Comparative Analysis of Machine-Learning Model Performance in Image Analysis: The Impact of Dataset Diversity and Size.

BACKGROUND: This study presents an analysis of machine-learning model performance in image analysis, with a specific focus on videolaryngoscopy procedures. The research aimed to explore how dataset diversity and size affect the performance of machine-learning models, an issue vital to the advancement of clinical artificial intelligence tools. METHODS: A total of 377 videolaryngoscopy videos from YouTube were used to create 6 varied datasets, each differing in patient diversity and image count. The study also incorporates data augmentation techniques to enhance these datasets further. Two machine-learning models, YOLOv5-Small and YOLOv8-Small, were trained and evaluated on metrics such as F1 score (a statistical measure that combines the precision and recall of the model into a single metric, reflecting its overall accuracy), precision, recall, mAP@50, and mAP@50-95. RESULTS: The findings indicate a significant impact of dataset configuration on model performance, especially the balance between diversity and quantity. The Multi-25 × 10 dataset, featuring 25 images from 10 different patients, demonstrates superior performance, highlighting the value of a well-balanced dataset. The study also finds that the effects of data augmentation vary across different types of datasets. CONCLUSIONS: Overall, this study emphasizes the critical role of dataset structure in the performance of machine-learning models in medical image analysis. It underscores the necessity of striking an optimal balance between dataset size and diversity, thereby illuminating the complexities inherent in data-driven machine-learning development.

Precision Genetic Therapies: Balancing Risk and Benefit in Patients with Heart Failure.

PURPOSE OF REVIEW: Precision genetic medicine is evolving at a rapid pace and bears significant implications for clinical cardiology. Herein, we discuss the latest advancements and emerging strategies in gene therapy for cardiomyopathy and heart failure. RECENT FINDINGS: Elucidating the genetic architecture of heart failure has paved the way for precision therapies in cardiovascular medicine. Recent preclinical studies and early-phase clinical trials have demonstrated encouraging results that support the development of gene therapies for heart failure arising from a variety of etiologies. In addition to the discovery of new therapeutic targets, innovative delivery platforms are being leveraged to improve the safety and efficacy of cardiac gene therapies. Precision genetic therapy represents a potentially safe and effective approach for improving outcomes in patients with heart failure. It holds promise for radically transforming the treatment paradigm for heart failure by directly targeting the underlying etiology. As this new generation of cardiovascular medicines progress to the clinic, it is especially important to carefully evaluate the benefits and risks for patients.

Genome sequences of human anelloviruses in the Lamedtorquevirus, Memtorquevirus, and Samektorquevirus genera identified from the female genital tract.

We identified and characterized seven anellovirus genome sequences in the female genital tract through virome metagenomic sequencing of cervicovaginal lavage specimens from women living with HIV in Peru. Phylogenetic and genomic analyses indicate that they belong to three newly proposed Lamedtorquevirus, Memtorquevirus, and Samektorquevirus genera in the Anelloviridae family.

Obstructive sleep apnea: Overlooked comorbidity in patients with diabetes.

In this review article, we explore the interplay between obstructive sleep apnea (OSA) and type 2 diabetes mellitus (T2DM), highlighting a significant yet often overlooked comorbidity. We delve into the pathophysiological links between OSA and diabetes, specifically how OSA exacerbates insulin resistance and disrupts glucose metabolism. The research examines the prevalence of OSA in diabetic patients and its role in worsening diabetes-related complications. Emphasizing the importance of comprehensive management, including weight control and positive airway pressure therapy, the study advocates integrated approaches to improve outcomes for patients with T2DM and OSA. This review underscores the necessity of recognizing and addressing OSA in diabetes care to ensure more effective treatment and better patient outcomes.

The Seraph 100® Microbind Affinity Blood Filter Does Not Alter Levels of Circulating or Mucosal Antibodies in Critical COVID-19 Patients.

