Effect of Cricket Frass Fertilizer on growth and pod production of green beans (Phaseolus vulgaris L.).

Cricket Frass Fertilizer (CFF) was tested for its efficiency and potential as a fertilizer on the growth of green beans (Phaseolus vulgaris L.) in central Madagascar from April 2020 to October 2020. We grew green beans experimentally for 93 days with seven different fertilizer treatments: NPK 200 kg/ha (0.47 g of N/plant), GUANOMAD (guano from bat) 300 kg/ha (0.26 g of N/ plant), CFF 100 kg/ha (0.12 g of N/plant), CFF 200 kg/ha (0.24 g of N/plant), CFF 300 kg/ha (0.38 g of N/plant), CFF 400 kg/ha (0.52 g of N/plant), and no fertilizer (0 g of N/plant). Three plant traits were measured: survival proportion, vegetative biomass, and pod biomass. The survival proportion of plants treated with the highest dose of CFF (400 kg/ha, 88.1%), NPK (79.8%), and GUANOMAD (81.2%) were similar, but plants treated with the former yielded significantly higher vegetative (35.5 g/plant) and pod biomass (11 g/plant). These results suggest that fertilizing green beans with CFF at a 400 kg/ha dose is sufficient for plant survival and growth, and improves pod production. In Madagascar where soil quality is poor, dependence on imported chemical fertilizers (NPK) and other organic fertilizer (GUANOMAD) can be reduced. Cricket Frass Fertilizer can be used as an alternative sustainable fertilizer for beans.

A Prospective Clinical Study to EvaluAte the AbiliTy of the CloudCath System to Detect Peritonitis During In-Home Peritoneal Dialysis (CATCH).

Introduction: Peritonitis is the leading complication of peritoneal dialysis (PD). Patients are instructed to seek care promptly for signs (cloudy effluent) or symptoms (abdominal pain), and earlier treatment improves outcomes. The CloudCath Peritoneal Dialysis Drain Set Monitoring (CloudCath) system monitors turbidity in dialysis effluent and sends notifications of changes signaling possible peritonitis. Methods: We conducted this single-arm, open-label, multicenter study of CloudCath system use during PD. We deactivated system notifications to participants and investigators, who followed standard-of-care for peritonitis signs and symptoms. Effectiveness endpoints measured time between CloudCath system notifications and peritonitis events using International Society of Peritoneal Dialysis (ISPD) criteria. Results: Two hundred forty-three participants used the CloudCath system for 178.8 patient-years. Of 71 potential peritonitis events, 51 events (0.29 per patient-year) met ISPD white blood cell (WBC) count criteria. The system triggered notifications for 41 of 51 events (80.4%), with a median lead time of 2.6 days (10%-90% range, -1.0 to 15.7; P < 0.0001). Excluding 6 peritonitis events that occurred when the system was not in use, the system triggered notifications for 41 of 45 events (91.1%), with a median lead time of 3.0 days (10%-90% range, -0.5 to 18.8; P < 0.0001). Of the 0.78 notifications per patient-year, the majority were peritonitis events or nonperitonitis events such as exit site and tunnel infections or catheter/cycler issues. Conclusion: The CloudCath system detected peritonitis events during PD several days earlier than the current standard-of-care and has the capacity to send notifications that could expedite peritonitis diagnosis and treatment.

Household income and health-related quality of life in children receiving treatment for acute myeloid leukemia: Potential impact of selection bias in health equity research.

OBJECTIVE: Examine the influence of household income on health-related quality of life (HRQOL) among children with newly diagnosed acute myeloid leukemia (AML). DESIGN: Secondary analysis of data prospectively collected from pediatric patients receiving treatment for AML at 14 hospitals across the United States. EXPOSURE: Household income was self-reported on a demographic survey. The examined mediators included the acuity of presentation and treatment toxicity. OUTCOME: Caregiver proxy reported assessment of patient HRQOL from the Peds QL 4.0 survey. RESULT: Children with AML (n = 131) and caregivers were prospectively enrolled to complete PedsQL assessments. HRQOL scores were better for patients in the lowest versus highest income category (mean ± SD: 76.0 ± 14 household income <$25,000 vs. 59.9 ± 17 income ≥$75,000; adjusted mean difference: 11.2, 95% CI: 2.2-20.2). Seven percent of enrolled patients presented with high acuity (ICU-level care in the first 72 h), and 16% had high toxicity (any ICU-level care); there were no identifiable differences by income, refuting mediating roles in the association between income and HRQOL. Enrolled patients were less likely to be Black/African American (9.9% vs. 22.2%), more likely to be privately insured (50.4% vs. 40.7%), and more likely to have been treated on a clinical trial (26.7% vs. 18.5%) compared to eligible unenrolled patients not enrolled. Evaluations of potential selection bias on the association between income and HRQOL suggested differences in HRQOL may be smaller than observed or even in the opposing direction. CONCLUSIONS: While primary analyses suggested lower household income was associated with superior HRQOL, differential participation may have biased these results. Future studies should partner with patients/families to identify strategies for equitable participation in clinical research.

