bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surrogate selection oversamples expanded T cell clonotypes
Authors: Yu Peng , Lian Yumin , Zuleger Cindy L. , Albertini Richard J. , Albertini Mark R. , Newton Michael A. 
Published: July 2023

Inference from immunological data on cells in the adaptive immune system may benefit from modeling specifications that describe variation in the sizes of various clonal sub-populations. We develop one such specification in order to quantify the effects of surrogate selection assays, which we confirm may lead to an enrichment for amplified, potentially disease-relevant T cell clones. Our specification couples within-clonotype birth-death processes with an exchangeable model across clonotypes. Beyond enrichment questions about the surrogate selection design, our framework enables a study of sampling properties of elementary sample diversity statistics; it also points to new statistics that may usefully measure the burden of somatic genomic alterations associated with clonal expansion. We examine statistical properties of immunological samples governed by the coupled model specification, and we illustrate calculations in surrogate selection studies of melanoma and in single-cell genomic studies of T cell repertoires.FundingThis research was supported in part by the National Science Foundation (grant 2023239-DMS), and by grants from the National Institutes of Health: R01 GM102756, P01 CA022443, P01 CA250972, P50 CA278595, UL1 TR002373, P50 CA269011, and P30 CA014520. This work was also supported by resources at the William S. Middleton Memorial Veterans Hospital, Madison, WI, USA, and the UW Carbone Comprehensive Cancer Center. Additional support was provided by Ann’s Hope Foundation, Taking on Melanoma, the Tim Eagle Memorial, and the Jay Van Sloan Memorial from the Steve Leuthold Family Foundation, philanthropic support in the USA. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or the views of the Dept. of Veterans Affairs or the United States Government.
Insight into the structural hierarchy of the protease cascade that regulates the mosquito melanization response
Authors: Saab Sally A. , Zhang Xiufeng , Zeineddine Suheir , Morejon Bianca , Michel Kristin , Osta Mike A. 
Published: July 2023

AbstractSerine protease cascades regulate important insect immune responses, including melanization and Toll pathway activation. In the context of melanization, central components of these cascades are clip domain serine proteases (CLIPs) including the catalytic,clip domainserineproteases (cSPs) and their non-catalytichomologs (cSPHs). Here, we define partially the structural hierarchy ofAn. gambiaecSPs of the CLIPB family, central players in melanization, and characterize their relative contributions to bacterial melanization and to mosquito susceptibility to bacterial infections. Usingin vivogenetic analysis we show that the protease cascade branches downstream of the cSPs CLIPB4 and CLIPB17 into two branches one converging on CLIPB10 and the second on CLIPB8. We also show that the contribution of key cSPHs to melanizationin vivoin response to diverse microbial challenges is more significant than any of the individual cSPs, possibly due to partial functional redundancy among the latter. Interestingly, we show that the key cSPH CLIPA8 which is essential for the efficient activation cleavage of CLIPBsin vivois efficiently cleaved itself by several CLIPBsin vitro, suggesting that cSPs and cSPHs regulate signal amplification and propagation in melanization cascades by providing positive reinforcement upstream and downstream of each other.
Diffusion-weighted magnetic resonance imaging for the diagnosis of giant cell arteritis – a comparison with T1-weighted black-blood imaging
Authors: Seitz Luca , Bucher Susana , Bütikofer Lukas , Maurer Britta , Bonel Harald M. , Wagner Franca , Lötscher Fabian , Seitz Pascal 
Published: July 2023

