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Abstract Background and Aims Bowel preparation is considered as major obstacle before colonoscopy, and it is often reported as the most feared part of the procedure. The aim of this study is to determine the difference in efficacy between a split dose of PEG and the previous day regimen in cleaning the colon, using Boston bowel preparation scale. In addition, also to evaluate patient satisfaction regarding the modality of preparation. Methods The study included 200 hospitalized patients undergoing colonoscopy at Beirut hospitals between 2021 and 2023. One of the two regimens will be prescribed randomly to the patients before colonoscopy: 98 (49%) in Group A (patients treated with PEG preparation as a split dose for 2 days), and 102 (51%) in Group B (patients taking PEG preparation as a whole dose). Data was analyzed using SPSS version 25. Results Patients were distributed between 105 (52.5%) males and 95 (47.5%) females. The top two indications for colonoscopy were bleeding (34%), change in bowel habits (constipation/diarrhea) (32%). Patients experienced adverse events noting cramps (48.5%), stomach ache (32%), headache (31%), vomiting (53%), nausea (53%), sleep disturbance (27%), bloating (26.5%), and malaise (26%). A statistically significant difference (p = 0.040) was detected in sleep disturbance: 20.4% of patients in group A and 33.3% of patients in group B. The average satisfaction score was 3.02 ± 1.03 over 4 (Group A) and 3.04 ± 0.99 over 4 (Group B) (p = 0.896). The average BBPS was 8.07 ± 1.14 (Group A) and 8.28 ± 1.0 (Group B) (p = 0.162). Conclusion The two administrations were almost similar in term of satisfaction and BBPS. As multiple factors like age, sexe, comorbidities may contribute in altering how much a given drug is safe and efficace, more research is needed to choose the best 3regimen for each patient.

Background/aims: Chronic inflammatory bowel diseases (IBDs), including Crohn's disease and ulcerative colitis are known for a combination of food intolerance, decreased oral intake, and malabsorption which all predispose patients to malnutrition and suboptimal dietary intake. The present study was conducted to 1) examine self-reported food intolerances and dietary supplement use 2) assess nutritional intake 3) assess the nutritional status and screen for malnutrition among patients with chronic inflammatory bowel disease (CIBD)., Methods: 48 patients with CIBDs (28 Crohn's disease, 15 ulcerative colitis and 7 with atypical forms of IBD) took part in this cross-sectional study. Participants completed a food frequency questionnaire targeting dietary intakes and food trends over time. A questionnaire about food intolerance was also used. The nutritional status of patients with CIBDs was evaluated by a detailed history (medical diagnosis and medications and supplements administered) and by using the subjective global assessment (SGA) tool. Anthropometric data including height, weight, and BMI with body composition assessment using automated scales and stadiometer, while Bio-impedancemetry was used to measure body fat and visceral fat. Statistical analysis was conducted using SPSS 27, employing mean values, standard deviations, absolute and relative frequencies and Pearson's chi-square test, with significance set at p ≤ 0.05., Results: Food intolerance was equally common in all the types of CIBD specifically for dairy products, spicy foods, and high-fiber food items (beans and raw vegetables). Individuals with CIBD were also complaining about meat and chicken products (68%), followed by alcohol and soda (64%) and fish and sea foods (59%). 17% of the patients were malnourished. A significant percentage of malnourished patients with CIBD had to follow a diet outside the flare, had a nutritional follow up, were currently taking corticosteroids and had a severe form of the disease compared to patients who were well nourished., Conclusions: This study has contributed valuable insights into the understanding that some food items could be associated to periods of increased disease activity in CIBD patients and that awareness/intervention regarding nutrition must be provided by healthcare professionals (dietitians, physicians…) to decrease the need for second line therapy. In addition, this self-reported food intolerance paper gives an insight for patients on food items usually avoided by CIBD patients during flares., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hoteit et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aim Estimate the prevalence of gastric polyps linked to long-term use of proton pump inhibitor (PPI), determine the various risk factors that promote this association, and identify the characteristics associated with these polyps. Methods This prospective cross-sectional study was conducted on approximately 1000 patients presenting to the Gastroenterology Endoscopic Department for upper GI endoscopy at two hospital centers in Beirut, Lebanon, over a period of 12 months from September 2021 to September 2022. The demographic and clinical data of patients who had been taking PPIs for at