bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnostic Accuracy of Carotid Plaque Instability by Noninvasive Imaging: A Systematic Review and Meta-analysis
Authors: Pakizer David , Kozel Jiří , Taffé Patrick , Elmers Jolanda , Feber Janusz , Michel Patrik , Školoudík David , Sirimarco Gaia 
Published: September 2023

AbstractBackgroundThere is increasing evidence that plaque instability in the extracranial carotid artery may lead to an increased stroke risk independently of the degree of stenosis. We aimed to determine diagnostic accuracy of vulnerable and stable plaque using noninvasive imaging modalities when compared to histology in patients with symptomatic and asymptomatic carotid atherosclerosis.MethodsMedline Ovid, Embase, Cochrane Library, and Web of Science were searched for diagnostic accuracy of noninvasive imaging modalities (CT, MRI, US) in the detection of 1) vulnerable/stable plaque, and 2) vulnerable/stable plaque characteristics, compared to histology. The quality of included studies was assessed by QUADAS-2 and univariate and bivariate random-effect meta-analyses were performed.ResultsWe included 36 vulnerable and 5 stable plaque studies in the meta-analysis, and out of 211 plaque characteristics from remaining studies, we classified 169 as vulnerable and 42 as stable characteristics (28 CT, 120 MRI, 104 US characteristics). We found that MRI had high accuracy (90% [95% CI:82–95%]) in the detection of vulnerable plaque, similar to CT (86% [95% CI:76–92%]; p>0.05), whereas US showed less accuracy (80% [95% CI:75– 84%]; p=0.013). CT showed a high diagnostic accuracy to visualize characteristics of vulnerable or stable plaques (89% and 90%) similar to MRI (86% and 89%; p>0.05); however US had lower accuracy (77%, p<0.001 and 82%, p>0.05).ConclusionsCT and MRI have a similar, high performance to detect vulnerable carotid plaques, whereas US showed significantly less diagnostic accuracy. Moreover, MRI visualized all vulnerable plaque characteristics allowing for a better stroke risk assessment.RegistrationPROSPERO ID CRD42022329690 (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=329690)
Cryo-EM structures of human SID-1 transmembrane family proteins and implications for their low-pH-dependent RNA transport activity
Authors: Zheng Le , Yang Tingting , Guo Hangtian , Qi Chen , Lu Yuchi , Xiao Haonan , Gao Yan , Liu Yue , Yang Yixuan , Zhou Mengru , Nguyen Henry C. , Zhu Yun , Sun Fei , Zhang Chen-yu , Ji Xiaoyun 
Published: September 2023

AbstractHuman SIDT1 and SIDT2 are closely related members of the systemic RNA interference (RNAi)-defective (SID-1) transmembrane family. Both mediate RNA internalization and intracellular transport and are involved in various biological processes. However, the molecular basis of RNA uptake, especially for exogenous small RNAs, remains elusive. Here, we present the cryo-electron microscopy (cryo-EM) structures of human SIDT1 and SIDT2. Both structures reveal the overall architecture of a dimeric arrangement contributed by the β-strand-rich extracellular domain (ECD) and the transmembrane domain (TMD) with 11 passes, highlighting the remarkable structural congruence. Thein situassays confirm that SIDT1 and SIDT2 exist as dimers or higher-order oligomers. We demonstrate that for both SIDT1 and SIDT2, the ECD binds small RNAs, such as dietary plant-derived miRNA, only under acidic conditions. In addition, RNA binding under low pH can trigger higher-order assembly of the ECD dimer, suggesting the potential importance of oligomerization during RNA uptake. Our results illustrate the molecular features of the conserved SID-1 family proteins to elucidate the mechanism of the low pH-dependent activation of RNA uptake mediated by SIDT1 and SIDT2. This study provides a promising understanding of the molecular basis of the nucleic acid delivery platform, which may potentially open new avenues for the design and optimization of RNA-based therapies.
A dynamic Hedgehog gradient orients tracheal cartilage rings
Authors: Kingsley Evan P. , Mishkind Darcy , Hiscock Tom W. , Tabin Clifford J. 
Published: September 2023

