bluuebunny/crossref_metadata_2025 huggingface dataset:
541 In-Process Quality Improvement Action Following an Urban Residential Explosion
Authors: Hagg Emily , Fuchko Danielle H , Bharadia Shyla K , Gabriel Vincent
Published: April 2024

Introduction

Burn centers need specialized plans for the management of burn mass casualty incidents for best outcomes. The ABA burn disaster response plan distributed in 2023 provides a communication plan for the association and burn centers. However, individual centers must develop local response plans. In this case, a Level 1 trauma and burn center with an institutional all-hazards, non-burn specific disaster plan responded to a home explosion in a city of 1.1 million. This event prompted a quality improvement project to assess the opportunities for development of burn-specific disaster response needs within the existing plan.

Methods

The Define, Measure, Analyze, Improve, and Control (DMAIC) approach to quality improvement was utilized. Defining the problem and measuring current performance was conducted based on information derived from the electronic medical record system, Fire Department report and team debriefs of the incident response.

Results

Seven male patients with a mean TBSA of 19% were admitted to the burn centre in a 1100 bed tertiary care hospital on a Monday morning. Three required ICU level care. The burn center had zero available beds at the time of incident and surge capacity was utilized. The total number of surgical procedures performed was 17. Mean length of stay was 34 days. There were 95 outpatient encounters in the six months following the incident (Table 1). All patients received specialized burn care and were discharged back to the community independent of basic activities of daily living. Increased human resources, equipment and consumable product use by physio and occupational therapy at the time of incident and in follow up was noted to be greater than anticipated. Social work needs exceeded capacity. On hand local specialized dressing supplies were exhausted within the first 24 hours and supplemental products were acquired from other centers and commercial vendors until available stock depleted. Strategies to improve initial communication have been implemented. Burn unit expansion is under discussion with the regional health authority. Stock levels and acquisition planning for supplies is underway. Additional physio, occupational therapy and social work needs require further measurement and analysis.

Conclusions

Assessment of this center’s response to multiple simultaneous burn patient presentations offered an opportunity to optimize an existing all-hazards disaster response plan. Simulated burn disaster response is necessary to further assess the changes implemented and proposed.

Applicability of Research to Practice

After event review may improve disaster response planning.
608 Timing of Nanocrystalline Silver-based Dressing Application – a Retrospective Single-center Pediatric Cohort Study
Authors: Thibedeau Marshall , Wenskus Julia , Zuccaro Jennifer , Gus Eduardo I
Published: April 2024

Introduction

Nanocrystalline silver-based dressings (NSBD) are commonly used at different stages of the treatment of burn wounds. They have been shown to reduce the incidence of surgical procedures, time to re-epithelialization in partial thickness burn injuries, and decrease pain with dressing changes compared to silver sulfadiazine in adult and pediatric populations. Recent evidence has demonstrated anti-inflammatory properties in addition to the known antimicrobial properties. We hypothesized that the timing of nanocrystalline silver-based dressings application ( < 24h after burn injury) may impact surgical treatment rates.

Methods

This study was a retrospective single-center cohort study. All pediatric patients ( < 18 years old) treated at a single academic pediatric center for acute partial thickness burn injuries, between January 1, 2020 and December 31, 2021 were included. Bivariate analysis and multivariable logistic regression were used to compare timing of nanocrystalline silver application and surgical treatment rates.

Results

Four hundred seventy-six patients were included for analysis. One hundred four (21.85%) had NSBD and 372 (78.11%) had non-silver non-adherent dressings applied within the first 24 hours post injury. No statistically significant difference was found in surgical treatment, age, sex, mechanism, anatomic location, or total body surface area (TBSA) on bivariate analysis. The multivariable logistic regression identified three statistically significant variables as predictors for surgical treatment: age (OR = 1.14, 95% CI [1.06-1.23]), TBSA (OR = 1.15, 95% CI [1.06-1.25]), and burns to buttocks/lower extremity burns (excluding feet) (OR = 2.39, 95% CI [1.26-4.53]). Immediate ( < 24h) application of NSBD has not been demonstrated to decrease the likelihood of surgical treatment.

Conclusions

Immediate ( < 24h) application of nanocrystalline silver-based dressings does not affect surgical treatment rates. Prospective randomized studies are required to investigate the potential anti-inflammatory benefits of early nanocrystalline silver-based dressings in the treatment of pediatric burn injuries.

Applicability of Research to Practice

Use of nanocrystalline silver should be recommended as per clinical indications.
711 Neuropathic Pain in Burn Patients - A Common Problem with Little Literature: A Systematic Review
Authors: Stanton Eloise , Won Paul , Manasyan Artur , Gurram Sandeep , Shirinian Anait , Gillenwater Justin , Yenikomshian Haig A
Published: April 2024

Introduction

The prevalence of neuropathic pain (NP) in burn patients is reported in the literature to be as high as 80%1. Given the complexity of NP in burn patients and the wide range of treatments available, a systematic review of the literature is warranted to summarize our current understanding of management and treatment of NP in this population.

Methods

This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The following databases were queried to identify relevant articles: PubMed, Cochrane, Embase, Scopus, Ovid, and Web of Science. The main outcome measures were incidence and management of NP. Secondary outcomes included risk factors for NP.