PURIFY-OBS-1 is an observational study evaluating the safety and efficacy of Seraph 100® Microbind Affinity Blood Filter (Seraph 100) use for COVID-19 patients with respiratory failure admitted to the intensive care unit (ICU). The Seraph 100 is a hemoperfusion device containing heparin-coated beads that can bind to, and reduce levels of, some circulating pathogens and inflammatory molecules. This study evaluated whether treatment with the Seraph 100 affected circulating and mucosal antibody levels in critically ill COVID-19 subjects. SARS-CoV-2 anti-spike and anti-nucleocapsid IgG and IgA levels in serum were evaluated at enrollment and on days 1, 4, 7, and 28 after Seraph 100 application, while anti-spike and nucleocapsid IgG, IgA, and secretory IgA levels in tracheal aspirates were evaluated at enrollment and on days 1, 2, 3, 7, and 28. Serum samples were also collected from the pre- and post-filter lines at 1 and 4 h following Seraph 100 application to evaluate the direct impact of the filter on circulating antibody levels. Treatment with the Seraph 100 did not alter the levels of circulating or mucosal antibodies in critically ill COVID-19 subjects admitted to the ICU.

Pulse Oximetry Accuracy in Children with Dark Skin Tones: Relevance to Acute Lower Respiratory Infection Care in Low- and Middle-Income Countries.

Acute lower respiratory infections (ALRI) are the leading post-neonatal cause of death in children under 5 years old. There is a high prevalence of pediatric ALRI-related hypoxemia in low- and middle-income countries. The WHO defines clinically meaningful hypoxemia in children as a SpO2 (peripheral oxygen saturation) <90%. Multiple studies put this convention into question and found SpO2 of 90% to 92% to be associated with child ALRI mortality. An evolving body of evidence suggests that pulse oximeters systematically overestimate oxygen saturation in individuals with dark skin tones. We conducted a narrative review of pediatric studies evaluating pulse oximeter accuracy in children without COVID-19. Four studies, one prospective, examined pulse oximeter accuracy in children of varying ages with dark skin tones. All studies had limitations that affect their generalizability. There is evidence that certain pulse oximeters may overestimate oxygen saturation in children with dark skin tones. Further prospective research is urgently needed to identify affected populations and clinical implications. Despite recognized challenges, we strongly urge continued and expanded use of pulse oximetry as its use will save lives.

Neurosarcoidosis With Panhypopituitarism: Two Cases and Literature Review.

Neurosarcoidosis (NS) with hypothalamic-pituitary (HP) involvement (HP-NS) is a rare clinical condition, conferring variable hormonal deficits that are typically irreversible. Here, we present 2 cases of NS with panhypopituitarism. The first patient presented with cauda equina syndrome and arginine vasopressin deficiency, while the second developed recurrent optic neuritis and vision loss in the setting of a sellar mass. In the first case, neurological symptoms resolved after therapy with high-dose glucocorticoids, infliximab, and methotrexate; while in the second, visual restoration followed resection of the granulomatous tissue and immunosuppressive therapy. In both cases, pituitary dysfunction persisted despite neurological improvement. We contextualized the presentations and outcomes through a literature review of HP-NS case reports and case series. This revealed high rates of extraneurologic sarcoidosis in HP-NS patients with panhypopituitarism, while underscoring the need for hormonal replacement-as endocrinopathies rarely respond to sarcoidosis-directed immunosuppression.

Model based analysis of trace metal dosing strategies to improve methane yield in anaerobic digestion systems.

Favourable effects of trace metals (TMs) on regulating anaerobic digestion (AD) performance are extensively utilised to improve methane yield. This study discusses a model-based approach to find out the best TM dosing strategies. The model has been applied to compare continuous, preloading, pulse dosing and in-situ loading. Simulations were also carried out to comprehend appropriate dosing form, dosing time and quantity of metals to be dosed. Model results show that the best way to dose TMs is repeated pulse dosing at low concentration levels in the optimum range with high frequency. Best dosing strategy for the system in this study was found to be 5 µM pulse loading at 5 days intervals as it gave maximum methane production and low effluent metal loss. Preferable dosing form depends on reactor configuration and this has been verified after model calibration with experimental data. Easily dissociable metal chlorides are ideal for continuous reactors.

Expression of CD6 in Aggressive NK/T-cell Neoplasms and Assessment as a Potential Therapeutic Target: A Bone Marrow Pathology Group Study.

