Developmental dynamics of the epigenome and methods to find relevant regulatory motifs

Studying the epigenome and which transcription factors interact with it gives us a better understanding of how developmental processes are regulated and harmoniously orchestrated. For sensory neurons, such signals correspond to environmental stimuli. A group of genes called immediate early genes (IEGs) are known to play important roles during development, and they are some of the first to respond to signals a cell receives. They tend to encode for transcription factors (TFs), are activated within minutes and regulate the activity of other genes. Studying the features of these genes, we found a new epigenetic signature that hints at why they can be induced so fast. They have the active H3K27ac mark on their promoters, and the repressive H3K27me3 mark on their gene bodies. We found a few hundred genes with this signature and called them ‘bipartite’ genes. Bipartite genes are very lowly expressed, or not at all. They are, however, in a poised state that is even more ready to be quickly induced than the known bivalent genes. The needed transcriptional machinery is already sitting at the promoter. We used t-distributed stochastic neighbor embedding to jointly visualize chromatin accessibility and several histone marks on all genes in barrelette neurons of the somatosensory system in mice. Moreover, we used several developmental time points to visualize genome-wide changes in chromatin states across development. This allowed us to visualize the epigenetic dynamics that bipartite genes undergo by observing how they move from one developmental time point to another in these chromatin landscapes. As mentioned, IEGs correspond to TFs that have important regulatory roles. Knowing which TFs play relevant or functional roles is key to understanding the underlying developmental processes. Motivated by the importance of finding relevant TFs, we developed computational methods that enable us to make predictions, in an unbiased way, about which TFs could explain an experimental measure of interest, typically coming from sequencing data. We created an R package called monaLisa, short for “motif analysis with Lisa”, that allows for these methods to be used in a user-friendly manner. The package offers two main ways of identifying regulatory motifs. In the first approach, we made use of an existing method of correcting for sequence composition differences to apply a binned motif enrichment analysis. This method links motif enrichment to an experimental value, for example changes in DNA methylation between two conditions. The second approach uses linear regression to select a set of TFs that are likely to explain the given observations. Specifically, we use randomized lasso stability selection to discover relevant motifs. The new epigenetic signature with the bipartite genes illustrates how the epigenome can control a timely transcriptional response during development, and the methods in monaLisa further enable us to decipher which TFs could be key players

Ground and space based optical analysis of materials degradation in low-Earth-orbit

There is strong interest in being able to accurately and sensitively monitor materials degradation in both ground-based and space-based environments. Two optical techniques for sensitive degradation monitoring are reviewed: spectroscopic ellipsometry and photothermal spectroscopy. These techniques complement each other in that ellipsometry is sensitive to atomically thin surface and subsurface changes, and photothermal spectroscopy is sensitive to local defects, pin-holes, subsurface defects, and delamination. Progress in applying these spectroscopies (both ex situ and in situ) to atomic oxygen degradation of space materials is reviewed

Advantages of Gel Oral Rehydration Solutions (ORS) for the Management of Acute Diarrhea: An Update

Currently, in the management of acute diarrhea, underuse of oral rehydration solutions (ORS), is still reported, being a strong rationale for their improvement to increase patient's acceptability and, in consequence, treatment compliance and therapeutic success, for example, in terms of palatability, and swallowability. In this article, we reviewed the advantages of new ORS gel formulations, with solid or semi-solid texture, that could help to overcome the inconveniences of conventional ORS. The main difficulty, the salty taste, can be masked using flavors, reconstituting and administering the gel product at low temperatures or using pleasant textures that resembles desserts or sweets. Another important critical point in the oral rehydration is the relatively large volumes administered, usually rejected by children. In gel formulations the volume is significantly reduced to around 100ml, and can be administered at small portions, thus avoiding its refusal and facilitating the role of parents or caregivers in administering it. Recent studies have shown these benefits, together with the demonstration of the electrolytes release at gastric level. However, more clinical trials are needed to compare gel formulations versus standard ORS

Ellipsometer

In an ellipsometer, a phase-modulated, polarized light beam is applied to a sample, electrical signals are obtained representing the orthogonal planes of polarization of the light after it has interacted with the sample and the constants of the sample are calculated from the two resulting electrical signals. The phase modulation is sufficiently small so that the calibration errors are negligible. For this purpose, the phase modulator, phase modulates the light within a range of no more than ten degrees peak to peak. The two electrical signals are expanded by Fourier analysis and the coefficients thereof utilized to calculate psi and delta

A multicenter analysis of the role of prophylactic transfusion of blood products in patients with cirrhosis and esophageal varices undergoing endoscopic band ligation

