Long-term durability between parent and child patient-reported outcomes in eosinophilic esophagitis.

BACKGROUND: Because young children cannot self-report symptoms, there is a need for parent surrogate reports. Although early work suggested parent-child alignment for eosinophil esophagitis (EoE) patient-reported outcomes (PROs), the longitudinal alignment is unclear. OBJECTIVE: We sought to assess the agreement and longitudinal stability of PROs between children with EoE and their parents. METHODS: A total of 292 parent-child respondents completed 723 questionnaires over 5 years in an observational trial in the Consortium of Eosinophilic Gastrointestinal Disease Researchers. The change in and agreement between parent and child Pediatric Eosinophilic Esophagitis Symptom Score version 2 (PEESSv2.0) and Pediatric Quality of Life Eosinophilic Esophagitis Module (PedsQL-EoE) PROs over time were assessed using Pearson correlation and Bland-Altman analyses. Clinical factors influencing PROs and their agreement were evaluated using linear mixed models. RESULTS: The cohort had a median disease duration equaling 3.7 years and was predominantly male (73.6%) and White (85.3%). Child and parent PEESSv2.0 response groups were identified and were stable over time. There was strong correlation between child and parent reports (PEESSv2.0, 0.83;PedsQL-EoE, 0.74), with minimal pairwise differences for symptoms. Longitudinally, parent-reported PedsQL-EoE scores were stable (P ≥ .32), whereas child-reported PedsQL-EoE scores improved (P = .026). A larger difference in parent and child PedsQL-EoE reports was associated with younger age (P < .001), and differences were driven by psychosocial PRO domains. CONCLUSIONS: There is strong longitudinal alignment between child and parent reports using EoE PROs. These data provide evidence that parent report is a stable proxy for objective EoE symptoms in their children.

Clinical and molecular correlates of the Index of Severity for Eosinophilic Esophagitis.

BACKGROUND: The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a new expert-defined clinical tool that classifies disease severity of eosinophilic esophagitis (EoE). OBJECTIVE: We aimed to determine whether I-SEE is associated with patient characteristics, molecular features of EoE, or both. METHODS: We analyzed a prospective cohort of patients with EoE from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Associations between I-SEE and clinical and molecular features (assessed by an EoE diagnostic panel [EDP]) were assessed. RESULTS: In 318 patients with chronic EoE (209 adults, 109 children), median total I-SEE score was 7.0, with a higher symptoms and complications score in children than adults (4.0 vs 1.0; P < .001) and higher inflammatory and fibrostenotic features scores in adults than children (3.0 vs 1.0 and 3.0 vs 0, respectively; both P < .001). Total I-SEE score had a bimodal distribution with the inactive to moderate categories and severe category. EDP score correlated with total I-SEE score (r = -0.352, P < .001) and both inflammatory and fibrostenotic features scores (r = -0.665, P < .001; r = -0.446, P < .001, respectively), but not with symptoms and complications scores (r = 0.047, P = .408). Molecular severity increased from inactive to mild and moderate, but not severe, categories. Longitudinal changes of modified I-SEE scores and inflammatory and fibrostenotic features scores reflected histologic and molecular activity. CONCLUSIONS: I-SEE score is associated with select clinical features across severity categories and with EoE molecular features for nonsevere categories, warranting further validation.

Oxygen-Donor Metalloligands Induce Slow Magnetization Relaxation in Zero Field for a Cobalt(II) Complex with {CoO4} Motif.

Most 3d metal-based single-molecule magnets (SMMs) use N-ligands or ligands with even softer donors to impart a particular coordination geometry and increase the zero-field splitting parameter |D|, while complexes with hard O-donor ligands showing slow magnetization relaxation are rare. Here, we report that a diamagnetic NiII complex of a tetradentate ligand featuring two N-heterocyclic carbene and two alkoxide-O donors, [LO,ONi], can serve as a {O,O'}-chelating metalloligand to give a trinuclear complex [(LO,ONi)Co(LO,ONi)](OTf)2 (2) with an elongated tetrahedral {CoIIO4} core, D = -74.3 cm-1, and a spin reversal barrier Ueff = 86.9 cm-1 in the absence of an external dc field. The influence of diamagnetic NiII on the electronic structure of the {CoO4} unit in comparison to [Co(OPh)4]2- (A) has been probed with multireference ab initio calculations. These reveal a contrapolarizing effect of the NiII, which forms stronger metal-alkoxide bonds than the central CoII, inducing a change in ligand field splitting and a 5-fold increase in the magnetic anisotropy in 2 compared to A, with an easy magnetization axis along the Ni-Co-Ni vector. This demonstrates a strategy to enhance the SMM properties of 3d metal complexes with hard O-donors by modulating the ligand field character via the coordination of diamagnetic ions and the benefit of robust metalloligands in that regard.

Hourglass-Shaped Homo- and Heteronuclear Nonanuclear Lanthanide Clusters: Structures, Magnetism, Photoluminescence, and Theoretical Analysis.

