Garside and quadratic normalisation: a survey

Starting from the seminal example of the greedy normal norm in braid monoids, we analyse the mechanism of the normal form in a Garside monoid and explain how it extends to the more general framework of Garside families. Extending the viewpoint even more, we then consider general quadratic normalisation procedures and characterise Garside normalisation among them.Comment: 30 page

Effects of Exercise Training on Bone Health Parameters in Individuals With Obesity:A Systematic Review and Meta-Analysis

International audienceBackground: Osteoporosis causes bone fragility, increasing the risk of fractures. Evidence suggests a strong correlation between obesity and fracture risk. Physical training is known to enhance bone resistance and protect from fracture; however, its osteogenic effect in the presence of obesity remains unknown.and nbsp;Objective: We sought to evaluate the influence of exercise training on bone health indices in individuals with obesity.and nbsp;Methods: This systematic literature search was conducted using common electronic databases from inception - December 2019. The following key terms (and synonyms searched for by the MeSH database) were included and combined using the operators "AND, " "OR, " "NOT ": [( "body mass index " OR obesity OR obese OR overweight OR fat mass) AND ( "bone mineral density " OR "bone mineral content " OR "peak bone mass " OR "mechanical loading " OR "Osteoporosis " OR "bone geometry " OR "bone resistance ") AND ( "exercise training " OR "physical training " OR "strength training, " OR "resistance training " OR "aerobic training " OR "combined training ")].and nbsp;Results: After screening, 10 studies (889 initial records) were included in the final analysis (8 different countries, 263 participants). Two studies investigated males, six females, and two, both sexes. The training duration was at least eight weeks with 2-3 sessions/week. Physical training displayed a significant trivial impact on the whole body (WB) BMD (0.13 SMD; 95% CI [0.00, 0.26], p = 0.046). Subgroup analyses indicated a significant small increase in the WB BMD (0.27 SMD; 95% CI [0.00, 0.53], p = 0.048) in the endurance training group, a non-significant trivial increase in the WB BMD (0.11 SMD; 95% CI [-0.06, 0.29], p = 0.203) in the resistance group, and a non-significant trivial increase in the WB BMD (0.03 SMD; 95% CI [-0.26, 0.32], p = 0.86) in the combined training group. In addition, a significant small decrease was found in the weight of trained subjects (-0.24 SMD; 95% CI [-0.42, -0.05], p = 0.011).and nbsp;Conclusion: Physical training has little to no effect on the WB BMD in subjects with overweight/obesity. Currently, insufficient evidence to advocate for any specific type of exercise for enhancing bone health exists for overweight/obese individuals. Investigations examining the impact of varying types of physical exercise on WB BMD of obese individuals are needed

Tumor suppressor p53 binds with high affinity to CTG-CAG trinucleotide repeats and induces topological alterations in mismatched duplexes

DNA binding is central to the ability of p53 to function as a tumor suppressor. In line with the remarkable functional versatility of p53, which can act on DNA as a transcription, repair, recombination, replication, and chromatin accessibility factor, the modes of p53 interaction with DNA are also versatile. One feature common to all modes of p53-DNA interaction is the extraordinary sensitivity of p53 to the topology of its target DNA. Whereas the strong impact of DNA topology has been demonstrated for p53 binding to sequence-specific sites or to DNA lesions, the possibility that DNA structure-dependent recognition may underlie p53 interaction with other types of DNA has not been addressed until now. We demonstrate for the first time that conformationally flexible CTG·CAG trinucleotide repeats comprise a novel class of p53-binding sites targeted by p53 in a DNA structure-dependent mode in vitro and in vivo. Our major finding is that p53 binds to CTG·CAG tracts by different modes depending on the conformation of DNA. Although p53 binds preferentially to hairpins formed by either CTG or CAG strands, it can also bind to linear forms of CTG·CAG tracts such as canonic B DNA or mismatched duplex. Intriguingly, by binding to a mismatched duplex p53 can induce further topological alterations in DNA, indicating that p53 may act as a DNA topology-modulating factor

The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction.

