dataesr/scientific-paragraphs-categorization huggingface dataset:
The raw data were deposited at the NCBI Gene Expression Omnibus (GEO) database (https://www. ncbi. nlm. nih. gov/geo/ q u e r y / a c c. c g i ? a cc = G S E 23 7 4 4 1 ) u n d e r t h e a cc e s s i o n number GSE237441. Differential gene expression across groups was analyzed using linear mixed effect models; differentially expressed genes (DEGs) were defined as fold-change > 2 or < -2, and Benjamini-Hochbergadjusted p < 0. 01. Analyses were conducted using R software (version 3. 2. 2; R Foundation for Statistical Computing, Vienna, Austria). The upregulated and downregulated DEGs were analyzed using DAVID Bioinformatics Resources software (version 2021; https:// david. ncifcrf. gov/) for functional annotations and gene set enrichment analysis. DAVID was used to obtain statistically enriched Gene Ontology (GO) terms for biological processes (GOTERM_BP_FAT).
GO terms with EASE score < 0. 05 were considered statistically enriched. Based on the known mechanisms in GCA, pathways of interest, signaling cascades, and molecules were selected from among the dysregulated GO terms. These selections are presented as dot plots using ggplot2 package of R software (version 3. 2. 2). Dysregulated genes per layer with a fold-change > 2 or < -2 were organized according to the STRING network (https://stringdb. org/). The one or two main networks were represented for each layer. Genes disconnected from the main network were removed. An interaction score with the highest confidence (0. 900) was used. The interaction sources excluded text mining. Using networks generated by the STRING network, a pharmacogenomic network was constructed by targeting existing druggable genes (https:// www.
Acknowledgments The authors thank the study participants, and the  UC San Diego Stem Cell Genomics Core , the  Stem Cell Program, La Jolla, CA , and  Cristian Quintero  for his assistance with the  Keyence microscope. We also thank  San Diego Pathology  and  David Tobias Vargas  for his technical assistance, as well as  NanoString  for the grant opportunity and the GeoMx DSP specialists in Seattle, WA. SP received a fellowship grant from the  Servier Institute France.
This paucity of data led us to design the GLOBOSTAD study (NCT03992417), which aims to inform clinician treatment choices by characterizing the patients who receive dupilumab for AD in a real-world setting with respect to their medical history, sociodemographic and disease characteristics, and prior and concomitant treatments for AD. Here, we describe the baseline demographics and clinical characteristics, including disease severity, comorbidities, treatment history and patient-reported outcomes, before treatment initiation with dupilumab, of patients with AD who are enrolled in the GLOBOSTAD registry.
Study Design The GLOBOSTAD registry (NCT03992417) is an ongoing, 5-year, international, longitudinal, prospective, observational study of adult and adolescent patients with AD who receive dupilumab according to country-specific prescribing information. Consecutive patients with AD at each study site who received an initial prescription for dupilumab were invited to participate. Analysis includes data from all patients who were eligible and consented to participate in the study from  July 11, 2019, to   March 31, 2022. GLOBOSTAD is being conducted in accordance with the Declaration of Helsinki, the International Conference on Harmonisation Good Clinical Practice guideline and applicable regulatory requirements. All subsequent amendments and the protocol were reviewed and approved by institutional review boards before patient recruitment, and all patients provided written informed consent before participating in the study.
However, patients were eligible for inclusion if they had already initiated treatment with dupilumab for AD within 6 months of their enrollment in the registry, provided that all core baseline data required by the registry protocol (i. e. , percent body surface area [BSA] affected, Eczema Area and Severity Index [EASI] total score, SCORing Atopic Dermatitis [SCORAD] total score, Patient-Oriented Eczema Measure [POEM] and Dermatology Life Quality Index [DLQI] total score) had been captured at the time of initiating dupilumab treatment and were available for entry in the registry database.
