bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-cell and genome-wide Mendelian randomization identifies causative genes for gout
Authors: Yang Yubiao , Hu Ping , Zhang Qinnan , Ma Boyuan , Chen Jinyu , Wang Bitao , Ma Jun , Liu Derong , Hao Jian , Zhou Xianhu 
Published: June 2024

Abstract
Background
Gout is a prevalent manifestation of metabolic osteoarthritis induced by elevated blood uric acid levels. The purpose of this study was to investigate the mechanisms of gene expression regulation in gout disease and elucidate its pathogenesis.

Methods
The study integrated gout genome-wide association study (GWAS) data, single-cell transcriptomics (scRNA-seq), expression quantitative trait loci (eQTL), and methylation quantitative trait loci (mQTL) data for analysis, and utilized two-sample Mendelian randomization study to comprehend the causal relationship between proteins and gout.

Results
We identified 17 association signals for gout at unique genetic loci, including four genes related by protein-protein interaction network (PPI) analysis: TRIM46, THBS3, MTX1, and KRTCAP2. Additionally, we discerned 22 methylation sites in relation to gout. The study also found that genes such as TRIM46, MAP3K11, KRTCAP2, and TM7SF2 could potentially elevate the risk of gout. Through a Mendelian randomization (MR) analysis, we identified three proteins causally associated with gout: ADH1B, BMP1, and HIST1H3A.

Conclusion
According to our findings, gout is linked with the expression and function of particular genes and proteins. These genes and proteins have the potential to function as novel diagnostic and therapeutic targets for gout. These discoveries shed new light on the pathological mechanisms of gout and clear the way for future research on this condition.
Fiscal space for the immunisation program in Zambia– an efficiency analysis approach
Authors: Chompolola Abson , Chama-Chiliba Chitalu Miriam , Simuyemba Moses Chikoti , Sinyangwe Aaron Chisha , Bchir Abdallah , Asiimwe Gilbert , Masiye Felix 
Published: June 2024

AbstractObjectiveThe immunisation programme in Zambia remains one of the most effective public health programmes. Its financial sustainability is, however, uncertain. Using administrative data on immunisation coverage rate, vaccine utilisation, the number of health facilities and human resources, expenditure on health promotion, and the provision of outreach services from 24 districts, we used Data Envelopment Analysis to determine the level of technical efficiency in the provision of immunisation services. Based on our calculated levels of technical efficiency, we determined the available fiscal space for immunisation.ResultsOut of the 24 districts in our sample, 9 (38%) were technically inefficient in the provision of immunisation services. The average efficiency score, however, was quite high, at 0.92 (CRS technology) and 0.95 (VRS technology). Based on the calculated level of technical efficiency, we estimated that an improvement in technical efficiency can save enough vaccine doses to supply between 5 and 14 additional districts. The challenge, however, lies in identifying and correcting for the sources of technical inefficiency.
Discrimination sensitivity of visual shapes sharpens in autistic adults but only after explicit category learning
Authors: Van Overwalle Jaana , Geusens Birte , Van der Donck Stephanie , Boets Bart , Wagemans Johan 
Published: June 2024

Abstract
Background
Categorization and its influence on perceptual discrimination are essential processes to organize information efficiently. Individuals with Autism Spectrum Condition (ASC) are suggested to display enhanced discrimination on the one hand, but also to experience difficulties with generalization and ignoring irrelevant differences on the other, which underlie categorization. Studies on categorization and discrimination in ASC have mainly focused on one process at a time, however, and typically only used either behavioral or neural measures in isolation. Here, we aim to investigate the interrelationships between these perceptual processes using novel stimuli sampled from a well-controlled artificial stimulus space. In addition, we complement standard behavioral psychophysical tasks with frequency-tagging EEG (FT-EEG) to obtain a direct, non-task related neural index of discrimination and categorization.

Methods
The study was completed by 38 adults with ASC and 38 matched neurotypical (NT) individuals. First, we assessed baseline discrimination sensitivity by administering FT-EEG measures and a complementary behavioral task. Second, participants were trained to categorize the stimuli into two groups. Finally, participants again completed the neural and behavioral discrimination sensitivity measures.

