bluuebunny/crossref_metadata_2025_split huggingface dataset:
Knowledge of cervical cancer screening and associated factors among women attending maternal health services at Aira Hospital, West Wollega, Ethiopia
Authors: Aredo Megersa Argaw , Sendo Endalew Gemechu , Deressa Jembere Tesfaye 
Published: September 2021

Background: Cervical cancer is one of the major noncommunicable public health problems among women globally. About 500,000 women develop cervical cancer each year, with an estimated 85% or more occurring in developing countries, including Ethiopia. Objective: The main objective of the study was to assess the knowledge of cervical cancer screening and its associated factors among women attending maternal health services at Aira hospital, West Wollega, Ethiopia. Methods: An institutional-based cross-sectional study design was conducted among 421 reproductive-age women. A systematic sampling method was used for the study. Data were collected using a pretested and structured questionnaire. Data analysis included descriptive statistics and the statistical association between the outcome variable and the explanatory variables tested by the binary logistic regression. Multivariable logistic regression was used to control confounding factors, the magnitude of the association between the different independent and dependent variable was measured using 95% confidence interval, and p values below 0.05 were considered as statistically significant. Results: A total of 421 women were responded with 100% response rate and with the mean age of 26.0 ± 5.15 (M ± SD) years. About 95.0% of the respondents ever heard of cervical cancer and 46.8% of the respondents had good knowledge about cervical cancer screening. Age, occupation, educational level, and monthly income were predictors associated with knowledge about cervical cancer screening. Conclusion: The study revealed 46.8% of study participants had knowledge about cervical cancer screening. The age of the participant, occupation, level of education, and monthly income were determinants of knowledge about cervical cancer screening. Prevention programs should focus on cervical cancer screening according to identified factors in the study.
The multidisciplinary, theory-based co-design of a new digital health intervention supporting the care of oesophageal cancer patients
Authors: Sun Kristi , Goodfellow Henry , Konstantara Emmanouela , Hill Alison , Lennard Debby , Lloyd-Dehler Elizabeth , Mughal Muntzer , Pritchard-Jones Kathy , Robson Chris , Murray Elizabeth 
Published: September 2021

Objective Oesophageal cancer patients have complex care needs. Cancer clinical nurse specialists play a key role in coordinating their care but often have heavy workloads. Digital health interventions can improve patient care but there are few examples for oesophageal cancer. This paper aims to describe the multidisciplinary co-design process of a digital health intervention to improve the experience of care and reduce unmet needs among patients with oesophageal cancer. Methods A theory-based, multi-disciplinary, co-design approach was used to inform the developmental process of the digital health intervention. Key user needs were elicited using mixed methodology from systematic reviews, focus groups and interviews and holistic need assessments. Overarching decisions were discussed among a core team of patients, carers, health care professionals including oncologists and cancer clinical nurse specialists, researchers and digital health providers. A series of workshops incorporating a summary of findings of key user needs resulted in the development of a minimum viable product. This was further refined after a pilot study based on feedback from end users. Results The final digital health intervention consists of a mobile app feature for patients and carers connected to a dashboard with supporting additional features for clinical nurse specialist. It contains a one-way messaging function for clinical nurse specialists to communicate with patients, functions for patients to record weight and holistic need assessment results which could be viewed by their clinical nurse specialists as well as a library of informative articles. Conclusions The multidisciplinary co-design of a digital health intervention providing support for oesophageal cancer patients and health care professionals has been described. Future studies to establish its impact on patient outcomes are planned.
The Medical Management of Gastroesophageal Reflux Disease: A Narrative Review
Authors: Kröner Paul T. , Cortés Pedro , Lukens Frank J. 
Published: September 2021

