bluuebunny/crossref_metadata_2025_split huggingface dataset:
AERIFY-1/2: two phase 3, randomised, controlled trials of itepekimab in former smokers with moderate-to-severe COPD
Authors: Rabe Klaus F. , Martinez Fernando J. , Bhatt Surya P. , Kawayama Tomotaka , Cosio Borja G. , Mroz Robert M. , Boomsma Maarten M. , Goulaouic Helene , Nivens Michael C. , Djandji Michel , Soler Xavier , Liu Ying , Kosloski Matthew P. , Xu Christine R. , Amin Nikhil , Staudinger Heribert , Lederer David J. , Abdulai Raolat M. 
Published: May 2024

BackgroundAccumulating data implicate interleukin (IL)-33, a proinflammatory cytokine released locally upon epithelial cell damage, in the pathogenesis of COPD. In a phase 2 study, itepekimab, a human monoclonal antibody against IL-33, reduced exacerbations and improved lung function in a subgroup analysis of former smokers with COPD with an acceptable safety profile.MethodsThe study designs of AERIFY-1 and AERIFY-2 are described in this article.DiscussionThe primary objective of AERIFY-1/2 (NCT04701983/NCT04751487), two phase 3 randomised, double-blind, placebo-controlled trials, is to assess the efficacy and safety of itepekimabversusplacebo in a population of former smokers with moderate-to-severe COPD over up to 52 weeks. An additional secondary population of current smokers are being enrolled in AERIFY-2. These two studies will enrol patients (aged 40–85 years) with COPD and chronic bronchitis who had ≥2 moderate or ≥ 1 severe exacerbations within the previous year despite standard-of-care triple or double background therapy. All participants are required to have ≥10-pack-year smoking history, and ≥6 months since smoking cessation for former smokers. The primary end-point is the annualised rate of moderate or severe acute exacerbation of COPD. Secondary end-points include change from baseline in pre- and post-bronchodilator forced expiratory volume in 1 s, and annualised frequency of severe exacerbations. Symptomatic end-points include Evaluating Respiratory Symptoms in COPD and St. George's Respiratory Questionnaire, safety and anti-drug antibody responses.
RLS-0071, a novel anti-inflammatory agent, significantly reduced inflammatory biomarkers in a randomised human evaluation of mechanisms and safety study
Authors: Cunnion Kenji , Goss Jessica , Hair Pamela , Dell Linda , Roberson Destrey , Thienel Ulrich , Müller Meike , Carstensen-Aurèche Saskia , Badorrek Philipp , Holz Olaf , Hohlfeld Jens M. 
Published: May 2024

BackgroundThis study was a randomised, double-blind, placebo-controlled study intended to establish the translatability of the RLS-0071 mechanisms of action from animal disease models to humans by inhibiting neutrophil-mediated inflammation at the tissue level and major inflammatory biomarkers. We hypothesised that RLS-0071 inhibits a temporary neutrophil-mediated inflammation in the lungs induced by inhalation of low-dose lipopolysaccharide (LPS) in healthy participants.MethodsParticipants were randomised to one of three arms to receive inhaled LPS followed by three doses of either low-dose (10 mg·kg−1) or high-dose (120 mg·kg−1loading dose followed by two doses of 40 mg·kg−1) RLS-0071i.v.or placebo (saline) every 8 h. Biomarkers evaluating inflammatory responses, with absolute neutrophil counts in induced sputum as the primary end-point, were collected before and at 6 and 24 h after LPS challenge.ResultsActive treatment with RLS-0071 showed a similar safety profile to participants receiving placebo. RLS-0071 significantly decreased the numbers of neutrophils in sputum at 6 h post LPS by approximately half (p=0.04). Neutrophil effectors myeloperoxidase, neutrophil elastase and interleukin-1β in sputum were also significantly decreased at 6 h for RLS-0071 compared with placebo. Several biomarkers showed trends suggesting sustained decreases for RLS-0071versusplacebo at 24 h.ConclusionThis clinical trial demonstrated that RLS-0071 was safe and well tolerated and modulated neutrophil-mediated inflammation in humans after inhaled LPS challenge, consistent with results from prior animal model studies.
Pulmonary perfusion defects or residual vascular obstruction and persistent symptoms after pulmonary embolism: a systematic review and meta-analysis
Authors: Cimini Ludovica Anna , Luijten Dieuwke , Barco Stefano , Ghanima Waleed , Jervan Øyvind , Kahn Susan R. , Konstantinides Stavros , Lachant Daniel , Nakano Yoshihisa , Ninaber Maarten , van Es Josien , van Mens Thijs , Vonk Noordegraaf Anton , Becattini Cecilia , Klok Frederikus A. 
Published: May 2024

