bluuebunny/crossref_metadata_2025 huggingface dataset:
Synaptic Density Reductions in MSA: A Potential Biomarker Identified Through [18F]SynVesT‐1 PET Imaging
Authors: Li Jian , Chen Daji , Tang Yongxiang , Chen Zhao , Zhou Ming , Wan Linlin , Xiao Ling , Fu You , He Zhiyou , Tang Zhichao , Hu Zhengqun , Yuan Xinrong , Yang Jinhui , Zhu Sudan , Guo Xuan , Ouyang Riwei , Qiu Rong , Tang Beisha , Guo Jifeng , Jiang Hong , Hu Shuo
Published: January 2025

Objective

The objective of this study was to delineate synaptic density alterations in multiple system atrophy (MSA) and explore its potential role as a biomarker for MSA diagnosis and disease severity monitoring using [18F]SynVesT‐1 positron emission tomography / computed tomography (PET CT).

Methods

In this prospective study, 60 patients with MSA (30 patients with MSA‐parkinsonian [MSA‐P] subtype and 30 patients with MSA‐cerebellar [MSA‐C] subtype), 30 patients with Parkinson's disease (PD), and 30 age‐matched healthy controls (HCs) underwent [18F]SynVesT‐1 PET/CT for synaptic density assessment. Visual, voxel, and volumetric region of interest (VOI) analyses were used to elucidate synaptic density patterns in the MSA brain and establish diagnostic criteria. The diagnostic performances of both visual and VOI‐based diagnostics were evaluated using receiver operating characteristic (ROC) analysis. Spearman correlation analyses were conducted to investigate the relationship between brain synaptic density and disease severity

Results

Patients with MSA displayed extensive reductions in synaptic density throughout the brain, notably affecting both primary VOIs (the cerebellum and putamen) and secondary VOIs including the medulla oblongata, ventral tegmental area, and pons. Notably, patients with MSA‐C exhibited a remarkable decrease in cerebellar synaptic density, whereas patients with MSA‐P demonstrated significant synaptic loss within the posterior putamen. Compared with patients with PD, the patients with MSA show a more pronounced reduction in synaptic density in infratentorial brain regions. VOI‐based diagnosis significantly outperformed visual analysis in diagnosing and differentiating MSA and its subtypes. Synaptic density in primary and multiple secondary VOIs correlated significantly with motor scales in patients with MSA.

Interpretation

Our study identified widespread synaptic density reductions in MSA, particularly in the basal ganglia and infratentorial region, suggesting [18F]SynVesT‐1 PET as a potential biomarker for diagnosing and evaluating the disease, and guiding synaptic restoration trials. ANN NEUROL 2025
Synthesis and Application of a Temperature Sensitive Poly(Acrylamide‐Co‐N‐Isopropylacrylamide‐Co‐Sodium P‐Styrene Sulfonate) as a New Water‐Based Drilling Fluid Plugging Agent
Authors: Yan Yancheng , Xue Zeyu , Wu Lianci , Luo Yumei , Bai Xiaodong
Published: January 2025

In the process of oil and gas production, the failure of drilling fluid caused it to invade the formation, leading to wellbore instability. N‐isopropylacrylamide (NIPAM), acrylamide (AM), and sodium p‐styrene sulfonate (SSS) were used as raw materials, and the P(NIPAM/AM/SSS) (abbreviated as NAS) temperature‐sensitive plugging agent was synthesized by inverse emulsion polymerization. The optimum synthesis conditions were obtained using a redox initiation system. Infrared measurements and UV–visible analysis showed that the target product was successfully prepared, and NAS exhibited a lower critical solution temperature (LCST) of 55°C, with sensitive temperature‐responsive behavior. Rheological and filtration tests, along with high‐temperature and high‐pressure (HTHP) sand tray tests, demonstrated that the temperature‐sensitive plugging agent effectively plugged the formation. Particle size analysis and Zeta potential analysis indicated that the addition of the temperature‐sensitive plugging agent increased the electrostatic stability of bentonite‐based slurry and polymer. Contact angle measurements and micro‐morphology of the mud cake revealed that a hydrophilic‐hydrophobic transition occurred at high temperatures in NAS, forming a dense hydrophobic film on the surface of the mud cake. This film effectively sealed cracks and micropores, reduced the invasion of free water, and improved wellbore stability.
Preparation and Characterization of a High Compressive Strength Polyamide 12T Microcellular Composite Foam Loaded With Short‐Chain Carbon Fiber and In Situ Generated Polytetrafluoroethylene Nanofiber
Authors: Liu Chao , Sun Yibo , Li Zhuolun , Chen Shihong , Wang Xiangdong
Published: January 2025

A high compressive strength composite microcellular foam using chain extended polyamide 12T (CEPT12T) as matrix with polyteterafluoroethylene (PTFE) and short‐cut carbon fiber as reinforcing materials was prepared by melt‐blending process using supercritical carbon dioxide as a foaming agent. The effects of different SCF contents on the rheological properties, crystallization behavior, cell structure, and compressive properties of the foam were systematically investigated. Thermal and rheological analysis results revealed that the incorporation of SCF slightly reduced the crystallinity of the material (from 40.14 to 37.58 J/g) while significantly enhancing its melt strength. Foaming results indicated that, with an SCF content of 6 phr, the average cell diameter decreased to 18 μm, exhibiting a uniform cell distribution, high cell density, and a closed‐cell structure. Compression tests revealed that, at a foaming ratio of 20, the foam with 6 phr SCF content exhibited a compressive strength of 0.37 MPa at 5% strain, which was a 90% increase compared to the unreinforced material. This high‐performance PA12T microcellular foam demonstrates a substantial potential for various applications, particularly in lightweight, insulation, and high‐strength applications, offering significant engineering value.
Lagrange‐dual‐based fully distributed economic dispatch in smart grids with transmission line losses
Authors: Lin Luxin , Chen Zhiyi , Wang Xiangyu , Li Shihua , Yu Xinghuo
Published: January 2025

