dataesr/scientific-paragraphs-categorization huggingface dataset:
, 2010). Three additional patients were subsequently reported as carrying either a similar PTC variant or a 1q21. 3 microdeletion encompassing GATAD2B, allowing the description of a recognizable syndrome  (de Ligt et al. , 2012; Willemsen et al. , 2013)  named GATAD2B-Associated Neurodevelopmental Disorder (GAND). It is now acknowledged that GATAD2B loss of function (LoF) is responsible for the main phenotypic traits of the 1q21. 3 microdeletion syndrome  (Shieh et al. , 2020; Tim-Aroon et al. , 2017; Willemsen et al. , 2013). Since then, more than 50 LoF variants have been reported in patient-specific databases including DECIPHER  (Firth et al. , 2009) , the Human Genome Mutation Database (HGMD,  (Stenson et al. , 2017) ) and ClinVar  (Landrum et al. , 2018) , suggesting that GAND is not among ultra-rare diseases.
Contrasting with this relatively high frequency in patient-specific databases, the detailed phenotype associated with GATAD2B pathogenic variants had been reported in a few patients only. While gathering clinical data for the current study, a series of 50 cases was published, confirming that GAND is not among the rarest causes of neurodevelopmental disorders of genetic origin  (Shieh et al. , 2020). The main features of GAND include global developmental delay, impaired speech, severe ID, childhood hypotonia, macrocephaly and dysmorphic features. We collected the clinical data of 19 patients with the aim to refine the GAND phenotype in order to improve clinical knowledge and management for caregivers and families.
Subjects and Methods Clinical data of GATAD2B pathogenic or likely pathogenic variant carriers were collected from France, Germany, Belgium, United Kingdom, and Italy from May 2018 to November 2019. Referring clinicians were contacted through the AnDDI-Rares platform, a French network for rare diseases, and from other European countries through the GeneMatcher website  (Sobreira et al. , 2015). Parents or legal representatives previously gave informed written consent for genetic analyses. Additional specific written consent was obtained from parents for the use of patient's photographs. Clinical data was collected through a questionnaire filled by the referring clinician. This study was approved by the Rouen ethics committee. Clinical data were collected from patient's medical charts. Postnatal growth measurements are reported by Z-score in standard deviation (SD) according to French reference charts or using a calculator based on the WHO Charts for Canada (available at http://www.
Funding This study was cosupported by  European Union and Région Normandie in the context of Recherche Innovation Normandie  ( RIN 2018 ). Europe gets involved in Normandie with the  European Regional Development Fund (ERDF). This work was generated within the  European Reference Network for Developmental Anomalies and Intellectual Disability. Sequencing of patient 16 was funded by  Margarete Müller-Bull Stiftung. BC is a Senior Clinical Investigator of the  Research Foundation -Flanders.
as epigenetic disorders sharing features with other overgrowth syndromes. Accession numbers: ClinVar: VCV000691267. 1; VCV000545032. 1; VCV000620074. 1; VCV000545450. 1; VCV000666293. 1; SCV000994577. 1; VCV000435290. 2; VCV000419723. 2; VCV000435288; VCV000445996. 1. ; SCV001250675. LOVD: #0000499839; #0000405572; #0000500690. Varsome: varso. me/LuMa.
This database complements the PAGES 2k Consortium 9 database of global paleotemperature records, which extends back 2000 years and is formatted similarly within the Linked PaleoData structure (LiPD 10 ). The PAGES Iso2k 11 database, which focuses on water isotope records over the past 2000 years, is also being developed in the LiPD structure. These higher-resolution (mostly annual) time series of 2000-year-long records provide a bridge between the overall lower-resolution time series of this database and the highly detailed, but relatively brief instrumental-based record of climate.
