Miracle-dz/UniFAR-FTUs huggingface dataset:
Application of a physiologically based pharmacokinetic model to predict isoniazid disposition during pregnancy

Pregnancy can increase the risk of latent tuberculosis infection (LTBI) progression to tuberculosis (TB) disease. Isoniazid (INH) is the preferred preventative treatment for LTBI in pregnancy. INH is mainly cleared by N‐acetyltransferase 2 (NAT2) but the pharmacokinetics (PK) of INH in different NAT2 phenotypes during pregnancy is not well characterized. To address this knowledge gap, we used physiologically based pharmacokinetic (PBPK) modeling to evaluate NAT2 phenotype‐specific effects of pregnancy on INH disposition. A whole‐body PBPK model for INH was developed and verified for non‐pregnant NAT2 fast (FA), intermediate (IA), and slow (SA) acetylators. Model predictive performance was assessed using a drug‐specific model acceptance criterion for mean plasma area under the curve (AUC) and peak plasma concentration (Cmax), and the absolute average fold error (AAFE) for individual plasma concentrations. The verified model was extended to simulate INH disposition during pregnancy in NAT2 SA, IA, and FA populations. A sensitivity analysis was conducted using the verified PBPK model and known changes in INH disposition during pregnancy to determine whether NAT2 activity changes during pregnancy or other INH clearance pathways are altered. This analysis suggested that NAT2 activity is unchanged while other INH clearance pathways increase by ~80% during pregnancy. The model was applied to explore the effect of pregnancy on INH disposition in two ethnic populations with different NAT2 phenotype distributions and with high TB burden. Our PBPK model can be used to predict INH disposition during pregnancy in diverse populations and expanded to other drugs cleared by NAT2 during pregnancy.
Impact of increased paternal age on neonatal outcomes in very-low-birth-weight infants

Abstract Objective Despite the trend of increasing paternal age, its impact on neonatal outcomes, particularly in preterm infants, has not been thoroughly investigated. We aimed to evaluate the perinatal characteristics and neonatal outcomes associated with paternal age. Methods Electronic medical records of very low-birthweight infants admitted to our unit from July 2013 to March 2022 were reviewed. Infants grouped according to paternal age (<35 years, 35–39 years, and ≥40 years) were analyzed for differences in perinatal findings and neonatal outcomes. Results A total of 637 infants were included (194, 294, and 149 in the <35, 35–39, and ≥40 years groups, respectively). The increase in paternal age paralleled the increase in maternal age. The Z-score of head circumference at birth was significantly different between the groups, showing the lowest median value in the ≥40 years group. Small-for-gestational age (Odds ratio 71.074, p < .001, 95% confidence interval 19.337 − 261.236) and male sex (Odds ratio 3.309, p < .034, 95% confidence interval 1.089 − 8.425), but not paternal or maternal age groups were significant factors associated with head circumference Z-scores less than −2 standard deviation based on the multivariable logistic regression analysis. Infants affected by chromosomal or genetic anomaly were more frequently identified (3.4 vs 0.0 vs 0.5%) in the ≥40 years group than in the other two groups. When infants with anomalies or critical illnesses were excluded, overall neonatal outcomes did not statistically differ according to paternal age. Conclusion Although increased paternal age ≥40 years may be associated with relatively smaller head circumferences, the impact on fetal head growth does not imply a definite risk for microcephaly. Nonetheless, based on the possible negative impact on chromosomal/genetic anomaly, increased paternal age warrants attention, even though neonatal outcomes concerning prematurity were not significantly affected. A large-scale longitudinal study is needed to further elucidate the impact of advanced paternal age in preterm infants and provide guidelines for appropriate antenatal counseling and surveillance.
and Training Performance: The Mediating Role of Other-Approach Goals. European Journal of Sport Science,