The mammalian target of rapamycin (mTOR) is a critical regulator of cell growth, integrating multiple signalling cues and pathways. Key among the downstream activities of mTOR is the control of the protein synthesis machinery. This is achieved, in part, via the co-ordinated regulation of mRNAs that contain a terminal oligopyrimidine tract (TOP) at their 5'ends, although the mechanisms by which this occurs downstream of mTOR signalling are still unclear. We used RNA-binding protein (RBP) capture to identify changes in the protein-RNA interaction landscape following mTOR inhibition. Upon mTOR inhibition, the binding of LARP1 to a number of mRNAs, including TOP-containing mRNAs, increased. Importantly, non-TOP-containing mRNAs bound by LARP1 are in a translationally-repressed state, even under control conditions. The mRNA interactome of the LARP1-associated protein PABPC1 was found to have a high degree of overlap with that of LARP1 and our data show that PABPC1 is required for the association of LARP1 with its specific mRNA targets. Finally, we demonstrate that mRNAs, including those encoding proteins critical for cell growth and survival, are translationally repressed when bound by both LARP1 and PABPC1

Development of Degradable, pH‐Sensitive Star Vectors for Enhancing the Cytoplasmic Delivery of Nucleic Acids

The report describes the synthesis of degradable, pH‐sensitive, membrane‐destabilizing, star‐shaped polymers where copolymers of hydrophobic hexyl methacrylate (HMA) and 2‐(dimethylamino)ethyl methacrylate (DMAEMA) monomers are grafted from the secondary face of a beta‐cyclodextrin (β‐CD) core via acid‐labile hydrazone linkages using atom transfer radical polymerization. The effect of the graft's molecular weight, HMA/DMAEMA molar ratio, and the fraction of DMAEMA converted to cationic N,N,N‐trimethylaminoethyl methacrylate (TMAEMA) monomers on polymer's transfection capacity is systematically investigated. Results show that all star‐shaped polymers condense anti‐GAPDH silencing RNA (siRNA) into nanosized particles at +/‐ ratio ≤ 4:1. Star polymers with shorter (25kDa) P(HMA‐ co ‐DMAEMA‐ co ‐TMAEMA) grafts are more efficient and less cytotoxic than carriers with longer (40kDa) grafts. The results show that increasing the ratio of hydrophobic HMA monomers in graft's composition higher than 50 mole% dramatically reduces polymer's aqueous solubility and abolishes their transfection capacity. Further, retention of DMAEMA monomers in graft's composition provide a buffering capacity that enhanced the endosomal escape and transfection capacity of the polymers. These systematic studies show that β‐CD‐P(HMA‐ co ‐DMAEMA‐ co ‐TMAEMA) 4.8 polymer with a 25 kDa average graft's molecular weight and a 50/25/25 ratio of HMA/DMAEMA/TMAEMA monomers is the most efficient carrier in delivering the siRNA cargo into the cytoplasm of epithelial cancer cells. A series of degradable, pH‐sensitive, membrane‐destabilizing, star‐shaped polymers is synthesized. Star polymers are engineered to “sense” the drop in endosomal pH, which triggers the hydrolysis of acid‐labile hydrazone linkages and release of membrane‐active grafts that rupture the endosomal membrane and release the loaded siRNA cargo into the cytoplasm to produce the desired knockdown of targeted gene expression at both the mRNA and protein levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99666/1/3885_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99666/2/adfm_201203762_sm_suppl.pd

Using artificial intelligence for exercise prescription in personalised health promotion: A critical evaluation of OpenAI’s GPT-4 model

The rise of artificial intelligence (AI) applications in healthcare provides new possibilities for personalized health management. AI-based fitness applications are becoming more common, facilitating the opportunity for individualised exercise prescription. However, the use of AI carries the risk of inadequate expert supervision, and the efficacy and validity of such applications have not been thoroughly investigated, particularly in the context of diverse health conditions. The aim of the study was to critically assess the efficacy of exercise prescriptions generated by OpenAI’s Generative Pre-Trained Transformer 4 (GPT-4) model for five example patient profiles with diverse health conditions and fitness goals. Our focus was to assess the model’s ability to generate exercise prescriptions based on a singular, initial interaction, akin to a typical user experience. The evaluation was conducted by leading experts in the field of exercise prescription. Five distinct scenarios were formulated, each representing a hypothetical individual with a specific health condition and fitness objective. Upon receiving details of each individual, the GPT-4 model was tasked with generating a 30-day exercise program. These AI-derived exercise programs were subsequently subjected to a thorough evaluation by experts in exercise prescription. The evaluation encompassed adherence to established principles of frequency, intensity, time, and exercise type; integration of perceived exertion levels; consideration for medication intake and the respective medical condition; and the extent of program individualization tailored to each hypothetical profile. The AI model could create general safety-conscious exercise programs for various scenarios. However, the AI-generated exercise prescriptions lacked precision in addressing individual health conditions and goals, often prioritizing excessive safety over the effectiveness of training. The AI-based approach aimed to ensure patient improvement through gradual increases in training load and intensity, but the model’s potential to fine-tune its recommendations through ongoing interaction was not fully satisfying. AI technologies, in their current state, can serve as supplemental tools in exercise prescription, particularly in enhancing accessibility for individuals unable to access, often costly, professional advice. However, AI technologies are not yet recommended as a substitute for personalized, progressive, and health condition specific prescriptions provided by healthcare and fitness professionals. Further research is needed to explore more interactive use of AI models and integration of real-time physiological feedback

