dataesr/scientific-paragraphs-categorization huggingface dataset:
Results Twelve centers reported data on 809 patients treated by PIPAC directed therapy in the ISSPP PIPAC Database between June 2020 and March 2023. The number of included patients ranged from 2-355 (median 10), but four centers provided 93 % of the included patients. Demographic data are listed in Table  1. Gastric, colon and ovarian cancer accounted for 2/3 of the included patients. Seventy percent of the patients were diagnosed with peritoneal metastasis (PM) within 6 months of their primary tumor, and 89 % received oncological treatment prior to their first PIPAC directed therapy.
Discussion The present data were registered in the ISSPP PIPAC Database over a period of 32 months (on 809 patients), and included data form the first 6 months (on 181 patients) which has previously been reported  [3]. Although not directly comparable, analysis of the present data from the ISSPP PIPAC Database seems to match results from recent narrative and extensive systematic reviews and meta-analysis of patients undergoing PIPAC directed therapy  [4, 5]. Variations regarding intraoperative settings like flow rate, exposure time, drugs and doses merely reflect experience and changes over time based on ongoing and completed trials, new aerosolizers, and updated PIPAC recommendations  [5] [6] [7] [8]. The results of several of the outcome variables suggest that most patients were well selected for PIPAC directed therapy, and that repeated PIPAC directed treatments were possible with the expected low rate of significant complications and adverse events.
Other variables including non-access rate, length of stay, number of PIPAC procedures, bi-directional treatment were also in line with the present literature  [4, 5, 9]. PRGS is probably the best objective marker of local response and surrogate marker of overall survival available at the moment  [10, 11]. The fact that at least four out of five patients where treatment response was monitored by PRGS had a score ≤2 at the third PIPAC procedure, also points towards a relevant patient selection. It is also interesting to note that the median survival was significantly higher in gastric cancer patients with PRGS response, defined according to a recent prospective study  [10] , compared to those without, and that we may expect similar results for other primary tumors (e. g. colon) when more long term follow up data become available in the database.
The inclusion of patients with PM from different primary tumors in prospective and randomized trials is important to elevate PIPAC directed therapy onto the next level  [9]. In that aspect, it is somewhat surprising that only a quarter of the patients in this database had their PIPAC directed treatment as part of a prospective study. As expected, disease progression was the most important reason (50 %) for stopping PIPAC treatment  [12]  but a more detailed evaluation of other reasons should be considered in future reports. The lack of randomized trials makes PIPAC survival data from an international database especially interesting. Despite potential differences in patient selection and treatment among the reporting centers, the combination of large real-world data show encouraging median overall survival rates from first PIPAC treatment (Table  7 ).
So far the present data represent one of the largest compilations of survival data from specific cancer populations treated by PIPAC and systemic chemotherapy  [5]. The ISSPP PIPAC database has several limitations. Most important, more than 90 % of the procedures were reported by three centers, only, and the database mainly reflects the combined results from three major European PIPAC centers or group of institutions. Thus, the results may not be representative for centers having initiated their PIPAC program recently. The number of missing or incomplete date are substantial for some of the variables (e. g. date of death), and the relatively short observation time for patients alive is also important in relation to the presented survival data. On the other hand, large real-world data are still important while awaiting randomized trials  [3, 9] , and the results from the database provides additional evidence supporting the present indications and details of PIPAC directed therapy.
In addition, some of the limitations like incomplete data, understanding and reporting variables, reminders to users, as well as easy linking to the database and the recruitment of more centers worldwide are all potentially solvable problems that are prioritized by the ISSPP Registry group. While recognizing these limitations it is also important to note that all international databases start with relative few centers, limited data and incomplete follow up. We believe that reporting even selected data may stimulate additional centers worldwide to actively participate in the ISSPP PIPAC database. In that aspect it is good news that several new PIPAC centers have started entering data in 2023 after deadline for this report, and they will be part of the next annual report, which is expected to include a substantial larger number of patients and procedures as well as a longer follow up.