Results

Included articles presented findings from 11 different countries, capturing outcomes for 4,366 patients. Risk factors for chronic pain in burn patients were identified, including older age, alcohol and substance abuse, current daily smoking, greater % total body surface area burns (TBSA), and longer hospitalizations. Pharmacologic treatments included gabapentin/pregabalin (n=7), ascorbic acid (n=1), and lidocaine (n=1). Overall, the studies showed varied results regarding the efficacy of pharmacological treatments. While certain studies demonstrated gabapentanoids to be effective in reducing neuropathic symptoms, others found conflicting results. With regards to non-pharmacologic treatments, electroconvulsive therapy (n=1), electropuncture (n=1), nerve release/reconstruction (n=2), and somatosensory feedback rehabilitation (n=1) were used and demonstrated promise in reducing pain intensity and improving functionality.

Conclusions

Despite NP afflicting the majority of burn patients long after their injury, this systematic review demonstrates that there is insufficient evidence on the pathophysiology, outcomes, and risk factors in NP, as well as the efficacy of various therapies. Future prospective and randomized studies evaluating the etiology of these factors can substantially improve our treatment strategies. This can allow for the development of well-delineated and evidence-based protocols in NP management in hopes of improving quality of life and both psychological and physical function in burn patients.

Applicability of Research to Practice

Neuropathic pain is a common cause of chronic morbidity in burn patients, often lasting for years and causing limitations in regard to quality of life and function, yet there is currently a lack of understanding in regard to optimal treatment regimens for this devastating condition. The current review summarizes our knowledge of existing treatment modalities and identifies gaps that can help guide future research.
713 Prevalence and Outcomes of Toxin Producing Staphylococcus Aureus in Paediatric Burn Wounds
Authors: Couves Adam , McGill David , Ramsay Sharon , Arkoulis Nikolaos
Published: April 2024

Introduction

Toxic Shock Syndrome is a rare but serious complication of burn injury in children. Illness is mediated by Toxic Shock Syndrome Toxin -1 (TSST-1) producing strains of staphylococcus aureus. Little is known about the prevalence of TSST-1 producing staphylococcus aureus in burn wounds and as such the role of antibiotic prophylaxis is unclear.

Methods

A prospectively maintained buns database was retrospectively reviewed for all cases of burn injury in paediatric patients of any aetiology over a three year period. Patients presented as inpatients or outpatients to the national burns centre in Scotland, UK. Patients were aged 0-16 years. Burn wounds were routinely swabbed on initial review. Specimens yielding staphylococcus aureus were sent for an overnight culture in enrichment medium followed by a commercially available latex agglutination assay to determine TSST-1 production. Electronic patient notes were reviewed to correlate clinical outcomes in these cases.

Results

1313 children attended with burn injuries with a total of 1365 swab results. No bacterial growth was present in most cultures (69%). The most common pathogen yielded was staphylococcus aureus: 293 results (21%) of which 12 (0.8%) were TSST-1 producing. All TSST-1 strains were sensitive to flucloxacillin. 3 patients (all under 2 years old) developed signs of toxic shock syndrome: 1 was already an inpatient and 2 were admitted from the community who had previously not been referred to the burns service and had not received standard treatment. No patients had severely altered physiology to warrant admission to a critical care environment or require anti-toxin therapy with fresh frozen plasma or immunoglobulin.

Conclusions

4% of staphylococcus aureus strains in our patient population were TSST-1 producing under laboratory conditions. The prevalence of TSST-1 producing staphylococcus aureus in paediatric burn wounds is 0.9%. We have demonstrated an acceptable safety profile of not giving routine antibiotic prophylaxis in paediatric burns to prevent toxic shock syndrome.

Applicability of Research to Practice

Latex agglutination assays to determine toxin production is an effective way of highlighting potentially at-risk patients to clinicians to refine the population exposed to prophylactic antibiotics.
737 Demographic Features and Length of Stay of Scald Injuries: Review from a Northeastern Burn Center
Authors: Chung Vivian , Dolinak Joan , Roberts Tamara L , Wratney Angela T
Published: April 2024

Introduction

Multitude of demographic and clinical features that affect the incidence and outcome of a burn injury have been identified. However, prognostic factors associated with the incidence and length of stay (LOS) of scald specific injuries is still unclear. The present study aims to identify and understand the factors that affect LOS in patients with scald injuries that present to a Northeastern tertiary burn center and characterize populations at risk for scald injury.

Methods

A retrospective nonexperimental descriptive study was performed from the record of all burn patients presenting to our ABA verified burn center from January 01, 2015 to December 31, 2022. Data of patients with scald injuries were isolated and organized using an Excel Spreadsheet. Scald admission variables reviewed and analyzed included: age, sex, race, suspected abuse, TBSA, Surgical visits, payor source, and LOS. SPSS version 29.0 was used to obtain descriptive statistics and perform Kruskal-Wallis 1-Way ANOVA and Mann Whitney U. Statistical significance was defined at p< 0.05

Results

A total of 2266 patients were admitted to the burn center during 2015-2022. From this, 383 patients were admitted for scald burns, which is 16.9% of all burn admissions. Scald burn patient’s demographics included male (62.1%), female (37.9%) with a mean age of 26.82. Major race was Caucasian (62.4%) and the primary payor source was Medicaid (52.7%). Approximately 12% of these cases were identified as suspected abuse. Of these abuse cases, pediatric patients composed the majority (80.4%). There was no significant difference in LOS when patients were stratified by sex (p=.366) or whether suspected abuse was involved (p=.186). However, there were differences in distribution of LOS when patients were stratified by age (p < .001), race (p=.013), surgical visits (p < .001), and primary payor (p < .001) The mean TBSA was 5.6%. There was no significant difference in the distribution of TBSA when patients were stratified by age, abuse, sex, race, or payor source. However, the association between TBSA and total surgical visits was found to be significant.