Economic dispatch constitutes an important element within the hierarchical control framework of smart grids. Its effective implementation is imperative for cost reduction in generation, enhancement of operational efficiency, and power systems stability. This paper tackles the distributed economic dispatch problem in smart grids with transmission line losses. First, the economic dispatch problem is transformed into its Lagrange dual problem using convex optimization theory, accompanied by a description of the strategy for addressing inequality constraints. Then, a fully distributed optimization algorithm is developed under free initial state through the fusion of nonsmooth analysis and the primal–dual method. Furthermore, based on this algorithm, a modified algorithm with lower communication overhead is presented. Finally, software simulations and hardware‐in‐the‐loop tests are performed to verify the developed scheme.
Optimal tracking performance of communication constrained systems with fading channel and quantization constraint
Authors: Jiang Mengxi , Zhan Xisheng , Wu Jie , Yan Huaicheng
Published: January 2025

This paper studies the optimal tracking performance (OTP) of multiple‐input multiple‐output (MIMO) discrete communication constrained systems (CCSs) with fading channel and quantization constraints. An equivalent average channel is used to replace the fading channel with colored noise, and the gain of the output ports of the two channels is consistent in the first and second moments. Combined with spectral decomposition, co‐prime decomposition, partial fractional decomposition and other methods, the quantitative explicit expression of OTP is eventually derived. The result shows that the OTP is related to nonminimum phase (NMP) zeros and unstable poles and their directions of controlled plant, and is also affected by quantization error and colored noise. At last, a numerical example is utilized to verify the theory.
Superhabitable Planets Around Mid‐Type K Dwarf Stars Enhance Simulated JWST Observability and Surface Habitability
Authors: Vilović Iva , Goyal Jayesh , Heller René , von Schauenburg Fanny Marie
Published: January 2025

In our search for life beyond the Solar System, certain planetary bodies may be more conducive to life than Earth. However, the observability of these “superhabitable” (SH) planets in the habitable zones around K dwarf stars has not been fully modeled. This study addresses this gap by modeling the atmospheres of SH exoplanets. We employed the 1D model Atmos to define the SH parameter space, POSEIDON to calculate synthetic transmission spectra, and PandExo to simulate JWST observations. Our results indicate that planets orbiting mid‐type K dwarfs, receiving 80% of Earth's solar flux, are optimal for life. These planets sustain temperate surfaces with moderate CO2 levels, unlike those receiving 60% flux, where necessarily higher CO2 levels could hinder biosphere development. Moreover, they are easier to observe, requiring significantly fewer transits for biosignature detection compared with Earth‐like planets around Sun‐like stars. For instance, detecting biosignature pairs like oxygen and methane from 30 pc would require 150 transits (43 years) for a SH planet, versus over 1700 transits (~1700 years) for Earth‐like planets. While such observation times lie outside of JWST mission timescales, our study underscores the necessity of next‐generation telescopes and provides valuable targets for future observations with, for example, the ELT.
From tobacco to biochar: a review of production processes, properties, and applications
Authors: Ramontja James , Iwuozor Kingsley O. , Emenike Ebuka Chizitere , Okorie Chika J. , Saka Harvis Bamidele , Ezzat Abdelrahman O. , Adeleke Joy A. , Saliu Oluwaseyi D. , Adeniyi Adewale George
Published: January 2025

Tobacco waste presents notable environmental challenges, such as soil and water contamination from nicotine and other harmful chemicals, compounded by inefficiencies in conventional waste management. Converting tobacco waste into biochar offers a promising solution to address these issues. This study reviews the production, properties, and applications of biochar derived from tobacco, using feedstocks such as stems, seeds, leaves, and tobacco fines. It has been observed that tobacco stems are the most commonly used precursor and pyrolysis is the most frequently employed thermochemical conversion process, with biochar yields ranging from 5% to 85%, depending on operational variables. Tobacco‐derived biochar exhibits surface areas typically between 2 and 50 m2/g, fixed carbon content of 4 to 63 wt%, and ash content ranging from 12% to 51%. Tobacco‐derived biochar has been applied in agriculture, water treatment, composting, and energy production, demonstrating its efficiency. It also plays an important role in soil pollution remediation. Despite existing research on tobacco‐based biochar, gaps remain in areas such as the gasification and torrefaction of tobacco biomass and the use of other tobacco‐related wastes like leftover cigarettes and fines. The findings of this study depict the dual benefits of utilizing tobacco waste for biochar production – addressing waste disposal challenges while creating a valuable material with multiple environmental and economic advantages.
Transition Metal Molybdates Emerging Materials for High‐Performance Supercapacitors: A Machine Learning Analysis
Authors: Sawant Digambar S. , Kulkarni Shrinivas B. , Dubal Deepak P. , Lohar Gaurav M.
Published: January 2025

