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Sepsis is a life-threatening condition and understanding the disease pathophysiology through the use of host immune response biomarkers is critical for patient stratification. Lack of accurate sepsis endotyping impedes clinicians from making timely decisions alongside insufficiencies in appropriate sepsis management. This work aims to demonstrate the potential feasibility of a data-driven validation model for supporting clinical decisions to predict sepsis host-immune response. Herein, we used a machine learning approach to determine the predictive potential of identifying sepsis host immune response for patient stratification by combining multiple biomarker measurements from a single plasma sample. Results were obtained using the following cytokines and chemokines IL-6, IL-8, IL-10, IP-10 and TRAIL where the test dataset was 70%. Supervised machine learning algorithm naïve Bayes and decision tree algorithm showed good accuracy of 96.64% and 94.64%. These promising findings indicate the proposed AI approach could be a valuable testing resource for promoting clinical decision making.

This study proposes a PLC-controlled omni wheel conveyor sorting system designed to address limitations in traditional sorting mechanisms by integrating barcode-based classification with high-speed and adaptable sorting capabilities. The system utilizes a Siemens S7-1200 PLC, omni wheels, a barcode scanner, and a conveyor motor to achieve precise, flexible, and efficient material handling. Mathematical analysis validated the system’s structural integrity, with deflections under , and operational efficiency, including a roller speed of to support a throughput of 2000 objects per hour at a conveyor speed of . Simulations conducted in Factory IO achieved a sorting accuracy of , demonstrating the seamless synchronization of barcode scanning and sorting operations through deterministic ladder logic. The omni wheels provided multidirectional flexibility, reducing energy losses and enabling rapid redirection of objects. Compared to reinforcement learning-based approaches, the proposed system offers simplicity, cost-effectiveness, and ease of implementation without compromising accuracy or scalability. However, the simulations assumed ideal conditions, and limitations such as environmental factors, dynamic loading, and real-world scalability remain unaddressed. Future research could explore integrating IoT-enabled monitoring, hybrid control strategies, and dynamic adaptability to enhance performance in complex industrial environments. The results highlight the potential of this system to revolutionize material handling across manufacturing, logistics, and e-commerce sectors.

Staphylococcus aureus is a common pathogen causing infections in humans with various degrees of severity, with pneumonia being one of the most severe infections. In as much as staphylococcal pneumonia is a disease driven in large part by α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL), we evaluated whether active immunization with attenuated forms of Hla (HlaH35L/H48L) alone, PVL components (LukS-PVT28F/K97A/S209A and LukF-PVK102A) alone, or combination of all 3 toxoids could prevent lethal challenge in a rabbit model of necrotizing pneumonia caused by the USA300 community-associated methicillin-resistant S. aureus (MRSA). Rabbits vaccinated with Hla toxoid alone or PVL components alone were only partially protected against lethal pneumonia, whereas those vaccinated with all 3 toxoids had 100% protection against lethality. Vaccine-mediated protection correlated with induction of polyclonal antibody response that neutralized not only α-hemolysin and PVL, but also other related toxins, produced by USA300 and other epidemic MRSA clones.

Eponymous cardiovascular surgeries have played an important role in the evolution of congenital and pediatric heart disease management. These procedures, named after pioneering surgeons, have significantly advanced surgical interventions for complex cardiac conditions. This review provides an overview of eponymous cardiovascular surgeries and their impact on managing congenital and pediatric heart diseases. We examine these procedures' historical significance, technical advancements, and evolving role in contemporary surgical practice. Historically, operations such as the Blalock-Taussig-Thomas shunt and the Fontan procedure have provided life-saving solutions for patients with congenital heart defects. Over time, many eponymous procedures have been refined or replaced as surgical techniques and technologies have evolved. For example, the Jatene procedure has largely supplanted the Mustard and Senning operations to transpose the great arteries, offering superior long-term outcomes. Similarly, in conditions of functional or anatomical absence of one ventricle, iterative improvements in the Fontan and Glenn procedures have enhanced survival rates and reduced complications. The advent of catheter-based interventions, hybrid surgical techniques, and three-dimensional imaging has further transformed the field, improving surgical precision and patient outcomes. Despite modifications and replacements, the legacy of these eponymous procedures remains foundational to cardiovascular surgery. Continued innovation, collaboration, and research will build upon these historical milestones, ensuring ongoing advancements in treating congenital and pediatric heart diseases.