Objective The medical management of gastroesophageal reflux disease (GERD) continues to evolve. Our aim was to systematically assess the literature to provide an updated review of the evidence on lifestyle modifications and pharmacological therapy for the management of GERD. Background The cornerstones of GERD medical management consist of lifestyle modifications and pharmacologic agents. Most recently, evidence has emerged linking anti-reflux pharmacologic therapy to adverse events, such as kidney injury, metabolic bone disease, myocardial infarction, and even dementia, among others. Methods A systematic search of the databases of PubMed/MEDLINE, Embase, and Cochrane Library was performed for articles on the medical management of GERD between inception and March 1, 2021. Conclusion Although pharmacological therapy has been associated with potential adverse events, further research is needed to determine if this association exists. For this reason, lifestyle modifications should be considered first-line, while pharmacologic therapy can be considered in patients in whom lifestyle modifications have proven to be ineffective in controlling their symptoms or cannot institute them. Naturally, extra-esophageal causes for GERD-like symptoms must be considered on suspected high-risk patients and excluded before considering treatment for GERD.
Teaching addition strategies to students with learning difficulties
Authors: Polo-Blanco Irene , González López Eva M 
Published: September 2021

Background & aims In recent years, there has been an increased interest in analyzing the mathematical performance of students with learning difficulties in order to provide them with teaching methods adapted to their needs. In particular, the importance of studying the type of informal strategy that students use when solving problems has been highlighted. Observing how these strategies emerge and develop in children with learning difficulties is crucial, as it allows us to understand how they develop a subsequent understanding of arithmetic operations. In this paper we study the effect of explicit instruction in addition strategies, focusing on the minimum addend strategy, and analyze the difficulties that arise during this process. Methods An adapted multiple-probe design across students with a microgenetic approach was employed to assess the effectiveness of the teaching instruction and the acquisition of the minimum addend strategy while solving addition word problems. The participants were three primary-school children (two boys and one girl) with learning difficulties, one of them diagnosed with autism spectrum disorder. The instruction on the minimum addend strategy was sequenced into levels of abstraction based on the addends represented with and without manipulatives. Results The results show that the three participants were able to acquire the minimum addend strategy and transfer it to two-step problems. They all showed difficulties during the instructional process, with quantity comparison difficulties predominating. The instruction provided to address these and other difficulties is detailed for each participant. Conclusions The teaching of the minimum addend strategy has proven effective, and all three students acquired it throughout the instruction. The results concerning the student diagnosed with autism spectrum disorder are especially interesting given the lack of studies that focus on the strategies employed by students with this disorder to solve arithmetic problems. In this sense, the use of the microgenetic approach was especially useful to observe the type of spontaneous strategies used by this participant, and how they varied in response to the instruction. Implications Each study participant faced different difficulties and needed different periods of time to assimilate the new strategy. Conclusions are drawn for educators to help children with learning difficulties advance to more sophisticated strategies, so they can acquire these and subsequent mathematical concepts.
Multiple Evanescent White-Dot Syndrome in a 9-Year-Old Girl
Authors: Shepherd E. Anne , Herst Brian S. , Parlitsis George J. , Shapiro Michael J. , Goldstein Debra A. , Merrill Pauline T. 
Published: September 2021

Purpose: This work describes a case of multiple evanescent white-dot syndrome (MEWDS) in a 9-year-old girl. Methods: A case report is presented. Results: A case of MEWDS in a 9-year-old girl is described. Conclusions: To our knowledge this is the youngest presentation of MEWDS discussed in the literature. MEWDS should be considered in the differential diagnosis of ocular inflammation in the first decade of life.
Don’t you forget about me(gakaryocytes)
Authors: Tilburg Julia , Becker Isabelle C. , Italiano Joseph E. 
Published: September 2021

AbstractPlatelets (small, anucleate cell fragments) derive from large precursor cells, megakaryocytes (MKs), that reside in the bone marrow. MKs emerge from hematopoietic stem cells in a complex differentiation process that involves cytoplasmic maturation, including the formation of the demarcation membrane system, and polyploidization. The main function of MKs is the generation of platelets, which predominantly occurs through the release of long, microtubule-rich proplatelets into vessel sinusoids. However, the idea of a 1-dimensional role of MKs as platelet precursors is currently being questioned because of advances in high-resolution microscopy and single-cell omics. On the one hand, recent findings suggest that proplatelet formation from bone marrow–derived MKs is not the only mechanism of platelet production, but that it may also occur through budding of the plasma membrane and in distant organs such as lung or liver. On the other hand, novel evidence suggests that MKs not only maintain physiological platelet levels but further contribute to bone marrow homeostasis through the release of extracellular vesicles or cytokines, such as transforming growth factor β1 or platelet factor 4. The notion of multitasking MKs was reinforced in recent studies by using single-cell RNA sequencing approaches on MKs derived from adult and fetal bone marrow and lungs, leading to the identification of different MK subsets that appeared to exhibit immunomodulatory or secretory roles. In the following article, novel insights into the mechanisms leading to proplatelet formation in vitro and in vivo will be reviewed and the hypothesis of MKs as immunoregulatory cells will be critically discussed.
The menin-MLL1 interaction is a molecular dependency in NUP98-rearranged AML
Authors: Heikamp Emily B. , Henrich Jill A. , Perner Florian , Wong Eric M. , Hatton Charles , Wen Yanhe , Barwe Sonali P. , Gopalakrishnapillai Anilkumar , Xu Haiming , Uckelmann Hannah J. , Takao Sumiko , Kazansky Yaniv , Pikman Yana , McGeehan Gerard M. , Kolb Edward A. , Kentsis Alex , Armstrong Scott A. 
Published: September 2021

