bluuebunny/crossref_metadata_2025_split huggingface dataset:
Performance and Advancement of the Kidney Solid Organ Response Test
Authors: Lee Joshua , Barbachan e Silva Mariel , Bao Yi , Whitmarsh Ryan , Banerjee Sukanta , O’Connor Jeannine , Holbert Jeffery , Bratton Tiffany K. , Broin Pilib Ó. , Akalin Enver 
Published: June 2023

Background.
The kidney solid organ response test (kSORT) has been investigated for the prediction of acute rejection in kidney transplant recipients with conflicting results. We aimed to investigate if the kSORT assay score is associated with rejection or immune quiescence.

Methods.
The blinded association between rejection and kSORT > 9 were investigated. Optimization of kSORT prediction was evaluated after unblinding to determine the optimal prediction cutoff value of kSORT score. Additionally, the predictive capability of the kSORT gene set was assessed using blinded normalized gene expression data from microarray (Affymetrix) and qPCR assays.

Results.
Of the 95 blood samples analyzed, 18 patients had blood samples before transplant, 77 patients after transplant and 71 had clinically indicated biopsies of which 15 biopsies showed acute rejection and 16 showed chronic active antibody-mediated rejection. When 31 patients with rejection were compared to the remaining 64 patients, positive predictive value (PPV) was 54.29% and negative predictive value (NPV) was 75% when stratified using a kSORT score > 9, and PPV was 57.89% and NPV was 78.95% when stratified using a kSORT score > 5. Using the kSORT assay for detection of rejection showed an area under the curve value of 0.71. Microarray data improved prediction accuracy with PPV of 53% and NPV of 84% compared to qPCR results (PPV and NPV were 36% and 66%), respectively.

Conclusions.
The kSORT assay has the potential to be used as a predictive tool for active rejection and/or immune quiescence, but additional studies will be useful in improving and refining the kSORT assay, in particular the prediction algorithm.
Detecting heterogeneous seizures in newborn infants using triple correlation
Authors: Smith Graham A , Henry Julia , van Drongelen Wim 
Published: June 2023

AbstractWe detect seizures in newborn infants using a novel method derived from triple correlation, which integrates spatial and temporal structure in neonatal electroencephalograms (EEGs). Triple correlation natively encompasses analogues to a variety of lower-order approaches (auto-correlation, cross-correlation) in addition to introducing higher-order signals, so we hypothesized that our approach would both effectively detect and differentiate notoriously difficult-to-detect and heterogeneous neonatal seizures. Indeed, our method in its simplest form performs comparably well to a current standard of care, amplitude-integrated EEG (aEEG), and by some measures outperforms aEEG, suggesting at a minimum that a combination of triple correlation and aEEG could produce a more effective first-line bedside detector. Moreover, we find that the triple correlation seizure-signal varies between patients, with 1) differences in dominance of either within or between channel correlations and 2) differing levels of higher order structure. We hope that our approach will provide a fertile field for future work in distinguishing and detecting seizures.
Determinants of Post-acute COVID-19 Syndrome among hospitalized severe COVID-19 patients: a 2-year follow up study
Authors: Elias Tamrat P. , Gebreamlak Tsegaye W. , Gebremeskel Tigist T. , Adde Binyam L. , Elias Bitaniya P. , Argaw Abel M. , Tenaw Addis A. 
Published: June 2023

