dataesr/scientific-paragraphs-categorization huggingface dataset:
, child verbal ability, child language of testing, maternal education, family income and single parenthood). While a limit of the backwards stepwise regression approach has been the use of an automated process to determine the best model for confirmatory purposes, it can offer an effective manner by which researchers can evaluate the suitability of multiple variables for future exploratory examination  (Ruengvirayudh & Brooks, 2016). Given the exploratory nature of our hypotheses pertaining to parent ANPS interactions with child sex, this approach was considered appropriate to determine which relevant variables (i. e. , interactions between parent ANPS subscale and child sex) should be further examined in models. Next, in the second step, significant associations between parent ANPS subscales and children's behaviour that emerged (main effect or in interaction with child sex) were further probed using the macro add-on Process in SPSS which allows for regression path analyses  (Hayes, 2017).
Strengths, limitations and future perspectives Key strengths of this study included the large number of participants and the minimisation of shared method variance given that parent-reported ANPS subscales were examined in relation to child-reported internalising and externalising behaviour. Including the children's own perspective of their behaviour adds valuable information. A further strength of this study pertained to the inclusion of data from fathers. In addition, the use of a biologically , rather than lexically , based measure of affective personality allowed for a more culturally consistent conceptualisation of personality  (Knezěvic´et al. , 2020). We were, however, faced with the following limitations. Firstly, the sample was not randomly selected and there was participant attrition from the initial time point until the present data collection.
, 2006; Mohamed Ali et al. , 2021). Furthermore, future analyses utilising latent class approaches to understand the relationship between child internalising and externalising behaviours could enhance the clinical understanding of the co-occurrence of such difficulties. Finally, the data pertaining to parental personality, parenting and child behaviours were collected at the same time point, thus precluding the ability to look at true mediation. Research evaluating parents' affective personality and child internalising and externalising behaviour could be used to optimise children's emotional development. For example, findings from our research could help to better identify targets such as parental levels of anger or sadness that could be evaluated in future interventions. Future studies could also examine the relevance of other mechanisms beyond parenting practices that have been previously linked to parental personality and child internalising and externalising behaviour.
ACKNOWLEDGEMENTS The data collection of this study was supported by the  Canadian Institutes of Health Research (CIHR)  ( MOP-79420 ,  IHD-107532 , and  POH-120254 ) and the  Canadian Council for Learning. C. H. holds a salary award from the  Fonds de Recherche du Quebec Santé (FRQS). A. T. held a doctoral bursary award from the  Social Sciences and Humanities Research Council (SSHRC). J. R. S. is supported by the  Fonds Monique Gaumond  pour la recherche en maladies affectives.
Trastuzumab deruxtecan (T-DXd) is an anti-HER2 (human epidermal growth factor receptor 2) antibodydrug conjugate which has previously shown e cacy in patients with HER2-overexpressing and HER2-low metastatic breast cancer (mBC). However, the mechanisms of action and resistance of this drug remain partially unclear. DAISY (NCT04132960) is a phase II, open-label study that included patients with mBC whose disease progressed after at least one line of chemotherapy in the metastatic setting. Patients were enrolled in three cohorts according to HER2 expression determined by immunohistochemistry (IHC); cohort 1: HER2-overexpressing (HER2 IHC 3 + or HER2 IHC 2+/ISH+, n = 72), cohort 2: HER2-low (HER2 IHC2+/ISH-or HER2 IHC 1+, n = 74), and cohort 3: HER2 IHC 0 mBC (n = 40). Patients were treated with T-DXd 5.
Study design and characteristics of the patients Between November 2019 and March 2021, 186 patients with mBC whose disease progressed after ≥ 1 line of chemotherapy were included in DAISY trial. Cohort 1 included 72 patients with HER2overexpressing mBC de ned as IHC 3 + or IHC 2+/ISH-positive; cohort 2 included 74 patients with HER2low mBC de ned as IHC 2+/ISH-negative or IHC 1 + and cohort 3 included 40 patients with HER2 IHC 0 mBC (see methods for de nition). Patients received T-DXd 5. 4 mg/kg until progressive disease or unacceptable toxicity. The study design is displayed in Extended Data Fig. 1  and the CONSORT (Consolidated Standards of Reporting Trials) diagram in Extended Data Fig. 2. Patient's characteristics in the Safety Population (n = 179) are reported in Extended Data Table  1.
