bluuebunny/crossref_metadata_2025_split huggingface dataset:
Decoding Complex Inherited Phenotypes in Rare Disorders: The DECIPHERD initiative for rare undiagnosed diseases in Chile.
Authors: Repetto Gabriela , Poli Cecilia , Rebolledo-Jaramillo Boris , Lagos Catalina , Orellana Joan , Moreno Gabriela , Martin Luz M , Encina Gonzalo , Böhme Daniela , Faundes Victor , Zavala M Jesús , Hasbún Trinidad , Fischer Sara , Brito Florencia , Araya Diego , Lira Manuel , Cruz Javiera de la , Astudillo Camila , Lay-Son Guillermo , Cares Carolina , Aracena Mariana , Martin Esteban San , Coban-Akdemir Zeynep , Posey Jennifer , Lupski James 
Published: September 2023

Abstract
Rare diseases affect millions of people worldwide, and most have a genetic etiology. The incorporation of next-generation sequencing into clinical settings, particularly exome and genome sequencing, has resulted in an unprecedented improvement in diagnosis and discovery in the past decade. Nevertheless, these tools are unavailable in many countries, increasing health care gaps between high- and low-and-middle-income countries and prolonging the “diagnostic odyssey” for patients. To advance genomic diagnoses in a setting of limited genomic resources, we developed DECIPHERD, an undiagnosed diseases program in Chile. DECIPHERD was implemented in two phases: training and local development. The training phase relied on international collaboration with Baylor College of Medicine, and the local development was structured as a hybrid model, where clinical and bioinformatics analysis were performed in-house and sequencing outsourced abroad, due to lack of high-throughput equipment in Chile. We describe the implementation process and findings of the first 103 patients. They had heterogeneous phenotypes, including congenital anomalies, intellectual disabilities and/or immune system dysfunction. Patients underwent clinical exome or research exome sequencing, as solo cases or with parents using a trio design. We identified pathogenic, likely pathogenic or variants of unknown significance in genes related to the patients´ phenotypes in 48 (46.6%) of them. Half were de novo informative variants, and half of the identified variants have not been previously reported in public databases. DECIPHERD ended the diagnostic odyssey for many participants. This hybrid strategy may be useful for settings of similarly limited genomic resources and lead to discoveries in understudied populations.
Landslide susceptibility mapping based on the deformation intensity
Authors: Jin Bijing , Zeng Taorui , Yin Kunlong , Gui Lei , Guo Zizheng , Wang Tengfei 
Published: September 2023

Abstract
Affected by the human engineering activities and extreme climate change, landslide disasters develop frequently in the channel of the Three Gorges Reservoir Area. The framework related to the extension of dynamic susceptibility modeling has largely not been explored. This work considered the Wanzhou channel of the Three Gorges Reservoir Area as the experimental site, which a transportation channel with significant economic value to carry out innovative research in two stages: (i) five machine learning models logistic regression (LR), multilayer perceptron neural network (MLPNN), support vector machine (SVM), random forest (RF) and decision tree (DT) were used to explore landslide susceptibility distribution based on detailed landslide boundaries; (ii) The PS-InSAR-based intensify factor was generated by the Persistent Scatterer Interferometric Synthetic Aperture Radar (PS-InSAR) technology. Then the intensify factor was combined with the proposed static factors and machine learning models to generate enhanced landslide susceptibility mapping (ELSM). The area under the receiver operating characteristic curve (AUC) was proposed as the evaluation indicator. Dynamic landslide susceptibility mapping has improved model accuracy, especially with DT models achieving 2% enhancement and the highest AUC value of 93.1%. The susceptibility results of introducing intensify factor are more in line with the spatial distribution of actual landslides. The research framework proposed in this study has important reference significance for the dynamic management and prevention of landslide disasters in the study area.
Study on Carbon Emission Reduction Countermeasures Based on Carbon Emission Influencing Factors and Trends
Authors: Xinfa Tang , Shuai Liu , Yonghua Wang , Youwei Wan 
Published: September 2023