SUMMARYThe patterning of periodic stripes during embryonic development generates similar structures that repeat at regular spatial intervals within a tissue. These patterns are often attributed to a Turing-like mechanism, which self-organizes characteristically spaced stripes, but these patterns are predicted to be disorganized. Conversely, well-oriented, parallel stripes are often observed in nature. We investigate this phenomenon during the formation of the cartilage rings that support the amniote airway. We find evidence that a Turing-like mechanism underpins the formation of the repeating cartilage elements. Additionally,SHHis transiently expressed in a thin dorsal domain along the length of the developing trachea, resulting in a dorsoventral gradient of Hedgehog activity that recedes over time. Using mathematical modelling, we predict that the spatiotemporal dynamics of the gradient are required to organize the stripes into parallel rings. Comparingin silicopredictions with experimental SHH manipulations shows that the Hedgehog gradient is essential for proper tracheal cartilage patterning.
Deep Learning based retinal layer segmentation in optical coherence tomography scans of patients with inherited retinal diseases
Authors: Eckardt Franziska , Mittas Robin , Horlava Nastassya , Schiefelbein Johannes , Asani Ben , Michalakis Stylianos , Gerhardt Maximilian , Priglinger Claudia , Keeser Daniel , Koutsouleris Nikolaos , Priglinger Siegfried , Theis Fabian , Peng Tingying , Schworm Benedikt 
Published: September 2023

AbstractBackgroundOn optical coherence tomography (OCT) scans of patients with inherited retinal diseases (IRDs), the outer nuclear layer (ONL) thickness measurement has been well established as a surrogate marker for photoreceptor preservation. Current automatic segmentation tools fail in OCT segmentation in IRDs, and manual segmentation is time consuming.Methods and MaterialPatients with IRD and the availability of an OCT scan were screened for the present study. Additionally, OCT scans of patients without retinal disease were included, to provide training data for the artificial intelligence (AI). We trained a U-net based model on healthy patients and applied a domain adaption technique to IRD patients’ scans.ResultsWe established an AI-based image segmentation algorithm that reliably segments the ONL in OCT scans of IRD patients. In a test dataset, the dice-score of the algorithm was98.7%. Furthermore, we generated thickness maps of the full retinal thickness and the ONL layer for each patient.ConclusionAccurate segmentation of anatomical layers on OCT scans plays a crucial role for predictive models linking retinal structure to visual function. The here-presented OCT image segmentation algorithm could provide the basis for further studies on IRDs.
Mode of inheritance needs to be accounted for in interpreting genotype-phenotype links in monogenic disorders
Authors: Riera-Escamilla Antoni , Welt Corrine Kolka , Laan Maris 
Published: September 2023

AbstractIntroductionA recently published study by Keet al. utilized whole exome sequencing (WES) to screen genetic variants contributing to premature ovarian insufficiency (POI) in a large cohort of 1,030 patients from China (doi: 10.1038/s41591-022-02194-3). The authors reported that 285 likely pathogenic (LP) and pathogenic (P) variants identified in 79 genes contributed to POI in 242 study subjects, representing 23.5% of the cohort. The majority, 191 patients (∼79%), carried monoallelic (heterozygous) variants.ObjectiveWe re-analyzed the contribution of reported genotypes considering the inheritance mode of POI and other inherited conditions linked to 79 genes with reported findings by Keet al.MethodsThe disease inheritance modes linked to targeted genes were retrieved from publicly available databases (OMIM, Genomic England PanelApp, PubMed, DOMINO, gnomAD). Genotypes of 242 cases reported by Keet al.were assessed in the context of known inheritance mode(s) of disorders linked to respective genes.ResultsMost, 48 of 79 genes were classified as recessive, whereas only 13 genes were dominant. Insufficient data was available for 18 genes to conclusively determine their inheritance mode. Nearly half of 242 cases reported by Keet al., 119 women (∼49%), carried heterozygous variants in known autosomal recessive genes and therefore these variants are not contributing to their POI phenotype. Only 68 of women (6.6%) carried biallelic variants in either recessive or dominant genes or monoallelic variants in dominant genes, hence contributing to the diagnostic yield. This is ∼3.5-fold lower than 23.5% claimed in Keet al. Additional 56 women (5.4%) were reported monoallelic variants in genes with insufficient data to determine the inheritance mode or multiple heterozygous variants in >1 recessive gene, whereby oligogenic contribution to POI cannot be excluded. But when even including these cases, the maximum estimated contributing yield is ∼12%, two times lower than claimed.ConclusionUsing WES to screen monogenic causes of POI as part of the diagnostic pipeline will improve patient management strategies, but overestimated diagnostic yield in genetic research can create unrealistic expectations in the POI clinical community, typically non-specialist in genetics.
Development and validation of the Japanese version of the Lesbian, Gay, Bisexual, and Transgender Development of Clinical Skills Scale
Authors: Kanakubo Yusuke , Sugiyama Yoshifumi , Yoshida Eriko , Aoki Takuya , Mutai Rieko , Matsushima Masato , Okada Tadao 
Published: September 2023

