Characterization of the RNA Mycovirome Associated with Grapevine Fungal Pathogens: Analysis of Mycovirus Distribution and Their Genetic Variability within a Collection of Botryosphaeriaceae Isolates.

Botryosphaeriaceae are fungi involved in the decay of various woody species, including the grapevine, leading to significant production losses. This fungal family is largely ubiquitous, and seven species of Botryosphaeriaceae have been identified in French vineyards, with variable levels of aggressiveness, both in vitro and in planta. Mycoviruses can impact the life traits of their fungal hosts, including aggressiveness, and are one of the factors influencing fungal pathogenicity. In this study, the RNA mycovirome of fifteen Botryosphaeriaceae isolates was characterized through the high-throughput sequencing of double-stranded RNA preparations from the respective samples. Eight mycoviruses were detected, including three potential novel species in the Narnaviridae family, as well as in the proposed Mycobunyaviridae and Fusagraviridae families. A large collection of Botryosphaeriaceae isolates was screened using RT-PCR assays specific for 20 Botryosphaeriaceae-infecting mycoviruses. Among the mycoviruses detected, some appeared to be specialists within a single host species, while others infected isolates belonging to multiple Botryosphaeriaceae species. This screening allowed us to conclude that one-third of the Botryosphaeriaceae isolates were infected by at least one mycovirus, and a significant proportion of isolates (43.5%) were found to be coinfected by several viruses, with very complex RNA mycoviromes for some N. parvum isolates.

Correction: Haegeman et al. Looking beyond Virus Detection in RNA Sequencing Data: Lessons Learned from a Community-Based Effort to Detect Cellular Plant Pathogens and Pests. Plants 2023, 12, 2139.

In the original publication [...].

Comparative performance evaluation of double-stranded RNA high-throughput sequencing for the detection of viral infection in temperate fruit crops.

There is limited information on the compared performance of currently used biological, serological and molecular assays with high-throughput sequencing (HTS) for viral indexing in temperate fruit crops. Here, using a range of samples of predetermined virological status, we compared two performance criteria (inclusivity and analytical sensitivity) of ELISA, molecular hybridization, RT-PCR and double-stranded RNA (dsRNA) HTS for the detection of a total of 14 viruses (10 genera) and four viroids (three genera). Using undiluted samples from individual plants, ELISA had the lowest performance, with an overall detection rate of 68.7%, followed by RT-PCR (82.5%) and HTS (90.7%, and 100% if considering only viruses). The lower performance of RT-PCR reflected the inability to amplify some isolates as a consequence of point mutations affecting primer-binding sites. In addition, HTS identified viruses that had not been identified by others assays in close to two-thirds of samples. Analysis of serial dilutions of fruit tree samples allowed to compare analytical sensitivity for various viruses. ELISA showed the lowest analytical sensitivity but RT-PCR showed higher analytical sensitivity than HTS for a majority of samples. Overall, these results confirm the superiority of HTS over biological indexing in terms of speed, and inclusivity and show that while absolute analytical sensitivity of RT-PCR tends to be higher than that of HTS, PCR inclusivity is affected by viral genetic diversity. Taken together these results make a strong case for the implementation of HTS-based approaches in fruit tree viral testing protocols supporting quarantine and certification programs.

Neurological involvement in hospitalized children with SARS-CoV-2 infection: a multinational study.