Introduction:Up to 50% of pulmonary embolism (PE) patients have perfusion defects or residual vascular obstruction during follow-up despite adequate anticoagulant treatment, and a similar percentage experience chronic functional limitations and/or dyspnoea post-PE. We aimed to evaluate the association between pulmonary perfusion defects or residual vascular obstruction and functional recovery after PE.Methods:We performed a systematic review and meta-analysis including studies assessing both the presence of perfusion defects or residual vascular obstruction and functional recovery (i.e.persistent symptoms, quality of life, exercise endurance). An odds ratio was pooled for perfusion defects or residual vascular obstruction and persistent symptoms using a random-effect model.Results:12 studies were included totalling 1888 PE patients; at a median of 6 months after PE (range 2–72 months), 34% had perfusion defects or residual vascular obstruction and 37% reported persistent symptoms. Among patients with perfusion defects or residual vascular obstruction, 48% (95% CI 37–60%, I2=82%) remained symptomatic during follow-up, compared to 34% (95% CI 20–51%, I2=96%) of patients without such defects. Presence of perfusion defects or residual vascular obstruction was associated with persistent symptoms (OR 2.15, 95% CI 1.66–2.78; I2=0%, τ=0). Notably, there was no association between these defects and quality of life or cardiopulmonary exercise test parameters.Conclusion:While the odds of having persistent symptoms was higher in patients with perfusion defects or residual vascular obstruction after acute PE, a significant proportion of these patients reported no limitations. A possible causality between perfusion defects or residual vascular obstruction and residual functional limitation therefore remains to be proven.
Effect of radius-dependent diffusion behavior of various gold nanoparticles on photothermal therapy
Authors: Kim Donghyuk , Kim Hyunjung 
Published: May 2024

AbstractAmong the various anti-cancer treatments, photothermal therapy (PTT) is gaining traction as it is a non-invasive treatment. PTT is a treatment technique involving the use of a laser to raise the temperature of the target tumor until it dies. In this study, the effects of PTT under various conditions of squamous cell carcinoma (SCC) occurring in the skin were numerically analyzed and optimized. Gold nanoparticles (AuNPs) with different radii were injected into the center of the SCC. Subsequently, the diffusion behavior of the AuNPs was analyzed to calculate the distribution area of the AuNPs that changed over time. Furthermore, at each elapsed time point after injection, the temperature distribution in the tissue was calculated, as treatment was performed using varying laser intensities. The diffusion coefficient of AuNPs was calculated using the Stokes–Einstein equation, and diffusion behavior of AuNPs in biological tissues was analyzed using the convection–diffusion equation. Additionally, temperature distribution was analyzed using the Pennes bioheat equation. The effect of PTT under each condition was quantitatively analyzed using apoptotic variables. As a result, As the radius of AuNPs increased, the optimal treatment start time was derived as 2 h, 8 h, 8 h, and 12 h, respectively, and the laser intensity at that time was derived as 0.44 W, 0.46 W, 0.42 W, and 0.42 W, respectively. The study findings will provide reference for the optimization of the efficacy of PTT.
Biclustering analysis on tree-shaped time-series single cell gene expression data of Caenorhabditis elegans
Authors: Guan Qi , Yan Xianzhong , Wu Yida , Zhou Da , Hu Jie 
Published: May 2024

Abstract
Background
In recent years, gene clustering analysis has become a widely used tool for studying gene functions, efficiently categorizing genes with similar expression patterns to aid in identifying gene functions. Caenorhabditis elegans is commonly used in embryonic research due to its consistent cell lineage from fertilized egg to adulthood. Biologists use 4D confocal imaging to observe gene expression dynamics at the single-cell level. However, on one hand, the observed tree-shaped time-series datasets have characteristics such as non-pairwise data points between different individuals. On the other hand, the influence of cell type heterogeneity should also be considered during clustering, aiming to obtain more biologically significant clustering results.

