OMMA enables population-scale analysis of complex genomic features and phylogenomic relationships from nanochannel-based optical maps.

BackgroundOptical mapping is an emerging technology that complements sequencing-based methods in genome analysis. It is widely used in improving genome assemblies and detecting structural variations by providing information over much longer (up to 1 Mb) reads. Current standards in optical mapping analysis involve assembling optical maps into contigs and aligning them to a reference, which is limited to pairwise comparison and becomes bias-prone when analyzing multiple samples.FindingsWe present a new method, OMMA, that extends optical mapping to the study of complex genomic features by simultaneously interrogating optical maps across many samples in a reference-independent manner. OMMA captures and characterizes complex genomic features, e.g., multiple haplotypes, copy number variations, and subtelomeric structures when applied to 154 human samples across the 26 populations sequenced in the 1000 Genomes Project. For small genomes such as pathogenic bacteria, OMMA accurately reconstructs the phylogenomic relationships and identifies functional elements across 21 Acinetobacter baumannii strains.ConclusionsWith the increasing data throughput of optical mapping system, the use of this technology in comparative genome analysis across many samples will become feasible. OMMA is a timely solution that can address such computational need. The OMMA software is available at https://github.com/TF-Chan-Lab/OMTools

How did the work impact me? Reflections of the researchers and facilitators of BME success projects

Programme leaders and members of programme teams attended inclusive teaching workshops focused on race equality. After the workshops, programme leaders were interviewed to discuss how they were going to implement inclusive practice enhancements. The core team who facilitated the workshops and conducted the interviews reflected on their experiences of leading change associated with reducing the BME attainment gap. Considering a critical incident which theyd experienced during the workshop or during the interviews, they each wrote personal narratives to explore emotions which the incident had stimulated as well as consideration of how theyd responded at the time and what they could have done differently. The four narratives were considered to identify key themes. Two common themes identified were the stimulation of negative emotions (e.g. anger) and the inability to challenge comments and stereotyping assumptions at the time of the incident. Considering the results in light of literature associated with staff development, the use of personal narrative and leading diversity related change, in addition to autoethnographical thoughts associated with the authors own experiences of race, racism and privilege, five recommendations for colleagues involved in race-related staff development were identified

Genome maps across 26 human populations reveal population-specific patterns of structural variation.

Large structural variants (SVs) in the human genome are difficult to detect and study by conventional sequencing technologies. With long-range genome analysis platforms, such as optical mapping, one can identify large SVs (>2 kb) across the genome in one experiment. Analyzing optical genome maps of 154 individuals from the 26 populations sequenced in the 1000 Genomes Project, we find that phylogenetic population patterns of large SVs are similar to those of single nucleotide variations in 86% of the human genome, while ~2% of the genome has high structural complexity. We are able to characterize SVs in many intractable regions of the genome, including segmental duplications and subtelomeric, pericentromeric, and acrocentric areas. In addition, we discover ~60 Mb of non-redundant genome content missing in the reference genome sequence assembly. Our results highlight the need for a comprehensive set of alternate haplotypes from different populations to represent SV patterns in the genome

Fluoroscopic Surrogate for Pharyngeal Strength: The Pharyngeal Constriction Ratio (PCR)

The pharyngeal constriction ratio (PCR), derived directly from videofluoroscopy without the need for manometry, requires validation as a surrogate for pharyngeal strength. A correlation of −0.70 was previously identified between PCR and pharyngeal clearing pressures (PP) on separate fluoroscopic and manometric studies. As PP increases, PCR decreases. The objective of the current study was to evaluate the correlation between PCR and PP in 25 patients undergoing simultaneous fluoroscopy and pharyngeal manometry. The effect of the manometric catheter on PCR was also investigated. The correlation between the PCR and averaged pharyngeal clearing pressures was −0.72 (p < 0.001). All patients with a PCR > 0.25 had a PP < 60 mmHg. PCR did not differ significantly as a consequence of the manometric catheter. Results suggest the utility of an objective fluoroscopic measure in assessing pharyngeal strength when manometry may not be available or possible

Consensus of the definitions of the OMERACT glucocorticoid impact core domain set for people with rheumatic and musculoskeletal diseases

Background: The Outcome Measures in Rheumatology (OMERACT) Glucocorticoid (GC) Impact Working Grouphas been working to develop a core domain set to measure the impact of GCs on patients living with rheumaticand musculoskeletal diseases. The mandatory domains previously identified for inclusion in all clinical trialsmeasuring the GC effects include infection, bone fragility, mood disturbance, hypertension, diabetes, weight,fatigue, and mortality. Before progressing to instrument selection, the Working Group sought to establish precisedefinitions of all mandatory domains within the core domain set.Methods: OMERACT methodology was applied with the use of evidence and consensus-based decision making ofall stakeholder groups (patient research partners, health care professionals, clinician researchers, industrymembers and methodologists) to develop detailed definitions for the broad domain, target domain and domaincomponents, taking into consideration sources of variability that could affect measurement of the domain. Theworking group synthesized prior qualitative studies, quantitative work, and results from Delphi rounds, todevelop a rich definition of ‘what’ is to be measured.Results: Between 2021 and 2023, the OMERACT Working Group on GC Impact conducted virtual meetings toestablish domain definitions. First, we mapped each domain onto an OMERACT Core Area. All domains wereprimarily represented within the Pathophysiological Manifestations Core Area, except from Fatigue which wasprimarily Life Impact and Weight which spanned both Core Areas. Sources of variability included cultural factors, age, gender, education level, socioeconomic status, personal experiences, emotional state, and languagebarriers. The domain definitions will form the foundation for instrument selection and the initial step of domain /concept match and content validity in the OMERACT pillar of ‘truth’ before moving on to feasibility anddiscrimination.Conclusion: The OMERACT GC Impact Working Group has developed and agreed upon detailed domain definitions for core domains. Future steps of the working group are to select instruments and develop the core outcom