Conclusions

Longer LOS was associated with patients > 65 when compared to patients < 18 and with patients 18-64 when compared to patients 5 and under. Longer LOS was also associated with Medicare patients in comparison to Medicaid, Private/Commercial, and self pay patients. The association between Race and LOS was also found to be statistically significant when comparing Caucasians to patients in the “Other” group. This study highlighted differences in scald injuries between age, race, and primary payor method.

Applicability of Research to Practice

The risk factors for scald specific injuries differ from previous literature addressing wider burn etiologies. Identification of populations at increased risk for scald injuries can guide public health initiatives and prevention.
738 Electrical Burn Injuries in Occupational and Non-occupational Settings from 2010 to 2021: Cross-sectional Design
Authors: Ayala Karen P , Teherán Aníbal A , Pombo Luis M , Tocanchon Ginna P , Zuluaga-Ortíz Carol A , Camero-Ramos Gabriel , Ávila Albert A
Published: April 2024

Introduction

Burns affect 11 million people worldwide annually. Electrically related burns are renowned for inflicting extensive harm and long-term consequences that can lead to severe illness and fatalities. In occupational and non-occupational settings people may be exposed to electrical burns (EBs), which can lead to functional or anatomical consequences. We identified sociodemographic features related to electrical burns in occupational (EBs-occ) and non-occupational (EBs-non_occ) settings.

Methods

A cross sectional design, using an open dataset of electrical injuries occurred during 2010-2021 period. Sociodemographic features of people injured in EBs-occ and EBs-non_occ were described counts (%), Incidence*million people (I0;95%CI). To identify related factors (age-sex adjusted) with injuries in EBs-occ and EBs-non_occ, we applied a Binary Logistic Regression (aOR).

Results

Over the course of 11 years occurred 1.274 EBs (I0: 2.47;2.34-2.61), 287 EBs-occ (I0: 1.35;1.20-1.51) and 987 EBs-non_occ (I0: 3.25;3.05-3.46). Age median was 31 years, most cases distributed in middle adulthood (52.8%), male (88.1%), and people with high school/technician (42.8%), urban location (73.7%), weekdays (95.3%), and during daytime hours (85.5%). Factors related to EBs-occ were male sex, middle adulthood, high school/technician, and occurred mainly on thursday and daytime hours. Otherwise, EBs-non_occ factors were early childhood, primary school, urban location, and occurred mostly on weekends.

Conclusions

Both occupational and non-occupational settings pose a risk of injuries to individuals in the workplace. We have identified sociodemographic factors related to these injuries in both occupational and non-occupational settings, which could help to avoid damages and long-term complications, especially among vulnerable individuals such as those at an extreme age.

Applicability of Research to Practice

This information could be helpful in refining existing preventive measures, particularly for non-occupational electrical burns.
770 Rehabilitation Evaluation and Treatment for the Management of Skin Graft Complication of the Genitalia
Authors: Tremblay Chloe , Jean Stephanie , Schneider Genevieve , Nedelec Bernadette , Edger-Lacoursière Zoë
Published: April 2024

Introduction

Skin graft complications can include pain, contractures, hypertrophic scars, sensitivity issues, recurrent wounds and infections. Genitalia, perineum and/or buttocks graft complications have a direct impact on walking, sitting, voiding, bowel elimination, sexual function, intimacy, thereby reducing quality of life. Perineal and pelvic rehabilitation is used for many pelvic floor disorders, however, has not been described after burn injury or necrotizing fasciitis. Thus, this case report describes, a new rehabilitation evaluation template following perineal grafting and treatment outcomes reported after necrotizing fasciitis.

Methods

Assessments included Patient and Observer Scar Assessment Scale (POSAS), penile deviation measure, sensitivity using monofilaments, Burn Survivor Fear Avoidance Questionnaire (BSFAQ), sexual function and satisfaction. Evaluation and treatment were conducted by a certified pelvic floor physiotherapist (PT) and occupational therapist (OT). The initial evaluation occurred 4 months post surgery with interventions occurring every 3-4 weeks thereafter.

Results

The patient is a 37-year-old male who had skin grafts and reconstructive surgery complications following necrotizing fasciitis of the perineum and the genitalia with 30% TBSA. He presented with complex wounds which closed in 4 months, contractures, hypertrophic scars, hypersensitivity, fecal incontinence, and sexual intimacy dysfunction. Treatment included pelvic floor approach, education, desensitization, vesical and bowel movement rehabilitation, adapted pressure garment, gel application, scar massage, cutaneous and myofascial stretching and manual therapy. There was an improvement in BSFAQ score (5 points), pelvic floor muscle tension, PT observed scar, resolution of fecal incontinence, reduced penile deviation in the frontal plane, decreased hypersensitivity and ability to engage in pain-free sexual intercourse after 2 months of treatment. The patient is still progressively accepting his new body image but feels more confident with sexual intimacy. The results for POSAS and sensitivity are still ongoing.

Conclusions

The patient has improved scars as well as reduced penile deviation, and sensitivity allowing masturbation and sexual intercourse without pain, which helped him regain intimacy with his partner.