Impact of temperature on the bionomics and geographical range margins of the two-spotted field cricket Gryllus bimaculatus in the world: Implications for its mass farming.

Gryllus bimaculatus (Orthoptera: Gryllidae) is widely considered an excellent nutrient source for food and feed. Despite its economic importance, there is limited information on the impact of temperature on the bionomics of this cricket to guide its effective and sustainable mass production in its geographical range. The biological parameters of G. bimaculatus were investigated at eight different temperatures ranging from 20-40˚C. The Insect Life-Cycle Modelling (ILCYM) program was used to fit linear and non-linear functions to the data to describe the influence of temperature on life history parameters and its farmability under the current and projected climate for 2050. Our results revealed that G. bimaculatus was able to complete its lifecycle in the temperature range of 20°C to 37°C with a maximum finite rate of population increase (= 1.14) at 35°C. The developmental time of G. bimaculatus decreased with increasing temperature. The least developmental time and mortality were attained at 32°C. The highest wet length and mass of G. bimaculatus occurred at 32°C. The lowest temperature threshold for G. bimaculatus egg and nymph development was approximated using linear regression functions to be at 15.9°C and 16.2°C with a temperature constant of 108.7 and 555.6 degree days. The maximum fecundity (2301.98 eggs per female), net reproductive rate (988.42 daughters/ generation), and intrinsic rate of natural increase (0.134 days) were recorded at 32°C and the shortest doubling of 5.2 days was observed at 35°C. Based on our findings G. bimaculatus can be farmed in countries with temperatures ranging between 20 and 37°C around the globe. These findings will help the cricket farmers understand and project the cricket population dynamics around the world as influenced by temperature, and as such, will contribute to more efficient farming.

Genetic Researchers' Use of and Interest in Research With Diverse Ancestral Groups.

Importance: Genetic researchers must have access to databases populated with data from diverse ancestral groups to ensure research is generalizable or targeted for historically excluded communities. Objective: To determine genetic researchers' interest in doing research with diverse ancestral populations, which database stewards offer adequate samples, and additional facilitators for use of diverse ancestral data. Design, Setting, and Participants: This survey study was conducted from June to December 2022 and was part of an exploratory sequential mixed-methods project in which previous qualitative results informed survey design. Eligible participants included genetic researchers who held US academic affiliations and conducted research using human genetic databases. Exposure: Internet-administered survey to genetic research professionals. Main Outcomes and Measures: The survey assessed respondents' experience and interest in research with diverse ancestral data, perceptions of adequacy of diverse data across database stewards (ie, private, government, or consortia), and identified facilitators for encouraging use of diverse ancestral data. Descriptive statistics, χ2 tests, and z tests were used to describe respondents' perspectives and experiences. Results: A total of 294 researchers (171 men [58.5%]; 121 women [41.2%]) were included in the study, resulting in a response rate of 20.4%. Across seniority level, 109 respondents (37.1%) were senior researchers, 85 (28.9%) were mid-level researchers, 71 (24.1%) were junior researchers, and 27 (9.2%) were trainees. Significantly more respondents worked with data from European ancestral populations (261 respondents [88.8%]) compared with any other ancestral population. Respondents who had not done research with Indigenous ancestral groups (210 respondents [71.4%]) were significantly more likely to report interest in doing so than not (121 respondents [41.2%] vs 89 respondents [30.3%]; P < .001). Respondents reported discrepancies in the adequacy of ancestral populations with significantly more reporting European samples as adequate across consortium (203 respondents [90.6%]), government (200 respondents [89.7%]), and private (42 respondents [80.8%]) databases, compared with any other ancestral population. There were no significant differences in reported adequacy of ancestral populations across database stewards. A majority of respondents without access to adequate diverse samples reported that increasing the ancestral diversity of existing databases (201 respondents [68.4%]) and increasing access to databases that are already diverse (166 respondents [56.5%]) would increase the likelihood of them using a more diverse sample. Conclusions and Relevance: In this survey study of US genetic researchers, respondents reported existing databases only provide adequate ancestral samples for European populations, despite their interest in other ancestral populations. These findings suggest there are specific gaps in access to and composition of genetic databases, highlighting the urgent need to boost diversity in research samples to improve inclusivity in genetic research practices.