Methods The Temperature 12k database comprises paleotemperature records generated using a wide variety of techniques. It gathers data from previously published studies, each of which describes the methodologies used to generate the various data types, the scientific underpinnings of the techniques used to interpret the data in terms of past temperature change, and the important uncertainties. A major feature of this database is the integration of these complementary proxy data types and the harmonization of the metadata that describe them. The database is also quality-controlled; it comprises time-series data of relatively high resolution (sample spacing finer than 400 years; see below) and with a relatively well-established time scale, with the goal of creating a cohesive and uniform data product.
This section describes the procedures used to assemble the database rather than the specific methods used to generate the individual data records that comprise the database. procedures -data sources. The Temperature 12k database builds on several published paleoclimate data compilations, including one recently used to reconstruct Holocene temperature gradients across the Northern Hemisphere 12 , which itself drew from earlier compilations  5, [13] [14] [15]. The majority of the pollen-based paleotemperature time series were obtained through the compilation of Marsicek et al. 16. The majority of the marine records were gathered as part of the US-based Data Assimilation for Deep Time (DADT) project, and some were selected from the compilations of the German Climate Modeling Initiative (PalMod 17 ).
For these, we focused on the subset of proxy types that record (near) sea-surface temperature. In addition to culling data from previous paleoclimate data compilations, we searched the literature and public data repositories (PANGAEA and World Data Service for Paleoclimatology, NOAA) for appropriate records. The remainder of the datasets were obtained through either the supplements of publications, or from individual data generators, some of whom are co-authors on this data product. Several records were not available from the original data generators. To rescue such data, particularly where they fill geographic gaps, time series were digitized from the source publication (as noted in the metadata). Most of the pollen-based paleotemperature time series, and data from marine and glacier-ice archives were previously available through public repositories.
In contrast, of the 105 records based on chironomids and biomarkers from terrestrial deposits, only 37% were previously available through public repositories. In addition, this data product includes an expanded and harmonized suite of metadata for all of the records, including those that we obtained from data repositories. The database also includes the chronological data used to develop the age scale for the proxy time series. For a large portion of studies, this chronological information was not previously archived along with the proxy records per se. Only data published in the peer-reviewed literature were considered. This restriction helps to assure that the data are high quality, intended for scientific reuse, and are supported by vetted, complete and often nuanced paleoclimate and geochronological interpretations.
a comprehensive database of paleoclimate records is needed to place recent warming into the longer-term context of natural climate variability. We present a global compilation of quality-controlled, published, temperature-sensitive proxy records extending back 12,000 years through the Holocene. Data were compiled from 679 sites where time series cover at least 4000 years, are resolved at sub-millennial scale (median spacing of 400 years or finer) and have at least one age control point every 3000 years, with cut-off values slackened in datasparse regions. The data derive from lake sediment (51%), marine sediment (31%), peat (11%), glacier ice (3%), and other natural archives. The database contains 1319 records, including 157 from the Southern Hemisphere. the multi-proxy database comprises paleotemperature time series based on ecological assemblages, as well as biophysical and geochemical indicators that reflect mean annual or seasonal temperatures, as encoded in the database.
Background & Summary Placing recent global warming in the context of natural climate variability requires the long-term perspective afforded by paleoclimate proxy records. Reconstructing past global climatic changes relies on a variety of evidence from a large number of well-distributed sites. Previous syntheses of Holocene temperature records have typically focused on specific time horizons (mostly 6000 years ago), and are based nearly entirely on pollen assemblages from terrestrial archives  [1] [2] [3] [4]  , or are dominated by sea-surface temperatures  5  near continental margins. Few global datasets have been compiled based on evidence from a wide variety of proxy types, including ecological, geochemical and biophysical evidence from both marine and terrestrial archives. Understanding of paleoclimate is enriched by a multi-proxy approach.