least one month were collected via a questionnaire. All patients with a previous Helicobacter pylori (H. pylori) infection, presence of hypergastrinemia, or a personal/family history of gastric polyps were excluded from this study. Statistical analyses were performed using SPSS 20 software. Categorical variables were compared by Fisher's exact test; p-values of less than 0.05 were considered statistically significant. Results The prevalence of gastric polyps linked to long-term PPI use was 30%. The minimum duration of daily PPI use required for the formation of polyps is around 24 months. The dosage did not play a significant role in increasing this prevalence. A significant correlation was found between chronic PPI use and factors such as sex, age range, duration, and type of PPI used. These polyps were predominantly found in females (with an OR of 2.9), increased with age, were mostly of the fundic gland type, and their size was proportionally linked to both the dosage and duration of daily PPI use. No cases of dysplasia within the fundic gland polyps (FGPs) were demonstrated in our study. Conclusion To date, there is no current data that prove an association between gastric cancer and PPI-induced FGPs. Additionally, the incidence of FGPs has increased with the widespread chronic use of PPIs. Therefore, attention should be drawn to the potential risk of dysplasia. Thus, the present study highlights the importance of limiting the prescription of PPIs to globally well-defined indications and determining the various risk factors that promote the association between gastric polyps and PPI use. This abstract was recently presented as an E-poster at the ESGE Days 2024 Congress on April 25-27, 2024, in Berlin, Germany., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Rafik Hariri University Hospital issued approval Rhuh 13/21. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Bouhairie et al.)

Chronic liver diseases are a major global health concern., Aims: this study investigated the links between medical, clinical, anthropometric, and dietary factors with dysfunction-associated steatotic liver disease (MASLD) in the Lebanese population using a case-control approach to uncover factors influencing visceral obesity, sarcopenia, and sarcopenic obesity., Methods and Materials: a total of 120 participants (20-70 years old) were divided into case and control groups based on liver disease diagnosis. Patient information was gathered through a questionnaire encompassing demographics, medical history, and beverage consumption. Anthropometric and body composition data were collected in a clinical setting., Results: our findings indicated a clear association between the presence of MASLD and obesity, hypertension, and diabetes. The positive association with higher body mass index and all three conditions remained consistent even when data was stratified by case and control groups. A greater proportion of MASLD patients exhibited sarcopenic obesity. Furthermore, MASLD cases showed higher consumption of sugary beverages and a reduced intake of milk and water in their diets., Conclusions: this study shed light on the health attributes and diets of the Lebanese population with liver diseases and suggested more research in this area and in a more ethnically diverse population.

Objectives: Responsive neurostimulation (RNS) is a relatively recent addition to the epilepsy surgery armory, gaining FDA approval in 2013 for use in adults with intractable focal epilepsy. Data for the use of RNS system in patients less than 18 years of age is limited. We aim to determine the safety and feasibility of RNS in children with refractory epilepsy., Methods: A retrospective chart review was conducted for all patients who underwent RNS implantation at an urban tertiary children's hospital. Demographics of the patients were obtained, including age at the time of implant, MRI findings, seizure onset zone identification, and RNS targets., Results: Out of a fourteen patient cohort, one patient had a post-operative complication of infection at surgical site requiring explantation. Thirteen out of 14 patients had immediate post-operative head imaging that was negative for hemorrhage, infarction, or skull fracture; one patient did not undergo head imaging. No patients reported a worsening clinical seizure frequency at a 6-month follow up visit. In the subset of patients who were implanted with RNS and did not undergo concurrent resections, there was a statistically significant reduction in the average number of long episodes at the most recent visit when compared to the 1-month post-operative visit (p = 0.0268)., Conclusions: RNS is a feasible and safe option for children as young as six years with refractory epilepsy when appropriate seizure focus identification has been performed with stereo CT and stereo EEG evaluations, and can be used in conjunction with other surgical epilepsy treatment modalities. Two canister RNS placement is achievable for patients with a broad epileptogenic network or multifocal seizure onset zones., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023. Published by Elsevier Ltd.)