Recent research found perfectionistic strivings to predict performance in a novel basketball task among novice basketball players. The current study builds on this research by examining whether this is also the case for performance in a familiar basketball training task among experienced basketball players, and whether achievement goals mediated any observed relationships. Perfectionistic strivings, perfectionistic concerns, and 3 × 2 achievement goals were assessed prior to basketball training performance in 90 basketball players (mean age 20.9 years). Regression analyses showed that perfectionistic strivings predicted better performance. Furthermore, mediation analyses showed that other-approach goals (e.g., beliefs that one should and can outperform others) accounted for this relationship. The findings suggest that perfectionistic strivings may predict better performance in both novel and familiar athletic contexts. In addition, beliefs about the importance and ability to outperform others may explain this relationship.
Current treatment landscape of HR+/HER2− advanced breast cancer in the Nordics: a modified Delphi study

Abstract Background This Delphi study aimed to assess current perspectives on hormone receptor-positive/human epidermal growth factor receptor 2-negative(HR+/HER2−) advanced breast cancer (aBC) treatment strategies across the Nordics, and to establish where consensus exists across the Nordics on HR+/HER2− aBC treatment. Material and methods A modified, three-round Delphi method was followed. A steering committee was appointed for study coordination, panellist selection, and questionnaire development. The questionnaires covered relevant topics on HR+/HER2− aBC treatment: treatment patterns in different lines of therapy (first [1L], second [2L], and third [3L]), oligometastatic disease, de novo aBC, brain metastases, age as influential factor, visceral crisis, radiotherapy, diagnostics, and clinical guidelines. Both open and closed-ended questions were included. Consensus was defined as at least 70% agreement. Results In total, 28 experienced BC oncologists participated in the study from all five Nordic countries. Overall, topics reaching consensus included: preferred treatment approach in 1L and 2L therapy, treatment of oligometastatic disease, visceral crisis, brain metastases, and age-related treatment considerations. No consensus was reached for 3L therapy and local treatment for primary tumour in de novo aBC. Endocrine therapy (ET) combined with a cyclin-dependent kinase (CDK)4/6 inhibitor was the treatment of choice for 1L and 2L therapy. Treatment patterns in clinical practice did not always follow recommendations in current Nordic guidelines, as seen in the case of recently approved treatments. Discussion ET in combination with a CDK4/6 inhibitor is the preferred frontline treatment for HR+/HER2− aBC in the Nordics. The observed discrepancy between current guidelines and clinical practice could be due to differences in the reimbursement of novel treatments in the Nordics. Collaborative research efforts are warranted for topics that lack consensus.
A Network Meta-Analysis of Success Rates following Low Dosage Anti-VEGF for Retinopathy of Prematurity

Abstract Purpose To search the low dosage of anti-VEGF best for primary therapies on retinopathy of prematurity (ROP) in terms of success rate. Methods We searched Medline(Pubmed), Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases only for randomized controlled trials that had been reported as of March 3, 2023. We included studies that used bevacizumab, aflibercept and conbercept for ROP with comparable cohorts and treatment criteria. This study was performed according the pre-specified protocol registered with PROSPERO (CRD42021270077) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis checklist. Those with animal and cell experiments, non-randomized case-control, or single case report were excluded. Frequentist network meta-analyses determined the surface under the cumulative ranking (SUCRA) of the success rate of each dose range group and compared pairs of treatments via STATA 15. Result Since non-RCT research were excluded, aflflibercept and conbercept studies were excluded. Therefore, only 6 bevacizumab studies were included in final meta-analysis: Inconsistency was not detected in this study via global inconsistent model test, loop inconsistency and local inconsistent model test (p > 0.05). In addition, a consistent model test has been passed in this study (p > 0.05). Little bias was detected via funnel plot. Since bevacizumab adult standard dose of single-injection is 1.25 mg, the concentration groups were converted according to the proportion of adult standard dose, such as 1/2, [1/5, 1/6.25], [1/10, 1/12.5], [1/19.8, 1/78.1], [1/156.3, 1/625]. The SUCRA of [1/10, 1/12.5] dose group were the best of largest probability to achieve success. However, [1/156.3, 1/625] dose group was the worst dose to achieve success in the five dose groups. The success rate ranking of league chart in this study is that [1/10, 1/12.5] > [1/5, 1/6.25] > 1/2 ≈ [1/19.8, 1/78.1] > [1/156.3, 1/625]. Conclusions [1/10, 1/12.5] were the best dosage ranges to achieve maximal medicine success. [1/156.3, 1/625] was the worst ineffective in the five dose ranges.
Implications of the COVID-19 Pandemic on Immediate Breast Reconstruction Access