Approach for defining human adenovirus infection and disease for central review adjudication in clinical studies.

BACKGROUND: Pediatric allogeneic hematopoietic cell transplant (allo-HCT) recipients are at risk for morbidity and mortality from human adenovirus (HAdV). HAdV can be detected in an asymptomatic state, referred to as infection or with signs or symptoms of illness, referred to as disease. Standardized case definitions are needed to distinguish infection from disease and allow for consistent reporting in both observational cohort studies and therapeutic clinical trials. METHODS: A working group of experts in virology, transplant infectious disease, and HCT was assembled to develop HAdV infection and disease definitions with the degree of certainty (i.e., possible, probable, and proven). Definitions were further refined through an iterative process and independently applied by two central review committees (CRCs) to 20 pediatric allo-HCT recipients with at least one HAdV-positive PCR. RESULTS: Initial HAdV infection and disease definitions were developed and updated through an iterative process after reviewing clinical and virological details for 81 subjects with at least one positive HAdV PCR detected in a clinical specimen. Independent application of final definitions to 20 HAdV positive allo-HCT recipients by two CRCs yielded similar number of HAdV infection or disease events but with variation of degree of certainty for some events. CONCLUSIONS: Application of definitions by a CRC for a study of HAdV infection and disease is feasible and can provide consistency in the assignment of outcomes. Definitions need further refinement to improve reproducibility and to provide guidance on determining clinical improvement or worsening after initial diagnosis of HAdV infection or disease.

Guideline for the management of Clostridioides difficile infection in pediatric patients with cancer and hematopoietic cell transplantation recipients: 2024 update.

Our objective was to update a clinical practice guideline for the prevention and treatment of Clostridioides difficile infection (CDI) in pediatric patients with cancer and hematopoietic cell transplantation recipients. We reconvened an international multi-disciplinary panel. A systematic review of randomized controlled trials (RCTs) for the prevention or treatment of CDI in any population was updated and identified 31 new RCTs. Strong recommendations were made to use either oral metronidazole or oral vancomycin for non-severe CDI treatment, and to use either oral vancomycin or oral fidaxomicin for severe CDI. A strong recommendation that fecal microbiota transplantation should not be routinely used to treat CDI was also made. The panel made two new good practice statements to follow infection control practices including isolation in patients experiencing CDI, and to minimize systemic antibacterial administration where feasible, especially in patients who have experienced CDI.

Proteomic Analysis of Arachis hypogaea Seeds from Different Maturity Classes.

Physiological maturity impacts seed quality through various mechanisms including vigor, desiccation tolerance, dormancy induction, synthesis of raw materials (including seed storage proteins), and the reorganization of metabolisms. Peanut seed development can be classified into seven classes with four incremental stages per class. Based on the mesocarp color, the final three stages are commonly referred to as "orange", "brown", and "black". In 2017, freshly harvested pods from one genotype of runner market-type peanuts grown under conventional practices were obtained from the University of Georgia research facility. The pods were removed from the plant material and 'pod blasted' to reveal the mesocarp. After separation, the remainder of the pod outer layer was removed, and the seeds were segregated for proteomic analysis. The raw peanuts were analyzed by bottom-up LC-MS/MS proteomics, which was conducted by the Proteomics Resource Center at the Rockefeller University, to identify the significant protein composition differences in each maturity class. The proteomic data revealed differentially expressed proteins as a function of maturity class with multiple functions including plant defense, metabolism, cell signaling, nutrient accumulation, and packaging. Understanding the processes needed for seed maturation will enable peanut scientists to evaluate the traits needed for robust germination, hardiness of the seed in response to disease, and nutrient quality.

Protective human monoclonal antibodies target conserved sites of vulnerability on the underside of influenza virus neuraminidase.