Using multiple proxy types can help expand geographic coverage while enabling an assessment of inherent proxy biases. However, assembling a comprehensive database of continuous (time-series instead of time-slice) Holocene paleotemperature proxy records supported by a uniform suite of metadata descriptors across a wide variety of proxy data types is challenging  6  , and has not yet been attempted. In addition, a large portion of the data and metadata that form the basis of published paleoclimate studies have not been made available through public repositories, prior to this data synthesis. This data descriptor presents version 1. 0. 0 of the Temperature 12k database (ref. 7 , with additional supporting information and updates at: www. ncdc. noaa. gov/paleo/study/27330). It describes the methods used to assemble the database, including the criteria for record inclusion, and it describes each of the metadata fields that enable intelligent and automated reuse of the time-series data (Table  1 ).
In addition, this data descriptor summarizes the major features of the records that comprise the database, including millennial-scale trends in Holocene temperature. The robustness of these major trends is explored by subdividing the dataset into various spatial, methodological, seasonal and other categories and visualizing the extent to which these data subsets represent the overall trends of the database both latitudinally, and through the past 12,000 years. The data are useful for addressing a variety of paleoclimate research questions at global to regional scales. For example, they are needed to help understand how the ocean-atmosphere circulation has evolved along with past global climate changes. The database is designed for comparison with model-based simulations of climate, with the goal of evaluating model performance while gaining insights into the mechanisms and feedbacks associated with global climate change.
Data DeScriptor opeN procedures -selection criteria. The Temperature 12k database was designed to address research questions involving temperature change over the Holocene at regional to global scales. Thousands of studies have been published that attest to Holocene temperature changes. These records have widely variable temporal resolution, duration, and chronological control. In order to provide a consistent, quality controlled data product, we selected records that meet specific, quantitative criteria. These criteria were designed for relatively broad inclusion, while concentrating on the highest-resolution and well-dated records. The criteria were adjusted for selected sites to fill major geographic gaps, or for other reasons as justified by authors in the 'QC Comments' section of the metadata.
The selection criteria were: Temperature sensitivity. Only those proxy records that have a demonstrated relation with temperature were included. Because most of the paleotemperature time series are not sufficiently resolved temporally to meaningfully compare with instrumental-based observations, this demonstration of temperature sensitivity is typically based on accepted understanding of the proxy systems. The specific approach and the calibration data used for the resulting paleotemperature estimates are typically described in the original publication for each study site and are specified within the metadata for most records ('Calibration Method'). That a proxy type is sensitive to temperature does not preclude its sensitivity to other environmental variables, such as moisture availability or salinity.
The extent to which a proxy indicator is temperature-dependent can vary among sites and through time. Proxy records with multiple simultaneous interpretations, such as those interpreted as a combination of changes in precipitation amount and temperature, were generally excluded from the database, unless the authors of the original studies identified temperature as the primary control on the proxy. Proxy data do not have to be converted to units of degrees to be useful indicators of past temperature. This database includes 43 relative temperature indicators that are reported in their native proxy variables (e. g. , δ  18  O of glacier ice). They are useful because (1) they attest to the timing and relative magnitude of change, which is sufficient for many statistical reconstruction methods, especially those that do not assume linearity between the proxy and the climate variable; (2) they are used in proxy-system modeling and in some cases can be compared directly to climate model output; and (3) they provide a more complete spatial coverage for the proxy network.
Data records This data descriptor presents version 1. 0. 0 of the Temperature 12k database (ref. 7 , www. ncdc. noaa. gov/paleo/ study/27330 and https://doi. org/10. 25921/4RY2-G808). Metadata. The database includes a large variety of metadata to facilitate subsampling, analysis, and intelligent reuse (described briefly in Table  1 ). The metadata (Suppl. 1 ) document information about the: (1) site location, including: 'Site Name,' 'Country Ocean' (based on NASA GCMD location keywords), latitude ('Latitude'), longitude ('Longitude'), and 'Elevation. ' Geodetic data are in units of decimal degrees with respect to the WGS84 ellipsoid. (2) bibliographic citations (DOI when available). 'Publication 1' typically refers to the original study that describes the data and was authored by the data generator, whereas 'Publication 2' typically refers to some refinement of the original study including subsequent paleotemperature analyses based on the original data.
