dataesr/scientific-paragraphs-categorization huggingface dataset:
Upon contact with the authors or at guichet. industriel. drc@aphp. fr an institutional data transfer agreement may be established, and data shared if the aims of data use are covered by ethical approval and patient consent. handle the alerts, offering solutions such as medical advice, referral to their GP, or hospitalization  [3]. All pregnant women with a positive COVID-19 PCR during pregnancy, registered in Covidom as an outpatient between March 10th, 2020 and November 30th, 2020, were included in this study if they completed the Covidom medical questionnaire and agreed to participate. Patient characteristics, including medical conditions prior to and during pregnancy, active smoking, and symptoms at inclusion, were collected through a self-reported medical questionnaire. Data on delivery, postpartum, and neonatal outcomes were collected retrospectively through phone contact with a standardized questionnaire.
Results In the Covidom cohort, 1613 pregnant women were included as outpatients, out of which 714 (44. 3%) agreed to participate and provided data on their delivery and neonate. The median age of participants was 32. 0 [IQR 29. 0-35. 0] years old, with a median BMI of 23. 8 [IQR 21. 3-27. 0]. The main comorbidity reported was smoking (7. 4%), while gestational diabetes mellitus was present in 15. 4% of cases. The most common symptoms were fatigue (45. 7%), cough (40. 3%), and headache (25. 7%), as well as anosmia (28. 4%), and agueusia (32. 3%). Table  1  presents the demographic and baseline characteristics of the participants. Adverse fetal outcomes occurred in 64 (9%) cases, which included 38 (5%) preterm births, 33 (5%) low birthweights, and 6 (1%) stillbirths. Three premature deaths were observed at 15 (due to cardiac arrest), 22 (due to antiphospholipid syndrome with multiple infarctions), and 24 (unexplained) weeks of gestation, as well as one case of aspiration pneumonia from amniotic fluid at birth, one case of placental abruption, and one case of severe intrauterine growth restriction.
Acknowledgments The authors would like to thank  Amira BOUROKBA ,  Estelle HORISZNY ,  Mouna LABIB , and  Celine MECHEMACHE  for their help during the follow-up of the pregnant patients included in the COVIDOM solution. AP-HP /   Universities / Inserm COVID -19  research collaboration members. Writing committee:  Dinh Aure  ´lien ( Infectious Disease Department, University Hospital Raymond-Poincare, Assistance Publique-Hopitaux de Paris, Garches, Paris Saclay University, Garches ,.
BAT Temperature Measurements iBAT skin temperature was measured using infrared technology (camera FLIR E95 24 • , Teledyne FLIR Systems, Wilsonville, OR, USA) and analyzed with its specific software, FLIR TOOLS Thermography Software. Videos were recorded on the first and the last day of treatment. As previously described, skin surrounding iBAT was shaved under isoflurane (IsoFlo ® , Zoetis, London, UK) anesthesia 2 days before recordings  [27]. The increment of iBAT temperature was calculated as the difference of temperature from last day to first day of treatment.
Data sources and analysis Retrospective cohort studies were performed in two datasets. The UK CF Registry was first established in 1995 and includes anonymised longitudinal clinical and demographic data on over 12 000 PwCF, with >99% coverage of the UK CF population. Cardiac outcomes were first included in 2016. Data is recorded annually by CF clinical teams. TriNetX is a healthcare data network with real-time access to anonymised electronic healthcare records from over 70 healthcare organisations internationally but predominantly within North America. Data within the platform include demographics, International Classification of Diseases, 10th Revision (ICD-10) disease codes, procedures (ICD-10 Procedure Coding system), medication details (rxNorm/Veterans affairs National Formulary codes) and laboratory measurements (coded as Logical Observation Identifiers Names and Codes (LOINC)).
Study population Adults (⩾18 years old in 2016) with CF were included for analysis in both datasets. In the UK CF Registry, only those with annual review data in 2016 were included. In the UK CF Registry, data were available from 2016 (when cardiac outcomes were first recorded) with 5 years of data up to the most recent data release from 2020. In TriNetX, all adults with a hospital (inpatient or outpatient) encounter in 2016 were included for analysis, with outcomes censored at 5 years. Throughout, comorbidities and outcomes were defined by presence of a single ICD-10 code, except for CF itself (given the validity and generalisability of ICD-10 code-based research in CF is unclear)  [10]. To optimise a CF definition we combined hospital encounters and frequency of CF (ICD-10 E84) codes into a cohort definition to more precisely identify PwCF.
