dataesr/scientific-paragraphs-categorization huggingface dataset:
(E and F) Expression of USH2A (exon 13) compared with GUSB. USH2A expression was relatively low in all samples; however, lowest in samples not treated with cycloheximide (CHX). effects on splicing of branchpoint variants, missense variants, synonymous variants, and non-canonical splice site variants will increase diagnostic yield in USH2A screening, and in genetic testing for hereditary disorders in general. Re-evaluation of targeted sequencing and WES data of currently still unsolved cases with a particular focus on splice-modulating properties is therefore recommended. The genetic diagnosis for 13 subjects could be completed after performing a minigene splice assay for variants that were selected based on our criteria for SpliceAI. Eight of these variants displayed an effect on all detected transcripts in the corresponding minigene splice assays (Figure  S1  and Table  S7 ).
To our knowledge, the c. 5573-19A>G variant, reported previously as VUS in both LOVD and ClinVar, is one of the first suggested branchpoint variants within USH2A resulting in a pathogenic effect. 35 The identification of an additional potential branchpoint variant c. 14583-26A>G (p. [¼,Tyr4862Alafs*22]) stresses the importance of including the evaluation of branchpoint variants in genetic screening efforts. Five variants that were tested in a minigene splice assay showed residual conventionally spliced transcripts along with a deleterious effect on splicing and they were therefore classified as VUS. Recent studies have been published on specificity and sensitivity of splice prediction tools. 36, 37 In a study by Rowlands et al. ,  36  SpliceAI (suggested D score R0. 2) outperformed other splice prediction tools, although false positive and false negative calls were observed.
Acknowledgments The work of J. R. was funded by the  Velux Stiftung  (Project number:  1129  to H. K. , S. R. , F. P. M. C. , and E. v. W. ). The work of S. R. is funded by the  Foundation Fighting Blindness-career development award  ( CD-GE-0621-0809-RAD  to S. R. ). The research was also supported by the  Algemene Nederlandse Vereniging ter voorkoming van Blindheid ,  Oogfonds ,  Landelijke Stichting voor Blinden en Slechtzienden ,  Rotterdamse Stichting Blindenbelangen, Stichting Blindenhulp, Stichting tot Verbetering van het Lot der Blinden , and  Stichting Blinden-Penning  (to S. R. and F. P. M. C. ). The work of S. E. d. B. was funded by the  European Union 's  Horizon 2020 Research and Innovation Program  under the  EJP RD COFUND-EJP N 825575  (to F. P. M. C. and S. R. ). The work of P.
Data and code availability Data are available upon request. Pathogenic variant data are uploaded to the Leiden Open (source) Variation Database (LOVD: https://databases. lovd. nl/shared/genes/USH2A). All other whole genome sequencing data are subject to controlled access because these may compromise research participant privacy. These data may become available upon a data transfer agreement approved by the local ethics committee and can be obtained from corresponding author S. R. upon reasonable request.
Patients A total of 176 KTRs receiving belatacept as a conversion protocol at two French transplant centers (Necker University Hospital and Rouen University Hospital) were converted to abatacept during the COVID-19 pandemic (Figure  1 ). All patients were 18 or older, had received either a living or a deceased donor kidney transplant, and had received no prior or concurrent non-renal solid organ transplant. Patient characteristics and biological data were collected from electronic medical records. According to French law (loi Jardé), because this was an anonymous retrospective study, institutional review board approval was not required.
Statistical Analysis Continuous variables were summarized in the form of means with SDs or medians with IQRs, and they were compared using Mann-Whitney or t-tests, as appropriate. Categorical variables were summarized in the form of numbers with proportions, and they were compared using Fisher's exact test. We used STATA (version 14, Data Analysis and Statistical Software) and R (version 3. 2. 1; R Foundation for Statistical Computing) to carry out descriptive analyses. A p-value <0. 05 was considered significant.
The data presented here on the use of subcutaneous injection of abatacept in a large cohort could be very useful for patients with CNI toxicity or intolerance and in need of conversion to belatacept but with poor vascular access, like many end-stage renal disease patients. This approach could also represent a solution in cases of belatacept shortage. Costimulation blockade with abatacept could potentially have a logistical advantage over belatacept in kidney transplant recipients. Nevertheless, our niche experience over 3 months does not allow us to make definitive assertions as to the potential benefits mentioned above. Our work has several limitations. The short duration of our follow-up period (3 months) prevents us from drawing a firm conclusion on the risks of rejection and infection in patients treated with abatacept as a maintenance therapy.
