bluuebunny/crossref_metadata_2025_split huggingface dataset:
Liver-Quant: Feature-Based Image Analysis Toolkit for Automatic Quantification of Metabolic Dysfunction-Associated Steatotic Liver Disease
Authors: Farzi Mohsen , McGenity Clare , Cratchley Alyn , Leplat Leo , Bankhead Peter , Wright Alexander , Treanor Darren 
Published: May 2024

AbstractIntroductionThe histological assessment of liver biopsies by pathologists serves as the gold standard for diagnosing metabolic dysfunction-associated steatotic liver disease (MASLD) and staging disease progression. Various machine learning and image analysis tools have been reported to automate the quantification of fatty liver and enhance patient risk stratification. However, the current software is either not open-source or not directly applicable to the whole slide images (WSIs).MethodsIn this paper, we introduce “Liver-Quant,” an open-source Python package designed for quantifying fat and fibrosis in liver WSIs. Employing colour and morphological features, Liver-Quant measures the Steatosis Proportionate Area (SPA) and Collagen Proportionate Area (CPA). The method’s accuracy and robustness were evaluated using an internal dataset of 424 WSIs from adult patients collected retrospectively from the archives at Leeds Teaching Hospitals NHS Trust between 2016 and 2022 and an external public dataset of 109 WSIs. For each slide, semi-quantitative scores were automatically extracted from free-text pathological reports. Furthermore, we investigated the impact of three different staining dyes including Van Gieson (VG), Picro Sirius Red (PSR), and Masson’s Trichrome (MTC) on fibrosis quantification.ResultsThe Spearman rank coefficient (ρ) was calculated to assess the correlation between the computed SPA/CPA values and the semi-quantitative pathologist scores. For steatosis quantification, we observed a substantial correlation (ρ=0.92), while fibrosis quantification exhibited a moderate correlation with human scores (ρ=0.51). To assess stain variation on CPA measurement, we collected N=18 cases and applied the three stains. Employing stain normalisation, an excellent agreement was observed in CPA measurements among the three stains using Bland-Altman plots. However, without stain normalisation, PSR emerged as the most effective dye due to its enhanced contrast in the Hue channel, displaying a strong correlation with human scores (ρ=0.9), followed by VG (ρ=0.8) and MTC (ρ=0.59). Additionally, we explored the impact of the apparent magnification on SPA and CPA. High resolution images collected at 0.25 microns per pixel (MPP) [apparent magnification = 40x] or 0.50 MPP [apparent magnification = 20x] were found to be essential for accurate SPA measurement, whereas for CPA measurement, low resolution images collected at 10 MPP [apparent magnification = 1x] were sufficient.ConclusionThe Liver-Quant package offers an open-source solution for rapid and precise liver quantification in WSIs applicable to multiple histological stains.
Longitudinal automated brain volumetry vs. expert visual assessment of atrophy progression on MRI is robust but caution is advised
Authors: Gebest Max , Weiß Christel , Cho Chang-Gyu , Hausner Lucrezia , Frölich Lutz , Förster Alex , Santhanam Nandhini , Fontana Johann , Groden Christoph , Wenz Holger , Maros Máté E. 
Published: May 2024

AbstractAutomated tools have been proposed to quantify brain volume for suspected dementia diagnoses. However, their robustness in longitudinal, real-life cohorts remains unexplored. We investigated if expert visual assessment (EVA) of atrophy progression is reflected by automated volumetric analyses (AVA) on sequential MR-imaging. We analyzed a random subset of 20 patients with two consecutive 3D T1-weighted examinations (median follow-up 4.0 years, LQ-UQ: 2.1-5.2, range: 0.2-10). Thirteen (65%) with cognitive decline, the remaining with other neuropsychiatric diseases. EVA was performed by two blinded neuroradiologists using a 3 or 5-point Likert scale for atrophy progression (scores ±0-2: no, probable and certain progression or decrease, respectively) in dementia-relevant brain regions (frontal-, parietal-, temporal lobes, hippocampi, ventricles). Differences of AVA-volumes were normalized to baseline (delta). Inter-rater agreement of EVA scores was excellent (κ=0.92). AVA-delta and EVA showed significant global associations for the right hippocampus (p=0.035), left temporal lobe (p=0.0092), ventricle volume (p=0.0091) and a weak association for the parietal lobe (p=0.067).Post hoctesting revealed a significant link for the left hippocampus (p=0.039). In conclusion, the associations between volumetric deltas and EVA of atrophy progression were robust for certain brain regions. However, AVA-deltas showed unexpected variance, and therefore should be used with caution in individual cases, especially when acquisition protocols vary.
Prevalence, Trends, and Associated Factors of Isolated Systolic, Diastolic, and Systolic-Diastolic Hypertension in Peru: A Nine-Year Analysis of the Demographic and Family Health Survey
Authors: Vera-Ponce Víctor Juan , Zuzunaga-Montoya Fiorella E. , Vásquez-Romero Luisa Erika Milagros , Loayza-Castro Joan A. , Gutierrez De Carrillo Carmen Inés , Vigil-Ventura Enrique 
Published: May 2024