Ten-Eleven Translocation (TET) proteins have recently come to light as important epigenetic regulators conserved in multicellular organisms. TET knockdown studies in rodents have highlighted the critical role of these proteins for proper brain development and function. Mutations in mammalian mTET proteins and mTET2 specifically are frequent and deregulated in leukaemia and glioma respectively. Accordingly, we examined the role of mTET2 in tumorigenesis in larval haemocytes and adult heads in Drosophila melanogaster . Our findings showed that expression of mutant and wild type mTET2 resulted in general phenotypic defects in adult flies and accumulation of abdominal melanotic masses. Notably, flies with mTET2-R43G mutation at the N-terminus of mTET2 exhibited locomotor and circadian behavioural deficits, as well as reduced lifespan. Flies with mTET2-R1261C mutation in the catalytic domain, a common mutation in acute myeloid leukaemia (AML), displayed alterations affecting haemocyte haemostasis. Using transcriptomic approach, we identified upregulated immune genes in fly heads that were not exclusive to TET2 mutants but also found in wild type mTET2 flies. Furthermore, inhibiting expression of genes that were found to be deregulated in mTET2 mutants, such as those involved in immune pathways, autophagy, and transcriptional regulation, led to a rescue in fly survival, behaviour, and hemocyte number. This study identifies the transcriptomic profile of wild type mTET2 versus mTET2 mutants (catalytic versus non-catalytic) with indications of TET2 role in normal central nervous system (CNS) function and innate immunity.

Background: Considerable improvements in the prognosis of pediatric cancer patients have been achieved over recent decades due to advances in treatment. Nevertheless, as the most common and distressing health issue for pediatrics with cancer, cancer-related pain is still a significant hurdle that impedes patients' journey to recovery, compromises their quality of life, and delays the positive outcome and effectiveness of their treatments., Purpose: Taking into consideration that acceptability studies are imperative for the design, evaluation, and implementation of healthcare interventions, this study aims to explore pediatric oncology patients' readiness to use a mobile health application that emphasizes social assistance and peer support in addition to conventional pain management methods., Design and Methods: This study followed the Qualitative description approach. Twelve participants were chosen based on purposive sampling and maximum variation sampling. Interviews were analyzed using the conventional content analysis., Results: Analysis of the interviews revealed four major categories: (A) The need for connectedness; (B) An innovative way to connect yet fearful; (C) A 3D approach; (D) Fears of the unfamiliar., Conclusions: This study is the first in Lebanon and the region to undertake an initiative towards introducing technology for pain assessment and management of children with cancer through a dedicated digital platform. The study results attested to the acceptability and potential utilization of this platform by children with cancer., Practice Implications: Nurses need to be trained to play an essential role in teaching children with cancer about the significance of social support and assisting them to establish their social support network. Children with cancer are encouraged to voice out their need for help. Our proposed application can create an enabling environment to harness the power of social support and provide children with cancer the opportunity to connect on a deeper level in a supportive and pity-free space., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Pediatric residencies are not preparing trainees well to manage patients with seizures and epilepsy. To address this, we implemented a six-session curriculum using active learning techniques with the goals of improving the knowledge and attitudes needed to effectively identify and treat seizures and epilepsy, and increase residents' comfort with counseling families about these topics., Methods: A structured curriculum was implemented over the course of one month for the pediatric resident learner using andragogical methods such as didactic presentation, small-group sessions, role play, and simulation. A 15 multiple-choice question (MCQ) assessment and 13-statement attitudes inventory (AI) using Likert scales were given before the start of the curriculum and after its completion. Pretest and post-test scores were compared for the residents who attended at least three of the six sessions., Results: Fifty residents completed the pretest, 34 residents completed the post-test, and 24 residents completed both. Of the 24, only 19 residents attended at least half the sessions. There was a significant improvement in scores for the MCQ assessment, for each grouped AI domain, and in the proportion of residents who reported comfort with 11 of 13 AI statements., Conclusion: The findings of this study demonstrate that given quality high-impact educational content, pediatric residents' knowledge about seizures and epilepsy improves significantly. It is feasible to implement active learning techniques during structured didactic time. The importance of closing the knowledge gap and improving pediatric comfort with seizures and epilepsy is essential and may translate to the much needed improvement in access to care for the patients with these disorders., Competing Interests: Declaration of competing interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Pediatric pineoblastomas (PBs) are rare and aggressive tumors of grade IV histology. Although some oncogenic drivers are characterized, including germline mutations in RB1 and DICER1, the role of epigenetic deregulation and cis -regulatory regions in PB pathogenesis and progression is largely unknown. Here, we generated genome-wide gene expression, chromatin accessibility, and H3K27ac profiles covering key time points of PB initiation and progression from pineal tissues of a mouse model of CCND1 -driven PB. We identified PB-specific enhancers and super-enhancers, and found that in some cases, the accessible genome dynamics precede transcriptomic changes, a characteristic that is underexplored in tumor progression. During progression of PB, newly acquired open chromatin regions lacking H3K27ac signal become enriched for repressive state elements and harbor motifs of repressor transcription factors like HINFP, GLI2, and YY1. Copy number variant analysis identified deletion events specific to the tumorigenic stage, affecting, among others, the histone gene cluster and Gas1 , the growth arrest specific gene. Gene set enrichment analysis and gene expression signatures positioned the model used here close to human PB samples, showing the potential of our findings for exploring new avenues in PB management and therapy. Overall, this study reports the first temporal and in vivo cis -regulatory, expression, and accessibility maps in PB., (© 2023 Idriss et al.; Published by Cold Spring Harbor Laboratory Press.)

Objectives: Map regional lymph node metastases for lateralized oral cavity squamous cell carcinoma (OCSCC) and evaluate factors associated with regional metastases and recurrence., Materials and Methods: Retrospective cohort study of 715 patients with lateralized OCSCC surgically treated in 1997-2011. Analysis was performed using log-rank, Kaplan-Meier, and multivariable logistic and Cox regression., Results: Regional metastases were identified in ipsilateral levels IIA (24%), IB (18%), III (13%), V (9%), IV (7%), IA (2%) and IIB (1%) and the contralateral neck (3%). Lymphovascular invasion (LVI) (Hazard Ratio [HR] 2.2, 95% Confidence Interval [CI] 1.2-3.9) and T category (T3 vs. T1: HR 4.1, 95% CI 1.9-9.3; T4 vs. T1: HR 2.3, 95% CI 1.2-4.3) were associated with regional metastases. Most (71%) isolated regional metastatic recurrences were in undissected levels of the neck, including 58% in levels IV and V. Tumors of the hard palate (HR 4.3, 95% CI 1.2-16.1), upper alveolus (HR 3.2, 95% CI 1.0-4.7) or with LVI (HR 2.0, 95% CI 1.0-3.9) were associated with isolated regional recurrence. For upper alveolar/hard palate tumors, depth of invasion (DOI) ≥4 mm (P = .003) and LVI (P = .04) were associated with regional metastases., Conclusions: For lateralized OCSCC, elective neck dissection of level IIB or the contralateral neck may rarely be needed, but additional surgical or radiation treatment of levels IV and V may be considered based on patient risk factors, including T category 3-4 or LVI. For upper alveolar/hard palate tumors, DOI ≥4 mm is an appropriate threshold for elective neck dissection., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mark