Statistical analysis UK CF Registry analyses were conducted in RStudio and TriNetX analyses were conducted within the TriNetX platform itself. All TriNetX analyses were conducted on 30 April 2023. Throughout, univariate analyses consisted of Chi-squared tests for categorical variables and independent samples t-tests for continuous variables. Missing data were only observed for LOINC variables, e. g. BMI (19. 8% missing). Given these values were only used in a descriptive context, no imputations for missing data were performed. In the TriNetX platform, comparisons were made between PwCF against the general population and active disease controls (SLE, rheumatoid arthritis and HIV). Standardised mean differences were used to show the distribution of demographic and clinical data among the groups and calculated as the difference in the means or proportions of a particular variable divided by the pooled estimate of standardised differences for that variable.
Results Data were available for 5649 adult PwCF in the UK CF Registry (mean±SD age 32. 1±11. 0 years) and 6265 adult PwCF in TriNetX (mean±SD age 27. 8±10. 1 years). Baseline characteristics are presented in table  1. There were similarities between datasets: obesity was present in 309 (5. 5%) and 338 (5. 4%) of the cohort in the UK CF Registry and TriNetX, respectively, mean BMI was 23. 1 and 24. 4 kg•m -2 , respectively, but.
MACE incidence and prevalence At index within the TriNetX dataset there was a baseline prevalence for MACE in 151 (2. 5%), annual incidence ranged from 0. 8% to 2. 6% and by 2020, MACE had occurred in 433 out of 6265 (6. 9%). In the same study period, MACE was recorded for 89 out of 5649 (1. 6%) in the UK CF Registry. Thus, annualised incidence was 1. 3% and 0. 3% for TriNetX and the UK CF Registry, respectively.
Discussion We used two independent datasets to investigate cardiac disease in CF. Our main findings are that PwCF have a significantly higher risk of cardiac disease than matched counterparts in the general population. Furthermore, cardiac risk in PwCF was equivalent to or higher than other chronic inflammatory diseases considered "high risk" for cardiac disease. Until recently, cardiac disease has been considered rare in CF. Early CF autopsy studies found normal coronary arteries in children who had died from CF and, more recently, pre-lung transplant angiograms were reported to be normal in 14 adults with CF  [14, 15]. However, these findings are unlikely to be generalisable to an increasingly older comorbid CF population where increased arterial stiffness and endothelial dysfunction, well-validated predictors of future cardiac disease, have been reported  [16, 17].
The results from this study, conducted across two datasets before the widespread availability of CFTR modulators, suggest annualised MACE incidence ranges from 0. 3% to 1. 3%. Importantly, our findings demonstrated that PwCF are already at higher risk of MACE than the general population and suggest urgent work is needed to understand how this risk changes with CFTR modulator therapy. Cardiac risk is usually determined by the presence of traditional risk factors, some of which, including diabetes and renal disease, are well appreciated in CF  [20, 21]. Hypertension is a key risk factor for cardiac disease in the general population, but PwCF are thought to generally exhibit lower blood pressure due to salt losses related to CFTR dysfunction  [22]. Accordingly, we found hypertension had a prevalence of 2-11% in adults with CF across datasets, much lower than the prevalence of ∼25% in the UK adult population  [23].
Hypertension was more prevalent in those with MACE, a consistent finding in both the UK CF Registry and TriNetX dataset, reinforcing the importance of hypertension as a risk factor for cardiac disease when present in CF. Similarly, diabetes is an important risk factor for cardiac disease and we found over half of people experiencing MACE had CF-related diabetes. Diabetes prevalence appeared variable between datasets, with 35. 3% prevalence in the UK CF Registry but 26. 7% in the TriNetX data. Given the poor prognostic outcomes of CF-related diabetes, early identification is a keystone of CF clinical care and as such is likely captured well within CF-specific disease registries like the UK CF Registry  [24]. Conversely, CF-related diabetes does not have a specific ICD-10 code and therefore may be prone to under-reporting or misclassification in non-disease-specific, ICD-10-dependent datasets such as TriNetX.
