bluuebunny/crossref_metadata_2025_split huggingface dataset:
PET Imaging of Metabolism, Perfusion, and Hypoxia
Authors: Pantel Austin R. , Bae Seong-Woo , Li Elizabeth J. , O'Brien Sophia R. , Manning H. Charles 
Published: May 2024

Abstract
Imaging glucose metabolism with [18F]fluorodeoxyglucose positron emission tomography has transformed the diagnostic and treatment algorithms of numerous malignancies in clinical practice. The cancer phenotype, though, extends beyond dysregulation of this single pathway. Reprogramming of other pathways of metabolism, as well as altered perfusion and hypoxia, also typifies malignancy. These features provide other opportunities for imaging that have been developed and advanced into humans. In this review, we discuss imaging metabolism, perfusion, and hypoxia in cancer, focusing on the underlying biology to provide context. We conclude by highlighting the ability to image multiple facets of biology to better characterize cancer and guide targeted treatment.
Radiopharmaceuticals for Cancer Diagnosis and Therapy
Authors: Taunk Neil K. , Escorcia Freddy E. , Lewis Jason S. , Bodei Lisa 
Published: May 2024

Abstract
Radiopharmaceutical therapy has emerged as a promising approach for the treatment of various cancers. The exploration of novel targets such as tumor-specific antigens, overexpressed receptors, and intracellular biomolecules using antibodies, peptides, or small molecules has expanded the scope of radiopharmaceutical therapy, enabling precise and effective cancer treatment for an increasing number of tumor types. Alpha emitters, characterized by their high linear energy transfer and short path length, offer unique advantages in targeted therapy due to their potent cytotoxicity against cancer cells while sparing healthy tissues. This article reviews recent advancements in identifying novel targets for radiopharmaceutical therapy and applications in utilizing α-emitters for targeted treatment.
Missing in action: A bibliometric analysis of military research in the medical literature since 1950
Authors: Lile Deacon J. , Bergman Alon , Rolfing James , Allard Rhonda J. , Davis Thomas A. , Gross Kirby R. , Elster Eric A. , Schwab C. William , Cannon Jeremy W. 
Published: May 2024

BACKGROUND
Top-tier general and specialty scientific journals serve as a bellwether for national research priorities. We hypothesize that military-relevant publications are underrepresented in the scientific literature and that such publications decrease significantly during peacetime.

METHODS
We identified high impact journals in the fields of Medicine, Surgery and Critical Care and developed Boolean searches for military-focused topics using National Library of Medicine Subject Headings terms. A PubMed search from 1950 to 2020 returned the number of research publications in relevant journals and the rate of military-focused publications by year. Rates of military publications were compared between peacetime and wartime. Publication rate trends were modeled with a quadratic function controlling for the start of active conflict and total casualty numbers. Baseline proportions of military physicians relative to the civilian sector served to estimate expected publication rates. Comparisons were performed using Pearson's χ2 and Mann-Whitney U test, with p < 0.05 considered a significant difference.

RESULTS
From 1950 to 2020, a total of 716,340 manuscripts were published in the journals queried. Of these, military-relevant manuscripts totaled 4,052 (0.57%). We found a significant difference in the rate of publication during times of peace and times of war (0.40% vs. 0.69%, p < 0.001). Subgroup analysis found significantly reduced rates of publication in medical and critical care journals during peacetime. For each conflict, the percentage of military-focused publications peaked during periods of war but then receded below baseline levels within a median of 2.5 years (interquartile range, 1.5–3.8 years) during peacetime. The proportion of military-focused publications never reached the current proportion of military physicians in the workforce.

CONCLUSION
There is marked reduction in rates of publication for military-focused articles in high impact journals during peacetime. Military-focused articles are underrepresented in high-impact journals. Investigators of military-relevant topics and editors of high-impact journals should seek to close this gap.
Evidence of Pericyte Damage in a Cognitively Normal Cohort
Authors: Haghdel Arsalan , Smith Natasha , Glodzik Lidia , Li Yi , Wang Xiuyuan , Crowder Tamara , Zhu Yuan-Shan , Butler Tracy , Blennow Kaj , McIntire Laura Beth , Pahlajani Silky , Osborne Joseph , Chiang Gloria , de Leon Mony , Ivanidze Jana 
Published: May 2024

Background:
Blood-brain barrier (BBB) dysfunction is emerging as an important pathophysiologic factor in Alzheimer’s disease (AD). Cerebrospinal fluid (CSF) platelet-derived growth factor receptor-β (PDGFRβ) is a biomarker of BBB pericyte injury and has been implicated in cognitive impairment and AD.