Nevertheless, the median half-life of belatacept is reported to be 8 days (range: 3. 1-11. 9)  [30] , and the very low incidence of TCMR during the weeks following abatacept initiation can be taken into account and is quite reassuring. Because of the ethical issues related to data scarcity on abatacept safety, and the possibility of in-home belatacept infusion, we could not accept the risk of continuing to pursue abatacept therapy once the first wave of SARS-CoV-2 had ended. The absence of a control group receiving ongoing belatacept injection is also problematic. However, our main goal was to avoid frequent hospital visits by immunocompromised KTRs during the initial period of the SARS-CoV-2 pandemic. Under these conditions, we chose to treat as many patients as possible with abatacept. A clinical trial NCT04955366 (https:// clinicaltrials.
Inventory Analysis Generic data and specific data were combined to obtain inventories, as described in Table  1. For System 1, specific data from the company were used to describe the type and quantities of ingredients, quantities of energy, and type of packaging used for the production of the additive (Table  2 ). Background data related to the production of ingredients and packaging, the transporting vehicles and infrastructures, and the production and delivery of the energy used were obtained from AGRIBALYSE v3. 0. 1 (2020) and Ecoinvent v3. 6 (2020). When it came to lemon extract, this ingredient was produced in Spain. However, due to the lack of specific data to model the lemon extraction process, data for tomato paste (AGRYBALYSE V3. 0) were adapted with a specific transformation yield of 6%.
For orange peels, Spanish oranges (Ecoinvent) were used instead of Moroccan oranges, since there were no specific data available. Additionally, transformation processes of the orange peel, including peeling and drying, were neglected. A ratio of juice to peel of 40% was applied to set the allocations, based on the AGRIBALYSE database and according to several studies found in literature  [13, 14]. Production at the Nor-Feed plant in France was modeled using specific data provided from 2019 (Table  3 ), considering a total production of 1,025,000 kg (CEFA included). Packaging of the finished product was modeled using specific data for one 25 kg bag of CEFA (Table  4 ). The distance of packaging transportation to the Nor-Feed plant was counted for 1450 km, while the distances of CEFA's ingredients delivery and final product distribution were estimated using Searates (https://www.
searates. com/fr/, accessed on 17 June 2020). Finally, all the data used for transports were calculated based on lorry, EURO5, and 16-32 tons (Ecoinvent 3. 8). Average end-of-life hypothesis in France: For the paper part: 70% recycled, 30% not recycled (of which 64% was incinerated with energy recovery, and 36% was buried) For the PE part: 100% not recycled (of which 64% was incinerated with energy recovery, and 36% was buried) Average end-of-life hypothesis in Thailand: For the paper part: 50% recycled, 50% not recycled (of which 6% was incinerated with energy recovery, and 94% was buried) For the PE part: 100% not recycled (of which 6% was incinerated with energy recovery, and 94% was buried) On the subject of system 2, AGRIBALYSE, a reference database of environmental impact indicators for agricultural products produced in France, was used as the reference for the comparison and adapted to represent performances obtained with the use of the additive using the MEANS InOut software, which implements recommended methodologies defined for the AGRIBALYSE program  [15].
This is mainly due to the fact that its principal raw material (lemon extract) is a co-product from juice industries. Thus, only 6% of the transformation process of citrus fruit was allocated to the lemon extract that was estimated according to the flow chart of lemon extract production. However, this estimate may constitute a bias on the environmental footprint of CEFA. The use of byproducts of the agro-industry is indeed only starting, as more and more interest is being drawn to this mass considered to be waste (and needed to be treated as such with associated environmental costs)  [13, 18]. Whilst many studies have recently been conducted on the potential bioactivities of such byproducts, the industrialization of their valorization is only at its debut, meaning that data on the allocation of resources to produce them from the overall resources required for the production of the main crop (here, lemon juice) are scarce.