All warrant further investigation given they are potentially modifiable  [34] [35] [36]. Similarly, all may be modified by highly effective CFTR modulator therapy, and a key avenue of future research is understanding the drivers of cardiac risk in PwCF and the net effect of the complex interplay between the improved CF-specific disease markers and increased exposures to cardiac risk factors as survival increases. Limitations to this study include the lack of independent adjudication of MACE outcomes and the retrospective nature of the studies. UK CF Registry data are well validated for key CF outcomes; however, the data completeness, quality or standardisation for rarer events, e. g. chronic kidney disease and cardiac disease, is not known and under-reporting may explain some differences in incidence between datasets.
Similarly, the study cohort may have had MACE events outside of the TriNetX network which would not be captured. TriNetX is a predominantly North American dataset and disparities between healthcare systems may also limit the generalisability of results. Similarly, TriNetX relies on real-time data collection from healthcare organisations' electronic healthcare records and some conditions or outcomes may also be under-reported/misclassified and aggregates can vary slightly over time. Due to limitations of data availability, we are unable to compare the risk of MACE between PwCF in the UK CF Registry and the general population in the UK. In the latter, the QResearch database (www. qresearch. org) suggests a crude incidence for cardiovascular disease of ∼1. 4-2. 8 per 1000 person-years for ages 35-44 years (the lowest reported age group).
The average age in the UK CF Registry population was lower, yet the crude rate here was higher, ∼3. 2 per 1000 person-years  [37]. Importantly, QResearch uses a much broader definition of cardiovascular disease, including non-acute events, e. g. stable angina, perhaps artificially narrowing the difference, but supporting our findings of the increased cardiovascular disease risk in PwCF. We included 2016-2020 data as the most up-to-date data available from the UK CF Registry, but this also includes data captured during the coronavirus disease 2019 pandemic, which had impacts on wider healthcare utilisation and cardiac disease diagnoses which may act as a potential confounder. ICD code disease classification can vary by condition and demographics, and limitations to using solely ICD codes for identification of CF have previously been reported.
We minimised this by more strictly defining our CF cohort such that the cohort more appropriately resembled well-validated CF populations. Furthermore, consistent findings across two datasets, including the non-ICD-code-dependent UK CF Registry, helps to reinforce the validity of our findings. We tried to minimise variation in outcome classification by standardising outcomes to those clearly reported/defined in all cohorts, but residual bias may still exist. For example, we have limited data on key cardiac risk factors such as physical activity which may differ between groups or populations. The cohorts are also inherently heterogenous in terms of patient inclusion and direct comparisons between healthcare systems/nations are therefore not possible. Instead, the datasets included in this study collectively provide insight into cardiac disease in CF from a spectrum of healthcare settings and serve as a useful benchmark in the understanding and estimation of cardiac disease risk in CF.
The cat virus sequence was directly related to virus sequences identified in the same area in December 2022  (Figure). Furthermore, the virus isolated from the neighboring duck farm (Figure) had only 2 nt differences (out of 13,507 total nts) compared with the cat virus, resulting in an E627K mutation in polymerase basic protein 2 and E26G mutation in nonstructural protein 2 in the cat virus. The E627K mutation has been described as a major marker of influenza virus adaptation to mammalian hosts  (1). The E26G mutation has a possible role in virus adaptation to temperature changes  (2). Since September 2021, a total of 90 sequences of HPAI H5N1 clade 2. 3. 4. 4b viruses detected in mammals have been available in the GISAID EpiFlu database (https:// www. gisaid. org), 20 of which have the E627K mutation, most probably indicating a rapid selection of this mutation in mammalian hosts (3).
Figure. Figure. Phylogenetic analysis of highly pathogenic avian influenza A(H5N1) clade 2. 3. 4. 4b virus detected in domestic cat, France, 2022. Tree was created by using MEGA 7 software (https://megasoftware. net) and the neighbor-joining method with 1,000 bootstrap replicates for complete concatenated HPAI H5N1 virus segments. All sequences belong to the A/duck/Saratov/29-02V/2021-like genotype. Red solid circle indicates virus sequence from cat; black solid circle indicates sequence from a nearby duck farm. Both sequences are available in the GISAID database (https://www. gisaid. org) under accession nos. EPI_ISL_16395206 (cat) and EPI_ISL_16740903 (duck). Red bracket indicates closely related sequences detected during the same period and area in France from domestic bird farms. Scale bar indicates nucleotide substitutions per site.