Methods:
We aimed to study CSF PDGFRβ protein levels, along with CSF biomarkers of brain amyloidosis and tau pathology in a well-characterized population of cognitively unimpaired individuals and correlated CSF findings with amyloid-PET positivity. We performed an institutional review board (IRB)-approved cross-sectional analysis of a prospectively enrolled cohort of 36 cognitively normal volunteers with available CSF, Pittsburgh compound B PET/CT, Mini-Mental State Exam score, Global Deterioration Scale, and known apolipoprotein E (APOE) ε4 status.

Results:
Thirty-six subjects were included. Mean age was 63.3 years; 31 of 36 were female, 6 of 36 were amyloid-PET-positive and 12 of 36 were APOE ε4 carriers. We found a moderate positive correlation between CSF PDGFRβ and both total Tau (r=0.45, P=0.006) and phosphorylated Tau 181 (r=0.51, P=0.002). CSF PDGFRβ levels were not associated with either the CSF Aβ42 or the amyloid-PET.

Conclusions:
We demonstrated a moderate positive correlation between PDGFRβ and both total Tau and phosphorylated Tau 181 in cognitively normal individuals. Our data support the hypothesis that BBB dysfunction represents an important early pathophysiologic step in AD, warranting larger prospective studies.

Trial registration:
ClinicalTrials.gov Identifier: NCT00094939.
Measurement of Allostatic Load in Caregivers of Older Hispanic People With Alzheimer Disease and Related Disorders
Authors: Teresi Jeanne A. , Ocepek-Welikson Katja , Eimicke Joseph P. , Ramirez Mildred , Liu Shelley , Silver Stephanie , Luchsinger Jose A. 
Published: May 2024

Background:
Allostatic load (AL) has been studied in the context of biomarkers that may be affected by environmental and contextual stressors, including social determinants of health. The specific stressor studied here is the provision of caregiving to older persons with Alzheimer disease and related disorders. The aims were to examine the factor structure of stress and nonstress biomarkers, different methods for calculating AL, and the relationship of AL with other variables.

Methods:
Latent variable models were used to examine biomarkers. Regression analyses were performed with the outcomes: AL calculated as percentile-based and clinically-based for both stress and nonstress components. The sample was 187 Hispanic caregivers to individuals with dementia.

Results:
The results of the confirmatory factor analyses (CFAs) suggested defining 2 factors: nonstress and stress-related. Performance was better for the CFA results and the associations with covariates when stress and nonstress components were examined separately. Despite some limitations, this is one of the first studies of biomarkers in Hispanic caregivers to patients with dementia. It was possible to explain almost 30% of the variance in the nonstress AL component.

Conclusion:
It may be important to differentiate among biomarkers indicative of cardiovascular, metabolic, and immune response as contrasted with the more stress-related biomarkers.
Engineered 3D Hydrogel Matrices to Modulate Trophoblast Stem Cell-Derived Placental Organoid Phenotype
Authors: Slaby Emily M. , Hansen Nathaniel , Sharma Ritin , Pirrotte Patrick , Weaver Jessica D. 
Published: May 2024