Transition metal molybdates (AMoO4 where A = Ni, Co, Mn, Fe, and Zn) have attracted much attention as promising electrode materials for energy storage devices due to their multi‐electron redox capability, higher electrical conductivity, good chemical and thermal stability, and stable crystal structure to get superior electrochemical performance. Transition metal molybdates and their graphene‐based composites possess multidimensional morphology for supercapacitors. The morphology‐dependent supercapacitor behavior has been reviewed in the present article. The formation mechanism of AMoO4 nanostructures in the form of 1D, 2D, and 3D has been identified and respective supercapacitor behavior is outlined. The density functional theory based on the calculated electronic properties of AMoO4 has been discussed. Additionally, the application of machine learning techniques in predicting and analyzing the relationships of AMoO4 has been discussed for the first time. By leveraging ML algorithms, we identify key parameters influencing their energy storage capabilities, providing insights into the rational design of molybdate‐based composites. Integrating experimental results with ML‐driven optimization offers a novel pathway for accelerating the development of next‐generation energy storage devices. In conclusion, future perspectives and challenges have been discussed.
The Association Between Neutrophil‐Percentage‐to‐Albumin Ratio (NPAR) and Mortality Among Individuals With Cancer: Insights From National Health and Nutrition Examination Survey
Authors: Li Xinyang , Wu Meng , Chen Minxin , Liu Rufei , Tao Qingxu , Hu Yun , Yu Jinming , Chen Dawei
Published: January 2025

Background

Neutrophils interact with tumor cells, potentially exacerbating cancer progression. Additionally, decreased albumin levels are a marker of poor cancer prognosis. The neutrophil‐percentage‐to‐albumin ratio (NPAR) has been used for prognostic assessment in non‐cancerous diseases, but its relationship with mortality risk in cancer patients has not been explored. Therefore, we utilized data from the National Health and Nutrition Examination Survey (NHANES) to investigate the correlation between NPAR and the risks of all‐cause mortality and cancer‐related mortality among cancer patients.

Methods

This study leveraged comprehensive NHANES data spanning 2005–2016. We analyzed the relationship between NPAR and the risks of cancer incidence, all‐cause mortality, and cancer‐related mortality using weighted Logistic and Cox regression models, as well as trend tests. Restricted cubic spline analysis was employed to investigate NPAR's nonlinear relationship with mortality risk. Furthermore, Kaplan–Meier survival analysis was utilized to assess patient prognoses across varying NPAR levels.

Results

Elevated NPAR was associated with an increased risk of all‐cause mortality and cancer‐related mortality in cancer patients (p < 0.05), with higher NPAR values correlating with greater risk (p‐trend < 0.05). However, no significant association between NPAR and cancer incidence was observed (p > 0.05). Our analysis further identified a non‐linear relationship between NPAR and all‐cause mortality risk (p‐nonlinear < 0.05), while no non‐linear relationship was found with cancer‐related mortality risk. The relationship is characterized by an optimal NPAR value, correlating with the lowest hazard ratio (HR). Deviations from this optimal NPAR result in increased all‐cause mortality risk (p < 0.05). Kaplan–Meier analysis indicated superior survival rates in patients with lower NPAR values compared to those with higher NPAR values (p < 0.05).

Conclusions

According to our study, higher NPAR was associated with an increased risk of all‐cause mortality and cancer‐related mortality in cancer patients.
4‐O‐Methylglucaric Acid Production from Xylan with Uronic Acid Oxidase and Comparison to Glucaric Acid from Glucose
Authors: Marrs Kevin , Vuong Thu V. , Master Emma R.
Published: January 2025

This study describes an enzymatic pathway to produce high purity 4‐O‐methylglucaric acid from xylan, an underutilized fraction of lignocellulosic biomass. Beechwood xylan was enzymatically hydrolysed using a commercial xylanase and an α‐glucuronidase from Amphibacillus xylanus to form 4‐O‐methylglucuronic acid, which was then purified by anion exchange chromatography and subsequently oxidized to 4‐O‐methylglucaric acid using a recombinantly produced uronic acid oxidase from Citrus sinensis. Enzymatic oxidation with uronic acid oxidase afforded 95 % yield in 72 hours which is considerably higher than yields previously achieved using a glucooligosaccharide oxidase from Sarocladium strictum. 4‐O‐methylglucaric acid was isolated by precipitation and purified by recrystallization. Characterization by liquid chromatography mass spectrometry and nuclear magnetic resonance spectroscopy confirmed product identity and high purity (97.8 % w/w). 4‐O‐methylglucaric acid's performance as a detergent builder was compared to commercial glucaric acid. At 10 : 1 molar ratios of detergent builder to calcium, 4‐O‐methylglucaric acid provided similar calcium sequestration performance to glucaric acid (less than 5 % difference) at pH 7 and pH 10 in the presence of surfactants, including sodium dodecylbenzene sulfonate. Given their similar calcium sequestration performance, 4‐O‐methylglucaric acid could effectively substitute for glucaric acid in detergent formulations.
Midterm Outcomes of Endovascular Pulmonary Artery Debanding in Children
Authors: Haddad Raymond N. , Sleiman Nelly , El Rassi Issam , Saliba Zakhia
Published: January 2025

Background

Pulmonary artery banding (PAB) palliates pulmonary over‐circulation, while endovascular debanding (ED) offers a less invasive alternative to repeat surgery.

Objectives

To evaluate our experience with ED.

Aims

Retrospective review of single‐center data (2015–2023) on children with single, multiple, or “Swiss‐cheese” muscular ventricular septal defects (MVSDs) undergoing ED.

