bluuebunny/crossref_metadata_2025_split huggingface dataset:
Standardising Workforce Cost Estimates Across Australian Jurisdictions: Genomic Testing as a Use Case
Authors: Mordaunt Dylan A 
Published: April 2024

AbstractIntroductionLabour costs are a key driver of healthcare costs and a key component of economic evaluations in healthcare. We undertook the current study to collect information about workforce costs related to clinical genomic testing in Australia, identifying key components of pay scales and contracts, and incorporating these into a matrix to enable modelling of disaggregated costs.MethodsWe undertook a microcosting study of health workforce labour costs in Australia, from a health services perspective. We mapped the genomic testing processes, identifying the relevant workforce. Data was collected on the identified workforce from publicly available pay scales. Estimates were used to model the total cost from a public health services employer perspective, undertaking deterministic and probabilistic sensitivity analyses.ResultsWe identified significant variability in the way in which pay scales and related conditions are both structured and the levels between jurisdictions. The total costs (2023-24 AUD $) ranged from 160,794 (113,848 - 233,350) for administrative staff to 703,206 (548,011 - 923,661) for pathology staff (full-time equivalent). Deterministic sensitivity analysis identified that the base salary accounts for the greatest source of uncertainty, from 24.8% (20.0% - 32.9%) for laboratory technicians to 53.6% (52.8% - 54.4%) for medical scientists.ConclusionVariations in remuneration levels and conditions between Australian jurisdictions account for considerable variation in the estimated cost of labour and may contribute significantly to the uncertainty of economic assessments of genomic testing and other labour-intensive health technologies. We outline an approach to standardise the collection and estimation of uncertainty for Australian health workforce costs and provide current estimates for labour costs.
Novel genetic insights into the roles of amino acids in metabolic dysfunction-associated steatotic liver disease
Authors: Liu Jun , Chen Yuxuan , Qian Jin , Cui Ri , Demirkan Ayse , Zheng Yihu 
Published: April 2024

AbstractBackgroundPrevious research has suggested potential links between amino acids and metabolic dysfunction-associated steatotic liver disease (MASLD), but the precise roles of amino acids in MASLD development are not well understood. This study aimed to obtain insights into the relationships between circulating amino acids and MASLD.MethodsUtilizing data from the UK Biobank, we examined the observational associations of ten amino acids with MASLD in a cohort of 72,626 MASLD cases and 128,102 controls. Bi-directional two-sample Mendelian randomization (MR) was conducted using genome-wide association study data to investigate the causal relationships between amino acids and MASLD. Multiple MR methods comprising MR-Egger and MR-PRESSO were applied to assess pleiotropy and heterogeneity, and multivariable MR was conducted to evaluate the impacts of body mass index (BMI) on these associations. Survival analysis assessed the link between baseline amino acid levels and the risk of major outcomes.ResultsWe identified nine amino acids significantly associated with MASLD in the observational study. The genetic predisposition towards higher leucine (odds ratio (OR) [95% confidence interval (CI)]: 2.1 [1.4, 3.2]), valine (OR [95% CI]: 1.8 [1.3, 2.7]), and alanine (OR [95% CI]: 1.4 [1.1, 1.8]) levels were significantly associated with MASLD. By contrast, the genetic predisposition for increased MASLD risk was significantly associated with phenylalanine (beta = 0.05,p= 4.0×10-4). Further analysis showed that valine may mediate the association between BMI and MASLD, and may also have an exclusive effect on MASLD in addition to the effect of obesity (beta = 1.3,p= 1.9×10-4). Elevated phenylalanine levels in MASLD patients were linked with an increased risk of metabolic dysfunction-associated steatohepatitis (MASH), hepatocellular carcinoma, cirrhosis, heart failure, stroke, and mortality.ConclusionWe found genetic associations between circulating branched-chain amino acids, particularly leucine and valine, and MASLD, independent of obesity. Phenylalanine was identified as a potential biomarker for MASLD prognostic complications. These results highlight the importance of amino acid metabolism in MASLD as well as suggest new possibilities for research and therapeutic intervention.
Exploring factors affected timely receiving intravitreal anti-VEGF treatment in patients with Diabetic Macular Edema: a qualitative interview study analyzed with COM-B model
Authors: Li Shu , Pan Jiani , Xu Yan , Tian Shiyu , Dai Zhengyue , Fang Qiong 
Published: April 2024