E. Zafereo reports research funding (PI clinical trials) from Merck and Eli Lilly not relevant to this research. Otherwise, the authors have no financial disclosures, nor conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Background : Celiac disease (CD) is an autoimmune disorder triggered by gluten, that occurs in susceptible individuals and is associated with dietary restriction and subsequent nutritional deficiencies. This study investigated the diet quality, nutrition imbalances and nutrition status among young children, adolescents and adults with CD who were referred to several hospitals in Lebanon. Methods: A cross-sectional study in 50 individuals (31.74 ± 15.64 years) with CD was conducted, using biochemical parameters, anthropometric measurements, dietary and physical activity assessments. Results : Of the 50 participants, 38% and 16% were presenting low serum levels of iron and vitamin B12, respectively. The majority of participants were physically inactive and around 40% of them had low muscle mass. A weight loss of 10% to 30% indicating mild to moderate malnutrition was shown in 14% of individuals. The assessment of food-related behaviors shows that 80% of participants were reading nutrition labels and 96% of them were following gluten-free diets (GFD). Some barriers including family ignorance (6%), language of the nutrition labels (20%) and expensive GF products (78%) were limiting the adherence to GFD. The inadequacy of the daily energy intake along with insufficient intakes of calcium and vitamin D were remarked among individuals with CD. However, protein and iron intake were exceeding the recommendations among all age groups, except in males aged 4-8 years and 19-30 years. Half the study participants were using dietary supplements where 38%, 10%, 46%, 18%, 16% and 4% used vitamin D, vitamin B12, iron, calcium, folate and probiotics, respectively. Conclusion:  GFD is the key treatment for CD. However, it is not without inadequacies and may cause certain deficiencies such as calcium and vitamin D leading to reduced bone density. This underlines the critical role of dietitians in education and maintenance of healthy GFD among individuals with CD., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Hoteit M et al.)

Background : Celiac disease is an autoimmune disorder triggered by gluten, that occurs in susceptible individuals and is associated with dietary restriction and subsequent nutritional deficiencies. This study investigated the diet quality, nutrition imbalances and nutrition status among young children,adolescents and adults with CD who followed a gluten free diet an who were referred to several hospitals in Lebanon. Methods: A cross-sectional study in 50 individuals (31.74 ± 15.64 years) with CD was conducted, using biochemical parameters, anthropometric measurements, dietary and physical activity assessments. Results : Of the 50 participants, 38% and 16% were presenting low serum levels of iron and vitamin B12, respectively. The majority of participants were physically inactive and around 40% of them had low muscle mass. A weight loss of 10% to 30% indicating mild to moderate malnutrition was shown in 14% of individuals. The assessment of food-related behaviors shows that 80% of participants were reading nutrition labels and 96% of them were following gluten-free diets. Some barriers including family ignorance (6%), language of the nutrition labels (20%) and expensive GF products (78%) were limiting the adherence to GFD. The inadequacy of the daily energy intake along with insufficient intakes of calcium and vitamin D were remarked among individuals with CD. However, protein and iron intake were exceeding the recommendations among all age groups, except in males aged 4-8 years and 19-30 years. Half the study participants were using dietary supplements where 38%, 10%, 46%, 18%, 16% and 4% used vitamin D, vitamin B12, iron, calcium, folate and probiotics, respectively. Conclusion:  GFD is the key treatment for CD. However, it is not without inadequacies and may cause certain deficiencies such as calcium and vitamin D leading to reduced bone density. This underlines the critical role of dietitians in education and maintenance of healthy GFD among individuals with CD., Competing Interests: No competing interests were disclosed., (Copyright: © 2022 Hoteit M et al.)