Applicability of Research to Practice

This is the first report of a standardized evaluation and treatment approach for the rehabilitation of skin graft complications after necrotizing fasciitis involving the perineum, genitalia and/or buttocks. Rehabilitation interventions improved his sexual function, body image satisfaction, and quality of life.
773 Managing Facial Contractures Through Intraoral Stretching
Authors: Kerr Kathleen , Arguello Lori
Published: April 2024

Introduction

Surgical management of scar tissue and contractures from facial burns has systematic approaches, yet nonsurgical management continues to lack consensus regarding therapeutic approaches capable of providing stretching of the facial skin and muscles for both treating and preventing microstomia and orofacial contractures. This exploratory study introduces an intraoral splinting system designed to provide low-load, prolonged stretching of orofacial skin and musculature to treat contractures following a facial burn injury. The treatment adjunct described here has potential application across disciplines treating microstomia and orofacial contractures.

Methods

An 18-year-old male with full thickness head and neck burns participated in a 5-week trial using intraoral splints to provide stretch to areas of contracture in the mid and lower face. The trial commenced 4 ½ months after his burn injury. Prescriptive placement, sizing and time for use of the splints were provided. Changes in distance between facial landmarks were identified for 13 measurements taken for 9 facial expressions. Change between landmarks was measured in millimeters of distance between landmarks.

Results

Lengthening (+measurements) or shortening (-measurements) of the distances between two landmarks indicated the potential benefit from stretching the oral cavity with intraoral splints. For the expression “open mouth wide”, increased distance between two endpoints was noted in 11 of 13 measurements, ranging from 1.6 mm to 10.8 mm. This represents a lengthening of tissue, allowing for wider oral opening. Negative measurements between two endpoints occurred in 2 of 13 measurements, demonstrating elevation of the left and right nostrils. Visual data also demonstrated the appearance of change over the 5-week trial. Pre- and post-treatment photographs are shown in Figure 1. Week 1 is shown above and week 5 is shown below. Facial expressions left to right are: open mouth wide, wrinkle nose, at rest. Figure 2 includes data from the expression "open wide".

Conclusions

When treating microstomia and orofacial contractures, consideration should be given to the use and further exploration of a more targeted intraoral methodology which uses a low load and prolonged stretch to improve functional and aesthetic deficits. Oral splinting using an intraoral methodology is underutilized in the burn patient population and has application in both the acute care and chronic phases of recovery.

Applicability of Research to Practice

This research methods described here are appropriate to incorporate into clinical practice patterns in both acute and post-acute rehabilitation of the patient with an orofacial burn or orofacial contractures. The methodology highlighted within this research is relevant to and has potential use for all members of the burn care team.
Potential zoonotic role of the tick Amblyomma cf. oblongoguttatum (Ixodida: Ixodidae) in the bacterial transmission of Ehrlichia chaffeensis (Rickettsiales: Anaplasmataceae) in a deciduous tropical forest in Mexico
Authors: Guzmán-Cornejo Carmen , Herrera-Mares Angel , García-Prieto Luis , Oceguera-Figueroa Alejandro , López-Pérez Andrés M , Dzul-Rosado Karla
Published: April 2024

Ehrlichia chaffeensis is a bacterium belonging to the Anaplasmataceae family. In Mexico, only 2 species have been recorded in association with tick species and humans. The objective of the present study was to detect the presence of bacteria of the genus Ehrlichia in ticks collected from the Chamela-Cuixmala Biosphere Reserve, Jalisco, Mexico. The collected ticks were identified and analyzed individually by polymerase chain reaction to amplify a fragment of the Anaplasmataceae 16S rRNA gene and the Ehrlichia-specific dsb gene. A total of 204 ticks, corresponding to 5 species of Ixodidae and 1 of Argasidae, were collected from 147 mammals of 6 species and 4 orders; 57 ticks collected from vegetation were also included. Among the total ticks collected, 1.47% (3/204) was positive for Ehrlichia sp. DNA was obtained using the primers EHR 16SD and EHR 16SR for 16S rRNA and DSB-330 and DSB-728 for dsb. The positive samples corresponded to a larva (Amblyomma sp.) associated with Didelphis virginiana and 2 nymphs (Amblyomma cf. oblongoguttatum) infesting Nasua narica. None of the ticks collected from the vegetation tested positive for Ehrlichia sp. DNA on the basis of the 16S rRNA and dsb genes. The sequences from the larvae of Amblyomma sp. and the nymphs of A. cf. oblongoguttatum were similar to those of E. chaffeensis. The phylogenetic analysis inferred with maximum likelihood corroborated the identity as E. chaffeensis. Although the role of these tick species as vectors of E. chaffeensis is still undetermined, the presence of infected ticks in the area indicates a potential zoonotic risk.
The ‘no greater rights’ principle: heading to a new Calvo Clause?
Authors: Alvarez Contreras Juan Miguel
Published: April 2024