Assessments Patient data for the Registry are collected at baseline (the time of treatment initiation with dupilumab, whether prior to or on/after the screening visit), month 3 (± 1 month), month 6 (± 2 months) and every 6 months (± 2 months) thereafter until the end of the total 5-year observational period. Baseline assessments are performed on the day of the screening/baseline visit and include investigator collection of sociodemographics, personal and family history of AD and selected atopic diseases and comorbidities, and AD treatments prior to baseline; concomitant medications, and reasons for initiating dupilumab. Baseline scores for physician-and patient-reported outcome measures of disease severity and burden are also collected. Physician-rated AD assessments include the EASI total score (0-72)  [19] , SCORAD total score (0-103)  [20]  and percent BSA affected.
History of While most patients in the GLOBOSTAD registry reported having at least one type 2 inflammatory comorbidity (77. 8%), other comorbidities were only reported by a small proportion of patients (35. 5%). This finding may, in part, be attributed to the relatively young age of this patient population (mean age 35. 5 years, with most patients in the 18-39 age group). Overall, patients enrolled in GLOBOSTAD were representative of the real-world population with AD. Patients had a longstanding history of AD, with a mean 24. 8 years since diagnosis. Approximately half (50. 4%) had a university/ higher education, and 63. 6% were in full-or part-time employment. This interim analysis of data from GLOBOS-TAD expands on data from previous and ongoing studies and further characterizes patients who receive dupilumab for AD in the real-world clinical setting.
The study includes adults and adolescents with AD initiating dupilumab treatment and reflects reimbursement practices according to country-specific prescribing information in 22 countries across the globe. Participating sites were selected to try to achieve a balance regarding geographic distribution, type of clinical setting (e. g. , academic versus community health centers) and prescriber specialty, which could reasonably represent the larger patient and prescriber community, thereby favoring worldwide generalizability of the results. The collection of comprehensive baseline data permitted a thorough characterization of disease severity, including physician-assessed and PRO measures, type 2 comorbidities, family history of AD and AD treatment history. Future analyses of data from GLOBOSTAD will permit the longitudinal observation of the effectiveness and safety of dupilumab in adults and adolescents with AD, in the real-world setting.
(Accelerating research & development for advanced therapies) project, under grant agreement No 945473. This Joint Undertaking receives support from the European Union's Horizon 2020 research and innovation program and EFPIA. M. B. J. was the recipient of a fellowship from Minist ère de l'enseignement sup érieur et de la recherche and of the 2022 Martin Villard Haemostasis Award (Grifols Scientific Awards) in basic research. P. J. L. receives research support from Pfizer, Roche, Sanofi, and Sobi.
Data are representative of 2 independent experiments. (E) The estimated procoagulant activity of emicizumab in mouse plasma was measured using a FVIII:C chromogenic assay with human FIXa and FX (Biophen FVIII:C, Hyphen Biomed). The data (mean ± SD) represent the percentage of procoagulant activity of emicizumab as a function of the activity measured in plasma just before the first injection of IdeS (at 6 hours: T6). Statistical significance was assessed using a two-way analysis of variance with Geisser-Greenhouse correction on the 9-to 72-hour time points (*: P <. 05; ***: P <. 001; ****: P <. 0001; ns: not significant). absence or presence of IVIg, respectively (Figure  4B ). The improved catabolism of IgG in the presence of IVIg reflects the increased proteolytic efficiency of IdeS at non-limiting substrate concentrations.
Funding information This work was supported by  Institut National de la Sant é et de la Recherche M édicale (INSERM) ,  Centre National de la Assistance Publique des H ôpitaux de Paris  and by grants from the  Bayer Hemophilia Award Program  ( BHAP 2019  and  BHAP 2021 ),  Agence Nationale de la Recherche  ( ANR-18-CE17-0010-02-Exfiltrins  and  ANR-21-CE17-0043-Persia ),  Spark Therapeutics Inc (Philadelphia , PA),  COordination M édicale pour l'Etude et le Traitement des  maladies H émorragiques constitutionnelles (CoMETH) and by the  Innovative Medicines Initiative 2 Joint Undertaking   ARDAT.
