bluuebunny/crossref_metadata_2025_split huggingface dataset:
p53 immunohistochemistry as an ancillary tool for rapid assessment of residual disease in TP53-mutated acute myeloid leukemia and myelodysplastic syndromes
Authors: Brar Nivaz , Lawrence Lauren , Fung Eula , Zehnder James L , Greenberg Peter L , Mannis Gabriel N , Zhang Tian Y , Gratzinger Dita , Oak Jean , Silva Oscar , Kurzer Jason , Tan Brent , Menke Joshua R , Fernandez-Pol Sebastian 
Published: April 2024

Abstract

Objectives
Measurable residual disease flow cytometry (MRD-FC) and molecular studies are the most sensitive methods for detecting residual malignant populations after therapy for TP53-mutated acute myeloid leukemia and myelodysplastic neoplasms (TP53+ AML/MDS). However, their sensitivity is limited in suboptimal aspirates or when the immunophenotype of the neoplastic blasts overlaps with erythroids or normal maturing myeloid cells. In this study, we set out to determine if p53 immunohistochemistry (IHC) correlates with MRD-FC and next-generation sequencing (NGS) in the posttherapy setting and to determine the utility of p53 IHC to detect residual disease in the setting of negative or equivocal MRD-FC.

Methods
We retrospectively identified 28 pre- and posttherapy bone marrow biopsy specimens from 9 patients with TP53+ AML/MDS and a p53 overexpressor phenotype by IHC (strong 3+ staining at initial diagnosis). Next-generation sequencing and/or MRD-FC results were collected for each specimen.

Results
Using a threshold of more than ten 2-3+ cells in any one 400× field, p53 IHC detected residual disease with a sensitivity of 94% and a specificity of 89%. The threshold used in this study showed a high degree of concordance among 6 blinded pathologists (Fleiss κ = 0.97).

Conclusions
Our study suggests that p53 IHC can be used as a rapid tool (within 24 hours) to aid in the detection of residual disease that may complement MRD-FC or NGS in cases in which the flow cytometry immunophenotype is equivocal and/or the bone marrow aspirate is suboptimal.
Introducing/Testing New SFL-Inspired Communication/Content/Function-Focused Measures for Assessing L2 Narrative Task Performance
Authors: Qin Jie , Liu Dilin 
Published: April 2024

Abstract
In response to calls for an assessment tool that provides a separate performance dimension from the linguistic quality-oriented measures of complexity, accuracy, and fluency (CAF) and guided by systemic functional linguistic (SFL) theories, this study introduces a set of fine-grained objective measures of communication/content/function (CCF)-related performance in second language (L2) narratives and empirically tests the validity of these measures using vigorous research procedures and statistical tests. The test results show that these CCF measures assessed their intended SFL functional dimensions, in contrast to the key CAF measures that evaluated mainly linguistic dimensions of narrative performance. More specifically, these CCF measures offered an objective evaluation of the communication/content quality of narrative task performance as evaluated by the subjective functional adequacy scales, while the key CAF measures provided an objective assessment of the linguistic quality of task performance as measured by the largely subjective International English Language Testing System (IELTS) scales. The study also discusses the implications of the results for making the assessment of L2 task performance more accurate and comprehensive.
An attentional and working memory theory of hallucination vulnerability in frontotemporal dementia
Authors: Devenney Emma M , Tse Nga Yan , O’Callaghan Claire , Kumfor Fiona , Ahmed Rebekah M , Caga Jashelle , Hazelton Jessica L , Carrick James , Halliday Glenda M , Piguet Olivier , Kiernan Matthew C , Hodges John R 
Published: April 2024