SUMMARYPlacental organoid models are a promising platform to study human placental development and function. Organoid systems typically use naturally derived hydrogel extracellular matrices (ECM), resulting in batch-to-batch variability that limits experimental reproducibility. As an alternative, synthetic ECM-mimicking hydrogel matrices offer greater consistency and control over environmental cues. Here, we generated trophoblast stem cell-derived placental organoids using poly(ethylene glycol) (PEG) hydrogels with tunable degradability and placenta-derived ECM cues to evaluate trophoblast differentiation relative to Matrigel and two-dimensional (2D) culture controls. Our data demonstrate that PEG hydrogels support trophoblast viability and metabolic function comparable to gold standard Matrigel. Additionally, phenotypic characterization via proteomic analysis revealed that PEG and Matrigel matrices drive syncytiotrophoblast and extravillous trophoblast-dominant placental organoid phenotypes, respectively. Further, three-dimensional (3D) environments promoted greater integrin expression and ECM production than 2D culture. This study demonstrates that engineered 3D culture environments can be used to reliably generate placental organoids and guide trophoblast differentiation.
Bivariate multilevel meta-analysis of log response ratio and standardized mean difference for robust and reproducible environmental and biological sciences
Authors: Yang Yefeng , Williams Coralie , Senior Alistair M. , Morrison Kyle , Ricolfi Lorenzo , Pan Jinming , Lagisz Malgorzata , Nakagawa Shinichi 
Published: May 2024

AbstractMeta-analytic modelling plays a pivotal role in synthesizing research and informing relevant policies. Yet researchers face many analytical challenges. In environmental and biological sciences, one of the most common yet unrecognised issues is the selection between two common effect size metrics, log response ratio (lnRR) and standardized mean difference (SMD); these two are the most popular and alternative effect sizes. Having to choose between them creates room for analytical flexibility, which is susceptible to researcher degrees of freedom. Another common issue is failure to deal with statistical dependence between effect sizes, resulting in invalid inferences on evidence. We propose addressing these two issues through the joint synthesis (dual use) of lnRR and SMD. Using 75 meta-analyses, including 3,887 environmental/biological primary studies (∼20,000 effect sizes), we show a high false positive rate (40%) in conventional meta-analytic practices (random-effects model) compared to the proposed bivariate multilevel meta-analysis of lnRR and SMD along with robust variance estimation. Relying solely on either lnRR or SMD results in non-trivial discrepancies in detecting statistically significant effects (18%) and occasional inconsistencies in sign (9%). Discrepancies in interpreting effect size, heterogeneity, and publication bias are prevalent between models using lnRR and SMD (e.g., 52% for publication bias). In contrast, bivariate synthesis of lnRR and SMD yields substantial information gain, reducing standard error in effect size estimates by 29%, equivalent to adding 40 additional effect sizes. We present a user-friendly website with a step-by-step implementation guide. Our proposed robust approach aspires to improve meta-analytic modelling using lnRR and SMD in environmental and biological evidence synthesis, amplifying their reproducibility and credibility.
Is an active hospital microbiology laboratory cost-effective in a resource-limited setting? - a case study from Timor-Leste
Authors: Lim Cherry , Swe Myo Maung Maung , Devine Angela , Oakley Tessa , Champlin Karen , Oo Pyae Sone , Sarmento Nevio , Barreto Ismael Da Costa , Givney Rodney C , Yan Jennifer , Francis Joshua R , Cooper Ben S 
Published: May 2024

AbstractMaintaining an active hospital microbiology laboratory allows definitive antibiotic treatment for bacterial infections to be given in a timely manner. This would be expected to improve patient outcomes and shorten length of hospital stay. However, many hospitals in low- and middle-income countries lack access to microbiology services, and the cost-effectiveness of an active microbiology service is unknown. We constructed a decision tree and performed a cost-effectiveness model analysis to determine whether maintaining an active microbiology laboratory service would be cost-effective in Timor-Leste, a lower middle-income country. The analysis was informed by local microbiology data, local patient treatment costs, results of an expert elicitation exercise and data from literature reviews. The results indicate that there is a high probability that maintaining an active microbiology laboratory is a cost-effective intervention that would both improve patient outcomes and reduce net costs (due to reduced intensive care admissions and potential costs of resistant infections) compared to no microbiological testing, especially for the hospitalised paediatric patients with suspected primary bacteraemia. This remained true under various one-way sensitivity analyses, including when accuracy of microbiological testing is low, prevalence of bacterial infection among patients with suspected bloodstream infection was high, and prevalence of antibiotic resistance was high.
PathoGD: an integrative genomics approach for CRISPR-based target design of rapid pathogen diagnostics
Authors: Low Soo Jen , O’Neill Matthew , Kerry William J. , Wild Natasha , Krysiak Marcelina , Nong Yi , Azzato Francesca , Hor Eileen , Williams Lewis , Taiaroa George , Steinig Eike , Pasricha Shivani , Williamson Deborah A. 
Published: May 2024

