bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigation of electrochromic band-shifts in the Soret region induced by the formation of TyrD•, TyrZ•, and QA•-in Photosystem II
Authors: Boussac Alain , Noguchi Takumi , Rutherford A. William , Sellés Julien , Sugiura Miwa , Viola Stefania 
Published: November 2024

AbstractThe effects of TyrD•, TyrZ•, and QA•-radical formation on the absorption spectrum in the Soret region were studied in Mn-depleted Photosystem II at pH 8.6 (in order to be in the TyrDstate after dark adaptation). Flash-induced difference spectra were recorded in several PSII samples from:i)Thermosynechococcus vestitus(formerlyT. elongatus),ii)Synechocystis sp.PCC 6803,iii)Chroococcidiopsis thermalisPCC 7203 grown under far-red light, andiv)Acaryochloris marina. In the case ofT. vestitus, mutants D1/H198Q, D1/T1789H, D2/I178H, and D2/Y160F, with PsbA1/Q130 instead of PsbA3/E130, were also studied for possible contributions from PD1, ChlD1, ChlD2, and PheD1, respectively. For a possible contribution from PD2, the D2/H197A mutant was studied inS. 6803. While PD1is clearly the species whose spectrum is blue-shifted by ∼3nm in the presence of QA•-, as has already been well documented in the literature, the species whose spectra shift upon the formation of TyrD•and TyrZ•remain to be clearly identified, as they appear different from PD1, PD2, PheD1, ChlD1, and ChlD2, as concluded by the lack of different light-induced difference spectra in the mutants listed above. Although we cannot rule out a weak effect, considering the accuracy of the experiments, it is proposed that other pigments, such as antenna Chl and/or Car, near the reaction center are involved. Additionally, it is shown that:i) there is no proton release into the bulk upon the oxidation of TyrDat pH 8.6, andii) the rearrangement of the electrostatic environment of the pigments involved in the light-induced difference spectra in the samples studied, upon the formation of TyrD•, TyrZ•, and QA•-, likely occurs differently from both a kinetic and structural perspective.
Pilot: Salivary Lactoferrin as a Biomarker of Alzheimer’s Disease
Authors: Hammerschlag BL , Butts B , Likos KDS , Verble DD , Nimmagadda N , Virani R , Ramanathan S , Wharton W. 
Published: November 2024

BackgroundAlzheimer’s disease (AD) research has focused on developing accessible biomarkers that accurately detect disease pathology and progression before symptoms present. Lactoferrin (Lf) is an iron-binding antimicrobial glycoprotein found in all biological fluids, and its concentration in saliva has been correlated with AD symptoms. This pilot project aimed to determine whether salivary lactoferrin (sLF) has potential as a biomarker for AD.MethodsParticipants were middle to older-aged non-Hispanic white (NHW) and Black Americans (BA) at risk for AD due to parental history. We collected saliva samples after an 8-hour fast and administered a cognitive battery assessing executive function, memory, visuospatial ability, attention, and verbal fluency. We examined the relationship between sLF and cognitive performance and evaluated protein concentration across races.ResultsSeventeen middle-to-older-aged (age = 60.29 ± 9.7 years) BA and NHWs were enrolled. After controlling for age, sex, race, and years of education, we found a significant r between sLF and Digit Span Memory Test (DSMT) scores (P= 0.013) and a modest correlation with Mental Rotation Test scores (P= 0.194). We found no difference in average concentration across races.ConclusionsMemory concerns and a worsening in visuospatial ability are early signs of cognitive decline in AD patients, and this pilot suggests a correlation of these symptoms with sLF. Bigger-scale longitudinal studies to examine the relationship between sLF and established AD biomarkers in diverse populations are needed to assess its clinical usefulness as an early biomarker for AD.
Use of the test-negative design to estimate the protective effect of a scalar immune measure: A simulation analysis
Authors: Zhang Ziyuan , Boyer Christopher Brian , Lipsitch Marc 
Published: November 2024