AbstractIntroductionWhile HTN is widely seen as a primary threat to cardiovascular conditions worldwide, it is essential to recognize that not all HTN is identical.ObjectiveTo determine the prevalence, trend, and factors associated with each type of HTN: isolated systolic (ISH), isolated diastolic (IDH), and systolic-diastolic (SDH).MethodsA secondary analysis of data from the Demographic and Family Health Survey from 2014– 2022 was conducted. For the analysis of associated factors, a Poisson regression model with robust variance was implemented to calculate adjusted Prevalence Ratios (aPR) along with their 95% confidence intervals.ResultsThe prevalence was 7.02%, 1.55%, and 3.28% for ISH, IDH, and SDH, respectively. ISH showed a decline in 2022, unlike the other two types, which seem to be on the rise. A statistically significant association was found in men and an increased risk with age for ISH and SDH, unlike IDH, where age acts as a protective factor. Additional factors identified include smoking and excessive alcohol consumption, while a high intake of fruits/vegetables offers a protective effect. Obesity and diabetes were associated with a higher risk, and significant variations by region and altitude, as well as among ethnic groups, were observed.ConclusionsSignificant differences in the prevalence of HTN subtypes have been found, underscoring the heterogeneity of this chronic condition, both in related factors and in trends over the years.
Economic burden of depressive disorders for people living with HIV in Uganda
Authors: Katana Patrick V. , Ross Ian , Kiconco Barbra Elsa , Tenywa Patrick , Neuman Melissa , Ssembajjwe Wilber , Sekitoleko Isaac , Katumba Kenneth Roger , Kinyanda Eugene , Laurence Yoko V. , Greco Giulia 
Published: May 2024

IntroductionBetween 8–39 % of people living with HIV (PLWH) in sub-Saharan Africa have depressive disorders (DD). Despite considerable gains in the treatment of PLWH, DD is increasingly recognised as a threat to successful treatment and prevention. PLWH are generally known to suffer from stress and incur higher health-related costs compared to the general population due to care management demand throughout their lifespan. There have been limited studies examining healthcare costs borne by PLWH with DD specifically.ObjectiveWe aimed to estimate the economic burden of DD and HIV amongst PLWH and explore their mechanisms of coping with high out of pocket (OOP) health expenditure.MethodologyThis is a cost of illness study nested in an ongoing cluster-randomised trial assessing the effectiveness of integrating treatment of DD into routine HIV care in Uganda (HIV+D trial). The study is using cross-sectional data collected from 1,115 PLWH at trial baseline, using the Patient Health Questionnaire (PHQ-9) to measure DD and a structured cost questionnaire was administered. Forty public health care facilities that provide HIV care in Kalungu, Masaka and Wakiso Districts were randomly selected, and study participants were recruited amongst their patients. Eligibility criteria were patients attending the HIV clinic, aged ≥ 18 years who screen positive for DD (PHQ-9 ≥ 10). Economic costs (OOP expenditure and opportunity costs) were estimated from the household perspective.ResultsMean monthly economic costs amongst those incurring any costs (n=1,115) were UGX 255,910 (US$ 68.64). Mean monthly OOP expenditures were UGX 94,500 (US$ 25.60). On average, respondents missed 6 days of work per month due to healthcare seeking or ill-health for any condition. Key cost drivers were facility bed charges and medication. The majority of respondents (73%) borrowed money from families and friends to cope with the economic burden. About 29.7% reported moderate (PHQ-9 15-19) and 5.12% severe (PHQ-9 ≥ 20) DD symptoms. Respondents with moderate or severe DD had slightly higher average monthly costs than those with mild DD (PHQ-10-14), but the difference was not statistically significant.ConclusionPeople living with HIV who experience DD incur in high OOP expenditure and productivity losses. The monthly OOP health expenditure is in the range of 23% of their monthly household income. Social protection mechanisms combined with the integration of the management of DD into routine HIV care could alleviate this burden.
Association of a pace of aging epigenetic clock with rate of cognitive decline in the Framingham Heart Study Offspring Cohort
Authors: Savin M.J. , Wang H. , Pei H. , Aiello A.E. , Assuras S. , Caspi A. , Moffitt T.E. , Muenning P.A. , Ryan C.P. , Shi B. , Stern Y. , Sugden K. , Valeri L. , Belsky D.W. 
Published: May 2024