BACKGROUND AND OBJECTIVES: Neurological involvement associated with SARS-CoV-2 infection is increasingly recognized. However, the specific characteristics and prevalence in pediatric patients remain unclear. The objective of this study was to describe the neurological involvement in a multinational cohort of hospitalized pediatric patients with SARS-CoV-2. METHODS: This was a multicenter observational study of children <18 years of age with confirmed SARS-CoV-2 infection or multisystemic inflammatory syndrome (MIS-C) and laboratory evidence of SARS-CoV-2 infection in children, admitted to 15 tertiary hospitals/healthcare centers in Canada, Costa Rica, and Iran February 2020-May 2021. Descriptive statistical analyses were performed and logistic regression was used to identify factors associated with neurological involvement. RESULTS: One-hundred forty-seven (21%) of 697 hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Headache (n = 103), encephalopathy (n = 28), and seizures (n = 30) were the most reported. Neurological signs/symptoms were significantly associated with ICU admission (OR: 1.71, 95% CI: 1.15-2.55; p = 0.008), satisfaction of MIS-C criteria (OR: 3.71, 95% CI: 2.46-5.59; p < 0.001), fever during hospitalization (OR: 2.15, 95% CI: 1.46-3.15; p < 0.001), and gastrointestinal involvement (OR: 2.31, 95% CI: 1.58-3.40; p < 0.001). Non-headache neurological manifestations were significantly associated with ICU admission (OR: 1.92, 95% CI: 1.08-3.42; p = 0.026), underlying neurological disorders (OR: 2.98, 95% CI: 1.49-5.97, p = 0.002), and a history of fever prior to hospital admission (OR: 2.76, 95% CI: 1.58-4.82; p < 0.001). DISCUSSION: In this study, approximately 21% of hospitalized children with SARS-CoV-2 infection had neurological signs/symptoms. Future studies should focus on pathogenesis and long-term outcomes in these children.

Association of cerebrospinal fluid parameters with treatment and complications among children with cerebrospinal fluid shunt infections: a multicenter study.

OBJECTIVE: Cerebrospinal fluid (CSF) white blood cell (WBC) count, neutrophil percentage, protein concentration, and glucose level are typically measured at diagnosis and serially during the treatment of CSF shunt infections. The objective of this retrospective cohort study was to describe the longitudinal profile of CSF parameters in children with CSF shunt infections and assess their association with treatment and outcome. METHODS: Participants were children treated at 11 tertiary pediatric hospitals in Canada and the United States for CSF shunt infection, from July 1, 2013, through June 30, 2019, with hardware removal, external ventricular drain placement, intravenous antibiotics, and subsequent permanent shunt reinsertion. The relationship between CSF parameters and a complicated course (a composite outcome representing children with at least one of the following: contiguous soft-tissue infection, worsening hydrocephalus, CSF leak, intracranial bleed, brain abscess, venous thrombosis, reinfection after insertion of the new shunt, other complication, ICU admission, or death) was analyzed. RESULTS: A total of 109 children (median age 2.8 years, 44% female) were included in this study. CSF pleocytosis, elevated protein, and hypoglycorrhachia had sensitivities of 69%, 47%, and 38% for the diagnosis of culture-confirmed CSF shunt infection, respectively. The longitudinal profile of the neutrophil percentage followed a monotonic trend, decreasing by 1.5% (95% CI 1.0%-2.0%, p < 0.0001) per day over the course of treatment. The initial WBC count differed significantly between pathogens (p = 0.011), but the proportion of neutrophils, protein concentration, and glucose level did not, and was lowest with Cutibacterium acnes. The duration of antibiotic treatment and the time to shunt reinsertion were longer in patients with a higher initial neutrophil percentage. Fifty-eight patients (53%) had one or more complications during their admission. A neutrophil percentage > 44% (Youden index) in the initial CSF sample was associated with a 1.8-fold (95% CI 1.2- to 2.8-fold) higher relative risk of a complicated course. In a random-intercept, random-slope linear mixed-effects model, the longitudinal neutrophil trajectory differed significantly between patients with and without complications (p = 0.030). CONCLUSIONS: A higher proportion of neutrophils in the CSF at diagnosis was associated with a complicated clinical course. Other CSF parameters were associated with treatment and outcome; however, wide variability in values may limit their clinical utility.

Incidence and risk factors for recurrent Clostridioides difficile infection in pediatric at-risk groups in selected Pediatric Investigators Collaborative Network on Infections in Canada (PICNIC) hospitals.

