Race-specific FRAX models are evidence-based and support equitable care: a response to the ASBMR Task Force report on Clinical Algorithms for Fracture Risk.

Task Force on 'Clinical Algorithms for Fracture Risk' commissioned by the American Society for Bone and Mineral Research (ASBMR) Professional Practice Committee has recommended that FRAX® models in the US do not include adjustment for race and ethnicity. This position paper finds that an agnostic model would unfairly discriminate against the Black, Asian and Hispanic communities and recommends the retention of ethnic and race-specific FRAX models for the US, preferably with updated data on fracture and death hazards. In contrast, the use of intervention thresholds based on a fixed bone mineral density unfairly discriminates against the Black, Asian and Hispanic communities in the US. This position of the Working Group on Epidemiology and Quality of Life of the International Osteoporosis Foundation (IOF) is endorsed both by the IOF and the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases (ESCEO).

ViViEchoformer: Deep Video Regressor Predicting Ejection Fraction.

Heart disease is the leading cause of death worldwide, and cardiac function as measured by ejection fraction (EF) is an important determinant of outcomes, making accurate measurement a critical parameter in PT evaluation. Echocardiograms are commonly used for measuring EF, but human interpretation has limitations in terms of intra- and inter-observer (or reader) variance. Deep learning (DL) has driven a resurgence in machine learning, leading to advancements in medical applications. We introduce the ViViEchoformer DL approach, which uses a video vision transformer to directly regress the left ventricular function (LVEF) from echocardiogram videos. The study used a dataset of 10,030 apical-4-chamber echocardiography videos from patients at Stanford University Hospital. The model accurately captures spatial information and preserves inter-frame relationships by extracting spatiotemporal tokens from video input, allowing for accurate, fully automatic EF predictions that aid human assessment and analysis. The ViViEchoformer's prediction of ejection fraction has a mean absolute error of 6.14%, a root mean squared error of 8.4%, a mean squared log error of 0.04, and an R 2 of 0.55. ViViEchoformer predicted heart failure with reduced ejection fraction (HFrEF) with an area under the curve of 0.83 and a classification accuracy of 87 using a standard threshold of less than 50% ejection fraction. Our video-based method provides precise left ventricular function quantification, offering a reliable alternative to human evaluation and establishing a fundamental basis for echocardiogram interpretation.

A cluster-randomized trial of client and provider directed financial interventions to align incentives with appropriate case management in private medicine retailers: Results of the TESTsmART trial in Lagos, Nigeria.

Malaria remains a major health priority in Nigeria. Among children with fever who seek care, less than a quarter gets tested for malaria, leading to inappropriate use of the recommended treatment for malaria; Artemisinin-based Combination Therapy (ACT). Here we test an innovative strategy to target ACT subsidies to clients seeking care in Nigeria's private retail health sector who have a confirmed malaria diagnosis. We supported point-of-care malaria testing (mRDTs) in 48 Private Medicine Retailers (PMRs) in the city of Lagos, Nigeria and randomized them to two study arms; a control arm offering subsidized mRDT testing for USD $0.66, and an intervention arm where, in addition to access to subsidized testing as in the control arm, clients who received a positive mRDT at the PMR were eligible for a free (fully subsidized) first-line ACT and PMRs received USD $0.2 for every mRDT performed. Our primary outcome was the proportion of ACTs dispensed to individuals with a positive diagnostic test. Secondary outcomes included proportion of clients who were tested at the PMR and adherence to diagnostic test results. Overall, 23% of clients chose to test at the PMR. Test results seemed to inform treatment decisions and resulted in enhanced targeting of ACTs to confirmed malaria cases with only 26% of test-negative clients purchasing an ACT compared to 58% of untested clients. However, the intervention did not offer further improvements, compared to the control arm, in testing rates or dispensing of ACTs to test-positive clients. We found that ACT subsidies were not passed on to clients testing positive in the intervention arm. We conclude that mRDTs could reduce ACT overconsumption in Nigeria's private retail health sector, but PMR-oriented incentive structures are difficult to implement and may need to be complemented with interventions targeting clients of PMRs to increase test uptake and adherence. Trials registration: Clinical Trials Registration Number: NCT04428307. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816435/ Correction: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9476591/.