AbstractBackgroundThe relationship between antibody levels (more generally, a scalar measure of immune protection) at the time of exposure to infection (so-called exposure-proximal correlates of protection) and the risk of infection given exposure is of central interest in evaluating the evolution of immune protection conferred by prior infection and/or vaccination. A version of the test-negative study design (TND), adapted from vaccine effectiveness studies, has been used to assess this relationship. However, the conditions under which such a study identifies the relationship between immune measurements and protection have not been defined.ObjectiveTo evaluate the conditions for TNDs to estimate the relationship between antibody levels or a similar scalar measurement of immunity (hereafter exposure-proximal correlates of protection, COP) and the relative incidence rate of infection given exposure.MethodIndividual-based transmission models, linking infection risk linearly and nonlinearly with COP value and accounting for waning immunity post-vaccination and –infection, were used. Simulations were performed of a TND with sampling on predetermined dates. Data from either one or multiple simulation days were analyzed using logistic regression and generalized additive models.ResultA correctly specified logistic regression model provided an unbiased estimate of the effectiveness of specific COP levels (analogous to vaccine effectiveness). Aggregating data across different simulation dates with incidence-density sampling also provided reliable estimates of protection. When, as is generally the case, the functional form relating COP level to protection is unknown, generalized additive models offer a more flexible alternative to traditional logistic regression approaches.ConclusionA TND can validly estimate the relative effect of an immune COP at the time of exposure on the incidence rate of infection via logistic regression if the functional form of the effect is known and appropriately modeled or unknown a semiparametric approach. Future research should further examine the dynamics of immunity waning and boosting for more reliable inference.
Novel Domain V mutation incfr-positive clinicalStaphylococcus haemolyticusisolates causing linezolid resistance in Egyptian ICU patients
Authors: Maghraby Saber , Dawoud Mohamed Ez El-Din , Eweis Mohamed , El-nagish Abdullah , Ghaith Doaa 
Published: November 2024

AbstractLinezolid resistance has become a focal point worldwide, particularly as linezolid stands as one of the last resort antibiotics against multiple-drug resistant bacterial strains. Despite its critical importance, the situation in Egypt remains relatively unexplored. As various linezolid resistance mechanisms have been identified in staphylococci, our investigation aims to uncover the molecular characteristics of staphylococci showing reduced susceptibility to Linezolid at Kasr-El-Eini Teaching Hospital. Thirty isolates were investigated in this study. The selected samples, identified by Vitek 2 system and confirmed by 16S rRNA, were examined by disc diffusion method. Of the 30 isolates, two were confirmed as linezolid resistant and screened for the presence of cfr gene and mutations in the Domain V of the 23S rRNA gene. Both of the studied strains, identified asStaphylococcus haemolyticus, SZ-2 and SZ-7 harbored two point mutations G2576T and G2602T in the Domain V of the 23S rRNA gene. A novel G2694C mutation reported for the first time was detected in strain SZ-7. The presence of cfr gene was confirmed in both isolates. Linezolid-resistantStaphylococcus haemolyticushad emerged in ICU patients with prior antibiotic exposure. The exact role of the novel G2694C mutation in linezolid resistance needs further investigations. The study underscores the importance of proper surveillance ofcfr-carrying strains in the healthcare settings in Egypt.
Index microvascular resistance (IMR)-guided management of heart transplantation (IMR-HT study): Study Protocol
Authors: Pérez-Guerrero Ainhoa , Vilchez-Tschischke Jean Paul , Almenar Bonet Luis , Diez Gil Jose Luis , Blasco Peiró Teresa , Brugaletta Salvatore , Gomez-Lara Josep , González Costello José , Antuña Paula , Alonso Fernández Vanesa , Sarnago Cebada Fernando , García-Cosio María Dolores , Hidalgo Lesmes Francisco , López Granados Amador , López-Palop Ramón , Paula Garrido Iris , Cardenal Piris Rosa María , Rangel Sousa Diego , Fuertes Ferre Georgina 
Published: November 2024