AbstractObjectivesTo explore factors affected untimely receiving intravitreal anti-Vascular endothelial growth factor (VEGF) injection based on the Capability, Opportunity and Motivation-Behavior (COM-B) model in patients with Diabetic Macular Edema (DME) and regard these factors as main targets for interventions.DesignAn exploratory qualitative study was conducted using semi-structured interviews with patients with DME. The COM-B model was used to guide data collection and analysis.SettingThe study was carried out in outpatient department of ophthalmology in China.Participants24 patients with DME who experienced anti-VEGF treatment at least one injection within one year were recruited using convenience and purposed sampling.ResultsThe themes and subthemes were identified. Physical capability included (1) lack of knowledge, (2) high treatment expenditure, and psychological capability included prioritized glycemic control rather than anti-VEGF. Social opportunity included (1) no anti-VEGF available, (2) Recommended eyedrops, laser and oral drug but not mentioned intravitreal anti-VEGF injection, (3) As an optional therapy, selected more convenient treatment rather than anti-VEGF agents, and physical opportunity included (1) no confidence in treatment from doctor, (2) communication between doctors and patients. Reflective motivation included (1) outcome expectancies, and automatic motivation included (1) fear of injection, (2) fear of blindness.ConclusionWe should attach importance to these eleven factors, especially to effective interaction between doctors and patients, and doctor’s authoritative treatment advice, which interventions were based on in the future.Strengths and limitations of this study⇒ The qualitative design was used to understand factors affecting timely intravitreal anti-VEGF injections in patients with DME and to explore the potential measures to change them.⇒The study highlighted the importance of efficient communication between clinicians and patients.⇒The study didn’t consider other clinical variables, such as the severity and duration of diabetes, which should be included in the future studies.
Antibody Responses to SARS-Cov-2 among Health Care Workers of a Tertiary Hospital in North-Eastern, Tanzania
Authors: Ibrahim Pendo M , Anthony Felix , Mshana Happiness , Rwegoshola Kevin , Semvua Hadija , Chilongola Jaffu 
Published: April 2024

AbstractBackgroundHealth Care Workers (HCWs) have been playing crucial role in treating patient with COVID-19. They have a higher occupational risk of contracting the disease than the general population, and a greater chance of them transmitting the disease to vulnerable patients under their care. Given their scarcity and low COVID-19 vaccine acceptance in Africa, it is essential that HCWs are seroprotected and their exposure to COVID-19 minimized. This study was therefore designed to determine IgG antibody response to SARS-CoV-2 among HCWs in North Eastern, Tanzania.MethodologyThis was a cross-sectional study carried out among 273 HCWs at Kilimanjaro Christian Medical Centre (KCMC), a tertiary, zonal referral hospital in Tanzania’s North Eastern region. Stratified sampling was used to select study participants. Data were obtained from each consenting participant using a validated questionnaire. Blood samples were collected for SARS-CoV-2 IgG antibodies quantification by using an indirect ELISA test. RedCap software was used to enter and manage data. Statistical analysis was done by using STATA statistical software version 15 and GraphPad Prism v 9.0. A p-value of < 0.05 was considered the cut-off for statistical significance.ResultsAmong 273 HCWS only 37.9 % reported to have received COVID-19 vaccine. Except for one person, all of the participants had SARS-CoV-2 IgG antibody concentrations that were positive, with 64.5% of them having strong seropositivity. Female gender, allied health professionals, active smoking, COVID-19 patient interactions, COVID-19 vaccination receptivity, and adherence to recommended hand hygiene were found to be significant predictors of variation of median SARS-CoV-2 antibody concentration. The usage of personal protective equipment, history of previously testing PCR positive for COVID-19, the number of COVID-19 patient exposure and age were found to cause no significant variation in median antibody concentration among participants.ConclusionsThis study reports a high seroprevalence of SARS-CoV-2 antibodies among healthcare workers in Kilimanjaro Christian Medical Centre. This suggests that HCWs have significant exposure to SARS-CoV-2 despite the low rate of vaccination acceptance even among HCWs. We recommend a strengthened Infectious Prevention and Control (IPC) in hospitals through provision of technical leadership and coordination according to WHO guidelines. We also recommend continued conduction of seroprevalence studies to estimate the magnitude and trends of SARS-CoV-2 infections in different populations in Tanzania. A better understanding of the past, current, and future transmission patterns of infectious pathogens is critical for preparedness and response planning, and to inform the optimal implementation of existing and novel interventions under the current and changing climate.
Reduced Continuity Index with Proactive Esophageal Cooling Compared to Luminal Temperature Monitoring During Radiofrequency Ablation
Authors: Lazarus Catherine , Sherman Jacob , Putzel Natalie , Zagrodzky William , Sharkoski Tiffany , Ro Alex , Nazari Jose , Fisher Westby , Kulstad Erik , Metzl Mark 
Published: April 2024