OBJECTIVES: Incidence and risk factors for recurrent Clostridioides difficile infection (rCDI) are well established in adults, though data are lacking in pediatrics. We aimed to determine incidence of and risk factors for rCDI in pediatrics. METHODS: This retrospective cohort study of pediatric patients was conducted at 3 tertiary-care hospitals in Canada with laboratory-confirmed CDI between April 1, 2012, and March 31, 2017. rCDI was defined as an episode of CDI occurring 8 weeks or less from diagnostic test date of the primary episode. We used logistic regression to determine and quantify risk factors significantly associated with rCDI. RESULTS: In total, 286 patients were included in this study. The incidence proportion for rCDI was 12.9%. Among hospitalized patients, the incidence rate was estimated at 2.6 cases of rCDI per 1,000 hospital days at risk (95% confidence interval [CI], 1.7-3.9). Immunocompromised patients had higher incidence of rCDI (17.5%; P = .03) and higher odds of developing rCDI independently of antibiotic treatment given for the primary episode (odds ratio [OR], 2.31; 95% CI, 1.12-5.09). Treatment with vancomycin monotherapy did not show statistically significant protection from rCDI, independently of immunocompromised status (OR, 0.33; 95% CI, 0.05-1.15]). CONCLUSIONS: The identification of increased risk of rCDI in immunocompromised pediatric patients warrants further research into alternative therapies, prophylaxis, and prevention strategies to prevent recurrent disease burden within these groups. Treatment of the initial episode with vancomycin did not show statistically significant protection from rCDI.

"I wanted to know what was hurting so much": a qualitative study exploring patients' expectations and experiences with primary care management.

BACKGROUND: The management of shoulder pain is challenging for primary care clinicians considering that 40% of affected individuals remain symptomatic one year after initial consultation. Developing tailored knowledge mobilization interventions founded on evidence-based recommendations while also considering patients' expectations could improve primary care for shoulder pain. The aim of this qualitative study is to explore patients' expectations and experiences of their primary care consultation for shoulder pain. METHODS: In this qualitative study, participants with shoulder pain and having consulted a primary care clinician in the past year were interviewed. All the semi-structured interviews were transcribed verbatim, and inductive thematic analysis was performed to identify themes related to the participants' expectations and experiences of primary care consultations for shoulder pain. RESULTS: Thirteen participants with shoulder pain were interviewed (8 women, 5 men; mean age 50 ± 12 years). Eleven of them initially consulted a family physician or an emergency physician, and two participants initially consulted a physiotherapist. Four overarching themes related to patients' expectations and experiences were identified from our thematic analysis: 1) I can't sleep because of my shoulder; 2) I need to know what is happening with my shoulder; 3) But… we need to really see what is going on to help me!; and 4) Please take some time with me so I can understand what to do!. Several participants waited until they experienced a high level of shoulder pain before making an appointment since they were not confident about what their family physician could do to manage their condition. Although some participants felt that their physician took the time to listen to their concerns, many were dissatisfied with the limited assessment and education provided by the clinician. CONCLUSIONS: Implementing evidence-based recommendations while considering patients' expectations is important as it may improve patients' satisfaction with healthcare. Several participants reported that their expectations were not met, especially when it came to the explanations provided. One unexpected finding that emerged from this study was the waiting period between the onset of shoulder pain and when patients decided to consult their primary care clinician.

Carrot populations in France and Spain host a complex virome rich in previously uncharacterized viruses.