Abstract
In order to promote the achievement of the dual-carbon goal, this paper proposes an extended STIRPAT model and a PSO-BP neural network prediction model to analyze and predict the factors influencing carbon emissions and future carbon emissions. To address the multicollinearity problem, the STIRPAT model was validated using ridge regression, and the BP neural network was optimized using the particle swarm algorithm (PSO) to improve the prediction accuracy of the model. Taking the metal smelting industry in China as the research object, the results show that the influencing factors of carbon emission in the metal smelting industry are, in descending order, population size, energy structure, urbanization rate, intensity of energy consumption, added value of the secondary industry, and per capita GDP. In the future, the carbon emission of the metal smelting industry in China will keep the downward trend of the industry year by year, and the adjustment of the energy structure is the key to the achievement of carbon emission reduction in this industry. Finally, a series of countermeasures are proposed to reduce carbon emissions in the metal smelting industry with regard to the influencing factors and trends of carbon emissions.
Inter-linkages between in-stream plant diversity and macroinvertebrate communities
Authors: Baattrup-Pedersen Annette , Friis Klaus Bertram , Larsen Søren , Friberg Nikolai , Riis Tenna 
Published: September 2023

Abstract
Evidence of freshwater biodiversity decline, species extinction and severe alterations in the biological structure and function of freshwater ecosystems is accumulating. Here we explore the role of macrophyte diversity in lowland streams for the abundance, taxon richness and composition of macroinvertebrate communities including also the abundance of different functional feeding groups. We applied a controlled in situ experiment in four small lowland stream reaches situated in rural landscapes in Denmark. We were able to explain a major fraction of variability in the macroinvertebrate communities by differences in total macrophyte surface areas among treatments, but the number of macrophyte species in the experimental treatment also played a highly significant role (i.e. one, two or three plant species) for both the abundance, richness and composition of the macroinvertebrate community. We strongly encourage managers to protect plant diversity in streams, not only because the plants in themselves constitute an important part of the biodiversity, but also because they positively affect the macroinvertebrate community. Moreover, macrophyte-friendly management can be seen as a nature-based solution to mitigate the degraded physical conditions characterising many streams in agricultural catchments.
The impact of non-urgent visits on Emergency Department’s waiting time in Saudi Arabia general hospitals’ main regions: an observation study
Authors: Althumairi Arwa , AlYousif Zainab Adnan , Alumran Arwa 
Published: September 2023

Abstract
Background:
Emergency department (ED) overcrowding is a serious issue worldwide. It is associated with longer waiting times for patients, which can have negative consequences for patient care. Non-urgent cases that are seen in the ED can often be treated in alternative primary health settings. This study aimed to assess the relationship between non-urgent patients' Canadian Emergency Department Triage and Acuity Scale (CTAS) scores and waiting times for urgent patients.
Methods:
This was a cross-sectional, retrospective observational study using secondary data. Data were presented as frequencies and means. T-tests and chi-square tests were used to assess the relationship between waiting times and level of cases' urgency.
Results:
A total of 136,668 ED visits were included in the study from three regions. The percentage of non-urgent cases ranged from 40% to 51%, which exceeded national and international acceptable levels. There was a significant difference between mean waiting times for urgent cases and non-urgent cases for the four key performance indicators (KPIs): door-to-doctor, doctor-to-decision, decision-to-disposition, and door-to-disposition (percentage of patients seen within 4 hours).
Conclusion:
The availability of non-urgent cases prolonged waiting times for urgent cases. Further measures need to be adopted to reduce waiting times and assess patient and visit characteristics for non-urgent cases.
Moderate- to vigorous-intensity physical activities for hemophilia A patients during low-dose pharmacokinetic-guided extended half-life factor VIII prophylaxis
Authors: Srichumpu Chonlatis , Rakmanotham Arunothai , Moonla Chatphatai , Sosothikul Darintr 
Published: September 2023