Modulation of tumor microenvironment We then investigated whether T-DXd modulates the immune microenvironment. Thirty-one paired biopsies from a metastatic lesion at baseline and on day 22-43 after cycle 1 (18 from cohort 1, 10 from cohort 2, and three from cohort 3) were assessed by Multiplex uorescent IHC. A signi cant decrease of PD-L1 expression in the cohort of patients with HER2 overexpressing mBC (n = 18; p = 0. 02) was observed. Conversely, PD-L1 decrease was not observed in cohort 2 and 3. Furthermore, no quantitative modulation of immune cells by T-DXd was detected (Fig. 2c ). Finally, the distance between immune and tumor cells did not decrease over T-DXd administration (data not shown).
Patients And Methods Patients and study design DAISY (NCT04132960) is a prospective, phase II, open-label, clinical trial that assessed T-DXd e cacy in patients with mBC and performed biomarker analyses. The rst patient was enrolled on 4th November 2019 and the last one on 3rd March 2021 at 15 study centers in France. The study design is reported in Extended Data Fig. 1. The rst and last version of the protocol are displayed in Annex 1 and 2. Patients with mBC were eligible if they have received at least one line of chemotherapy in the metastatic setting, have at least one non-bone metastatic site easily accessible to biopsy, and have signed the informed consent for biopsies throughout the study. Mandatory and optional tissue and blood biopsies performed during the study are described in the protocol (Annex 1 and 2).
Treatments and follow-up After signature of the informed consent and veri cation of all eligibility criteria, patients were treated with T-DXd intravenously 5. 4 mg/kg every 3 weeks until disease progression or unacceptable toxicity, as de ned by the investigator. Recommendations for dose reductions are described in the V1 of the protocol (Annex 1). Treatment e cacy was monitored by a computed tomography (CT) scan every 6 weeks during the initial 12 months and every 12 weeks thereafter. The CT-scan should be repeated at least 4 weeks after assessment of a partial response (PR) or a complete response (CR). The Response Evaluation Criteria in Solid Tumors (v1. 1) were used to determine response and progression  24. Toxicity data were collected at each visit and were classi ed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (v5.
Immunohistochemistry (IHC) ER, PR, and HER2 status were determined locally for screening. For cohort assignment, HER2 status determination on the baseline biopsy was performed within the GEFPICS pathologist network (national group of French pathologists experienced in breast cancer pathology, which publishes national breast cancer guidelines)  25  ; i. e. each HER2 determination was mandatorily assessed by an expert breast cancer pathologist belonging to the GEFPICS' group. Centers that did not belong to the GEFPICS' group had therefore to send their sample to a member of this group, prior to cohort assignment. After HER2 central determination, thirteen and seventeen patients planned to be included in cohort 1 (n = 72) and 3 (n = 40) respectively, were included in cohort 2 (n = 74). Additionally, if HER2-expression from the biopsy at baseline was different from the status at screening, the patient was switched to the corresponding cohort (see Extended Data Fig.
The cocktail of eight antibodies was applied at the beginning and uorescent probes (complementary to each barcode label) were detected 4 by 4. Next, slides were stained for HES. After each detection cycle and HES staining, slides were imaged using the Akoya Biosciences PhenoImager HT (formerly Vectra Polaris). For each sample, the three Whole Slide Images (WSI) were stacked in one by Ultivue. The resulting stacked WSI were analyzed in QuPath software. ROIs were manually delineated by a pathologist (MLT). Inside these regions, tissue was automatically detected using a trained classi er. Cells were detected on the Dapi channel and thresholding of each uorescent channel allowed for phenotyping each cell, depending on the amount of signal present in the cell on each channel. Results were expressed, for each phenotype, as the number of stained cells per square millimeter of analyzed tissue.