Results
A biclustering model is proposed for tree-shaped single-cell gene expression data of Caenorhabditis elegans. Detailedly, a tree-shaped piecewise polynomial function is first employed to fit non-pairwise gene expression time series data. Then, four factors are considered in the objective function, including Pearson correlation coefficients capturing gene correlations, p-values from the Kolmogorov-Smirnov test measuring the similarity between cells, as well as gene expression size and bicluster overlapping size. After that, Genetic Algorithm is utilized to optimize the function.

Conclusion
The results on the small-scale dataset analysis validate the feasibility and effectiveness of our model and are superior to existing classical biclustering models. Besides, gene enrichment analysis is employed to assess the results on the complete real dataset analysis, confirming that the discovered biclustering results hold significant biological relevance.
GNNGL-PPI: multi-category prediction of protein-protein interactions using graph neural networks based on global graphs and local subgraphs
Authors: Zeng Xin , Meng Fan-Fang , Wen Meng-Liang , Li Shu-Juan , Li Yi 
Published: May 2024

AbstractMost proteins exert their functions by interacting with other proteins, making the identification of protein-protein interactions (PPI) crucial for understanding biological activities, pathological mechanisms, and clinical therapies. Developing effective and reliable computational methods for predicting PPI can significantly reduce the time-consuming and labor-intensive associated traditional biological experiments. However, accurately identifying the specific categories of protein-protein interactions and improving the prediction accuracy of the computational methods remain dual challenges. To tackle these challenges, we proposed a novel graph neural network method called GNNGL-PPI for multi-category prediction of PPI based on global graphs and local subgraphs. GNNGL-PPI consisted of two main components: using Graph Isomorphism Network (GIN) to extract global graph features from PPI network graph, and employing GIN As Kernel (GIN-AK) to extract local subgraph features from the subgraphs of protein vertices. Additionally, considering the imbalanced distribution of samples in each category within the benchmark datasets, we introduced an Asymmetric Loss (ASL) function to further enhance the predictive performance of the method. Through evaluations on six benchmark test sets formed by three different dataset partitioning algorithms (Random, BFS, DFS), GNNGL-PPI outperformed the state-of-the-art multi-category prediction methods of PPI, as measured by the comprehensive performance evaluation metric F1-measure. Furthermore, interpretability analysis confirmed the effectiveness of GNNGL-PPI as a reliable multi-category prediction method for predicting protein-protein interactions.
Rejuvenating potato growth and yield in challenging semiarid and saline sandy Cholistan: harnessing PGPB-coated N and P application strategies
Authors: Haider Muhammad Wasim , Nafees Muhammad , Iqbal Rashid , Ali Sajid , Asad Habat Ullah , Azeem Farrukh , Gaafar Abdel-Rhman Z. , Elshikh Mohamed S. , Rizwana Humaira , Elsalahy Heba H. , Elshamly Ayman M. S. , Mohammed Kassem A. S. 
Published: May 2024