AbstractIntroductionThe geroscience hypothesis proposes systemic biological aging is a root cause of cognitive decline.MethodsWe analyzed Framingham Heart Study Offspring Cohort data (n=2,296; 46% male; baseline ageM=62, SD=9, range=25-101y). We measured cognitive decline across two decades of neuropsychological-testing follow-up. We measured pace of aging using the DunedinPACE epigenetic clock. Analysis tested if participants with faster DunedinPACE values experienced more rapid preclinical cognitive decline as compared to those with slower DunedinPACE values.ResultsParticipants with faster DunedinPACE had poorer cognitive functioning at baseline and experienced more rapid cognitive decline over follow-up. Results were robust to confounders and consistent across population strata. Findings were similar for the PhenoAge and GrimAge epigenetic clocks.DiscussionFaster pace of aging is a risk factor for preclinical cognitive decline. Metrics of biological aging may inform risk stratification in clinical trials and prognosis in patient care.
Predictors of perinatal mortality in the seven major hospitals of Lusaka Zambia: A Case Control Study
Authors: Makasa Musonda , Kaonga Patrick , Jacobs Choolwe , Makasa Mpundu , Vwalika Bellington 
Published: May 2024

AbstractBackgroundOver 2.6 million babies are lost later in pregnancy, during labour, and or in the first week of life. Global perinatal mortality reduced from 5.7 million since 2000 to 4.1 million in 2015. High-income countries account for 45% of this data. The rest are in low-income countries, 77% of which are in sub-Saharan Africa. Perinatal mortality rates for sub-Saharan Africa and Zambia are 42.95 and 33/1000 live births, respectively. The aim of this study was to determine the predictors of perinatal mortality at the seven major hospitals of Lusaka, Zambia.MethodsThis was a multi- centre unmatched case control study from September 2023 to January 2024. Cases included perinatal death (>24 weeks gestation or >500g stillborn, and death of neonate within seven days of life) and controls were live births. Stepwise multivariate logistic regression analysis determined predictors using adjusted odd ratios and p-values.ResultsThe study had 630 participants, 210 cases and 420 controls were analysed: ratio 1:2. Antenatal care booking after 12 weeks gestation had almost three times odds of experiencing perinatal (AOR 2.909, 95% CI: 1.97-4.296), p <0.001 compared to those who booked early. Walking as means of reaching healthcare facility had over three odds perinatal mortality (AOR3.482, 95% CI: 1.87-6.49) than personal transport users. Anaemia during pregnancy had over three times risk of perinatal death (AOR 3.581, 95% CI: 1.72- 7.44) than those without it. History of loss of baby before birth had five fold odds to experience perinatal mortality than to those who had not (AOR 5.047, 95% CI: 2.99-8.51).ConclusionThis study revealed that late antenatal care booking, walking, as means of transport to access health facility, anaemia in pregnancy, and previous history of loss of baby before birth perinatal death were the main predictors with statistical significance of perinatal death experience.
Understanding Diagnostic Error Patterns and Contributing Factors: A Descriptive Analysis of Medical Error Reports at a Tertiary Hospital in Kenya 2019-2021
Authors: Okutoyi Lydia , Godia Pamela , Adam Mary , Sitati Fred , Jaoko Walter 
Published: May 2024

