Transforming scholarship in the archives through handwritten text recognition:Transkribus as a case study

Purpose: An overview of the current use of handwritten text recognition (HTR) on archival manuscript material, as provided by the EU H2020 funded Transkribus platform. It explains HTR, demonstrates Transkribus, gives examples of use cases, highlights the affect HTR may have on scholarship, and evidences this turning point of the advanced use of digitised heritage content. The paper aims to discuss these issues. - Design/methodology/approach: This paper adopts a case study approach, using the development and delivery of the one openly available HTR platform for manuscript material. - Findings: Transkribus has demonstrated that HTR is now a useable technology that can be employed in conjunction with mass digitisation to generate accurate transcripts of archival material. Use cases are demonstrated, and a cooperative model is suggested as a way to ensure sustainability and scaling of the platform. However, funding and resourcing issues are identified. - Research limitations/implications: The paper presents results from projects: further user studies could be undertaken involving interviews, surveys, etc. - Practical implications: Only HTR provided via Transkribus is covered: however, this is the only publicly available platform for HTR on individual collections of historical documents at time of writing and it represents the current state-of-the-art in this field. - Social implications: The increased access to information contained within historical texts has the potential to be transformational for both institutions and individuals. - Originality/value: This is the first published overview of how HTR is used by a wide archival studies community, reporting and showcasing current application of handwriting technology in the cultural heritage sector

Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura

Publisher Copyright: © 2023, The Author(s).Migraine is a complex neurovascular disease with a range of severity and symptoms, yet mostly studied as one phenotype in genome-wide association studies (GWAS). Here we combine large GWAS datasets from six European populations to study the main migraine subtypes, migraine with aura (MA) and migraine without aura (MO). We identified four new MA-associated variants (in PRRT2, PALMD, ABO and LRRK2) and classified 13 MO-associated variants. Rare variants with large effects highlight three genes. A rare frameshift variant in brain-expressed PRRT2 confers large risk of MA and epilepsy, but not MO. A burden test of rare loss-of-function variants in SCN11A, encoding a neuron-expressed sodium channel with a key role in pain sensation, shows strong protection against migraine. Finally, a rare variant with cis-regulatory effects on KCNK5 confers large protection against migraine and brain aneurysms. Our findings offer new insights with therapeutic potential into the complex biology of migraine and its subtypes.Peer reviewe

Perioperative Complications of Cesarean Delivery Myomectomy A Meta-analysis

OBJECTIVE: To assess the association of myomectomy during cesarean delivery with intraoperative and peri-operative maternal morbidity. DATA SOURCES: We searched MEDLINE (1966-2017), Scopus (2004-2017), ClinicalTrials.gov (2008-2017), EM-BASE (1980-2017), and Cochrane Central Register of Controlled Trials CENTRAL (1999-2017) databases. METHODS OF STUDY SELECTION: We selected all observational studies that reported outcomes on patients undergoing myomectomy at the time of cesarean delivery. Statistical meta-analysis was performed with RevMan 5.3. RESULTS: Nineteen studies were included in our systematic review with a total number of 3,900 women. Among them, 2,301 women had myomectomy during cesarean delivery and 1,599 had cesarean delivery only. Women undergoing concomitant myomectomy had a mild decline in hemoglobin compared with those who had cesarean delivery only (mean difference 0.25 mg/dL, 95% CI 0.06-0.45). Myomectomy at the time of cesarean delivery is associated with longer surgical time compared with cesarean delivery alone (mean difference 13.87 minutes, 95% CI 4.78-22.95). Blood transfusion (odds ratio [OR] 1.41, 95% CI 0.96-2.07) and postoperative fever (OR 1.12, 95% CI 0.80-1.56) rates did not differ between the two groups (myomectomy compared with no myomectomy). A statistically, but not clinically, significant increase in postoperative hospitalization was evident in the myomectomy group (mean difference 0.35 days, 95% CI 0.25-0.46). CONCLUSION: This systematic review and meta-analysis of observational studies demonstrated an association with increased operative time and hemoglobin drop in patients who underwent cesarean myomectomy compared with cesarean delivery alone. No increased rate of major hemorrhage or need for transfusion was identified. Cesarean myomectomy may be considered in cases of isolated myomas, although randomized trials are needed