AbstractObjectivesTo investigate the diagnostic performance of diffusion-weighted imaging (DWI) of the superficial cranial arteries in the diagnosis of giant cell arteritis (GCA).MethodsRetrospectively, 156 patients with clinically suspected GCA were included. A new 4-point ordinal DWI rating scale was developed. A post-contrast, fat-suppressed, T1-weighted “black-blood” sequence (T1-BB) was rated for comparison. Ten arterial segments were assessed: common superficial temporal arteries, temporal and parietal branches, occipital and posterior auricular arteries bilaterally. The expert clinical diagnosis after ≥ 6 months of follow-up was the diagnostic reference standard. Diagnostic accuracy was evaluated for different rating methods.ResultsThe study cohort consisted of 87 patients with and 69 without GCA. For DWI, the area under the curve was 0.90. For a cut-off of ≥ 2 consecutive pathological slices, DWI showed a sensitivity of 75.9%, a specificity of 94.2% and a positive likelihood ratio of 13.09. With a cut-off of ≥ 3 consecutive pathological slices, sensitivity was 70.1%, specificity was 98.6%, and the positive likelihood ratio was 48.38. For the T1-BB, values were 88.5%, 88.4% and 7.63, respectively. The inter-rater analysis for DWI with a cut-off of ≥ 2 pathological slices showed a kappa of 1.00 on the patient level and 0.85 on the arterial segment level. For the T1-BB the kappa was 0.78 and 0.79, respectively.ConclusionDWI of the superficial cranial arteries demonstrates a good diagnostic accuracy and reliability for the diagnosis of GCA. DWI is widely available and can be used immediately in clinical practice for patients with suspected GCA.
ChatGPT may free time needed by the interventional radiologist for administration / documentation: A study on the RSNA PICC line reporting template
Authors: Senge Jan F. , McMurray Matthew T. , Haupt Fabian , Breiding Philipe S. , Beisbart Claus , Daneshvar Keivan , Komarek Alois , Nöldge Gerd , Mosler Frank , Bosbach Wolfram A. 
Published: July 2023

AbstractMotiveDocumentation and administration, unpleasant necessities, take a substantial part of the working time in the subspecialty of interventional radiology. With increasing future demand for clinical radiology predicted, time savings from use of text drafting technologies could be a valuable contribution towards our field.MethodThree cases of peripherally inserted central catheter (PICC) line insertion were defined for the present study. The current version of ChatGPT was tasked with drafting reports, following the Radiological Society of North America (RSNA) template.Key resultsScore card evaluation by human radiologists indicates that time savings in documentation / administration can be expected without loss of quality from using ChatGPT. Further, automatically generated texts were not assessed to be clearly identifiable as AI-produced.ConclusionsPatients, doctors, and hospital administrators would welcome a reduction of the time that interventional radiologists need for documentation and administration these days. If AI-tools as tested in the present study are brought into clinical application, questions about trust into those systems eg with regard to medical complications will have to be addressed.
Honey Experiment on LeProsy Ulcer (HELP) Study Protocol: A Randomised Control Trial of Raw, Unadulterated African Honey for Ulcer Healing in Leprosy: A Study Protocol
Authors: Udo Sunday Odihiri , Sunday Pius Ogbu , Tsaku Paul Alumbugu , Oladejo Israel Olaoluwa , Meka Anthony , Ugwu Linda , Ajisola Motunrayo , Akinyemi Joshua , Omigbodun Akinyinka , Choudhury Sopna , Sartori Jo , Ilozumba Onaedo , Watson Samuel I. , Lilford Richard J 
Published: July 2023

AbstractBackgroundAs in diabetes, ulcers in leprosy occur as a result of nerve damage and loss of sensation due to neuropathy. The aim of this study is to evaluate the healing properties of raw, undiluted African honey in comparison with normal saline dressing of leprosy ulcers.MethodsThis is a multi-centre, comparative, prospective, single-blinded, parallel-group, 1:1 individually randomised controlled trial to be conducted at The Leprosy Referral Hospital, Chanchaga, Niger state in central Nigeria and St. Benedict Hospital, Ogoja, Cross River state, South-south Nigeria. Raw, unadulterated honey will be used in the ulcer dressing of the eligible consenting participants in the intervention group while those in the control group will be treated by dressing with normal saline. The main outcomes will be the proportion of complete healing and the rate of healing up to 84 days post-randomisation. Follow-up will be for 6 months from randomisation. We aim to enter 90-130 participants into the study. Observations will be made by blinded observers examining photographs of ulcers.DiscussionOur study will provide an unbiased estimate of the effect of honey on the healing of neuropathic ulcers.Trial registrationISRCTN10093277. Registered on 22 December 2021.
The principal component-based clinical aging clock (PCAge) identifies signatures of healthy aging and provides normative targets for clinical intervention
Authors: Fong Sheng , Pabis Kamil , Latumalea Djakim , Dugersuren Nomuundari , Unfried Maximilian , Tolwinski Nicholas , Kennedy Brian , Gruber Jan 
Published: July 2023