BACKGROUND: Aggressive NK/T-Cell neoplasms are rare hematological malignancies characterized by the abnormal proliferation of NK or NK-like T (NK/T) cells. CD6 is a transmembrane signal transducing receptor involved in lymphocyte activation and differentiation. This study aimed to investigate the CD6 expression in these malignancies and explore the potential of targeting CD6 in these diseases. MATERIALS AND METHODS: We conducted a retrospective study with totally 41 cases to investigate the expression of CD6 by immunohistochemistry, including aggressive NK-cell leukemia/lymphoma (ANKLL: N = 10) and extranodal NK/T-cell lymphoma (ENKTL: N = 31). A novel ANKLL model was applied for proof-of-concept functional studies of a CD6 antibody-drug-conjugate (CD6-ADC) both in vitro and in animal trial. RESULTS: CD6 was expressed in 68.3% (28/41) of cases (70% (7/10) of ANKLL and 67.7% (21/31) of ENKTL). The median overall survival (OS) for ANKLL and ENTKL cases was 1 and 12 months, respectively, with no significant difference in OS based on CD6 expression (p > 0.05, Kaplan-Meier with log-rank test). In vitro exposure of the CCANKL cell line, derived from an ANKL patient, to an anti-CD6ADC resulted in dose dependent induction of apoptosis. Furthermore, CCANKL engraftment in NSG mice could be blocked by treatment with the anti-CD6 ADC. CONCLUSION: To date, this is the first report to explore the expression of CD6 in ANKLL and ENKTL and confirms its expression in the majority of cases. The in vitro and in vivo data support further investigation of CD6 as a potential therapeutic target in these aggressive NK/T-cell malignancies.

Parent-reported outcome measures evaluating communication in individuals with rare neurodevelopmental disorders: A systematic review.

BACKGROUND: Communication impairments are a leading concern for parent caregivers of individuals with rare neurodevelopmental disorders (RNDDs). Clinical trials of disease modifying therapies require valid and responsive outcome measures that are relevant to individuals with RNDDs. Identifying and evaluating current psychometric properties for communication measures is a critical step towards the selection and use of appropriate instruments. AIMS: This systematic review offers (1) a description of parent-reported communication measures and (2) evidence for their psychometric properties, in RNDDs. METHODS: The systematic review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022334649). MEDLINE (Ovid), Embase, PsychINFO, Web of Science, CINAHL Plus, Cochrane Library, ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry were searched from inception to August 2023. Methodological assessment of quality was completed using the COnsensus-based Standards for the selection of health status Measurement INstruments (COSMIN) checklist. Parent-reported measures used in observational studies and clinical trials were identified. Data on utility, reliability and validity for RNDDs were extracted. MAIN CONTRIBUTION: Sixteen parent-reported communication measures were used in RNDD research, the Vineland Adaptive Behavior Scales being most commonly used. Validation data in RNDDs were identified for six of these measures. Limitations related to sample size or the scope of psychometric testing. CONCLUSIONS: Many communication measures have been used for RNDDs but there are few data validating their use. Valid and reliable methods of measuring communication in persons with RNDDs is a priority for future high-quality clinical trials. WHAT THIS PAPER ADDS: What is already known on the subject Communication is a critical domain for families with a child with a rare neurodevelopmental disorder (RNDD). Validated outcome measures are essential for accurate evaluation and interpretation of responses to treatments in clinical trials. What this paper adds to existing knowledge We identified 16 parent-reported communication measures that have been used with RNDDs, but only six measures had validation data for at least one RNDD. High quality evidence is accumulating, with all validation studies in this review published between 2020 to 2023. Modifications of existing measures may be required to assess communication for RNDDs. What are the clinical implications of this work? This systematic review catalogues the available psychometric data for communication measures and indicates an ongoing need for new validation studies to ensure they are fit-for-purpose for upcoming clinical trials in RNDDs. This review will inform the selection of communication measures for clinical trials and research studies.

Light-Controlled Electric Stimulation with Organic Electrolytic Photocapacitors Achieves Complex Neuronal Network Activation: Semi-Chronic Study in Cortical Cell Culture and Rat Model.