ABSTRACTThe design of highly specific primers and guide RNAs (gRNA) for CRISPR-based diagnostics is often a laborious process. Several tools exist for gRNA design, but most are tailored for genome editing applications. Here, we present PathoGD, an end-to-end bioinformatic pipeline comprising pangenome andk-mer modules for rapid and high-throughput design of primers and gRNAs for CRISPR-Cas12a-based pathogen detection. We validated and demonstrated high specificity of a subset of PathoGD-designed primers and gRNAs for the detection ofNeisseria gonorrhoeaeandStreptococcus pyogenes.PathoGD will serve as an important resource for designing CRISPR-based diagnostic assays for current and emerging pathogens.
Novel Anti-virulence Compounds Disrupt Exotoxin Expression in MRSA
Authors: Balogh Halie , Anthony Amaiya , Stempel Robin , Vossen Lauren , Federico Victoria A. , Valenzano Gabriel Z. , Blackledge Meghan S. , Miller Heather B. 
Published: May 2024

AbstractHemolysins are lytic exotoxins expressed in most strains ofS. aureus, but hemolytic activity varies between strains. We have previously reported several novel anti-virulence compounds that disrupt theS. aureustranscriptome, including hemolysin gene expression. This report delves further into our two lead compounds, loratadine and a structurally related brominated carbazole, and their effects on hemolysin production in MRSA. To gain understanding into how these compounds affect hemolysis, we analyzed these exotoxins at the DNA, RNA, and protein level after in vitro treatment. While lysis of red blood cells varied between strains, DNA sequence variation did not account for it. We hypothesized that our compounds would modulate gene expression of multiple hemolysins in a laboratory strain and a clinically relevant hospital-acquired strain of MRSA, both with SCCmectype II. RNA-seq analysis of differential gene expression in untreated and compound-treated cultures revealed hundreds of differentially expressed genes, with a significant enrichment in genes involved in hemolysis. The brominated carbazole and loratadine both displayed the ability to reduce hemolysis in the laboratory strain, but displayed differential activity in a hospital-acquired strain. These results corroborate gene expression studies as well as western blots of alpha hemolysin. Together, this work suggests that small molecules may alter exotoxin production in MRSA, but that the directionality and/or magnitude of the difference is likely strain-dependent.
Molecular mechanisms driving divergent development of the human frontal and visual cortex during prenatal development
Authors: Epihova Gabriela , Epihov Dimitar Z. , Akarca Danyal , Astle Duncan E. 
Published: May 2024

AbstractKey principles of structural brain organization are established very early in fetal development. The frontal cortex is an important hub for integration and control of information, and its integrity and connectivity within the wider neural system are linked to individual differences across multiple cognitive domains and neurodevelopmental conditions. Here we leveraged fetal brain transcriptomics to investigate molecular mechanisms during prenatal development that drive early differences between the two regions at the opposite poles of the physical and representational gradient of the brain - the frontal and visual cortex. We show that the frontal cortex exhibits significantly higher cumulative gene expression for pathways involved in the continued growth and maintenance of larger neurons. These pathways include the gene ontology terms of neuron development and neuronal cell body as well as glucose metabolism important in trophically supporting larger cell sizes. Whole pathways for axonal growth (axonal growth cone, microtubules, filopodia, lamellipodia) and single genes involved in circuit connectivity exhibited increased expression in the frontal cortex. In contrast, in line with the established earlier completion of neurogenesis and lower number of neurons in the anterior cortex, expression of genes involved in DNA replication was significantly lower relative to the visual cortex. We further demonstrate differential cellular composition with higher expression of marker genes for inhibitory neurons in the prenatal frontal cortex. Together, these results suggest that the cellular architecture and composition facilitates earlier connectivity in the frontal cortex which may determine its role as an integrative hub in the global brain organization.
Exploring environmental microfungal diversity through serial single cell screening
Authors: Mariz Joana , Nawaz Ali , Bösch Yvonne , Wurzbacher Christian 
Published: May 2024