High-throughput sequencing (HTS) has proven a powerful tool to uncover the virome of cultivated and wild plants and offers the opportunity to study virus movements across the agroecological interface. The carrot model consisting of cultivated (Daucus carota ssp. sativus) and wild carrot (Daucus carota ssp. carota) populations, is particularly interesting with respect to comparisons of virus communities due to the low genetic barrier to virus flow since both population types belong to the same plant species. Using a highly purified double-stranded RNA-based HTS approach, we analyzed on a large scale the virome of 45 carrot populations including cultivated, wild and off-type carrots (carrots growing within the field and likely representing hybrids between cultivated and wild carrots) in France and six additional carrot populations from central Spain. Globally, we identified a very rich virome comprising 45 viruses of which 25 are novel or tentatively novel. Most of the identified novel viruses showed preferential associations with wild carrots, either occurring exclusively in wild populations or infecting only a small proportion of cultivated populations, indicating the role of wild carrots as reservoir of viral diversity. The carrot virome proved particularly rich in viruses involved in complex mutual interdependencies for aphid transmission such as poleroviruses, umbraviruses and associated satellites, which can be the basis for further investigations of synergistic or antagonistic virus-vector-host relationships.

Looking beyond Virus Detection in RNA Sequencing Data: Lessons Learned from a Community-Based Effort to Detect Cellular Plant Pathogens and Pests.

High-throughput sequencing (HTS), more specifically RNA sequencing of plant tissues, has become an indispensable tool for plant virologists to detect and identify plant viruses. During the data analysis step, plant virologists typically compare the obtained sequences to reference virus databases. In this way, they are neglecting sequences without homologies to viruses, which usually represent the majority of sequencing reads. We hypothesized that traces of other pathogens might be detected in this unused sequence data. In the present study, our goal was to investigate whether total RNA-seq data, as generated for plant virus detection, is also suitable for the detection of other plant pathogens and pests. As proof of concept, we first analyzed RNA-seq datasets of plant materials with confirmed infections by cellular pathogens in order to check whether these non-viral pathogens could be easily detected in the data. Next, we set up a community effort to re-analyze existing Illumina RNA-seq datasets used for virus detection to check for the potential presence of non-viral pathogens or pests. In total, 101 datasets from 15 participants derived from 51 different plant species were re-analyzed, of which 37 were selected for subsequent in-depth analyses. In 29 of the 37 selected samples (78%), we found convincing traces of non-viral plant pathogens or pests. The organisms most frequently detected in this way were fungi (15/37 datasets), followed by insects (13/37) and mites (9/37). The presence of some of the detected pathogens was confirmed by independent (q)PCRs analyses. After communicating the results, 6 out of the 15 participants indicated that they were unaware of the possible presence of these pathogens in their sample(s). All participants indicated that they would broaden the scope of their bioinformatic analyses in future studies and thus check for the presence of non-viral pathogens. In conclusion, we show that it is possible to detect non-viral pathogens or pests from total RNA-seq datasets, in this case primarily fungi, insects, and mites. With this study, we hope to raise awareness among plant virologists that their data might be useful for fellow plant pathologists in other disciplines (mycology, entomology, bacteriology) as well.

Trends in Severe Outcomes Among Adult and Pediatric Patients Hospitalized With COVID-19 in the Canadian Nosocomial Infection Surveillance Program, March 2020 to May 2022.

Importance: Trends in COVID-19 severe outcomes have significant implications for the health care system and are key to informing public health measures. However, data summarizing trends in severe outcomes among patients hospitalized with COVID-19 in Canada are not well described. Objective: To describe trends in severe outcomes among patients hospitalized with COVID-19 during the first 2 years of the COVID-19 pandemic. Design, Setting, and Participants: Active prospective surveillance in this cohort study was conducted from March 15, 2020, to May 28, 2022, at a sentinel network of 155 acute care hospitals across Canada. Participants included adult (aged ≥18 years) and pediatric (aged 0-17 years) patients hospitalized with laboratory-confirmed COVID-19 at a Canadian Nosocomial Infection Surveillance Program (CNISP)-participating hospital. Exposures: COVID-19 waves, COVID-19 vaccination status, and age group. Main Outcomes and Measures: The CNISP collected weekly aggregate data on the following severe outcomes: hospitalization, admission to an intensive care unit (ICU), receipt of mechanical ventilation, receipt of extracorporeal membrane oxygenation, and all-cause in-hospital death. Results: Among 1 513 065 admissions, the proportion of adult (n = 51 679) and pediatric (n = 4035) patients hospitalized with laboratory-confirmed COVID-19 was highest in waves 5 and 6 of the pandemic compared with waves 1 to 4 (77.3 vs 24.7 per 1000 patient admissions). Despite this, the proportion of patients with positive test results for COVID-19 who were admitted to an ICU, received mechanical ventilation, received extracorporeal membrane oxygenation, and died were each significantly lower in waves 5 and 6 when compared with waves 1 through 4. Admission to the ICU and in-hospital all-cause death rates were significantly higher among those who were unvaccinated against COVID-19 when compared with those who were fully vaccinated (incidence rate ratio, 4.3 and 3.9, respectively) or fully vaccinated with an additional dose (incidence rate ratio, 12.2 and 15.1, respectively). Conclusions and Relevance: The findings of this cohort study of patients hospitalized with laboratory-confirmed COVID-19 suggest that COVID-19 vaccination is important to reduce the burden on the Canadian health care system as well as severe outcomes associated with COVID-19.