Results
Before training, NT participants immediately revealed a categorical tuning of discrimination, unlike ASC participants who showed largely similar discrimination sensitivity across the stimuli. During training, both autistic and non-autistic participants were able to categorize the stimuli into two groups. However, in the initial training phase, ASC participants were less accurate and showed more variability, as compared to their non-autistic peers. After training, ASC participants showed significantly enhanced neural and behavioral discrimination sensitivity across the category boundary. Behavioral indices of a reduced categorical processing and perception were related to the presence of more severe autistic traits. Bayesian analyses confirmed overall results.

Limitations
Data-collection occurred during the COVID-19 pandemic.

Conclusions
Our behavioral and neural findings indicate that adults with and without ASC are able to categorize highly similar stimuli. However, while categorical tuning of discrimination sensitivity was spontaneously present in the NT group, it only emerged in the autistic group after explicit categorization training. Additionally, during training, adults with autism were slower at category learning. Finally, this multi-level approach sheds light on the mechanisms underlying sensory and information processing issues in ASC.
Enhanced osteochondral repair by leukocyte-depleted platelet-rich plasma in combination with adipose-derived mesenchymal stromal cells encapsulated in a three-dimensional photocrosslinked injectable hydrogel in a rabbit model
Authors: Iseki Tomoya , Rothrauff Benjamin B. , Kihara Shinsuke , Overholt Kalon J. , Taha Tarek , Lin Hang , Alexander Peter G. , Tuan Rocky S. 
Published: June 2024

Abstract
Introduction
Intra-articular injection of adipose-derived mesenchymal stromal cells (ASCs) and/or platelet-rich plasma (PRP) have been reported to independently and synergistically improve healing of osteochondral lesions in animal models. However, their independent and combined effects when localized to an osteochondral lesion by encapsulation within a photocrosslinkable methacrylated gelatin hydrogel (GelMA) have not been explored. Herein we investigated a unique combination of allogeneic ASCs and PRP embedded in GelMA as a single-stage treatment for osteochondral regeneration in a rabbit model.

Methods
Thirty mature rabbits were divided into six experimental groups: (1) Sham; (2) Defect; (3) GelMA; (4) GelMA + ASCs; (5) GelMA + PRP; and (6) GelMA + ASCs + PRP.At 12 weeks following surgical repair, osteochondral regeneration was assessed on the basis of gross appearance, biomechanical properties, histological and immunohistochemical characteristics, and subchondral bone volume.

Results
In terms of mechanical property reflecting the ability of neotissue to bear stress, PRP only group were significantly lower than the Sham group (p = 0.0098). On the other hand, ASCs only and ASCs combined with PRP groups did not exhibit significantly difference, which suggesting that incorporation of ASCs assists in restoring the ability of the neotissue to bear stresses similarly to native tissue (p = 0.346, p = 0.40, respectively). Safranin O in ASCs combined with PRP group was significantly higher than the Defect and GelMA only groups (p = 0.0009, p = 0.0017, respectively). Additionally, ASCs only and ASCs combined with PRP groups presented especially strong staining for collagen type II. Surprisingly, PRP only and PRP + ASCs groups tended to exhibit higher collagen type I and collagen type X staining compared to ASCs only group, suggesting a potential PRP-mediated hypertrophic effect.

Conclusion
Regeneration of a focal osteochondral defect in a rabbit model was improved by a single-stage treatment of a photocrosslinked hydrogel containing allogenic ASCs and autologous PRP, with the combination of ASCs and PRP producing superior benefit than either alone. No experimental construct fully restored all properties of the native, healthy osteochondral unit, which may require longer follow-up or further modification of PRP and/or ASCs characteristics.
A systematic review and meta-analysis of systematic and topical tranexamic acid administration in aesthetic plastic surgery
Authors: Kolasiński Jerzy , Reysner Tomasz , Kolenda Małgorzata , Kołacz Szymon , Domagalska Małgorzata 
Published: June 2024

Abstract
Introduction
Tranexamic acid has been widely used in plastic surgery. However, its efficacy has yet to be fully established. This meta-analysis aimed to determine its effectiveness in aesthetic plastic surgery.