Recently, the very developed countries that championed the spread of international investment agreements began to challenge these treaties on the grounds that they afford foreign investors with greater rights vis-à-vis domestic investors and thus violate the constitutional principle of equality. This represented, under the banner of the ‘no greater rights’ principle, the resurgence of a once fiercely opposed doctrine of international law that originated in Latin America during the XIX century: The Calvo Doctrine. This contribution seeks to establish the actual breadth and significance of this new Calvo Doctrine. It concludes that the ‘no greater rights’ has a political, rather than a legal meaning, and is thus generally unsuitable to assure the desired equality between foreign and domestic investors. It also reveals that a recent decision of the Colombian Constitutional Court may give the ‘no greater rights’ a new (more real) meaning, by reviving a forgotten by-product of the Calvo Doctrine, the Calvo Clause.
Temporal variations in international air travel: implications for modelling the spread of infectious diseases
Authors: Wardle Jack , Bhatia Sangeeta , Cori Anne , Nouvellet Pierre
Published: April 2024

Background

The international flight network creates multiple routes by which pathogens can quickly spread across the globe. In the early stages of infectious disease outbreaks, analyses using flight passenger data to identify countries at risk of importing the pathogen are common and can help inform disease control efforts. A challenge faced in this modelling is that the latest aviation statistics (referred to as contemporary data) are typically not immediately available. Therefore, flight patterns from a previous year are often used (referred to as historical data). We explored the suitability of historical data for predicting the spatial spread of emerging epidemics.

Methods

We analysed monthly flight passenger data from the International Air Transport Association to assess how baseline air travel patterns were affected by outbreaks of Middle East respiratory syndrome (MERS), Zika and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) over the past decade. We then used a stochastic discrete time susceptible-exposed-infected-recovered (SEIR) metapopulation model to simulate the global spread of different pathogens, comparing how epidemic dynamics differed in simulations based on historical and contemporary data.

Results

We observed local, short-term disruptions to air travel from South Korea and Brazil for the MERS and Zika outbreaks we studied, whereas global and longer-term flight disruptions occurred during the SARS-CoV-2 pandemic. For outbreak events that were accompanied by local, small and short-term changes in air travel, epidemic models using historical flight data gave similar projections of the timing and locations of disease spread as when using contemporary flight data. However, historical data were less reliable to model the spread of an atypical outbreak such as SARS-CoV-2, in which there were durable and extensive levels of global travel disruption.

Conclusion

The use of historical flight data as a proxy in epidemic models is an acceptable practice, except in rare, large epidemics that lead to substantial disruptions to international travel.
A practical guide to the discovery of biomolecules with biostimulant activity
Authors: Li Jing , Lardon Robin , Mangelinckx Sven , Geelen Danny
Published: April 2024

The growing demand for sustainable solutions in agriculture, which are critical for crop productivity and food quality in the face of climate change and the need to reduce agrochemical usage, has brought biostimulants into the spotlight as valuable tools for regenerative agriculture. With their diverse biological activities, biostimulants can contribute to crop growth, nutrient use efficiency, and abiotic stress resilience, as well as to the restoration of soil health. Biomolecules include humic substances, protein lysates, phenolics, and carbohydrates have undergone thorough investigation because of their demonstrated biostimulant activities. Here, we review the process of the discovery and development of extract-based biostimulants, and propose a practical step-by-step pipeline that starts with initial identification of biomolecules, followed by extraction and isolation, determination of bioactivity, identification of active compound(s), elucidation of mechanisms, formulation, and assessment of effectiveness. The different steps generate a roadmap that aims to expedite the transfer of interdisciplinary knowledge from laboratory-scale studies to pilot-scale production in practical scenarios that are aligned with the prevailing regulatory frameworks.
Inequality of opportunity and life satisfaction
Authors: Becchetti Leonardo , Colcerasa Francesco , Peragine Vitorocco , Pisani Fabio
Published: April 2024

This article attempts to shed light on the contrasting findings about the effect of inequality on subjective wellbeing by decomposing income inequality into inequality of opportunity (due to factors that individuals cannot control) and inequality of effort. The two inequality components, calculated using EU-SILC data at regional and wave level, are matched with individual data on life satisfaction and its controls from the European Social Survey. We find that inequality of opportunity affects negatively and significantly subjective wellbeing, while inequality due to effort does not play a negative role. The negative effect of inequality of opportunity is stronger for women, the young, and the less educated. Our findings support the hypothesis that individuals are generally hit by that component of inequality (inequality of opportunity) that they perceive as unfair and beyond their control.
Taurine Inhibits Lung Metastasis in Triple-Negative Breast Cancer by Modulating Macrophage Polarization Through PTEN-PI3K/Akt/mTOR Pathway
Authors: Lin Yufeng , Huang Yongtong , Zheng Yifan , Chen Wanting , Zhang Yongcheng , Yang Yongxia , Huang Wenbin
Published: April 2024