Continuously evolving influenza viruses cause seasonal epidemics and pose global pandemic threats. Although viral neuraminidase (NA) is an effective drug and vaccine target, our understanding of the NA antigenic landscape still remains incomplete. Here, we describe NA-specific human antibodies that target the underside of the NA globular head domain, inhibit viral propagation of a wide range of human H3N2, swine-origin variant H3N2, and H2N2 viruses, and confer both pre- and post-exposure protection against lethal H3N2 infection in mice. Cryo-EM structures of two such antibodies in complex with NA reveal non-overlapping epitopes covering the underside of the NA head. These sites are highly conserved among N2 NAs yet inaccessible unless the NA head tilts or dissociates. Our findings help guide the development of effective countermeasures against ever-changing influenza viruses by identifying hidden conserved sites of vulnerability on the NA underside.

Description of a national, multi-center registry of patients with sickle cell disease and SARS-CoV-2 infection: Data from the Pediatric COVID-19 United States Registry.

Children with sickle cell disease (SCD) are at risk of complications from viral infections, including SARS-CoV-2. We present the clinical characteristics and outcomes of pediatric patients with SCD from the Pediatric COVID-19 United States Registry who developed acute COVID-19 due to SARS-CoV-2 infection (n = 259) or multisystem inflammatory syndrome in children (MIS-C; n = 4). Nearly half of hospitalized children with SCD and SARS-CoV-2 infection required supplemental oxygen, though children with SCD had fewer intensive care (ICU) admissions compared to the general pediatric and immunocompromised populations. All registry patients with both SCD and MIS-C required ICU admission. Children with SCD are at risk of severe disease with SARS-CoV-2 infection, highlighting the importance of vaccination in this vulnerable population.

Critical misconceptions and knowledge gaps regarding alcohol cessation and risk of relapse in alcohol-related liver disease patients: A qualitative mental models study.

INTRODUCTION: Despite the mortality benefits of alcohol cessation and alcohol treatment, few patients with alcohol-related liver disease (ALD) get such treatment. To understand reasons for low treatment rates, we performed a qualitative mental models study to explore how ALD patients understand factors influencing alcohol cessation, relapse and their liver health. METHODS: Using a mental models framework, we interviewed experts in alcohol use disorder (AUD) and ALD to determine factors influencing alcohol cessation, risk of relapse and liver health. An expert influence diagram was constructed and used to develop a patient interview guide. We recruited participants with ALD enrolled in hepatology or transplant clinics at a single tertiary-care center. We conducted interviews either face-to-face or by phone, per participant preference. We transcribed all interviews verbatim and analyzed them using combined deductive coding schema based on both the interview guide and emergent coding. RESULTS: 25 (10 women, 15 men) participants with a mean age of 57 years completed interviews. 68 % had decompensated cirrhosis. Major omissions included gender (as a factor in alcohol use or liver disease) and the influence of benzodiazepines/opioids on relapse. Misconceptions were common, in particular the idea that the absence of urges to drink meant participants were safe from relapse. Conceptual differences from the expert model emerged as well. Participants tended to view the self as primary and the only thing that could influence relapse in many cases, resulting in a linear mental model with few nodes influencing alcohol cessation. Participants' risky drinking signals (i.e., elevated liver enzymes) differed from known definitions of hazardous or high-risk drinking, which largely emphasize dose of alcohol consumed irrespective of consequences. Finally, participants sometimes viewed stopping on one's own as the primary means of stopping alcohol use, not recognizing the many other nodes in the influence diagram impacting ability to stop alcohol. CONCLUSION: Patients with ALD had critical misconceptions, omissions, and conceptual reorganizations in their mental models of the ability to stop alcohol use. Attention to these differences may allow clinicians and researchers to craft more impactful interventions to improve rates of alcohol abstinence and AUD treatment engagement.

The details matter: personalized prediction of live birth after in vitro fertilization in women with polycystic ovary syndrome.