Abstract
Background
Low-dose pharmacokinetic (PK)-guided extended half-life (EHL) factor VIII (FVIII) prophylaxis can reduce the bleeding risk in hemophilia A (HA) patients. An increase in physical activities for promoting musculoskeletal health may enhance the benefits of prophylactic therapy.
Objectives
To determine the clinical impact of moderate- to vigorous-intensity physical activities in HA patients during low-dose PK-guided EHL FVIII prophylaxis.
Patients/Methods:
This prospective study enrolled patients with moderate/severe HA (a baseline FVIII level ≤ 5 IU/dL) who received low-dose PK-guided EHL FVIII prophylaxis for ≥ 6 months. An individualized exercise protocol was introduced to each participant, targeting a 65% increase in the maximum predicted heart rate for ≥ 150 minutes/week, while continuing EHL FVIII prophylaxis for 6 months. Before and after implementing the intervention, annualized bleeding rates (ABR), annualized joint bleeding rates (AJBR), Hemophilia Joint Health Scores (HJHS), skeletal muscle mass, hemophilia-specific quality-of-life (QoL) scores and annualized FVIII consumption were compared.
Results
Of 13 participants (mean age ± standard deviation [SD]: 20.1 ± 6.8 years), ABR, AJBR, and HJHS were significantly reduced (mean differences [MD] ± SD: -5.7 ± 2.6 bleeds/year, -4.2 ± 2.6 joint bleeds/year, and − 4.3 ± 9.7 marks, respectively; P < 0.05) after applying the 6-month exercise protocol. Skeletal muscle mass (P < 0.05) and QoL (P < 0.001) had also improved, while FVIII usage had decreased (MD ± SD: -129.1 ± 419.2 IU/kg/year; P < 0.05).
Conclusions
The combination of moderate- to vigorous-intensity physical activities with low-dose PK-guided EHL FVIII prophylaxis improves bleeding prevention, musculoskeletal status and QoL in patients with moderate/severe HA. By minimizing FVIII consumption, this strategy helps optimize hemophilia care in countries with budget constraints. ClinicalTrials.gov NCT05728528.
Indistinguishable monocyte pathway activation in adeno-associated virus positive and negative paediatric liver explants
Authors: de Kleine Ruben H. , Carbo Ellen C. , Jochems Simon P. , Lexmond Willem S. , Zhou Xuewei W. , Mei Hailiang , Bontemps Sander T.H. , Hennevelt Rick , Gard Lilli , Sidorov Igor A. , Boers Stefan A. , Heuvel Marius C. van den , Buddingh Emilie P. , Kroes Aloys C.M. , de Meijer Vincent E. , Schölvinck Elisabeth H. , von Eije Karin J. , de Vries Jutte J.C. 
Published: September 2023

Abstract
Adeno-associated virus 2 (AAV2) has recently been epidemiologically associated with severe childhood hepatitis, however the pathogenesis remains unclear. Here, we report excessive activation of monocyte pathways in liver explant tissue from cases compared with paediatric controls. Remarkably, this signature was indistinguishable for AAV2 positive and negative transplant cases. Our findings suggest a common pathway triggered by different viruses circulating during the outbreak, with similar severe clinical outcome.
Deuteration-enhanced neutron contrast to probe amorphous domain size in organic photovoltaic bulk heterojunction films
Authors: Lu Xinhui , Cai Guilong , Li Yuhao , Fu Yuang , Yang Hua , Mei Le , Li Tengfei , Liu Heng , Ke Yubin , Wang Xun-Li , Bredas Jean-Luc , Chen Xian-Kai , Zhan Xiaowei 
Published: September 2023

Abstract
An organic photovoltaic bulk heterojunction is comprised of a mixture of organic donor (D) and acceptor (A) materials, generally forming a semi-crystalline thin film with both crystalline and amorphous domains. The sizes of the donor and acceptor domains critically impact the device performance; however, conventional X-ray scattering techniques lack the ability to detect the D/A contrast within the amorphous D/A intermixing regions. In this study, we employed neutron scattering and targeted deuteration to enhance the D/A contrast by nearly one order of magnitude. Remarkably, the PM6:deuterated Y6 (d-Y6) system revealed a new length scale, indicating short-range aggregation of d-Y6 molecules in the amorphous intermixing regions. All-atom molecular dynamics simulations confirmed that this short-range aggregation is an inherent morphological advantage of Y6 which effectively assists charge extraction and suppresses charge recombination as demonstrated by capacitance spectroscopy. For the first time, our findings uncovered the amorphous nanomorphology of organic photovoltaic thin films, providing crucial insights into the morphology-driven device performance.
Correlation and Path-coefficient Analysis for Oil and Its Fatty Acids Traits in Indian Mustard [brassica Juncea (L.) Czern &amp; Coss.]
Authors: Kumar Rajneesh , Pandey Manoj Kumar , Chand Pooran 
Published: September 2023