Gs-Coupled Adenosine Receptors Differentially Limit Antigen-Induced Mast Cell Activation

Mast cell activation results in the immediate release of proinflammatory mediators prestored in cytoplasmic granules, as well as initiation of lipid mediator production and cytokine synthesis by these resident tissue leukocytes. Allergen-induced mast cell activation is central to the pathogenesis of asthma and other allergic diseases. Presently, most pharmacological agents for the treatment of allergic disease target receptors for inflammatory mediators. Many of these mediators, such as histamine, are released by mast cells. Targeting pathways that limit antigen-induced mast cell activation may have greater therapeutic efficacy by inhibiting the synthesis and release of many proinflammatory mediators produced in the mast cell. In vitro studies using cultured human and mouse mast cells, and studies of mice lacking A2B receptors, suggest that adenosine receptors, specifically the Gs-coupled A2A and A2B receptors, might provide such a target. Here, using a panel of mice lacking various combinations of adenosine receptors, and mast cells derived from these animals, we show that adenosine receptor agonists provide an effective means of inhibition of mast cell degranulation and induction of cytokine production both in vitro and in vivo. We identify A2B as the primary receptor limiting mast cell degranulation, whereas the combined activity of A2A and A2B is required for the inhibition of cytokine synthesis

Breast cancer early detection : a phased approach to implementation

Q1Q1When breast cancer is detected and treated early, the chances of survival are very high. However, women in many settings face complex barriers to early detection, including social, economic, geographic, and other interrelated factors, which can limit their access to timely, affordable, and effective breast health care services. Previously, the Breast Health Global Initiative (BHGI) developed resource-stratified guidelines for the early detection and diagnosis of breast cancer. In this consensus article from the sixth BHGI Global Summit held in October 2018, the authors describe phases of early detection program development, beginning with management strategies required for the diagnosis of clinically detectable disease based on awareness education and technical training, history and physical examination, and accurate tissue diagnosis. The core issues address include finance and governance, which pertain to successful planning, implementation, and the iterative process of program improvement and are needed for a breast cancer early detection program to succeed in any resource setting. Examples are presented of implementation, process, and clinical outcome metrics that assist in program implementation monitoring. Country case examples are presented to highlight the challenges and opportunities of implementing successful breast cancer early detection programs, and the complex interplay of barriers and facilitators to achieving early detection for breast cancer in real-world settings are considered.https://scholar.google.com/citations?user=xFiKCkMAAAAJ&hl=eshttp://scienti.colciencias.gov.co:8081/cvlac/visualizador/generarCurriculoCv.do?cod_rh=0000264474Revista Nacional - Indexad

Examining patient-reported late toxicity and its association with quality of life and unmet need for symptom management among nasopharyngeal cancer survivors: a cross-sectional survey

IntroductionAlongside the improved survival of nasopharyngeal cancer (NPC), late radiation toxicities are alarmingly hampering survivors’ quality of life. A patient-reported symptom burden survey is lacking to address the unmet need for symptom management among local NPC survivors.MethodsA single-center cross-sectional survey was conducted on 211 NPC survivors who had completed radiation therapy for three to 120 months. We employed the Chinese version M. D. Anderson Symptom Inventory - Head &amp; Neck Module (MDASI-HN-C), Functional Assessment of Cancer Therapy - Head &amp; Neck (FACT-HN-C), and a question extracted from the Cancer Survivors’ Unmet Needs Measure (CaSUN).ResultsTwo hundred valid responses were collected. Participants suffered from at least four moderate to severe symptoms (mean = 4.84, SD = 4.99). The top five severe symptoms were dry mouth, mucus problems, difficulty swallowing or chewing, teeth or gum problems, and memory problems. MDASI-HN-C subscales were negatively correlated with the physical, emotional, functional, and HN-specific domains of the FACT-HN-C. The unmet need for symptom management was positively associated with symptom burden, either general symptoms (Adjusted odds ratio [ORadj] = 1.566, 95% CI = 1.282 – 1.914, p &lt; 0.001) or top-5 symptoms (ORadj = 1.379, 95% CI = 1.185 – 1.604, p &lt; 0.001), while negatively associated with post-RT time (ORadj = 0.981, 95% CI [0.972, 0.991], p &lt; 0.001).ConclusionVirtually all NPC survivors suffer from late toxicities, which interplay with survivors’ perceptions intricately to affect their unmet needs for symptom management. Personalized supportive care strategies with regular assessments and stratifications are warranted