AbstractBackgroundCoronavirus disease-19 (COVID-19), emerged as a public health threat in December 2019. The number of COVID-19 cases worldwide is now more than 765 million with more than 6.9 million dead. During follow-up visits following discharge, a large percentage of patients were discovered to still be suffering from health issues that lower their quality of life and ability to return to work. This study assessed the prevalence and associated risk factors of post-acute COVID-19 syndrome (PACS) among severe COVID-19 patients who were discharged from Millennium COVID-19 care center, Addis Ababa, Ethiopia.MethodsA cross-sectional study using data collected from patient charts and a follow-up telephone interview after two years of discharge. Systematic random samplingwas used to select a total of 400 patients. A structured questionnaire developed from the case report form for PACS of WHO was used. Frequency and cross-tabulation were used for descriptive statistics. Predictor variables with a p-value <0.25 in bivariate analyses were included in the logistic regression.ResultOut of the 400 patients, 20 patients were dead, 14 patients refused to give consent, and 26 patients couldn’t be reached because their phone wasn’t working. Finally, 340 were included in the study. The majority (68.5%) were males and the mean age was 53.9 (±13.3 SD) years. Most of the patients (60%) has one or more comorbidity. The most common symptom at presentation was cough (93.5%), followed by shortness of breath (82.1%) and fatigue (69.7%). The mean duration of hospital admission was 12.3 (±6.5 SD) days. More than a third (38.1%) of the patients reported the persistence of at least one symptom after hospital discharge. The most common symptoms were fatigue (27.5%) and Cough (15.3%). older age (AOR 1.04, 95% CI 1.02 – 1.07), female sex (AOR 1.82, 95% CI 1.00 – 3.29), presence of comorbidity (AOR 2.38, 95% CI 1.35 – 4.19), alcohol use (AOR 3.05, 95% CI 1.49 – 6.26), fatigue at presentation (AOR 2.18, 95% CI 1.21 – 3.95), and longer hospital stay (AOR 1.06, 95% CI 1.02 – 1.10) were found to increase the odds of developing post-acute COVID-19 syndrome. Higher hemoglobin level was found to decrease the risk of subsequent post-acute COVID-19 syndrome (AOR 0.84, 95% CI 0.71 – 0.99).Conclusionestablishing a dedicated PACS follow-up clinic, especially for those with a higher risk can help to provide comprehensive care for the patients and improve their quality of life.
Loss-of-function variants inCUL3cause a syndromic neurodevelopmental disorder
Authors: Blackburn Patrick R. , Ebstein Frédéric , Hsieh Tzung-Chien , Motta Marialetizia , Radio Francesca Clementina , Herkert Johanna C. , Rinne Tuula , Thiffault Isabelle , Rapp Michele , Alders Mariel , Maas Saskia , Gerard Bénédicte , Smol Thomas , Vincent-Delorme Catherine , Cogné Benjamin , Isidor Bertrand , Vincent Marie , Bachmann-Gagescu Ruxandra , Rauch Anita , Joset Pascal , Ferrero Giovanni Battista , Ciolfi Andrea , Husson Thomas , Guerrot Anne-Marie , Bacino Carlos , Macmurdo Colleen , Thompson Stephanie S. , Rosenfeld Jill A. , Faivre Laurence , Mau-Them Frederic Tran , Deb Wallid , Vignard Virginie , Agrawal Pankaj B. , Madden Jill A. , Goldenberg Alice , Lecoquierre François , Zech Michael , Prokisch Holger , Necpál Ján , Jech Robert , Winkelmann Juliane , Koprušáková Monika Turčanová , Konstantopoulou Vassiliki , Younce John R. , Shinawi Marwan , Mighton Chloe , Fung Charlotte , Morel Chantal , Ellis Jordan Lerner- , DiTroia Stephanie , Barth Magalie , Bonneau Dominique , Krapels Ingrid , Stegmann Sander , Schoot Vyne van der , Brunet Theresa , Bußmann Cornelia , Mignot Cyril , Courtin Thomas , Ravelli Claudia , Keren Boris , Ziegler Alban , Hasadsri Linda , Pichurin Pavel N. , Klee Eric W. , Grand Katheryn , Sanchez-Lara Pedro A. , Krüger Elke , Bézieau Stéphane , Klinkhammer Hannah , Krawitz Peter Michael , Eichler Evan E. , Tartaglia Marco , Küry Sébastien , Wang Tianyun 
Published: June 2023

AbstractPurposeDe novovariants inCUL3(Cullin-3 ubiquitin ligase) have been strongly associated with neurodevelopmental disorders (NDDs), but no large case series have been reported so far. Here we aimed to collect sporadic cases carrying rare variants inCUL3,describe the genotype-phenotype correlation, and investigate the underlying pathogenic mechanism.MethodsGenetic data and detailed clinical records were collected via multi-center collaboration. Dysmorphic facial features were analyzed using GestaltMatcher. Variant effects on CUL3 protein stability were assessed using patient-derived T-cells.ResultsWe assembled a cohort of 35 individuals with heterozygousCUL3variants presenting a syndromic NDD characterized by intellectual disability with or without autistic features. Of these, 33 have loss-of-function (LoF) and two have missense variants.CUL3LoF variants in patients may affect protein stability leading to perturbations in protein homeostasis, as evidenced by decreased ubiquitin-protein conjugatesin vitro. Specifically, we show that cyclin E1 (CCNE1) and 4E-BP1 (EIF4EBP1), two prominent substrates of CUL3, fail to be targeted for proteasomal degradation in patient-derived cells.ConclusionOur study further refines the clinical and mutational spectrum ofCUL3-associated NDDs, expands the spectrum of cullin RING E3 ligase-associated neuropsychiatric disorders, and suggests haploinsufficiency via LoF variants is the predominant pathogenic mechanism.
Diagnostic accuracy of chest ultrasound scan in the diagnosis of childhood tuberculosis
Authors: Erem Geoffrey , Otike Caroline , Okuja Maxwell , Ameda Faith , Nalyweyiso Dorothy Irene , Mubuuke Aloysius Gonzaga , Kakinda Michael 
Published: June 2023