Measuring the Direct Medical Costs of Hospital-Onset Infections Using an Analogy Costing Framework.

BACKGROUND: The majority of recent estimates on the direct medical cost attributable to hospital-onset infections (HOIs) has focused on device- or procedure-associated HOIs. The attributable costs of HOIs that are not associated with device use or procedures have not been extensively studied. OBJECTIVE: We developed simulation models of attributable cost for 16 HOIs and estimated the total direct medical cost, including nondevice-related HOIs in the USA for 2011 and 2015. DATA AND METHODS: We used total discharge costs associated with HOI-related hospitalization from the National Inpatient Sample and applied an analogy costing methodology to develop simulation models of the costs attributable to HOIs. The mean attributable cost estimate from the simulation analysis was then multiplied by previously published estimates of the number of HOIs for 2011 and 2015 to generate national estimates of direct medical costs. RESULTS: After adjusting all estimates to 2017 US dollars, attributable cost estimates for select nondevice-related infections attributable cost estimates ranged from $7661 for ear, eye, nose, throat, and mouth (EENTM) infections to $27,709 for cardiovascular system infections in 2011; and from $8394 for EENTM to $26,445 for central nervous system infections in 2016 (based on 2015 incidence data). The national direct medical costs for all HOIs were $14.6 billion in 2011 and $12.1 billion in 2016. Nondevice- and nonprocedure-associated HOIs comprise approximately 26-28% of total HOI costs. CONCLUSION: Results suggest that nondevice- and nonprocedure-related HOIs result in considerable costs to the healthcare system.

Mitochondrial Dysfunction and Fatigue in Sjögren's Disease.

Objectives: Sjögren's disease (SjD) is a common exocrine disorder typified by chronic inflammation and dryness, but also profound fatigue, suggesting a pathological basis in cellular bioenergetics. In healthy states, damaged or dysfunctional mitochondrial components are broken down and recycled by mitophagy, a specialized form of autophagy. In many autoimmune disorders, however, evidence suggests that dysfunctional mitophagy allows poorly functioning mitochondria to persist and contribute to a cellular milieu with elevated reactive oxygen species. We hypothesized that mitophagic processes are dysregulated in SjD and that dysfunctional mitochondria contribute to overall fatigue. We sought to link fatigue with mitochondrial dysfunction directly in SjD, heretofore unexamined, and further sought to assess the pathogenic extent and implications of dysregulated mitophagy in SjD. Methods: We isolated pan T cells via negative selection from the peripheral blood mononuclear cells of 17 SjD and 8 age-matched healthy subjects, all of whom completed fatigue questionnaires prior to phlebotomy. Isolated T cells were analyzed for mitochondrial oxygen consumption rate (OCR) and glycolysis using Seahorse, and linear correlations with fatigue measures were assessed. A mitophagy transcriptional signature in SjD was identified by reanalysis of whole-blood microarray data from 190 SjD and 32 healthy subjects. Differential expression analyses were performed by case/control and subgroup analyses comparing SjD patients by mitophagy transcriptional cluster against healthy subjects followed by bioinformatic interpretation using gene set enrichment analysis. Results: Basal OCR, ATP-linked respiration, maximal respiration, and reserve capacity were significantly lower in SjD compared to healthy subjects with no observed differences in non-mitochondrial respiration, basal glycolysis, or glycolytic stress. SjD lymphocytic mitochondria show structural alterations compared to healthy subjects. Fatigue scores related to pain/discomfort in SjD correlated with the altered OCR. Results from subgroup analyses by mitophagic SjD clusters revealed highly variable inter-cluster differentially expressed genes (DEGs) and expanded the number of SjD-associated gene targets by tenfold within the same dataset. Conclusion: Mitochondrial dysfunction, associated with fatigue, is a significant problem in SjD and warrants further investigation.

Evolution of Virtual Surgical Planning Use Among Craniofacial Surgeons.