AbstractClinical healthy aging recommendations are disease-centric and reactive rather than focusing on holistic, organismal aging. In contrast, biological age (BA) estimation informs risk stratification by predicting all-cause mortality, however current BA clocks do not pinpoint aging mechanisms making it difficult to intervene clinically. To generate actionable BA clocks, we developed and validated a principal component (PC)-based clinical aging clock (PCAge) that identifies signatures (PCs) associated with healthy and unhealthy aging trajectories. We observed that by intervening in PC-specific space, angiotensin-converting-enzyme inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) normalize several modifiable clinical parameters, involved in renal and cardiac function as well as inflammation. Proactive treatment with ACE-I/ARBs appeared to significantly reduce future mortality risk and prevented BA acceleration. Finally, we developed a reduced BA clock (PC_mAge), based directly on PCAge, which has equivalent predictive power, but is optimized for immediate application in clinical practice. Our Geroscience approach points to mechanisms associated with BA providing targets for preventative medicine to modulate biological process(es) that drive the shift from healthy functioning toward aging and the eventual manifestations of age-related disease(s).
Extended Hematology-Oncology Fellowships in Bone Marrow Transplantation, Leukemia, Lymphoma, and Myeloma: What Proportion of Trainees Train and Remain at these Centers?
Authors: Prasad Vinay 
Published: July 2023

AbstractIntroductionA number of extra fellowships after traditional hematology oncology training have started in recent years, including training in lymphoma, myeloma, bone marrow transplantation, and leukemia. The benefit of this additional training is disputed.Methods and MaterialsWe sought to quantify, from publicly reported data, what percentage of trainees either performed the extra year at the same location as they performed their fellowship– raising the question why they did not gain this training during the regular fellowship years– and what fraction stayed on at the same institution–raising the question of why the training was not performed on the job. Google and LinkedIn searches were performed to assemble the dataset.ResultsWe examined 6 programs that made their graduate information public. We found 30% (17/56) of fellows either trained at the same institution or remained at the same institution as their extra fellowship.ConclusionNearly 1 in 3 trainees that forgo an extra year do so in a context where they had opportunity to work at that center before or afterwards, raising the question as to whether the extra year was needed or could have been built into existing professional obligations.
Alternations in gut microbiota and host transcriptome of patients with coronary artery disease
Authors: Chen Liuying , Mou Xuanting , Li Jingjing , Li Miaofu , Ye Caijie , Gao Xiaofei , Liu Xiaohua , Ma Yunlong , Xu Yizhou , Zhong Yigang 
Published: July 2023

AbstractBackgroundCoronary artery disease (CAD) is a widespread heart condition caused by atherosclerosis and influences millions of people worldwide. Early detection of CAD is challenging due to the lack of specific biomarkers. The gut microbiota and host-microbiota interactions have been well documented to affect human health. However, investigation that reveals the role of gut microbes in CAD is still limited. This study aims to uncover the synergistic effects of host genes and gut microbes associated with CAD through integrative genomic analyses.ResultsHerein, we collected 54 fecal and 54 blood samples from CAD patients and matched controls, and performed amplicon and transcriptomic sequencing on these samples, respectively. By comparing CAD patients with health controls, we found that dysregulated gut microbes were significantly associated with CAD. By leveraging the Random Forest method, we found that 10 bacteria biomarkers can distinguish CAD patients from health controls with a high performance (AUC = 0.939). We observed that there existed prominent associations of gut microbes with several clinical indices relevant to heart functions. Integration analysis revealed that CAD-relevant gut microbegenus Fusicatenibacterwas associated with expression of CAD-risk genes, such asGBP2,MLKL, andCPR65. In addition, the upregulation of immune-related pathways in CAD patients were identified to be primarily associated with higher abundance of genusBlautia,Eubacterium,Fusicatenibacter, andMonoglobus.ConclusionsOur results highlight that dysregulated gut microbes contribute risk to CAD by interacting with host genes. These identified microbes and interacted risk genes may have high potentials as biomarkers for CAD.
Label-free cell detection of acute leukemia using ghost cytometry
Authors: Kawamura Yoko , Nakanishi Kayoko , Murata Yuri , Teranishi Kazuki , Miyazaki Ryusuke , Toda Keisuke , Imai Toru , Kajiwara Yasuhiro , Nakagawa Keiji , Matsuo Hidemasa , Adachi Souichi , Ota Sadao , Hiramatsu Hidefumi 
Published: July 2023