ABSTRACTBackgroundAcute allograft rejection (AAR) is an important cause of morbi-mortality in heart transplant (HT) patients, particularly during the first year. Endomyocardial biopsy (EMB) is the “gold standard” to guide post-heart transplantation treatment. However, it is associated with complications that can be potentially serious. Index of microvascular resistance (IMR) is a specific physiological parameter to measure microvascular function. An increased IMR measured early after HT has been associated with acute cellular rejection (ACR), higher all-cause mortality and adverse cardiac events. As far as we know, no study has evaluated IMR impact on post-HT management (number of EMB performed). Our aim will be to assess if post-HT patient management may be modified based on IMR value.Study designThe IMR-HT study (NCT 06656065) is a multicenter, prospective study that will include post-HT consecutive stable patients undergoing coronary physiological assessment in the first three months and one year. Depending on IMR values the physician will be able to reduce the number of biopsies established in each center protocol.ConclusionsManagement after heart transplant (number of biopsies) could be modified depending on IMR values.
Risk prediction models for pneumonia in hospitalized stroke patients: A systematic review
Authors: Yan Manlin , Huang Weirong , Zhang Zhihui , Song Meixuan , Li Xianrong 
Published: November 2024

AbstractObjectiveTo systematically evaluate risk prediction models for pneumonia occurrence during hospitalization in stroke patients.MethodsComputer searches were conducted in the PubMed, Embase, Web of Science, Cochrane Library, and EBSCO databases for literature related to risk prediction models for pneumonia in hospitalized stroke patients, with search dates ranging from database inception to June 13, 2024. Two researchers independently screened the literature, extracted the data, and evaluated the risk of bias and applicability of the included studies via the Prediction Model Risk of Bias ASsessment Tool (PROBAST).ResultsA total of 43 studies were included, among which 33 studies developed a total of 56 new models, and 25 studies externally validated 19 models. Among the 56 new models, 29 used a logistic regression model (LR), 25 used a machine learning model (ML), 1 used a classification and regression tree model (CART), and 1 used a linear regression model. The reported area under the curve (AUC) ranged from 0.565 to 0.960. The number of predictors explicitly reported for one model was 1,046, with the top three predictors most commonly used being age, the National Institutes of Health Stroke Scale (NIHSS) score, and dysphagia. The PROBAST results revealed that all 43 studies had a high risk of bias, and 27 studies had poor applicability.ConclusionAlthough the pneumonia risk prediction models for hospitalized stroke patients in the included studies achieved good predictive performance, the overall quality needs improvement. Future research should follow stricter study designs, standardized reporting practices, and multicenter large-sample external validation.
A generalised vision transformer-based self-supervised model for diagnosing and grading prostate cancer using histological images
Authors: Chaurasia Abadh K , Harris Helen C , Toohey Patrick W , Hewitt Alex W 
Published: November 2024

ABSTRACTBackgroundGleason grading remains the gold standard for prostate cancer histological classification and prognosis, yet its subjectivity leads to grade variability between pathologists, potentially impacting clinical decision-making. Herein, we trained and validated a generalised AI-driven system for diagnosing prostate cancer using diverse datasets from tissue microarray (TMA) core and whole slide images (WSIs) with Hematoxylin and Eosin staining.MethodsWe analysed eight prostate cancer datasets, which included 12,711 histological images from 3,648 patients, incorporating TMA core images and WSIs. The Macenko method was used to normalise colours for consistency across diverse images. Subsequently, we trained a multi-resolution (5x, 10x, 20x, and 40x) binary classifier to identify benign and malignant tissue. We then implemented a multi-class classifier for Gleason patterns (GP) sub-categorisation from malignant tissue. Finally, the models were externally validated on 11,132 histology images from 2,176 patients to determine the International Society of Urological Pathology (ISUP) grade. Models were assessed using various classification metrics, and the agreement between the model’s predictions and the ground truth was quantified using the quadratic weighted Cohen’s Kappa (κ) score.ResultsOur multi-resolution binary classifier demonstrated robust performance in distinguishing malignant from benign tissue withκscores of 0.967 on internal validation. The model achievedκscores ranging from 0.876 to 0.995 across four unseen testing datasets. The multi-class classifier also distinguished GP3, GP4, and GPs with an overallκscore of 0.841. This model was further tested across four datasets, obtainingκscores ranging from 0.774 to 0.888. The models’ performance was compared against an independent pathologist’s annotation on an external dataset, achieving aκscore of 0.752 for four classes.ConclusionThe self-supervised ViT-based model effectively diagnoses and grades prostate cancer using histological images, distinguishing benign and malignant tissues and classifying malignancies by aggressiveness. External validation highlights its robustness and clinical applicability in digital pathology.
Smallpox bioterrorism scenarios and reactive intervention protocol: mathematical model-based analysis
Authors: Ko Youngsuk , Seo Yubin , Park Jin Ju , Kim Eun Jung , Moon Jong Youn , Kim Tark , Eom Joong Sik , Oh Hong Sang , Kim Arim , Kim Jin Yong , Lee Jacob , Jung Eunok 
Published: November 2024