Virtual surgical planning (VSP) has benefits in craniofacial surgery with growing popularity. However, while specific use cases are highlighted in the literature, no studies exist providing an overview of VSP use among craniofacial surgeons, and little is known about the extent of exposure to VSP during plastic surgery training. This study surveyed members of The American Society of Maxillofacial Surgeons (ASMS) to better characterize both the landscape of VSP use among practicing craniofacial surgeons and the extent of exposure to VSP throughout surgical training. An electronic survey was administered in the fall of 2023. Response data included surgeon demographics, VSP usage, including the use in residency/fellowship, procedures for which VSP is used, and assessment of VSP's impact on the surgeon's practice. Demographics and VSP use were analyzed using descriptive statistics, while categorical and continuous variables were analyzed using χ2 tests and t-tests, respectively. Of the 44 respondents, 40 (90.9%) completed a craniofacial surgery fellowship, and 18 (40.9%) utilized VSP in either residency or fellowship. In respondents' current practice, VSP is utilized most commonly for orthognathic surgery (n=32, 91.4%), postablative reconstruction (n=23, 82.1%), and facial feminization (n=11, 73.3%). Shorter operative time and improved esthetic outcomes were frequently reported as benefits derived from VSP use. Finally, surgeons in practice for less than 10 years were significantly more likely to have used VSP in both residency (OR=20.3, P<0.01) and in fellowship (OR=40.6, P<0.01) than those practicing for more than 10 years. These findings suggest that craniofacial surgeons apply VSP more commonly for certain procedure types. Our results additionally suggest that incorporation of VSP into residency and fellowship training has become significantly more common over time, with a pivot towards integration in the last decade.

The Peer Review Process: Past, Present, and Future.

The peer review process is a fundamental aspect of modern scientific paper publishing, underpinning essential quality control. First conceptualised in the 1700s, it is an iterative process that aims to elevate scientific literature to the highest standards whilst preventing publication of scientifically unsound, potentially misleading, and even plagiarised information. It is widely accepted that the peer review of scientific papers is an irreplaceable and fundamental aspect of the research process. However, the rapid growth of research and technology has led to a huge increase in the number of publications. This has led to increased pressure on the peer review system. There are several established peer review methodologies, ranging from single and double blind to open and transparent review, but their implementation across journals and research fields varies greatly. Some journals are testing entirely novel approaches (such as collaborative reviews), whilst others are piloting changes to established methods. Given the unprecedented growth in publication numbers, and the ensuing burden on journals, editors, and reviewers, it is imperative to improve the quality and efficiency of the peer review process. Herein we evaluate the peer review process, from its historical origins to current practice and future directions.

Patient-reported outcomes in HSCT for autoimmune diseases: Considerations on behalf of the EBMT ADWP, PAC, and Nurses Group.

Background: Over the last 3 decades, hematopoietic stem cell transplantation (HSCT) has been successfully used to treat severe and refractory autoimmune diseases (AIDs). A multidisciplinary appraisal of potential benefits and risks by disease and transplant specialists is essential to determine individual suitability for HSCT. Objective: Our aim was to observe that patient-reported outcomes (PROs) and health-related quality of life instruments can capture the unique patient perspective on disease burden and impact of treatment. Methods: Herein, we describe the basis and complexity of end points measuring patient-reported perceptions of efficacy and tolerability used in clinical practice and trials for patients with AIDs undergoing autologous HSCT. Results: PRO measures and patient-reported experience measures are key tools to evaluate the impact and extent of disease burden for patients affected by AIDs. For formal scientific assessment, it is essential that validated general instruments are used, whereas adaptations have resulted in disease-specific instruments that may help guide tailored interventions. An additional approach relates to qualitative evaluations, from carefully structured qualitative research to informal narratives, as patient stories. The patients' subjectively reported responses to HSCT may be influenced by their preprocedure expectations and investment in the HSCT journey. Conclusions: The complexity of AIDs advocates for individualized and multidisciplinary approach to positively affect the patient journey. PROs and health-related quality of life need to be collected using validated instruments in clinical practice and trials to enable robustness of data and to ensure the impact of the intervention is comprehensively assessed, addressing the main questions and needs of the involved stakeholders.

Impacts of ocean warming on fish size reductions on the world's hottest coral reefs.