Cirrhosis; Endoscopic band ligation; Esophageal varices; Platelet transfusionCirrosis; Ligadura endoscópica con banda; Varices esofágicas; Transfusión de plaquetasCirrosi; Lligadura de banda endoscòpica; Varices esofàgiques; Transfusió de plaquetesBackground & aims: Prophylactic administration of platelets and fresh frozen plasma (FFP) has been recommended in patients with cirrhosis with low platelets and/or prolonged international normalized ratio (INR) without scientific evidence to support this practice. In this analysis, we evaluated the use of prophylactic administration of blood products in outpatients with cirrhosis undergoing endoscopic band ligation (EBL). Methods: This is a multicenter retrospective analysis of consecutive EBL procedures in patients with cirrhosis at 4 hospitals in Spain from 01/2010-01/2017. FFP and/or platelet transfusion were given at the discretion of the physician if INR was >1.5 and/or platelet count <50x109/L. Patient demographics, endoscopic findings, bleeding events after EBL, and the use of prophylactic FFP or platelets were recorded. Results: A total of 536 patients underwent 1,472 EBL procedures: 72% male; main etiology HCV and alcohol (72%); median MELD score 11; Child-Pugh A/B/C (59/33/8%). EBL procedures were performed for primary (51%) or secondary (49%) prophylaxis. A median of 2 procedures per patient were performed.1-4 FFP and/or platelets were administered in 41 patients (7.6%). The prophylactic transfusion protocol was followed in 16% and 28% of procedures with high INR and/or low platelets, respectively. Post-EBL bleeding occurred in 26 out of 536 patients (4.8%) and in 33 out of 1,472 procedures (2.2%). Bleeding was due to post-EBL ulcers in 21 patients and due to band dislodgment in 5. In 6 patients, bleeding occurred within 24 hours and in the remaining patients it occurred within 2 weeks after EBL. In those that bled, 7 met criteria for transfusion (2 for FFP and 5 for platelets), of whom only 1 received FFP and 4 received platelets; the remaining 19 patients did not meet criteria for transfusion. There was no association between INR or platelet count and bleeding events. Univariate and multivariate analysis revealed that Child-Pugh and MELD scores were risk factors for post-EBL bleeding. Conclusions: The incidence of post-EBL bleeding is low and is associated with advanced liver disease. Post-EBL bleeding was not related to baseline INR/platelet count and most outpatients with post-EBL bleeding did not meet criteria for prophylactic transfusion. Lay summary: Patients with chronic liver disease or cirrhosis and enlarged veins (varices) of the esophagus that can potentially bleed commonly need an endoscopy to treat these varices with elastic rubber bands (endoscopic band ligation). Some patients have low platelet counts or prolonged coagulation tests. This analysis of 4 centers evaluated the use of prophylactic administration of blood products in outpatients with cirrhosis undergoing endoscopic band ligation. The results showed that bleeding after band ligation is uncommon and that if bleeding occurs it does not seem to be related with coagulation tests or the administration of blood products to prevent bleeding after band ligation of esophageal varices

National Alliance of Stakeholders for the Wheat Sector in Lebanon: Multistakeholder Workshop Report

On July 24, 2023, the International Center for Agricultural Research in the Dry Areas (ICARDA) and the Lebanese Agricultural Research Institute (LARI) under the Ministry of Agriculture organized a Multistakeholder Workshop on “National Alliance of Stakeholders for the Wheat Sector in Lebanon”. The agenda of the workshop is provided in Appendix 1. More than 20 representatives of various stakeholders attended the workshop, including officials of key government ministries and agencies, researchers from multiple research institutes, non-governmental and non-profit organizations, representatives of the United Nations (UN) agencies, and the private sector

Satisfaction and experience with colorectal cancer screening : a systematic review of validated patient reported outcome measures

Background: Patient satisfaction or experience with colorectal cancer screening can determine adherence to screening programs. An evaluation of validated patient reported outcome measures (PROMs) for measuring experience or satisfaction with colorectal cancer screening does not exist. Our objective was to identify and critically appraise validated questionnaires for measuring patient satisfaction or experience with colorectal cancer screening. Methods: We conducted a systematic review following the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) methodology. We conducted searches on MEDLINE, EMBASE, PsychINFO, CINAHL and BiblioPRO and assessed the methodological quality of studies and measurement properties of questionnaires according to the COSMIN guidelines for systematic reviews of PROMs. PROSPERO registration number: CRD42019118527. Results: We included 80 studies that used 75 questionnaires, of which only 5 were validated. Four questionnaires measured satisfaction with endoscopy: two in the context of colorectal cancer screening (for colonoscopy and sigmoidoscopy) and two for non-screening endoscopy. One questionnaire measured satisfaction with bowel preparation. The methodological quality of studies was variable. The questionnaires with evidence for sufficient content validity and internal consistency were: the CSSQP questionnaire, which measures safety and satisfaction with screening colonoscopy, and the Post-Procedure questionnaire which measures satisfaction with non-screening endoscopic procedures. Conclusions: This systematic review shows that a minority of existing PROMs for measuring patient satisfaction with colorectal cancer screening are validated. We identified two questionnaires with high potential for further use (CSSQP and the Post-Procedure questionnaire)