AbstractChest Ultrasound Scan (CUS) has been utilized in place of CXR in the diagnosis of adult pneumonia with similar or higher sensitivity and specificity to CXR. However, there is a paucity of data on the use of CUS for the diagnosis of childhood TB. This study aimed to determine the diagnostic accuracy of CUS for childhood TB.This cross-sectional study was conducted at the Mulago National Referral Hospital in Uganda. Eighty children up to 14 years of age with presumptive TB were enrolled. They all had CUS and CXR performed and interpreted independently by radiologists. The radiologist who performed the CXR was blinded to the CUS findings, and vice versa. Radiologists noted whether TB was likely or unlikely. A two-by-two table was developed to compare the absolute number of children as either TB likely or TB unlikely on CXR or CUS. This was used to calculate the sensitivity and specificity of CUS when screening for TB in children, with a correction to accommodate the use of CXR as a reference test.The sensitivity of CUS was 64% (95% CI 48.5%-77.3%), while its specificity was 42.7% (95% CI 25.5%-60.8%). Both the CUS and CXR found 29 children with a likelihood of TB, and 27 children unlikely to have TB.CUS met the sensitivity target set by the WHO TPP for Triage, and it had a sensitivity and specificity comparable to that of CXR.
Admission biomarkers may not have an association with cardiovascular involvement in Latin American patients with Multisystem Inflammatory Syndrome in Children (MIS-C)
Authors: Galindo-Hayashi Jose M , González-Moctezuma Karen , Tamez-Rivera Oscar , Villarreal-Treviño Ana Victoria 
Published: June 2023

AbstractObjectivesThe aim of the study is to determine if there is an association between altered biomarkers and cardiovascular involvement in Latin American patients with MIS-C.DesignThe researchers of this study conducted a retrospective cohort study.SettingSecondary care maternal unit hospital in Monterrey, NL, Mexico.ParticipantsAny register of a Latin-American pediatric patient with MIS-C within the database from March 2019 to February 2022.Primary and secondary outcome measuresCut, mean, odds ratio (OR), relative ratio (RR), 95% confidence interval (CI) andpvalues of inflammatory markers associated with cardiovascular affection in MIS-C. As a secondary outcome we measure being male as an independent risk factor.ResultsNone of the biomarkers and gender variables taken were significant (Table 1).ConclusionsThe researchers’ analysis suggests there is no evidence of cause-effect association between admission biomarkers and the presence of cardiovascular affection in MIS-C. Remarkably, neutrophilia and ESR had a high odds ratio and a nearly significant p-value, which makes them ideal for further analysis with a bigger sample. Additionally, gender was included as a risk factor and was analyzed independently, nonetheless, it was not associated with a higher risk of presenting cardiovascular affection.Article summaryStrengths and limitations of this studyFirst study measuring the association of a series of available and economical biomarkers with a higher incidence of cardiovascular involvement in MIS-C in a Latin-American population.Set ground for further research regarding the current treatment of MIS-CSample size non-representative.Since this is an observational study we can’t fully control confounding and bias (e.j. reporting bias)
Single-exon deletions ofZNRF3exon 2 cause congenital adrenal hypoplasia
Authors: Amano Naoko , Narumi Satoshi , Aizu Katsuya , Miyazawa Mari , Okamura Kohji , Ohashi Hirofumi , Katsumata Noriyuki , Ishii Tomohiro , Hasegawa Tomonobu 
Published: June 2023

