MLH1 gene promoter methylation status partially overlaps with CpG methylator phenotype (CIMP) in colorectal adenocarcinoma

Background RAS/BRAF mutations, mismatch DNA repair complex deficiency (MMRd)/microsatellite instability (MSI), and CpG methylator phenotype (CIMP) are key molecular actors in colorectal carcinogenesis. To date, conflicting evidence about the correlations between these molecular features has been reported. Materials and methods A retrospectively selected cohort of 123 CRCs was divided into 3 groups based on the molecular characteristics: MMR proficient (MMRp)/BRAF p.V600E mutated (BRAF(mut)), MMRd/BRAF(mut), and MMRd/BRAF wild type (BRAF(wt)). MLH1 promoter (pMLH1) methylation status was assessed by pyrosequencing. For 82 samples the CIMP phenotype was evaluated using the EpiTect (R) MethyLight kit. Results The MMRd/BRAF(mut) group showed a higher pMLH1 methylation rate compared to both the MMRd/BRAF(wt) and the MMRp/BRAF(mut) groups. Overall, the two MMRd groups had a higher methylation rate compared to the MMRp cases independently from the mutational status of BRAF (p-value <0.0001). The MMRd/BRAF(mut) group was characterized by a 90.0 % of CIMP high (CIMP-H) tumors of which 97.2 % were pMLH1 methylated. Instead, the MMRd/BRAF(wt) group presented 50.0 % of CIMP-H adenocarcinomas. Conclusions Our study demonstrates that pMLH1 hypermethylation, MMRd, BRAF(mut) and CIMP phenotype do not completely overlap in CRC. These findings further refine the knowledge on the molecular landscape of CRC and may have critical implications also for the clinical management of the disease

Unveiling the fitness of Saccharomyces cerevisiae strains for lignocellulosic bioethanol: a genomic exploration through fermentation stress tests

Lignocellulosic biomass holds significant promise as a substrate for bioethanol production, yet the financial viability of lignocellulosic fermentation poses challenges. The pre-treatment step needed for lignocellulosic substrates generates inhibitors that impede Saccharomyces cerevisiae growth, affecting the fermentation process and overall yield. In modern sugarcane-to-ethanol plants, a rapid succession of yeast strains occurs, with dominant strains prevailing. Therefore, yeast strains with both dominance potential and inhibitor tolerance are crucial towards the development of superior strains with industrial fitness. This study adopted a hybrid approach combining biotechnology and bioinformatics to explore a cluster of 20 S. cerevisiae strains, including industrial and oenological strains exhibiting diverse phenotypic features. In-depth genomic analyses focusing on gene copy number variations (CNVs) and single nucleotide polymorphisms (SNPs) were conducted and compared with results from fermentation tests once inoculated in multiple strains kinetics under stressing conditions such as low nitrogen availability and high formic or acetic acid levels. Some strains showed high resistance to biotic stress and acetic acid. Moreover, four out of 20 strains – namely S. cerevisiae YI30, Fp89, Fp90 and CESPLG05 - displayed promising resistance also to formic acid, the most impactful weak acids in pre-treated lignocellulosic biomass. These strains have the potential to be used for the development of superior S. cerevisiae strains tailored for lignocellulosic bioethanol production

Clinical and radiographic outcomes of extra-short implants (≤ 6 mm) in the posterior atrophic jaws: a retrospective cohort study

Objective: This study aimed at investigating implant survival rate and marginal bone loss (MBL) around extra-short implants. The impact of the loading protocol and of the use of an intermediate abutment was also evaluated, to explore possible differences in terms of the outcome measures. Materials and methods: Patients with single or multiple mandibular or maxillary posterior edentulism rehabilitated using extra-short 5-6 mm long implants were included. Different prosthetic protocols were used. Clinical and radiological follow-up was 5 years. The outcomes measures were implant survival and MBL. Results: The analysis included 56 implants placed in 34 adults (12 males and 22 females; mean age 60 years, SD 11). Six implants failed during a median follow-up of 5 years and 4 of them were recorded in one patient at 2-year follow-up. The 5-year implant survival was 89% overall (87% in conventional and 94% in immediate loading). At univariate analysis, during follow-up immediate loading was associated with higher MBL (mean variation 0.21 mm, 95%CI 0.01 to 0.40; p = 0.02), while intermediate abutment was associated with lower MBL (mean variation -0.23 mm, 95%CI -0.39 to -0.09; p = 0.003). Multivariable analysis confirmed that immediate loading was associated with higher MBL. Conclusion: Within its limitations, this study showed that extra-short implants under immediate loading conditions can be a reliable solution. The application of horizontal and vertical platform switching with the use of intermediate abutments seems to be able to contribute to the reduction of MBL