Synthesis of nonameric cationic clusters [Dy9(acac)16(µ3-OH)8(µ4-OH)2]OH·6H2O (1), [Dy8Tb (acac)16(µ3-OH)8(µ4-OH)2]OH·2H2O (2), and [Gd9(acac)16(µ3-OH)8(µ4-OH)2]OH·6H2O (3) (acac = acetylacetonate) is reported. The emission spectrum of 1 shows Dy(III) ion characteristic bands assignable to the 4F9/2 → 6HJ (J = 15/2 to 9/2) transitions. Emission due to both Dy(III) and Tb(III) ions is observed for 2 in the visible range, with Tb(III) specific bands appearing due to the 5D4 → 7FJ (J = 6, 4, and 3) transitions. Cluster 3 exhibits a significant magnetocaloric effect (MCE), with -ΔSm values increasing with decrease in temperature and increase in field, reaching -ΔSmmax = 20.98 J kg-1 K-1 at 2 K and 9 T. Isotropic magnetic coupling constants (Js) in 3 derived from density functional theory (DFT) calculations reveal that the exchange interactions are antiferromagnetic and weak. Compound 3 possesses S = 7/2 ground state arising from the central Gd(III) ion along with several nested excited states due to competing antiferromagnetic interactions that yield reasonably large MCE values. Utilizing computed exchange coupling interactions, we have performed ab initio CASSCF/RASSI-SO/POL_ANISO calculations on antiferromagnetic 1 and 2 to estimate the exchange interactions using the Lines model. For 2, Dy(III)···Tb(III) exchange interactions were extracted for the first time and were found to be weakly antiferromagnetically coupled.

Joint ESPGHAN/NASPGHAN Guidelines on Childhood Eosinophilic Gastrointestinal Disorders Beyond Eosinophilic Esophagitis.

INTRODUCTION: Eosinophilic gastrointestinal disorders beyond eosinophilic esophagitis (non-EoE EGIDs) are rare chronic inflammatory disorders of the gastrointestinal (GI) tract. Diagnosis is based on clinical symptoms and histologic findings of eosinophilic inflammation after exclusion of a secondary cause or systemic disease. Currently, no guidelines exist for the evaluation of non-EoE EGIDs. Therefore, the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) formed a task force group to provide consensus guidelines for childhood non-EoE EGIDs. METHODS: The working group was composed of pediatric gastroenterologists, adult gastroenterologists, allergists/immunologists, and pathologists. An extensive electronic literature search of the MEDLINE, EMBASE, and Cochrane databases was conducted up to February 2022. General methodology was used in the formulation of recommendations according to the Appraisal of Guidelines for Research and Evaluation (AGREE) II and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to meet current standards of evidence assessment. RESULTS: The guidelines provide information on the current concept of non-EoE EGIDs, disease pathogenesis, epidemiology, clinical manifestations, diagnostic and disease surveillance procedures, and current treatment options. Thirty-four statements based on available evidence and 41 recommendations based on expert opinion and best clinical practices were developed. CONCLUSION: Non-EoE EGIDs literature is limited in scope and depth, making clear recommendations difficult. These consensus-based clinical practice guidelines are intended to assist clinicians caring for children affected by non-EoE EGIDs and to facilitate high-quality randomized controlled trials of various treatment modalities using standardized, uniform disease definitions.

Pharmacologic Management of Non-Eosinophilic Esophagitis Eosinophilic Gastrointestinal Diseases.

Data for pharmacologic treatments for non-eosinophilic esophagitis (EoE) eosinophilic gastrointestinal diseases (EGIDs) are limited. Nevertheless, because of the increasing understanding of EGID pathogenesis, a number of medications are used to treat EGIDs, though all are currently off-label. Initial therapy generally starts with corticosteroids, and "topical" delivery is preferred over systemic due to long-term side effects. A number of other small molecules could potentially be used, ranging from allergy medications to immunosuppressants. Biologics are also being used and investigated for EGIDs and represent promising targeted therapies. Multiple therapeutic targets have also been identified, many of which overlap with EoE targets.

Assessment in Undergraduate Competency-Based Medical Education: A Systematic Review.