Results

Ten patients (50% male) underwent ED at a median age of 5 years (IQR, 1.8–6.8) and weight of 15 kg (IQR, 10.6–19.7). Four patients had single MVSD, six had multiple MVSDs. Debanding occurred at a median of 52.8 months (IQR, 18.4–76.6) post‐PAB, utilizing six non‐compliant Numed Z‐MED and four semi‐compliant Balt Cristal high‐pressure balloons. Median pulmonary valve annulus (PVA) diameters were 15.5 mm (IQR, 12.5–16.8) angiographically. Median balloon‐to‐PVA diameter ratio was 1 (IQR, 1–1), and median balloon‐to‐band diameter ratio was 2 (IQR, 1.8–2). Median trans‐PAB gradient decreased from 100 mmHg (IQR, 86–108) to 40 mmHg (IQR, 26–46) (p < 0.01) and oxygen saturation improved from a median of 92% (IQR, 86%–97%) to 98% (IQR, 96%–98%) (p < 0.05). There were no procedural complications. Four patients underwent MVSD device closure a median of 7 months (IQR, 3–15) before ED, while seven had concomitant closures, including two with prior closures. Over a median follow‐up of 91.7 months (IQR, 71.8–130.7), two patients required redo ED at 23 and 36 months, one with a contained vessel tear. Last recorded maximal Doppler gradient was 27 mmHg (IQR, 9–39).

Conclusions

Total ED is safe with satisfactory midterm outcomes, though repeat dilations may be necessary during follow‐up.
Comparative Pharmacokinetics and Bioequivalence of 2 Formulations of Bosentan Dispersible Tablets in Healthy Chinese Volunteers Under Fasting and Fed Conditions
Authors: Huang Zhaoming , Yu Panpan , Hu Jiawei , Zhang Wanyong
Published: January 2025

Bosentan is a dual endothelin receptor antagonist widely used in the treatment of pulmonary artery hypertension. However, there are few reports on the pharmacokinetics (PK) and bioequivalence of bosentan dispersible tablets (32 mg) in the Chinese population. This study aimed to evaluate the PK characteristics and bioequivalence of the test and reference formulations of bosentan dispersible tablets in healthy Chinese volunteers under fasting and fed conditions. A randomized, single‐dose, 2‐sequence, 2‐period crossover study (fasting) and a 4‐period replicate crossover study (fed) were conducted with 48 and 30 healthy volunteers, respectively. The bosentan plasma concentrations were measured by a validated ultra‐performance liquid chromatography coupled with a tandem mass spectrometry method, and PK parameters were analyzed using noncompartmental methods. The bioequivalence statistical analysis showed that 90% confidence intervals for the geometric mean ratios of peak plasma concentration, area under the concentration–time curve (AUC) from time zero to the last measurable concentration, and AUC from time zero to infinity for the test and reference formulations were within the bioequivalence range of 80%‐125% under both fasting and fed conditions. After the administration of bosentan dispersible tablets under fed conditions, the systemic exposure (based on AUC from time zero to infinity) was increased by approximately 15%‐20%. These findings confirm the bioequivalence of the 2 formulations, and both formulations were well tolerated, with no safety‐related adverse events reported. Given the wide therapeutic dose range of bosentan dispersible tablets for the treatment of pulmonary artery hypertension in children, the impact of food on its PK is not considered clinically significant.
Current Practices and Perspectives of Artificial Intelligence in the Clinical Management of Eating Disorders: Insights From Clinicians and Community Participants
Authors: Linardon Jake , Liu Claudia , Messer Mariel , McClure Zoe , Anderson Cleo , Jarman Hannah K.
Published: January 2025

Objective

Artificial intelligence (AI) could revolutionize the delivery of mental health care, helping to streamline clinician workflows and assist with diagnostic and treatment decisions. Yet, before AI can be integrated into practice, it is necessary to understand perspectives of these tools to inform facilitators and barriers to their uptake. We gathered data on clinician and community participant perspectives of incorporating AI in the clinical management of eating disorders.

Method

A survey was distributed internationally to clinicians (n = 116) with experience in eating disorder treatment (psychologists, psychiatrists, etc.) and community participants (n = 155) who reported occurrence of eating disorder behaviors.

Results

59% of clinicians reported use of AI systems (most commonly ChatGPT) for professional reasons, compared to 18% of community participants using them for help‐related purposes. While more than half of clinicians (58%) and community participants (53%) were open for AI to help support them, fewer were enthusiastic about their integration (40% and 27%, respectively) and believed that they would significantly improve client outcomes (28% and 13%, respectively). Nine in 10 agreed that AI may be improperly used if individuals are not adequately trained, and could pose new data privacy and security concerns. Most agreed that AI will be convenient, beneficial for administrative tasks, and an avenue for continuous support, but will never outperform human clinicians on relational skills.

Conclusion

While many clinicians and community participants are open to the use of AI in eating disorder treatment and recognize its possible wide‐ranging benefits, most remain cautious and uncertain about its implementation.
The role of dopants in mitigating the chemo‐mechanical degradation of Ni‐rich cathode: A critical review
Authors: Rambukwella Imesha , Ponnuru Hanisha , Yan Cheng
Published: January 2025

Ni‐rich cathodes are more promising candidates to the increasing demand for high capacity and the ability to operate at high voltages. However, the high Ni content creates a trade‐off between energy density and cycling stability, mainly caused by the chemo‐mechanical degradation. Oxygen evolution, cation mixing, rock salt formation, phase transition, and crack formation contribute to the degradation process. To overcome this problem, strategies such as doping, surface coating, and core‐shell structures have been employed. The advantage of doping is to engineer the cathode surface, structure, and particle morphology simultaneously. This review aims to summarize recent advances in understanding chemo‐mechanical degradation mechanism and the role of different dopants in enhancing the thermal stability and overall electrochemical performance. The pinning and pillaring effects of dopants on suppressing oxygen evolution, cation mixing, and phase transition are introduced. It is found that the higher ionic radii enable dopants to reside on cathode particles, preserving the particle surface and refining particle morphology to suppress crack formation. Finally, the effect of doping on Li ion diffusion, rate capability, and long‐term stability are discussed.
Guideline‐directed medical therapy rates in heart failure patients with reduced ejection fraction in a diverse cohort
Authors: Berry Natalia C. , Sheu Yi‐Shin , Chesbrough Karen , Bishop R. Clayton , Vupputuri Suma
Published: January 2025

Aims

Guideline‐directed medical therapy (GDMT) is recommended for all patients with heart failure with reduced ejection fraction (HFrEF). Despite this, little data exist describing GDMT use in diverse, real‐world populations including the use of vasodilators, prescribed primarily to Black populations. We sought, among a diverse population of HFrEF patients, to determine (1) GDMT use rates and target dosing by medication class and (2) predictors of GDMT use and target dosing by medication class.