Aims As a result of COVID-19, there have been restrictions on surgical interventions across Canada. Immediate breast reconstruction (IBR), while an essential component of cancer care, is classified as elective surgery and therefore has been restricted in access over the course of the pandemic. The purpose of this study was to compare wait times for breast cancer patients undergoing surgical intervention for IBR before and since the COVID-19 pandemic. Methods This was a retrospective cross-sectional study of consecutive patients who underwent IBR between July 2018 and October 2021 by 5 plastic surgeons at a single Canadian health center. Wait times to consultation and surgical intervention between pre- and post-COVID cohorts were analyzed. Results A total of 161 patients met inclusion criteria. For ablative surgery, there was no difference in wait times to surgical oncology consultation (14.0 ± 12.3 vs 14.0 ± 11.0 days, P = 0.991) and surgical intervention with IBR (41.0 ± 49.8 vs 35.0 ± 58.0 days, P = 0.621) between the pre- and post-COVID cohorts. For breast reconstruction, while time to consultation with plastic surgery (12.5 ± 14.8 vs 11.0 ± 12.8 days, P = 0.775) remained unchanged, usage of autologous techniques was reduced [n = 13 (16%) vs n = 2 (2%), P = 0.006], and time to second-stage alloplastic reconstruction increased (230 ± 102 vs 325 ± 224 days, P = 0.044) post-COVID. Conclusions Swift adoption of evidence driven protocols has resulted in comparable wait times for breast cancer ablative procedures. However, utilization of autologous techniques and wait times to second-stage reconstructions have increased.
Développement d'une méthode de géolocalisation à l'intérieur de bâtiments par classification des fingerprints GSM et fusion de données de capteurs embarqués

L’objet de cette these est l’etude de la localisation et de la navigation a l’interieur de bâtiments a l’aide des signaux disponibles dans les systemes mobiles cellulaires et, en particulier, les signaux GSM.Le systeme GPS est aujourd’hui couramment utilise en exterieur pour determiner la position d’un objet, mais les signaux GPS ne sont pas adaptes a la localisation en interieurIci, la localisation en interieur est obtenue a partir de la technique des «empreintes» de puissance des signaux recus sur les canaux utilises par les reseaux GSM. Elle est realisee a l’echelle de la piece. Une classification est effectuee a partir de machines a vecteurs supports et les descripteurs utilises sont les puissances de toutes les porteuses GSM. D’autres capteurs physiques disponibles dans les telephones portables fournissent des informations utiles pour determiner la position ou le deplacement de l’utilisateur. Celles-ci, ainsi que la cartographie de l’environnement, sont associees aux resultats obtenus a partir des «empreintes» GSM au sein de filtres particulaires afin d’obtenir une localisation plus precise, et sous forme de coordonnees continues.Les resultats obtenus montrent que l’utilisation des seules empreintes GSM permet de determiner la piece correcte dans 94% des cas sur une duree courte et que les performances restent stables pendant plusieurs mois, de l’ordre de 80%, si les donnees d’apprentissage sont enregistrees sur quelques jours. L’association de la cartographie du lieu et des informations issues des autres capteurs aux donnees de classification permettent d’obtenir les coordonnees de la trajectoire du systeme mobile avec une bonne precision et une bonne fiabilite.
EPS Mid-Career Award 2006: Understanding anterograde amnesia: Disconnections and hidden lesions

Three emerging strands of evidence are helping to resolve the causes of the anterograde amnesia associated with damage to the diencephalon. First, new anatomical studies have refined our understanding of the links between diencephalic and temporal brain regions associated with amnesia. These studies direct attention to the limited numbers of routes linking the two regions. Second, neuropsychological studies of patients with colloid cysts confirm the importance of at least one of these routes, the fornix, for episodic memory. By combining these anatomical and neuropsychological data strong evidence emerges for the view that damage to hippocampal—mammillary body—anterior thalamic interactions is sufficient to induce amnesia. A third development is the possibility that the retrosplenial cortex provides an integrating link in this functional system. Furthermore, recent evidence indicates that the retrosplenial cortex may suffer “covert” pathology (i.e., it is functionally lesioned) following damage to the anterior thalamic nuclei or hippocampus. This shared indirect “lesion” effect on the retrosplenial cortex not only broadens our concept of the neural basis of amnesia but may also help to explain the many similarities between temporal lobe and diencephalic amnesia.
Deciphering mechanisms of blaNDM gene transmission between human and animals: a genomics study of bacterial isolates from various sources in China, 2015 to 2017