Abstract
The rate and prevalence of hallucinations in behavioural variant frontotemporal dementia is well established. The mechanisms for underlying vulnerability however are the least well described in FTD compared with other neuropsychiatric conditions, despite the presence of these features significantly complicating the diagnostic process. As such, this present study aimed to provide a detailed characterization of the neural, cognitive and behavioural profile associated with a predisposition to hallucinatory experiences in behavioural variant frontotemporal dementia. In total, 153 patients with behavioural variant frontotemporal dementia were recruited sequentially for this study. A group of patients with well characterized hallucinations and good-quality volumetric MRI scans (n = 23) were genetically and demographically matched to a group without hallucinations (n = 23) and a healthy control cohort (n = 23). All patients were assessed at their initial visit by means of a detailed clinical interview, a comprehensive battery of neuropsychological tests and MRI. Data were analysed according to three levels: (i) the relationship between neural structures, cognition, behaviour and hallucinations in behavioural variant frontotemporal dementia; (ii) the impact of the C9orf72 expansion; and (iii) hallucination subtype on expression of hallucinations. Basic and complex attentional (including divided attention and working memory) and visual function measures differed between groups (all P &lt; 0.001) with hallucinators demonstrating poorer performance, along with evidence of structural changes centred on the prefrontal cortex, caudate and cerebellum (corrected for False Discovery Rate at P &lt; 0.05 with a cluster threshold of 100 contiguous voxels). Attentional processes were also implicated in C9orf72 carriers with hallucinations with structural changes selectively involving the thalamus. Patients with visual hallucinations in isolation showed a similar pattern with emphasis on cerebellar atrophy. Our findings provided novel insights that attentional and visual function subsystems and related distributed brain structures are implicated in the generation of hallucinations in behavioural variant frontotemporal dementia, that dissociate across C9orf72, sporadic behavioural variant frontotemporal dementia and for the visual subtype of hallucinations. This loading on attentional and working memory measures is in line with current mechanistic models of hallucinations that frequently suggest a failure of integration of cognitive and perceptual processes. We therefore propose a novel cognitive and neural model for hallucination predisposition in behavioural variant frontotemporal dementia that aligns with a transdiagnostic model for hallucinations across neurodegeneration and psychiatry.
Development and Validation of Fast and Sensitive RP-HPLC Stability-Indicating Method for Quantification of Piroxicam in Bulk Drug
Authors: Chauhan Vikas , Grover Parul , Bhardwaj Monika , Kumar Sandeep , Nagarajan K 
Published: April 2024

Abstract
A simple, rapid, sensitive, and cost-effective green solvent-assisted reverse-phase high-performance liquid chromatographic technique, coupled with a photodiode array detector, was developed and validated for the estimation of piroxicam (PRXM). The chromatographic separation was achieved by using a C-18 (250 × 4.6) mm, 5-μm stationary phase and a mobile phase consisting of methanol and 0.1% ortho-phosphoric acid in water in a ratio of (80:20) v/v at a flow rate of 1 ml/min. The detection was carried out at a wavelength of 254 nm with a constant injection volume of 10 μL throughout the analysis. The calibration curve was observed to be linear over the optimum concentration range of 50–300 μg mL−1, with an R2 value of 0.9995. The developed method was validated as per the International Council for Harmonisation (ICH) Q2 (R1) guideline. Various parameters like selectivity/specificity, accuracy/recovery, linearity, precision, detection limit, quantitation limit, robustness and stability of analyte in solution were performed for the method validation. The PRXM was evaluated under stressed conditions, including acidic, basic, oxidative, thermal and photolytic, as per ICH Q1 (R2) guidelines. Significant degradation was observed in acidic and basic degradation conditions. Conversely, the drug substance showed stability when exposed to oxidative, photolytic and thermal degradation conditions.
Safety and Immunogenicity of Accelerated Heterologous 2-Dose Ebola Vaccine Regimens in Adults With and Without Human Immunodeficiency Virus in Africa
Authors: Mwesigwa Betty , Sawe Fredrick , Oyieko Janet , Mwakisisile Joel , Viegas Edna , Akintunde Gideon Akindiran , Kosgei Josphat , Kokogho Afoke , Ntinginya Nyanda , Jani Ilesh , Shukarev Georgi , Hooper Jay W , Kwilas Steven A , Ward Lucy A , Rusnak Janice , Bounds Callie , Overman Rachel , Badorrek Christopher S , Eller Leigh Anne , Eller Michael A , Polyak Christina S , Moodley Amber , Tran Chi L , Costanzo Margaret C , Leggat David J , Paquin-Proulx Dominic , Naluyima Prossy , Anumendem Dickson Nkafu , Gaddah Auguste , Luhn Kerstin , Hendriks Jenny , McLean Chelsea , Douoguih Macaya , Kibuuka Hannah , Robb Merlin L , Robinson Cynthia , Ake Julie A 
Published: April 2024

Abstract

Background
Shorter prophylactic vaccine schedules may offer more rapid protection against Ebola in resource-limited settings.