AbstractIntroductionThe Lesbian, Gay, Bisexual, and Transgender Development of Clinical Skills Scale (LGBT-DOCSS) is a validated self-assessment tool for health and mental health professionals who provide care for sexual and gender minority patients. This study aimed to develop and validate a Japanese version of LGBT-DOCSS (LGBT-DOCSS-JP) and examine its psychometric properties.MethodsLGBT-DOCSS was translated into Japanese and cross-culturally validated using cognitive debriefing. We then evaluated the structural validity, convergent and discriminant validity, internal consistency, and test–retest reliability of LGBT-DOCSS-JP using an online survey.ResultsData were analyzed for 381 health and mental health professionals aged 20 years or older from three suburban medical institutions. The confirmatory factor analysis indicated that the original three-factor model did not fit well with LGBT-DOCSS-JP. Exploratory factor analysis revealed four new factors: Attitudinal Awareness, Basic Knowledge, Clinical Preparedness, and Clinical Training. Convergent and discriminant validity were supported using four established scales that measured attitudes toward lesbians and gay men, genderism and transphobia, authoritarianism and conventionalism, and social desirability. The internal consistency of LGBT-DOCSS-JP was supported by the Cronbach’s alpha values for the overall scale (0.84), as well for each of its subscales (Attitudinal Awareness and Basic Knowledge both 0.87, Clinical Preparedness 0.78, and Clinical Training 0.97). The test–retest reliability for the overall LGBT-DOCSS-JP was supported by an intraclass correlation coefficient score of 0.86.ConclusionsLGBT-DOCSS-JP has the potential to serve as a valuable tool in the development and assessment of effective curricula for LGBT care education, as well as a means to promote self-reflection among trainees and professionals.
Evaluation ofHOTAIR,HOXD8,HOXD9,HOXD11Gene Expression Levels in Turkish Patients with Acute Myeloid Leukemia and Chronic Myeloid Leukemia: A Single Center Experience
Authors: Saraymen Esma , Erdem Yakut , Akalın Hilal , Taşçıoğlu Nazife , Saraymen Berkay , Çelik Serhat , Özdemir Yeşim , Kaynar Leylagül , Çetin Mustafa , Özkul Yusuf 
Published: September 2023

ABSTRACTBACKGRAUNDHomeobox (HOX) transcript antisense RNA (HOTAIR) andHOXgenes are reported to be more expressed in various cancers in humans in recent studies. The role ofHOTAIRandHOXDgenes in acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) is not well known.MATERIALS AND METHODSIn this study, expression levels ofHOXD8,HOXD9andHOXD11fromHOXDgene family andHOTAIRwere determined from peripheral blood samples of 30 AML and 30 CML patients and 20 healthy volunteers by quantitative Real Time PCR.RESULTSWe determined that the expression levels ofHOXD9andHOXD11in the AML patients were significantly lower than the control group (p<0.001 and p=0.002, respectively). There was no significant difference in the expression levels ofHOTAIRandHOXD8when compared to the control group. In the CML patients there was a significant increase in the expression level ofHOTAIRwhen compared to the control group (p=0.002). The expression levels ofHOXD9andHOXD11were found to be significantly lower than the control group (p<0.001).CONCLUSIONOur study showed thatHOTAIRmay not be a biomarker in the diagnosis and is not significantly correlated with the clinicopathological prognostic characteristics of AML. Additionally; it can be said thatHOTAIRis oncogenic by suppressing the expression ofHOXD9andHOXD11but notHOXD8in CML patients. The expression profiles ofHOTAIRmay be a potential biomarker in the diagnosis of CML patients in predicting and monitoring drug resistance.
Predicting survival and trial outcome in non-small cell lung cancer integrating tumor and blood markers kinetics with machine learning
Authors: Benzekry Sébastien , Karlsen Mélanie , Bigarré Célestin , Kaoutari Abdessamad El , Gomes Bruno , Stern Martin , Neubert Ales , Bruno Rene , Mercier François , Vatakuti Suresh , Curle Peter , Jamois Candice 
Published: September 2023