The impact of ocean warming on fish and fisheries is vigorously debated. Leading theories project limited adaptive capacity of tropical fishes and 14-39% size reductions by 2050 due to mass-scaling limitations of oxygen supply in larger individuals. Using the world's hottest coral reefs in the Persian/Arabian Gulf as a natural laboratory for ocean warming - where species have survived >35.0 °C summer temperatures for over 6000 years and are 14-40% smaller at maximum size compared to cooler locations - we identified two adaptive pathways that enhance survival at elevated temperatures across 10 metabolic and swimming performance metrics. Comparing Lutjanus ehrenbergii and Scolopsis ghanam from reefs both inside and outside the Persian/Arabian Gulf across temperatures of 27.0 °C, 31.5 °C and 35.5 °C, we reveal that these species show a lower-than-expected rise in basal metabolic demands and a right-shifted thermal window, which aids in maintaining oxygen supply and aerobic performance to 35.5 °C. Importantly, our findings challenge traditional oxygen-limitation theories, suggesting a mismatch in energy acquisition and demand as the primary driver of size reductions. Our data support a modified resource-acquisition theory to explain how ocean warming leads to species-specific size reductions and why smaller individuals are evolutionarily favored under elevated temperatures.

Lipid Trolling to Optimize A3 Adenosine Receptor-Positive Allosteric Modulators (PAMs).

A3 adenosine receptor (A3AR) positive allosteric modulators (PAMs) (2,4-disubstituted-1H-imidazo[4,5-c]quinolin-4-amines) allosterically increase the Emax of A3AR agonists, but not potency, due to concurrent orthosteric antagonism. Following mutagenesis/homology modeling of the proposed lipid-exposed allosteric binding site on the cytosolic side, we functionalized the scaffold, including heteroatom substitutions and exocyclic phenylamine extensions, to increase allosteric binding. Strategically appended linear alkyl-alkynyl chains with terminal amino/guanidino groups improved allosteric effects at both human and mouse A3ARs. The chain length, functionality, and attachment position were varied to modulate A3AR PAM activity. For example, 26 (MRS8247, p-alkyne-linked 8 methylenes) and homologues increased agonist Cl-IB-MECA's Emax and potency ([35S]GTPγS binding). The putative mechanism involves a flexible, terminally cationic chain penetrating the lipid environment for stable electrostatic anchoring to cytosolic phospholipid head groups, suggesting "lipid trolling", supported by molecular dynamic simulation of the active-state model. Thus, we have improved A3AR PAM activity through rational design based on an extrahelical, lipidic binding site.

Controlled Study of Metabolic Syndrome Among Offspring of Parents With Bipolar Disorder.

Objectives: Bipolar disorder (BD) is highly heritable and associated with increased rates of metabolic syndrome (MetS). However, little is known about MetS in offspring of parents with BD. We therefore examined this topic in the Pittsburgh Bipolar Offspring Study cohort.Methods: Participants included 199 parents (n = 116 BD, diagnosed using DSM-IV; n = 83 non-BD) and 330 offspring (mean age 19.9 ± 5.3 years), including 198 high-risk offspring of parents with BD (n = 80 affected with a mood disorder) and 132 control offspring. We defined MetS and its components using International Diabetes Federation (IDF) guidelines (primary) and National Cholesterol Education Program (NCEP) guidelines (secondary). Multivariable analyses controlled for age and socioeconomic status in offspring. Sensitivity analyses controlled for psychotropic medications.Results: There was higher prevalence of MetS in parents with BD as compared to controls. NCEP-defined MetS was significantly more prevalent among affected high-risk offspring (16.3%) and controls (15.2%) vs unaffected high-risk offspring (6.0%; χ2 = 6.54, P = .04). There was greater mean number of MetS components (IDF: 1.7 ± 1.1; NCEP: 1.4 ± 1.0) among affected high-risk offspring vs unaffected high-risk offspring (IDF: 1.2 ± 1.0; NCEP: 1.0 ± 1.0) and controls (IDF: 1.3 ± 1.2; NCEP: 1.1 ± 1.1; IDF: H[2] = 10.26, P = .006; NCEP: H[2] = 9.18, P = .01). Most findings became nonsignificant in multivariable analyses. Some between-group results became nonsignificant after controlling for second-generation antipsychotics.Conclusions: This preliminary study found increased risk of MetS among affected high-risk offspring, which may be attributable to socioeconomic status. Prospective studies may determine timing of MetS onset in relation to mood disorder onset, and the role of socioeconomic status in moderating this association.

