bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and Safety of Single-dose Pegfilgrastim for CD34+ Cell Mobilization in Healthy Volunteers: A Phase 2 Study
Authors: Goto Hideki , Sugita Junichi , Hasegawa Yuta , Hayasaka Koji , Sunagoya Kana , Hatase Rie , Nishida Mutsumi , Ichihashi Yuki , Odera Mitsuhiko , Senjo Hajime , Yokoyama Shota , Ara Takahide , Shiratori Souichi , Endo Tomoyuki , Hino Masayuki , Maeda Yoshinobu , Sawa Masashi , Sato Norihiro , Teshima Takanori 
Published: November 2023

Background.
Pegfilgrastim, a long-acting form of granulocyte-colony stimulating factor, with a convenient single-injection dosage, is being investigated for peripheral blood stem cell (PBSC) mobilization in healthy volunteers. However, data on the adequate dose of pegfilgrastim for PBSC mobilization are limited. This phase 2, single-arm study evaluated the efficacy and safety of pegfilgrastim for PBSC mobilization in healthy volunteers.

Methods.
The study comprised 2 phases: pilot (steps 1–3, dose escalation, a single subcutaneous dose of 3.6, 7.2, and 10.8 mg pegfilgrastim, respectively) and evaluation (step 4, efficacy and safety assessments). The primary endpoint was the proportion of subjects who achieved mobilization of ≥20 × 106/L cluster of differentiation 34 positive (CD34+) cells.

Results.
Thirty-five subjects (6 each in steps 1 and 2 and 23 in step 4) were included. In the pilot phase, step 3 with a 10.8 mg dose was not conducted due to favorable outcomes in step 2 (desired CD34+ cell count), at 7.2 mg pegfilgrastim, which was identified as the optimal dose for the evaluation phase. In the evaluation phase, successful CD34+ mobilization was achieved in all 23 subjects. The mean peripheral blood CD34+ cells count peaked on day 5. Back pain, thrombocytopenia, transient elevations of alkaline phosphatase, and lactate dehydrogenase were the most common adverse events. All adverse events were mild, and none led to study discontinuation.

Conclusions.
A single-dose pegfilgrastim successfully mobilized an optimal number of CD34+ cells and was well tolerated. Pegfilgrastim could be an alternative option for PBSC mobilization in healthy volunteers. The trial was registered at www.clinicaltrials.gov (NCT03993639).
Altered placental immune cell composition and gene expression with isolated fetal spina bifida
Authors: White Marina , Abdo Hasan , Grynspan David , Van Mieghem Tim , Connor Kristin L 
Published: November 2023

AbstractProblemMaternal B vitamin deficiency increases the risk of fetal spina bifida (SB) and placental maldevelopment. It is unclear whether placental processes involving folate are altered in fetuses with SB in a contemporary cohort. We hypothesised that fetal SB would associate with reduced expression of key folate transporters (folate receptor-α [FRα], proton coupled folate receptor [PCFT], and reduced folate carrier [RFC]), and an increase in Hofbauer cell (HBC) abundance and folate receptor-β(FRβ)expression by HBCs.Method of StudyFRα, PCFT, and RFC protein localisation and expression (immunohistochemistry) and HBC phenotypes (RNAin situhybridization) were assessed in placentae from fetuses with SB (cases; n=12) and with no congenital anomalies (controls; n=22).ResultsCases (vs. gestational age [GA]-matched controls) had a higher proportion of placental villous cells that were HBCs (6.9% vs. 2.4%, p=0.0001) and higher averageFRβexpression by HBCs (3.2 mRNA molecules per HBC vs. 2.3, p=0.03). HBCs in cases were largely polarised to a regulatory phenotype (median 92.1% of HBCs). In sex-stratified analyses, male, but not female, cases had higher HBC levels andFRβexpression by HBCs than GA-matched controls. There were no differences between groups in the total percent of syncytium and stromal cells that were positive for FRα, PCFT, or RFC protein immunolabelling.ConclusionsHBC abundance andFRβexpression by HBCs are increased in placentae of fetuses with isolated SB, suggesting immune-mediated dysregulation in placental development and function, and could contribute to SB-associated comorbidities, such as poor fetal growth.
Metal complexes and conjugation: Harnessing the power of cobalt complexes to curtail plasmid transfer
Authors: Alav Ilyas , Pordelkhaki Parisa , de Resende Pedro Ernesto , Partington Hannah , Gibbons Simon , Lord Rianne , Buckner Michelle M.C. 
Published: November 2023