For most of the pollen records from North American and Europe, 'Publication 1' is the first of the citations listed for the dataset as referenced in the Neotoma Paleoecology Database (hereafter, "Neotoma") and 'Publication 2' is the synthesis study of Marsicek et al. 16  , the most recent and comprehensive analysis of pollen data from this region. (3) data source. 'Original Data Citation' is the data citation (persistent identifier) used to locate the proxy data and paleotemperature values in a long-term and publicly accessible repository. Data from online supplements of articles are often behind paywalls and therefore not public, and some have been superseded by versions that were subsequently modified and stored in data repositories. Data transferred to a public repository for the first time as part of this data product are listed as 'Original Data Citation' = 'this compilation.
' Taxonomic assemblage data are beyond the scope of this paleoclimate-oriented database. For pollen, information is provided in the metadata to access the assemblage and other information in Neotoma. Namely, 'Neotoma ID' is either the dataset identifier or the DOI for the landing page, which includes assemblage and other (meta) data for pollen records that are currently curated in Neotoma. For some marine microfossil records, 'Original Data Citation' is a link to the assemblage data stored at PANGAEA and WDS-NOAA Paleoclimatology. (4) bio-physical indicator and method used to infer past temperature, including: ' Archive Type, ' 'Proxy General' , and 'Proxy Type, ' 'Proxy Detail. ' The latter is particularly useful for proxy records that are based on isotope and geochemical analyses for which the specific sensor species or material type is essential information.
'Proxy General' is used to group proxy types to simplify plotting of figures. The 'Calibration Method' used to translate proxy data to temperature is stated for most calibrated proxy records, or is typically stated within the original publication. 'Paleo Data Notes' provides additional pertinent information about the proxy record, including its limitations as represented by the original study. (5) climate interpretation. All of the records included in this data product are temperature sensitive ('Climate Variable' = 'T'), and most are calibrated ('Variable Name' = 'temperature'), either as absolute temperature ('Datum' = 'abs') or as a temperature anomaly ('Datum' = 'anom'). 'Climate Variable Detail' provides further information about what environmental temperature is represented by the sensor (air, surface water, subsurface water).
Preference was generally given to the highest resolution or most recent rendition of a proxy record. When there was no clear basis for selection, and different interpretations were based on the same proxy data (e. g. , two different training sets were applied to the same assemblage data), the time series were combined, first by subtracting the record means to avoid artifacts related to combining time series of different lengths or number of samples, then by averaging to express temperatures as temperature anomalies ('Datum' = 'anom'). These composited temperature records are designated, 'Variable Name' = 'temperatureComposite' and are noted in the 'QC comments'. The paleotemperature time series used in the composites are retained in the database. Paleo temperatures from sites within the margins of former ice sheets were not corrected for the effect of isostatic rebound.
(  6 ) time of year represented by the climate variable ('Seasonality'). When available, specific months are listed according to the corresponding calendar-month number. Because of the wide variety of specific seasonalities included in the database, 'Season General' is used to generalize the seasonality as either annual, summer or winter. Several marine records represent transitional seasons; for these, spring was grouped with summer and fall with winter. Six or more months overlapping with June were categorized as annual. This field is also used to distinguish sites for which there are both summer and annual (= 'summer+' and 'annual') from sites where summer records are not paired with an annual counterpart (= 'summerOnly'), with an equivalent formulation for 'winter+' and 'winterOnly. ' This enables easy filtering of the database to select sites with either seasonal or annual time series, or both.
When 'Variable Name' = 'temperatureComposite, ' this time series is the average of winter and summer time series, which were calculated for this database to approximate annual values when no annual values are available, as indicated in the 'QC comments. ' 'Calibration Season' (when available) specifies the exact month(s) to which the climate variable have been calibrated. For example, many Northern Hemisphere chironomid records are considered to represent summer temperature ('Seasonality' = '6 7 8'); however, they are usually calibrated against only July or August temperatures ('Calibration Season' = '7' or '8'). For most records, 'Calibration Season' and 'Seasonality' are identical. (  7 ) chronology, including: youngest sample age ('Min Year'), oldest sample age ('Max Year'), and the median time-series resolution ('Resolution'), which is calculated as the median difference between the modeled ages of consecutive proxy samples, extending back 12,000 years.