Methods
Following PRISMA guidelines, we conducted a meta-analysis of prospective randomised clinical trials that compared the effects of topical or systematic administration of tranexamic acid versus the control group in aesthetic plastic surgeries. The study was registered on the International Register of Systematic Reviews (PROSPERO) and is available online (www.crd.york.uk/prospero, CRD42023492585).

Results
Eleven studies encompassing 960 patients were included for the synthesis after critical evaluation. Systematic (MD − 18.05, 95% Cl, − 22.01, − 14.09, p < 0.00001) and topical (MD − 74.93, 95% Cl, − 88.79, − 61.07, p < 0.00001) administration of tranexamic acid reduced total blood loss. Topical tranexamic acid reduced drainage output (p < 0.0006).

Conclusion
Tranexamic acid reduced blood loss in aesthetic plastic surgery. More strictly defined RCTs, using high-quality methodology, are needed to evaluate the advantages and disadvantages of tranexamic acid in aesthetic plastic surgery.
High efficacy of huCD20-targeted AcTaferon in humanized patient derived xenograft models of aggressive B cell lymphoma
Authors: Daneels Willem , Van Parys Alexander , Huyghe Leander , Rogge Elke , De Rouck Steffi , Christiaen Ruben , Zabeau Lennart , Taveirne Sylvie , Van Dorpe Jo , Kley Niko , Cauwels Anje , Depla Erik , Tavernier Jan , Offner Fritz 
Published: June 2024

AbstractType I interferon (IFN) is a potent antitumoral drug, with an important history in the treatment of hematologic malignancies. However, its pleiotropic nature leads to severe dose-limiting toxicities that blunt its therapeutic potential. To achieve selective targeting of specific immune or tumor cells, AcTakines (Activity-on-Target Cytokines), i.e., immunocytokines utilizing attenuated cytokines, and clinically optimized A-Kines™ were developed. In syngeneic murine models, the CD20-targeted murine IFNα2-based AcTaferons (AFNs) have demonstrated clear antitumoral effects, with excellent tolerability. The current study explores the antitumoral potential of the humanized huCD20-Fc-AFN in 5 different humanized patient derived xenograft (PDX) models of huCD20+ aggressive B non-Hodgkin lymphomas (B-NHLs). The huCD20-Fc-AFN consists of a huCD20-specific single-domain antibody (VHH) linked through a heterodimeric ‘knob-in-hole’ human IgG1 Fc molecule to an attenuated huIFNα2 sequence. An in vitro targeting efficacy of up to 1.000-fold could be obtained, without detectable in vivo toxicities, except for selective (on-target) and reversible B cell depletion. Treatment with huCD20-Fc-AFN significantly increased the median overall survival (mOS) in both non-humanized (mOS 31 to 45 days; HR = 0.26; p = 0.001), and humanized NSG/NOG mice (mOS 34 to 80 days; HR = 0.37; p < 0.0001). In humanized mice, there was a trend for increased survival when compared to equimolar rituximab (mOS 49 to 80 days; HR = 0.73; p = 0.09). The antitumoral effects of huCD20-Fc-AFN were partly due to direct effects of type I IFN on the tumor cells, but additional effects via the human immune system are essential to obtain long-term remissions. To conclude, huCD20-Fc-AFN could provide a novel therapeutic strategy for huCD20-expressing aggressive B-NHLs.
Graphical Abstract
Discordant conceptualisations of eating disorder recovery and their influence on the construct of terminality
Authors: Elwyn Rosiel , Adams Marissa , Sharpe Sam L. , Silverstein Scout , LaMarre Andrea , Downs James , Burnette C. Blair 
Published: June 2024