Factors associated with mortality in patients with drug-susceptible pulmonary tuberculosis

<p>Abstract</p> <p>Background</p> <p>Tuberculosis is a leading cause of death worldwide, yet the determinants of death are not well understood. We sought to determine risk factors for mortality during treatment of drug-susceptible pulmonary tuberculosis under program settings.</p> <p>Methods</p> <p>Retrospective chart review of patients with drug-susceptible tuberculosis reported to the San Francisco Tuberculosis Control Program from 1990-2001.</p> <p>Results</p> <p>Of 565 patients meeting eligibility criteria, 37 (6.6%) died during the study period. Of 37 deaths, 12 (32.4%) had tuberculosis listed as a contributing factor. In multivariate analysis controlling for follow-up time, four characteristics were independently associated with mortality: HIV co-infection (HR = 2.57, p = 0.02), older age at tuberculosis diagnosis (HR = 1.52 per 10 years, p = 0.001); initial sputum smear positive for acid fast bacilli (HR = 3.07, p = 0.004); and experiencing an interruption in tuberculosis therapy (HR = 3.15, p = 0.002). The association between treatment interruption and risk of death was due to non-adherence during the intensive phase of treatment (HR = 3.20, p = 0.001). The median duration of treatment interruption did not differ significantly in either intensive or continuation phases between those who died and survived (23 versus 18 days, and 37 versus 29 days, respectively). No deaths were directly attributed to adverse drug reactions.</p> <p>Conclusions</p> <p>In addition to advanced age, HIV and characteristics of advanced tuberculosis, experiencing an interruption in anti-tuberculosis therapy, primarily due to non-adherence, was also independently associated with increased risk of death. Improving adherence early during treatment for tuberculosis may both improve tuberculosis outcomes as well as decrease mortality.</p

Development of a Standardized Screening Rule for Tuberculosis in People Living with HIV in Resource-Constrained Settings: Individual Participant Data Meta-analysis of Observational Studies

Haileyesus Getahun and colleagues report the development of a simple, standardized tuberculosis (TB) screening rule for resource-constrained settings, to identify people living with HIV who need further investigation for TB disease

Bridging the gap: safety and outcomes of intensivist-led ECMO retrievals

PurposeMost extracorporeal membrane oxygenation (ECMO) cannulations are performed by cardiothoracic surgeons (CTS). Due to an increase in utilization of ECMO and limited availability of CTS, there is a mismatch between ECMO demand and CTS accessibility for remote cannulations. We report our intensivist-led program’s experience in remote ECMO cannulations, retrievals, complications, and outcomes.Materials and methodsA prospective, single-center, observational study was performed on patients that required ECMO cannulation at the referring facilities and were transported to our institution between program initiation, on October 1, 2014 to September 30, 2022. Results were presented as mean ± SD, median (min – max) or number (%).ResultsSince program commencement, 305 patients were accepted for ECMO retrieval. Three hundred and three patients were placed on ECMO at the 47 referring hospitals among 5 states. In our study, 185 (61%) patients required veno-arterial ECMO and 115 (38%) were placed on veno-venous ECMO. Three patients (1%) were cannulated for veno-arteriovenous ECMO. Twenty patients were cannulated under cardio-pulmonary resuscitation. Most of the patients were transported by ambulance (79%), 14% by helicopter, and 7% by airplane. Six out of the 303 patients did not leave the referring facility. All patients that left the referring hospitals arrived safely to our institution. No major complications occurred in route.ConclusionOur study’s findings indicate that non-CTS physicians can successfully cannulate and retrieve patients with a low complication profile