To quantify the frequency of age-control points, 'Ages Per kyr' is calculated as the average number of radiocarbon (the vast majority of age types), tephra, and U/Th ages per 1000 years back to 12,000 years. (8) quality control, including the initials of the author(s) ('QC Certification') of this data product who was (were) responsible for assuring that an individual record meets the selection criteria, or for justifying the inclusion of records that do not meet the criteria, and for entering additional comments to improve the reusability of the proxy record ('QC Comments'). (9) link to the data, including a browser-based interface for LiPD files ('Link to LiPDverse') with data-viewing and download capabilities (LiPD and. csv formats).
Number and type of proxy records. In this data descriptor, the term "site" refers to a single location (or limited area) where various analyses were conducted to generate one or more "proxy time series" (Fig. 1 ). Each proxy time series is interpreted in terms of temperatures for one or more seasons, collectively and generally referred to as "records". The Temperature 12k database includes proxy time series from 470 terrestrial and 209 marine sites (Suppl. Table  2 ; Fig. 2 ). In total, this database comprises 1319 paleotemperature records. Multiple seasons are represented as different records at most sites, especially those based on pollen assemblages. In some cases, multiple records from the same site are based on different proxy types, most commonly planktic foraminifera δ 18 O, Mg/Ca, and alkenones from the same marine sediment core.
The database includes 715 records from lake sediments, 359 records from marine sediments, and 245 from other terrestrial archives (e. g. , glacier ice and speleothem). Alkenones and isotopes are the dominant sea-surface temperature proxies, whereas pollen and chironomids are the most common terrestrial temperature proxy types. In addition, the database includes paleotemperature evidence from a wide variety of other proxy types, such as assemblages of vegetation macrofossils from pack-rat middens, dinocysts from marine sediment, the composition of glycerol dialkyl glycerol tetraethers (GDGTs), abundance of chlorophyll from lake sediment, or the isotopic composition of pore ice in permafrost, to name a few. The most frequent proxy type is pollen. Unlike other compilations of large-scale, pollen-based climate reconstructions, records in this database were screened for resolution and chronological control.
In addition, the Temperature 12k database includes links (DOIs) to the primary pollen assemblage and additional data as curated in Neotoma. Most of the pollen-based paleotemperature time series from North America and Europe in this database are from the synthesis of Marsicek et al. 16  , which used the modern analogue technique to calculate paleotemperatures back to around 11 ka, and screened records using the PalaeoSig 19 package ('randomTF' function with a 95% confidence level). Data from 209 of their 642 sites met our selection criteria. This database expands on the original data archive for ref. 16  (www. ncdc. noaa. gov/paleo-search/study/22992) by also including warmest-month temperatures based on the same pollen data and procedures, along with the mean annual temperatures. The 'Original Data Citation' for these extended records are therefore indicated as 'this compilation'.
In addition, this database includes the native-resolution time series for those datasets, whereas the original data archive features temperatures summarized in 100-year intervals. The most frequent marine proxy types are δ 18 O, alkenones (U K ' 37 ), and Mg/Ca, including data from 135 out of 260 sites that were assimilated from the DADT project. For nearly all of these records, plus those based on TEX 86 , we generated paleotemperature time series by using the Bayesian calibration methods of Malevich et al. 20  , Tierney and Tingley  21, 22  , and Tierney et al. 23  respectively, with their published model parameters, as specified in 'Calibration Method'. The original temperature time series are retained among the ancillary records in the larger collection of temperature-sensitive datasets ('In Compilation' = Tverse, see below) and are noted as such in the 'QC Comments' field.