BACKGROUND: Studies that have methodically compiled the body of research on the competency-based medical education (CBME) assessment procedure and pinpointed knowledge gaps about the structure of the assessment process are few. Thus, the goals of the study were to create a model assessment framework for competency-based medical education that would be applicable in the Indian setting as well as to thoroughly examine the competency-based medical education assessment framework. METHODS: PubMed, MEDLINE (Ovid), EMBASE (Ovid), Scopus, Web of Science, and Google Scholar were the databases that were searched. The search parameters were restricted to English language publications about competency-based education and assessment methods, which were published between January 2006 and December 2020. A descriptive overview of the included research (in tabular form) served as the foundation for the data synthesis. RESULTS: Databases provided 732 records; out of which 36 fulfilled the inclusion and exclusion criteria. Thirty-six studies comprised a mix of randomized controlled trials, focus group interviews, and questionnaire studies, including cross-sectional studies, qualitative studies (03), mixed-method studies, etc. The papers were published in 10 different journals. The greatest number was published in BMC Medical Education (18). The average quality score for included studies was 62.53% (range: 35.71-83.33%). Most authors are from the UK (07), followed by the USA (05). The included studies were grouped into seven categories based on their dominant focus: moving away from a behavioristic approach to a constructive approach of assessment (01 studies), formative assessment (FA) and feedback (10 studies), the hurdles in the implementation of feedback (04 studies), utilization of computer or online based formative test with automated feedback (05 studies), video feedback (02 studies), e-learning platforms for formative assessment (04 studies), studies related to workplace-based assessment (WBA)/mini-clinical evaluation exercise (mini-CEX)/direct observation of procedural skills (DOPS) (10 studies). CONCLUSIONS: Various constructivist techniques, such as concept maps, portfolios, and rubrics, can be used for assessments. Self-regulated learning, peer feedback, online formative assessment, an online computer-based formative test with automated feedback, the use of a computerized web-based objective structured clinical examination (OSCE) evaluation system, and the use of narrative feedback instead of numerical scores in mini-CEX are all ways to increase student involvement in the design and implementation of the formative assessment.

Magnetic anisotropy in octahedral Dy(III) and Yb(III) complexes.

New organophosphate complexes [Ln(dippH)3(dippH2)3]·(H2O)6, (Ln = Dy, Yb and Y; dippH2 = 2,6-diisopropylphenyl phosphate), displaying octahedral coordination geometry around the metal ion, exhibit unusual slow relaxation of magnetisation, which is investigated through experimental studies and ab initio CASSCF calculations.

Nonepithelial Gene Expression Correlates With Symptom Severity in Adults With Eosinophilic Esophagitis.

BACKGROUND: The mechanistic basis of the variable symptomatology seen in eosinophilic esophagitis (EoE) remains poorly understood. OBJECTIVE: We examined the correlation of a validated, patient-reported outcome metric with a broad spectrum of esophageal transcripts to uncover potential symptom pathogenesis. METHODS: We extracted data from 146 adults with EoE through the Consortium of Eosinophilic Gastrointestinal Disease Researchers. Patients were subgrouped by esophageal dilation history. We compared a validated patient-reported outcome metric, the EoE Activity Index (EEsAI), with a set of transcripts expressed in the esophagus of patients with EoE, the EoE Diagnostic Panel (EDP). We used single-cell RNA sequencing data to identify the cellular source of EEsAI-related EDP genes and further analyzed patients with mild and severe symptoms. RESULTS: The EEsAI correlated with the EDP total score, especially in patients without recent esophageal dilation (r = -0.31; P = .003). We identified 14 EDP genes that correlated with EEsAI scores (r ≥ 0.3; P < .05). Of these, 11 were expressed in nonepithelial cells and three in epithelial cells. During histologic remission, only four of 11 nonepithelial genes (36%) versus all three epithelial genes (100%) had decreased expression to less than 50% of that in active EoE. Fibroblasts expressed five of 11 nonepithelial EEsAI-associated EDP genes (45%). A subset of nonepithelial genes (eight of 11; 73%), but not EoE-representative genes (none of four; 0%; CCL26, CAPN14, DSG1, and SPINK7), was upregulated in patients with EoE with the highest versus lowest symptom burden. CONCLUSION: The correlation of symptoms and nonepithelial esophageal gene expression substantiates that nonepithelial cells (eg, fibroblasts) likely contribute to symptom severity.

The expert's knowledge combined with AI outperforms AI alone in seizure onset zone localization using resting state fMRI.

We evaluated whether integration of expert guidance on seizure onset zone (SOZ) identification from resting state functional MRI (rs-fMRI) connectomics combined with deep learning (DL) techniques enhances the SOZ delineation in patients with refractory epilepsy (RE), compared to utilizing DL alone. Rs-fMRI was collected from 52 children with RE who had subsequently undergone ic-EEG and then, if indicated, surgery for seizure control (n = 25). The resting state functional connectomics data were previously independently classified by two expert epileptologists, as indicative of measurement noise, typical resting state network connectivity, or SOZ. An expert knowledge integrated deep network was trained on functional connectomics data to identify SOZ. Expert knowledge integrated with DL showed a SOZ localization accuracy of 84.8 ± 4.5% and F1 score, harmonic mean of positive predictive value and sensitivity, of 91.7 ± 2.6%. Conversely, a DL only model yielded an accuracy of <50% (F1 score 63%). Activations that initiate in gray matter, extend through white matter, and end in vascular regions are seen as the most discriminative expert-identified SOZ characteristics. Integration of expert knowledge of functional connectomics can not only enhance the performance of DL in localizing SOZ in RE but also lead toward potentially useful explanations of prevalent co-activation patterns in SOZ. RE with surgical outcomes and preoperative rs-fMRI studies can yield expert knowledge most salient for SOZ identification.