Treatment was optimised or resumed in case of relapse in all groups. Participants, those assessing outcomes, and those analysing the data were not masked to group assignment. The coprimary endpoints were the relapse rate (superiority analysis) and time in remission over 2 years (non-inferiority analysis, non-inferiority margin 35 days). Analyses were done on an intention-to-treat basis. This study is registered with ClinicalTrials. gov, NCT02177071, and with EU Clinical Trials Register, EUDRACT 2014-002311-41. The trial was completed in April, 2021. Findings Between Nov 2, 2015, and April 24, 2019, 254 patients were screened. Of these, 211 were randomised and 207 were included in the final analysis (n=67 in the combination group, n=71 in the infliximab withdrawal group, and n=69 in the immunosuppressant withdrawal group).
Protocol deviations (eg, violations of inclusion or exclusion criteria or incorrect treatment or dose) were monitored at study entry and throughout the study. All protocol deviations were assessed in real time for their effect on data integrity and patient safety to determine whether the patient should continue in the study. The study duration was 104 weeks. Major changes in the protocol are explained in the appendix (p 1). Of these, a recalculation of the required sample size was made in November, 2018, following publication of the results of a Crohn's disease patient survey performed in France and in the USA, which provided new information on the acceptability to the patients of time spent with active disease to allow treatment de-escalation, in particular withdrawal of biologics or anti-metabolites, or both.
50 imputed datasets were generated with 20 iterations. Conditional imputations were realised using linear models and predictive mean matching. All reported p values are two-sided; a p value of less than 0•05 was considered statistically significant. Statistical analyses were performed with SAS (version 9. 4) and R (version 4. 1. 2) statistical software. This study is registered with ClinicalTrials. gov (NCT02177071) and with EU Clinical Trials Register (EUDRACT 2014-002311-41), under the name SPARE.
Another limitation is the relatively low number of events, reducing accuracy in determining risk factors associated with either relapse or treatment failure. We also acknowledge some missing data for biomarkers, particularly faecal calprotectin at baseline and end of study, and endoscopy at end of study. Finally, although infliximab trough levels and antiinfliximab antibodies were measured for secondary endpoints in the trial, they were not used for treatment optimisation. In conclusion, the results of the SPARE trial show that discontinuation of infliximab in patients on combination therapy is associated with an increase in the risk of relapse compared with patients continuing combination therapy and also with those switching to infliximab monotherapy. We were able to identify clinical characteristics of patients with high risk of relapse and failure.
92, p=0. 0313), respiratory failure (OR 0. 36, 95% CI 0. 14-0. 90, p=0. 0281), and aspiration pneumonia (OR 0. 37, 95% CI 0. 14-0. 99, p=0. 0486). Conclusions: Half of antibiotic prescriptions remain non-compliant with guidelines. Intensivists should daily reassess the bene t of using several or broad-spectrum antimicrobials and stop antibiotics that are no longer indicated. Developing consensus about treating speci c illnesses and using service protocols seem necessary to reduce errors. A daily ASP could also improve compliance in these error-prone situations. Trial registration: This trial was approved by Toulouse University Hospital, and is registered in its register of data study, number RnIPH2019-79, and with ClinicalTrials. gov, number NCT04642560. The date of rst trial registration in ClinicalTrials.
Study design, setting, and participants We conducted an observational, prospective, multicenter study in eight French Pediatric and Neonatal ICUs during six separate time periods between June, 2020, and May, 2021 (Appendix 1). Intensivists were the only prescribers. All participating ICUs had possible audit with infectious disease specialist by phone call and most had an antimicrobial stewardship program (ASP) organized in a once weekly multidisciplinary (intensivists, microbiologists, and pediatric infectious disease specialists) staff meeting with prospective audit and feedback (Table  1 ). We asked them about their local microbiological data for the years 2018 and 2019. This study was supported by the Groupe Francophone de Réanimation et d'Urgences Pédiatriques (GFRUP). All methods were performed in accordance with relevant guidelines and regulations.