AbstractPrimary adrenal insufficiency (PAI) is a life-threatening condition characterized by the inability of the adrenal cortex to produce sufficient steroid hormones. E3 ubiquitin protein ligase zinc and ring finger 3 (ZNRF3) is a negative regulator of Wnt/β-catenin signaling. R-spondin 1 (RSPO1) enhances Wnt/β-catenin signaling via binding and removal of ZNRF3 from the cell surface. To explore a novel genetic form of PAI, we analyzed nine childhood-onset patients with PAI of biochemically and genetically unknown etiology using array comparative genomic hybridization. We identified various-sized single-exon deletions encompassing ofZNRF3exon 2 in three patients, who showed neonatal-onset adrenal hypoplasia with glucocorticoid and mineralocorticoid deficiencies. RT-PCR analysis showed that the three distinct single exon deletions were commonly transcribed into a 126-nucleotide deleted mRNA and translated into 42-amino acid deleted protein (ΔEx2-ZNRF3). Three-dimensional structure modeling predicted that interaction between ZNRF3 and RSPO1 was disturbed in ΔEx2-ZNRF3, suggesting loss of RSPO1-dependent activation of Wnt/β-catenin signaling. Cell-based functional assays with the TCF-LEF reporter showed that RSPO1-dependent activation of Wnt/β-catenin signaling was attenuated in cells expressing ΔEx2-ZNRF3 as compared with those expressing wild-type ZNRF3. In summary, we provided genetic evidence linking deletions encompassing ZNRF3 exon 2 and congenital adrenal hypoplasia, which might be related to constitutive inactivation of Wnt/β-catenin signaling by ΔEx2-ZNRF3.
Protein-truncating variants inBSNare associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease
Authors: Zhao Yajie , Chukanova Maria , Kentistou Katherine A , Fairhurst-Hunter Zammy , Siegert Anna Maria , Jia Raina , Dowsett Georgina , Gardner Eugene J , Day Felix R , Kaisinger Lena R , Tung Yi-Chun Loraine , Hong Lam Brian Yee , Chen Hsiao-Jou Cortina , Wang Quanli , Berumen-Campos Jaime , Kuri-Morales Pablo , Tapia-Conyer Roberto , Alegre-Diaz Jesus , Emberson Jonathan , Torres Jason M , Collins Rory , Saleheen Danish , Smith Katherine R , Paul Dirk S , Merkle Florian , Wareham Nick J , Petrovski Slavé , O’Rahilly Steve , Ong Ken K , Yeo Giles S H , Perry John R B 
Published: June 2023

AbstractObesity is a major risk factor for many common diseases and has a significant heritable component. While clinical and large-scale population studies have identified several genes harbouring rare alleles with large effects on obesity risk, there are likely many unknown genes with highly penetrant effects remaining. To this end, we performed whole exome-sequence analyses for adult body mass index (BMI) in up to 587,027 individuals. We identified rare, loss of function variants in two genes –BSNandAPBA1– with effects on BMI substantially larger than well-established obesity genes such asMC4R. One in ∼6500 individuals carry a heterozygous protein truncating variant (PTV) inBSN, which confers a 6.6, 3.7 and 3-fold higher risk of severe obesity (BMI >40kg/m2), non-alcoholic fatty liver disease and type 2 diabetes, respectively. In contrast to most other obesity-related genes, rare variants inBSNandAPBA1had no apparent effect on childhood adiposity. Furthermore,BSNPTVs magnified the influence of common genetic variants associated with BMI, with a common polygenic score exhibiting an effect on BMI twice as large inBSNPTV carriers than non-carriers. Finally, we explored the plasma proteomic signatures ofBSNPTV carriers as well as the functional consequences ofBSNdeletion in human iPSC-derived hypothalamic neurons. These approaches highlighted a network of differentially expressed genes that were collectively enriched for genomic regions associated with BMI, and suggest a role for degenerative neuronal synaptic function and neurotransmitter release in the etiology of obesity.
The relative effectiveness of a high-dose quadrivalent influenza vaccine vs standard-dose quadrivalent influenza vaccines in older adults in France: a retrospective cohort study during the 2021-22 influenza season
Authors: Hélène Bricout , Marie-Cécile Levant , Nada Assi , Pascal Crépey , Alexandre Descamps , Karine Mari , Jacques Gaillat , Gaétan Gavazzi , Benjamin Grenier , Odile Launay , Anne Mosnier , Fanny Raguideau , Laurence Watier , Harris Rebecca C , Ayman Chit 
Published: June 2023