Repurposing surgical wards in pandemics - An appraisal of outcomes of COVID-19 patients treated in Orthopaedic wards.

Background: The COVID-19 pandemic resulted in a shift in the way healthcare resources were used. While India faced limited effects in the first COVID wave primarily due to strict lockdown of the county, it was one of the worst affected in the second wave and at one time reported the highest number of daily cases. To address the lack of intensive care units (ICU) beds, the surgical wards of our institute were repurposed to take care of patients requiring supplementary oxygen and other supportive care till either they improved or an ICU bed was available. The medical personnel in charge of the surgical wards were entrusted with the care of patients with support from intensive care support teams (ICST). Aims: We aimed to examine the clinical details of patients admitted in the repurposed orthopaedic wards during the second COVID wave and to evaluate the factors that might affect the clinical outcomes in such patients. Methods: This was a retrospective review of records of patients admitted in the repurposed orthopaedic wards between 16 April 2021 and 20 May 2021. Details related to demography, COVID-19 presentation, COVID-19-related management and clinical course, including transfers to ICUs, and outcomes in terms of either discharge to home or death were recorded. They were analysed using statistical software. Results: One hundred and twenty three patients were treated during the said period. Twenty patients died during treatment, resulting in a mortality rate of 16.3%. Age, gender, RT-PCR status, pre-existing comorbidities, SpO2 at admission, method of supplemental oxygen supply, total leukocyte counts, haemoglobin values, serum C-reactive protein, Lactate dehydrogenase (LDH) and creatinine values had no statistically significant association with death of a patient during treatment. Conclusion: Based on the results, one can state that clinicians of surgical specialities having background knowledge of internal medicine from undergraduate education can manage patients of COVID-19 with support from ICST with reasonable outcomes. In case of future pandemics, surgical wards can be repurposed to tide over exigencies. Additionally, primary care physicians, who are often the first point of contact for patients, can allay their apprehensions adequately in future pandemics, thus preventing widespread panic and burdening of healthcare resources.

Creation and Validation of a Novel 3-Dimensional Pediatric Hip Ultrasound Model.

OBJECTIVES: The aim of this study was to create and validate a 3-dimensional (3D) ultrasound model with normal and abnormal pediatric hip joint anatomy that is comparable to a pediatric hip joint in appearance and anatomy and replicates sonographic characteristics of a pediatric hip joint. METHODS: A 3D rendering of the bone and soft tissue was created from a computed tomography pelvic scan of a pediatric patient. This rendering was modified to include a unilateral joint effusion. The bone was 3D printed with a photopolymer plastic, whereas the soft tissue was cast with a silicone mixture in a 3D-printed mold. The effusion was simulated by injecting saline into the soft tissue cavity surrounding the bone. The ultrasound model was validated by pediatric point-of-care ultrasonographers at an international pediatric ultrasound conference. RESULTS: A pediatric hip ultrasound model was developed that simulates both normal and abnormal pediatric hip joint anatomy, each with an appropriately sized, measurable joint effusion. Validation by pediatric point-of-care ultrasonographers showed that the key aspects of a normal pediatric hip joint (femoral physis, sloped femoral neck, and adequate soft tissue) with an identifiable and measurable effusion were included in the ultrasound model. CONCLUSIONS: In this study, we successfully created a cost-effective, reusable, and reproducible 3D pediatric hip ultrasound model. The majority of pediatric point-of-care ultrasonographers who evaluated the model agreed that this model is comparable to a pediatric patient for the purpose of teaching ultrasound skills and joint space measurement.

Pediatric sport and nonsport concussions presenting to emergency departments: injury circumstances, characteristics, and clinical management.