According to the French ethic and regulatory law (public health code), this trial is cover by the reference methodology MR-004 of the French National Commission for Informatics and Liberties. It was approved by Toulouse University Hospital, and is registered in its register of data study, number RnIPH2019-79, and with ClinicalTrials. gov, number NCT04642560. The date of rst trial registration in ClinicalTrials. gov was 24/11/2020. antibiotic treatment for less than 24 hours for a suspected or proven community-acquired or nosocomial BI were assessed for eligibility. We called this episode " rst suspected or proven BI episode" to distinguish it from a possible BI recurrence occurring later. Exclusion criteria were: newborns < 72 hours old; neonates < 37 weeks postmenstrual age; age ≥ 18 years; children with antibiotic for prophylaxis; and children previously included in an interventional study in progress.
Data collection Data on patient characteristics and the rst suspected or proven BI episode (characteristics, organ dysfunction scores, antibiotic therapy, and concomitant therapeutics other than antibiotics) were prospectively daily collected by medical study site investigators so long as patient received antibiotics in hospital for the rst suspected or proven BI episode (ICU and general pediatric ward if antibiotic therapy was not completed in the ICU) (Appendix 1). D0 was the day of antibiotic therapy initiation. Additional data on the length of ICU and hospital stay, mortality, ambulatory antibiotic therapy (if present), and recurrence of BI occurring within 28 days following D0 were registered at hospital discharge. Antibiotics used for any other infections during the 28 days following D0 or for antibiotic prophylaxis were not taken into account.
To transform quantitative variables into classes when necessary, we determined the thresholds using the Youden's index. To determine the independent predictive factors of non-compliance, we then carried out a multivariate analysis by stepwise logistic regression after selecting the independent qualitative variables associated with the dependent variable with p < 0. 20. The association between variables was signi cant if p < 0. 05. Odds ratios (ORs) and 95% con dence intervals (CIs) were calculated for the signi cant variables. When one or more centers were signi cant in multivariate analysis, ORs were adjusted for center. All statistical analyses were performed using SAS software (version 9. 4,Cary,NC,USA).
Introduction: The yield per elution of a 68 Ge/ 68 Ga generator decreases during its lifespan. This affects the number of patients injected per elution or the injected dose per patient, thereby negatively affecting the cost of examinations and the quality of PET images due to increased image noise. We aimed to investigate whether AI-based PET denoising can offset this decrease in image quality parameters. Methods: All patients addressed to our PET unit for a 68 Ga-DOTATOC PET/CT from April 2020 to February 2021 were enrolled. Forty-four patients underwent their PET scans according to Protocol_FixedDose (150 MBq) and 32 according to Protocol_WeightDose (1. 5 MBq/kg). Protocol_WeightDose examinations were processed using the Subtle PET software (Protocol_WeightDose AI ). Liver and vascular SUV mean were recorded as well as SUVmax, SUVmean and metabolic tumour volume (MTV) of the most intense tumoural lesion and its background SUVmean.
To optimize the use of the 68 Ge/ 68 Ga generator while maintaining PET image quality, innovative approaches based on artificial intelligence (AI) are opening up new perspectives. By using AI, the acquisition time per exam and/or the injected activity can be reduced without compromising image quality. Notably, several AI-based post-reconstruction PET/CT image enhancements have been recently developed  (7). A post-reconstruction PET denoising software (SubtlePET TM , Subtle Medical©, Stanford, USA provided by Incepto©, France) that was recently developed by using a deep convolutional neural network on a library of millions of paired images (native and low-dose images) to learn and tune the optimal parameters to compute an estimate of the native image. Currently, only a few clinical publications have evaluated its use in oncology, all of them dealing with 18 F-FDG PET images  (8) (9) (10) (11) (12).
Abbreviations: PET, positron emission tomography; AI, artificial intelligence; SUV, standardized uptake value; MTV, metabolic tumour volume; NETs, NeuroEndocrine tumours; VOI, volume of interest; GPF, Gaussian post filter; CV, coefficient of variation; BMI, body mass index; PSMA, prostate-specific membrane antigen; FDA, food and drug administration; CE, European conformity; SD, standard deviation; FDG, fluorodeoxyglucose. At present, SubtlePET TM is FDA (Food and Drug Administration)approved for use with 18F-FDG and 18F-Amyloid tracers and is now CE (European Conformity)-marked for use with 18F-FDG, 18F-Amyloid, 18F-Fluciclovine, 18F-DOPA, 18F-Choline, 18F-DCFPyL, Ga-68 Dotatate, and Ga-68 PSMA PET images (13). However, no clinical study has demonstrated the value of this software to enhance the quality of low-dose 68 Ga PET images, even though nuclear medicine departments are concerned about this issue.