Objective: To analyze the implementation of the Principles of Care (PoC) in primary immunodeficiencies (PID) in Southeast Asia (SEA) countries -six years after its call of action. Methodology: Using the newly developed PID Life Index software, the index of implementation of principles of care in the management of PIDs patients involving the six participating SEA countries (Cambodia, Indonesia, Malaysia, Vietnam, Thailand, and Philippines) were extracted. For each of the six separate principles, the index from the six countries will be compared and presented based on the calculated index. Results: Comparative analysis of the six principles of care of PID in the SEA countries showed low diagnostic rate with minimal availability of diagnostic tests options. Generally, almost all SEA countries provide curative treatments, vaccines, and anti-infectious therapies although the reimbursement scheme varied in relieving patients' financial burden.
Materials and method Our study analyzed data extracted from the PID Life Index on a virtual platform. We explored the index from 6 SEA countries namely i) Cambodia ii) Indonesia iii) Malaysia iv) Thailand v) Philippines and vi) Vietnam. Descriptive analysis was applied throughout this study and the results were expressed in n (%), where n represented the total number of countries involved in each principle. The score of each principle was assessed separately and tabulated into tables and figures for regional comparison. This study presents the findings of data collected in 2022 from six SEA countries, providing a comprehensive overview of general status of the Principles of Care in the region.
Severe combined immunodeficiencies (SCID) newborn screening Although there is growing evidence supporting the implementation of newborn screening for early detection of severe combined immunodeficiencies (SCID), most countries in SEA have not yet adopted this screening program. Over the years, active detection was mainly done in families who had already lost a previous child due to SCID. Within the six SEA countries, only Vietnam has regional implementation of the SCID newborn screening. The only other SEA country which had started on SCID newborn screening program is Singapore, however it is not included in our analysis as Singapore is not part of the contributing countries for PID Life Index. Nonetheless, through the Singapore's experience, within a span of one year, the newborn screening program (NBS) had successfully identified 13 cases of non-SCID T-cell lymphopenia using T-cell receptor excision circle (TREC) assay performed in dried blood spots of 35888 newborns (15).
Coverage of curative therapies for patients with PID According to the PID Life Index, over half of the SEA countries have expertise for HSCT as the only curative treatment (4). Of the four countries, Vietnam had the highest reimbursement rate at approximately 70 to 90%, followed by Malaysia (51 to 69%) and Thailand (up to 50%). It is important to note that HSCT is a costly procedure as it involves not only the medical procedure but also logistic expenses such as traveling and hospitalization fees, pharmaceutical costs, diagnostic costs, and also indirect expenses such as lost income due to absenteeism from work to care for PID patients  (23). Unfortunately, despite these financial challenges, a Indicates that the treatment options were not available in the country, hence had no data on the coverage level.
Principle 5: National patient organizations Over the years, national patient organizations for PID have become an increasingly important stakeholder in the decision- FIGURE 2 Overall universal health coverage in six Southeast Asia (SEA) countries. Notes: This data was derived from the summary of PID Life Index which demonstrated the coverage level of treatment from its total cost in each country. The coverage rate was expressed in percentage (%). making process for the care of rare diseases. It is generally acknowledged that patient representatives are well-informed of their conditions and treatment, thus able to provide personal perspectives which are unique in advocating for their community. Aside from creating a supportive environment for patients and family members to exchange experiences and receive guidance, many organizations also actively advocate to improve diagnosis, treatment, and care for patients in individual countries  (24).
There were no diagnostic tools and treatment available in this country except supportive therapies (anti-infectious and vaccine prophylaxis) which were fully funded by patients. Similarly in Malaysia, Intan et al. found that only 51 PID cases were detected in the span of 20 years, supporting the low diagnosis rate of 0. 4 which was very low compared to other Asian countries  (29). Our findings from the PID Life Index agreed to the conceptualized idea that this could be attributed to the unavailability of PID patient database registry, inadequate immunodiagnostic capacity, unavailability of national newborn screening program and reduced awareness among healthcare workers on early detection of PID. As of 2022, there were only seven clinical immunologists in Malaysia, of which six were centered in the heart of Kuala Lumpur.
We identified several limitations in our study. Firstly, the utilization of PID Life Index, which is a crucial tool in gathering the data on the landscape of PID in SEA, may have some shortcomings. Although data was gathered systematically through IPOPI's network of national member organizations or medical contact in countries where no patient organization existed, some respondents may have considered this as an opportunity to promote their country's progress in the field of PID. This bias is also evident when the Index does not generalize the overall situation in the country, especially in regions where only one medical expert was known. Thus, this shortcoming was not able to provide an overall perspective in a given country. Secondly, our findings relied solely on data from the PID Life Index, without expert validation in the involved SEA countries.