AbstractBackgroundPotato serves as a major non-cereal food crop and income source for small-scale growers in Punjab, Pakistan. Unfortunately, improper fertilization practices have led to low crop yields, worsened by challenging environmental conditions and poor groundwater quality in the Cholistan region. To address this, we conducted an experiment to assess the impact of two fertilizer application approaches on potato cv. Barna using plant growth-promoting bacteria (PGPB) coated biofertilizers. The first approach, termed conventional fertilizer application (CFA), involved four split applications of PGPB-coated fertilizers at a rate of 100:75 kg acre–1(N and P). The second, modified fertilizer application (MFA), employed nine split applications at a rate of 80:40 kg acre–1.ResultsThe MFA approach significantly improved various plant attributes compared to the CFA. This included increased plant height (28%), stem number (45%), leaf count (46%), leaf area index (36%), leaf thickness (three-folds), chlorophyll content (53%), quantum yield of photosystem II (45%), photosynthetically active radiations (56%), electrochromic shift (5.6%), proton flux (24.6%), proton conductivity (71%), linear electron flow (72%), photosynthetic rate (35%), water use efficiency (76%), and substomatal CO2(two-folds), and lowered non-photochemical quenching (56%), non-regulatory energy dissipation (33%), transpiration rate (59%), and stomatal conductance (70%). Additionally, the MFA approach resulted in higher tuber production per plant (21%), average tuber weight (21.9%), tuber diameter (24.5%), total tuber yield (29.1%), marketable yield (22.7%), seed-grade yield (9%), specific gravity (9.6%), and soluble solids (7.1%). It also reduced undesirable factors like goli and downgrade yields by 57.6% and 98.8%, respectively. Furthermore, plants under the MFA approach exhibited enhanced nitrogen (27.8%) and phosphorus uptake (40.6%), with improved N (26.1%) and P uptake efficiency (43.7%) compared to the CFA approach.ConclusionThe use of PGPB-coated N and P fertilizers with a higher number of splits at a lower rate significantly boosts potato production in the alkaline sandy soils of Cholistan.
Recovery of left ventricular systolic function in peripartum cardiomyopathy: an observational study from rural Tanzania
Authors: Katende Andrew , Roos Laurine , Urio Victor Z. , Mahundi Evance , Myovela Victor , Mnzava Dorcas , Mlula Chipegwa , Chitimbwa Christamonica , Raphael Dominick M. , Gingo Winfrid , Franzeck Fabian C. , Paris Daniel H. , Elzi Luigia , Weisser Maja , Rohacek Martin 
Published: May 2024

Abstract
Background
The aim of this study was to evaluate the recovery rate of the left ventricular systolic function of women diagnosed with peripartum cardiomyopathy receiving specialized care in rural Tanzania.

Methods
In this observational study, women diagnosed with peripartum cardiomyopathy at a referral center in rural Tanzania between December 2015 and September 2021 were included. Women diagnosed between February and September 2021 were followed prospectively, those diagnosed between December 2015 and January 2021 were tracked back for a follow-up echocardiography. All participants received a clinical examination, a comprehensive echocardiogram, and a prescription of guideline-directed medical therapy. The primary outcome was recovery of the left ventricular systolic function (left ventricular ejection fraction > 50%).

Results
Median age of the 110 participants was 28.5 years (range 17–45). At enrolment, 49 (45%) participants were already on cardiac medication, 50 (45%) had severe eccentric hypertrophy of the left ventricle, and the median left ventricular ejection fraction was 30% (range 15–46). After a median follow-up of 8.98 months (IQR 5.72–29.37), 61 (55%) participants were still on cardiac medication. Full recovery of the left ventricular systolic function was diagnosed in 76 (69%, 95% CI 59.6–77.6%) participants. In the multivariate analysis, a higher left ventricular ejection fraction at baseline was positively associated with full recovery (each 5% increase; OR 1.7, 95% CI 1.10–2.62, p = 0.012), while higher age was inversely associated (each 10 years increase; OR 0.40, 95% CI 0.19–0.82, p = 0.012).

Conclusion
Left ventricular systolic function recovered completely in 69% of study participants with peripartum cardiomyopathy from rural Tanzania under specialized care.
Perspectives on low-value care and barriers to de-implementation among primary care physicians: a multinational survey
Authors: Raudasoja Aleksi , Tikkinen Kari A. O. , Bellini Benedetta , Ben-Sheleg Eliana , Ellen Moriah E , Francesconi Paolo , Hussien Muaad , Kaji Yuki , Karlafti Eleni , Koizumi Shunzo , Ouahrani Emir , Paier-Abuzahra Muna , Savopoulos Christos , Spary-Kainz Ulrike , Komulainen Jorma , Sipilä Raija 
Published: May 2024

Abstract
Background
Healthcare costs are rising worldwide. At the same time, a considerable proportion of care does not benefit or may even be harmful to patients. We aimed to explore attitudes towards low-value care and identify the most important barriers to the de-implementation of low-value care use in primary care in high-income countries.