AbstractSmallpox, caused by the variola virus, is one of the most devastating diseases in human history and was eradicated through global vaccination efforts by 1980. Despite its eradication, the virus remains in high-security laboratories for research purposes, posing the potential risk of bioterrorism. This study developed a mathematical model to analyze potential smallpox epidemics by incorporating factors such as age groups, heterogeneous contact patterns, and various intervention strategies including contact tracing, ring vaccination, and mass vaccination. The model simulations indicated that the Republic of Korea’s current plans for negative-pressure isolation beds should suffice under most scenarios, but extreme worst-case scenarios could overwhelm healthcare capacity. This study highlights the critical importance of non-pharmaceutical interventions and strategic vaccination prioritization for controlling outbreaks. These findings provide valuable guidance for public health officials and policymakers in preparing for potential bioterrorism threats and emerging infectious diseases. Furthermore, emphasizes the need for comprehensive preparedness and robust response strategies. The proposed framework applies to smallpox and to other infectious diseases, offering insights for future outbreak management.
Article Processing Charges Threaten Global Health Equity: Open Access is Closed Science
Authors: Hyman Gabriella Y. , Wurdeman Taylor , Kumar Nikathan , Alty Isaac G. , Forbes Callum , Riviello Robert , Raykar Nakul P. 
Published: November 2024

AbstractIntroductionThe shift from subscription-based to open-access (OA) publishing sought to democratize scientific knowledge by eliminating access barriers. However, article processing charges (APCs) have raised concerns about equity, particularly for researchers from low- and middle-income countries (LMICs). APCs shift costs from readers to authors, potentially limiting the ability of researchers to disseminate their work. This study aimed to quantify the effect of APCs on equity in global surgery by examining current APC costs and their association with journal metrics and LMIC authorship.MethodsA structured review was conducted on journals’ APCs and bibliometrics using data from the Scientific Journal Rankings (SJR) and PubMed. Journals were included if they actively published human health research and had at least 100 articles with first author information. APC data were obtained from five major publishers (Elsevier, Wiley, Oxford, Sage, and Springer Nature) and supplemented manually. Journals were categorized into surgery, public health, and other groups. Data on APCs, bibliometrics (SJR ranking, H-index), and first author affiliations were analyzed using linear regression models to assess their relationship with APC costs and LMIC authorship.ResultsThe study included 2,001 journals with a median APC of $3,700 USD showing no significant cost differences across journal categories. The median percentage of LMIC first authors was 4%, with a significant negative association between APCs and LMIC authorship: each $500 increase in APC was linked to a 0.7% decrease in LMIC first authorship. While higher APCs correlated with slightly higher bibliometric indices, the academic impact was limited.ConclusionAPCs present a significant barrier to LMIC authors, undermining the equity goals of OA publishing. Alternative funding models, such as tiered pricing or expanded waivers, are needed to ensure OA remains accessible and equitable across all economic contexts.
Mutation Spectrum and Associated Risks of Medullary Thyroid Cancer and All-Cause Mortality in Incidentally Identified MEN2A-CausingRETVariants
Authors: West Courtney E. , Mirshahi Uyenlinh L. , Ruth Katherine S. , Sharp Luke N. , Arni Ankit M. , Turnbull Clare , Wright Caroline F. , Vaidya Bijay , Owens Martina M. , Carey David J. , Patel Kashyap A. 
Published: November 2024