AbstractExisting survival prediction models rely only on baseline or tumor kinetics data and lack machine learning integration. We introduce a novel kinetics-machine learning (kML) model that integrates baseline markers, tumor kinetics and four on-treatment simple blood markers (albumin, CRP, lactate dehydrogenase and neutrophils). Developed for immune-checkpoint inhibition (ICI) in non-small cell lung cancer on three phase 2 trials (533 patients), kML was validated on the two arms of a phase 3 trial (ICI and chemotherapy, 377 and 354 patients). It outperformed the current state-of-the-art for individual predictions with a test set c-index of 0.790, a 12-months survival accuracy of 78.7% and a hazard ratio of 25.2 (95% CI: 10.4 – 61.3,p< 0.0001) to identify long-term survivors. Critically, kML predicted the success of the phase 3 trial using only 25 weeks of on-study data (predicted HR = 0.814 (0.64 – 0.994) versus final study HR = 0.778 (0.65 – 0.931)). Our model constitutes a valuable approach to support personalized medicine and drug development.
Longitudinal analysis within one hospital in sub-Saharan Africa over 20 years reveals repeated replacements of dominant clones ofKlebsiella pneumoniaeand stresses the importance to include temporal patterns for vaccine design considerations
Authors: Heinz Eva , Pearse Oliver , Zuza Allan , Bilima Sithembile , Msefula Chisomo , Musicha Patrick , Siyabu Patriciah , Tewesa Edith , Graf Fabrice E , Lester Rebecca , Lissauer Samantha , Cornick Jennifer , Lewis Joseph M , Kawaza Kondwani , Thomson Nicholas R , Feasey Nicholas A 
Published: September 2023

AbstractInfections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistantKlebsiella pneumoniaeas a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology ofKlebsiella pneumoniaecan inform management strategies but data from sub-Saharan Africa are lacking.We present a longitudinal analysis of all invasiveK. pneumoniaeisolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998-2020, combining clinical data with genome sequence analysis of the isolates. We show that after a dramatic increase in the number of infections from 2016K. pneumoniaebecomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development.Our data highlight a clear need for new interventions to prevent rather than treatK. pneumoniaeinfections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare associated infections and not just one.
Hematologic setpoints are a stable and patient-specific deep phenotype
Authors: Foy Brody H , Petherbridge Rachel , Roth Maxwell , Mow Christopher , Patel Hasmukh R , Patel Chhaya H , Ho Samantha N , Lam Evie , Karczewski Konrad J , Tozzo Veronica , Higgins John M 
Published: September 2023

AbstractThe complete blood count is an important screening tool for healthy adults and is the most commonly ordered test at periodic physical exams. However, results are usually interpreted relative to one-size-fits-all reference intervals, undermining the goal of precision medicine to tailor medical care to the needs of individual patients based on their unique characteristics. Here we show that standard complete blood count indices in healthy adults have robust homeostatic setpoints that are patient-specific and stable, with the typical healthy adult’s set of 9 blood count setpoints distinguishable from 98% of others, and with these differences persisting for decades. These setpoints reflect a deep physiologic phenotype, enabling improved detection of both acquired and genetic determinants of hematologic regulation, including discovery of multiple novel loci via GWAS analyses. Patient-specific reference intervals derived from setpoints enable more accurate personalized risk assessment, and the setpoints themselves are significantly correlated with mortality risk, providing new opportunities to enhance patient-specific screening and early intervention. This study shows complete blood count setpoints are sufficiently stable and patient-specific to help realize the promise of precision medicine for healthy adults.
Real World Experience and Clinical Utility of EsoGuard® - Interim Data from the Lucid Registry
Authors: Englehardt Richard , Samarasena Jason B. , Bildzukewicz Nikolai A. , Hamblin Rachelle , Lee Victoria T. , Verma Suman , deGuzman Brian J. , Aklog Lishan 
Published: September 2023