Antimicrobial use among paediatric inpatients at hospital sites within the Canadian Nosocomial Infection Surveillance Program, 2017/2018.

BACKGROUND: Antimicrobial resistance threatens the ability to successfully prevent and treat infections. While hospital benchmarks regarding antimicrobial use (AMU) have been well documented among adult populations, there is less information from among paediatric inpatients. This study presents benchmark rates of antimicrobial use (AMU) for paediatric inpatients in nine Canadian acute-care hospitals. METHODS: Acute-care hospitals participating in the Canadian Nosocomial Infection Surveillance Program submitted annual AMU data from paediatric inpatients from 2017 and 2018. All systemic antimicrobials were included. Data were available for neonatal intensive care units (NICUs), pediatric ICUs (PICUs), and non-ICU wards. Data were analyzed using days of therapy (DOT) per 1000 patient days (DOT/1000pd). RESULTS: Nine hospitals provided paediatric AMU data. Data from seven NICU and PICU wards were included. Overall AMU was 481 (95% CI 409-554) DOT/1000pd. There was high variability in AMU between hospitals. AMU was higher on PICU wards (784 DOT/1000pd) than on non-ICU (494 DOT/1000pd) or NICU wards (333 DOT/1000pd). On non-ICU wards, the antimicrobials with the highest use were cefazolin (66 DOT/1000pd), ceftriaxone (59 DOT/1000pd) and piperacillin-tazobactam (48 DOT/1000pd). On PICU wards, the antimicrobials with the highest use were ceftriaxone (115 DOT/1000pd), piperacillin-tazobactam (115 DOT/1000pd), and cefazolin (111 DOT/1000pd). On NICU wards, the antimicrobials with the highest use were ampicillin (102 DOT/1000pd), gentamicin/tobramycin (78 DOT/1000pd), and cefotaxime (38 DOT/1000pd). CONCLUSIONS: This study represents the largest collection of antimicrobial use data among hospitalized paediatric inpatients in Canada to date. In 2017/2018, overall AMU was 481 DOT/1000pd. National surveillance of AMU among paediatric inpatients is necessary for establishing benchmarks and informing antimicrobial stewardship efforts.

Impact of the COVID-19 pandemic on healthcare-associated viral respiratory infections at a tertiary care pediatric hospital.

The incidence of healthcare-associated viral respiratory infections in a pediatric hospital decreased from 1.6 /1,000 patient-days in 2019 to 0.2 /1,000 patient-days in 2020 (P < .01), and this was maintained in 2021 despite an increase in community circulation of respiratory viruses. Universal masking, stricter infection control measures, and pandemic public health interventions likely accounted for this improvement.

SARS-CoV-2 infection in technology-dependent children: a multicenter case series.

