bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monitoring corn stover processing by the fungus Ustilago maydis
Authors: Robertz Stefan , Philipp Magnus , Schipper Kerstin , Richter Paul , Miebach Katharina , Magnus Jorgen , Pauly Markus , Ramírez Vicente 
Published: September 2024

AbstractA key aspect of sustainable bioeconomy is the recirculation of renewable, agricultural waste streams as substrates for microbial production of high-value compounds. One approach is the bioconversion of corn stover, an abundant maize crop byproduct, using the fungal maize pathogen Ustilago maydis. U. maydis is already used as a unicellular biocatalyst in the production of several industrially-relevant compounds using plant biomass hydrolysates. In this study, we demonstrate that U. maydis can grow using untreated corn stover as its sole carbon source. We developed a small-scale bioreactor platform to investigate U. maydis processing of corn stover, combining online monitoring of fungal growth and metabolic activity profiles with biochemical analyses of the pre- and post-fermentation residues. Our results reveal that U. maydis primarily utilizes soluble sugars i.e., glucose, sucrose and fructose present in corn stover, with only limited exploitation of the abundant lignocellulosic carbohydrates. Thus, we further explored the biotechnological potential of enhancing U. maydis´ lignocellulosic utilization. Additive performance improvements of up to 120 % were achieved when using a maize mutant with increased biomass digestibility, co-fermentation with a commercial cellulolytic enzyme cocktail, and exploiting engineered fungal strains expressing diverse lignocellulose-degrading enzymes. This work represents a key step towards scaling up the production of sustainable compounds from corn stover using U. maydis and provides a tool for the detailed monitoring of the fungal processing of plant biomass substrates.
Graphical abstract
Quantitative SPECT imaging of 155Tb and 161Tb for preclinical theranostic radiopharmaceutical development
Authors: Koniar Helena , McNeil Scott , Wharton Luke , Ingham Aidan , Van de Voorde Michiel , Ooms Maarten , Sekar Sathiya , Rodríguez-Rodríguez Cristina , Kunz Peter , Radchenko Valery , Rahmim Arman , Uribe Carlos , Yang Hua , Schaffer Paul 
Published: September 2024

Abstract
Background
Element-equivalent matched theranostic pairs facilitate quantitative in vivo imaging to establish pharmacokinetics and dosimetry estimates in the development of preclinical radiopharmaceuticals. Terbium radionuclides have significant potential as matched theranostic pairs for multipurpose applications in nuclear medicine. In particular, 155Tb (t1/2 = 5.32 d) and 161Tb (t1/2 = 6.89 d) have been proposed as a theranostic pair for their respective applications in single photon emission computed tomography (SPECT) imaging and targeted beta therapy. Our study assessed the performance of preclinical quantitative SPECT imaging with 155Tb and 161Tb. A hot rod resolution phantom with rod diameters ranging between 0.85 and 1.70 mm was filled with either 155Tb (21.8 ± 1.7 MBq/mL) or 161Tb (23.6 ± 1.9 MBq/mL) and scanned with the VECTor preclinical SPECT/CT scanner. Image performance was evaluated with two collimators: a high energy ultra high resolution (HEUHR) collimator and an extra ultra high sensitivity (UHS) collimator. SPECT images were reconstructed from photopeaks at 43.0 keV, 86.6 keV, and 105.3 keV for 155Tb and 48.9 keV and 74.6 keV for 161Tb. Quantitative SPECT images of the resolution phantoms were analyzed to report inter-rod contrast, recovery coefficients, and contrast-to-noise metrics.

Results
Quantitative SPECT images of the resolution phantom established that the HEUHR collimator resolved all rods for 155Tb and 161Tb, and the UHS collimator resolved rods ≥ 1.10 mm for 161Tb and ≥ 1.30 mm for 155Tb. The HEUHR collimator maintained better quantitative accuracy than the UHS collimator with recovery coefficients up to 92%. Contrast-to-noise metrics were also superior with the HEUHR collimator.