Assessment of HER2 spatial distribution by AI Among the 68 patients from cohort 1, six patients with no digitized HER2 slide at baseline or not exploitable after pathologist review were removed. One patient presenting only one digitized HER2 slide at baseline scanned with another scanner was also moved away to ensure homogeneous scanning conditions (see Extended Data Fig. 8 ). Digitized HER2 IHC slides collected at baseline (n = 61) were analyzed through an unsupervised scheme to identify homogeneous regions across patients, not relying on any prior assumptions linking speci c tissue areas to objective response to treatment. These regions were segmented using a clustering algorithm on features extracted from pre-processed tissues; and region association to objective response was assessed through classic statistical analysis based on each cluster's relative percentage (see Extended Data Fig.
Each collection of oligo tags from one well (from the tissue section), was indexed using Illumina's index 1 (i7) and index 2 (i5) unique dual indexes system using GeoMx SeqCode primers with 18 cycles of PCR. After PCR, indexed ROIs were pooled and puri ed in two rounds of AMPure XP PCR puri cation using 1. 2x bead:sample ratio. The resulting library fragments contain a unique molecular identi er (UMI), readout tag sequence identi er (RTS ID) that identi es the target, and the necessary regions for sequencing with Illumina platforms. GeoMx NGS libraries are sequenced with 2 x 27 bp paired-end reads using the unique dual index work ow with 8 bp for Index 1 (i7) and Index. The number of samples per sequencing run depends on the sequencing system and ROI size and number. Sequenced oligonucleotides are processed then imported back into the GeoMx DSP analysis software for integration with the slide image and ROI selections for spatially resolved RNA expression.
abs_segtabs. xed. txt and TCGA_mastercalls. abs_tables_JSedit. xed. txt. These les were reduced to select only BRCA samples. The same categorization and ltering of CNAs as described in the previous paragraph was employed. e. Catalogue of driver events Oncogenic events were identi ed by intersecting point mutations and small indels that passed all lters as well as all HomD, MLG, and HLG spanning less 10 Mb with the OncoKB database 39. Among the point mutations and indels that were annotated by oncokb-annotator, all events with MUTATION_EFFECT as "Likely Neutral", "Neutral" or "Unknown" were discarded unless ONCOGENIC eld was "Likely Oncogenic" or "Predicted Oncogenic". Experiment in BC cell lines Cell MCF-7 and SK-BR-3 cells were purchased from DSMZ (Germany). MCF-7 cells were grown in DMEM (Gibco) supplemented with 1% glutamax (Gibco) and SK-BR-3 in McCoy's 5A medium (Gibco) in standard incubation conditions at 37°C with 5% CO 2.
Nearly 60% of enrolled patients with NAA tests had add-on NAA following positive smear microscopy, suggesting that NAA tests have been considerably underused to reduce delayed diagnosis of TB in smear-negative cases in Taiwan. Death without anti-TB treatment has been previously assessed in a limited number of studies. In the US, 5. 1% of TB was diagnosed at death, from 1985 to 1988, a percentage that was reduced to 2. 1% in 2005  11, 19   20, 21. To reduce the number of patients that die without anti-TB treatment, early diagnosis of TB is crucial. Our study showed trend of fewer cases of death without anti-TB treatment in patients with frontline NAA as compared to those with add-on NAA, although without statistical significance. Meanwhile, our data revealed that a majority of TB cases with death before anti-TB treatment died of non-TB causes.
Methods Patients and settings. This was a retrospective cohort study performed in seven referral hospitals in Taiwan. Pulmonary presumptive TB patients, who had undergone NAA tests from January 2017 to December 2018 and were subsequently notified to Taiwan CDC with diagnosis of pulmonary TB, were enrolled. Pulmonary TB patients notified from January 2013 to December 2014 without NAA tests were included as a reference group (no NAA group), because NAA test had not yet been recommended as an initial diagnostic test by the Taiwan TB guidelines during that period. Exclusion criteria were: patients below 20 years old, active TB patients without pulmonary involvement, and active TB patients without sputum smear microscopy. Data regarding the age, sex, type of NAA tests, and detailed information of smear microscopy, including examination date and results, were collected from medical chart reviews.
