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من حكايا الغوايانا
الحكاية هي خير مرآة تعكس لنا أفكار الشعوب ومعتقداتهم وأنماط حياتهم، سواء أكانت من قديم الزمان أم من العصور غير البعيدة، فهي قد اخترقت الزمن والحدود وتنقلت بين الثقافات واللغات دون أن تفقد سحرها وجمالها وهذه السلسلة تقودنا مع كل كتاب في رحلة شيقة إلى أماكن مختلفة، فنعيش نشوة السفر إلى عوالم لا نعرفها ونستمتع بما تحكي الشعوب.
BOOK
Quality assessment of gene repertoire annotations with OMArk
In the era of biodiversity genomics, it is crucial to ensure that annotations of protein-coding gene repertoires are accurate. State-of-the-art tools to assess genome annotations measure the completeness of a gene repertoire but are blind to other errors, such as gene overprediction or contamination. We introduce OMArk, a software package that relies on fast, alignment-free sequence comparisons between a query proteome and precomputed gene families across the tree of life. OMArk assesses not only the completeness but also the consistency of the gene repertoire as a whole relative to closely related species and reports likely contamination events. Analysis of 1,805 UniProt Eukaryotic Reference Proteomes with OMArk demonstrated strong evidence of contamination in 73 proteomes and identified error propagation in avian gene annotation resulting from the use of a fragmented zebra finch proteome as a reference. This study illustrates the importance of comparing and prioritizing proteomes based on their quality measures.
A new tool checks the quality of gene annotations in genome sequences.
Journal Article
The cooperative binding of TDP-43 to GU-rich RNA repeats antagonizes TDP-43 aggregation
TDP-43 is a nuclear RNA-binding protein that forms neuronal cytoplasmic inclusions in two major neurodegenerative diseases, ALS and FTLD. While the self-assembly of TDP-43 by its structured N-terminal and intrinsically disordered C-terminal domains has been widely studied, the mechanism by which mRNA preserves TDP-43 solubility in the nucleus has not been addressed. Here, we demonstrate that tandem RNA recognition motifs of TDP-43 bind to long GU-repeats in a cooperative manner through intermolecular interactions. Moreover, using mutants whose cooperativity is impaired, we found that the cooperative binding of TDP-43 to mRNA may be critical to maintain the solubility of TDP-43 in the nucleus and the miscibility of TDP-43 in cytoplasmic stress granules. We anticipate that the knowledge of a higher order assembly of TDP-43 on mRNA may clarify its role in intron processing and provide a means of interfering with the cytoplasmic aggregation of TDP-43.
Journal Article
Exploring psychiatrists’ perspectives on supporting parents with mental health Challenges: A mixed-methods study
Parenting responsibilities can be particularly challenging for patients receiving mental health services, often resulting in a range of negative impacts on children. Incorporating a family-focused approach into the usual care of parents with mental illness has been recommended to promote patient recovery while supporting the well-being of children and the entire family unit. This study aimed to document the family-focused practices undertaken by psychiatrists working with parents who have a mental illness and to explore potential facilitators and barriers to these practices.
A sequential explanatory mixed-method design was used, combining an online survey and individual interviews. Family-focused practices were reported by 27 psychiatrists through the French version of the Family-Focused Mental Health Practice Questionnaire. Follow-up qualitative individual interviews were conducted with 5 psychiatrists. Item-by-item analysis of the quantitative data was performed, followed by a thematic analysis of the qualitative data, integrating findings from both sources.
Although psychiatrists acknowledge their patients' parenting role, most are reluctant to provide further support. Key barriers to family-focused practice include the predominantly individual-focused nature of psychiatric care, stigma, consent issues, and limited collaboration between adult and child services. Facilitators include psychiatrists' professional autonomy, personal experience, and confidence in conducting family meetings.
Psychiatrists can play a pivotal role in identifying, acknowledging, and providing appropriate support to parents with mental illness and their families, including children. Developing comprehensive guidelines and targeted training is essential to equip psychiatrists with effective strategies for addressing parenting challenges in patients with complex mental health issues. Additionally, psychoeducational resources for children should be incorporated. Implementing these initiatives may lead to more compassionate, targeted care and improved outcomes for parents and their families.
Journal Article
Future impacts of colectomy healthcare pathways on quality of care in bundled payment experiments, a national retrospective cohort in France
To perform an ex-ante evaluation of French bundled payment experiments to evaluate the potential effects on hospital readmission and length of stay (LOS), and whether it could be used as a lever for improving quality of care after initial stays for surgery.
A retrospective cohort analysis was performed using data from the French National Health Data System (SNDS).
We used hospital and ambulatory data for colectomy between 2014 and 2016 (exhaustive French national data). The national database included 42,603 cancer colectomy stays during the study period.