Abstract
Translocations involving the NUP98 gene produce NUP98-fusion proteins and are associated with a poor prognosis in acute myeloid leukemia (AML). MLL1 is a molecular dependency in NUP98-fusion leukemia, and therefore we investigated the efficacy of therapeutic blockade of the menin-MLL1 interaction in NUP98-fusion leukemia models. Using mouse leukemia cell lines driven by NUP98-HOXA9 and NUP98-JARID1A fusion oncoproteins, we demonstrate that NUP98-fusion-driven leukemia is sensitive to the menin-MLL1 inhibitor VTP50469, with an IC50 similar to what we have previously reported for MLL-rearranged and NPM1c leukemia cells. Menin-MLL1 inhibition upregulates markers of differentiation such as CD11b and downregulates expression of proleukemogenic transcription factors such as Meis1 in NUP98-fusion-transformed leukemia cells. We demonstrate that MLL1 and the NUP98 fusion protein itself are evicted from chromatin at a critical set of genes that are essential for the maintenance of the malignant phenotype. In addition to these in vitro studies, we established patient-derived xenograft (PDX) models of NUP98-fusion-driven AML to test the in vivo efficacy of menin-MLL1 inhibition. Treatment with VTP50469 significantly prolongs survival of mice engrafted with NUP98-NSD1 and NUP98-JARID1A leukemias. Gene expression analysis revealed that menin-MLL1 inhibition simultaneously suppresses a proleukemogenic gene expression program, including downregulation of the HOXa cluster, and upregulates tissue-specific markers of differentiation. These preclinical results suggest that menin-MLL1 inhibition may represent a rational, targeted therapy for patients with NUP98-rearranged leukemias.
Impact of sickle cell trait on morbidity and mortality from SARS-CoV-2 infection
Authors: Merz Lauren E. , Mistry Kavita , Neuberg Donna , Freedman Revital , Menard Gerda , Dorfman David M. , Park Hae Soo , Jolley Katherine , Achebe Maureen O. 
Published: September 2021

Abstract
The COVID-19 pandemic has highlighted racial health disparities within the United States. Although social determinants of health are the most likely drivers of this disparity, it is possible that genetic traits enriched in the black population like sickle cell trait (SCT) could worsen the morbidity and mortality of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Patients admitted for SARS-CoV-2 infection who identified as black or African American were included in the study (n = 166). Blood remnants were tested for SCT, and clinical data were abstracted from the chart. There was no difference in mortality between those with SCT and those without. There was no difference in respiratory complications between groups, but those without SCT had a much higher burden of chronic lung disease (P = .004). Those with SCT had higher creatinine on admission (P = .004), but no difference in in-hospital renal complications (P = .532). Notably, 12% of the cohort had SCT, which is higher than the expected 7.31% (P = .025). Our study did not show any evidence of increased end organ damage, morbidity, or mortality from SARS-CoV-2 infection among patients with SCT but did show differences in admission creatinine and preexisting lung disease.
G protein–coupled receptor kinase 5 regulates thrombin signaling in platelets via PAR-1
Authors: Downes Kate , Zhao Xuefei , Gleadall Nicholas S. , McKinney Harriet , Kempster Carly , Batista Joana , Thomas Patrick L. , Cooper Matthew , Michael James V. , Kreuzhuber Roman , Wedderburn Katherine , Waller Kathryn , Varney Bianca , Verdier Hippolyte , Kriek Neline , Ashford Sofie E. , Stirrups Kathleen E. , Dunster Joanne L. , McKenzie Steven E. , Ouwehand Willem H. , Gibbins Jonathan M. , Yang Jing , Astle William J. , Ma Peisong 
Published: September 2021

