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Olivia decides to throw her mother a surprise birthday party, and with a little help from her father, her grandmother, and her brother she fixes a menu of red foods and gets everything ready.

Among critically ill adults undergoing tracheal intubation, hypoxemia increases the risk of cardiac arrest and death. The effect of preoxygenation with noninvasive ventilation, as compared with preoxygenation with an oxygen mask, on the incidence of hypoxemia during tracheal intubation is uncertain. In a multicenter, randomized trial conducted at 24 emergency departments and intensive care units in the United States, we randomly assigned critically ill adults (age, ≥18 years) undergoing tracheal intubation to receive preoxygenation with either noninvasive ventilation or an oxygen mask. The primary outcome was hypoxemia during intubation, defined by an oxygen saturation of less than 85% during the interval between induction of anesthesia and 2 minutes after tracheal intubation. Among the 1301 patients enrolled, hypoxemia occurred in 57 of 624 patients (9.1%) in the noninvasive-ventilation group and in 118 of 637 patients (18.5%) in the oxygen-mask group (difference, -9.4 percentage points; 95% confidence interval [CI], -13.2 to -5.6; P<0.001). Cardiac arrest occurred in 1 patient (0.2%) in the noninvasive-ventilation group and in 7 patients (1.1%) in the oxygen-mask group (difference, -0.9 percentage points; 95% CI, -1.8 to -0.1). Aspiration occurred in 6 patients (0.9%) in the noninvasive-ventilation group and in 9 patients (1.4%) in the oxygen-mask group (difference, -0.4 percentage points; 95% CI, -1.6 to 0.7). Among critically ill adults undergoing tracheal intubation, preoxygenation with noninvasive ventilation resulted in a lower incidence of hypoxemia during intubation than preoxygenation with an oxygen mask. (Funded by the U.S. Department of Defense; PREOXI ClinicalTrials.gov number, NCT05267652.).

Assigned the less-than-leading role of \"Cow Number 2\" in her school's play, Olivia manages to secure her place in the spotlight after all.

The growing number of next-generation sequencing (NGS) data presents a unique opportunity to study the combined impact of mitochondrial and nuclear-encoded genetic variation in complex disease. Mitochondrial DNA variants and in particular, heteroplasmic variants, are critical for determining human disease severity. While there are approaches for obtaining mitochondrial DNA variants from NGS data, these software do not account for the unique characteristics of mitochondrial genetics and can be inaccurate even for homoplasmic variants. We introduce MitoScape, a novel, big-data, software for extracting mitochondrial DNA sequences from NGS. MitoScape adopts a novel departure from other algorithms by using machine learning to model the unique characteristics of mitochondrial genetics. We also employ a novel approach of using rho-zero (mitochondrial DNA-depleted) data to model nuclear-encoded mitochondrial sequences. We showed that MitoScape produces accurate heteroplasmy estimates using gold-standard mitochondrial DNA data. We provide a comprehensive comparison of the most common tools for obtaining mtDNA variants from NGS and showed that MitoScape had superior performance to compared tools in every statistically category we compared, including false positives and false negatives. By applying MitoScape to common disease examples, we illustrate how MitoScape facilitates important heteroplasmy-disease association discoveries by expanding upon a reported association between hypertrophic cardiomyopathy and mitochondrial haplogroup T in men (adjusted p-value = 0.003). The improved accuracy of mitochondrial DNA variants produced by MitoScape will be instrumental in diagnosing disease in the context of personalized medicine and clinical diagnostics.

Despite the growing prevalence of people with complex conditions and evidence of the positive impact of telemonitoring for single conditions, little research exists on telemonitoring for this population. This randomized controlled trial and embedded qualitative study aims to evaluate the impact on and experiences of patients and health care providers (HCPs) using a telemonitoring system with decision support to manage patients with complex conditions, including those with multiple chronic conditions, compared with the standard of care. A pragmatic, unblinded, 6-month randomized controlled trial sought to recruit 146 patients with ≥1 diagnosis of heart failure (HF), uncontrolled hypertension (HT), and insulin-requiring diabetes mellitus (DM) from outpatient specialty settings in Toronto, Ontario, Canada. Participants were randomized into the control and telemonitoring groups, with the latter being instructed to take readings relevant to their conditions. The telemonitoring system contained an algorithm that generated decision support in the form of actionable self-care directives to patients and alerts to HCPs. The primary outcome was health status (36-Item Short Form Health Survey questionnaire). Secondary outcomes included anxiety and depression, self-efficacy in chronic disease management, and self-reported health service use. HF-related quality of life and self-care measures were also collected from patients followed for HF. Within- and between-group change scores were analyzed for statistical significance (P<.05). A convenience sample of HCPs and patients in the intervention group was interviewed about their experiences. A total of 96 patients were recruited and randomized. Recruitment was terminated early because of implementation challenges and the onset of the COVID-19 pandemic. No significant within- and between-group differences were found for the main primary and secondary outcomes. However, a within-group analysis of patients with HF found improvements in self-care maintenance (P=.04) and physical quality of life (P=.046). Opinions expressed by the 5 HCPs and 13 patients who were interviewed differed based on the monitored conditions. Although patients with HF reported benefitting from actionable self-care guidance and meaningful interactions with their HCPs, patient and HCP users of the DM and HT modules did not think telemonitoring improved the clinical management of those conditions to the same degree. These differing experiences were largely attributed to the siloed nature of specialty care and the design of the decision support, whereby fluctuations in the status of HT and DM typically required less urgent interventions compared with patients with HF. We recommend that future research conceive telemonitoring as a program and that self-management and clinical decision support are necessary but not sufficient components of such programs for patients with complex conditions and lower acuity. We conclude that telemonitoring for patients with complex conditions or within multidisciplinary care settings may be best operationalized through nurse-led models of care. ClinicalTrials.gov NCT03127852; https://clinicaltrials.gov/ct2/show/NCT03127852. RR2-10.2196/resprot.8367.