Methods
Between May and June 2022, we email surveyed primary care physicians in six high-income countries (Austria, Finland, Greece, Italy, Japan, and Sweden). Physician respondents were eligible if they had worked in primary care during the previous 24 months. The survey included four sections with categorized questions on (1) background information, (2) familiarity with Choosing Wisely recommendations, (3) attitudes towards overdiagnosis and overtreatment, and (4) barriers to de-implementation, as well as a section with open-ended questions on interventions and possible facilitators for de-implementation. We used descriptive statistics to present the results.

Results
Of the 16,935 primary care physicians, 1,731 answered (response rate 10.2%), 1,505 had worked in primary care practice in the last 24 months and were included in the analysis. Of the respondents, 53% had read Choosing Wisely recommendations. Of the respondents, 52% perceived overdiagnosis and 50% overtreatment as at least a problem to some extent in their own practice. Corresponding figures were 85% and 81% when they were asked regarding their country’s healthcare. Respondents considered patient expectations (85% answered either moderate or major importance), patient’s requests for treatments and tests (83%), fear of medical error (81%), workload/lack of time (81%), and fear of underdiagnosis or undertreatment (79%) as the most important barriers for de-implementation. Attitudes and perceptions of barriers differed significantly between countries.

Conclusions
More than 80% of primary care physicians consider overtreatment and overdiagnosis as a problem in their country’s healthcare but fewer (around 50%) in their own practice. Lack of time, fear of error, and patient pressures are common barriers to de-implementation in high-income countries and should be acknowledged when planning future healthcare. Due to the wide variety of barriers to de-implementation and differences in their importance in different contexts, understanding local barriers is crucial when planning de-implementation strategies.
Optimizing shoulder elevation assist rate in exoskeletal rehabilitation based on muscular activity indices: a clinical feasibility study
Authors: Ito Daisuke , Fukuda Mori , Hosoi Yuichiro , Hirose Ryotaro , Teramae Tatsuya , Kamimoto Takayuki , Yamada Yuka , Tsuji Tetsuya , Noda Tomoyuki , Kawakami Michiyuki 
Published: May 2024

Abstract
Background
Restoring shoulder function is critical for upper-extremity rehabilitation following a stroke. The complex musculoskeletal anatomy of the shoulder presents a challenge for safely assisting elevation movements through robotic interventions. The level of shoulder elevation assistance in rehabilitation is often based on clinical judgment. There is no standardized method for deriving an optimal level of assistance, underscoring the importance of addressing abnormal movements during shoulder elevation, such as abnormal synergies and compensatory actions. This study aimed to investigate the effectiveness and safety of a newly developed shoulder elevation exoskeleton robot by applying a novel optimization technique derived from the muscle synergy index.

Methods
Twelve chronic stroke participants underwent an intervention consisting of 100 robot-assisted shoulder elevation exercises (10 × 10 times, approximately 40 min) for 10 days (4–5 times/week). The optimal robot assist rate was derived by detecting the change points using the co-contraction index, calculated from electromyogram (EMG) data obtained from the anterior deltoid and biceps brachii muscles during shoulder elevation at the initial evaluation. The primary outcomes were the Fugl–Meyer assessment-upper extremity (FMA-UE) shoulder/elbow/forearm score, kinematic outcomes (maximum angle of voluntary shoulder flexion and elbow flexion ratio during shoulder elevation), and shoulder pain outcomes (pain-free passive shoulder flexion range of motion [ROM] and visual analogue scale for pain severity during shoulder flexion). The effectiveness and safety of robotic therapy were examined using the Wilcoxon signed-rank sum test.

Results
All 12 patients completed the procedure without any adverse events. Two participants were excluded from the analysis because the EMG of the biceps brachii was not obtained. Ten participants (five men and five women; mean age: 57.0 [5.5] years; mean FMA-UE total score: 18.7 [10.5] points) showed significant improvement in the FMA-UE shoulder/elbow/forearm score, kinematic outcomes, and pain-free passive shoulder flexion ROM (P < 0.05). The shoulder pain outcomes remained unchanged or improved in all patients.

Conclusions
The study presents a method for deriving the optimal robotic assist rate. Rehabilitation using a shoulder robot based on this derived optimal assist rate showed the possibility of safely improving the upper-extremity function in patients with severe stroke in the chronic phase.