Motivation: Identifying histone tail modifications using ChIP-seq is commonly used in time-series experiments in development and disease. These assays, however, cover specific time-points leaving intermediate or early stages with missing information. Although several machine learning methods were developed to predict histone marks, none exploited the dependence that exists in time-series experiments between data generated at specific time-points to extrapolate these findings to time-points where data cannot be generated for lack or scarcity of materials (i.e. early developmental stages)., Results: Here, we train a deep learning model named TempoMAGE, to predict the presence or absence of H3K27ac in open chromatin regions by integrating information from sequence, gene expression, chromatin accessibility and the estimated change in H3K27ac state from a reference time-point. We show that adding reference time-point information systematically improves the overall model's performance. In addition, sequence signatures extracted from our method were exclusive to the training dataset indicating that our model learned data-specific features. As an application, TempoMAGE was able to predict the activity of enhancers from pre-validated in-vivo dataset highlighting its ability to be used for functional annotation of putative enhancers., Availability and Implementation: TempoMAGE is freely available through GitHub at https://github.com/pkhoueiry/TempoMAGE., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The inflammasome plays an essential role in lower risk MDS and immune subversion, with the up-regulation of immune checkpoint molecules in the progression to higher-risk disease. In this study, we explored the utility of immune-related biomarkers for the diagnosis and prognosis of MDS., Methods: We performed an exploratory, case-control study with 20 randomly selected MDS patients and nine controls with non-inflammatory ( n = 3) and inflammatory conditions ( n = 6). Patients were stratified in groups of lower ( n = 10) and higher risk ( n = 10) using IPSS-R. For the exploration of inflammasome and immune checkpoint activities, the expression of caspase-1 (Casp1), programmed cell death protein 1 (PD-1) and its ligand (PD-L1) were assessed in bone marrow samples using immunohistochemistry., Results: In multivariate analysis, we observed significant differences for Casp1 but not PD1/PD-L1 expression in our four conditions ( p = 0.003). We found a discordant co-expression of Casp1/PD-L1 in MDS (rho = -0.41, p = 0.07) compared with a concordant co-expression in controls (rho = 0.64, p = 0.06). Neutrophil counts correlated directly with Casp1 (rho = 0.57, p = 0.009) but inversely with PD-L1 expression (rho = -0.58, p = 0.007)., Conclusion: We identified characteristic discordant co-expression patterns in lower- (Casp1 high /PD-L1 low ) and higher-risk MDS (Casp1 low /PD-L1 high ), contrasting with concordant patterns in the non-inflammatory (Casp1 low /PD-L1 low ) and inflammatory conditions (Casp1 high /PD-L1 high ). Further validation is warranted in larger, prospective studies.

Background: Despite the introduction of targeted therapies, most patients with myeloid malignancies will not be cured and progress. Genomics is useful to elucidate the mutational landscape but remains limited in the prediction of therapeutic outcome and identification of targets for resistance. Dysregulation of phosphorylation-based signaling pathways is a hallmark of cancer, and therefore, kinase-inhibitors are playing an increasingly important role as targeted treatments. Untargeted phosphoproteomics analysis pipelines have been published but show limitations in inferring kinase-activities and identifying potential biomarkers of response and resistance., Methods: We developed a phosphoproteomics workflow based on titanium dioxide phosphopeptide enrichment with subsequent analysis by liquid chromatography tandem mass spectrometry (LC-MS). We applied a novel Kinase-Activity Enrichment Analysis (KAEA) pipeline on differential phosphoproteomics profiles, which is based on the recently published SetRank enrichment algorithm  with reduced false positive rates. Kinase activities were inferred by this algorithm using an extensive reference database comprising five experimentally validated kinase-substrate meta-databases complemented with the NetworKIN in-silico prediction tool. For the proof of concept, we used human myeloid cell lines (K562, NB4, THP1, OCI-AML3, MOLM13 and MV4-11) with known oncogenic drivers and exposed them to clinically established kinase-inhibitors., Results: Biologically meaningful over- and under-active kinases were identified by KAEA in the unperturbed human myeloid cell lines (K562, NB4, THP1, OCI-AML3 and MOLM13). To increase the inhibition signal of the driving oncogenic kinases, we exposed the K562 (BCR-ABL1) and MOLM13/MV4-11 (FLT3-ITD) cell lines to either Nilotinib or Midostaurin kinase inhibitors, respectively. We observed correct detection of expected direct (ABL, KIT, SRC) and indirect (MAPK) targets of Nilotinib in K562 as well as indirect (PRKC, MAPK, AKT, RPS6K) targets of Midostaurin in MOLM13/MV4-11, respectively. Moreover, our pipeline was able to characterize unexplored kinase-activities within the corresponding signaling networks., Conclusions: We developed and validated a novel KAEA pipeline for the analysis of differential phosphoproteomics MS profiling data. We provide translational researchers with an improved instrument to characterize the biological behavior of kinases in response or resistance to targeted treatment. Further investigations are warranted to determine the utility of KAEA to characterize mechanisms of disease progression and treatment failure using primary patient samples.