Abstract
The interindividual variation in the functional response of platelets to activation by agonists is heritable. Genome-wide association studies (GWASs) of quantitative measures of platelet function have identified fewer than 20 distinctly associated variants, some with unknown mechanisms. Here, we report GWASs of pathway-specific functional responses to agonism by adenosine 5′-diphosphate, a glycoprotein VI–specific collagen mimetic, and thrombin receptor-agonist peptides, each specific to 1 of the G protein–coupled receptors PAR-1 and PAR-4, in subsets of 1562 individuals. We identified an association (P = 2.75 × 10−40) between a common intronic variant, rs10886430, in the G protein–coupled receptor kinase 5 gene (GRK5) and the sensitivity of platelets to activate through PAR-1. The variant resides in a megakaryocyte-specific enhancer that is bound by the transcription factors GATA1 and MEIS1. The minor allele (G) is associated with fewer GRK5 transcripts in platelets and the greater sensitivity of platelets to activate through PAR-1. We show that thrombin-mediated activation of human platelets causes binding of GRK5 to PAR-1 and that deletion of the mouse homolog Grk5 enhances thrombin-induced platelet activation sensitivity and increases platelet accumulation at the site of vascular injury. This corroborates evidence that the human G allele of rs10886430 is associated with a greater risk for cardiovascular disease. In summary, by combining the results of pathway-specific GWASs and expression quantitative trait locus studies in humans with the results from platelet function studies in Grk5−/− mice, we obtain evidence that GRK5 regulates the human platelet response to thrombin via the PAR-1 pathway.
A systematic bioinformatics approach for large-scale identification and characterization of host-pathogen shared sequences
Authors: James Stephen Among , Ong Hui San , Hari Ranjeev , Khan Asif M. 
Published: September 2021

Abstract
Background
Biology has entered the era of big data with the advent of high-throughput omics technologies. Biological databases provide public access to petabytes of data and information facilitating knowledge discovery. Over the years, sequence data of pathogens has seen a large increase in the number of records, given the relatively small genome size and their important role as infectious and symbiotic agents. Humans are host to numerous pathogenic diseases, such as that by viruses, many of which are responsible for high mortality and morbidity. The interaction between pathogens and humans over the evolutionary history has resulted in sharing of sequences, with important biological and evolutionary implications.

Results
This study describes a large-scale, systematic bioinformatics approach for identification and characterization of shared sequences between the host and pathogen. An application of the approach is demonstrated through identification and characterization of the Flaviviridae-human share-ome. A total of 2430 nonamers represented the Flaviviridae-human share-ome with 100% identity. Although the share-ome represented a small fraction of the repertoire of Flaviviridae (~ 0.12%) and human (~ 0.013%) non-redundant nonamers, the 2430 shared nonamers mapped to 16,946 Flaviviridae and 7506 human non-redundant protein sequences. The shared nonamer sequences mapped to 125 species of Flaviviridae, including several with unclassified genus. The majority (~ 68%) of the shared sequences mapped to Hepacivirus C species; West Nile, dengue and Zika viruses of the Flavivirus genus accounted for ~ 11%, ~ 7%, and ~ 3%, respectively, of the Flaviviridae protein sequences (16,946) mapped by the share-ome. Further characterization of the share-ome provided important structural-functional insights to Flaviviridae-human interactions.