Ultra-low temperature cryoablation (ULTC) using near-critical nitrogen (À196 o C) has been shown to produce durable, contiguous, transmural lesions in ventricles of animal models. This report summarizes acute experience with ULTC in the first-ever 13 patients with recurrent monomorphic ventricular tachycardias (VTs) of both ischemic cardiomyopathy and nonischemic etiologies enrolled in the CryoCure-VT (Cryoablation for Monomorphic Ventricular Tachycardia; NCT04893317) clinical trial. After an average of 9. 6 AE 4. 6 endocardial ULTC lesions per patient, no clinical ventricular tachycardias were inducible in 91% of patients. Two procedure-related serious adverse events recorded in 2 patients resolved post-procedurally without clinical sequelae. Further investigation of both acute and chronic outcomes is war-.
to RF. Recently, a new ultra-low temperature cryoablation (ULTC) technology using near-critical nitrogen at temperature close to T b ¼ À196 o C has been described for ablation of atrial flutter and atrial fibrillation with excellent results. 8, 9 In preclinical studies, ULTC has been shown to produce durable, contiguous, transmural lesions in ventricular tissue controlled by the duration of the freeze, including over the ischemic scar region. 10 Lesions of such depth and commensurate surface dimensions have the potential to interrupt a majority of the re-entrant VT circuits from the endocardial surface alone, thus simplifying ablation procedures and increasing acute and chronic effectiveness of the treatment. METHODSCryocure-VT (NCT04893317) is a prospective, singlearm, multicenter clinical study, evaluating the safety and performance of ULTC in patients with recurring monomorphic VTs due to cardiomyopathy of both ischemic and nonischemic etiologies.
g. 2mg/kg prednisolone or methylprednisolone)  (2). In case the treatment with steroids is not successful, the term steroid-refractory aGVHD (SR-aGVHD) is used. There is no published high-quality data from larger mulitcenter patient populations on the incidence and outcome of SR-aGVHD. However, approximatly one third of patients with aGVHD treated with steriods become refractory and have increased non-relapse mortality  (3, 4). Patients with SR-aGVHD have typicallly a high mortality despite effective novel drugs, such as ruxolitinib, and there is urgent medical need to develop new strategies  (5). Extracorporal photopheresis (ECP) has been successfully used for treatment of SR-aGVHD  (6) (7) (8). During ECP autologous mononuclear peripheral blood cells are collected by apheresis and exposed to ultraviolet A light as well as 8methoxypsoralen.
Methods This is a retrospective multicentre analysis using the data set of the EBMT registry. The EBMT is a voluntary working group of more than 600 transplant centres that are required to report regular follow up on all consecutive stem cell transplantations. Audits are routinely performed to determine the accuracy of the data. The study was planned and approved by the Transplant Complications Working Party of the EBMT. All patients gave their written informed consent to use their personal information for research purposes. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice guidelines. We first identified all patients in the registry who had a grade II-IV aGvHD and invited these 227 centers to report if their patients had received ECP/Ruxo treatment for SR aGvHD.
We then asked centers if they were willing to participate in this study by completing a data form (Med-C, Supplementary Data) with very detailed information on GVHD grading, -therapy, -dosing, -response and complications for each included patient. 31 centers responded positively (14%) and we included all patients receiving alloSCT between 1/2017-7/2019 and treated with ECP or Ruxolitinib for SR-aGVHD grades II-IV from these centers. Inclusion criteria were: 1. AlloSCT recipients in the EBMT database who developed SR-aGVHD after first alloSCT on or after Jan 1st, 2017 but before July 1st, 2019. 2. Patients who initiated treatment with ECP or ruxolitinib within 60 days of onset of SR-aGvHD. 3. Overall grade: II-IV aGVHD only at time of treatment initiation of either ECP or ruxolitinib. 4. Patients who are ≥ 18 years at time of treatment initiation.
Exclusion criteria were: 1. Patients on a clinical trial for GVHD in the retrospective period. 2. Patients who received ECP or ruxolitinib before the onset of steroid-refractory acute GvHD. Data collected included recipient and donor characteristics (age, sex, cytomegalovirus serostatus and Karnofsky performance status score), diagnosis and status at transplant, interval from diagnosis to transplant, and transplant-related factors, including conditioning regimen, use of anti-thymocyte globulin or Alemtuzumab for pretransplant in vivo T-cell depletion, stem cell source, ex-vivo T-cell depletion and post-transplant GVHD prophylaxis. Grading of acute GvHD was performed using established criteria  (9). For the purpose of this study, all necessary data were collected according to the EBMT guidelines, using the EBMT Minimum Essential Data forms as well as Med-C forms (see Supplementary Data).