TB outcome evaluation. Outcomes of interest in the present study included the number and proportion of TB patients that died without anti-TB treatment, the interval between sputum examination and initiation of anti-TB treatment (delayed diagnosis), and misdiagnosis of TB. Misdiagnosis of pulmonary TB was defined as notified pulmonary TB cases, who were advised by clinicians to stop anti-TB treatment before completion of the treatment course and were de-notified, due to TB misdiagnosis. Information regarding diagnosis change (misdiagnosis), date of death, and treatment initiation were retrieved from the TB registration database of Taiwan CDC. The date of first sputum examination, including smear microscopy, mycobacterium culture, and NAA tests, were acquired from chart reviews.
Validating experiments in intra-operative planning for percutaneous interventions requires to localize the needle with a tracking system. As commercial optical trackers are expensive, we present MANGO, a low-cost OpenSource solution for needle tracking. We first present the design of our system, which localizes colored orbs using a stereo-camera setup. Based on this setup, we investigate the static and dynamic error of the system, and experiment with signal filtering to improve tracking performance. With the MANGO, we are able to meet the positional accuracy margin of 5 mm usually required in percutaneous interventions. Orientational accuracy, measured by needle tip localization accuracy as a proxy measure, exceeds this margin. We plan to investigate this further in future research. Releasing our code, data and 3D models, we aim to provide a low-cost and reproducible platform for needle tracking and validation of intra-operative planning in research environments.
Validation Protocol We assessed the tracking accuracy of the MANGO system by comparing the tracking results with an NDI Polaris Vicra system. The Polaris Vicra has a stated accuracy of 0. 5 mm (CI-95), and thus serves as a proper reference standard we can use for our experiments. The needle and attached marker set was partly inserted and fixed into a rigid foam structure to reduce oscillations due to movements, as shown in Fig. 6  (right). This setup was manually moved so that the needle tip sequentially covered a grid of  points evenly spaced by 2 cm×2 cm. The positions of the orbs were measured with both MANGO and Polaris systems simultaneously and continuously recorded. At each point of the grid, we let the needle and markers stabilize for 20 s. The recorded data points were first aligned to a common coordinate frame by using Horn's method  [5]  under the use of eight extra calibration points that were collected with a similar protocol.
The time vector for both system was collect using the UNIX timestamp. As the MANGO sample rate is 30 Frames per Second (FPS) and the Polaris NDI sample rate is 50 FPS, the reference time vector used was that of MANGO. For each data point of the MANGO the comparison was done with the closest corresponding timestamp of the NDI Polaris. In a second step, we estimated the series of positions of the needle tip for both tracking devices to properly compare the systems in six DOF. A sequence of stabilized positions was computed for the marker and the needle tip by clustering the time series of positions. DBSCAN was used for this clustering  [3]  (ϵ = 1. 5 mm, 200 samples), as it is well-established and separates noisy samples outside the cluster centers (we used these outliers to calculate the dynamic error in Sec.
4. 3). Unlike traditional k-means,  DBSCAN does not require the number of cluster centers to be known beforehand. Rather, DBSCAN separates data points based on the cluster density, such that the distribution of cluster points would not need to be spherical. The density parameter ϵ was gauged between twice the stated accuracy of the Polaris (1 mm) and half the distance between measuring points (10 mm), to allow for slight deviations of measurements from the stated tracking accuracy still being considered static measurements when analyzing static vs. dynamic accuracy. All experimental code was written in Python with the use of OpenCV framework  [2].
Static vs. Dynamic Error To assess the dynamic and static error of the MANGO, we separated the stabilized points obtained with the DBSCAN clustering from the outliers, the latter corresponding to the needle movements in between the points. For each corresponding timestamp of the two datasets (Polaris and MANGO), we compared the corresponding points for (a) static inliers and (b) dynamic outliers to calculate an error estimate. The static and dynamic errors are reported in Tab. 2 for both the full and the optimal tracking volumes. We can see that the MANGO also meets the accuracy requirements if the needle is in motion, as the dynamic error is only slightly higher but still below the 5 mm margin. The dynamic accuracy is sufficient in the full tracking volume, but is significantly better when confined to the optimal tracking space.