Venous phlebotomy performed by trained personnel is critical for patient diagnosis and monitoring of chronic disease, but has limitations in resource-constrained settings, and represents an infection control challenge during outbreaks. Self-collection devices have the potential to shift phlebotomy closer to the point of care, supporting telemedicine strategies and virtual clinical trials. Here we assess a capillary blood micro-sampling device, the Tasso Serum Separator Tube (SST), for measuring blood protein levels in healthy subjects and non-hospitalized COVID-19 patients. 57 healthy controls and 56 participants with mild/moderate COVID-19 were recruited at two U.S. military healthcare facilities. Healthy controls donated Tasso SST capillary serum, venous plasma and venous serum samples at multiple time points, while COVID-19 patients donated a single Tasso SST serum sample at enrolment. Concentrations of 17 protein inflammatory biomarkers were measured in all biospecimens by Ella multi-analyte immune-assay. Tasso SST serum protein measurements in healthy control subjects were highly reproducible, but their agreements with matched venous samples varied. Most of the selected proteins, including CRP, Ferritin, IL-6 and PCT, were well-correlated between Tasso SST and venous serum with little sample type bias, but concentrations of D-dimer, IL-1B and IL-1Ra were not. Self-collection at home with delayed sample processing was associated with significant concentrations differences for several analytes compared to supervised, in-clinic collection with rapid processing. Finally, Tasso SST serum protein concentrations were significantly elevated in in non-hospitalized COVID-19 patients compared with healthy controls. Self-collection of capillary blood with micro-sampling devices provides an attractive alternative to routine phlebotomy. However, concentrations of certain analytes may differ significantly from those in venous samples, and factors including user proficiency, temperature control and time lags between specimen collection and processing need to be considered for their effect on sample quality and reproducibility.

Our limited understanding of the pathophysiological mechanisms that operate during sepsis is an obstacle to rational treatment and clinical trial design. There is a critical lack of data from low- and middle-income countries where the sepsis burden is increased which inhibits generalized strategies for therapeutic intervention. Here we perform RNA sequencing of whole blood to investigate longitudinal host response to sepsis in a Ghanaian cohort. Data dimensional reduction reveals dynamic gene expression patterns that describe cell type-specific molecular phenotypes including a dysregulated myeloid compartment shared between sepsis and COVID-19. The gene expression signatures reported here define a landscape of host response to sepsis that supports interventions via targeting immunophenotypes to improve outcomes. Sepsis is a global challenge and a significant burden in Sub-Saharan Africa. Here, Chenoweth et al profile host gene expression signatures from a cohort in Ghana to define molecular phenotypes and identify potential targets to improve patient outcomes.

Dr. Krishna Manohar Soman Rema (SR) (1956-2022) was a pioneering congenital cardiac surgeon and an inspiring educator who dedicated his life to advancing pediatric cardiac care and mentoring the next generation of surgeons. Trained in cardiac surgery at the Sree Chitra Tirunal Institute for Medical Sciences and Technology in Kerala, he served as faculty there for 20 years, contributing significantly to the development of the Chitra Heart Valve. His career also included tenures at the Madras Medical Mission, Frontier Lifeline Hospital, and the Sri Sathya Sai Hospital in Whitefield, Bengaluru. Dr. Krishna Manohar's most enduring contribution was his role in establishing cardiac surgical services at the Sri Sathya Sai Sanjeevani International Centre for Child Heart Care and Research in Palwal, Haryana, part of a network of hospitals offering free congenital heart surgery to underprivileged children. Under his leadership, these centers performed over 22,000 open-heart and interventional procedures over a decade, achieving excellent outcomes. An exceptional mentor, Dr. Krishna Manohar introduced a transformative  framework for cardiac surgery, emphasizing adaptability, befriending collaboration, compassion, and discipline. He employed innovative teaching methods, such as the  technique, to simplify complex concepts for trainees. Recognized for his dedication, he received numerous accolades, including the Lifetime Achievement Award from the Pediatric Cardiac Society of India in 2023. Dr. Krishna Manohar's legacy lives on through his students and the institutions he helped build, inspiring future generations to continue his mission of providing high-quality, accessible care to children with congenital heart disease (CHD).