AbstractBackgroundProactive esophageal cooling is FDA cleared to reduce the likelihood of esophageal injury during radiofrequency ablation for treatment of atrial fibrillation (AF). Long-term follow-up data have also shown improved freedom from arrhythmia with proactive esophageal cooling compared to luminal esophageal temperature (LET) monitoring during pulmonary vein isolation (PVI). One hypothesized mechanism is improved lesion contiguity (as measured by the Continuity Index) with the use of cooling. We aimed to compare the Continuity Index of PVI cases using proactive esophageal cooling to those using LET monitoring.MethodsContinuity Index was calculated for PVI cases at two different hospitals within the same health system using a slightly modified Continuity Index to facilitate both real-time calculation during observation of PVI cases and retrospective determination from recorded cases. The results were then compared between proactively cooled cases and those using LET monitoring.ResultsContinuity Indices for a total of 101 cases were obtained; 77 cases using proactive esophageal cooling and 24 cases using traditional LET monitoring. With proactive esophageal cooling, the average Continuity Index was 2.7 (1.3 on the left pulmonary vein, and 1.5 on the right pulmonary vein). With LET monitoring, the average Continuity Index was 27.3 (14.3 on the left, and 12.9 on the right), for a difference of 24.6 (p < 0.001).ConclusionProactive esophageal cooling during PVI is associated with significantly improved lesion contiguity when compared to LET monitoring. This finding may offer a mechanism for the greater freedom from arrhythmia seen with proactive cooling in long-term follow-up.
ASCVD risk refinement with NT-proBNP for statin allocation among low- and intermediate risk individuals
Authors: Pavlović Jelena , Kavousi Maryam , Ikram M. Kamran , Bos Daniel , Ikram M. Arfan , Leening Maarten J.G. 
Published: April 2024

ABSTRACTBackgroundStatin trials targeting low- to intermediate risk individuals, namely MEGA, JUPITER, and HOPE-3, have demonstrated benefit of statin use for primary prevention of atherosclerotic cardiovascular disease (ASCVD), but are poorly reflected in guideline recommendations for primary prevention of ASCVD. N-terminal pro-B-type natriuretic peptide (NT-proBNP) may refine ASCVD risk in low-to intermediate risk individuals eligible for HOPE-3, JUPITER and MEGA, and aid statin initiation in low- to intermediate risk populations.Methods5434 participants, aged 45 years and above from the prospective population-based Rotterdam Study, free of ASCVD, heart failure, and diabetes, were included between 1997 and 2008. Eligibility criteria for MEGA, JUPITER, and HOPE-3 trials were checked for each participant. ASCVD event rates, hazard ratios (HR), 5-year numbers needed to treat (NNT5y), and screen (NNS5y) per trial eligible population and NT-proBNP category (≤50, 50-100, and >100 pg/mL) were calculated.ResultsMedian age was 61.6 years, 58.9% were women, median NT-proBNP was 60 pg/mL. The proportions of participants eligible for MEGA, JUPITER and HOPE-3 were 34.9%, 10.4% and 23.7%. Incidence rates per 1000 person-years for ASCVD were 10.4 (95%CI: 60.1-67.9) for MEGA, 16.8 (95%CI: 13.6-20.6) for JUPITER, and 12.1 (95%CI: 10.3-14) for HOPE-3. Adjusted HR in trial eligible individuals for NT-proBNP >100 pg/mL compared to ≤50 pg/mL level were 1.73 (95%CI: 1.21-2.47), 1.46 (95%CI: 0.80-2.66) and 1.50 (95%CI: 0.99-2.26), respectively. Estimated NNT5yamong trial eligible individuals with NT-proBNP levels >100 pg/mL based on high-intensity statin treatment, varied from 23 to 34 to prevent one ASCVD event, while NNS5yranged between 56 and 134.ConclusionsNT-proBNP level >100 pg/mL identifies individuals at the highest ASCVD risk among low- to intermediate risk populations who are likely to benefit from statin treatment at acceptable NNT5yand NNS5y.Clinical PerspectiveWhat is New?NT-proBNP level >100 pg/mL can identify individuals at the highest ASCVD risk among low- to intermediate risk populations who are likely to benefit from statin treatment at acceptable numbers needed to treat and screen.Among apparently healthy individuals without prior ASCVD and diabetes mellitus, 60% was deemed to be at low- to intermediate risk by qualifying for at least one of three RCT based on the trial eligibility criteria, and one out four individuals had NT-proBNP level >100 pg/mL.What are the Clinical Implications?NT-proBNP level can be used for risk refining in low- to intermediate risk individuals who are most likely to benefit from statin initiation for ASCVD primary prevention.
Development of a Real-Time Risk Tracking Model for Neurological Deterioration in Ischemic Stroke Patients Based on Blood Pressure Dynamics
Authors: Kang Jihoon , Noh Maeng Seok , Lee Juneyoung , Lee Youngjo , Bae Hee-Joon 
Published: April 2024