ABSTRACTBackgroundDiagnostic errors in healthcare pose substantial risks, leading to increased costs, patient anxiety, and delayed diagnoses. Despite its prevalence, diagnostic errors have historically received less attention compared to other medical errors, necessitating urgent action to address these critical issues. This is more so in the low- and middle-income countries. (LMICs). This study aimed to analyze patterns and associated factors of diagnostic error reported to the Patient Safety Unit of Kenyatta National Hospital (KNH), a tertiary teaching hospital in Nairobi, Kenya.MethodsThis was a descriptive retrospective study of medical error reports(MER) forms submitted to KNH from 2019-2021.Type of medical errors, contributing factors, site, timing of error, and outcome were recorded. Descriptive statistics, chi-square tests, and logistic regression were employed to assess error types, contributing factors, and associated likelihoods.ResultsAmong 640 MER forms analysed, diagnostic errors were reported in 40 percent of cases, predominantly associated with delayed diagnosis, wrong diagnosis, and failure to test. Contributing factors to MER included communication issues (36.1%), staff-related factors (48.9%), and equipment issues (15.6%). Diagnostic errors were more likely during non-working hours (OR 1.969, p < 0.047) and in Accident and Emergency department (OR 2.36, p < 0.022) within KNH.ConclusionDiagnostic errors represent a significant proportion of medical errors at KNH, particularly in Accident and Emergency settings. Strategies to involve more physicians in error reporting and enhance communication practices are recommended.
External UK validation of the ENDPAC model to predict pancreatic cancer risk: A registered report protocol
Authors: Price Claire A. , Claridge Hugh , de Lusignan Simon , Khalaf Natalia , Mold Freda , Smith Nadia A. S. , Winn Martyn , Lemanska Agnieszka 
Published: May 2024

AbstractIntroductionOverall cancer survival has increased over recent decades, but the very low survival rates of pancreatic cancer have hardly changed in the last 50 years. This is attributed to late diagnosis. Pancreatic cancer symptoms are non-specific which makes early diagnosis challenging. Data-driven approaches, including algorithms using combinations of symptoms to predict cancer risk, can aid clinicians. A simple but effective algorithm called Enriching New-Onset Diabetes for Pancreatic Cancer (ENDPAC) has been developed in the United States (US). ENDPAC has not yet been used in the United Kingdom (UK), our aim is to translate ENDPAC into the UK setting. The objectives are to validate ENDPAC and report its predictive utility within primary care.MethodsA retrospective cohort study of people with new-onset diabetes using the nationally representative Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub (ORCHID) database. ORCHID holds over 10 million primary care electronic healthcare records. ENDPAC scores will be calculated for eligible people along with positive predictive value, negative predictive value, sensitivity and specificity of the algorithm. We will evaluate the optimal cut-off for defining people with high-risk of having pancreatic cancer.DiscussionOnce validated within the UK, ENDPAC could be implemented in practice to improve early pancreatic cancer diagnosis by using routine data. ENDPAC is currently being tested in the US in a clinical trial to evaluate its effectiveness. ENDPAC offers an automatable and inexpensive way to improve early diagnosis as part of a sequential approach to identify individuals at high-risk of having undiagnosed pancreatic cancer.How this fits inPancreatic cancer is a devasting disease which is hard to diagnose. An algorithm called ENDPAC has been developed in the United States to help clinicians identify people at risk of having undiagnosed pancreatic cancer. These people can be referred for an imaging investigation to diagnose or rule out cancer. This protocol outlines a United Kingdom (UK) validation of ENDPAC so that it could be used in clinical practice in the UK.
Trends in Repeat Administration of Magnesium for an Exacerbation of Postpartum Preeclampsia: A National Survey
Authors: Dellapiana Gabriela , Thompson Keona , Gregory Kimberly D 
Published: May 2024

BackgroundMagnesium (Mg) infusion is first-line for seizure prophylaxis in preeclampsia with severe features (PESF). Guidance is lacking regarding utility of an additional course of Mg for disease exacerbation following completion of an initial course. We aimed to determine the national trend among academic institutions for administration of a second course of Mg in patients with an exacerbation of PESF.MethodsA REDCap survey querying response to clinical scenarios related to Mg administration was sent to Maternal-Fetal Medicine program directors (or surrogate if no response) using publicly available contact information. Participants received a $10 incentive.ResultsResponses were received from 66 of 95 institutions (69%), representing all 12 ACOG districts. An institutional protocol for postpartum Mg was reported by 70% (N=46) of respondents. Overall, 68% (N=45) would give a second course of Mg for an exacerbation of PESF, with no geographic variation (P=0.969). Most would administer a second course of Mg if the patient had a headache (N=52, 79%) or blood pressure ≥180/120 (N=35, 53%). The decision for a second course of Mg was not influenced by worsening laboratory values, gestational age at delivery, latency from delivery, or maternal demographics.ConclusionsAlthough there are no standardized guidelines for seizure prophylaxis in postpartum exacerbations of PESF, this national survey suggests that most academic programs favor giving a second course of Mg, especially in patients with headache or severe BP. A randomized trial comparing outcomes in patients who did or did not receive an additional course of Mg is warranted.
Medial temporal lobe atrophy patterns in early- versus late-onset amnestic Alzheimer’s disease
Authors: Wuestefeld Anika , Pichet Binette Alexa , van Westen Danielle , Strandberg Olof , Stomrud Erik , Mattsson-Carlgren Niklas , Janelidze Shorena , Smith Ruben , Palmqvist Sebastian , Baumeister Hannah , Berron David , Yushkevich Paul A. , Hansson Oskar , Spotorno Nicola , Wisse Laura EM 
Published: May 2024