Neurostimulation employing photoactive organic semiconductors offers an appealing alternative to conventional techniques, enabling targeted action and wireless control through light. In this study, organic electrolytic photocapacitors (OEPC) are employed to investigate the effects of light-controlled electric stimulation on neuronal networks in vitro and in vivo. The interactions between the devices and biological systems are characterized. Stimulation of primary rat cortical neurons results in an elevated expression of c-Fos within a mature neuronal network. OEPC implantation for three weeks and subsequent stimulation of the somatosensory cortex leads to an increase of c-Fos in neurons at the stimulation site and in connected brain regions (entorhinal cortex, hippocampus), both in the ipsi- and contralateral hemispheres. Reactivity of glial and immune cells after semi-chronic implantation of OEPC in the rat brain is comparable to that of surgical controls, indicating minimal foreign body response. Device functionality is further substantiated through retained charging dynamics following explantation. OEPC-based, light-controlled electric stimulation has a significant impact on neural responsiveness. The absence of detrimental effects on both the brain and device encourages further use of OEPC as cortical implants. These findings highlight its potential as a novel mode of neurostimulation and instigate further exploration into applications in fundamental neuroscience.

Does format matter? A naturalistic study of digital and provider-led cognitive behavioral therapy for insomnia implemented in a healthcare system.

OBJECTIVES: Cognitive Behavioral Therapy for Insomnia (CBTi) is a first-line treatment for a prevalent and impairing disorder. Digital CBTi programs increase access to internet-based self-directed care. However, the clinical effect of offering different forms of CBTi in a healthcare setting is not clearly understood. This study examines treatment engagement and clinical outcomes for individuals referred to either digital or provider-led CBTi. METHODS: Over two years, providers at a Veterans Health Administration (VHA) facility referred patients to digital CBTi with telephone coaching support or traditional provider-led CBTi. Characteristics of those referred, proportions engaging in and completing treatment, as well as insomnia severity were compared among those referred to each format. RESULTS: Providers referred 139 individuals to digital CBTi, 340 to provider-led CBTi, and 14 to both formats. Individuals referred to digital CBTi were older with less severe insomnia. Despite lower levels of program engagement and completion in the digital CBTi cohort, measures of insomnia symptom change were similar between the groups. CONCLUSIONS: This is the first study to evaluate both digital and provider-led evidence-based treatments for insomnia disorder simultaneously deployed in a healthcare setting. While engagement in digital CBTi lagged that for provider-led CBTi, offering both formats may expand access to different groups, while fostering similar outcomes.

The global distribution and climate resilience of marine heterotrophic prokaryotes.

Heterotrophic Bacteria and Archaea (prokaryotes) are a major component of marine food webs and global biogeochemical cycles. Yet, there is limited understanding about how prokaryotes vary across global environmental gradients, and how their global abundance and metabolic activity (production and respiration) may be affected by climate change. Using global datasets of prokaryotic abundance, cell carbon and metabolic activity we reveal that mean prokaryotic biomass varies by just under 3-fold across the global surface ocean, while total prokaryotic metabolic activity increases by more than one order of magnitude from polar to tropical coastal and upwelling regions. Under climate change, global prokaryotic biomass in surface waters is projected to decline ~1.5% per °C of warming, while prokaryotic respiration will increase ~3.5% ( ~ 0.85 Pg C yr-1). The rate of prokaryotic biomass decline is one-third that of zooplankton and fish, while the rate of increase in prokaryotic respiration is double. This suggests that future, warmer oceans could be increasingly dominated by prokaryotes, diverting a growing proportion of primary production into microbial food webs and away from higher trophic levels as well as reducing the capacity of the deep ocean to sequester carbon, all else being equal.

Analysis of the intensity of engagement with CuidaTEXT, a text message intervention for dementia caregiver support among Latinos/as.