AbstractObjectivesUsing the significant link between blood pressure fluctuations and neurological deterioration (ND) in patients with ischemic stroke, this study aims to develop a predictive model capable of real-time tracking of ND risk, enabling timely detection of high-risk periods.MethodsA total of 3,906 consecutive ischemic stroke patients were recruited. As an initial predictive model, a polytomous logistic regression model, incorporating clinical parameters to estimate a probability of ND occurring within and beyond 12 hours post-stroke onset, was developed. To refine ND risk assessments over time, we subsequently introduced an iterative risk-tracking model that utilizes continuously updated blood pressure measurements. We endeavored to integrate these models, assessing their combined discriminative capacity and clinical utility, with a particular emphasis on pinpointing time periods of increased ND risk.ResultsND rates were observed at 6.1% within the first 12 hours and 7.3% during the following 60 hours. We noted variations in incidence rates and their distribution over time across predefined patient groups. Significant predictors of ND varied among these subgroups and across different time periods. The iterative risk-tracking model maintained a consistent relationship between blood pressure variables and ND risk across different patient groups, successfully forecasting ND within a 12-hour window. The integrated models achieved an area under the receiver operating characteristic curve (AUC) ranging from 0.68 to 0.76. This performance effectively narrowed down the critical window for ND risk identification without sacrificing predictive accuracy across diverse patient groups. At 90% and 70% sensitivity settings, the combined model precisely identified the periods of highest ND risk, showing slightly higher or comparable specificity and positive predictive values relative to other models.ConclusionThis study presents a novel approach for real-time monitoring of ND risk in ischemic stroke patients, utilizing BP trends to identify critical periods for potential intervention.
Gpr37 modulates the severity of inflammation-induced GI dysmotility by regulating enteric reactive gliosis
Authors: Robertson Keiramarie , Hahn Oliver , Robinson Beatriz G. , Faruk Arwa T. , Janakiraman Mathangi , Namkoong Hong , Kim Kwangkon , Ye Jiayu , Bishop Estelle Spear , Hall Randy A. , Wyss-Coray Tony , Becker Laren S. , Kaltschmidt Julia A. 
Published: April 2024

SummaryThe enteric nervous system (ENS) is contained within two layers of the gut wall and is made up of neurons, immune cells, and enteric glia cells (EGCs) that regulate gastrointestinal (GI) function. EGCs in both inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) change in response to inflammation, referred to as reactive gliosis. Whether EGCs restricted to a specific layer or region within the GI tract alone can influence intestinal immune response is unknown. Using bulk RNA-sequencing andin situhybridization, we identify G-protein coupled receptorGpr37, as a gene expressed only in EGCs of the myenteric plexus, one of the two layers of the ENS. We show that Gpr37 contributes to key components of LPS-induced reactive gliosis including activation of NF-kB and IFN-y signaling and response genes, lymphocyte recruitment, and inflammation-induced GI dysmotility. Targeting Gpr37 in EGCs presents a potential avenue for modifying inflammatory processes in the ENS.
Glutamylation imbalance leads to photoreceptor cell degeneration
Authors: Mercey Olivier , Gadadhar Sudarshan , Magiera Maria M. , Lebrun Laura , Kostic Corinne , Moulin Alexandre , Arsenijevic Yvan , Janke Carsten , Guichard Paul , Hamel Virginie 
Published: April 2024