Methods

We utilized electronic health records (EHRs) from Kaiser Permanente (KP) Mid‐Atlantic States, a large integrated health system. Included patients had heart failure and left ventricular ejection fraction (EF) of ≤40% between 2015 and 2021. GDMT was defined by five medication classes—angiotensin‐converting enzyme (ACE) inhibitors (ACEis)/angiotensin receptor blockers (ARBs)/angiotensin receptor–neprilysin inhibitors (ARNis), beta‐blockers (BBs), mineralocorticoid receptor antagonists (MRAs), sodium–glucose cotransporter 2 inhibitors (SGLT2is) and vasodilators (Black patients only). Proportions of patients on GDMT and target dose rates were examined. Logistic regression determined, within each class, predictors of medication use and being at ≥80% of the target dose.

Results

A total of 3154 patients were included. Among the 93.8% on some form of GDMT, 82.8%, 81.4%, 23.5%, 3.6% and 13.4% were on ACEis/ARBs/ARNis, BBs, MRAs, SGLT2is and vasodilators (Black patients only), respectively. Among treated patients, 45.8%, 21.4%, 77.6%, 100% and 14.7% were treated at ≥80% of the target dose for ACEis/ARBs/ARNis, BBs, MRAs, SGLT2is and vasodilators, respectively. Overall, increasing age, higher EF, atrial fibrillation/flutter, chronic obstructive pulmonary disease (COPD), prior stroke and dementia were associated with decreased odds of GDMT use. Conversely, higher body mass index (BMI), Black race, higher glomerular filtration rate (GFR), recent echo and cardiac defibrillator were associated with increased odds of GDMT use. Among treated, higher BMI, higher systolic blood pressure, haemoglobin A1C ≥ 6.5% and cardiac defibrillator were associated with higher odds of being at ≥80% of the target dose.

Conclusions

Our study using real‐world data from a diverse health system demonstrated gaps in GDMT use among patients with HFrEF, specifically older patients with more comorbidities.
Relaxin mimetic in pulmonary hypertension associated with left heart disease: Design and rationale of Re‐PHIRE
Authors: Ufnal Marcin , Connolly Kathleen , Millegard Marcus , Surkova Elena , Guazzi Marco , Bonderman Diana , Ezekowitz Justin , Gustafsson Finn , Ciurzyński Michał , Vilella Raquel López , Ahmad Tariq , Gardner Roy , Jansa Pavel , van Wijk Sandra , Kinugawa Koichiro , Björklund Erik , Jing Zhi‐Cheng , Rosenkranz Stephan
Published: January 2025

Aims

Despite receiving guideline‐directed medical heart failure (HF) therapy, patients with pulmonary hypertension associated with left heart disease (PH‐LHD) experience higher mortality and hospitalization rates than the general HF population. AZD3427 is a functionally selective, long‐acting mimetic of relaxin, a hormone that has the potential to induce vasodilation and prevent fibrosis. In a phase 1b study conducted in patients with HF, AZD3427 demonstrated a favourable safety and pharmacokinetic profile. To address the unmet medical need in patients with PH‐LHD in the context of HF, AZD3427 is currently under development as a potential treatment option.

Methods and results

The Re‐PHIRE study is a phase 2b, randomized, double‐blind, placebo‐controlled, multicentre, dose‐ranging study to evaluate the effect of AZD3427 on a broad range of PH‐LHD phenotypes. In total, 220 patients will be randomized to four treatment groups to receive a subcutaneous injection of AZD3427 or placebo every 2 weeks for 24 weeks. The primary endpoint of the study is the change in pulmonary vascular resistance in patients treated with AZD3427 versus placebo after 24 weeks of treatment. Key secondary endpoints include changes in mean pulmonary arterial pressure, pulmonary artery wedge pressure, systemic vascular resistance, 6‐min walking distance, N‐terminal pro B‐type natriuretic peptide levels, echocardiographic parameters, and health‐related quality of life (assessed by the Kansas City Cardiomyopathy Questionnaire).

Conclusions

Re‐PHIRE is the first study of a relaxin mimetic in patients with PH‐LHD. The insights gained from the Re‐PHIRE study are expected to inform the further development of AZD3427 in the PH‐LHD population, including identifying the most suitable pulmonary hypertension and HF phenotypes for treatment.
Research on the Development of Rural Human Settlement Environment in the Upper Reaches of the Lancang River Based on Ecological Carrying Capacity Constraints
Authors: Zhao Xiaoliang , Li Junhuan
Published: January 2025