Population All patients were informed about the use of their clinical and PET data for research purposes. Patients had the right to refuse the transmission of data covered by medical confidentiality used and processed in the context of this research. The procedure was declared to the National Institute for Health Data with the registration no. F20210720123322. Patients over 18 years old addressed to our PET unit for a 68 Ga-DOTATOC PET from April 2020 to February 2021 were enrolled. Sex, age and body mass index (BMI) were extracted from electronic patient records.
This protocol is subsequently referred to as protocol_FixedDose. Between December 2020 and February 2021, i. e. , the last months of the generator's lifespan, patients were injected intravenously with 1. 5 MBq/kg of 68 Ga-DOTATOC. This protocol is subsequently referred to as protocol_WeightDose. These PET examinations were then processed using Subtle PET TM software and was subsequently referred to as protocol_WeightDose AI. In addition, NEMA-NU2 image quality phantom acquisitions were performed and analyzed to find a specific Gaussian postfilter (GPF). This GPF will allow the protocol_WeightDose to recover a noise in the image equivalent to the former protocol_FixedDose  (17). Measurements were made with a sphereto-background ratio set at six and two background 68 Ga solution concentrations: 2.
Clinical PET data extraction Positron emission tomography scans were equally and randomly assigned to two senior nuclear physicians. PET images were reviewed on MIM (MIM Software, Cleveland, OH, USA, version 5. 6. 5). The following features were recorded separately for each PET acquisition: • Liver SUV mean (mean standard uptake value) and standard deviation (SD) from a 3 cm diameter spherical volume of interest (VOI) placed on the right liver lobe. • Vascular SUV mean and SD from a 2 cm diameter spherical-VOI placed on the descending aorta. • Muscular SUV mean and SD from a 2 cm spherical-VOI placed on the left erector spinae muscle at the height of the adrenals. • Tumour SUV max , SUV mean and metabolic tumour volume (MTV) from a 40% isocontour VOI placed on the most intense lesion, as well as its location.
Statistical analysis Data was presented as mean (SD) unless otherwise specified. Unmatched data were compared using Mann-Whitney and Kruskal-Wallis tests for quantitative data as appropriate. Wilcoxon and Friedman tests, and Bland-Altman analyses were used to compare paired quantitative data as appropriate. Statistical analysis and figure design were performed using XLSTAT software (XLSTAT 2019: Data Analysis and Statistical  Solution for Microsoft Excel, Addinsoft). P-values < 0. 05 were considered statistically significant.
Also, the article by Liu et al. focusing on a cross-tracer and cross-protocol deep transfer learning method for noise reduction indicated that the network trained with FDG datasets can effectively reduce noise in low-dose PET images from less commonly used tracers (i. e. , 68 Ga-DOTATATE) while preserving diagnostic information  (18). We used two methods to evaluate tumour contrast: The tumour-to-background ratio using a doughnut-shaped VOI and the tumour-to-liver ratio. For the doughnut-shaped VOI, the choice of the tumour-contouring method was crucial to ensure the reliability of the resulting background noise measurements. We chose to use a thresholding value set in reference to SUV max , which was previously demonstrated in the study by  Reddy et al. (19)  to be the most accurate measurement when compared to morphological volumes.
This integrated approach may help identify areas of high risk for chondrichthyans bycatch and therefore guides targeted conservation efforts. The Adriatic Sea, situated in the central Mediterranean, has a long history of chondrichthyans fisheries and has experienced depletion of several species in the last few decades  (Dulvy et al. , 2003; Ferretti et al. , 2013; Jukic-Peladic et al. , 2001; Lotze et al. , 2011). Among the chondrichthyan species commonly caught or observed in this region are the dogfish (Scyliorhinus spp. ), brown skate (Raja miraletus), spurdog (Squalus acanthias), thornback skate (Raja clavata), and smooth-hound (Mustelus spp. )  (Barausse et al. , 2014; Clodia database, 2020; Ferretti et al. , 2013; Maioli et al. , 2023). Presently, approximately 70% of the chondrichthyan species in the Adriatic Sea are regionally threatened according to International Union for Conservation of Nature (IUCN) Red List Criteria (www.