Taurine (Tau) has been found to inhibit triple-negative breast cancer (TNBC) invasion and metastasis. However, its effect on tumor-promoting macrophages and tumor suppressor macrophages in breast cancer progression remains unknown. In this study, we investigated the effects of Tau on macrophage polarization and its role in TNBC cell growth, invasion, and metastasis. We induced human THP-1 monocytes to differentiate into M2 macrophages through exogenous addition of interleukin-4. We used the TNBC cell lines MDA-MB-231 and BT-549 cultured in a conditioned medium from M2 macrophages to investigate the effect of Tau on tumor growth and invasion. We analyzed macrophage subset distribution, M1 and M2 macrophage-associated markers, and mRNA expression by quantitative polymerase chain reaction. We also detected the PTEN-PI3K/Akt/mTOR signaling pathway that mediates M1 macrophage to suppress tumor invasion using western blotting. Our results showed that Tau inhibits breast cancer metastasis to the lungs in vivo and cell invasion by altering the polarization of tumor-associated macrophage in vitro. In addition, Tau can up-regulate PTEN expression, suppress the PI3K-Akt signaling pathway, and promote the M1 polarization of macrophages, which ultimately inhibits the metastasis of TNBC cells. Our findings suggest that Tau inhibits the activation of the PI3K-Akt-mTOR signaling pathway by up-regulating PTEN, promotes the proportion of M1 macrophages in tumor-associated macrophage, and suppresses the invasion and metastasis of TNBC. This provides a potential therapeutic approach to influence cancer progression and metastasis.
Development of Recombinant Proteins for Vaccine Candidates Against Serotype O and A of Foot and Mouth Disease Virus in Bangladesh
Authors: Akter Salma , Rahman M. Shaminur , Islam M. Rafiul , Akther Masuda , Anjume Humaira , Marjia Mafruha , Rahaman Md Mizanur , Hossain M Anwar , Sultana Munawar
Published: April 2024

Frequent vaccine failure leading to recurrent outbreaks of Foot-and-Mouth Disease (FMD) in livestock populations necessitates the development of a customizable vaccine platform comprising potential antigenic determinants of circulating lineages of FMD viruses. Artificially designed, chimeric peptide-based recombinant vaccines are novel approaches to combat the phylogenetically diverse FMD Virus (FMDV) strains. Among seven recognized serotypes, only serotypes O and A are dominantly circulating in Bangladesh and neighboring countries of Asia, where transboundary transmission, recurrent outbreaks and emergence of novel lineages of FMDV are highly prevalent. The objective of this study was to develop multi-epitope recombinant peptides, procuring immunogenicity against circulating diverse genotypes of FMDV serotypes O and A. Two chimeric peptides, named B1 (41.0 kDa) and B3 (39.3 kDa), have been designed to incorporate potential B-cell and T-cell epitopes selected from multiple FMDV strains, including previously reported and newly emerged sub-lineages. After expression, characterization and immunization of guineapigs with considerable antigen load of B1 and B3 followed by the serological assays revealed the significant protective immunogenicity, developed from the higher (100 µg) doses of both antigens, against most of the currently prevalent serotype O and A strains of FMDV. The efficient expression, antigenic stability, and multivalent immunogenic potency of the chimeric peptides strongly indicate their credibility as novel vaccine candidates for existing serotypes O and A of FMDV in Bangladesh and surrounding territories.
Klebsiella pneumoniae sequence type 147: a high-risk clone increasingly associated with plasmids carrying both resistance and virulence elements
Authors: Turton Jane F. , Perry Claire , McGowan Kim , Turton Jack A. , Hope Russell
Published: April 2024

Introduction. The first hybrid resistance/virulence plasmid, combining elements from virulence plasmids described in hypervirulent types of Klebsiella pneumoniae with those from conjugative resistance plasmids, was described in an isolate of sequence type (ST) 147 from 2016. Subsequently, this type has been increasingly associated with these plasmids.

Hypothesis or gap statement. The extent of carriage of hybrid virulence/resistance plasmids in nosocomial isolates of K. pneumoniae requires further investigation.

Aim. To describe the occurrence of virulence/resistance plasmids among isolates of K. pneumoniae received by the UK reference laboratory, particularly among representatives of ST147, and to compare their sequences.

Methodology. Isolates received by the laboratory during 2022 and the first half of 2023 (n=1278) were screened for virulence plasmids by PCR detection of rmpA/rmpA2 and typed by variable-number tandem repeat analysis. Twenty-nine representatives of ST147 (including a single-locus variant) from seven hospital laboratories were subjected to long-read nanopore sequencing using high-accuracy q20 chemistry to provide complete assemblies.

Results.
rmpA/rmpA2 were detected in 110 isolates, of which 59 belonged to hypervirulent K1-ST23, K2-ST86 and K2-ST65/375. Of the remainder, representatives of ST147 formed the largest group, with 22 rmpA/rmpA2-positive representatives (out of 47 isolates). Representatives were from 19 hospital laboratories, with rmpA/rmpA2-positive isolates from 10. Nanopore sequencing of 29 representatives of ST147 divided them into those with no virulence plasmid (n=12), those with non-New Delhi metallo-β-lactamase (NDM) virulence plasmids (n=6) and those carrying bla
NDM-5 (n=9) or bla
NDM-1 (n=2) virulence plasmids. These plasmids were of IncFIB(pNDM-Mar)/IncHI1B(pNDM-MAR) replicon types. Most of the non-NDM virulence plasmids were highly similar to the originally described KpvST147L_NDM plasmid. Those carrying bla
NDM-5 were highly similar to one another and to previously described plasmids in ST383 and carried an extensive array of resistance genes. Comparison of the fully assembled chromosomes indicated multiple introductions of ST147 in UK hospitals.

Conclusion. This study highlights the high proportion of representatives of ST147 that carry IncFIB(pNDM-Mar)/IncHI1B(pNDM-MAR) hybrid resistance virulence plasmids. It is important to be aware of the high probability that representatives of this type carry these plasmids combining resistance and virulence determinants and of the consequent increased risk to patients.
Development and Validation of the VIOSync Sepsis Prediction Index: A Novel Machine Learning Model for Sepsis Prediction in ICU Patients
Authors: Liliopoulos Sotirios G. , Dejaco Alexander , Dimakopoulos Vasileios S. , Gkouzionis Ioannis A.
Published: April 2024

Background

Sepsis is the third leading cause of death worldwide and the main cause of in-hospital mortality. Despite decades of research, sepsis remains a major challenge faced by patients, clinicians, and medical systems worldwide. Early identification and prediction of patients at risk of sepsis and adverse outcomes associated with sepsis are critical. In this work, we aimed to develop an artificial intelligence algorithm that can predict sepsis early.