AbstractThe stereotypic structure of microtubules, assembled from conserved α/β-tubulin dimers is subject to a complex diversity of Post-translational Modifications (PTMs). PTMs are predicted to fine-tune microtubule properties and interactions with other proteins, thus allowing microtubules to perform specific functions. Cilia accumulate several types of tubulin PTMs, such as polyglutamylation, polyglycylation, detyrosination and acetylation, whose functions are not yet fully understood. Recently, mutations ofAGBL5, coding for the deglutamylating enzyme CCP5, have been associated to retinitis pigmentosa, suggesting that perturbation of polyglutamylation leads to the degeneration of photoreceptor cells. However, the molecular mechanisms underlying this degeneration remain unknown. Here, using super-resolution Ultrastructure Expansion Microscopy in mouse and human photoreceptor cells, we found that most tubulin PTMs are accumulated at the level of the connecting cilium, a structure linking the outer and inner segments of photoreceptor cells. Using mouse models with increased glutamylation (Ccp5-/-andCcp1-/-), or loss of tubulin acetylation (Atat1-/-), we demonstrated that aberrant glutamylation, but not loss of acetylation, resulted in perturbed molecular architecture of the outer segment, with the loss of the bulge region and destabilization of the distal axoneme. Concurrently, we observed a substantial impairment in tubulin glycylation and intraflagellar transport. Altogether our results indicate that glutamylation plays a crucial role in the maintenance of the molecular architecture of the outer segment and point to tubulin PTM imbalance as possible culprit in retinal degeneration.
Integrative multi-omic analysis identifies genes associated with cuticular wax biogenesis in adult maize leaves
Authors: Lin Meng , Bacher Harel , Bourgault Richard , Qiao Pengfei , Matschi Susanne , Vasquez Miguel F. , Mohammadi Marc , van Boerdonk Sarah , Scanlon Michael J. , Smith Laurie G. , Molina Isabel , Gore Michael A. 
Published: April 2024

SUMMARYStudying the genetic basis of leaf wax composition and its correlation with leaf cuticular conductance (gc) is crucial for improving crop water-use efficiency. The leaf cuticle, which comprises a cutin matrix and various waxes, functions as an extracellular hydrophobic layer, protecting against water loss upon stomatal closure. To address the limited understanding of genes associated with the natural variation of leaf cuticular waxes and their connection togc, we conducted statistical genetic analyses using leaf transcriptomic, metabolomic, and physiological data sets collected from a maize (Zea maysL.) panel of ∼300 inbred lines. Through a random forest analysis with 60 cuticular wax traits, it was shown that high molecular weight wax esters play an important role in predictinggc. Integrating results from genome-wide and transcriptome-wide studies (GWAS and TWAS) via a Fisher’s combined test revealed 231 candidate genes detected by all three association tests. Among these, 11 genes exhibit known or predicted roles in cuticle-related processes. Throughout the genome, multiple hotspots consisting of GWAS signals for several traits from one or more wax classes were discovered, identifying four additional plausible candidate genes and providing insights into the genetic basis of correlated wax traits. Establishing a partially shared genetic architecture, we identified 35 genes for bothgcand at least one wax trait, with four considered plausible candidates. Our study uncovered the genetic control of maize leaf waxes, establishing a link between wax composition andgc, with implications for potentially breeding more water-use efficient maize.SIGNIFICANCE STATEMENTWe exploited natural variation in the abundance of maize leaf cuticular waxes to identify genetic determinants of wax composition and its relationship to cuticle function as a barrier against water loss. We identified a set of strongly supported candidate genes with plausible functions in cuticular wax biosynthesis or deposition and added to the evidence for wax esters as the most important wax for water barrier function, offering new tools for modification of cuticle-dependent traits.