AbstractKnown for its remarkable diversity and ecological importance, the fungal kingdom remains largely unexplored. In fact, the number of unknown and undescribed fungi is predicted to exceed the number of known fungal species by far. Despite efforts to uncover these dark fungal taxa, we still face inherent sampling biases and methodological limitations. Here, we present a framework that combines taxonomic knowledge, molecular biology, and data processing to explore the fungal biodiversity of enigmatic aquatic fungal lineages. Our work is based on serial screening of environmental fungal cells to approach unknown fungal taxa. Microscopic documentation is followed by DNA analysis of laser micro-dissected cells, coupled with a ribosomal operon barcoding step realized by long-read sequencing, followed by an optional whole genome sequencing step. We tested this approach on a range of aquatic fungal cells mostly belonging to the group of aquatic hyphomycetes derived from environmental samples. From this initial screening, we were able to identify thirty-two potentially new fungal taxa in the target dataset. By extending this methodology to other fungal lineages associated with different habitats, we expect to increasingly characterize the molecular barcodes of dark fungal taxa in diverse environmental samples. This work offers a promising solution to the challenges posed by unknown and unculturable fungi and holds the potential to be applied to the diverse lineages of undescribed microeukaryotes.
Consumers’ willingness to pay in socially sustainable restaurants: an application of the decent work scale
Authors: Mejia Cynthia 
Published: May 2024

PurposeRestaurant and foodservice workers who were formally “essential” throughout the global pandemic were disproportionately subjected to layoffs and furloughs, and are now slowly returning to the industry with expectations of equitable pay and benefits. Given the recent acceleration of the UN’s Sustainability Development Goals and its focus on decent work, the purpose of this study was to determine if restaurant consumers would be willing to pay for decent work that supported the social sustainability of restaurant workers.Design/methodology/approachData were collected from 317 restaurant consumers during August 2023. Confirmatory factor analysis was used to validate the Decent Work Scale adapted for consumers. Structural equation modeling was employed to test the full behavioral model of decent work predicting willingness to pay, while bootstrapping was used to test the mediation.FindingsThe adapted Decent Work Scale for consumers strongly predicted their willingness to pay through a full mediation of Theory of Planned Behavior constructs (attitude, subjective norm, perceived behavioral control).Originality/valueThis study demonstrated that restaurant consumers were willing to pay for the decent work and social sustainability of restaurant workers. This study validated an adapted Decent Work Scale in the consumer context, whereas prior research utilizing the scale was of worker self-reports of decent work.
Packaging customization in the Italian food industry. When is it really worth it?
Authors: Ottolenghi Chiara , D'Amico Simona , Iasevoli Gennaro 
Published: May 2024

PurposeThe objective of this study is to investigate consumer motivations and purchase behaviors with respect to cookies with customized packaging and consumer interest in different types of customization in the Italian food industry.Design/methodology/approachThe study was conducted by performing a quantitative analysis of 642 surveys collected via Google Forms. A repeated-measures ANOVA, univariate ANOVA, chi-squared test, correlation analysis and linear regression analysis were conducted using SPSS.FindingsCustomers buy cookies with customized packaging as personal gifts to someone they care about. The ability to insert their initials or a personalized phrase appears to increase customers’ positive attitudes toward buying cookies with customized packaging. Those interested in this type of customization are willing to pay more, regardless of the type of customization.Research limitations/implicationsIn the survey, only some types of customization not previously extracted from a focus group are explored, and the analysis covers only the food industry and does not take a cross-sectional approach. In addition, we specifically refer to the Italian market, which means that results cannot be generalized.Practical implicationsFrom a managerial perspective, our results highlight that food industry companies should take advantage of the opportunity to segment the demand for customized packaging with respect to consumers’ attitudes and their motivation toward food products.Originality/valueFrom a theoretical perspective, this study analyzes consumer attitudes and behaviors toward purchasing cookies with customized packaging. From a managerial perspective, the results of the study highlight interesting courses of action for companies in the food industry that would like to use the tool of customization by intervening in terms of the packaging rather than the product itself.