AbstractBackgroundHigh-dose quadrivalent influenza vaccine (HD-QIV) was introduced during the 2021/22 influenza season in France for adults aged ≥65 years as an alternative to standard-dose quadrivalent influenza vaccines (SD-QIV). This is the first study to estimate the relative vaccine effectiveness (rVE) of HD-QIV versus SD-QIV against influenza-related hospitalizations in France.MethodsCommunity-dwelling individuals aged ≥65 years with reimbursed influenza vaccine claims during the 2021/22 influenza season were included from the French national health insurance database. Individuals were followed up from vaccination day to 30 June 2022, nursing home admission or death date. Baseline socio-demographic and health characteristics were identified from medical records over the 5 previous years. Hospitalizations due to influenza and other causes were recorded from 14 days after vaccination to end of follow-up. HD-QIV and SD-QIV vaccinees were matched using 1:4 propensity score matching with an exact constraint on age group, sex, week of vaccination and region. Incidence rate ratios (IRR) were estimated using zero-inflated Poisson or zero-inflated negative binomial regression models.ResultsWe matched 405,385 (99.9%) HD-QIV to 1,621,540 SD-QIV vaccinees. HD-QIV was associated with a 23.3% (95%CI: 8.4–35.8) lower rate of influenza hospitalizations compared to SD-QIV. Post-matching, we observed higher rates in the HD-QIV group for hospitalizations non-specific to influenza and for negative control outcomes, suggesting residual confounding by indication.ConclusionsHD-QIV was associated with lower influenza-related hospitalization rates versus SD-QIV, consistent with existing evidence, in the context of high SARS-CoV-2 circulation in France and likely prioritization of HD-QIV for older/more comorbid individuals.
Metabolic signature and proteasome activity controls synovial migration ofCDC42hiCD14+cells in rheumatoid arthritis
Authors: Malmhäll-Bah Eric , Andersson Karin M.E. , Erlandsson Malin C. , Silfverswärd Sofia T. , Pullerits Rille , Bokarewa Maria I. 
Published: June 2023

SummaryObjectiveActivation of Rho-GTPases in macrophages causes inflammation and severe arthritis in mice. In this study, we explore if Rho-GTPases define the joint destination of pathogenic leukocytes in rheumatoid arthritis (RA) and how JAK inhibition mitigates these effects.MethodsCD14+cells of 136 RA patients were characterized by RNA-sequencing, and cytokine measurement to identify biological processes and transcriptional regulators specific forCDC42hiCD14+cells, which were summarized in a metabolic signature. Effect of hypoxia, and IFN-γ signaling on the metabolic signature of CD14+cells was assessed experimentally. To investigate its connection with joint inflammation, the signature was translated into the single cell characteristics ofCDC42hisynovial tissue macrophages. Sensitivity of the metabolic signature to the RA disease activity and treatment effect was assessed experimentally and clinically.ResultsCDC42hiCD14+cells carried the metabolic signature of genes functional in the oxidative phosphorylation and proteasome-dependent cell remodeling, which correlated with the cytokine-rich migratory phenotype and antigen presenting capacity of these cells. Integration ofCDC42hiCD14+and synovial macrophages marked with the metabolic signature revealed the important role of the interferon-rich environment and immunoproteasome expression in homeostasis of these pathogenic macrophages. TheCDC42hiCD14+cells were targeted by JAK-inhibitors and responded with downregulation of immunoproteasome and MHC-II molecules, which disintegrated the immunological synapse, reduced cytokine production and alleviated arthritis.ConclusionThis study shows that the CDC42-related metabolic signature identifies the antigen-presenting CD14+cells that migrate to joints to coordinate autoimmunity. Accumulation ofCDC42hiCD14+cells disclose patients perceptive to JAKi treatment.
Personalising Alzheimer’s Disease progression using brain atrophy markers
Authors: Verdi Serena , Rutherford Saige , Fraza Charlotte , Tosun Duygu , Altmann Andre , Raket Lars Lau , Schott Jonathan M. , Marquand Andre F. , Cole James H. 
Published: June 2023

AbstractINTRODUCTION: Neuroanatomical normative modelling can capture individual variability in Alzheimer’s Disease (AD). We used neuroanatomical normative modelling to track individuals’ disease progression in people with mild cognitive impairment (MCI) and patients with AD.METHODS: Cortical thickness and subcortical volume neuroanatomical normative models were generated using healthy controls (n∼58k). These models were used to calculate regional Z-scores in 4361 T1-weighted MRI time-series scans. Regions with Z-scores <-1.96 were classified as outliers and mapped on the brain, and also summarised by total outlier count (tOC).RESULTS: Rate of change in tOC increased in AD and in people with MCI who converted to AD and correlated with multiple non-imaging markers. Moreover, a higher annual rate of change in tOC increased the risk of MCI progression to AD. Brain Z-score maps showed that the hippocampus had the highest rate of atrophy change.CONCLUSIONS: Individual-level atrophy rates can be tracked by using regional outlier maps and tOC.