OBJECTIVE: To derive and internally validate a clinical prediction model for live birth (LB) in women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF). DESIGN: Retrospective cohort study. SETTING: Four academic reproductive endocrinology clinics. PATIENTS: A total of 207 women with PCOS confirmed using Rotterdam criteria undergoing their first fresh IVF cycle. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: The primary outcome was cumulative LB per IVF cycle start. This included any LB that resulted from either fresh embryo transfer or any subsequent frozen embryo transfer from embryos obtained at the index oocyte retrieval. A prediction model was derived using multivariable logistic regression. Covariates considered for inclusion in the prediction model included demographic characteristics, medical history, and prior fertility treatment. Predicted probabilities for LB were calculated using the prediction model which included the 90% shrinkage factor for each adjusted odds ratio. RESULTS: The final model, on the basis of maximization of the area under the receiver operating characteristic curve, included age < 35 years, White race, presence of polycystic ovaries on ultrasound (polycystic ovary morphology), normal body mass index (<25 kg/m2), being metabolically healthy (no metabolic risk factors), and being a nonresponder to ovulation induction agents including letrozole and clomiphene citrate. The area under the receiver operating characteristic curve score for the model was 0.68 (95% confidence interval [CI]: 0.60, 0.77). Predicted probabilities of LB ranged from 8.1% (95% CI: 2.8, 21.5) for a woman who had no favorable predictors to 74.2% (95% CI: 59.5, 84.9) for a woman who had all favorable predictors. CONCLUSION: Our study demonstrated that, in addition to anovulation, the underlying pathophysiology and associated comorbidities alter the likelihood of a successful pregnancy in women with PCOS undergoing IVF. Further validation of this model is needed before it can serve as a tool to personalize prediction estimates for the probability of LB in women with PCOS.

Pipeline of Novel Antifungals for Invasive Fungal Disease in Transplant Recipients: A Pediatric Perspective.

Invasive fungal disease (IFD) remains a significant cause of morbidity and mortality in children undergoing transplantation. There is a growing armamentarium of novel antifungal agents recently approved for use or in late stages of clinical development. The overarching goal of this review is to discuss the mechanisms of action, spectrum of activity, stage of development, and pediatric-specific data for the following agents: encochleated amphotericin B deoxycholate, fosmanogepix, ibrexafungerp, isavuconazole, olorofim, opelconazole, oteseconazole, and rezafungin. Additionally, key drug attributes of these novel agents and their potential future therapeutic roles in pediatric transplant recipients are discussed.

The Comparative Effectiveness of Perioperative Antibiotic Regimens to Prevent Surgical Site Infections in Pediatric Liver Transplant Recipients.

INTRODUCTION: Surgical site infections (SSIs) are a common complication in liver transplant(LT) recipients. Lack of pediatric prophylaxis guidelines results in variation in preventative antibiotic regimens. METHODS: We performed a retrospective observational study of LT recipients under 18 years using a merged dataset that included data from PHIS and UNOS between 2006 and 2017. The exposure was defined as the antibiotic(s) received within 24 hours of LT; with 6 categories, ranging from narrow (category 1: cefazolin), to broad). The primary outcome was presence or absence of SSI in the index admission. Mixed-effects logistic regression compared the effectiveness of each category relative to category 1 in preventing SSI. RESULTS: Of the 2586 LT, 284 (11%) met SSI criteria. SSI rate was higher (16.2%) in the younger sub-cohort compared to older (8.6%), necessitating a stratified analysis. Antibiotics from category 5 were most commonly used. In the younger sub-cohort, the adjusted risk was increased in all categories compared to the reference, most notably in category 3 (OR 2.58; 0.69-9.59) and category 6 (OR 2.76; 0.66-11.56). In the older sub-cohort, estimated ORs were also increased for each category, most notably in category 4 (2.49; 0.99-6.27). None of the ORs suggested benefit from broader-spectrum prophylaxis. Our E value assessment suggests it's unlikely there is unmeasured confounding by indication to the degree necessary to revert ORs to protective. CONCLUSION: There was wide variation in antibiotic prophylaxis. Adjusted analyses did not reveal a protective benefit of broader-spectrum prophylaxis in either sub-cohort, suggesting that narrower regimens may be adequate.

Clinical practice guideline-inconsistent management of fever and neutropenia in pediatric oncology: A Children's Oncology Group study.