Structural, biophysical and genetic analyses reveal that Schizosaccharomyces pombe Ctp1 forms a flexible tetramer with multivalent DNA-binding and bridging activities that contribute to Ctp1's role in repair of DNA double-strand breaks. Ctp1 (also known as CtIP or Sae2) collaborates with Mre11–Rad50–Nbs1 to initiate repair of DNA double-strand breaks (DSBs), but its functions remain enigmatic. We report that tetrameric Schizosaccharomyces pombe Ctp1 contains multivalent DNA-binding and DNA-bridging activities. Through structural and biophysical analyses of the Ctp1 tetramer, we define the salient features of Ctp1 architecture: an N-terminal interlocking tetrameric helical dimer-of-dimers (THDD) domain and a central intrinsically disordered region (IDR) linked to C-terminal 'RHR' DNA-interaction motifs. The THDD, IDR and RHR are required for Ctp1 DNA-bridging activity in vitro , and both the THDD and RHR are required for efficient DSB repair in S. pombe . Our results establish non-nucleolytic roles of Ctp1 in binding and coordination of DSB-repair intermediates and suggest that ablation of human CtIP DNA binding by truncating mutations underlie the CtIP-linked Seckel and Jawad syndromes.

The Playbook Workflow Builder (PWB) is a web-based platform to dynamically construct and execute bioinformatics workflows by utilizing a growing network of input datasets, semantically annotated API endpoints, and data visualization tools contributed by an ecosystem of collaborators. Via a user-friendly user interface, workflows can be constructed from contributed building-blocks without technical expertise. The output of each step of the workflow is added into reports containing textual descriptions, figures, tables, and references. To construct workflows, users can click on cards that represent each step in a workflow, or construct workflows via a chat interface that is assisted by a large language model (LLM). Completed workflows are compatible with Common Workflow Language (CWL) and can be published as research publications, slideshows, and posters. To demonstrate how the PWB generates meaningful hypotheses that draw knowledge from across multiple resources, we present several use cases. For example, one of these use cases prioritizes drug targets for individual cancer patients using data from the NIH Common Fund programs GTEx, LINCS, Metabolomics, GlyGen, and ExRNA. The workflows created with PWB can be repurposed to tackle similar use cases using different inputs. The PWB platform is available from: https://playbook-workflow-builder.cloud/ .

ObjectivesTo develop a practical step-by-step technique to precisely identify and differentiate tendons and ligaments attaching to the humeral epicondyles, to confirm through gross anatomical study the accurate structure identification provided by this technique and to determine the frequency at which each structure can be identified in healthy volunteers.Materials and methodsFirst, ten fresh frozen cadavers (6 men, age at death = 58–92 years) were examined by two musculoskeletal radiologists and a step-by-step technique for the identification of tendons and ligaments at the level of humeral epicondyles was developed. Second, the accurate identification of structures was confirmed through gross anatomical study including anatomical sections on five specimens and layer-by-layer dissection technique on five others. Finally, 12 healthy volunteers (6 men, average age = 36, range = 28–52) were scanned by two radiologists following the same technique.ResultsAn ultrasonographic technique based on the recognition of bony landmarks and the use of ultrasonographic signs to differentiate overlapping structures was developed and validated through gross anatomical study. In healthy volunteers, most tendons and ligaments were identified and well-defined in ≥ 80% of cases, except for the extensor carpi radialis brevis and extensor digiti minimi tendons on the lateral epicondyle (having common attachments with the extensor digitorum communis) and the palmaris longus tendon on the medial epicondyle (absent, or common attachment with the flexor carpi radialis).ConclusionA step-by-step approach to the ultrasonographic assessment of tendons and ligaments at the humeral epicondyles allowed accurate identification of and differentiation among these structures, in particular those relevant to pathological conditions.