AbstractBackgroundThe medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer’s disease (EOAD). Yet, detailed examination of MTL subfield volumes and drivers of atrophy in amnestic EOAD is lacking.MethodsBioFINDER-2 participants with memory impairment, abnormal amyloid-β status and tau-PET were included. Forty-one EOAD individuals aged ≥65 years and, as comparison, late-onset AD (LOAD, ≤70 years, n=154) and Aβ-negative cognitively unimpaired controls were included. MTL subregions and biomarkers of (co-)pathologies were measured.ResultsAD groups showed smaller MTL subregions compared to controls. Atrophy patterns were similar across AD groups, although LOAD showed thinner entorhinal cortices compared to EOAD. EOAD showed lower WMH compared to LOAD. No differences in MTL tau-PET or transactive response DNA binding protein 43-proxy positivity was found.ConclusionsWe found in vivo evidence for MTL atrophy in amnestic EOAD and overall similar levels to LOAD of MTL tau pathology and co-pathologies.
Centromere protection requires strict mitotic inactivation of the Bloom syndrome helicase complex
Authors: Fernández-Casañas María , Karanika Eleftheria , Olukoga Tomisin , Herbert Alex , Aliyaskarova Umit , Day Matthew , Chan Kok-Lung 
Published: May 2024

AbstractThe BTRR (BLM/TOP3A/RMI1/RMI2) complex resolves various DNA replication and recombination intermediates to suppress genome instability. Alongside PICH, they target mitotic DNA intertwinements, known as ultrafine DNA bridges, facilitating chromosome segregation. Both BLM and PICH undergo transient mitotic hyper-phosphorylation, but the biological significance of this remains elusive. Here, we uncover that during early mitosis, multiple protein kinases act together to strictly constrain the BTRR complex for the protection of centromeres. Mechanistically, CDK1 destabilises the complex and suppresses its association with PICH at the chromatin underneath kinetochores. Inactivating the BLM and TOP3A interaction compromises the UFB-binding complex mitotic functions and can prevent centromere destruction. We further unravel how different clusters of mitotic phosphorylation on BLM affect its interaction with the TOP3A/RMI1/RMI2 subcomplex and illegitimate centromere unwinding. Furthermore, we identify specific phosphorylation sites targeted by the MPS1-PLK1 axis functioning to prevent BLM hyper-activation at centromeres. Notably, unleashing such activity after sister-chromatid cohesion loss facilitates separation of entangled chromosomes. Together, our study defines a centromere protection pathway in human mitotic cells, heavily reliant on a tight spatiotemporal control of the BTRR complex.
Large scale loss-of-function mutations during chicken evolution and domestication
Authors: Wu Siwen , Wang Kun , Ge Xuehai , Dou Tengfei , Yuan Sisi , Yan Shixiong , Xu Zhiqiang , Liu Yong , Jian Zonghui , Zhao Jingying , Zhao Rouhan , Zi Xiannian , Gu Dahai , Liu Lixian , Li Qihua , Wu Dong-Dong , Jia Junjing , Ge Changrong , Su Zhengchang 
Published: May 2024

AbstractDespite recent progresses, the driving force of evolution and domestication of chickens remains poorly understood. To fill this gap, we recently sequenced and assembled genomes of four distinct indigenous chickens from Yunnan, China. Unexpectedly, we found large numbers of pseudogenes which have lost their functions and are fixed in their corresponding populations, and we also found highly variable proteomes in the genomes of the four indigenous chickens as well as the sequenced wild red jungle fowl (RJF) (GRCg6a). Although the four indigenous chicken breeds are closely related to theG. g. spadiceoussubspecies, for the first time, we found that the RJF (GRCg6a) is of theG. g. bankivaorigin. Thus, the five chicken share the most recent common ancestor (MRCA) before subspeciation. Our results support a scenario that the MRCA of the four indigenous chickens and the RJF possessed at least 21,972 genes, of which 7,993 are dispensable. Each chicken has lost functions of thousands of the dispensable genes during their evolution and domestication via complete gene loss and pseudogenization. The occurring pattens of completely lost genes and pseudogenes segregate the chickens as their phylogenetic tree does. Therefore, loss-of-function mutations might play important roles in chicken evolution and domestication.