A genome-wide association study of social trust in 33,882 Danish blood donors

Social trust is a heritable trait that has been linked with physical health and longevity. In this study, we performed genome-wide association studies of self-reported social trust in n = 33,882 Danish blood donors. We observed genome-wide and local evidence of genetic similarity with other brain-related phenotypes and estimated the single nucleotide polymorphism-based heritability of trust to be 6% (95% confidence interval = (2.1, 9.9)). In our discovery cohort (n = 25,819), we identified one significantly associated locus (lead variant: rs12776883) in an intronic enhancer region of PLPP4, a gene highly expressed in brain, kidneys, and testes. However, we could not replicate the signal in an independent set of donors who were phenotyped a year later (n = 8063). In the subsequent meta-analysis, we found a second significantly associated variant (rs71543507) in an intergenic enhancer region. Overall, our work confirms that social trust is heritable, and provides an initial look into the genetic factors that influence it.</p

Variants at the Interleukin 1 Gene Locus and Pericarditis

Importance: Recurrent pericarditis is a treatment challenge and often a debilitating condition. Drugs inhibiting interleukin 1 cytokines are a promising new treatment option, but their use is based on scarce biological evidence and clinical trials of modest sizes, and the contributions of innate and adaptive immune processes to the pathophysiology are incompletely understood. Objective: To use human genomics, transcriptomics, and proteomics to shed light on the pathogenesis of pericarditis. Design, Setting, and Participants: This was a meta-analysis of genome-wide association studies of pericarditis from 5 countries. Associations were examined between the pericarditis-associated variants and pericarditis subtypes (including recurrent pericarditis) and secondary phenotypes. To explore mechanisms, associations with messenger RNA expression (cis-eQTL), plasma protein levels (pQTL), and CpG methylation of DNA (ASM-QTL) were assessed. Data from Iceland (deCODE genetics, 1983-2020), Denmark (Copenhagen Hospital Biobank/Danish Blood Donor Study, 1977-2022), the UK (UK Biobank, 1953-2021), the US (Intermountain, 1996-2022), and Finland (FinnGen, 1970-2022) were included. Data were analyzed from September 2022 to August 2023.Genotype. Main Outcomes and Measures: Pericarditis. Results: In this genome-wide association study of 4894 individuals with pericarditis (mean [SD] age at diagnosis, 51.4 [17.9] years, 2734 [67.6%] male, excluding the FinnGen cohort), associations were identified with 2 independent common intergenic variants at the interleukin 1 locus on chromosome 2q14. The lead variant was rs12992780 (T) (effect allele frequency [EAF], 31%-40%; odds ratio [OR], 0.83; 95% CI, 0.79-0.87; P = 6.67 × 10-16), downstream of IL1B and the secondary variant rs7575402 (A or T) (EAF, 45%-55%; adjusted OR, 0.89; 95% CI, 0.85-0.93; adjusted P = 9.6 × 10-8). The lead variant rs12992780 had a smaller odds ratio for recurrent pericarditis (0.76) than the acute form (0.86) (P for heterogeneity = .03) and rs7575402 was associated with CpG methylation overlapping binding sites of 4 transcription factors known to regulate interleukin 1 production: PU.1 (encoded by SPI1), STAT1, STAT3, and CCAAT/enhancer-binding protein β (encoded by CEBPB). Conclusions and Relevance: This study found an association between pericarditis and 2 independent sequence variants at the interleukin 1 gene locus. This finding has the potential to contribute to development of more targeted and personalized therapy of pericarditis with interleukin 1-blocking drugs.</p