AbstractBackgroundAntimicrobial resistance genes (ARG), such as extended spectrum β-lactamase (ESBL) and carbapenemase genes, are commonly carried on plasmids. Plasmids can transmit between bacteria, disseminate globally, and cause clinically important resistance. Therefore, targeting plasmids could reduce ARG prevalence, and restore the efficacy of existing antibiotics. Here, we assessed the effect of four previously characterised bis(N-picolinamido)cobalt(II) complexes on the conjugative transfer of plasmids inEscherichia coliandKlebsiella pneumoniae.MethodsLiquid broth and solid agar conjugation assays were used to measure complex activity on four plasmids inE. coli. Additionally, the effect of cobalt complexes was tested on the transmission of the fluorescently tagged extended spectrum β-lactamase encoding pCTgfpplasmid inE. coliand carbapenemase encoding pKpQILgfpplasmid inK. pneumoniae, using flow cytometry.ResultsAntimicrobial susceptibility testing of cobalt complexes revealed no antibacterial activity. The cobalt complexes significantly reduced conjugative transfer of RP4, R6K, and R388 plasmids on solid agar inE. coliand pKpQILgfptransmission inK. pneumoniae.None affected conjugative transfer of pKM101 or transmission of fluorescently tagged pCT inE. coli. The cobalt complexes had no effect on plasmid persistence, suggesting that they target conjugation rather than plasmid prevalence.ConclusionsTo the best of our knowledge, this is the first study to report reduced transmission of clinically relevant plasmids with cobalt complexes. These cobalt complexes are not cytotoxic towards mammalian cells and are not antibacterial, therefore they could be optimised and employed as conjugation inhibitors to reduce prevalence of AMR and/or virulence genes in animals and humans.SignificanceAntimicrobial resistance is a growing problem that poses a significant threat to modern medicine. Some of the most problematic resistance genes are carried on genetic elements, called plasmids, that can spread between bacteria. While our understanding of the mechanisms and drivers of gene transfer amongst bacteria is increasing, we lack effective tools to slow down/control these processes. Here we demonstrate for the first time that novel cobalt-based compounds have anti-plasmid activity on a subset ofE. coliplasmids, and are extremely potent inK. pneumoniaecarrying a clinical carbapenem-resistance plasmid, without impacting plasmid maintenance. This finding forms the foundations of a potential strategy to control the transfer of genes within Gram-negative bacteria, which has implications for AMR and virulence.
Depressive symptoms are associated with differential cognitive and neuroanatomical alterations in young and older adults
Authors: Bergmann Eyal , Harlev Daniel ,   Cam-CAN, Wolpe Noham 
Published: November 2023

AbstractObjectiveDepression is a heterogeneous disorder. The purpose of this article is to examine the contribution of age to this heterogeneity by characterizing the associations of depressive symptoms with cognitive performance and brain structure across the lifespan.MethodsThe authors analyzed demographic variables (age, gender, education), affective measures (Hospital Anxiety and Depression Scale), and cognitive assessments (The Addenbrooke’s Cognitive Examination Revised) from the Cambridge Centre for Ageing Neuroscience (Cam-CAN) cohort (N=2591, age 18-99). A subset of this cohort (N=647) underwent structural MRI, which was used for voxel-based brain morphometry.ResultsA linear regression model revealed a significant interaction between age and depression score, indicating that depression-related cognitive dysfunction is more severe in older adults. A comparison of different cognitive domains showed that this effect was consistent across all tested domains but significantly more prominent for fluency. A complementary voxel-based morphometry analysis, based on similar regression models, revealed age by depression interactions in several brain regions, demonstrating preferential age-related reduction in grey matter volume in the left and right hippocampi in older adults. The reciprocal contrast revealed preferential reduction in grey matter in the left superior frontal gyrus, left middle frontal gyrus, and left superior parietal lobule in younger adults.ConclusionsThese findings indicate that the associations of depression with cognitive performance and brain structure are age-dependent, suggesting that the neuropathological mechanisms underlying depression may differ between young and older adults. Recognizing these differences will support the development of better diagnostic tools and therapeutic interventions for depression across the lifespan.
Angiographic Report Generation for the 3rdAPTOS’s Competition: Dataset and Baseline Methods
Authors: Zhang Weiyi , Chotcomwongse Peranut , Chen Xiaolan , Chung Florence H.T. , Song Fan , Zhang Xueli , He Mingguang , Shi Danli , Ruamviboonsuk Paisan 
Published: November 2023