Materials and Methods

We developed a predictive model for sepsis using data from the Physionet Cardiology Challenge 2019 ICU database. Our cohort consisted of adult patients who were admitted to the ICU. Sepsis diagnoses were determined using the Sepsis-3 criteria. The model, built with the XGBoost algorithm, was designed to anticipate sepsis prior to the appearance of clinical symptoms. An internal validation was conducted using a hold-off test dataset to evaluate the AI model’s predictive performance.

Results

We have developed the VIOSync Sepsis Prediction Index (SPI), an AI-based predictive model designed to forecast sepsis up to six hours before its clinical onset, as defined by Sepsis-3 criteria. The AI model, trained on a dataset comprising approximately 40,000 adult patients, integrates variables such as vital signs, laboratory data, and demographic information. The model demonstrated a high prediction accuracy rate of 97%, with a sensitivity of 87% and a specificity of 98% in predicting sepsis up to 6 hours before the onset. When compared to the established qSOFA score, which has a specificity of 89% for sepsis prediction, our VIOSync SPI algorithm significantly enhances predictive reliability, potentially reducing false positive rates by a factor of 5.5.

Conclusions

The VIOSync SPI demonstrated superior prediction performance over current sepsis early warning scores and predictive algorithms for sepsis onset. To validate the generalizability of our method across populations and treatment protocols, external validation studies are essential.
Reduction of Cystatin B results in increased cathepsin B activity in disomic but not Trisomy21 human cellular and mouse models
Authors: Wu Yixing , Cleverley Karen , Wiseman Frances K.
Published: April 2024

Down syndrome, resulting from trisomy of human chromosome 21, is a common form of chromosomal disorder that results in intellectual disability and altered risk of several medical conditions. Individuals with Down syndrome have a greatly increased risk of Alzheimer’s disease (DSAD), due to the presence of theAPPgene on chromosome 21 that encodes the amyloid-β precursor protein (APP). APP can be processed to generate amyloid-β, which accumulates in plaques in the brains of people who have Alzheimer’s disease and is the upstream trigger of disease. Cathepsin B has potential roles in both APP processing and amyloid-β degradation and has been suggested to contribute to amyloid-β accumulation. An endogenous inhibitor of Cathepsin B, Cystatin B (CSTB), is encoded on chromosome 21. The abundance of this protein is increased in the brains of individuals with DSAD, which may be associated with a decrease in Cathepsin B activity compared to individuals who have Alzheimer’s disease in the general population. Whether targetingCSTBcan modulate Cathepsin B activity in the context of trisomy of chromosome 21 is unclear. Here we test if reducing CSTB can alter Cathepsin B activity in a mouse and a cellular model of trisomy of chromosome 21. We find that reducing CSTB abundance increases Cathepsin B activity in disomic controls but not in the presence of trisomy of chromosome 21. These findings offer new insights into the role of CSTB in regulating Cathepsin B activity.
Seed sequences mediate off-target activity in the CRISPR-interference (CRISPRi) system
Authors: Rohatgi Neha , Fortin JP , Lau Ted , Ying Yi , Zhang Yue , Costa Mike , Reja Rohit
Published: April 2024

The CRISPR interference (CRISPRi) system is a powerful tool that is widely used to selectively and efficiently silence genes in functional genomics research applications. However, the extent of off-target activity associated with the CRISPRi system has not been systematically investigated. Here, we utilized a genome-wide CRISPRi Cas9 single guide RNA (sgRNA) library to investigate the presence of off-target activity and its effects on gene expression. Our findings suggest that off-target effects in CRISPRi are quite pervasive and have direct and indirect impact on gene expression. Most of the identified off-target activities can be accounted for by complementarity of the PAM-proximal genomic sequence with the 3’ half of the sgRNA spacer sequence, the seed sequence. We also report that not all PAM proximal positions are equally important for binding of sgRNA to the DNA and that mismatches in the PAM-proximal regions can be tolerated depending on the sequence context.
Antiviral RNA interference targets viral transcripts but not genomes of RNA viruses inDrosophila melanogaster
Authors: Silva Emanuele G. , Ferreira Álvaro G. A. , Jiran Thiago Henrique L. , de Faria Isaque João S. , Armache Juliana N. , Amadou Siad C. G. , Haas Gabrielle , Martin Franck , Luc-Imler Jean , Marques João T.
Published: April 2024

RNA interference (RNAi) mediated by the small interfering RNA (siRNA) pathway is a major antiviral mechanism in insects. This pathway is triggered when double-stranded RNA (dsRNA) produced during virus replication is recognized by Dicer-2, leading to the formation of virus-derived siRNA duplexes. These siRNAs are loaded onto the programmable nuclease Argonaute-2 (AGO2), with one strand serving as a guide to target and cleave fully complementary sequences of viral RNAs. While siRNAs are generated from viral dsRNA, the specific viral RNA species targeted for silencing during RNA virus replication remains unclear. In this study, we characterized the primary viral RNA targets of theDrosophilasiRNA pathway during infections caused by negative and positive RNA viruses, namely Vesicular stomatitis virus (VSV) and Sindbis virus (SINV). Our findings reveal that polyadenylated transcripts of VSV and SINV are the major targets of silencing by the siRNA pathway during infection, likely when they are poised for translation. Consistent with earlier findings, we confirmed that AGO2 copurifies with ribosomes, and this is not affected by virus infection. Therefore, we propose that the inhibition of the replication of RNA viruses inDrosophilaresults from the silencing of incoming viral transcripts, facilitated by the association of AGO2 with ribosomes.