OBJECTIVE: The aim of this study was to compare injury circumstances, characteristics, and clinical management of emergency department (ED) presentations for sports-related concussion (SRC) and non-SRC. METHODS: This multicenter prospective observational study identified patients 5-17 years old who presented to EDs within 24 hours of head injury, with one or more signs or symptoms of concussion. Participants had a Glasgow Coma Scale score of 13-15 and no abnormalities on CT (if performed). Data were stratified by age: young children (5-8 years), older children (9-12 years), and adolescents (13-17 years). RESULTS: Of 4709 patients meeting the concussion criteria, non-SRC accounted for 56.3% of overall concussions, including 80.9% of younger child, 51.1% of older child, and 37.0% of adolescent concussions. The most common mechanism of non-SRC was falls for all ages. The most common activity accounting for SRC was bike riding for younger children, and rugby for older children and adolescents. Concussions occurring in sports areas, home, and educational settings accounted for 26.2%, 21.8%, and 19.0% of overall concussions. Concussions occurring in a sports area increased with age, while occurrences in home and educational settings decreased with age. The presence of amnesia significantly differed for SRC and non-SRC for all age groups, while vomiting and disorientation differed for older children and adolescents. Adolescents with non-SRC were admitted to a ward and underwent CT at higher proportions than those with SRC. CONCLUSIONS: Non-SRC more commonly presented to EDs overall, with SRC more common with increasing age. These data provide important information to inform public health policies, guidelines, and prevention efforts.

Safety of Early Discharge After Coronary Artery Bypass Grafting: A Nationwide Readmissions Analysis.

BACKGROUND: We determined the safety of early discharge after coronary artery bypass grafting (CABG) in patients with uncomplicated postoperative courses and compared outcomes to routine discharge in a national cohort. We identified preoperative factors associated with readmission following early discharge after CABG. METHODS: The Nationwide Readmissions Database was queried to identify patients undergoing CABG from 01/2016-12/2018. Patients were stratified based on length of stay (LOS) as early (≤4 days) versus routine (5-10 days) discharge. Patients were excluded with hospital courses indicative of complicated stays (emergent procedures, LOS>10 days, discharge to extended care facility or with home health, index-hospitalization mortality). Propensity-score matching was performed to compare outcomes between cohorts. Multivariable logistic regression models were used to identify factors associated with readmission following early discharge. RESULTS: A total of 91,861 patients underwent CABG with an uncomplicated postoperative course during the study period (≈20% of CABG population). Of these 31% (28,790/91,861) were discharged early and 69% (63,071/91,861) routine. After propensity-score matching, patients discharged early had lower readmission rates at 30-days, 90-days, and up to one year (P<.001, all). Index-hospitalization cost was lower with early discharge ($26,676 versus $32,859; P<.001). Early discharge was associated with a lower incidence of nosocomial infection at index-hospitalization (0.17% versus 0.81%, P<.001) and readmission from infection (14.5% versus 18%, P=.016). CONCLUSIONS: Early discharge after uncomplicated CABG can be considered in a highly selective patient population. Early discharge patients are readmitted less frequently than matched routine discharge patients, with a lower incidence of readmission from infection. Appropriate post-discharge processes to facilitate early discharge after CABG should be further pursued.

Lymph node dissection after neoadjuvant chemotherapy improves overall survival in clinical stage III endometrial cancer.

OBJECTIVE: To investigate whether performing a lymph node dissection during hysterectomy improves overall survival in patients with clinical stage III endometrial cancer who received neoadjuvant chemotherapy. METHODS: The National Cancer Database was queried to identify all patients with clinical stage III endometrial cancer who had undergone pre-operative chemotherapy as first course of treatment followed by hysterectomy with or without lymph node dissection between the years 2004 and 2020. Univariable and multivariable models were performed to investigate prognostic factors on overall survival. RESULTS: This study analyzed 2882 patients with clinical stage III endometrial cancer who received upfront chemotherapy. Among those who underwent lymph node dissection, 38% had positive lymph nodes. Factors found to be independently associated with improved survival included lymph node dissection (p<0.001), adjuvant radiation (p<0.001), histology (p<0.001), tumor grade (p<0.001), pathologic node status (p<0.001), age (p<0.001), type of insurance (p=0.027), and race (p<0.001). Patients who underwent lymph node dissection at time of hysterectomy had a significantly better overall survival (107 vs 85 months; p<0.001). Multivariate and propensity score analyses robustly demonstrated that lymph node dissection significantly improved overall survival (HR 0.69, 95% CI 0.57 to 0.84, p<0.001), even among patients with pathologically negative lymph nodes. CONCLUSION: Our study suggests that performing lymph node dissection at the time of hysterectomy is associated with improved overall survival in all patients with stage III endometrial cancer who receive upfront chemotherapy, regardless of age, race, insurance status, histologic subtype, tumor grade, pathologic node status, adjuvant radiation or chemotherapy. Notably, patients with high-risk disease may particularly benefit from this approach.