OBJECTIVES: To examine the associations between participant intensity of engagement with a text message intervention, CuidaTEXT, and socio-demographic factors, acceptability measures, and clinical outcomes among Latino/a caregivers of individuals with dementia. METHODS: CuidaTEXT is a six-month, bilingual, and bidirectional intervention. We enrolled 24 Latino/a caregivers in a one-arm feasibility trial. Participants received approximately one automatic daily text message and could engage with the intervention by texting specific keywords (e.g. STRESS to receive messages about stress-coping), and by chat-texting with a live coach. We used metrics and psychometric scales to quantify variables. RESULTS: Participants sent a total of 1847 messages to CuidaTEXT. Higher intensity of engagement was associated with higher intervention satisfaction (r = 0.6, p = 0.007), as were several other acceptability outcomes. We found no associations between intensity of engagement with CuidaTEXT and sociodemographic or clinical outcomes (p > 0.05). CONCLUSION: Encouraging more intense engagement with CuidaTEXT might lead to higher levels of satisfaction with the intervention. However, it is possible that those who are highly satisfied, engage more intensely with CuidaTEXT. Future research should determine the directionality of these associations to optimize text message interventions. CLINICAL IMPLICATIONS: Creating more opportunities to increase the intensity of text message engagement with caregiver support interventions may improve caregiver satisfaction with them.

PuCl3{CoCp[OP(OEt)2]3}: transuranic elements entering the field of heterometallic molecular chemistry.

Recent advances enabled the discovery of heterometallic molecules for many metals: main group, d-block, lanthanides, and some actinides (U, Th). These complexes have at least two different metals joined by bridging ligands or by direct metal-metal bonding interactions. They are attractive because they can enable chemical cooperativity between metals from different parts of the periodic table. Some heterometallics provide access to unique reactivity and others exhibit physical properties that cannot be accessed by homometallic species. We envisioned that transuranic heterometallics might similarly enable new transuranic chemistry, though synthetic routes to such compounds have yet to be developed. Reported here is the first synthesis of a molecular transuranic complex that contains plutonium (Pu) and cobalt (Co). Our analyses of PuCl3{CoCp[OP(OEt)2]3} showed Pu(iv) and Co(iii) were present and suggested that the Pu(iv) oxidation state was stabilized by the electron donating phosphite ligands. This synthetic method - and the demonstration that Pu(iv) can be stabilized in a heterobimetallic molecular setting - provides a foundation for further exploration of transuranic multimetallic chemistry.

Mediators of monocyte chemotaxis and matrix remodeling are associated with mortality and pulmonary fibroproliferation in patients with severe COVID-19.

Acute respiratory distress syndrome (ARDS) has a fibroproliferative phase that may be followed by pulmonary fibrosis. Pulmonary fibrosis following COVID-19 pneumonia has been described at autopsy and following lung transplantation. We hypothesized that protein mediators of tissue remodeling and monocyte chemotaxis are elevated in the plasma and endotracheal aspirates of critically ill patients with COVID-19 who subsequently develop features of pulmonary fibroproliferation. We enrolled COVID-19 patients admitted to the ICU with hypoxemic respiratory failure. (n = 195). Plasma was collected within 24h of ICU admission and at 7d. In mechanically ventilated patients, endotracheal aspirates (ETA) were collected. Protein concentrations were measured by immunoassay. We tested for associations between protein concentrations and respiratory outcomes using logistic regression adjusting for age, sex, treatment with steroids, and APACHE III score. In a subset of patients who had CT scans during hospitalization (n = 75), we tested for associations between protein concentrations and radiographic features of fibroproliferation. Among the entire cohort, plasma IL-6, TNF-α, CCL2, and Amphiregulin levels were significantly associated with in-hospital mortality. In addition, higher plasma concentrations of CCL2, IL-6, TNF-α, Amphiregulin, and CXCL12 were associated with fewer ventilator-free days. We identified 20/75 patients (26%) with features of fibroproliferation. Within 24h of ICU admission, no measured plasma proteins were associated with a fibroproliferative response. However, when measured 96h-128h after admission, Amphiregulin was elevated in those that developed fibroproliferation. ETAs were not correlated with plasma measurements and did not show any association with mortality, ventilator-free days (VFDs), or fibroproliferative response. This cohort study identifies proteins of tissue remodeling and monocyte recruitment are associated with in-hospital mortality, fewer VFDs, and radiographic fibroproliferative response. Measuring changes in these proteins over time may allow for early identification of patients with severe COVID-19 at risk for fibroproliferation.

Preoperative Hypoalbuminemia Predicts 30-day Complications in Head and Neck Microvascular Surgery.