AbstractFundus angiography, including fundus fluorescein angiography (FFA) and indocyanine green angiography (ICGA), are essential examination tools for visualizing lesions and changes in retinal and choroidal vasculature. However, the interpretation of angiography images is labor-intensive and time-consuming. In response to this, we are organizing the third APTOS competition for automated and interpretable angiographic report generation. For this purpose, we have released the first angiographic dataset, which includes over 50,000 images labeled by retinal specialists. This dataset covers 24 conditions and provides detailed descriptions of the type, location, shape, size and pattern of abnormal fluorescence to enhance interpretability and accessibility. Additionally, we have implemented two baseline methods that achieve an overall score of 7.966 and 7.947 using the classification method and language generation method in the test set, respectively. We anticipate that this initiative will expedite the application of artificial intelligence in automatic report generation, thereby reducing the workload of clinicians and benefiting patients on a broader scale.
Validation of Left Ventricular High Frame Rate Echo-Particle Image Velocimetry against 4D Flow MRI in Patients
Authors: Han Yichuang , Bowen Daniel J. , Barreto Bernardo Loff , Zwaan Robert. R. , Strachinaru Mihai , van der Geest Rob J. , Hirsch Alexander , van den Bosch Annemien E. , Bosch Johan G. , Voorneveld Jason 
Published: November 2023

AbstractAimsAccurately measuring intracardiac flow patterns could provide insights into cardiac disease pathophysiology, potentially enhancing diagnostic and prognostic capabilities. This study aims to validate Echo-Particle Image Velocimetry (echoPIV) forin-vivoleft ventricular intracardiac flow imaging against 4D flow MRI.Methods and ResultsWe acquired HFR contrast-enhanced ultrasound images from three standard apical views of 26 patients who required cardiac MRI. 4D flow MRI was obtained for each patient. Only echo image planes with sufficient quality and alignment with MRI were included for validation. Regional velocity, kinetic energy and viscous energy loss were compared between modalities using normalized mean absolute error, cosine similarity and Bland-Altman analysis.Among 24 included apical view acquisitions, we observed good correspondence between echoPIV and MRI regarding spatial flow patterns and vortex traces. The velocity profile at base-level (mitral valve) cross-section had cosine similarity of 0.92 ± 0.06 and normalized mean absolute error of 14 ± 5%. Peak spatial mean velocity differed by 3 ± 6 cm/s in systole and 6 ± 10 cm/s in diastole. The kinetic energy and rate of energy loss also revealed a high level of cosine similarity (0.89 ± 0.09 and 0.91 ± 0.06) with normalized mean absolute error of 23 ± 7% and 52 ± 16%.ConclusionsGiven good B-mode image quality, echoPIV provides a reliable estimation of left ventricular flow, exhibiting spatial-temporal velocity distributions comparable to 4D flow MRI. Both modalities present respective strengths and limitations: echoPIV captured inter-beat variability and had higher temporal resolution, while MRI was more robust to patient BMI and anatomy.
Hepatitis B virus prevalence and transmission in the households of pregnant women in Kinshasa, Democratic Republic of Congo
Authors: Morgan Camille E. , Ngimbi Patrick , Boisson-Walsh Alix JN , Ntambua Sarah , Matondo Jolie , Tabala Martine , Kashamuka Melchior Mwandaglirwa , Emch Michael , Edwards Jessie K. , Powers Kimberly A. , James Linda , Mbonze Nana , Mampunza Samuel , Yotebieng Marcel , Thompson Peyton , Parr Jonathan B. 
Published: November 2023