Superantigens (SAgs) play a major role in the pathogenesis of Staphylococcus aureus and are associated with several diseases, including food poisoning, bacterial arthritis, and toxic shock syndrome. Monoclonal antibodies to these SAgs, primarily TSST-1, SEB and SEA have been shown to provide protection in animal studies and to reduce clinical severity in bacteremic patients. Here we quantify the pre-existing antibodies against SAgs in many human plasma and IVIG samples and demonstrate that in a major portion of the population these antibody titers are suboptimal and IVIG therapy only incrementally elevates the anti-SAg titers. Our in vitro neutralization studies show that a combination of antibodies against SEA, SEB,and TSST-1 can provide broad neutralization of staphylococcal SAgs. We report a single fusion protein (TBA 225 ) consisting of the toxoid versions of TSST-1, SEB and SEA and demonstrate its immunogenicity and protective efficacy in a mouse model of toxic shock. Antibodies raised against this fusion vaccine provide broad neutralization of purified SAgs and culture supernatants of multiple clinically relevant S . aureus strains. Our data strongly supports the use of this fusion protein as a component of an anti-virulence based multivalent toxoid vaccine against S . aureus disease.

ObjectivesWe evaluated the performance of commonly used sepsis screening tools across prospective sepsis cohorts in the USA, Cambodia and Ghana.DesignProspective cohort studies.Setting and participantsFrom 2014 to 2021, participants with two or more SIRS (Systemic Inflammatory Response Syndrome) criteria and suspected infection were enrolled in emergency departments and medical wards at hospitals in Cambodia and Ghana and hospitalised participants with suspected infection were enrolled in the USA. Cox proportional hazards regression was performed, and Harrell’s C-statistic calculated to determine 28-day mortality prediction performance of the quick Sequential Organ Failure Assessment (qSOFA) score ≥2, SIRS score ≥3, National Early Warning Score (NEWS) ≥5, Modified Early Warning Score (MEWS) ≥5 or Universal Vital Assessment (UVA) score ≥2. Screening tools were compared with baseline risk (age and sex) with the Wald test.ResultsThe cohorts included 567 participants (42.9% women) including 187 participants from Kumasi, Ghana, 200 participants from Takeo, Cambodia and 180 participants from Durham, North Carolina in the USA. The pooled mortality was 16.4% at 28 days. The mortality prediction accuracy increased from baseline risk with the MEWS (C-statistic: 0.63, 95% CI 0.58 to 0.68; p=0.002), NEWS (C-statistic: 0.68; 95% CI 0.64 to 0.73; p<0.001), qSOFA (C-statistic: 0.70, 95% CI 0.64 to 0.75; p<0.001), UVA score (C-statistic: 0.73, 95% CI 0.69 to 0.78; p<0.001), but not with SIRS (0.60; 95% CI 0.54 to 0.65; p=0.13). Within individual cohorts, only the UVA score in Ghana performed better than baseline risk (C-statistic: 0.77; 95% CI 0.71 to 0.83; p<0.001).ConclusionsAmong the cohorts, MEWS, NEWS, qSOFA and UVA scores performed better than baseline risk, largely driven by accuracy improvements in Ghana, while SIRS scores did not improve prognostication accuracy. Prognostication scores should be validated within the target population prior to clinical use.

Background. Palivizumab is a US Food and Drug Administration—approved monoclonal antibody for the prevention of respiratory syncytial virus (RSV) lower respiratory disease in high-risk infants. Motavizumab, derived from palivizumab with enhanced antiviral activity, has recently been tested in humans. Although palivizumab escape mutants have been generated in the laboratory, the development of resistant RSV in patients receiving palivizumab has not been reported previously. Methods. We generated palivizumab and motavizumab escape mutants in vitro and examined the development of resistant mutants in RSV-breakthrough patients receiving immunoprophylaxis. The effect of these mutations on neutralization by palivizumab and motavizumab and in vitro fitness was studied. Results. Antibody-resistant RSV variants selected in vitro had mutations at position 272 of the fusion protein, from lysine to asparagine, methionine, threonine, glutamine, or glutamate. Variants containing mutations at positions 272 and 275 were detected in breakthrough patients. All these variants were resistant to palivizumab, but only the glutamate variant at position 272 demonstrated resistance to motavizumab. Mixtures of wild-type and variant RSV soon lost the resistant phenotype in the absence of selection. Conclusions. Resistant RSV variants were detected in a small subset (∼5%) of RSV breakthrough cases. The fitness of these variants was impaired, compared to wild-type RSV.