The inclusion criteria were stays coded in the database with a principal diagnosis of colon cancer and a colectomy procedure excluding total colectomy, identified from the diagnosis related group. All partial colectomies performed in France from the 1st January 2014 to the 30th June 2016 were included, except those that met exclusion criteria, which were: admission to emergency departments, having already undergone a total colectomy (no time limit), or having undergone a partial colectomy in the previous year. Patients who died during the bundled payment period (45 days before the index stay and up to 90 days after) were excluded from the analysis. These criteria were selected and validated by the stakeholders who developed the bundled payment specifications.
The main outcome was the variation in readmissions as a function of the initial LOS using a segmented regression method, and controlling with variables used by the health authorities. We also produced models by sector (public/private) and practice (Enhanced Recovery After Surgery [ERAS] model or not).
We obtained a J-shaped curve including two distinct parts, with a breakpoint at five days for patients without major comorbidities. Before the breakpoint, increased LOS was associated with a lower probability of readmission (coefficient = -0.016, 95%CI [-0.011;-0.021], p < 0.01). After the breakpoint, there was a progressive increase in readmissions as LOS increased.
Our work suggests that improving the care pathway could reduce readmissions. Hospitals should focus on getting closer to the breakpoint, and care pathway models that reduce LOS, such as ERAS, should be encouraged for colectomy stays.
Journal Article
From TDP-43/RNA complex formation to disease-linked TDP-43 aggregation through a structural and cellular approach
Many RNA-binding proteins (RBP) have been associated to several neurodegenerative diseases for which RBP-rich cytoplasmic inclusions represent a major histological hallmark. However, among RBPs, the occurrence with which TDP-43, a nuclear mRNA-binding protein, is detected in cytoplasmic inclusions is exceptionally high. To unravel the underlying mechanisms, we focus our analysis on the structured N-terminal domain (NTD) of TDP-43, which is distinct among RBPs as this domain mostly initiates TDP-43 homotypic interactions. Through an in depth structural analysis, we successively show that the cooperative binding of TDP-43 along long GU-rich intronic sequences antagonizes NTD/NTD interactions between adjacent TDP-43 along mRNA. In contrast, the TDP-43 cooperativity facilitates NTD/NTD interactions between TDP-43 located on distinct GU-rich sequences. We hypothesize that NTD/NTD interactions between distinct GU-rich sequences efficiently allow the compaction of long introns in neurons under physiological conditions. However, when the binding of TDP-43 to RNA is discontinuous because of a lack of cooperativity, aberrant NTD/NTD interactions between adjacent TDP-43 take place, promoting the aggregation of TDP-43 RRMs (RNA Recognition Motifs) under stress conditions. Altogether, we provide a detailed view of the physiological assembly of TDP-43 on introns and the putative weaknesses of TDP-43 that makes it distinct in its propensity for aggregation compared to other RBPs.
Feng et al. unravel the structural basis of TDP-43 higher-order assemblies with mRNA and the structural changes leading to TDP-43 aggregation, which are associated with neurodegenerative diseases such as Amyotrophic Lateral Sclerosis.
Journal Article
Structure and functional impact of glycosaminoglycan modification of HSulf-2 endosulfatase revealed by atomic force microscopy and mass spectrometry
The human sulfatase HSulf-2 is one of only two known endosulfatases that play a decisive role in modulating the binding properties of heparan sulfate proteoglycans on the cell surface and in the extracellular matrix. Recently, HSulf-2 was shown to exhibit an unusual post-translational modification consisting of a sulfated glycosaminoglycan chain. This study describes the structural characterization of this glycosaminoglycan (GAG) and provides new data on its impact on the catalytic properties of HSulf-2. The unrevealed nature of this GAG chain is identified as a chondroitin/dermatan sulfate (CS/DS) mixed chain, as shown by mass spectrometry combined with NMR analysis. It consists primarily of 6-
O
and 4-
O
monosulfated disaccharide units, with a slight predominance of the 4-
O
-sulfation. Using atomic force microscopy, we show that this unique post-translational modification dramatically impacts the enzyme hydrodynamic volume. We identified human hyaluronidase-4 as a secreted hydrolase that can digest HSulf-2 GAG chain. We also showed that HSulf-2 is able to efficiently 6-
O
-desulfate antithrombin III binding pentasaccharide motif, and that this activity was enhanced upon removal of the GAG chain. Finally, we identified five N-glycosylation sites on the protein and showed that, although required, reduced N-glycosylation profiles were sufficient to sustain HSulf-2 integrity.
Journal Article
Making sense of the French public hospital system: a network-based approach to hospital clustering using unsupervised learning methods
Background
Hospitals in the public and private sectors tend to join larger organizations to form hospital groups. This increasingly frequent mode of functioning raises the question of how countries should organize their health system, according to the interactions already present between their hospitals. The objective of this study was to identify distinctive profiles of French hospitals according to their characteristics and their role in the French hospital network.