AbstractBackgroundDespite routine infant vaccination and blood donor screening, the Democratic Republic of Congo (DRC) has high hepatitis B virus (HBV) prevalence compared to the United States and Europe. Through the cross-sectional Horizontal and Vertical Transmission of Hepatitis B (HOVER-HBV) study, we characterized household prevalence in DRC’s capital, Kinshasa, to inform additional prevention efforts.MethodsWe introduced HBV surface antigen (HBsAg) screening alongside existing HIV screening as part of routine antenatal care (ANC) in high-volume maternity clinics in Kinshasa. We recruited households of pregnant women who were HBsAg-positive and HBsAg-negative, defining households as “exposed” and “unexposed,” respectively. Household members underwent HBsAg testing and an epidemiological survey. We evaluated HBsAg prevalence and potential transmission correlates.ResultsWe enrolled 1,006 participants from 200 households (100 exposed, 100 unexposed) across Kinshasa. HBsAg prevalence was more than twice as high in exposed households (5.0%; 95% CI: 2.8%-7.1%) as in unexposed households (1.9%; 0.6%-3.2%). Exposed direct offspring had 3.3 (0.9, 11.8) times the prevalence of unexposed direct offspring. Factors associated with HBsAg-positivity included older age, marriage, and having multiple recent partners or any new sexual partners among index mothers; and older age, lower household wealth, sharing nail clippers, and using street salons among exposed offspring.ConclusionsVertical and horizontal HBV transmission within households is ongoing in Kinshasa. Factors associated with infection reveal opportunities for HBV prevention efforts, including perinatal prevention, protection during sexual contact, and sanitation of shared personal items.
Clinician-Trained Artificial Intelligence for Enhanced Routing of Patient Portal Messages in the Electronic Health Record
Authors: Harzand Arash , Zia ul Haq Muhammad , Hornback Andrew M. , Cowan Alison D. , Anderson Blake 
Published: November 2023

ABSTRACTBackgroundIncreased use of electronic health records (EHR) and patient-initiated messaging has led to inefficiency, staff shortages, and provider burnout. We evaluated the impact of a natural language processing (NLP) algorithm for message routing on communication dynamics.MethodsWe developed an NLP model to accurately label inbound EHR messages from patients using a pre-trained classifier with fine-tuning based on clinician feedback. In a real-world study, the model was deployed to prospectively label and route messages sent to participating physicians at an integrated health system. A parallel control group of unrouted messages was generated for comparative analysis. The primary endpoints for assessing model performance were the time to first message interaction, the time to conversation resolution, and the total number of message interactions by staff, compared with the control group. Secondary endpoints were the precision, recall, F1 score (a measure of positive predictive value and sensitivity), and accuracy for correct message classification.ResultsThe model prospectively labeled and routed 469 unique conversations over 14 days from the inbaskets of participating physicians. Compared to a control group of 402 unrouted conversations from the same time period, conversations in the routed group had an 83.3% reduction in the time to first interaction (median difference [MD], −1 hour; P<0.001), an 84.4% reduction in the time to conversation resolution (MD, −22.5 hours; P<0.001), and a 40% reduction in the total number of staff interactions after application of intervention (MD, −2.0 interactions; P<0.001). The model demonstrated high precision (>97.6%), recall (>95%), and F1 scores (>96.5%) for accurate prediction of all five message classes, with a total accuracy of 97.8%.ConclusionsReal-time message routing using advanced NLP was associated with significantly reduced message response and resolution times.
Genomic epidemiology of SARS-CoV-2 in Sudan: A retrospective analysis 2020-2022
Authors: Mburu Maureen W. , Lambisia Arnold W. , Elnegoumi Musab , Nour Eman O. M. , Khair Osama M. M. , Abualas Elamin , Elhassan Rehab M , Adam Muatsim A. M. , Mohammed Khadija Said , Morobe John M. , Ndwiga Leonard , Moraa Edidah O. , Makori Timothy O. , Murunga Nickson , Katama Esther Nyadzua , Waruguru Dorcas W. , Mwangi Sarah , Tessema Sofonias K. , Adam Mawahib H. E. , Mahmoud Iman , Mohamed Hanan SalmanBabikir , Mustafa Yousif A. A. , Mohamed Mohamedtaha M. A. , Ahmed Rasheeda H.A. , Mohamed Nuha Y.I. , Ali Rahma H. , Ebraheem Rasha S.M. , Ahmed Huda H.H. , Abdalla Hamadelniel E. , Mukhtar Izdihar , Alla Abdalkhalig E. M. W. , Elsheikh Omer H. A. , Musa Abdualmoniem O. , Faki Mahmoud Taha , Ahmed Gada Mustfa , Ahmed Thoyba E. R. , Abdalla Mohammed A. O. , Mohamed Mujtaba O. K. , Ahmed Rayan A. A. , AwadElkarim Samah M. M. , Ahmed Basamat A. E. M. , Shumo Zainab A. I. , Ahmed Eiman N. A. , Rushwan Samia S. A. , Bejon Phillip , Nokes D. James , Ochola-Oyier Lynette Isabella , Agoti Charles N. , Githinji George , Bedri Shahinaz A. 
Published: November 2023