Conclusions
Both 155Tb and 161Tb demonstrated potential for applications in preclinical quantitative SPECT imaging. The high-resolution collimator achieves < 0.85 mm resolution and maintains quantitative accuracy in small volumes which is advantageous for assessing sub organ activity distributions in small animals. This imaging method can provide critical quantitative information for assessing and optimizing preclinical Tb-radiopharmaceuticals.
Silica infiltration as a strategy to overcome zirconia degradation
Authors: Alfrisany Najm M. , Somogyi-Ganss Eszter , Tam Laura E , Hatton Benjamin D. , Sodhi Rana N. S. , Yin Ling , De Souza Grace M. 
Published: September 2024

AbstractThe excellent clinical performance of yttria-partially stabilized zirconias (Y-SZs) makes them promising materials for indirect restorations. However, the Y-SZ phase stability is a concern, and infiltrating Y-SZs with a silica nanofilm may delay their degradation processes. In this study, we analyzed stabilities of silica-infiltrated zirconia surfaces after exposure to artificial aging (AA).Four zirconia materials with different translucencies (n = 40) were used, including low translucency 3 mol% Y-SZ (3Y-LT, Ceramill ZI, Amann Girrbach); high translucency 4 mol% Y-SZ (4Y-HT, Ceramill Zolid); and two high translucency 5 mol% Y-SZs (5Y-HT, Lava Esthetic, 3M and 5Y-SHT, Ceramill Zolid, FX white). Sintered specimens were exposed to 40 cycles of silica (SiO2) through room temperature atomic layer deposition (RT-ALD) using tetramethoxysilane (TMOS) and ammonium hydroxide (NH4OH). AA was applied for 15 h in an autoclave (134°C, 2 bar pressure). Stabilities of zirconia-silica surfaces were characterized in terms of hardness and Young's modulus using nanoindentation techniques and crystalline contents using x-ray diffraction (XRD) analyses. Silica deposition was also characterized by X-ray photoelectron spectroscopy (XPS).There was a significant effect of the interaction of materials and surface treatments on the hardness and Young's modulus values of zirconia-silica surfaces (p < 0.001). Silica deposition on zirconia surfaces improved the material resistance to degradation by AA.
A post-marketing study to evaluate the safety and immunogenicity of a quadrivalent influenza split-virion vaccine in elderly people aged 60 years and older
Authors: Kou Zengqiang , Li Xiaoyu , Liu Ti , Fan Bei , An Wenqi , An Wenjue , Dang Mingan , Zhang Ke , Tang Jingning , Zhu Nan , Pan Ruowen 
Published: September 2024

Abstract
Background
Influenza remains a global public health concern. Understanding the vaccination-induced response in an aging population, which is susceptible and at high risk, is essential for disease prevention and control. Here, we report findings on the safety and immunogenicity of a quadrivalent influenza split-virion vaccine (15 µg/subtype/0.5 ml/dose) (hereinafter referred to as the “quadrivalent influenza vaccine”) in a population aged ≥ 60 years.

Methods
This open-label, pragmatic post-marketing trial enrolled 1399 older adults to receive one dose of an approved commercially available quadrivalent influenza vaccine manufactured by Hualan Biological Bacterin Inc. (hereinafter referred to as “Hualan Bio”). Participants with contraindications for the vaccine were excluded, while poor health condition was acceptable. All vaccinated subjects experienced adverse events collection within 30 days and serious adverse events within 180 days post-vaccination. 25% subjects, selected randomly, underwent venous blood sampling pre-vaccination and 30 days after post-vaccination, for detecting antibody titers against each subtype of influenza virus by hemagglutination inhibition assay. The incidences of adverse events and antibody titers against each subtype of influenza virus were statistically analyzed using SAS 9.4.

Results
No grade 3 adverse reactions occurred within 30 days post-vaccination. The incidences of overall adverse reactions, local adverse reactions and systemic adverse reactions were 3.79%, 2.86% and 1.00%, respectively. No serious adverse reactions occurred within 180 days post-vaccination. There were 350 subjects who completed venous blood sampling pre-vaccination, among whom 348 subjects completed venous blood sampling at 30 days post-vaccination for immunogenicity assessment. With respect to hemagglutination inhibition antibodies against influenza viruses H1N1, H3N2, BV and BY subtypes, at 30 days post-vaccination, the seroconversion rates were 87.64%, 75.57%, 73.28% and 78.74%, respectively; the seropositive rates were 93.97%, 98.56%, 79.31% and 95.40%, respectively; and the geometric mean increase (GMI) in post-immunization/pre-immunization antibodies was 24.80, 7.26, 10.39 and 7.39, respectively.