Methods
Data were extracted from the national hospital database for year 2016. The database was restricted to public hospitals that practiced medicine, surgery or obstetrics. Hospitals profiles were determined using the k-means method. The variables entered in the clustering algorithm were: the number of stays, the effective diversity of hospital activity, and a network-based mobility indicator (proportion of stays followed by another stay in a different hospital of the same Regional Hospital Group within 90 days).
Results
Three hospital groups were identified by the clustering algorithm. The first group was constituted of 34 large hospitals (median 82,100 annual stays, interquartile range 69,004 – 117,774) with a very diverse activity. The second group contained medium-sized hospitals (with a median of 258 beds, interquartile range 164 - 377). The third group featured less diversity regarding the type of stay (with a mean of 8 effective activity domains, standard deviation 2.73), a smaller size and a higher proportion of patients that subsequently visited other hospitals (11%). The most frequent type of patient mobility occurred from the hospitals in group 2 to the hospitals in group 1 (29%). The reverse direction was less frequent (19%).
Conclusions
The French hospital network is organized around three categories of public hospitals, with an unbalanced and disassortative patient flow. This type of organization has implications for hospital planning and infectious diseases control.
Journal Article
Developmental and sequenced one-to-one educational intervention (DS1-EI) for autism spectrum disorder and intellectual disability: a two-year interim report of a randomized single-blind multicenter controlled trial
Background
Children with autism spectrum disorder (ASD) and moderate to severe intellectual disability (ID) face many challenges. There is little evidence-based research into educational settings for children with ID and ASD and in France. Little is known about how this unserved population could benefit from intervention and education. This study assessed the feasibility and efficacy of a new intervention model using an individualized educational approach.
Methods
We conducted a randomized, single-blind controlled trial to assess a novel intervention: the “Developmental and Sequenced One-to-One Intervention (DS1-EI)”. In DS1-EI, trained teachers worked one-to-one with each child in a small classroom setting, offering 10 h per week of the intervention. The focus was on encouraging spontaneous communication, promoting skills through play with peers, supporting positive interactions, and developmental and sequenced learning. We enrolled 5- to 9-year-old children with ASD and ID across 11 French child care institutions for children with co-occurring ASD and ID. Participants were matched in dyads by developmental quotient and randomized to the treatment-as-usual (TAU) group or the DS1-EI group. Independent raters blindly assessed the primary variables: The Childhood Autism Rating scale (CARS) and the Psychoeducational Profile, third edition (PEP-3). The secondary variables included the Vineland Adaptive Behavior Scale II (VABS-II) and the Clinical Global Assessment Scale (CGAS). Here we perform interim analyses at 24 months.
Results
At baseline, 72 participants were randomized. Nine patients (5 in the DS1-EI group and 4 in the TAU group) dropped out of the study. Using linear mixed models, both intent-to-treat (ITT) and per-protocol (PP) analyses at the 12-, 18- and 24-month outcomes showed no significant group nor group-by-time interaction effects. However, we found significant improvements in most primary and secondary variables over time in both groups.
Conclusions
The study did not show that DS1-EI was superior to TAU in treating children with ASD and ID over 24 months. However, the low dropout rate shows that DS1-EI is feasible, and well accepted. As the study is still ongoing, we need to wait for data at 36 months to ensure whether DS1-EI could be recommended.
Trial registration
ANSM130282B-31 (April 16, 2013) and
ACTRN12616000592448
. Registered 6 May 2016, retrospectively registered,
http://www.anzctr.org.au/
Journal Article
Longitudinal Association Between Risk Profiles, School Dropout Risk, and Substance Abuse in Adolescence
BackgroundYouth psychosocial and school adjustment results from complex developmental transactions between their individual characteristics and diverse environmental influences, which appear as risk or protective factors throughout one’s development.ObjectiveFrom an ecosystemic and developmental perspective, this study aims to: (1) identify risk profiles among 13-year-old adolescents, and (2) associate these specific profiles with school dropout risk and substance abuse at age 15 years.MethodData comes from a large Canadian study, the Quebec Longitudinal Study of Development through which adolescents (n = 1312) answered questionnaires at 13 and 15 years old.ResultsFirst, through latent profile analyses, five profiles were identified based on individual, family, social, and school-based risk factors. Some profiles present higher levels of risk factors, while others comprise risk factors that are under the sample average level. Higher-risk profiles show stronger longitudinal associations with later adjustment difficulties.ConclusionsThe findings help provide a deeper understanding of how the co-occurrence of various risk factors in adolescence is associated with later adjustment. The combination of the developmental psychopathology and ecosystemic frameworks, as well as the person-centered approach allowed by the latent profile analyses, helps shed new light on individual and developmental risk.
Journal Article