Background In China, the blaNDM gene has been recovered from human bacterial isolates since 2011. After 2014, detections of this gene in animal and food bacterial isolates have increasingly been reported. Aim We aimed to understand how blaNDM-bearing bacteria could spread between humans, animals, and animal-derived food. Methods A total of 288 non-duplicate Escherichia coli strains, including 130 blaNDM-carrying and 158 blaNDM-negative strains were collected from clinical (humans), food-producing animals (pigs) and food (retail pork) sources between 2015 and 2017. The strains were whole genome sequenced. Core-genome-multilocus-sequence-typing was conducted. To investigate if sequence types (STs) found in human, animal or food samples could have a prior origin in a clinical, animal or food-borne animal reservoir, discriminant analysis of principal components (DAPC) was used. Plasmids bearing blaNDM were characterised. Results The 130 blaNDM-carrying E. coli strains comprised a total of 60 STs, with ST167 (10/51), ST77 (6/33) and ST48 (6/46) being most prevalent in clinical, animal and food sources, respectively. Some ST10 and ST167 strains were respectively found among all three sources sampled, suggesting they might enable transfer of blaNDM between sources. DAPC analysis indicated possible transmissions of ST167 from humans to animals and ST10 from animals to human. In 114 of 130 blaNDM-carrying isolates, blaNDM was located on an IncX3 plasmid. Conclusion This study in a Chinese context suggests that cross-species transmission of certain STs of E. coli harbouring blaNDM on mobile elements, may facilitate the spread of carbapenem-resistant Enterobacteriaceae. Stringent monitoring of blaNDM-bearing E. coli in ecosystems is important.
WORKING PAPER SERIES 2

the results of the CNB’s research projects as well as the other research activities of both the staff of the CNB and collaborating outside contributors, including invited speakers. The Series aims to present original research contributions relevant to central banks. It is refereed internationally. The referee process is managed by the CNB Research Department. The working papers are circulated to stimulate discussion. The views expressed are those of the authors and do not necessarily reflect the official views of the CNB.
Maternal postnatal depression and offspring depression at age 24 years in a UK-birth cohort: the mediating role of maternal nurturing behaviours concerning feeding, crying and sleeping [version 1; peer review: awaiting peer review]

Background: Maternal postnatal depression (PND) is a risk factor for offspring depression in adulthood. However, few longitudinal studies have examined the role of maternal nurturing parenting behaviours in the association between maternal PND and offspring depression in adulthood. Methods: We examined pathways from maternal PND measured using self-reported Edinburgh Postnatal Depression Scale at 8 weeks to offspring ICD-10 depression diagnosed using the Clinical Interview Schedule-Revised computerised assessment at 24 years through maternal-reported nurturing behaviours concerning feeding, sleeping and crying measured from pregnancy to age 3 years 6 months in 5,881 members of the UK-based birth cohort study, the Avon Longitudinal Study of Parents and Children. Results: The fully adjusted model revealed an indirect effect from PND to adult offspring depression through the combination of all parenting factors (probit regression coefficient [B]=0.038, 95% confidence interval [CI] 0.005, 0.071); however, there was no evidence Open Peer Review Reviewer Status AWAITING PEER REVIEW Any reports and responses or comments on the article can be found at the end of the article. Page 1 of 15 Wellcome Open Research 2021, 6:187 Last updated: 22 JUL 2021
Connectome architecture shapes large-scale cortical alterations in schizophrenia: a worldwide ENIGMA study