AbstractEating disorders (EDs) are complex, multifaceted conditions that significantly impact quality-of-life, often co-occur with multiple medical and psychiatric diagnoses, and are associated with a high risk of medical sequelae and mortality. Fortunately, many people recover even after decades of illness, although there are different conceptualisations of recovery and understandings of how recovery is experienced. Differences in these conceptualisations influence categorisations of ED experiences (e.g., longstanding vs. short-duration EDs), prognoses, recommended treatment pathways, and research into treatment outcomes. Within recent years, the proposal of a ‘terminal’ illness stage for a subset of individuals with anorexia nervosa and arguments for the prescription of end-of-life pathways for such individuals has ignited debate. Semantic choices are influential in ED care, and it is critical to consider how conceptualisations of illness and recovery and power dynamics influence outcomes and the ED ‘staging’ discourse. Conceptually, ‘terminality’ interrelates with understandings of recovery, efficacy of available treatments, iatrogenic harm, and complex co-occurring diagnoses, as well as the functions of an individual’s eating disorder, and the personal and symbolic meanings an individual may hold regarding suffering, self-starvation, death, health and life. Our authorship represents a wide range of lived and living experiences of EDs, treatment, and recovery, ranging from longstanding and severe EDs that may meet descriptors of a ‘terminal’ ED to a variety of definitions of ‘recovery’. Our experiences have given rise to a shared motivation to analyse how existing discourses of terminality and recovery, as found in existing research literature and policy, may shape the conceptualisations, beliefs, and actions of individuals with EDs and the healthcare systems that seek to serve them.
Gut microbiota and metabolites signatures of clinical response in anti-PD-1/PD-L1 based immunotherapy of biliary tract cancer
Authors: Zhu Chengpei , Wang Yunchao , Zhu Ruijuan , Wang Shanshan , Xue Jingnan , Zhang Dongya , Lan Zhou , Zhang Chenchen , Liang Yajun , Zhang Nan , Xun Ziyu , Zhang Longhao , Ning Cong , Yang Xu , Chao Jiashuo , Long Junyu , Yang Xiaobo , Wang Hanping , Sang Xinting , Jiang Xianzhi , Zhao Haitao 
Published: June 2024

Abstract
Background
Accumulating evidence suggests that the gut microbiota and metabolites can modulate tumor responses to immunotherapy; however, limited data has been reported on biliary tract cancer (BTC). This study used metagenomics and metabolomics to identify characteristics of the gut microbiome and metabolites in immunotherapy-treated BTC and their potential as prognostic and predictive biomarkers.

Methods
This prospective cohort study enrolled 88 patients with BTC who received PD-1/PD-L1 inhibitors from November 2018 to May 2022. The microbiota and metabolites significantly enriched in different immunotherapy response groups were identified through metagenomics and LC-MS/MS. Associations between microbiota and metabolites, microbiota and clinical factors, and metabolites and clinical factors were explored.

Results
Significantly different bacteria and their metabolites were both identified in the durable clinical benefit (DCB) and non-durable clinical benefit (NDB) groups. Of these, 20 bacteria and two metabolites were significantly associated with survival. Alistipes were positively correlated with survival, while Bacilli, Lactobacillales, and Pyrrolidine were negatively correlated with survival. Predictive models based on six bacteria, four metabolites, and the combination of three bacteria and two metabolites could all discriminated between patients in the DCB and NDB groups with high accuracy. Beta diversity between two groups was significantly different, and the composition varied with differences in the use of immunotherapy.

Conclusions
Patients with BTC receiving immunotherapy have specific alterations in the interactions between microbiota and metabolites. These findings suggest that gut microbiota and metabolites are potential prognostic and predictive biomarkers for clinical outcomes of anti-PD-1/PD-L1-treated BTC.
Biomass yield and metal phytoextraction efficiency of Salix and Populus clones harvested at different rotation lengths in the field experiment
Authors: Prouzová Nikola , Kubátová Pavla , Mercl Filip , Száková Jiřina , Najmanová Jana , Tlustoš Pavel 
Published: June 2024

Abstract
Background
Phytoextraction belongs to environmentally well-accepted remediation technologies to remove metals from contaminated soils. Due to long-time requirement, sufficient data for proper phytoextraction evaluation are missing. Four clones of fast-growing trees: two willow species (S1), Salix viminalis L. (Salix schwerinii E.L.Wolf × S. viminalis) × S. viminalis) and (S2)—Salix smithiana (Salix × smithiana Willd.), and two poplar clones (P1), Populus Max-4 (Populus nigra L. × Populus maximowiczii A. Henry) and (P2) Wolterson (P. nigra L.) were cultivated under field conditions at medium-to-high Cd and Pb, and low Zn soil contamination to assess trees’ long-term ability of biomass production and removal of potentially toxic elements (PTEs). The biomass yield and PTE uptake were measured during 8 years of regular growth under three rotation lengths: four harvests following 2-year periods (4 × 2y), two harvests in 4-year periods (2 × 4y), and one harvest representing 8 years of growth (1 × 8y).