Conclusions The ISSPP PIPAC database provides substantial real-world data supporting the use of PIPAC directed therapy in patients with PM from different primary tumors. PIPAC is a safe procedure, and PIPAC directed therapymostly in combination with systemic chemotherapy, can induce objective local tumor response that may lead to prolonged survival in selected cancer patients. Contributions to the ISSPP PIPAC database so far are mainly from Europe, and the ISSPP Registry Group hopes that additional centers worldwide will join and include their patients in the database.
Acknowledgments:  Naoual Bakrin ,  Isabelle Bonnefoy ,  Anne-Cecile Ezanno ,  Martin Graversen ,  Kim Guowei ,  Pernille Schjødt Hansen ,  Kim Hyung-Ho ,  Vahan Kepenekian ,  Laura Ley ,  Bettina Lieske ,  Pirilti Özcan ,  Laura Sabiani ,  Omar Thaher ,  Laurent Villeneuve  are thanked for their contribution to the ISSPP PIPAC Database. Research ethics: The ISSPP PIPAC database and the study protocol were approved by the  Region of Southern Denmark  (GDPR, 20/18204) on April 21st, 2020, the Institutional Review Board of the  University of Southern Denmark  ( SDU REC 20/ 24559 ) on May 5th, 2020, and by the hosting unit Odense Patient data Explorative Network (OPEN) on May 19th, 2020 ( OP-114019/49984 ). Informed consent: Informed consent was obtained from all individuals included in this study.
To evaluate the safety and tolerability of the fixed-dose, single-tablet regimen sofosbuvir/velpatasvir (SOF/VEL) for the treatment of hepatitis C virus (HCV) infection in three Phase 3 studies in patients with and without compensated cirrhosis. Data from three registrational trials (ASTRAL-1, NCT02201940; ASTRAL-2, NCT02220998; ASTRAL-3, NCT02201953) were pooled by treatment regimen. Researchers assessed treatment-emergent adverse events (TEAEs) and laboratory abnormalities in patients randomized to SOF/VEL or placebo for 12 weeks in ASTRAL-1 and SOF/VEL for 12 weeks in ASTRAL-2 and ASTRAL-3. Overall, 1035 patients were treated with SOF/ VEL, and 116 patients received placebo. Rates of any TEAE were generally similar between patients receiving SOF/VEL (79. 4%) and those receiving placebo (76.
| Study design Patient-level data were pooled from three Phase 3 clinical trials (ASTRAL-1, NCT002201940; ASTRAL-2, NCT02220998; and ASTRAL-3, NCT02201953). Study designs are shown in Figure  1 ; details of individual study methods have been published previously. 18, 19 Data were pooled for the SOF/VEL treatment arms. Eligible patients were 18 years of age or older and had chronic HCV infection with genotype 1, 2, 3, 4, 5 or 6. 18, 19  The protocols allowed for up to 20% of patients to show evidence of compensated cirrhosis. Patients could be treatment-naive or treatment-experienced (limited to 20% of the study population; defined as having had prior treatment failure with a regimen containing interferon either with or without ribavirin that was completed at least 8 weeks prior to baseline/Day 1).
| RE SULTS The pooled dataset included 1151 patients. Over 12 weeks, 1035 patients received SOF/VEL, and 116 received placebo. Demographics were generally similar across treatment groups. Across datasets, at least 10% of patients were 65 years or older, at least 14% had compensated cirrhosis, and at least 32% had an eGFR value <90 mL/ min/1. 73 m 2 at baseline (Table  1 ). Across treatment groups, the overall rates of TEAEs appeared comparable for SOF/VEL and placebo (Table  2 ). The most common TEAEs (occurring in >10% of patients) reported by SOF/VEL-treated patients were headache, fatigue, nausea and nasopharyngitis (Table  2 ); these were also the most commonly reported TEAEs among patients in the placebo group. Diarrhoea was reported in 73 (7. 1%) patients receiving SOF/VEL and 8 (6. 9%) receiving placebo.