While schizophrenia is considered a prototypical network disorder characterized by widespread brain-morphological alterations, it still remains unclear whether distributed structural alterations robustly reflect underlying network layout. Here, we tested whether large-scale structural alterations in schizophrenia relate to normative structural and functional connectome architecture, and systematically evaluated robustness and generalizability of these network-level alterations. Leveraging anatomical MRI scans from 2,439 adults with schizophrenia and 2,867 healthy controls from 26 ENIGMA sites and normative data from the Human Connectome Project (n=207), we evaluated structural alterations of schizophrenia against two network susceptibility models: i) hub vulnerability, which examines associations between regional network centrality and magnitude of disease-related alterations; ii) epicenter mapping, which identify regions whose typical connectivity profile most closely resembles the disease-related morphological alterations. To assess generalizability and specificity, we contextualized the influence of site, disease stages, and individual clinical factors and compared network associations of schizophrenia with that found in affective disorders. Schizophrenia-related structural alterations co-localized with interconnected functional and structural hubs and harbored temporo-paralimbic and frontal epicenters. Findings were robust across sites and related to individual symptom profiles. We observed localized unique epicenters for first-episode psychosis and early stages, and transmodal epicenters that were shared across first-episode to chronic stages. Moreover, transdiagnostic comparisons revealed overlapping epicenters in schizophrenia and bipolar, but not major depressive disorder, yielding insights in pathophysiological continuity within the schizophrenia-bipolar-spectrum. In sum, cortical alterations over the course of schizophrenia robustly follow brain network architecture, emphasizing marked hub susceptibility and temporo-frontal epicenters at both the level of the group and the individual. Subtle variations of epicenters across disease stages suggest interacting pathological processes, while associations with patient-specific symptoms support additional inter-individual variability of hub vulnerability and epicenters in schizophrenia. Our work contributes to recognizing potentially common pathways to better understand macroscale structural alterations, and inter-individual variability in schizophrenia.
Cumulative Incidence and Risk Factors for Severe COVID-19 in French People with Cystic Fibrosis

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are closely monitored in people with cystic fibrosis (pwCF), with a special emphasis on severe cases. Previous studies used hospitalization rates as proxy for severity. Methods We evaluated data from coronavirus disease 2019 (COVID-19) cases diagnosed in French pwCF followed in one of the 47 French CF center over the first year of the pandemic. Objective criteria were applied for defining severity (e.g., respiratory failure and/or death). Data were compared to those from all French pwCF using the French CF Registry. Results As of April 30, 2021, 223 pwCF were diagnosed with COVID-19, with higher risks in adults (≥18 years, odds ratio [OR] = 2.52, 95% confidence interval [CI] = 1.82-3.48) and post-transplant individuals (OR = 2.68, 95% CI = 1.98-3.63). Sixty (26.9%) patients were hospitalized, with an increased risk in post-transplant individuals (OR = 4.74, 95% CI = 2.49-9.02). In 34 (15%) cases, COVID-19 was considered severe; 28/60 (46.7%) hospitalizations occurred in patients without objective criteria of severity. Severe cases occurred mostly in adults (85.3%) and post-transplant pwCF (61.8%, OR = 6.02, 95% CI = 2.77-13.06). In non-transplanted pwCF, risk factors for severity included low lung function (median ppFEV1 54.6% vs. 75.1%, OR = 1.04, 95% CI = 1.01-1.08) and CF-associated diabetes (OR = 3.26, 95% CI = 1.02-10.4). While most cases recovered without sequelae (n = 204, 91.5%), 16 (13%) were followed for possible sequelae, and three post-transplant females died. Conclusions Severe COVID-19 cases occurred infrequently during the first year of the pandemic in French pwCF. Non-transplanted adults with severe respiratory disease or diabetes and post-transplant individuals were at risk for severe COVID-19. Thus, specific preventive measures should be proposed.
Aerosol lidar observations for wind power meteorology

With the advancement in wind power meteorology and the growth of the modern wind turbines, the need to measure and estimate meteorological parameters other than wind speed and direction has become more and more important. The effect on the wind profile, e.g. of the boundary-layer height h, has not (yet) been fully understood and investigated in the wind energy community, nor in the meteorological one. h has a significant effect on the wind profile at heights above 100 m and even lower when the atmospheric conditions are stable, e.g. during nighttime when low-level jets evolve. These heights are already being exploited by large wind turbines.