The development of rural human settlement environments in ecologically sensitive areas, particularly the upper reaches of the Lancang River within the Sanjiangyuan region, has garnered significant attention due to its paramount importance in balancing economic growth and ecological conservation. However, the comprehension of sustainable development strategies within the confines of ecological carrying capacity in these regions remains inadequate. The present study aims to investigate the rural human settlement environment in Nangqen County, situated within the Sanjiangyuan region, and to explore adaptive construction strategies that facilitate harmonious coexistence between human settlements and the natural environment. Utilizing an ecological footprint model integrated with the ArcGIS platform, this research evaluates the ecological carrying capacity and its variations from 2000 to 2020. The results indicate that, despite the land ecological environment being generally safe, the total ecological footprint has surpassed a twofold increase, primarily driven by the expansion of animal husbandry activities. Furthermore, the study conducts a suitability assessment of rural settlements in Nangqen County, pinpointing areas that are most conducive to sustainable development and those that necessitate protection.
Clinical Assessment of Drug Transporter Inhibition Using Biomarkers: Review of the Literature (2015–2024)
Authors: Rodrigues David , Wezalis Stephanie
Published: January 2025

As part of a narrative review of various publications describing the clinical use of urine‐ and plasma‐based drug transporter biomarkers, it was determined that the utilization of coproporphyrin I, a hepatic organic anion transporting polypeptide (OATP) 1B1 and OATP1B3 biomarker, has been reported for 28 different drug–drug interaction (DDI) perpetrator drugs. Similarly, biomarkers for liver organic cation transporter 1 (isobutyryl‐l‐carnitine, N = 7 inhibitors), renal organic cation transporter 2 and multidrug and toxin extrusion proteins (N1‐methylnicotinamide, N = 13 inhibitors), renal organic anion transporter (OAT) 1 and 3 (pyridoxic acid, N = 7 inhibitors), and breast cancer resistance protein (riboflavin, N = 3 inhibitors) have also been described. Increased use of biomarkers has also been accompanied by modeling efforts to enable DDI predictions and development of multiplexed methods to facilitate their bioanalysis. Overall, there is consensus that exploratory biomarkers such as coproporphyrin I can be integrated into decision trees encompassing in vitro transporter inhibition data, DDI risk assessments, and follow‐up Phase 1 studies. Therefore, sponsors can leverage biomarkers to evaluate dose‐dependent inhibition of selected transporters, use them jointly with drug probes to deconvolute DDI mechanisms, and integrate in vitro data packages to establish calibrated (biomarker informed) DDI risk assessment cutoffs. Although transporter biomarker science has progressed, reflected by its inclusion in the recently issued International Council for Harmonisation DDI guidance document (M12), some biomarkers still require further validation. There is also a need for biomarkers that can differentiate specific transporters (e.g., OATP1B3 vs OATP1B1 and OAT1 vs OAT3).
Effectiveness of E‐Learning Method on Exodontia for Dental Students: A Theoretical Domain Framework Study
Authors: Abed Hassan , Demyati Abrar
Published: January 2025

Aims

The study aimed to assess the impact of e‐learning tools using teaching videos on dental extraction for dental students.

Material and Methods

Teaching videos on dental extraction were sent to each participating dental students. The theoretical domain framework (TDF) was used to assess dental students’ self‐reported behavior on dental extraction.

Results

The response rate was 77%. Male students found teaching videos support their practice significantly in dental extraction by their skills, beliefs about capabilities, optimism, environment context and resources, social influences, and emotion (p‐value <0.001 and <0.05). T‐Test showed that male students reported significant improvement in the overall TDF compared to female students (male = 130.26 ± 21.4 vs. female = 115.09 ± 26.8, p‐value = 0.007). Results showed that there are positive correlations between skills (r = 0.419), beliefs about capabilities (r = 0.511), optimism (r = 0.414), emotion (r = 0.411), beliefs about consequences (r = 0.314), reinforcement (r = 0.396), intentions (r = 0.322), goals (r = 0.329), memory, attention and decision process (r = 0.356), environment context and resources (r = 0.318), and social influences (r = 0.367) with students’ satisfaction rate when practicing dental extraction after watching the teaching videos (p‐value <0.001 and <0.05). The one‐way analysis of variance (ANOVA) test showed that students at higher levels have higher scores on the theoretical framework's domains as measured by the means on 10 domains out of 13 (p‐value < 0.001).

Conclusions

Incorporating video‐based teaching materials into the dental curriculum can be valuable in improving students' skills and proficiency in performing dental extractions.
Edaravone Mitigates Hippocampal Neuronal Death and Cognitive Dysfunction by Upregulating BDNF Expression in Neonatal Hypoxic–Ischemic Rats
Authors: Zhang Rui , Yang Yongkai , Lin Yijun
Published: January 2025

Neonatal hypoxic–ischemic encephalopathy (HIE) is a severe neurological injury during infancy, often resulting in long‐term cognitive deficits. This study aimed to investigate the neuroprotective effects of Edaravone (EDA), a free radical scavenger, and elucidate the potential role of brain‐derived neurotrophic factor (BDNF) in mediating these effects in neonatal HIE rats. Using the Rice‐Vannucci model, HIE was induced in neonatal rats, followed by immediate administration of EDA after the hypoxic–ischemic insult. To examine the role of BDNF, a separate group of rats received intrahippocampal injections of a lentiviral vector for BDNF knockdown prior to the induction of HIE and subsequent EDA treatment. Neuronal survival and apoptosis in the hippocampal region were assessed by immunofluorescence and TUNEL staining, respectively. BDNF expression levels in the hippocampus were analysed using enzyme‐linked immunosorbent assay (ELISA). Cognitive function was evaluated using the Morris water maze (MWM) and Y maze tests. Results demonstrated that EDA significantly reduced hippocampal neuronal apoptosis and death, increased neuronal survival, and enhanced BDNF expression compared to the control group. However, the therapeutic effects of EDA were mitigated in the BDNF knockdown group, indicating a crucial role of BDNF in mediating the neuroprotective effects of EDA. Behavioural testing confirmed that EDA treatment significantly improved spatial learning and memory abilities in HIE rats, but these improvements were not observed in rats with BDNF knockdown. In conclusion, our study suggests that EDA treatment mitigates hippocampal neuronal death and improves cognitive dysfunction in HIE rats primarily by upregulating BDNF expression. These findings provide experimental support for the potential application of EDA in the treatment of HIE and highlight the essential role of BDNF in neuroprotection and cognitive recovery post‐HIE.
Effect of Proteinuria Before Lenvatinib Administration on Treatment Response After Atezolizumab Bevacizumab Combination Therapy
Authors: Ochi Hironori , Kurosaki Masayuki , Tanaka Takaaki , Tamaki Nobuharu , Tsuchiya Kaoru , Yasui Yutaka , Marusawa Hiroyuki , Tada Toshifumi , Nakamura Shinichiro , Akahane Takehiro , Okamoto Eisuke , Kobashi Haruhiko , Arai Hirotaka , Nonogi Michiko , Izumi Namiki
Published: January 2025