Author Summary

The small interfering RNA (siRNA) pathway mediates major antiviral immune response in insects, functioning to cleave viral RNA. While this pathway has been extensively studied in the fruit flyDrosophila melanogaster, the specific molecular targets of inhibition by the siRNA pathway have remained unclear. In this study, we aimed to elucidate these targets. Our findings demonstrate that polyadenylated transcripts produced during viral infection are the primary targets of the Drosophila siRNA pathway, in the case of both negative and positive single-stranded RNA viruses. The silencing of these transcripts accounts for the antiviral effect of the siRNA pathway, suggesting that direct targeting of viral RNA genomes is unlikely to occur. We confirmed that Argonaute-2 (AGO2), the core component of the silencing complex, co-purifies with ribosomes and also show that this association is not affected by viral infection. This suggests that AGO2 is in permanent association with ribosomes where it can efficiently scan viral transcripts before they undergo translation by the cellular machinery, thereby preventing viral replication. These results provide valuable insights into the mechanism of gene silencing the siRNA pathway.
The landscape of regional missense mutational intolerance quantified from 125,748 exomes
Authors: Chao Katherine R. , Wang Lily , Panchal Ruchit , Liao Calwing , Abderrazzaq Haneen , Ye Robert , Schultz Patrick , Compitello John , Grant Riley H. , Kosmicki Jack A. , Weisburd Ben , Phu William , Wilson Michael W. , Laricchia Kristen M. , Goodrich Julia K. , Goldstein Daniel , Goldstein Jacqueline I. , Vittal Christopher , Poterba Timothy , Baxter Samantha , Watts Nicholas A. , Solomonson Matthew ,   gnomAD Consortium, Tiao Grace , Rehm Heidi L. , Neale Benjamin M. , Talkowski Michael E. , MacArthur Daniel G. , O’Donnell-Luria Anne , Karczewski Konrad J. , Radivojac Predrag , Daly Mark J. , Samocha Kaitlin E.
Published: April 2024

Missense variants can have a range of functional impacts depending on factors such as the specific amino acid substitution and location within the gene. To interpret their deleteriousness, studies have sought to identify regions within genes that are specifically intolerant of missense variation1–12. Here, we leverage the patterns of rare missense variation in 125,748 individuals in the Genome Aggregation Database (gnomAD)13against a null mutational model to identify transcripts that display regional differences in missense constraint. Missense-depleted regions are enriched for ClinVar14pathogenic variants,de novomissense variants from individuals with neurodevelopmental disorders (NDDs)15,16, and complex trait heritability. Following ClinGen calibration recommendations for the ACMG/AMP guidelines, we establish that regions with less than 20% of their expected missense variation achieve moderate support for pathogenicity. We create a missense deleteriousness metric (MPC) that incorporates regional constraint and outperforms other deleteriousness scores at stratifying case and controlde novomissense variation, with a strong enrichment in NDDs. These results provide additional tools to aid in missense variant interpretation.
Comparative genomics and transcriptomics reveal differences in effector complement and expression between races ofFusarium oxysporumf.sp.lactucae
Authors: Bates Helen J. , Pike Jamie , Price R. Jordan , Jenkins Sascha , Connell John , Legg Andrew , Armitage Andrew , Harrison Richard J. , Clarkson John P.
Published: April 2024

This study presents the first genome and transcriptome analyses forFusarium oxysporumf.sp.lactucae(Fola) which causes Fusarium wilt disease of lettuce. Long-read genome sequencing of three race 1 (Fola1) and three race 4 (Fola4) isolates revealed key differences in putative effector complement between races and with otherF. oxysporumf.spp. followingmimp-based bioinformatic analyses. Notably, homologues ofSecreted in Xylem(SIX) genes, also present in many otherF. oxysporumf.spp, were identified in Fola, with bothSIX9andSIX14(multiple copies with sequence variants) present in both Fola1 and Fola4. All Fola4 isolates also contained an additional single copy ofSIX8. RNAseq of lettuce following infection with Fola1 and Fola4 isolates identified highly expressed effectors, some of which were homologues of those reported in otherF. oxysporumf.spp. including several inF. oxysporumf.sp.apii. AlthoughSIX8,SIX9andSIX14were all highly expressed in Fola4, of the twoSIXgenes present in Fola1, onlySIX9was expressed as further analysis revealed that copies ofSIX14gene copies were disrupted by insertion of a transposable element. Two variants of Fola4 were also identified based on different genome and effector-based analyses. This included two differentSIX8sequence variants which were divergently transcribed from a shared promoter with eitherPSE1orPSL1respectively. In addition there was evidence of two independent instances of HCT in the different Fola4 variants. The involvement of helitrons in Fola genome rearrangement and gene expression is discussed.