistic regression models were used to evaluate characteristics associated with IACI treatment. Our study included 3,241 participants, the majority of whom were white (85%), female (71%) and had oligoarticular JIA (39%). IACI was administered at least once in 23% of participants, the majority of whom had oligoarticular disease (52.5%), but overall use in oligoarticular participants was low at 30.8%. IACI use varied significantly between treatment centers and use was associated with oligoarticular disease, ANA positivity, and use of other systemic medications. This study demonstrates that participants with JIA enrolled in the PR-COIN registry between 2011 and 2015 with persistent oligoarticular disease, ANA positivity, and use of other systemic medications were more likely to receive IACI. However, IACI use was lower than expected for oligoarticular participants.

Joint sparse optimization: lower-order regularization method and application in cell fate conversion

Multiple measurement signals are commonly collected in practical applications, and joint sparse optimization adopts the synchronous effect within multiple measurement signals to improve model analysis and sparse recovery capability. In this paper, we investigate the joint sparse optimization problem via ℓp,q regularization ( 0⩽q⩽1⩽p ) in three aspects: theory, algorithm and application. In the theoretical aspect, we introduce a weak notion of joint restricted Frobenius norm condition associated with the ℓp,q regularization, and apply it to establish an oracle property and a recovery bound for the ℓp,q regularization of joint sparse optimization problem. In the algorithmic aspect, we apply the well-known proximal gradient algorithm to solve the ℓp,q regularization problems, provide analytical formulas for proximal subproblems of certain specific ℓp,q regularizations, and establish the global convergence and linear convergence rate of the proximal gradient algorithm under some mild conditions. More importantly, we propose two types of proximal gradient algorithms with the truncation technique and the continuation technique, respectively, and establish their convergence to the ground true joint sparse solution within a tolerance relevant to the noise level and the recovery bound under the assumption of restricted isometry property. In the aspect of application, we develop a novel method, based on joint sparse optimization with lower-order regularization and proximal gradient algorithm, to infer the master transcription factors for cell fate conversion, which is a powerful tool in developmental biology and regenerative medicine. Numerical results indicate that the novel method facilitates fast identification of master transcription factors, give raise to the possibility of higher successful conversion rate and in the hope of reducing biological experimental cost.

PredicTTE: An accessible and optimal tool for time-to-event prediction in neurological diseases.

Time-to-event prediction is a key task for biological discovery, experimental medicine, and clinical care. This is particularly true for neurological diseases where development of reliable biomarkers is often limited by difficulty visualising and sampling relevant cell and molecular pathobiology. To date, much work has relied on Cox regression because of ease-of-use, despite evidence that this model includes incorrect assumptions. We have implemented a set of deep learning and spline models for time-to-event modelling within a fully customizable 'app' and accompanying online portal, both of which can be used for any time-to-event analysis in any disease by a non-expert user. Our online portal includes capacity for end-users including patients, Neurology clinicians, and researchers, to access and perform predictions using a trained model, and to contribute new data for model improvement, all within a data-secure environment. We demonstrate a pipeline for use of our app with three use-cases including imputation of missing data, hyperparameter tuning, model training and independent validation. We show that predictions are optimal for use in downstream applications such as genetic discovery, biomarker interpretation, and personalised choice of medication. We demonstrate the efficiency of an ensemble configuration, including focused training of a deep learning model. We have optimised a pipeline for imputation of missing data in combination with time-to-event prediction models. Overall, we provide a powerful and accessible tool to develop, access and share time-to-event prediction models; all software and tutorials are available at www.predictte.org .