Methods
This randomized, observer-blind, placebo-controlled, phase 2 trial conducted in 5 sub-Saharan African countries included people without human immunodeficiency virus (HIV) (PWOH, n = 249) and people with HIV (PWH, n = 250). Adult participants received 1 of 2 accelerated Ebola vaccine regimens (MVA-BN-Filo, Ad26.ZEBOV administered 14 days apart [n = 79] or Ad26.ZEBOV, MVA-BN-Filo administered 28 days apart [n = 322]) or saline/placebo (n = 98). The primary endpoints were safety (adverse events [AEs]) and immunogenicity (Ebola virus [EBOV] glycoprotein–specific binding antibody responses). Binding antibody responders were defined as participants with a &gt;2.5-fold increase from baseline or the lower limit of quantification if negative at baseline.

Results
The mean age was 33.4 years, 52% of participants were female, and among PWH, the median CD4+ cell count was 560.0 (interquartile range, 418.0–752.0) cells/μL. AEs were generally mild/moderate with no vaccine-related serious AEs or remarkable safety profile differences by HIV status. At 21 days post–dose 2, EBOV glycoprotein–specific binding antibody response rates in vaccine recipients were 99% for the 14-day regimen (geometric mean concentrations [GMCs]: 5168 enzyme-linked immunosorbent assay units [EU]/mL in PWOH; 2509 EU/mL in PWH) and 98% for the 28-day regimen (GMCs: 6037 EU/mL in PWOH; 2939 EU/mL in PWH). At 12 months post–dose 2, GMCs in PWOH and PWH were 635 and 514 EU/mL, respectively, for the 14-day regimen and 331 and 360 EU/mL, respectively, for the 28-day regimen.

Conclusions
Accelerated 14- and 28-day Ebola vaccine regimens were safe and immunogenic in PWOH and PWH in Africa.
Clinical Trials Registration. NCT02598388.
NLRP3 inflammasome-mediated premature immunosenescence drives diabetic vascular aging dependent on the induction of perivascular adipose tissue dysfunction
Authors: Tai Guang-Jie , Ma Yan-Jie , Feng Jun-Lin , Li Jia-Peng , Qiu Shu , Yu Qing-Qing , Liu Ren-Hua , Wankumbu Silumbwe Ceaser , Wang Xin , Li Xiao-Xue , Xu Ming 
Published: April 2024

Abstract

Aims
The vascular aging process accelerated by type 2 diabetes mellitus (T2DM) is responsible for the elevated risk of associated cardiovascular diseases. Metabolic disorder-induced immune senescence has been implicated in multi-organ/tissue damage. Herein, we sought to determine the role of immunosenescence in diabetic vascular aging and to investigate the underlying mechanisms.

Methods and results
Aging hallmarks of the immune system appear prior to the vasculature in streptozotocin (STZ)/high-fat diet (HFD)-induced T2DM mice or db/db mice. Transplantation of aged splenocytes or diabetic splenocytes into young mice triggered vascular senescence and injury compared with normal control splenocyte transfer. RNA sequencing profile and validation in immune tissues revealed that the toll-like receptor 4–nuclear factor-kappa B–NLRP3 axis might be the mediator of diabetic premature immunosenescence. The absence of Nlrp3 attenuated immune senescence and vascular aging during T2DM. Importantly, senescent immune cells, particularly T cells, provoked perivascular adipose tissue (PVAT) dysfunction and alternations in its secretome, which in turn impair vascular biology. In addition, senescent immune cells may uniquely affect vasoconstriction via influencing PVAT. Lastly, rapamycin alleviated diabetic immune senescence and vascular aging, which may be partly due to NLRP3 signalling inhibition.