AbstractSARS-CoV-2 was first detected in Sudan on 13thMarch 2020. Here, we describe the genomic epidemiology of SARS-CoV-2 in Sudan between May 2020 and April 2022 to understand the introduction and transmission of SARS-CoV-2 variants in the country. A total of 667 SARS-CoV-2 positive samples were successfully sequenced using the nCoV-19 Artic protocol on the Oxford Nanopore Technology (≥70% genome completeness). The genomes were compared with a select contemporaneous global dataset to determine genetic relatedness and estimate import/export events. The genomes were classified into 37 Pango lineages within theancestral strain(107 isolates across 13 Pango lineages),Eta variant of interest (VOI)(78 isolates in 1 lineage),Alpha variant of concern (VOC)(10 isolates in 2 lineages),Beta VOC(26 isolates in 1 lineage),Delta VOC(171 isolates across 8 lineages) andOmicron VOC(242 isolates across 12 lineages). We estimated a total of 144 introductions of the observed variants from different countries across the globe. Multiple introductions of the Eta VOI, Beta VOC and Omicron VOC were observed in Sudan mainly from Europe and Africa. These findings suggest a need for continuous genomic surveillance of SARS-CoV-2 to monitor their introduction and spread consequently inform public health measures to combat SARS-CoV-2 transmission.
Deep generative modeling of the human proteome reveals over a hundred novel genes involved in rare genetic disorders
Authors: Orenbuch Rose , Kollasch Aaron W. , Spinner Hansen D. , Shearer Courtney A. , Hopf Thomas A. , Franceschi Dinko , Dias Mafalda , Frazer Jonathan , Marks Debora S. 
Published: November 2023

AbstractIdentifying causal mutations accelerates genetic disease diagnosis, and therapeutic development. Missense variants present a bottleneck in genetic diagnoses as their effects are less straightforward than truncations or nonsense mutations. While computational prediction methods are increasingly successful at prediction for variants inknowndisease genes, they do not generalize well to other genes as the scores are not calibrated across the proteome. To address this, we developed a deep generative model, popEVE, that combines evolutionary information with population sequence data and achieves state-of-the-art performance at ranking variants by severity to distinguish patients with severe developmental disorders from potentially healthy individuals. popEVE identifies 442 genes in a cohort of developmental disorder cases, including evidence of 119 novel genetic disorders without the need for gene-level enrichment and without overestimating the prevalence of pathogenic variants in the population. By placing variants on a unified scale, our model offers a comprehensive perspective on the distribution of fitness effects across the entire proteome and the broader human population. popEVE provides compelling evidence for genetic diagnoses even in exceptionally rare single-patient disorders where conventional techniques relying on repeated observations may not be applicable. Interactive web viewer and downloads available atpop.evemodel.org.
The association between SARS-CoV-2 infections in English primary and secondary school children and staff, and infections in members of their household in the schoolyear 2020-2021: a self-controlled case-series analysis
Authors: McClenaghan Elliot , Nguipdop-Djomo Patrick , Lewin Alexandra , Warren-Gash Charlotte , Cook Sarah , Mangtani Punam 
Published: November 2023

AbstractBackgroundThe role of children and staff in SARS-CoV-2 transmission outside and within households is still not fully understood when large numbers are in regular, frequent contact in schools.MethodsWe used the self-controlled case-series method during the alpha- and delta-dominant periods to explore the incidence of infection in periods around a household member infection, relative to periods without household infection, in a cohort of primary and secondary English school children and staff from November 2020 to July 2021.ResultsWe found the relative incidence of infection in students and staff was highest in the 1-7 days following household infection, remaining high up to 14 days after, with risk also elevated in the 6-12 days before household infection. Younger students had a higher relative incidence following household infection, suggesting household transmission may play a more prominent role compared with older students. The relative incidence was also higher amongst students in the alpha variant dominant period.ConclusionsThis analysis suggests SARS-CoV2 infection in children, young people and staff at English schools were more likely to be associated with within-household transmission than from outside the household, but that a small increased risk of seeding from outside is observed.Key messagesQuestion: With respect to incidence of SARS-CoV-2 infection before and after household member infection, is within-household transmission more likely than community transmission amongst school children and staff?Findings: In this self-controlled case-series analysis, the relative incidence of infection in students and staff was highest in the 1-7 days following household infection, remaining high up to 14 days after, with the highest relative incidence found in younger, primary school-aged children.Importance: Within-household transmission is more likely than from outside the household, but a small increased risk of seeding from outside the household is observed as well as variation by age and variant dominant period.