AbstractEarly diagnosis and prompt initiation of appropriate treatment are critical for improving the prognosis of acute leukemia. Currently, acute leukemia is diagnosed by microscopic morphological examination of bone marrow smears and flow cytometric immunophenotyping of bone marrow cells stained with fluorophore-conjugated antibodies. However, these diagnostic processes require trained professionals and are time and resource-intensive. Here, we present a novel diagnostic approach using ghost cytometry, a recently developed high-content flow cytometric approach, which enables machine vision-based, stain-free, high-speed analysis of cells, leveraging their detailed morphological information. We demonstrate that ghost cytometry can detect leukemic cells from the bone marrow cells of patients diagnosed with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML), without relying on biological staining. The method presented here holds promise as a precise, simple, swift, and cost-effective method for the diagnosis of acute leukemia in clinical practice.
The PREVENT Dementia programme: Baseline demographic, lifestyle, imaging and cognitive data from a midlife cohort study investigating risk factors for dementia
Authors: Ritchie Craig W. , Wells Katie , Gregory Sarah , Carriere Isabelle , Danso Samuel O. , Driscoll David , Dounavi Maria-Eleni , Hillary Robert , Koychev Ivan , Lawlor Brian , Li Su , Low Audrey , Mak Elijah , Malhotra Paresh , Manson Jean , Marioni Riccardo , Murphy Lee , Naci Lorina , O’Brien John T , Stewart William , Muniz-Terrera Graciela , Ritchie Karen 
Published: July 2023

AbstractPREVENT is a multi-centre prospective cohort study in the UK and Ireland that aims to examine mid-life risk factors for dementia, identify and describe the earliest indices of disease development. The PREVENT dementia programme is one of the original epidemiological initiatives targeting midlife as a critical window for intervention in neurodegenerative conditions. This paper provides an overview of the study protocol and presents the first summary results from the initial baseline data to describe the cohort.Participants in the PREVENT cohort provide demographic data, biological samples (blood, saliva, urine and optional cerebrospinal fluid), lifestyle and psychological questionnaires, undergo a comprehensive cognitive test battery, and are imaged using multi-modal 3T magnetic resonance imaging (MRI) scanning, with both structural and functional sequences. The PREVENT cohort governance structure is described, which includes a steering committee, a scientific advisory board and core patient and public involvement groups. A number of sub-studies which supplement the main PREVENT cohort are also described.The PREVENT cohort baseline data includes 700 participants recruited between 2014 and 2020 across five sites in the UK and Ireland (Cambridge, Dublin, Edinburgh, London and Oxford). At baseline, participants had a mean age of 51.2 years (range 40-59, SD ±5.47), with the majority female (n=433, 61.9%). There was a near equal distribution of participants with and without a parental history of dementia (51.4% vs 48.6%) and a relatively high prevalence ofAPOE⍰4carriers (n=264, 38.0%). Participants were highly educated (16.7 ± 3.44 years of education), were mainly of European Ancestry (n=672, 95.9%) and were cognitively healthy as measured by the Addenbrookes Cognitive Examination-III (ACE-III) (Total score 95.6 ±4.06). Mean white matter hyperintensity (WMH) volume at recruitment was 2.26 ± 2.77 ml (median = 1.39ml), with hippocampal volume 8.15 ± 0.79ml. There was good representation of known dementia risk factors in the cohort.The PREVENT cohort offers a novel dataset to explore midlife risk factors and early signs of neurodegenerative disease. Data are available open access at no cost via the Alzheimer’s Disease Data Initiative (ADDI) platform and Dementia Platforms UK (DPUK) platform pending approval of the data access request from the PREVENT steering group committee.
Early Biological Markers of Post-Acute Sequelae of SARS-CoV-2 Infection
Authors: Lu Scott , Peluso Michael J. , Glidden David V. , Davidson Michelle C. , Lugtu Kara , Pineda-Ramirez Jesus , Tassetto Michel , Garcia-Knight Miguel , Zhang Amethyst , Goldberg Sarah A. , Chen Jessica Y. , Fortes-Cobby Maya , Park Sara , Martinez Ana , So Matthew , Donovan Aidan , Viswanathan Badri , Hoh Rebecca , Donohue Kevin , McIlwain David R. , Gaudiliere Brice , Anglin Khamal , Yee Brandon C. , Chenna Ahmed , Winslow John W. , Petropoulos Christos , Deeks Steven G. , Briggs-Hagen Melissa , Andino Raul , Midgley Claire M. , Martin Jeffrey N. , Saydah Sharon , Kelly J. Daniel 
Published: July 2023