Aim

We investigated the impact of proteinuria on the therapeutic effect before lenvatinib administration as second‐line treatment after atezolizumab‐bevacizumab.

Methods

We examined 64 patients who were administered lenvatinib as second‐line treatment after discontinuation of atezolizumab and bevacizumab. Proteinuria assessed before lenvatinib administration was considered severe if the qualitative value test (QV) was 3+ or the urine protein/creatinine ratio (UPCR) was ≥ 2.0 (group A, n = 13) and non‐severe if the UPCR was < 2.0 or the QV was ≤ 2+ (group B, n = 51).

Results

In the entire cohort, the modified albumin–bilirubin grades were grades 1, 2a, 2b, and 3 in 12, 21, 26, and 5 patients, respectively. Regarding the Barcelona Clinic of Liver Cancer stage, 2, 22, and 40 patients had stages A, B, and C, respectively. The objective response rate (ORR) was 14.0% and the disease control rate (DCR) was 59.3%. The median survival time and progression free survival after administration of lenvatinib was 14.8 (95% confidence interval [CI], 11.3–18.4) and 5.5 (95% CI, 3.6–7.5) months, respectively. The ORR and DCR were 0% and 38.4% for group A (n = 13) and 17.6% and 64.7% for group B (n = 51), respectively. The median time to treatment failure was 2.2 months in group A and 4.2 months in group B (p = 0.120).

Conclusions

Severe proteinuria before lenvatinib as a second‐line therapy after atezolizumab‐bevacizumab treatment may affect the duration of lenvatinib administration and treatment efficacy.
Increased Risk of Femoral Neck Stress Fractures in Patients With Cam or Pincer Morphology
Authors: Rynecki Nicole D. , DeClouette Brittany , Gantz Owen B. , Berzolla Emily , Li Zachary , Garra Sharif , Akpinar Berckan D. , Youm Thomas
Published: January 2025

Previous studies suggest a relationship between femoroacetabular impingement (FAI) and femoral neck stress fractures (FNSF), due to pathologic biomechanics in the setting of femoral head abutment (cam morphology) and/or acetabular overcoverage (pincer morphology). The purpose of this study is to evaluate the association between cam or pincer morphology and FNSF, compared to a control group of patients without hip pain. A retrospective review of the electronic medical record at a single institution was queried for patients with FNSF over a 10‐year time period from January 2011–2021. These patients were compared to a control group with diagnostic radiographs and a chief complaint that was not hip pain presenting to the institution's emergency department. Hip morphology was evaluated radiographically. A multivariate logistic regression was used to investigate an association between FNSF and cam or pincer morphology. Eighty‐three patients with FNSF and a mean age of 38.6 years were compared to 55 healthy controls with a mean age of 35.8 years. Patients in the FNSF group were more often female, white, and had lower BMI. These patients were also more likely to have associated cam morphology (p = 0.010). Binary logistic regression demonstrated a statistically significant independent association between both cam (OR 5.2, p = 0.01) and pincer (OR 4.6, p = 0.022) morphology with FNSF when controlling for demographic variables. Black race and higher BMI were protective factors for FNSF (OR 0.09, OR 0.84, p < 0.01). In summary, radiographic cam morphology, superolateral acetabular overcoverage, female sex, and lower BMI are risk factors for sustaining FNSF, while the black race was found to be protective.
Helicobacter pylori infection is associated with significant elevations to fecal calprotectin, systemic inflammatory markers
Authors: Villalba‐Davila Priscila , Aronson Stephanie , Lat Jessica , Charles Cassandra , Schroeder Bryce , Pittman Meredith , Tang Vivian , Wallach Thomas
Published: January 2025

Objectives

Fecal calprotectin (FC) is a marker commonly used in the diagnosis and follow‐up of inflammatory bowel diseases (IBD). However, other gastrointestinal conditions, like H. pylori (HP) infection, can result in increased neutrophil activity as well. We set out to assess the impact of HP infection on FC and downstream gastrointestinal care via a retrospective study.

Methods

In this study, we collected data from two institutions in Brooklyn, NY, in a high immigrant density community. We reviewed data from patients who underwent esophagogastroduodenoscopy (EGD) between January 2017 and October 2022. Patients aged 6–18 years old with an FC level 6 months prior to EGD and HP testing were included.

Results

Of 129 patients, 37 (28.7%) tested positive for HP infection. The mean FC level was significantly elevated in HP‐positive patients (241.2, confidence interval [CI]: 161.0–321.3) as compared with HP‐negative patients (88.1, CI: 59.1–117.0) (p < 0.001). Patients with higher FC levels were also more likely to undergo colonoscopies (p = 0.003).