PURPOSE: The objective of this study was to describe the clinical course and outcomes in children with technology dependence (TD) hospitalized with SARS-CoV-2 infection. METHODS: Seventeen pediatric hospitals (15 Canadian and one each in Iran and Costa Rica) included children up to 17 years of age admitted February 1, 2020, through May 31, 2021, with detection of SARS-CoV-2. For those with TD, data were collected on demographics, clinical course and outcome. RESULTS: Of 691 children entered in the database, 42 (6%) had TD of which 22 had feeding tube dependence only, 9 were on supplemental oxygen only, 3 had feeding tube dependence and were on supplemental oxygen, 2 had a tracheostomy but were not ventilated, 4 were on non-invasive ventilation, and 2 were on mechanical ventilation prior to admission. Three of 42 had incidental SARS-CoV-2 infection. Two with end-stage underlying conditions were transitioned to comfort care and died. Sixteen (43%) of the remaining 37 cases required increased respiratory support from baseline due to COVID-19 while 21 (57%) did not. All survivors were discharged home. CONCLUSION: Children with TD appear to have an increased risk of COVID-19 hospitalization. However, in the absence of end-stage chronic conditions, all survived to discharge.

Cerebrospinal fluid shunt-associated surgical site infection with three-month versus twelve-month surveillance periods in Canadian hospitals.

Cerebrospinal fluid shunt-associated surgical site infection surveillance for 3 months compared to 12 months after surgery captures 83% of cases with no significant differences in patient characteristics, surgery types, or pathogens. A shorter 3-month follow-up can reduce resource use and allow for more timely reporting of healthcare-associated infection rates for hospitals.

Nirmatrelvir-ritonavir use among adults hospitalized with COVID-19 during the Omicron phase of the COVID-19 pandemic, Canadian Nosocomial Infection Surveillance Program.

Background: Recent studies have demonstrated the effectiveness of nirmatrelvir-ritonavir in reducing the risk of progression to severe disease among outpatients with mild to moderate coronavirus disease 2019 (COVID-19); however, data are limited regarding the use and role of nirmatrelvir-ritonavir among hospitalized patients. This study describes the use and outcomes of nirmatrelvir-ritonavir among adults hospitalized with COVID-19 in a sentinel network of Canadian acute care hospitals during the Omicron variant phase of the pandemic. Methods: The Canadian Nosocomial Infection Surveillance Program conducts surveillance of hospitalized patients with COVID-19 in acute care hospitals across Canada. Demographic, clinical, treatment and 30-day outcome data were collected by chart review by trained infection control professionals using standardized questionnaires. Results: From January 1 to December 31, 2022, 13% (n=490/3,731) of adult patients (18 years of age and older) hospitalized with COVID-19 in 40 acute care hospitals received nirmatrelvir-ritonavir either at admission or during hospitalization. Most inpatients who received nirmatrelvir-ritonavir, 79% of whom were fully vaccinated, had at least one pre-existing comorbidity (97%) and were of advanced age (median=79 years). Few were admitted to an intensive care unit (2.3%) and among the 490 nirmatrelvir-ritonavir treated inpatients, there were 13 (2.7%) deaths attributable to COVID-19. Conclusion: These findings from a large sentinel network of Canadian acute-care hospitals suggest that nirmatrelvir-ritonavir is being used to treat adult COVID-19 patients at admission who are at risk of progression to severe disease or those who acquired COVID-19 in hospital. Additional research on the efficacy and indications for nirmatrelvir-ritonavir use in hospitalized patients is warranted to inform future policies and guidelines.

Risk factors for severe PCR-positive SARS-CoV-2 infection in hospitalised children.