Conclusion
These results indicated that NLRP3 inflammasome-mediated immunosenescence precedes and drives diabetic vascular aging. The contribution of senescent immune cells to vascular aging is a combined effect of their direct effects and induction of PVAT dysfunction, the latter of which can uniquely affect vasoconstriction. We further demonstrated that infiltration of senescent T cells in PVAT was increased and associated with PVAT secretome alterations. Our findings suggest that blocking the NLRP3 pathway may prevent early immunosenescence and thus mitigate diabetic vascular aging and damage, and targeting senescent T cells or PVAT might also be the potential therapeutic approach.
When does antimicrobial resistance increase bacterial fitness? Effects of dosing, social interactions, and frequency dependence on the benefits of AmpC β-lactamases in broth, biofilms, and a gut infection model
Authors: Penkova Elitsa , Raymond Ben 
Published: April 2024

Abstract
One of the longstanding puzzles of antimicrobial resistance is why the frequency of resistance persists at intermediate levels. Theoretical explanations for the lack of fixation of resistance include cryptic costs of resistance or negative frequency-dependence but are seldom explored experimentally. β-lactamases, which detoxify penicillin-related antibiotics, have well-characterized frequency-dependent dynamics driven by cheating and cooperation. However, bacterial physiology determines whether β-lactamases are cooperative, and we know little about the sociality or fitness of β-lactamase producers in infections. Moreover, media-based experiments constrain how we measure fitness and ignore important parameters such as infectivity and transmission among hosts. Here, we investigated the fitness effects of broad-spectrum AmpC β-lactamases in Enterobacter cloacae in broth, biofilms, and gut infections in a model insect. We quantified frequency- and dose-dependent fitness using cefotaxime, a third-generation cephalosporin. We predicted that infection dynamics would be similar to those observed in biofilms, with social protection extending over a wide dose range. We found evidence for the sociality of β-lactamases in all contexts with negative frequency-dependent selection, ensuring the persistence of wild-type bacteria, although cooperation was less prevalent in biofilms, contrary to predictions. While competitive fitness in gut infections and broth had similar dynamics, incorporating infectivity into measurements of fitness in infections significantly affected conclusions. Resistant bacteria had reduced infectivity, which limited the fitness benefits of resistance to infections challenged with low antibiotic doses and low initial frequencies of resistance. The fitness of resistant bacteria in more physiologically tolerant states (in biofilms, in infections) could be constrained by the presence of wild-type bacteria, high antibiotic doses, and limited availability of β-lactamases. One conclusion is that increased tolerance of β-lactams does not necessarily increase selection pressure for resistance. Overall, both cryptic fitness costs and frequency dependence curtailed the fitness benefits of resistance in this study.
Local adaptation and reproductive isolation: when does speciation start?
Authors: Butlin Roger K , Faria Rui 
Published: April 2024

Abstract
The speciation process often takes a long time. The speciation continuum framework has been useful to reconstruct the evolutionary processes that result in the formation of new species but defining when this continuum starts is far from trivial. Although a panmictic population is often considered the initial condition of speciation, this is unrealistic for almost all species. Local or divergent adaptation are viewed by many researchers as processes that shape intraspecific diversity and thus are not part of speciation. We propose that speciation starts when reproductive isolation becomes greater than zero, arguing in favour of the alternative view that local adaptation necessarily involves some reproductive isolation, independently of whether it results in the completion of speciation. Given that local adaptation is widespread, the consequence is that most species are constantly in the process of speciating. The process of speciation is best represented as the formation of separate subnetworks, defined by reproductive isolation, within extended and fluid spatial networks of populations.
Intellectual Property as Business Loan Collateral: A Taxonomy of Institutional and Economic Determinants
Authors: Heller David , Leitzinger Leo , Walz Uwe 
Published: April 2024

Abstract
As a promising strategy to secure debt financing, firms can use their intellectual property rights (IPR) as collateral. Despite an ongoing shift to a more technology-based economy, the collateralization of IPR is still trailing behind the use of more traditional asset classes. In this paper, we address the challenges and opportunities of using IPR as collateral from a legal and economic angle by also exploring the role of and consequences for IP law. We develop a new taxonomy, i.e., a classification of the key determinants of using IPR as collateral. The taxonomy defines two pillars that govern the use of IPR collateral that distinguish between institutional and economic determinants. The institutional determinants cover contract law, IPR registries, and banking regulations. The economic determinants constitute the influence of IPR characteristics on the trade-off between the economic costs and benefits of collateralizing IPR. We apply the derived taxonomy to the legal and economic status quo in several industrialized economies to identify potential impediments to IPR-backed debt financing. Taken together, our taxonomy can be viewed as providing guidance for future research in the fields of law and economics on IPR as loan collateral for businesses.
Quality improvement initiative to increase radial artery usage as a second arterial conduit in coronary artery bypass grafting
Authors: Moya-Mendez Mary E , DeLaura Isabel , Thornton Steven W , Williams Adam R , Zwischenberger Brittany A 
Published: April 2024