AbstractImportanceRETpathogenic variants cause Multiple Endocrine Neoplasia type 2 (MEN2), characterised by medullary thyroid cancer (MTC). With increasing incidental identification of these variants in asymptomatic individuals outside family screening, their risk of MTC and all-cause mortality without intervention remain unknown in this context.ObjectiveTo determine the risk of MTC and all-cause mortality in clinically unselected individuals and assess how the risk of MTC differ from clinically ascertained cases.Design, Setting, and ParticipantsProspective cohort study of 383,914 unrelated individuals from the clinically unselected UK population (UK Biobank) and 122,640 from the US health system (Geisinger cohort). We compared MTC risk in these cohorts to 1,078 individuals who were clinically ascertained with suspicion of MEN2 from UK routine practice.ExposuresRETpathogenic variants causing MEN2Main Outcomes and MeasuresFrequency and the spectrum of pathogenicRETvariants, Risk of clinically presented MTC, all-cause mortality without thyroidectomy.ResultsPathogenicRETvariants were found in 0.04% of individuals from UK population cohort and 0.08% of individuals from US health system cohort. They were predominantly from moderate-risk category as per American Thyroid Association guideline (99.4% and 94.8% respectively). MTC risk by age 75 in variant carriers in the UK population was 2.2% (95% CI 0.7-6.8) and 19% (95% CI 5.7-30) in US health system cohort. This was significantly lower than the clinically ascertained cohort with the matched variants (95.7%, 95% CI 82.1-99.7 p<0.0001). In the UK Biobank, most variant carriers (98.2%) did not undergo thyroidectomy and their all-cause mortality by age 75 was similar to non-carriers (6.1%, 95% CI 2.7-13.8 vs 5.7%, 5.6-5.8, p=0.79), with consistent findings in the US health system cohort.Conclusions and RelevanceModerate-riskRETvariants are most common in incidental cases. These variants carry substantially lower MTC risk than clinically ascertained cases. This evidence addresses a current knowledge gap, enabling more informed clinical decision-making.
CharacterisingStreptococcus pneumoniaeTransmission Patterns in Malawi Through Genomic and Statistical Modelling
Authors: Cave Rory , Chirombo James , Obolski Uri , Belman Sophie , Kalizang’oma Akuzike , Mwalukomo Thandie S. , Kamng’ona Arox , Brown Comfort , Msefula Jacquline , Bonomali Farouck , Nyirenda Roseline , Swarthout Todd D. , Kwambana-Adams Brenda , French Neil , Heyderman Robert S. 
Published: November 2024

AbstractControlling the carriage and transmission ofStreptococcus pneumoniaein children from high- disease burden countries is crucial for disease prevention. To assess the rate of spread, and the factors associated with the high frequency of transmission despite pneumococcal conjugate vaccine (PCV) introduction, we measured evolution divergence time using the whole genome sequences ofS. pneumoniaecollected from 1,617 child participants from Blantyre, Malawi between 2015 and 2019. These children included both PCV13 vaccinated children aged 2 to 7 years and PCV13 unvaccinated children aged 5 to 10 years who were age ineligible when PCV was introduced. Using a generalized additive mixed model (GAMM) and relative risk (RR) frameworks, while accounting for household geospatial distances, we found that the spread of lineages became widespread across the population of Blantyre over approximately four years, with transmission being more likely between neighbouring households. Logistic regression and random forest models predicted a higher incidence of events among preschool children in densely populated, higher socioeconomic areas. Additionally, recent transmission was linked to recently expanding, non-vaccine serotype lineages that are penicillin non-susceptible. Our findings suggest that enhancing vaccine-mediated immunity among preschool-aged children in high density settings could reduce transmission of disease-causing and antimicrobial-resistant pneumococcal lineages, therefore strengthening herd protection for vulnerable individuals (e.g. very young children and people living with HIV).