AbstractTo understand the roles of acute phase viral dynamics and host immune responses in PASC, we enrolled 136 participants within 5 days of their first positive SARS-CoV-2 real-time PCR. Participants self-collected nasal specimens up to 21 times within the first 28 days after symptom onset; Interviewer-administered clinical questionnaires and blood samples were collected at enrollment and days 9, 14, 21, 28, and month 4 and 8 post-symptom. Defining PASC as the presence of any symptom new or worse since infection reported at their 4-month visit, we compared viral markers (quantity and duration of viral RNA load, infectious viral load, and plasma N-antigen level) and host immune markers (IL-6, IL-10, TNF-α, IFN-α, IFN-γ, MCP, IP-10, and Spike IgG) over the acute period. In comparison to those who fully recovered, those who developed PASC demonstrated significantly higher maximum levels of SARS-CoV-2 RNA, infectious virus, and N-antigen, longer duration of viral shedding, and lower Spike-specific IgG levels within the first 10 days of the acute phase of illness. No significant differences were identified among a panel of host immune markers, though there was a trend toward higher initial levels of certain markers (e.g., MCP-1, IFN-α, and IFN-γ) in those who went on to develop PASC. Early viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC. These findings highlight the importance of understanding the early biological markers from acute SARS-CoV-2 infection in the natural history of PASC.Onset Sentence SummaryEarly viral dynamics and the associated host immune responses play a role in the pathogenesis of PASC.
Novel CSF tau biomarkers can be used for disease staging of sporadic Alzheimer’s disease
Authors: Salvadó Gemma , Horie Kanta , Barthélemy Nicolas R. , Vogel Jacob W. , Binette Alexa Pichet , Chen Charles D. , Aschenbrenner Andrew J , Gordon Brian A. , Benzinger Tammie L.S. , Holtzman David M. , Morris John C. , Palmqvist Sebastian , Stomrud Erik , Janelidze Shorena , Ossenkoppele Rik , Schindler Suzanne E. , Bateman Randall J. , Hansson Oskar 
Published: July 2023

AbstractBiological staging of individuals with Alzheimer’s disease (AD) may improve diagnostic and prognostic work-up of dementia in clinical practice and the design of clinical trials. Here, we created a staging model using the Subtype and Stage Inference (SuStaIn) algorithm by evaluating cerebrospinal fluid (CSF) amyloid-β (Aβ) and tau biomarkers in 426 participants from BioFINDER-2, that represent the entire spectrum of AD. The model composition and main analyses were replicated in 222 participants from the Knight ADRC cohort. SuStaIn revealed in the two cohorts that the data was best explained by a single biomarker sequence (one subtype), and that five CSF biomarkers (ordered: Aβ42/40, tau phosphorylation occupancies at the residues 217 and 205 [pT217/T217 and pT205/T205], microtubule-binding region of tau containing the residue 243 [MTBR-tau243], and total tau) were sufficient to create an accurate disease staging model. Increasing CSF stages (0-5) were associated with increased abnormality in other AD-related biomarkers, such as Aβ- and tau-PET, and aligned with different phases of longitudinal biomarker changes consistent with current models of AD progression. Higher CSF stages at baseline were associated with higher hazard ratio of clinical decline. Our findings indicate that a common pathophysiologic molecular pathway develops across all AD patients, and that a single CSF collection is sufficient to reliably indicate the presence of both AD pathologies and the degree and stage of disease progression.
Risk of severe outcomes among Omicron sub-lineages BA.4.6, BA.2.75 and BQ.1 compared to BA.5 in England
Authors: Seghezzo Giulia , Nash Sophie G , Aziz Nurin Abdul , Hope Russel , Bernal Jamie Lopez , Gallagher Eileen , Dabrera Gavin , Thelwall Simon 
Published: July 2023

AbstractSince the emergence of Omicron variant of SARS-CoV-2 in late 2021, a number of sub-lineages have arisen and circulated internationally. Little is known about the relative severity of Omicron sub-lineages BA.2.75, BA.4.6 and BQ.1. We undertook a case-control analysis to determine the clinical severity of these lineages relative to BA.5, using whole genome sequenced, PCR-confirmed infections, between 1 August 2022 to 27 November 2022, among those who presented to emergency care in England 14 days after and up to one day prior to the positive specimen. A total of 10,375 episodes were included in the analysis, of which 5,207 (50.2%) were admitted to hospital or died. Multivariable conditional regression analyses found no evidence for greater odds of hospital admission or death among those with BA.2.75 (OR= 0.96, 95% CI: 0.84 to 1.09), and BA.4.6 (OR= 1.02, 95% CI: 0.88 to 1.17) or BQ.1 (OR= 1.03, 95 % CI: 0.94 to 1.13) compared to BA.5. Future lineages may not follow the same trend and there remains a need for continued surveillance of COVID-19 variants and their clinical outcomes to inform the public health response.