Conclusion
One 15 µg/subtype dose of the vaccine had a good safety profile and elicited favorable immunogenicity among subjects aged ≥ 60 years. The results of this study indicate that Hualan Bio quadrivalent influenza vaccine strike balance between safety and immunogenicity, supporting unnecessity to increase dosage or inoculation frequency for further enhancing immunogenicity.

Trial registration
Registered on ClinicalTrials.gov. Registration number: NCT06334510. Registered on 28/03/2024 (retrospectively registered).
Moving forward: scaling-up the integration of an HIV and hypertension program in Akwa Ibom State, Nigeria
Authors: Mishra Shivani , Aifah Angela A. , Henry Daniel , Uzoigwe Nina , Udoh Ememobong Bassey , Idang Esther , Munagala Jahnavi , Onakomaiya Deborah , Kanneh Nafesa , Ekanem Anyiekere , Attah Eno Angela , Ogedegbe Gbenga , Ojji Dike 
Published: September 2024

AbstractAs people living with HIV experience increased life expectancy, there is a growing concern about the burden of comorbid non-communicable diseases, particularly hypertension. This brief describes the current policy landscape on the management of HIV and hypertension in Akwa Ibom State, Nigeria, stakeholder engagement meetings, and the resulting five policy recommendations rooted in an ongoing research study designed to integrate hypertension management into HIV care across primary health centers in the State. In order to identify the current gaps in integrated care, discussion sessions with three stakeholder groups (i.e., healthcare providers, patient advocacy groups, and policy makers) were held separately in November 2022. The discussions were purposed to brainstorm policy-level solutions for integrating hypertension into HIV treatment. After all the sessions were concluded, there were five recommendations provided by the stakeholders for integrating HIV and hypertension care in the Akwa Ibom State. Stakeholders unanimously agreed with the need to integrate hypertension care for HIV impacted communities in the State. Specifically, stakeholders recommended to: (1) engage retired community health nurses as mentors; (2) actively link communities to integrated care in clinics; (3) integrate hypertension management with HIV education; (4) expand health insurance accessibility; and (5) formally integrate hypertension management into primary healthcare centers in Akwa Ibom State.
Identification of novel likely pathogenic variant in CDH23 causing non-syndromic hearing loss, and a novel variant in OTOGL in an extended Iranian family
Authors: Mohammadi Aliasgar , Hoseinzadeh Marziyeh , Narrei Sina , Pourreza Mohammad Reza , Mohammadi Yousof , Norouzi Mahnaz , Sadeghian Ladan , Tabatabaiefar Mohammad Amin 
Published: September 2024

Abstract
Background
Sensorineural hearing loss (SNHL) is a clinically and genetically heterogeneous group of disorders of the auditory system. SNHL can occur as a symptom in more than 400 syndromes, and mutations in more than 150 genes can lead to SNHL. Mutations in the GJB2 and GJB6 genes are among the most common causes of SNHL worldwide. Mutations in Cadherin 23 (CDH23) can cause Usher syndrome and/or non-syndromic hearing loss (NSHL).

Material and methods
In this study, the Whole Exome Sequencing (WES) was used to detect the cause of hearing loss in a large consanguineous Iranian family with two patients. All family members underwent a thorough Genotype–phenotype correlation assessment and co-segregation analysis to understand the inheritance pattern within the family. The candidate variants were further confirmed by Sanger sequencing. In addition, in silico analysis was performed to predict the functional impact of the variants; the interpretation of the variants was performed in accordance with the American College of Medical Genetics (ACMG) guidelines.

Results
WES results identified two novel variants, a homozygous missense variant in CDH23 (c.2961T > G) and a heterozygous splice site variant in OTOGL that was compatible with the autosomal recessive pattern of inheritance. Bioinformatics studies confirmed the pathogenic effects of novel variants. The c.2961T > G variant was classified as likely pathogenic.