Reduced ATP turnover during hibernation in relaxed skeletal muscle

Hibernating brown bears, due to a drastic reduction in metabolic rate, show only moderate muscle wasting. Here, we evaluate if ATPase activity of resting skeletal muscle myosin can contribute to this energy sparing. By analyzing single muscle fibers taken from the same bears, either during hibernation or in summer, we find that fibers from hibernating bears have a mild decline in force production and a significant reduction in ATPase activity. Single fiber proteomics, western blotting, and immunohistochemical analyses reveal major remodeling of the mitochondrial proteome during hibernation. Furthermore, using bioinformatical approaches and western blotting we find that phosphorylated myosin light chain, a known stimulator of basal myosin ATPase activity, is decreased in hibernating and disused muscles. These results suggest that skeletal muscle limits energy loss by reducing myosin ATPase activity, indicating a possible role for myosin ATPase activity modulation in multiple muscle wasting conditions

Ink and pixels: Impact of highlighting and reading self-efficacy on adolescents' cognitive load, epistemic emotions, and text comprehension

This study investigated the impact of reading texts on paper versus on screen on lower-secondary school students' perception of cognitive load, epistemic emotions, and text comprehension, while considering contextual and individual factors, that is, the strategy of highlighting and the motivational variable of reading self-efficacy. In a mixed-design experiment, 191 seventh graders read two informational texts, one in print and the other on screen. Half of the participants only read the texts, while the other half highlighted them to support comprehension. Students self-reported their perception of cognitive load and epistemic emotions immediately after reading. Text comprehension was assessed using literal and inferential multiple-choice questions. The study also examined whether the supportive role of self-efficacy varied across reading media. Findings suggest that adolescents' digital reading reduced cognitive load without affecting their text comprehension. However, limited benefits of highlighting and reading self-efficacy emerged in digital reading

Identifying consensus and areas for future research in chondrosarcoma : a report from the Birmingham Orthopaedic Oncology Meeting

Aims: The Birmingham Orthopaedic Oncology Meeting (BOOM), held in January 2024, convened 309 delegates from 53 countries to discuss and refine 21 consensus statements on the optimal management of chondrosarcoma. Methods: With representation from Europe (43%; n = 133), North America (17%; n = 53), South America (16%; n = 49), Asia (13%; n = 40), Australasia (5%; n = 16), the Middle East (4%; n = 12), and Africa (2%; n = 6), the combined experience of treating bone sarcomas among attendees totalled approximately 30,000 cases annually, equivalent to 66 years of experience in the UK alone. The meeting's process began with the formation of a local organizing committee, regional leads, and a scientific committee comprising representatives from 150 specialist units across 47 countries. Supported by major orthopaedic oncology organizations, the meeting used a modified Delphi process to develop consensus statements through online questionnaires, thematic groupings, narrative reviews, and anonymous pre-meeting polling. Results: Strong (> 80%) consensus was achieved on 19 out of 21 statements, reflecting agreement among delegates. Key areas of consensus included the role of radiology in diagnosis and surveillance, the management of locally recurrent disease, and the treatment of dedifferentiated chondrosarcoma. Notably, there was agreement that routine chemotherapy has no role in chondrosarcoma treatment, and radiological surveillance is safe for intraosseous chondrosarcomas. Despite the overall consensus, areas of controversy remain, particularly regarding the treatment of atypical cartilage tumours and surgical margins. These unresolved issues underscore the need for further research and collaboration within the orthopaedic oncology community. Conclusion: BOOM represents the largest global consensus meeting in orthopaedic oncology, providing valuable guidance for clinicians managing chondrosarcoma worldwide. The consensus statements offer a reference for clinical practice, highlight key research priorities, and aim to improve patient outcomes on a global scale