AbstractBackgroundBarrett’s Esophagus (BE) is the only known precursor to esophageal adenocarcinoma (EAC), and guidelines exist for screening, surveillance, and treatment. However, historically most high-risk individuals have not been reliably screened, likely due to a combination of factors associated with patient/physician awareness and use of upper endoscopy (UE) as the traditional screening test. EsoGuard® (EG) is a DNA biomarker assay, and EsoCheck® (EC) is a non-invasive, swallowable capsule device designed to collect cells from a targeted region of the esophagus. EG and EC in combination offers a well-tolerated, accessible, in-office triage test to improve detection of BE in patients with multiple risk factors. The Lucid Registry captures real-world data from the commercial use of EC with EG, and we present an interim review of clinical utility data from the first 517 enrolled subjects.MethodsMulticenter, prospective, registry designed to capture data from patients undergoing EC cell collection and EG testing in the commercial setting. Data collection consists of demographics, risk factors, test results, provider management, and early clinical outcomes (through a maximum of four months post-EG). This data snapshot includes subjects enrolled from the start of the registry (April 14, 2023), through August 16, 2023. The primary assessment of clinical utility was agreement between EG assay results and physicians’ decision on whether to refer the patient for subsequent UE. The relationship between BE/EAC risk factors and EG positivity rates was assessed.ResultsAmong 517 subjects enrolled, average age was 47.9±14.3 years, 47.2% had history of gastroesophageal reflux disease (GERD), and 63.8% had a minimum of 3 established BE risk factors (i.e., met American Gastroenterological Association (AGA) criteria for screening). 58.8% of subjects were firefighters; when firefighting i.e., occupational exposure to smoke and carcinogens is treated as an additional BE/EAC risk factor (+) those of the AGA, 81.2% of the study population had ≥3 risks, making up the “AGA(+)” cohort. EG positivity was 14.1%. 437 subjects contributed data for the clinical utility endpoint: agreement between positive EG results and subsequent referral for UE was 100%; agreement between negative EG results and non-referral for UE was 99.4%; concordance between EG results and UE referral decisions was 97.9%. These findings were comparable between the AGA and AGA(+) cohorts.ConclusionsExperience from the Lucid Registry demonstrates that physicians who have adopted EC/EG in the commercial setting are reliably utilizing EG as a triage test to inform decision making on which patients to refer for further endoscopic evaluation of BE.
Assessing Folic Acid Supplementation Adherence Among Pregnant Women in LMICs and its Impact on Neural Tube Defect Incidence: A Systematic Review Protocol
Authors: Daniel Jeremiah Oluwatomi Itodo , Sulaiman Abdulmuizz Oluwatomi , Isiakpona Chiwendu , Igoli Joanne , Chukwumaeze Chukwunonso Emmanuel , Morgan Eghosa , Olukoya Olatomiwa 
Published: September 2023

AbstractIntroductionNeural tube defects (NTDs) are treatable but incurable birth defects, causing permanent disability and potential mortality if neglected. Despite its global significance, there has not been any systematic review exploring the link between folic acid adherence and NTD incidence in low-and-middle-income countries (LMICs), where its impact is disproportionately felt. This systematic review primarily aims to analyze the impact of folic acid supplementation adherence among expectant mothers on the incidence of NTDs in LMICs.Methods and AnalysisFollowing the PRISMA guidelines, we will conduct a comprehensive search of original research articles and observational studies using the electronic databases of PubMed, Scopus, Medline, and Embase from inception till date. Our search comprises keywords related to our PICO framework and objectives. We will analyze data using tables and diagrams for qualitative presentation and conduct a random-effect Bayesian meta-analysis when applicable.Two reviewers will screen titles and abstracts independently, conduct full-text reviews, and extract study data. In case of disagreements, a third reviewer will resolve them. We will present study details and assess bias risk. We will also assess the overall certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation framework.Ethics and DisseminationEthical approval is unnecessary as this study involves a systematic review of published studies. We aim to publish our findings in a peer-reviewed journal.