Despite the availability of methods for analyzing protein complexes, systematic analysis of complexes under multiple conditions remains challenging. Approaches based on biochemical fractionation of intact, native complexes and correlation of protein profiles have shown promise. However, most approaches for interpreting cofractionation datasets to yield complex composition and rearrangements between samples depend considerably on protein-protein interaction inference. We introduce PCprophet, a toolkit built on size exclusion chromatography-sequential window acquisition of all theoretical mass spectrometry (SEC-SWATH-MS) data to predict protein complexes and characterize their changes across experimental conditions. We demonstrate improved performance of PCprophet over state-of-the-art approaches and introduce a Bayesian approach to analyze altered protein-protein interactions across conditions. We provide both command-line and graphical interfaces to support the application of PCprophet to any cofractionation MS dataset, independent of separation or quantitative liquid chromatography-MS workflow, for the detection and quantitative tracking of protein complexes and their physiological dynamics.

Introduction: Patients presenting to the pediatric emergency department (ED) often undergo unnecessary testing that leads to prolonged ED visits. Lower ED length of stay has been linked to improved patient experience and may reduce ED overcrowding, a costly burden on a health system., Methods: This is a retrospective cohort study involving patient records over the period of 6 months at an urban tertiary children's hospital who presented with seizures. Febrile seizures, seizures associated with trauma, and charts of patients who did not present initially through our ED were excluded., Results: 328 charts were obtained through this search criteria. Head imaging was performed in 52 (16%) patients and consisted of 81% CT (n = 42) and 19% (n = 10) magnetic resonance imaging (MRI). Obtaining an MRI was associated with a 3.5 h longer ED visit (p = 0.07); obtaining a CT was associated with a 1.5 h longer ED visit (p = 0.005). An Electroencephalogram (EEG) was obtained for 67 (20%) visits and was associated with a 3.0 h longer ED length of stay (p < 0.001). Ten % of the CT scans showed new or progressive findings and 40% of the MRIs done provided useful information for management. Thirty-seven % of EEGs performed in new onset seizure patients revealed epileptiform findings and 5% of EEGs in established seizure patients provided meaningful findings important to management., Conclusion: Obtaining neurodiagnostic studies significantly prolongs duration of stay in the ED. Electroencephalograms appear to have the greatest yield in new onset seizure patients and can help make a diagnosis of an epilepsy syndrome in children., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Anemic patients with lower risk myelodysplastic syndromes are frequently treated with erythropoiesis stimulating agents (ESA), eventually in combination with granulocyte colony stimulating factor (G-CSF). However, the evidence for the efficacy of a combined treatment remains controversial. The goal of our analysis was to assess the available evidence for a combined treatment. We performed a systematic review and identified only nine eligible studies. In two randomized controlled trials (n = 98), erythroid response rates were 33% and 40% after low-/standard-doses of ESA alone (10,000-30,000 rHuEPO equivalents/week) versus 65% and 73% after combination treatment. In seven trials with sequential drug administration (n = 393), erythroid response rates ranged from 12% to 71% after full-doses of ESA alone (60,000-80,000 rHuEPO equivalents/week) and from 35% to 74% after combination therapy. Our analysis supports an additional efficacy of G-CSF added to low-/standard-dose ESA, but the available data remains controversial, if G-CSF is added to full-dose ESA., (Copyright © 2019 Elsevier B.V. All rights reserved.)