Discussion

HP infection is associated with increased calprotectin, and calprotectin increases in HP patients are associated with an increased risk of colonoscopy.
Investigation of protein structure and quality of Acipenser sinensis frozen by liquid nitrogen
Authors: Tan Ling , Chen Jiwang , Li Zihan , Liao E , Xiong Youling , Lu Hongyan
Published: January 2025

Background

The quality of Acipenser sinensis deteriorates significantly during frozen storage due to its high water, protein, and unsaturated fatty acid content. Conventional freezing methods are insufficient to preserve it effectively. This study investigated the effects of liquid nitrogen freezing (LNF) on the quality and myofibrillar protein (MP) characteristics of A. sinensis during frozen storage.

Results

Freezing A. sinensis with LNF resulted in faster freezing, lower free water content, smaller ice crystals, and less structural damage to MPs than refrigerator freezing (RF). It also resulted in higher shear force, Ca2+‐ATPase activity, and total sulfhydryl content, as well as lower total volatile basic nitrogen (TVBN) values, thawing loss rate, and disulfide bond content, demonstrating that LNF can inhibit protein denaturation and delay the deterioration in the quality of A. sinensis during frozen storage. There were no significant differences between LNF‐80 and LNF‐110 in quality and myofibrillar protein characteristics of A. sinensis.

Conclusions

Liquid nitrogen freezing can maintain the quality of A. sinensis and reduce the degree of MP denaturation and oxidation during frozen storage. Freezing with LNF at −80 °C might be more appropriate for A. sinensis. The study has important implications for the application of cryogenic storage technology to aquatic products. © 2025 Society of Chemical Industry.
Effect of platelet‐rich plasma and platelet‐rich fibrin on healing of burn wound with dual‐species biofilm
Authors: Li Wen‐Dan , Lin Fang , Sun Yu , Zhu Zi‐Jing , Luo Mei‐Liang , Zeng Yi‐Qi , Lin Zhen , Zhou Mou
Published: January 2025

This study evaluated the impact of platelet‐rich plasma (PRP) and platelet‐rich fibrin (PRF) on burn wound with dual‐species biofilm. Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) were applied to infect the burn wound in rats to establish a dual‐species biofilm model. After infection, the wound was treated with ionized silver (AG), PRF, and PRP. Silver scanning electron microscopy (SEM) was used to assess adhesion after infection. PRF and PRP reduced wound size from day 8 after burn injuries, while AG significantly promoted burn wound healing at day 12. New collagen was formed in the shortest time in PRF and PRP groups compared to AG and control groups. PRF and PRP greatly lowered the bacterial numbers in wounds with S. aureus and P. aeruginosa biofilm, whereas AG showed weak bacteriostatic effects. AG, PRF, and PRP treatments significantly reduced inflammatory mediators and induced VEGFA. However, AG treatment increased TNF‐α. PRF and PRP accelerate wound healing in the presence of dual‐species biofilm infection and show strong antibacterial activity against S. aureus and P. aeruginosa, indicating that PRF and PRP could be potential therapies for burn wounds with dual‐species biofilm infection.
Synchronization‐Free Single‐Photon 3D Imaging
Authors: Wang Li , Yan Zeng‐Quan , Jiang Ze‐Kun , Zhang Zheng , Wang Xiao‐Wei , Zhou Wen‐Hao , Jin Xian‐Min
Published: January 2025

3D imaging using single‐photon time‐of‐flight (ToF) detection has emerged as a potential solution for sensing in challenging scenarios. However, most schemes require strict synchronization between the illuminating light transmitter and the detector, which greatly limits their practicality and flexibility. Here, a synchronization‐free single‐photon 3D imaging scheme that exploits only binary‐encoded illumination light and a photon time‐stamping high‐speed detection system are proposed. The correlation between the arrival times of photons detected by individual pixels is utilized to achieve clock synchronization, and further calculate the ToF differences of photons detected by different pixels to extract the depth information of the imaging target. This scheme can adapt to conditions with signals as weak as photons per pulse per pixel. This work provides a simple, flexible method for realizing 3D imaging in long‐range and high‐loss scenes, paving the way for future applications in large‐scale, high‐complexity real‐world scenarios.
Weyl‐Related Surface Circular Photogalvanic Effect in Nonsymmorphic‐Symmetry ZrGeTe4 Semiconductor
Authors: Bai Ruixue , Du Xiaoshan , Zhou Rui , Zhu Yaojie , Zhang Xilin , Liu Yulun , Yan Zuowei , Li Wei , Ma Hui , Jiang Chongyun
Published: January 2025

Weyl semiconductors, combining the high tunability features of semiconductors with the exotic topological properties of Weyl materials, are of great significance for fundamental physics studies and functional topological devices. Despite the potential theoretical implications, few Weyl semiconductors are experimentally discovered. Chirality is an extraordinary feature of Weyl nodes, which can give rise to helicity‐resolved photocurrents, known as the circular photogalvanic effect (CPGE). Here, this work discloses the surface CPGE in nonsymmorphic‐symmetry ZrGeTe4 semiconductors via a specific excitation and detection geometry, demonstrating that it originates from asymmetric helicity‐dependent optical transitions between two Kramers–Weyl nodes in the conduction and valence bands. Wavelength‐dependent experiments support the chirality‐related Weyl features of the CPGE in ZrGeTe4 semiconductors. It is experimentally confirmed that the Weyl‐related surface CPGE is an intrinsic phenomenon that can be flexibly tuned with an in‐plane electric field. The work provides a new platform for designing spintronic, optoelectronic, and quantum devices by integrating the advantages of topological materials with versatile semiconductors.