Understanding the application of handwritten text recognition technology in heritage contexts: a systematic review of Transkribus in published research.

Handwritten Text Recognition (HTR) technology is now a mature machine learning tool, becoming integrated in the digitisation processes of libraries and archives, speeding up the transcription of primary sources and facilitating full text searching and analysis of historic texts at scale. However, research into how HTR is changing our information environment is scant. This paper presents a systematic literature review regarding how researchers are using one particular HTR platform, Transkribus, to indicate the domains where HTR is applied, the approach taken, and how the technology is understood. 381 papers from 2015 to 2020 were gathered from Google Scholar, Scopus, and Web of Science, then grouped and coded into categories using quantitative and qualitative approaches. Published research that mentions Transkribus is international and rapidly growing. Transkribus features primarily in archival and library science publications, while a long tail of broad and eclectic disciplines, including history, computer science, citizen science, law and education, demonstrate the wider applicability of the tool. The most common paper categories were humanities applications (67%), technological (25%), users (5%) and tutorials (3%). This paper presents the first overarching review of HTR as featured in published research, while also elucidating how HTR is affecting the information environment.

Addressing Barriers to Health Care Access of Congenital Heart Disease Patients in Guyana.

In order to mitigate the late presentation and resulting poor outcomes of children with advanced cardiac disease, the Ministry of Public Health (MOPH) in Guyana has expressed interest in identifying ways to improve access to health care for these children. The goal of this study was to identify barriers faced by CHD patients and their families in accessing pediatric cardiology services in Guyana, and to identify limitations to the diagnosis and referral of CHD patients by health care professionals. Two surveys were used to gain insight into the experiences of practicing health care professionals and the parent(s) or guardian(s) of children with CHD. Patients were identified based on convenience sampling at cardiology clinics and outreach clinics in both urban and rural Guyana. Physicians were identified using convenience sampling at health posts in rural Guyana. Fifty-two (n = 52) families were identified and interviewed throughout the regions visited. The majority of families identified distance, the need to travel, and their inability, financially and practically, to attend clinic as the main barrier to accessing specialized care. Twelve (n = 12) health care providers were interviewed. They identified limited knowledge surrounding the diagnosis and management of CHD, and perceived impracticality of referring patients to specialized services, despite being aware of the referral process. This study identifies the need for improved outreach and support for health care providers and families, especially those living in rural communities. It identifies some of the challenges faced in managing patients with CHD in Guyana, while establishing specific areas for quality improvement.

Profiling the ethnic characteristics of domestic injuries in children younger than age 5 years.

The home remains a very common location for deadly injuries among children younger than 5 years. The aim of this study is to describe the demographic and injury characteristics of domestic injuries in children younger than 5 years. The National Trauma Data Bank's National Sample Program data set was queried for children younger than 5 years with the injury site classified as home. Bivariate analysis was performed to determine unadjusted differences by ethnicity. Appropriate weight was applied to the sample to determine accurate national estimates. A total of 7,364 children, representing 32,033 children, were analyzed. Overall mortality was 1.6 per cent. Among whites, blacks, Hispanics, Asians, and Native Americans, intentional injuries accounted for 6.5, 12.8, 10.2, 5.2, and 19.0 per cent of all injuries by intent, respectively (P < 0.003). Burn injury was disproportionately higher in blacks (24.1%) followed by Native Americans and Asians (15.3 and 11.5%, P = 0.008). On multivariate analysis, black ethnicity was associated with increased length of stay. Intentional injuries were significantly higher in blacks and Native Americans with black patients sustaining a disproportionately higher proportion of burn injury. Therefore, greater attention is needed to provide more effective home safety interventions to children among high-risk ethnic groups.

Surgical treatment for women with breast cancer: do randomized clinical trials represent current medical practices?

Randomized clinical trials have not shown survival differences between breast cancer patients who undergo breast-conserving surgery and those who undergo modified radical mastectomy (MRM). Recent studies however, have suggested that these randomized clinical trials findings may not be representative of the entire population or the nature of current patient care. A retrospective analysis of female invasive breast cancer patients who underwent surgery in the Surveillance, Epidemiology, and End Results database (1990-2003) was performed. Survival was compared amongst women who underwent partial mastectomy, partial mastectomy plus radiation (PMR), or MRM. Cox proportional hazards regressions were used to investigate the impact of method of treatment upon survival, after adjusting for patient and tumor characteristics. A total of 218,043 patients, mean age 62 years, were identified. MRM accounted for 51.5 per cent of the study population whereas PMR accounted for 34.9 per cent. On multivariate analyses, significant improvement was observed in patient survival associated with PMR when compared with MRM patients (hazard ratio = 0.71, 95% confidence interval = 0.67-0.74, P < 0.001). This population-based study suggests that there is a survival benefit for women undergoing PMR in the treatment of breast cancer.

Mechanism of regulation and suppression of melanoma invasiveness by novel retinoic acid receptor-gamma target gene carbohydrate sulfotransferase 10.