Comparable quality of bowel preparation with single‐day versus three‐day low‐residue diet: Randomized controlled trial

Background and aims: There is controversy about the length of low-residue diet (LRD) for colonoscopy preparation. The aim of the study was to compare one-day vs. three-day LRD associated to standard laxative treatment for achieving an adequate colonoscopy preparation in average risk subjects with positive fecal immunochemical test undergoing screening colonoscopy. Methods: A non-inferiority, randomized, controlled, parallel-group clinical trial was performed in the setting of average risk colorectal cancer screening program. Participants were randomized to receive 1-day vs. 3-day LRD in addition to standard polyethilenglicol treatment. Adequacy of preparation was evaluated using the Boston Bowel Preparation Scale (BBPS). Primary outcome was achieving a BBPS ≥ 2 in all colon segments. Analysis was performed for a non-inferiority margin of 5%, a 95% statistical power and one-sided 0.05 significance level. Results: A total of 855 patients were randomized. Adequate bowel preparation was similar between groups: 97.9% of patients in the 1-day LRD group vs 96.9% in the 3-day LRD group achieved the primary outcome (P-value for non-inferiority < 0.001). The percentage of patients with BBPS scores ≥ 8 was superior in the 1-day LRD group (254 vs 221 in the 3-day LRD group, P = 0.032). The 1-day regimen was better tolerated than the 3-day diet. 47.7% (vs 28.7%, P < 0.05) of patients rated the 1-day LRD as very easy to follow. Conclusion: The 1-day LRD is non-inferior to 3-day LRD for achieving an adequate colon cleansing before average risk screening colonoscopy and it is better tolerated. Keywords: bowel preparation; colonoscopy; colorectal cancer; screening

Effectiveness of Innovation Platforms in Enhancing the Viability of the Wheat Seed Sector in Terbol Station, Lebanon

The objective of this research was to assess the effectiveness of the innovation platform (IP) (Terbol Station) on the wheat seed sector in Lebanon. Data were collected from 16 seed producers after identifying and mapping the key stakeholders in the seed sector. Descriptive statistics was used to categorize and evaluate the efficacy of the innovation platform by identifying six groups: seed availability and access, knowledge and training, seed production and market impact, incentives, joint planning, and the situation of the seed sector in Lebanon. Incentives and joint planning were found to be the primary groups of the IP that the farmers emphasized their importance. The correlation between different groups was found to be statistically significant. Farmers noted that the wheat seed sector is non-profitable and, therefore, needs financial support and joint planning of the value chain. The study recommends the intervention of the government and the Ministries of Agriculture and Economy & Trade by customizing governance strategies and policies. In addition, the adaptation of regulatory measures of the wheat seed sector and agricultural guidance can provide essential information, recommendations, and expertise to optimize the production, distribution, and utilization of seeds in Lebanon

A unique bipartite Polycomb signature regulates stimulus-response transcription during development

Rapid cellular responses to environmental stimuli are fundamental for development and maturation. Immediate early genes can be transcriptionally induced within minutes in response to a variety of signals. How their induction levels are regulated and their untimely activation by spurious signals prevented during development is poorly understood. We found that in developing sensory neurons, before perinatal sensory-activity-dependent induction, immediate early genes are embedded into a unique bipartite Polycomb chromatin signature, carrying active H3K27ac on promoters but repressive Ezh2-dependent H3K27me3 on gene bodies. This bipartite signature is widely present in developing cell types, including embryonic stem cells. Polycomb marking of gene bodies inhibits mRNA elongation, dampening productive transcription, while still allowing for fast stimulus-dependent mark removal and bipartite gene induction. We reveal a developmental epigenetic mechanism regulating the rapidity and amplitude of the transcriptional response to relevant stimuli, while preventing inappropriate activation of stimulus-response genes.T.K. was supported by a Japan Society for the Promotion of Science fellowship, and O.J. was supported by an EMBO Long-Term fellowship. F.M.R. was supported by the Swiss National Science Foundation (31003A_149573 and 31003A_175776). This project has also received funding from the European Research Council under the European Union’s Horizon 2020 research and innovation programme (grant no. 810111-EpiCrest2Reg). F.M.R. and M.B.S. were also supported by the Novartis Research Foundation.Peer reviewe