INTRODUCTION: Hypoalbuminemia, a marker for poor nutritional status, has been associated with postoperative complications, including head and neck cancer surgery. This study investigates the impact of hypoalbuminemia on head and neck microvascular free tissue transfer reconstruction. METHODS: This retrospective cohort study queried the 2005-2021 American College of Surgeons National Surgical Quality Improvement Program databases. Reconstructive cases performed by otolaryngologists (CPT: 15756, 15757, 15758, 15842, 20955, 20956, 20957, 20962, 20969, 20970, 20972, 20973, 43116, 43496, 49006, and 49906) with available preoperative albumin, BMI, and age were included. Hypoalbuminemia was defined as a preoperative albumin <3.5 g/dL. Univariate and multivariable logistic regression were performed. RESULTS: A total of 3,886 cases met the inclusion criteria, of which 835 (21.5%) had hypoalbuminemia. The hypoalbuminemia cohort was older, had lower BMI, had higher ASA classification, and had worse functional health status. Adjusted multivariable logistic regression showed that hypoalbuminemia was associated with unplanned return to the operating room within 30 days (OR: 1.36, p < 0.01), unplanned reoperation (OR: 1.36, p < 0.01), any complication (OR: 1.77, p < 0.01), surgical complications (OR: 1.94, p < 0.01), and medical complications (OR: 1.34, p = 0.01). Hypoalbuminemia was correlated with a longer hospital stay, superficial surgical site infection, wound dehiscence, transfusion, deep vein thrombosis, and acute renal failure. CONCLUSION: Hypoalbuminemia is a risk factor for postoperative complications after microvascular free tissue transfer for head and neck reconstruction. This study suggests that preoperative optimization of hypoalbuminemia may be beneficial for these patients. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

Optimizing Cost-Effective Care for Chronic Constipation in General Gastroenterology Using an Office-Based, Point-Of-Care Test (RED): Cost-Effectiveness and Cost-Minimization Analysis.

INTRODUCTION: We aimed to evaluate the cost-effectiveness/cost-savings of point-of-care anorectal function testing with an investigational device (RED) to triage therapy for chronic constipation in general gastroenterology. METHODS: A Markov model was constructed to evaluate cost-effectiveness/cost-savings over a 1-year time horizon comparing empiric drug/pelvic floor physical therapy to testing guided care. RESULTS: RED appears to inform the cost-effective strategy for chronic constipation. Compared with usual care without RED, it reduces insurer costs by $810 and patient costs by $6,903. DISCUSSION: Point-of-care testing using RED appears cost-effective/cost-saving to triage chronic constipation care in general gastroenterology.

Positive Trends in Racial Disparities for Head and Neck Microvascular Reconstructive Surgery.

OBJECTIVE: To evaluate national trends in racial disparities for patients undergoing head and neck reconstructive surgery. METHODS: Retrospective analysis using the 2008 to 2021 American College of Surgeons National Surgical Quality Improvement Program database. Patients receiving microvascular free tissue transfer were eligible for inclusion. Pediatric patients and those treated by non-otolaryngologists were excluded. Outcomes were analyzed with univariate and multivariable models. RESULTS: A total of 5831 head and neck free flap cases were analyzed, 4869 (83.5%) were White, 560 (9.6%) were Black or African American, and 402 (6.9%) were Asian, Native American, or other groups (ANAOG). The proportion of Black or African American patients and ANAOG patients undergoing free tissue transfer increased significantly over the time period (p = 0.047 and p = 0.010, respectively). However, there was a downtrend that started around 2017. In a multivariable model, Black or African American race was not associated with readmission (OR = 0.99 [95% CI 0.74, 1.31], p > 0.05), returning to the operating room (OR = 1.20 [95% CI 0.96, 1.49], p > 0.05), or any post-operative complication (OR = 0.83 [95% CI 0.68, 1.01], p > 0.05). There were also no significant associations found in the ANAOG population on multivariate analysis (p > 0.05 for all). CONCLUSION: The percentage of free tissue transfer performed in patients from minority backgrounds with head and neck cancer has been increasing in the United States. Outcomes after head and neck microvascular reconstruction are similar when stratified by race. However, racial disparities remain and further work is necessary to reduce these disparities. LEVEL OF EVIDENCE: Level IV Laryngoscope, 2024.