Retinoic acid (RA) induces growth arrest and differentiation of S91 murine melanoma cells and serves as a valuable model for this disease. RA acts through activation of RA receptors (RAR), which are members of the nuclear receptor superfamily of ligand-inducible transcription factors. Interestingly, differentiation is mediated by RARgamma, but not by RARalpha or RARbeta, suggesting that RARgamma possesses unique and uncharacterized molecular properties. To address this question, DNA microarrays in combination with RAR isoform-specific agonists were employed to identify novel RARgamma target genes that may play a role in this process. Here, we identified and validated carbohydrate sulfotransferase 10 (CHST10) as a novel RARgamma target gene in S91 cells. The RARgamma-inducible CHST10 promoter was obtained, and two atypical, independently functioning RA response elements were identified in a 425 bp region. Surprisingly, this fragment is bound by RARgamma, but not by RARalpha or RARbeta, thus providing a mechanism for the observed RARgamma-specific regulation. CHST10 is a sulfotransferase that forms HNK-1 glycan on neural cell adhesion proteins and glycolipids, and HNK-1 is thought to modulate cell adhesion and possibly metastasis. We show that CHST10 is also regulated by RARgamma in a significant subset of human melanoma cells, and three-dimensional cell culture migration assays suggest that CHST10 functions as a suppressor of invasiveness, but not proliferation, in these cells. Induction of CHST10 by RARgamma-activating retinoids may present a novel therapeutic strategy to inhibit invasiveness in a subset of melanoma patients.

Apoptosis factor EI24/PIG8 is a novel endoplasmic reticulum-localized Bcl-2-binding protein which is associated with suppression of breast cancer invasiveness.

p53 is a critical tumor suppressor which removes cells with DNA damage by regulating expression and activity of a select group of p53-induced genes (PIG) that subsequently induce apoptosis. PIG8 was also identified as a gene induced by etoposide and named etoposide-induced gene 24 (EI24). Later experiments established EI24/PIG8 as a proapoptotic factor and suggested that it may function as a tumor suppressor. Indeed, EI24/PIG8 is relatively highly mutated in aggressive breast cancers and is located in a region which expresses frequent loss of heterozygosity. However, despite these important observations, the activity and role of EI24/PIG8 remain largely unknown. We used (immmuno)fluorescence microscopy and subcellular fractionation techniques to show that EI24/PIG8 is localized in the endoplasmic reticulum (ER). Pull-down experiments showed that it specifically binds with Bcl-2, a death regulator known to reside in mitochondria, ER, and the nuclear envelope. EI24/PIG8-Bcl-2 binding was corroborated by coimmunoprecipitation and other in vitro and in vivo protein-protein binding assays. Further analysis showed that EI24/PIG8 uses its N-terminal region to bind the BH3 domain in Bcl-2. Finally, we used immunohistochemical techniques to analyze expression of EI24/PIG8 in breast cancer tissue progression arrays and showed that loss of EI24/PIG8 is associated with tumor invasiveness but not with the development of the primary tumor. These results suggest that EI24/PIG8 is a novel, ER-localized Bcl-2-binding protein which may contribute to apoptosis by modulating the activity and/or function of Bcl-2 in this organelle. EI24/PIG8 may serve to prevent tumor spreading, consistent with its suspected role as a tumor suppressor.

Regulation of nuclear receptor activity by a pseudouridine synthase through posttranscriptional modification of steroid receptor RNA activator.

Nuclear receptors (NRs) induce transcription through association with coactivator complexes. We identified a pseudouridine synthase (PUS), mPus1p, as a coactivator for retinoic acid receptor (mRAR)gamma and other NR-dependent transactivation. mPus1p is a member of the truA subfamily of PUSs, a class of enzymes that isomerize uridine to pseudouridine in noncoding RNAs, such as tRNA, to ensure proper folding and function. mPus1p binds the first zinc finger of mRARgamma and also associates with other NRs. Interestingly, mPus1p pseudouridylates coactivator Steroid Receptor RNA Activator (SRA), and when coexpressed, mPus1p and SRA cooperatively enhance mRARgamma-mediated transcription. mPus1p, mRARgamma, and SRA exist in a retinoid-independent, promoter bound complex in the nucleus although mPus1p is also expressed in the nucleolus, where it likely modifies tRNA. Finally, we show that mPus1p-coactivator function required SRA, mPus1p-associated mRARgamma binding, and PUS activities. mPus1p-dependent pseudouridylation of SRA represents an additional type of posttranscriptional modification of a NR-coactivator complex that is important for NR signaling.

Amplification of wild-type K-ras promotes growth of head and neck squamous cell carcinoma.

In contrast to many other tumors of different lineage, oncogenic ras mutations are rarely found within head and neck squamous cell carcinoma (HNSCC). On the other hand, increased expression of wild-type K-ras in HNSCC tumor material has been noticed, but the potential physiological consequences of this observation have not yet been experimentally assessed. The current study addresses this issue by modulating K-ras expression in HNSCC cell lines and primary keratinocytes and determining its effects on cell growth and survival in vitro. Consistent with earlier reports using patient tumor material, Western blot analysis of four HNSCC lines (SCC-9, SCC-15, SCC-25, and FaDu) revealed varying but universally increased protein expression of K-ras relative to keratinocytes. All HNSCC lines expressed wild-type K-ras mRNA based on a random sequencing of eight K-ras cDNA samples obtained by reverse transcription-PCR from each HNSCC line (P