Needle Tip Tracking Error Until now we only evaluated the tracking of three DOF of the marker, i. e. the tracking of the orb at the origin of the marker coordinate frame (or the translation vector between the marker frame and the camera frame). In this section we evaluate the tracking of the needle tip, which requires all six DOF, and allows to indirectly assess the measured orientation of our marker. Fig. 10  shows the comparison between the tracking of the needle tip with MANGO and with the Polaris System inside the optimal volume. Tab. 3 shows the errors for the three coordinates. The Polaris system itself provides measurement data for all six degrees of freedom out-of-the-box. While the error is below the accuracy margin of 5mm  [4]  requested for our intended use case in the x and y directions, it can be observed that the error in the z coordinate is around ten millimeters, which exceeds the margin.
Acknowledgements This work of the  Interdisciplinary Thematic Institute HealthTech , as part of the  ITI 2021-2028 program  of the  University of Strasbourg ,  CNRS  and  Inserm , was supported by  IdEx Unistra  ( ANR-10-IDEX-0002 ) and  SFRI  ( STRAT ' US  project,  ANR-20-SFRI-0012 ) under the framework of the  French Investments for the Future Program.
onlinelibrary. wiley. com/doi/10. 1111/cobi. 14002 by Cochrane France, Wiley Online Library on [29/10/2022]. See the Terms and Conditions (https://onlinelibrary. wiley. com/terms-and-conditions) on Wiley Online Library for rules of use; OA articles are governed by the applicable Creative Commons License MOVEBANK  (Kays et al. , 2021) , much of the existing data are fragmented and confined to the academic literature  (Fraser et al. , 2018) , and remain difficult to find and access  (Davidson et al. , 2020). Second, given that tracking studies are initiated with different underlying motivations (e. g. , scientific, conservation) and their feasibility is constrained by a diversity of considerations (e. g. , technology, species' ecology, access to funding), existing data tend to be biased towards particular regions and species  (Bernard et al.
Definition of migratory link An individual migratory bird typically crosses the borders of multiple countries during its annual cycle, including where it breeds, stops over during migration, and spends the non-breeding season. Here, we focused on just two countries per individual: the one where it breeds (hereafter 'breeding country'); and the one where it spends the most time during the non-breeding season ('nonbreeding country'). As we extracted data from available studies rather than from raw tracking data (see below), we were unable to extract finer details (e. g. , on stopover sites) across all individuals. We define a 'migratory link' as the connection between two countries established by birds from a population as they migrate from a European breeding country to a sub-Saharan African nonbreeding country.
Compiling migration records from studies We focused on tracking data obtained from birds fitted with GLS, PTT or GPS devices, aiming to obtain as many migration records as possible for the analyzed species. A 'migration record' corresponds to the minimum information needed to identify a migratory link, i. e. , evidence that an individual of a given species migrated from its breeding country in Europe to its non-breeding country in sub-Saharan Africa. Although ringing data can provide robust insights on migratory connectivity  (Ambrosini et al. , 2009) , we did not attempt to incorporate these data in our analysis because ring recoveries do not provide information on how long the individual spent at a given location. Indeed, ringing recoveries provide location information for single points in time and often only one recovery location is available for each individual (e.
g. ,  Strandberg et al. , 2009) , making it impossible to determine if it corresponds to the main non-breeding country (as defined above). We conducted a review of published articles in ISI Web of Science core collection (https://www. webofknowledge. com/) and Google Scholar (https://scholar. google. com/), complemented by additional studies (details in Appendix S3). From each selected study, we extracted as many migration records as possible, each record corresponding to an individual bird for which we obtained: the species, the breeding-country (in Europe), and the non-breeding country (i. e. , where the bird stayed the longest in sub-Saharan African) (details in Appendix S4, including how we dealt with highly mobile species). For four species in our dataset -European nightjar (Caprimulgus europaeus), Eurasian bee-eater (Merops apiaster), barn swallow (Hirundo rustica), and collared flycatcher (Ficedula albicollis) -the tracking data revealed non-breeding ranges covering more countries than those identified by (BirdLife International and Handbook of the Birds of the World, 2018).