Results
In most cases, the highest annual dry biomass yield was achieved with a 2 × 4y rotation (P1 = 20.9 t ha−1 y−1, S2 = 18.4 t ha−1y−1), and the yield decreased in order 2 × 4y > 1 × 8y > 4 × 2y of harvesting periods. Only clone S1 showed a different pattern. The differences in biomass yield substantially affected the PTE phytoextraction. The greatest amount of Cd and Zn was removed by willow S2, with the highest biomass yield, and the strongest ability to accumulate PTEs. With 2 × 4y rotation, S2 removed a substantial amount of Cd (9.07%) and Zn (3.43%) from the topsoil horizon (0–20 cm) and 5.62% Cd and 2.04% Zn from horizon 20–40 cm; phytoextraction rate was slightly lower for 1 × 8y rotation. The poplar P1 removed the most Pb in the 1 × 8y rotation, but the overall Pb phytoextraction was negligible. The results indicated that lignin and cellulose contents increased, and hemicellulose content decreased with increased concentrations of Cd, Pb and Zn in poplars wood.

Conclusions
The data confirmed that phytoextraction over longer harvest periods offered promising results for removing Cd from medium- to high-level contaminated soils; however, the ability of Pb removal was extremely low. The longer harvest period should be more economically feasible.

Graphical Abstract
[18F]FAPI adds value to [18F]FDG PET/CT for diagnosing lymph node metastases in stage I-IIIA non-small cell lung cancer: a prospective study
Authors: Li Youcai , Zhang Yin , Guo Zhihua , Hou Peng , Lv Jie , Ke Miao , Liu Shaoyu , Li Siwen , Yin Weiqiang , He Jianxing , Wang Xinlu 
Published: June 2024

Abstract
Background
This study investigates the value of fluorine 18 ([18F])-labeled fibroblast activation protein inhibitor (FAPI) for lymph node (LN) metastases in patients with stage I-IIIA non-small cell lung cancer (NSCLC).

Methods
From November 2021 to October 2022, 53 patients with stage I-IIIA NSCLC who underwent radical resection were prospectively included. [18F]-fluorodeoxyglucose (FDG) and [18F]FAPI examinations were performed within one week. LN staging was validated using surgical and pathological findings. [18F]FDG and [18F]FAPI uptake was compared using the Wilcoxon signed-ranks test. Furthermore, the diagnostic value of nodal groups was investigated.

Results
In 53 patients (median age, 64 years, range: 31–76 years), the specificity of [18F]FAPI for detecting LN metastasis was significantly higher than that of [18F]FDG (P < 0.001). High LN risk category, greater LN short-axis dimension(≥ 1.0 cm), absence of LN calcification or high-attenuation, and higher LN FDG SUVmax (≥ 10.1) were risk factors for LN metastasis(P < 0.05). The concurrence of these four risk factors accurately predicted LN metastases (Positive Predictive Value [PPV] 100%), whereas the presence of one to three risk factors was unable to accurately discriminate the nature of LNs (PPV 21.7%). Adding [18F]FAPI in this circumstance improved the diagnostic value. LNs with an [18F]FAPI SUVmax<6.2 were diagnosed as benign (Negative Predictive Value 93.8%), and LNs with an [18F]FAPI SUVmax≥6.2 without calcification or high-attenuation were diagnosed as LN metastasis (PPV 87.5%). Ultimately, the integration of [18F]FDG and [18F]FAPI PET/CT resulted in the highest accuracy for N stage (83.0%) and clinical decision revisions for 29 patients.

Conclusion
In patients with stage I-IIIA NSCLC, [18F]FAPI contributed additional valuable information to reduce LN diagnostic uncertainties after [18F]FDG PET/CT. Integrating [18F]FDG and [18F]FAPI PET/CT resulted in more precise clinical decisions.

Trial registration
The Chinese Clinical Trial Registry: ChiCTR2100044944 (Registered: 1 April 2021, https://www.chictr.org.cn/showprojEN.html?proj=123995).