BACKGROUND: The primary objective was to measure the proportion of episodes where care delivery was inconsistent with selected recommendations of a clinical practice guideline (CPG) on fever and neutropenia (FN) management. The influence of site size on CPG-inconsistent care delivery, and association between patient outcomes and CPG-inconsistent care were described. METHODS: This retrospective, multicenter study included patients less than 21 years old with cancer who were at high risk of poor FN outcomes and were previously enrolled to a Children's Oncology Group (COG) study at participating National Cancer Institute Community Oncology Research Program (NCORP) institutions from January 2014 through December 2015. Patients were randomly selected for chart review by participating sites from a COG-generated list. Care delivered in each episode was adjudicated (CPG-consistent or CPG-inconsistent) against each of five selected recommendations. RESULTS: A total of 107 patients from 22 sites, representing 157 FN episodes, were included. The most common CPG-inconsistent care delivered was omission of pulmonary computerized tomography in patients with persistent FN (60.3%). Of 74 episodes where assessment of four (episodes without persistent FN) or five (episodes with persistent FN) recommendations was possible, CPG-inconsistent care was delivered with respect to at least one recommendation in 63 (85%) episodes. Site size was not associated with CPG-inconsistent care delivery. No statistically significant association between CPG-inconsistent care and fever recurrence was observed. CONCLUSIONS: In this cohort of pediatric patients at high risk of poor FN outcomes, CPG-inconsistent care was common. Opportunities to optimize resource stewardship by boosting supportive care CPG implementation are highlighted.

Disparities in Cytomegalovirus Infection Rates by Race and Ethnicity among Pediatric Allogeneic Hematopoietic Cell Transplantation Recipients at a Single Center.

Previous literature has reported cytomegalovirus (CMV) infection rate disparities among racial/ethnic groups of hematopoietic cell transplantation (HCT) recipients. Because race and ethnicity categorizations are social constructs unlikely to affect biological systems, it is likely there are covariates on the pathway to CMV detection, known as mediators, that can explain the observed disparity. Recent developments in mediation analysis methods enable the analysis of time-to-event outcomes, allowing an investigation of these disparities to also consider the timing of CMV infection detection relative to HCT. This study aimed to explore whether racial and ethnic CMV infection disparities existed within a population of HCT recipients at our center, and whether clinical covariates explained any observed association. The study cohort included all recipients of allogeneic HCT performed at the Children's Hospital of Philadelphia between January 2004 and April 2017 who were CMV PCR-negative pretransplantation, had known donor/recipient CMV serology, and were under blood CMV PCR surveillance. Subjects were followed for 100 days post-HCT. Accelerated failure time models using subject's reported race/ethnicity, dichotomized into non-Hispanic White (NHW) and non-NHW, and exposure and time to CMV detection as outcomes examined whether selected clinical factors-donor/recipient CMV serostatus, recipient age, indication for HCT, hematopoietic cell source, match quality-mediated any identified exposure-outcome association. The analysis included 348 HCTs performed in 335 subjects, with 86 episodes (24.7%) in which CMV was detected via PCR analysis. The accelerated failure time model without mediators estimated that non-NHW subjects had fewer CMV-free survival days (time ratio, .21; 95% confidence interval, .10 to .44). Any hypothesized mediator mediated at most 5% of the total association between race/ethnicity and time to CMV detection. Non-NHW HCT recipients had fewer CMV-free survival days than NHW recipients; none of the clinical factors hypothesized to mediate this association accounted for a significant component of total association. Further research should focus on nonclinical factors influenced by systemic racism to better understand their effect on CMV infection among HCT recipients.

Prefusion stabilization of the Hendra and Langya virus F proteins.

Nipah virus (NiV) and Hendra virus (HeV) are pathogenic paramyxoviruses that cause mild-to-severe disease in humans. As members of the Henipavirus genus, NiV and HeV use an attachment (G) glycoprotein and a class I fusion (F) glycoprotein to invade host cells. The F protein rearranges from a metastable prefusion form to an extended postfusion form to facilitate host cell entry. Prefusion NiV F elicits higher neutralizing antibody titers than postfusion NiV F, indicating that stabilization of prefusion F may aid vaccine development. A combination of amino acid substitutions (L104C/I114C, L172F, and S191P) is known to stabilize NiV F in its prefusion conformation, although the extent to which substitutions transfer to other henipavirus F proteins is not known. Here, we perform biophysical and structural studies to investigate the mechanism of prefusion stabilization in F proteins from three henipaviruses: NiV, HeV, and Langya virus (LayV). Three known stabilizing substitutions from NiV F transfer to HeV F and exert similar structural and functional effects. One engineered disulfide bond, located near the fusion peptide, is sufficient to stabilize the prefusion conformations of both HeV F and LayV F. Although LayV F shares low overall sequence identity with NiV F and HeV F, the region around the fusion peptide exhibits high sequence conservation across all henipaviruses. Our findings indicate that substitutions targeting this site of conformational change might be applicable to prefusion stabilization of other henipavirus F proteins and support the use of NiV as a prototypical pathogen for henipavirus vaccine antigen design.IMPORTANCEPathogenic henipaviruses such as Nipah virus (NiV) and Hendra virus (HeV) cause respiratory symptoms, with severe cases resulting in encephalitis, seizures, and coma. The work described here shows that the NiV and HeV fusion (F) proteins share common structural features with the F protein from an emerging henipavirus, Langya virus (LayV). Sequence alignment alone was sufficient to predict which known prefusion-stabilizing amino acid substitutions from NiV F would stabilize the prefusion conformations of HeV F and LayV F. This work also reveals an unexpected oligomeric interface shared by prefusion HeV F and NiV F. Together, these advances lay a foundation for future antigen design targeting henipavirus F proteins. In this way, Nipah virus can serve as a prototypical pathogen for the development of protective vaccines and monoclonal antibodies to prepare for potential henipavirus outbreaks.