Conclusion
Mapping of the host-pathogen share-ome has important implications for the design of vaccines and drugs, diagnostics, disease surveillance and the discovery of unknown, potential host-pathogen interactions. The generic workflow presented herein is potentially applicable to a variety of pathogens, such as of viral, bacterial or parasitic origin.
Decreased mortality seen in rifampicin/multidrug-resistant tuberculous meningitis treated with linezolid in Shenzhen, China
Authors: Fang Mu-Tong , Su You-Feng , An Hui-Ru , Zhang Pei-Ze , Deng Guo-Fang , Liu Hou-Ming , Mao Zhi , Zeng Jian-Feng , Li Guobao , Yang Qian-Ting , Wang Zhong-Yuan 
Published: September 2021

Abstract
Background
The morbidity of rifampicin/multidrug-resistant tuberculous meningitis (RR/MDR-TBM) has shown an increasing trend globally. Its mortality rate is significantly higher than that of non-rifampicin/multidrug-resistant tuberculous meningitis (NRR/MDR-TBM). This article aimed to explore risk factors related to RR/MDR-TBM, and compare therapeutic effects of linezolid (LZD)- and non-linezolid-containing regimen for RR/MDR-TB patients in Shenzhen city. Furthermore, we aimed to find a better therapy for pathogen-negative TBM with RR/MDR-TBM related risk factors.

Methods
We conducted a retrospective study enrolling 137 hospitalized cases with confirmed TBM from June 2014 to March 2020. All patients were divided into RR/MDR-TBM group (12 cases) and NRR/MDR-TBM group (125 cases) based on GeneXpert MTB/RIF and (or) phenotypic drug susceptibility test results using cerebral spinal fluid (CSF). The risk factors related to RR/MDR-TBM were investigated through comparing clinical and examination features between the two groups. The mortality rate of RR/MDR-TBM patients treated with different regimens was analyzed to compare their respective therapeutic effects. A difference of P < 0.05 was considered statistically significant.

Results
Most patients (111/137, 81%) were from southern or southwestern China, and a large proportion (72/137, 52.55%) belonged to migrant workers. 12 cases were RR/MDR-TBM (12/137, 8.8%) while 125 cases were NRR/MDR-TBM (125/137, 91.2%). The proportion of patients having prior TB treatment history in the RR/MDR-TBM group was significantly higher than that of the NRR/MDR-TBM group (6/12 vs. 12/125, 50% vs. 10.5%, P < 0.01). No significant difference was observed on other clinical and examination features between the two groups. Mortality was significantly lower in RR/MDR-TBM patients on linezolid-containing treatment regimen than those who were not (0/7 versus 3/5, 0% versus 60%, P = 0.045).

Conclusions
The main related risk factor of RR/MDR-TBM is the history of anti-tuberculosis treatment. Linezolid-containing regimen appears to lower mortality rate of RR/MDR-TBM significantly in our study. We think Linezolid should be evaluated prospectively in the treatment of RR/MDR-TBM.
Differentiating T1a–T1b from T2 in gastric cancer lesions with three different measurement approaches based on contrast-enhanced T1W imaging at 3.0 T
Authors: Yuan Yuan , Ren Shengnan , Wang Tiegong , Shen Fu , Hao Qiang , Lu Jianping 
Published: September 2021

Abstract
Background
To explore the diagnostic value of three different measurement approaches in differentiating T1a–T1b from T2 gastric cancer (GC) lesions.

Methods
A total of 95 consecutive patients with T1a–T2 stage of GC who performed preoperative MRI were retrospectively enrolled between January 2017 and November 2020. The parameters MRI T stage (subjective evaluation), thickness, maximum area and volume of the lesions were evaluated by two radiologists. Specific indicators including AUC, optimal cutoff, sensitivity, specificity, accuracy, positive likelihood ratio (PLR), negative likelihood ratio (NLR), positive predictive value (PPV) and negative predictive value (NPV) of MRI T stage, thickness, maximum area and volume for differentiating T1a–T1b from T2 stage lesions were calculated. The ROC curves were compared by the Delong test. Decision curve analysis (DCA) was used to evaluate the clinical benefit.

Results
The ROC curves for thickness (AUC = 0.926), maximum area (AUC = 0.902) and volume (AUC = 0.897) were all significantly better than those of the MRI T stage (AUC = 0.807) in differentiating T1a–T1b from T2 lesions, with p values of 0.004, 0.034 and 0.041, respectively. The values corresponding to the thickness (including AUC, sensitivity, specificity, accuracy, PPV, NPV, PLR and NLR) were all higher than those corresponding to the MRI T stage, maximum area and volume. The DCA curves indicated that the parameter thickness could provide the highest clinical benefit if the threshold probability was above 35%.

Conclusions
Thickness may provide an efficient approach to rapidly distinguish T1a–T1b from T2 stage GC lesions.