Given the scarcity of available studies on the epidemiological status of PID in SEA, it was difficult to fully grasp the implementation of these principles. Thirdly, we did not enquire further about the national policies in-place for PID patients, nor did we explore the existing discrepancies between national laws and the day-to-day reality of PID patients. Therefore, we were unable to justify the current implementation of health policies in a given country for PID patients and their families. Lastly, our study did not encompass the entire SEA region, as national data from countries such as Singapore, Myanmar, Laos, and Brunei were not included in the PID Life Index database.
Acknowledgments We would like to express utmost gratitude to IPOPI collaborators worldwide for their support in making the PID Life Index possible and also for their submission of country data towards this project. We would also thank  IPOPI  and  SEAPID consortium  for their experts' advice in ensuring updated information delivered in this publication. On top of that, we are also grateful to the  Faculty of Medicine , The  National University of Malaysia (UKM)  for their continuous support towards this study.
Methods The present study was designed as an observational, retrospective, naturalistic 12-month mirror-image study. We compared outcomes 12 months before to outcomes 12 months after initiation of dual-LAIs. The use of dual-LAIs is regularly reported in the study center. The study was approved by the Data Protection Officer and by the local IRB of the study center (Centre Hospitalier Alpes-Isère, Saint-Egrève, France; approval number -2021-01-01). The data was collected retrospectively between September 2014 and January 2022, which implies that dual-LAIs was not initiated at the same moment for all subjects. To this aim, we used the electronic medical records software of the study center that allows for secure, password-protected recording, storage, and retrieval of daily clinical data. Inclusion criteria were: i) patients hospitalized at least once at the Centre Hospitalier Alpes-Isère in Saint-Egrève, France; ii) patients ≥18 years old and diagnosed with schizophrenia or schizoaffective disorder according to DSM-5; iii) treatment-resistant defined by the persistence of symptoms despite at least two trials of antipsychotics drugs of adequate dose and duration (i.
e. , 6-8 weeks) with documented adherence, iv) patients with 12 months of regular dual-LAIs with documented adherence. Descriptive socio-demographics and clinical data including medication, reasons for hospitalization, and the following efficacy and tolerance outcomes were collected: number of hospitalization, total hospitalization length of stay, body mass index, agranulocytosis, lipid profile, and sugar levels. The initiation of dual-LAIs (index date) was defined as the first injection of the second LAI. If the patient was hospitalized when the combined treatment was started, this hospitalization was included in the hospitalization count of the month period preceding dual-LAIs. Analyses were performed using R (v4. 1. 2). The normality of the distribution of the outcomes was investigated with Shapiro-Wilk tests.
Statistics Statistical significance was determined with one-way analysis of variance tests (ANOVA), followed by Turkey-Kramer testing using GraphPad Prism software, Version 9 (Graphpad). The distribution of data was analyzed using a D'Agostino-Pearson Omnibus test. Normal data were tested with parametric tests: for two datasets we used a student's t-test. For more than two datasets, we used a one-way analysis of variance test (ANOVA).
Acknowledgments We thank  T. Littelton ,  P. Verstreken ,  Neufeld ,  G. Juhasz , the  Bloomington Drosophila Stock Center, FlyORF  and the  Developmental Studies Hybridoma  bank for reagents. We thank  Dr. James Sutherland ,  Prof. Volker Haucke ,  Prof. Eckart D. Gundelfinger ,  Dr. Benjamin Dehay , and  Dr. Erwan Bezard  for critical reading and proof-reading on the manuscript. Research in the laboratory is supported by the  Initiative d'Excellence de l'Université de Bordeaux (IDEX Neurocampus Chair)  and the  Region Nouvelle-Aquitaine. This study received financial support from the  French government  in the framework of the  University of Bordeaux 's  IdEx "Investments for the Future" program  /  GPR BRAIN_2030.