Extremity necrosis 1 (<1) 0 Abbreviations: AE, adverse event; SOF, sofosbuvir; VEL, velpatasvir. a 23 patients had a total of 28 serious adverse events. cirrhosis and mild renal impairment), there were no treatmentrelated SAEs, and only one patient with mild renal impairment discontinued due to AEs. [8]  The safe use of SOF/VEL with a simplified treatment paradigm is supported by the results of the MINMON (NCT03512210) trial, in which 400 enrolled patients with HCV received a 12-week course of SOF/VEL without pretreatment genotyping and no scheduled in-person visits or laboratory monitoring while on treatment. 23 The results showed a sustained virologic response rate of 95. 0% (95% CI, 92. 4-96. 7); 4% of patients reported SAEs, none of which were considered related to treatment. 23 Assessing patient and clinician opinions on HCV treatment has shown a clear preference for treatments with minimal pretreatment testing and fewer side effects.
Acknowledgements These lecture notes summarize the work that has been done throughout the past 10 years in collaboration with many researchers, students and postdocs at  Yale University (Applied Physics Department and Yale Quantum Institute)  and at  Quantic team  (a joint team between  Inria ,  Mines Paristech, ENS ,  Sorbonne Université  and  CNRS based in Paris ). Mazyar Mirrahimi  is grateful to his colleagues at  Yale ,  Michel Devoret ,  Steven Girvin ,  Robert Schoelkopf ,  Liang Jiang ,  Leonid Glazman  and their group members for having welcomed him and his students from 2011 to 2019, the period through which most of these ideas have been developed. The authors also thank  Zaki Leghtas ,  Pierre Rouchon ,  Alain Sarlette ,  Philippe Campagne-Ibarcq  and all other members of Quantic team in Paris who have been developing and pushing these ideas both towards their experimental realization and towards a general mathematical theory of quantum systems.
Study Design and Treatment This was a phase II, multicenter, randomized, placebo-controlled, double-blind study (Clini-calTrials. gov identifier: NCT03926169). The study included two treatment periods: a randomized, double-blind, placebo-controlled period from weeks 0 to 16 and an open-label risankizumab treatment period from weeks 16 to 68. During the 16-week double-blind treatment period, patients were randomized 1:1:1 to receive subcutaneous risankizumab 180 mg; risankizumab 360 mg; or placebo at weeks 0, 1, 2, 4, and 12. The final efficacy evaluation for the double-blind period was performed at week  16. In the open-label treatment period, patients initially randomized to placebo received blinded risankizumab 360 mg at weeks 16, 17, and 18, while patients initially randomized to risankizumab received blinded matching placebo at the same time points to maintain blinding (administration of placebo at weeks 16, 17, and 18 did not affect the risankizumab dosing schedule).
Statistical Analysis The primary endpoint was evaluated between each risankizumab dose and placebo using the Cochran-Mantel-Haenszel test, adjusting for stratification factors (prior exposure to anti-TNF therapies and baseline worst Hurley stage). Missing efficacy values during the double-blind period were handled using nonresponder imputation incorporating multiple imputation to handle missing data due to COVID-19 as the primary approach for categorical endpoints and mixed-effect model repeat measures for continuous endpoints. All safety analyses were performed on the safety populations, defined as all patients who received at least one dose of study drug in the respective study period. The number and percentage of patients experiencing TEAEs were tabulated using the Medical Dictionary For Regulatory Activities (version 24.
Variable responses to adalimumab in patients with HS have been reported, with one study reporting 42-59% of patients achieving HiSCR after 12 weeks of treatment  [7]. Our findings demonstrate that risankizumab therapy (at the evaluated doses of 180 mg and 360 mg) does not improve the signs and symptoms of HS. Guselkumab, another anti-IL-23 monoclonal antibody, also failed to demonstrate significant clinical improvements over placebo after 16 weeks of treatment in a recent phase II study of patients with moderate-tosevere HS (ClinicalTrials. gov identifier: NCT03628924)  [21]. These results suggest that IL-23 may not be a relevant therapeutic target for HS and that inhibition of IL-23 in the doses evaluated in clinical trials thus far is not an effective strategy to treat HS. Several other investigational treatments are also being evaluated for the treatment of HS; agents targeting IL-17 and Janus kinase 1 have recently demonstrated promise in placebo-controlled studies, and evaluation of other novel therapies are also underway.