Patient-and transplantation characteristics We identified 53 and 40 patients with grades II-IV SR-aGVHD who were treated with ECP or ruxolitinib, respectively between January 1st, 2017 and July 1st, 2019 in the EBMT database. Major patient-disease-and transplant characteristics were evenly distributed between the groups (Table  1 ). Patients were transplanted for Acute Leukemia (53. 8%), MDS/MPN (25. 8%), Chronic Leukemia (11. 8%) or Lymphoma (8. 6%). Stem cell donors were unrelated (65. 4%), identical siblings (18. 3%) or haploidentical (18. 3%). Patient median age was 52. 5 years, with a majority of female recipients (52. 7%) and male donors (65. 6%). Anti-T-cell globulin (ATG, also termed anti-thymocyte globulin) was given in 39. 6%. GVHD.
Acknowledgments OP acknowledges the support of  JoséCarreras Leukämie-Stiftung  ( 3R/2019 ,  23R/2021 ),  Deutsche Krebshilfe  ( 70113519 ),  Deutsche Forschungsgemeinschaft  ( PE 1450/7-1 ,  PE 1450/9-1 ,  PE 1450/10-1 ) and  Stiftung CharitéBIH  ( BIH_PRO_549 ,  Focus Group Vascular Biomedicine).
3] [104] [105]  Similar correlations were found using other approaches for calculating the HLA-MML. 6] [107]  In general, the degree of class II eplet-MML exhibits a linear relationship with the risk of developing a primary alloimmune response. 103 In the context of biomarker-guided enrichment approach for clinical trials of drug development, thresholds are required to provide strata of risk. An important caveat to keep in mind is that while empiric data from retrospective diverse cohorts support the notion that low HLA-MMLs tolerate less immunosuppression without developing alloimmunity, emerging data demonstrate empirically unsupported assumptions used by the HLAMatchmaker software. 108 Further studies demonstrated that the immunogenicity of certain mismatches can be higher than others,  [109] [110] [111]  thus questioning the rigor in assigning the same value to all mismatches.
| Study design Data were obtained from the CANcer TOxicities (CANTO) cohort. This is a French prospective cohort that includes women diagnosed with BC stage I-III. Cohort participants were recruited at the moment of diagnosis across Metropolitan France between 2012 and 2018. 19 As shown in Figure  1 , data were collected at diagnosis, and 1, 2 and 3 years after diagnosis (T1, T2 and T3 respectively) through self-reported questionnaires, patient-reported outcomes and during a clinical exam.
Abbreviations TSP Transsulfuration pathway PLP Pyridoxal 5′-phosphate CBS Cystathionine β-synthase CSE Cystathionine γ-lyase CST Cystathionine D-pen D-penicillamine PDB Protein data bank RMSD Root mean square deviation RMSF Root mean square fluctuation Hydrogen sulfide (H 2 S) is a gaseous signaling molecule that participates in various signaling functions in the vascular and neuronal systems, and in the regulation of the inflammatory response. It also contributes to the adaptive response and acts as a pleiotropic pro-resolving gaseous mediator in inflammatory diseases  [1] [2] [3] [4] [5] [6]. In mammals, endogenous biogenesis of H 2 S is carried out by the transsulfuration pathway (TSP), constituted of two pyridoxal 5′-phosphate (PLP)-dependent enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE), and by the mitochondrial catabolism of cysteine (Cys) that involves cysteine aminotransferase (CAT) in combination with 3-mercaptopyruvate sulfur transferase (3-MST).
Last, D-pen can lead to the formation of hydrogen peroxide (H 2 O 2 ) through the oxidase activity of certain hemoproteins  35. H 2 O 2 being involved in the regulation of rodent coronary artery blood flow  48  , the effect produced by H 2 O 2 thus generated could be added to the points already developed to partly explain the vasodilatation variation observed by Brancaleone et al. in the presence of D-pen. Next the K i of D-pen for CSE was assessed in the H 2 S assay in the presence of varying concentration of Cys. Surprisingly, Lineweaver-Burk analysis of the data suggests that D-pen followed a mixed inhibition mechanism (Fig. S3 ) to impede H 2 S biogenesis, since the plots intersect outside the x-and y-axes (Fig. S4A ). As a result, Michaelis-Menten plots were individually fitted with Eq.