Conclusions
The novel identified variant in the CDH23 was the cause of congenital profound progressive form of HL. Samples were not available from the second family to distinguish which variant is responsible for the molecular pathology of the disease. Further studies and functional examinations are suggested for investigating the role of OTOGL: c. 1863-1G > T in deafness.
Seismic fragility analysis of long-span rigid-frame bridge on mountainous soft clay site
Authors: Zhang Gao , Zhang Jin , Liu Yang , Cao Yating 
Published: September 2024

AbstractIn order to assess the damage condition of bridge components for a large-span rigid bridge in a soft clay site in a mountainous area in China southwest, a finite element model of a large-span rigid bridge is established based on the OpenSees software, and the joint probability density distribution function of the ground motion strength and seismic demand and the marginal distribution function of the ground motion are introduced into the kernel density function. As a basis to get the method of calculating the fragility of the bridge members, and the method is verified for its feasibility, on this basis, the damage condition of the bridge components are analyzed, and finally the damage condition of the bridge system are analyzed by the first-order bounds method and the improved PCM method (IPCM). The results showed that: (1) Kernel density method (KDE) can effectively calculate the damage probability of each component, for example, under ground motions with PGA equal to 0.2 g, the probability of slight damage of the 1# pier is 29%, that of the intermediate consolidation pier (2# pier ~ 4# pier) is about 90%; the probability of slight damage of the 1# bearing is 48%, and that of the 2# bearing is 87%. (2) Reasonable value of the expansion joints can effectively reduce the probability of main beam collision. In this investigation, the value is taken as 0.18 m ~ 0.24 m. (3) The bridge system is more likely to be damaged than a single component in the system, and the damage probability of a single component cannot be used as a criterion for the bridge system in the actual working condition. Comparing the first-order boundary law with the IPCM method, the IPCM method has higher accuracy.
Loss-of-function mutation in anthocyanidin reductase activates the anthocyanin synthesis pathway in strawberry
Authors: Xu Pengbo , Li Maobai , Ma Chao , Li Xinyu , Bai Peng , Lin Anqi , Wang Chong , Zhang Liqing , Kuang Huiyun , Lian Hongli 
Published: September 2024

AbstractFruit color substantially affects consumer preferences, with darker red strawberries being economically more valuable due to their higher anthocyanin content. However, the molecular basis for the dark red coloration remains unclear. Through screening of an ethyl methanesulfonate mutant library, we identified a rg418 mutant, that demonstrated anthocyanin accumulation during early fruit development stages. Furthermore, the ripening fruits of this mutant had higher anthocyanin content than wild-type (WT) fruits. An analysis of flavonoid content in WT and rg418 mutant fruits revealed substantial changes in metabolic fluxes, with the mutant exhibiting increased levels of anthocyanins and flavonols and decreased levels of proanthocyanidins. Bulked sergeant analysis sequencing indicated that the mutant gene was anthocyanidin reductase (ANR), a key gene in the proanthocyanidin synthesis pathway. Furthermore, transcriptome sequencing revealed the increased expression of MYB105 during the early development stage of mutant fruits, which promoted the expression of UFGT (UDP-glucose flavonoid 3-O-glucosyltransferase), a key gene involved in anthocyanin synthesis, thus substantially enhancing the anthocyanin content in the mutant fruits. Additionally, mutating ANR in a white-fruited strawberry variant (myb10 mutant) resulted in appealing pink-colored fruits, suggesting the diverse roles of ANR in fruit color regulation. Our study provides valuable theoretical insights for improving strawberry fruit color.
Somapacitan in Children Born SGA: 52-Week Efficacy, Safety, and IGF-I Response Results From the Phase 2 REAL5 Study
Authors: Juul Anders , Backeljauw Philippe , Højby Michael , Frystyk Jan , Kawai Masanobu , Kildemoes Rasmus Juul , Lemminger Anders Krogh , Linglart Agnès , Zuckerman-Levin Nehama , Horikawa Reiko 
Published: September 2024

Abstract

Context
Somapacitan, a once-weekly reversible albumin-binding growth hormone (GH) derivative, is evaluated in short children born small for gestational age (SGA).

Objective
Evaluate efficacy, safety, tolerability as well as total and bioactive insulin-like growth factor I (IGF-I) response of once-weekly somapacitan compared to daily GH in children born SGA.

Methods
REAL5 is a randomized, multicenter, open-label, controlled phase 2 study comprising a 26-week main phase, a 26-week extension, and an ongoing 4-year safety extension (NCT03878446), conducted at 38 sites across 12 countries. A total of 62 GH-treatment-naïve, prepubertal short children born SGA were randomized; 61 completed 52-weeks of treatment. Patients were randomized (1:1:1:1:1) to somapacitan (0.16, 0.20, or 0.24 mg/kg/week) or daily GH (0.035 or 0.067 mg/kg/day), all administered subcutaneously.