The Universal Health Coverage index is among the highest in Africa, with no or little out-of-pocket costs for BC diagnosis and treatment. Public schemes exist to provide funds and free transportation and accommodation to patients with BC during treatment. 8  Namibia is one of the countries that participated in the African Breast Cancer-Disparities in Outcomes (ABC-DO) prospective hospital-based cohort study, which collected comprehensive data on the full BC journey. 9  Previous ABC-DO publications have focused on individual segments of the BC journey. [10] [11] [12] [13] [14]  The present article analyzes the entire journey-from BC symptom recognition to diagnosis and through treatment-of Namibian women with BC who reached the main national public oncology center. We assess the extent to which GBCI pillars key performance indicator (KPI) benchmarks have been achieved to inform where and how the BC journey can be strengthened to ultimately reduce BC mortality in Namibia.
Data Sources At enrollment, women's sociodemographic characteristics, including self-reported ethnicity, BC knowledge and beliefs, and details of their prior BC journey (dates of first symptom and dates of and travel times to previous visits to HCPs) were obtained in a nurse-led structured face-to-face interview. 12, 16  Residential addresses were geocoded, from which travel times to reach WCH were estimated via geospatial methods in AccessMod version 5. 7. 8 (World Health Organization). 11, 17  TNM stage at diagnosis and tumor subtype were extracted from medical and pathology records. 10  Treatment and women's vital status were updated from medical records and trimonthly follow-up telephone interviews with the patient or her next-of-kin. 13, 18  Among women diagnosed with nonmetastatic BC who survived at least 6 months after diagnosis, treatment indication, completion, and abandonment were defined as in the National Comprehensive Cancer Network Harmonized Guidelines.
Autopsy According to the French law, complete fetal autopsy was performed after parental consent and according to standardized protocols. Detailed examination included X-ray, photographs, macroscopic and histological examination of all viscera. Fetal biometric data were assessed according to the morphometric criteria of Guihard-Costa and colleagues  [19]. All tissue specimens were immediately fixed in 10% formalin solution and processed routinely for embedding in paraffin wax. They were stained with hematoxylin, eosin and safran (HES). Then the slides were examined by light microscopy. Kidney sample were stained with Periodic Acid Schiff, and immune labeling was performed with anti-CD10 and anti-EMA. Fetal tissue samples were frozen at -80 °C for molecular genetic tests with parental consent.
Immunohistochemistry Double immunolabelings were performed on 7 µm thick sections of midbrain and hindbrain from fetus 3 and an age-matched control using ZO-1 (Thermofisher 617,300), PKCι (BD Biosciences 610,175), PKCζ (Santa Cruz SC17781), β-catenin (BD Biosciences 610,154) and N-cadherin (BD Biosciences 610,921) antibodies (Additional File 1: Table  S1 ). Confocal images were taken on a Zeiss LSM 700 microscope and were analyzed with ImageJ software.
7% covered at least at 30X. Variant calling was carried out with the Genome Analysis Toolkit (GATK), SAMtools, and Picard Tools. Single nucleotide variants were called with GATK Unified Genotyper, whereas indel calls were made with the GATK IndelGenotyper_v2. All variants with a read coverage ≤ 2 × and a Phred-scaled quality of ≤ 20 were filtered out. All the variants were annotated and filtered using an in-house developed annotation software system. We first focused our analyses on non-synonymous variants, splice site variants, and coding indels. Variants' pathogenicity was evaluated using SIFT (cutoff ≤ 0. 05), PolyPhen2 (HumVar scores, cutoff ≥ 0. 447) and Mutation Taster (cutoff: qualitative prediction as pathogenic) prediction algorithms. We also assessed frequency in control populations and datasets including the ExAC database, dbSNP129, the 1000 Genomes Project, ClinVar, HGMD and in-house exome data.
1b ). The 16 bp duplication is also a recurrent variation, previously reported in a patient with ventriculomegaly  [10]. This duplication leads to a frameshift and the creation of a premature termination codon with subsequent potential targeting of the mutated transcript for nonsense-mediated mRNA decay (NMD). While both variations are reported heterozygous in gnomAD, in 58 and 28 individuals respectively for the missense and the duplication, none of them was reported homozygous in the database.