OBJECTIVE: To identify risk factors for severe disease in children hospitalised for SARS-CoV-2 infection. DESIGN: Multicentre retrospective cohort study. SETTING: 18 hospitals in Canada, Iran and Costa Rica from 1 February 2020 to 31 May 2021. PATIENTS: Children<18 years of age hospitalised for symptomatic PCR-positive SARS-CoV-2 infection, including PCR-positive multisystem inflammatory syndrome in children (MIS-C). MAIN OUTCOME MEASURE: Severity on the WHO COVID-19 Clinical Progression Scale was used for ordinal logistic regression analyses. RESULTS: We identified 403 hospitalisations. Median age was 3.78 years (IQR 0.53-10.77). At least one comorbidity was present in 46.4% (187/403) and multiple comorbidities in 18.6% (75/403). Eighty-one children (20.1%) met WHO criteria for PCR-positive MIS-C. Progression to WHO clinical scale score ≥6 occurred in 25.3% (102/403). In multivariable ordinal logistic regression analyses adjusted for age, chest imaging findings, laboratory-confirmed bacterial and/or viral coinfection, and MIS-C diagnosis, presence of a single (adjusted OR (aOR) 1.90, 95% CI 1.13 to 3.20) or multiple chronic comorbidities (aOR 2.12, 95% CI 1.19 to 3.79), obesity (aOR 3.42, 95% CI 1.76 to 6.66) and chromosomal disorders (aOR 4.47, 95% CI 1.25 to 16.01) were independent risk factors for severity. Age was not an independent risk factor, but different age-specific comorbidities were associated with more severe disease in age-stratified adjusted analyses: cardiac (aOR 2.90, 95% CI 1.11 to 7.56) and non-asthma pulmonary disorders (aOR 3.07, 95% CI 1.26 to 7.49) in children<12 years old and obesity (aOR 3.69, 1.45-9.40) in adolescents≥12 years old. Among infants<1 year old, neurological (aOR 10.72, 95% CI 1.01 to 113.35) and cardiac disorders (aOR 10.13, 95% CI 1.69 to 60.54) were independent predictors of severe disease. CONCLUSION: We identified risk factors for disease severity among children hospitalised for PCR-positive SARS-CoV-2 infection. Comorbidities predisposing children to more severe disease may vary by age. These findings can potentially guide vaccination programmes and treatment approaches in children.

Food preferences throughout the menstrual cycle - A computer-assisted neuro-endocrino-psychological investigation.

BACKGROUND: As eating behavior changes in relation to the menstrual cycle and weight changes with menopausal transition, ovarian hormones appear to be involved in regulating eating behavior. However, observations are contradictory and are difficult to compare, due to methodological problems related to nutritional epidemiology. To better understand the relationship between ovarian steroid hormones and eating behavior, our study evaluates women's responses to visual food cues at different points in the menstrual cycle with their specific serum estrogen/progesterone levels and women's responses in the case of strong estrogen changes in the context of fertility treatments. METHODS: We collected data from 129 women, 44 of whom received in vitro fertilization (IVF) at the Department of Reproductive Endocrinology, University Hospital Zurich. A total of 85 women with natural cycles were recruited at the University Hospital Zurich (n = 37) and at the Hannover Medical School (n = 48). Our observational study used 4 different measurement time points across the natural cycle and 2 measurement time points in women with supraphysiological estradiol levels during fertility treatments. Using a second cycle, we then tested our results for replication. At these predefined time points, women were shown pictures of 11 categories of food, with 4 items for each category and blood samples for measurement of hormone levels were taken. Food preferences registered at the time of the investigation were indicated on a visual analogue scale (0-100). RESULTS: We did not find any statistically significant association between women's serum hormone levels and the rating of visually presented food, either during the menstrual cycle or during fertility treatments after controlling for multiple testing (all p > 0.005). Ratings for fruits, vegetables, and carbohydrates showed a significant linear decline throughout the first menstrual cycle (p < 0.01), which did not replicate in the second cycle (p > 0.05). In contrast, the ratings for sweets showed a significant linear decline in both cycles (both p < 0.01), with a mean rating of 54.2 and 48.8 in the menstrual phase of the first and second cycle, respectively, to a mean rating of 47.7 and 43.4 in the premenstrual phase of the first and second cycle, respectively. During fertility treatments, no food rating showed a significant change (all p > 0.05). Mood such as negative and positive affects did not influence ratings for visual food cues neither throughout the menstrual cycles nor during fertility treatment. CONCLUSIONS: Serum levels of estradiol and progesterone do not correlate with food ratings in women, even when estradiol levels are above the physiological level of a natural menstrual cycle. Since, except for sweets, significant changes in food ratings in a first cycle did not replicate in a second menstrual cycle, significant findings from the literature based on animal or human studies focusing on a single-cycle have to be interpreted with caution.