Secukinumab (an anti-IL-17a monoclonal antibody) demonstrated superiority over placebo after 16 weeks of treatment in patients with moderate-to-severe HS in two recent phase III studies (SUNSHINE [ClinicalTrials. gov identifier NCT03713619] and SUNRISE [ClinicalTrials. gov identifier NCT03713632])  [22]. Clinically meaningful improvements have also been reported from open-label cohort studies for brodalumab (an IL-17a receptor antagonist)  [23, 24]  and from phase II randomized controlled trials for HS with bimekizumab (an anti-IL-17a /IL-17F monoclonal antibody)  [25]  and povorcitinib (an oral, small-molecule Janus kinase 1 inhibitor)  [26]. Clinical responses reported with anti-IL-17 agents, but not anti-IL-23 antibodies might suggest that IL-17-producing cells other than T helper 17 cells may be involved in the pathophysiology of HS.
The study protocol was reviewed and approved by central (Advarra IRB Services, Columbia, MD, USA) and by local independent ethics committees and/or institutional review boards at each study site. Patients provided written informed consent prior to screening or undergoing studyspecific procedures. Data Availability. The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized individual and trial-level data (analysis data sets), as well as other information (e. g. , protocols, clinical study reports, or analysis plans), as long as the trials are not part of an ongoing or planned regulatory submission.
This includes requests for clinical trial data for unlicensed products and indications. These clinical trial data can be requested by any qualified researchers who engage in rigorous, independent, scientific research, and will be provided following review and approval of a research proposal, Statistical Analysis Plan (SAP), and execution of a Data Sharing Agreement (DSA). Data requests can be submitted at any time after approval in the US and Europe and after acceptance of this manuscript for publication. The data will be accessible for 12 months, with possible extensions considered. For more information on the process or to submit a request, visit the following link: https://www. abbvieclinicaltrials. com/hcp/data-sharing/. html. Open Access. This article is licensed under a Creative Commons Attribution-NonCommercial 4.
ACKNOWLEDGEMENTS AbbVie and authors thank all the trial investigators and patients who participated in this clinical trial Funding. AbbVie funded this study and participated in the study design, research, analysis, data collection, interpretation of data, reviewing, and approval of the publication. All authors had access to relevant data and participated in the drafting, review, and approval of this publication. No honoraria or payments were made for authorship. AbbVie also provided funding for the journal's  Rapid Service Fee. Medical Writing and Editorial Assistance. Medical writing support was provided by  Callie AS Corsa, PhD , of  JB Ashtin  and funded by  AbbVie. JB Ashtin adheres to Good Publication Practice (GPP3) guidelines and  International Committee of Medical Journal Editors (ICMJE)  recommendations.
Data and methods The analysis is based on Demobel data provided by Statistics Belgium gathering residential information from National Population Registers for the years 2010 to 2020. The data contain the entire Belgian resident population and include information on household members, municipality of residence, and the link between parents and their children. A child can be registered with only one parent even though they may be living in shared physical custody. Findings from the Netherlands show that the vast majority of children of separated parents spend most of their time at the address where they are registered (van der Wiel and Kooiman 2019). We selected children aged 0 to 6 (in the year after separation) whose parents separated in 2010. We defined separation as follows. First, we took all couples with a joint child who shared a household on January 1, 2010.
Discussion The purpose of this paper was to explore the stability of children's residential arrangements whose parents separate early in their life course. By doing so, this study contributes to the study of children's postseparation well-being. We used Belgian register data to follow these children from 2010 to 2020 (i. e. , in the 10 years following the separation). The most widely adopted arrangement -children registered initially with the mother (85%) -is also the most stable one. For every 10 children in such arrangements, 9. 2 stayed registered with their mother in the long term. Children registered with their mother often saw their father moving farther away with the years elapsed since separation. We estimated that 10 years after the separation about 10% of initially nonresident fathers moved away from Belgium.
Acknowledgments We acknowledge support from the  European Research Council (ERC)  under the European Union's  Horizon 2020 research and innovation programme (FamilyTies project : Grant Agreement No. 740113  ( 2017-2022 ), PI:  Clara H. Mulder ,  Rijksuniversiteit Groningen ). We thank  Statbel (Directorate-General Statistics -Statistics Belgium ) for access to the Demobel (adaptation of the National Register). Computational resources were provided by the supercomputing facilities of the  Université Catholique de Louvain (CISM/UCL)  and the  Consortium des Équipements de Calcul Intensif en Fédération Wallonie Bruxelles (CÉCI) , funded by the  Fond de la Recherche Scientifique de Belgique (F. R. S. -FNRS)  under convention  2. 5020. 11  and by the  Walloon Region.