Functional stress responses in Glaucophyta: Evidence of ethylene and abscisic acid functions in Cyanophora paradoxa.

Glaucophytes, an enigmatic group of freshwater algae, occupy a pivotal position within the Archaeplastida, providing insights into the early evolutionary history of plastids and their host cells. These algae possess unique plastids, known as cyanelles that retain certain ancestral features, enabling a better understanding of the plastid transition from cyanobacteria. In this study, we investigated the role of ethylene, a potent hormone used by land plants to coordinate stress responses, in the glaucophyte alga Cyanophora paradoxa. We demonstrate that C. paradoxa produces gaseous ethylene when supplied with exogenous 1-aminocyclopropane-1-carboxylic acid (ACC), the ethylene precursor in land plants. In addition, we show that cells produce ethylene natively in response to abiotic stress, and that another plant hormone, abscisic acid (ABA), interferes with ethylene synthesis from exogenously supplied ACC, while positively regulating reactive oxygen species (ROS) accumulation. ROS synthesis also occurred following abiotic stress and ACC treatment, possibly acting as a second messenger in stress responses. A physiological response of C. paradoxa to ACC treatment is growth inhibition. Using transcriptomics, we reveal that ACC treatment induces the upregulation of senescence-associated proteases, consistent with the observation of growth inhibition. This is the first report of hormone usage in a glaucophyte alga, extending our understanding of hormone-mediated stress response coordination into the Glaucophyta, with implications for the evolution of signaling modalities across Archaeplastida.

Interrupting marine fouling with active buffered coatings.

Biofouling on marine surfaces causes immense material and financial harm for maritime vessels and related marine industries. Previous reports have shown the effectiveness of amphiphilic coating systems based on poly(dimethylsiloxane) (PDMS) against such marine foulers. Recent studies on biofouling mechanisms have also demonstrated acidic microenvironments in biofilms and stronger adhesion at low-pH conditions. This report presents the design and utilization of amphiphilic polymer coatings with buffer functionalities as an active disruptor against four different marine foulers. Specifically, this study explores both neutral and zwitterionic buffer systems for marine coatings, offering insights into coating design. Overall, these buffer systems were found to improve foulant removal, and unexpectedly were the most effective against the diatom Navicula incerta.

Benefits for children with suspected cancer from routine whole-genome sequencing.

Clinical whole-genome sequencing (WGS) has been shown to deliver potential benefits to children with cancer and to alter treatment in high-risk patient groups. It remains unknown whether offering WGS to every child with suspected cancer can change patient management. We collected WGS variant calls and clinical and diagnostic information from 281 children (282 tumors) across two English units (n = 152 from a hematology center, n = 130 from a solid tumor center) where WGS had become a routine test. Our key finding was that variants uniquely attributable to WGS changed the management in ~7% (20 out of 282) of cases while providing additional disease-relevant findings, beyond standard-of-care molecular tests, in 108 instances for 83 (29%) cases. Furthermore, WGS faithfully reproduced every standard-of-care molecular test (n = 738) and revealed several previously unknown genomic features of childhood tumors. We show that WGS can be delivered as part of routine clinical care to children with suspected cancer and can change clinical management by delivering unexpected genomic insights. Our experience portrays WGS as a clinically impactful assay for routine practice, providing opportunities for assay consolidation and for delivery of molecularly informed patient care.