Results
Estimated mean height velocity (HV; cm/year) at week 52 was 8.5, 10.4, and 10.7 cm/year for somapacitan 0.16, 0.20, and 0.24 mg/kg/week, respectively, and 9.3 and 11.2 cm/year for daily GH 0.035 and 0.067 mg/kg/day, respectively. Dose-dependent increases in total IGF-I, as well as peak IGF-I bioactivity, were observed for both treatments and were similar between comparator groups. For somapacitan, exposure-response modeling indicated highest efficacy with 0.24 mg/kg/week after 52 weeks of treatment. Similar safety and tolerability were demonstrated across all groups.

Conclusion
A sustained dose-dependent growth response was demonstrated for somapacitan after 52 weeks of treatment. Overall, somapacitan 0.24 mg/kg/week provides similar efficacy, safety, and tolerability, as well as comparable bioactive and total IGF-I response, as daily GH (0.067 mg/kg/day) in children born SGA.
Data-Driven Strategies for Carbimazole Titration: Exploring Machine Learning Solutions in Hyperthyroidism Control
Authors: Reich Thilo , Bakirov Rashid , Budka Dominika , Kelly Derek , Smith James , Richardson Tristan , Budka Marcin 
Published: September 2024

Abstract

Background
University Hospitals Dorset (UHD) has more than 1000 thyroid patient contacts annually. These are primarily patients with autoimmune hyperthyroidism treated with carbimazole titration. Dose adjustments are made by a healthcare professional (HCP) based on the results of thyroid function tests, who then prescribes a dose and communicates this to the patient via letter. This is time consuming and introduces treatment delays. This study aimed to replace some time-intensive manual dose adjustments with a machine learning model to determine carbimazole dosing. This can in the future serve patients with rapid and safe dose determination and ease the pressures on HCPs.

Methods
Data from 421 hyperthyroidism patients at UHD were extracted and anonymized. A total of 353 patients (83.85%) were included in the study. Different machine learning classification algorithms were tested under several data processing regimes. Using an iterative approach, consisting of an initial model selection followed by a feature selection method, the performance was improved. Models were evaluated using weighted F1 scores and Brier scores to select the best model with the highest confidence.

Results
The best performance is achieved using a random forest (RF) approach, resulting in good average F1 scores of 0.731. A model was selected based on a balanced assessment considering the accuracy of the prediction (F1 = 0.751) and the confidence of the model (Brier score = 0.38).

Conclusion
To simulate a use-case, the accumulation of the prediction error over time was assessed. It was determined that an improvement in accuracy is expected if this model was to be deployed in practice.
Thyroid Hormone and Alzheimer Disease: Bridging Epidemiology to Mechanism
Authors: Escamilla Sergio , Salas-Lucia Federico 
Published: September 2024

Abstract
The identification of critical factors that can worsen the mechanisms contributing to the pathophysiology of Alzheimer disease is of paramount importance. Thyroid hormones (TH) fit this criterion. Epidemiological studies have identified an association between altered circulating TH levels and Alzheimer disease. The study of human and animal models indicates that TH can affect all the main cellular, molecular, and genetic mechanisms known as hallmarks of Alzheimer disease. This is true not only for the excessive production in the brain of protein aggregates leading to amyloid plaques and neurofibrillary tangles but also for the clearance of these molecules from the brain parenchyma via the blood-brain barrier and for the escalated process of neuroinflammation—and even for the effects of carrying Alzheimer-associated genetic variants. Suboptimal TH levels result in a greater accumulation of protein aggregates in the brain. The direct TH regulation of critical genes involved in amyloid beta production and clearance is remarkable, affecting the expression of multiple genes, including APP (related to amyloid beta production), APOE, LRP1, TREM2, AQP4, and ABCB1 (related to amyloid beta clearance). TH also affects microglia by increasing their migration and function and directly regulating the immunosuppressor gene CD73, impacting the immune response of these cells. Studies aiming to understand the mechanisms that could explain how changes in TH levels can contribute to the brain alterations seen in patients with Alzheimer disease are ongoing. These studies have potential implications for the management of patients with Alzheimer disease and ultimately can contribute to devising new interventions for these conditions.