Applying machine learning to identify pediatric patients with newly diagnosed acute lymphoblastic leukemia using administrative data.

Case identification in administrative databases is challenging as diagnosis codes alone are not adequate for case ascertainment. We utilized machine learning (ML) to efficiently identify pediatric patients with newly diagnosed acute lymphoblastic leukemia. We tested nine ML models and validated the best model internally and externally. The optimal model had 97% positive predictive value (PPV) and 99% sensitivity in internal validation; 94% PPV and 82% sensitivity in external validation. Our ML model identified a large cohort of 21,044 patients, demonstrating an efficient approach for cohort assembly and enhancing the usability of administrative data.

Effect of cytomegalovirus infection on post-transplant hospitalization days among children undergoing allogeneic hematopoietic cell transplantation: A marginal structural model approach.

BACKGROUND: Cytomegalovirus (CMV) commonly reactivates after allogeneic hematopoietic cell transplant (HCT), potentially leading to CMV disease and significant morbidity and mortality. To reduce morbidity and mortality, many centers conduct weekly CMV blood polymerase chain reaction (PCR) surveillance testing with subsequent initiation of antiviral therapy upon CMV DNAemia detection. However, the impact of CMV DNAemia on subsequent hospitalization risk has not been assessed using models accounting for the time-varying nature of the exposure, outcome, and confounders. METHODS: All allogeneic HCTs at the Children's Hospital of Philadelphia from January 2004-April 2017 were considered for inclusion. Patients were monitored with CMV surveillance via PCR testing for up to 105 days after HCT receipt. We estimated the association between CMV DNAemia and rate of hospitalization using marginal structural models (MSM). RESULTS: There were 343 allogeneic HCT episodes in 330 with CMV surveillance; median age was 9.0 (range: 0.1-26.2) and 46.5% were female. And 24.1% of HCT patients had at least one positive CMV blood PCR during the follow-up period. Median time to CMV DNAemia detection was 19 days (range: 4-97). The MSM estimated the incidence rate ratios for an association of CMV DNAemia with hospitalization to be 1.24, (95% confidence interval: 1.04-1.47). CONCLUSIONS: CMV DNAemia was associated with an increased hospitalization in the post-HCT period. The MSM accounted for time-varying nature of the outcome, exposure and confounders. The findings support prevention of CMV DNAemia in this population. We recommend further investigation into the effectiveness and safety of prophylaxis versus pre-emptive CMV prevention approaches.

Do you want to promote recall, perceptions, or behavior? The best data visualization depends on the communication goal.

Data visualizations can be effective and inclusive means for helping people understand health-related data. Yet numerous high-quality studies comparing data visualizations have yielded relatively little practical design guidance because of a lack of clarity about what communicators want their audience to accomplish. When conducting rigorous evaluations of communication (eg, applying the ISO 9186 method), describing the process simply as evaluating "comprehension" or "interpretation" of visualizations fails to do justice to the true range of outcomes being studied. We present newly developed taxonomies of outcome measures and tasks that are guiding a large-scale systematic review of the health numbers communication literature. Using these taxonomies allows a designer to determine whether a specific data presentation format or feature supports or inhibits the desired audience cognitions, feelings, or behaviors. We argue that taking a granular, outcomes-based approach to designing and evaluating information visualization research is essential to deriving practical, actionable knowledge from it.