Thrombosis and hemorrhage experienced by hospitalized children with SARS-CoV-2 infection or MIS-C: Results of the PICNIC registry.

INTRODUCTION: Coagulopathy and thrombosis associated with SARS-CoV-2 infection are well defined in hospitalized adults and leads to adverse outcomes. Pediatric studies are limited. METHODS: An international multicentered (n = 15) retrospective registry collected information on the clinical manifestations of SARS-CoV-2 and multisystem inflammatory syndrome (MIS-C) in hospitalized children from February 1, 2020 through May 31, 2021. This sub-study focused on coagulopathy. Study variables included patient demographics, comorbidities, clinical presentation, hospital course, laboratory parameters, management, and outcomes. RESULTS: Nine hundred eighty-five children were enrolled, of which 915 (93%) had clinical information available; 385 (42%) had symptomatic SARS-CoV-2 infection, 288 had MIS-C (31.4%), and 242 (26.4%) had SARS-CoV-2 identified incidentally. Ten children (1%) experienced thrombosis, 16 (1.7%) experienced hemorrhage, and two (0.2%) experienced both thrombosis and hemorrhage. Significantly prevalent prothrombotic comorbidities included congenital heart disease (p-value .007), respiratory support (p-value .006), central venous catheter (CVC) (p = .04) in children with primary SARS-CoV-2 and in those with MIS-C included respiratory support (p-value .03), obesity (p-value .002), and cytokine storm (p = .012). Comorbidities prevalent in children with hemorrhage included age >10 years (p = .04), CVC (p = .03) in children with primary SARS-CoV-2 infection and in those with MIS-C encompassed thrombocytopenia (p = .001) and cytokine storm (p = .02). Eleven patients died (1.2%), with no deaths attributed to thrombosis or hemorrhage. CONCLUSION: Thrombosis and hemorrhage are uncommon events in children with SARS-CoV-2; largely experienced by those with pre-existing comorbidities. Understanding the complete spectrum of coagulopathy in children with SARS-CoV-2 infection requires ongoing research.

PeakForest: a multi-platform digital infrastructure for interoperable metabolite spectral data and metadata management.

INTRODUCTION: Accuracy of feature annotation and metabolite identification in biological samples is a key element in metabolomics research. However, the annotation process is often hampered by the lack of spectral reference data in experimental conditions, as well as logistical difficulties in the spectral data management and exchange of annotations between laboratories. OBJECTIVES: To design an open-source infrastructure allowing hosting both nuclear magnetic resonance (NMR) and mass spectra (MS), with an ergonomic Web interface and Web services to support metabolite annotation and laboratory data management. METHODS: We developed the PeakForest infrastructure, an open-source Java tool with automatic programming interfaces that can be deployed locally to organize spectral data for metabolome annotation in laboratories. Standardized operating procedures and formats were included to ensure data quality and interoperability, in line with international recommendations and FAIR principles. RESULTS: PeakForest is able to capture and store experimental spectral MS and NMR metadata as well as collect and display signal annotations. This modular system provides a structured database with inbuilt tools to curate information, browse and reuse spectral information in data treatment. PeakForest offers data formalization and centralization at the laboratory level, facilitating shared spectral data across laboratories and integration into public databases. CONCLUSION: PeakForest is a comprehensive resource which addresses a technical bottleneck, namely large-scale spectral data annotation and metabolite identification for metabolomics laboratories with multiple instruments. PeakForest databases can be used in conjunction with bespoke data analysis pipelines in the Galaxy environment, offering the opportunity to meet the evolving needs of metabolomics research. Developed and tested by the French metabolomics community, PeakForest is freely-available at https://github.com/peakforest .