Abstract

OBJECTIVES
Use of radial artery as a second arterial graft, compared to a saphenous vein, in coronary artery bypass grafting (CABG) can improve late outcomes. However, the radial artery remains underutilized. We initiated a quality improvement (QI) initiative to increase the usage of radial artery grafts.

METHODS
During our 4-month lead period, we disseminated evidence for radial artery graft usage to surgeons, developed a radial artery decision-making algorithm and adopted endoscopic harvesting. Our QI initiative was conducted over a 6-month period and included a postoperative survey of decision-making for graft selection and obstacles to radial artery usage.

RESULTS
Over the 6-month study period, 247 patients received isolated CABG which included 98 (40%) with radial arteries as a second arterial graft and 144 (58%) with greater saphenous veins. Radial artery usage increased with QI initiative implementation by 67% compared to 6 months prior to the study period (60 radial arteries/252 isolated CABG, 24%) (P = 0.006). The survey response rate was 93% (231/247). Barriers to radial artery graft usage were poor quality target vessel or stenosis &lt;80% (24%), patient age &gt;75 years (20%), ejection fraction ≤35% (8%) and renal insufficiency/dialysis (7%). No patients experienced significant complications from radial artery harvest.

CONCLUSIONS
Our institutional QI initiative was successful in (i) increasing the usage of radial artery as a second arterial graft and (ii) understanding barriers to radial artery graft usage. Implementation of a QI program can improve radial artery usage in CABG with low risk of patient morbidity from radial artery harvest.
Enriching Cultural Heritage Communities: New Tools and Technologies
Authors: Dix Alan , Jones Elizabeth , Cowgill Rachel , Armstrong Charlotte , Ridgewell Rupert , Twidale Michael , Downie J Stephen , Reagan Maureen , Bashford Christina , Bainbridge David , Neads Carys-Ann , Davies Vince 
Published: April 2024

Abstract
This paper explores ways in which scholarly skill and expertise might be embodied in tools and sustainable practices that enable communities to create and manage their own digital archives. We focus particularly on tools and practices related to the recording and annotation of digitized materials. The paper is based on co-production practice in two very different kinds of community. Although the communities are different we find that tools designed for a specific community are valuable for others, thus offering the promise of general tools to support community-centred digitization and potentially also traditional archival practice.
Retrospective analysis of pathogens for guided creation of an EMPIRIc antibiotic prEscribing pathway (EMPIRE)
Authors: Todor Lorraine A , Hill David M 
Published: April 2024

Abstract
The objective of this study was to evaluate the susceptibilities of pathogens isolated from cultures within the first 7 days of admission to the burn center and in the absence of healthcare-associated infection risk factors (HAIRF) to determine if current empiric antibiotics can be narrowed for refinement of an empiric antibiotic prescribing pathway according to the suspected source. A 3-year sample of patients and cultures was utilized in hopes of obtaining at least 30 isolates of the most common pathogens and their respective susceptibilities. A total of 268 clinically relevant (e.g., deemed infectious, versus colonization) pathogens were included in the final sample with sources including wounds, respiratory, blood, urine, and bone. Of the 268 pathogens included, 45% were Gram-negative and 69% of all pathogens were isolated from wound cultures. The existing empiric pathway, vancomycin plus cefepime, covered 98% and 84% of all Gram-positive and Gram-negative pathogens, respectively. In patients without HAIRF, coverage rose to 98% and 90%, respectively. Initial use of vancomycin and cefepime remains adequate for pathogens isolated within 1 week of admission in patients without HAIRF. For pneumonias, a narrower spectrum beta-lactam would not sufficiently cover respiratory pathogens isolated within the first week of admission. Regarding early wound infections, difficult-to-treat pathogens remain as a rare isolate of wound cultures within 1 week of admission.