Global cognitive functioning was evaluated using the MMSE (possible score range: 0-30). 20 rbal episodic memory was assessed using the Encoding, Storage and Retrieval free recall measure (ESR, 0-16). 32 Higher scores indicate better performances for all tests. In the current study, we used the CDS, MMSE and ESR scores collected at baseline in all participants (main objective), but also the follow-up data collected 18 months and/or 36 months after baseline in a subsample of participants for longitudinal analyses (secondary objectives).
44, 45  Note that data in ADNI for SCD patients should be considered with caution given the criteria for SCD specifying that "the informant should not equate the expressed concern with progressive memory impairment". This is likely to explain the lack of result in ADNI SCD patients, together with the fact that they were recruited from the community and not from a memory clinic as in IMAP+. 22, 46 nally, complementary longitudinal analyses showed that baseline I-SMD was not predictive of further cognitive decline over a 2-year follow-up in any clinical group; while it predicted a 2-year increase in global amyloid load in IMAP+ SCD patients. Although weak (not surviving FDR correction), this relationship suggests that patients combining a significant concern about their memory (i. e. , SCD patients) and a high I-SMD level could be at higher risk of increased subsequent amyloid pathology.
MRI) and positron emission tomography (PET) cameras, and followed up every 18 months, over 36 months. Scans used in the current study were performed from January 24, 2008, to March 22, 2019. For replication and validation, the Alzheimer's Disease Neuroimaging Initiative (ADNI) was used as an independent multicenter cohort with a larger sample size and participants included from more than 50 sites throughout the United States and Canada (http://www. adni-info. org). For the present study, data accessed from the ADNI database on October 18, 2018 (ADNI2, ADNIGO and ADNI3 phases) was used, with scans performed from June 17, 2010, to May 19, 2014 (http://adni. loni. usc. edu).
Imagerie Multimodale de la maladie d'Alzheimer à un stade Précoce (IMAP+) Participants MRI) and positron emission tomography (PET) cameras, and followed up every 18 months, over 36 months. Scans used in the current study were performed from January 24, 2008, to March 22, 2019. For replication and validation, the Alzheimer's Disease Neuroimaging Initiative (ADNI) was used as an independent multicenter cohort with a larger sample size and participants included from more than 50 sites throughout the United States and Canada (http://www. adni-info. org). For the present study, data accessed from the ADNI database on October 18, 2018 (ADNI2, ADNIGO and ADNI3 phases) was used, with scans performed from June 17, 2010, to May 19, 2014 (http://adni. loni. usc. edu). FLAIR-weighted hyperintensities, and a modified Hachinski ischemic score ≤ 2 25 ).
They were recruited from two main sources, public advertising for controls, and from local memory clinics for patients with SCD, MCI and AD dementia. The participants inclusion and group classification were based on a clinical interview and a standardized neuropsychological assessment according to internationally agreed criteria for SCD (i. e. , memory concern without objective cognitive deficits), 1 amnestic MCI 26 and probable Alzheimer's disease, 27 but did not rely on neuroimaging biomarkers (i. e. , ATN classification). Controls participants and SCD patients had MMSE scores of 26 or higher; MCI patients had MMSE scores of 22 Analyses were conducted from June 6, 2019 to December 07, 2021. or higher; and AD dementia patients had MMSE scores of 12 to 26. CPP Nord-Ouest III) and registered at http://clinicaltrials.
Search strategy and selection criteria References for this review were identified through searches of PubMed and Google Scholar for articles published in English from database inception to July 31, 2023, by use of the terms "metrics of glycaemic variability", "glycaemic control continuous glucose monitoring metrics", "metrics of HbA1c variability in diabetes", "HbA1c variability glycaemic targets", "metrics of long-term glycaemic variability", "glycaemic variability and hypoglycaemia", "variability independent of the mean". We reviewed and selected retrieved references on the basis of their relevance. We gave priority to those published from 2010 onwards, even though key older references are also cited.