Abstract
In this study, fourteen genotypes of Brassica (B. juncea) were analyze for correlation co-efficient between oil and its major fatty acid traits and path co-efficient analysis to examine the cause and consequences relationship with direct and indirect components. Correlation coefficient for the major fatty acids revealed that oil content exhibit highly significant with positive correlation and significant for linoleic acid.Moreover, oil content correlated with positively in the direction for palmitic acid, stearic acid, oleic acid, linoleic acid, linolenic acid and erucic acid. Howeverit exhibit in negative direction and non-significant for eicosenoic acid. When dependent characters was oil content and all other residual 7 characters / all fatty acid traits considered as independent contributing characters, linoleic acid (0.180) displayed high order of direct effect on oil content and it is followed by erucic acid (0.154), oleic acid (0.148), Linolenic acid (0.096), palmitic acid (0.095), and stearic acid (0.068). At phenotypic level, linoleic acid (0.115) exhibit high order of direct effect on oil content and it is follow by erucic acid (0.101), oleic acid (0.095), palmitic acid (0.062), Linolenic acid (0.055) and stearic acid (0.045). Residual effect at genotypic level (0.959) and phenotypic (0.983) were high which indicate that most of the characters contributing to the oil content has taken in the present study. Palmitic acid contributed to oil content indirectly via eicosenoic acid; stearic acid via linoleic acid; linoleic acid via stearic acid; Linolenic acid via eicosenoic acid; eicosenoic acid via oleic acid & erucic acid via eicosenoic acid. These characters also been identified as major direct and indirect contributors towards oil contents and fatty acid profile in Indian mustard.
Tetramerization of PKM2 alleviates traumatic brain injury by ameliorating mitochondrial damage in microglia
Authors: Zhu Haiyan , Zhang Huiwen , Zhao Xiao-Jing , Zhang Lingyuan , Liu Xue , Zhang Zhi-Yuan , Ren Yi-Zhi , Feng Yong 
Published: September 2023

Abstract

Background
Traumatic brain injury (TBI) is a leading cause of death and disability worldwide. Microglial activation and neuroinflammation are key cellular events that determine the outcome of TBI, especially neuronal and cognitive function. Studies have suggested that the metabolic characteristics of microglia dictate their inflammatory response. The pyruvate kinase isoform M2 (PKM2), a key glycolytic enzyme, is involved in the regulation of various cellular metabolic processes, including mitochondrial metabolism. This suggests that PKM2 may also participate in the regulation of microglial activation during TBI. Therefore, the present study aimed to evaluate the role of PKM2 in regulating microglial activation and neuroinflammation and its effects on cognitive function following TBI.
Methods
A controlled cortical impact (CCI) mouse model and inflammation-induced primary mouse microglial cells in vitro were used to investigate the potential effects of PKM2 inhibition and regulation.
Results
PKM2 was significantly increased during the acute and subacute phases of TBI and was predominantly detected in microglia rather than in neurons. PKM2 inhibition by TEPP46 and shikonin inhibited microglial M1-like activation and attenuated neuroinflammation following TBI. The effects of general inhibition and tetramerization of PKM2 on microglial activation were compared, and we confirmed that the nuclear translocation of PKM2 is required for the generation of the pro-inflammatory microglial M1 phenotype. PKM2 tetramerization effectively transitioned microglial activation to an anti-inflammatory phenotype and maintained normal mitochondrial morphology by enhancing the interaction between PKM2 and mitofusin 2 (MFN2) in pro-inflammatory activated microglia. General inhibition and tetramerization of PKM2 attenuated cognitive function caused by TBI, whereas PKM2 tetramerization exhibited a better treatment effect.
Conclusion
Our experiments demonstrated the non-metabolic role of PKM2 in the regulation of microglial activation following TBI. Tetramerization or suppression of PKM2 can prevent the pro-inflammatory M1 microglia phenotype and improve cognitive function after TBI.
In vitro antioxidant and anticancer potentials of sulfated polysaccharides from Chnoospora implexa J. Agardh: A Sustainable Approach
Authors: Viswanathan Shyamala , Riyaz S.U. Mohammed , Dhayalan Manikandan , Shah Mohd Asif , Mallik Saurav , Dinesh Rakshi Anuja , Giri Jayant , Natarajane Anandakumar , Mohammad Faruq 
Published: September 2023

Abstract
The synthesis, characterization, and biological efficacy of sulfated polysaccharides namely fucoidan from the thallus of Chnoospora implexa J Agardh which is extracted with 0.1 M HCl and processed by DEAE cellulose to yield portions of fucoidan with molar mass of 20, 30, and 25 kDa, serially. The yields of fucoidan in F1, F2, and F3 are 18.3%, 27.7%, and 15.1%, respectively. F2 has the greatest sulphate concentration (23.7%), followed by F3 (12.1%) and F1 (7.8%). Following this, the fractions in vitro antioxidant activity was determined by employing the superoxide radical-scavenging test and hydroxyl radical-scavenging assay at different doses in g/m. The analysis demonstrated outstanding antioxidant activity for all the three fractions, with the F2 fucoidan showing the highest antioxidant activity. Further analysis of anticancer activity of F2 fucoidan was conducted on human breast cancer (MCF-7) cells using the MTT assay, LDH assay, Phase-contrast fluorescence microscopic analysis, DAPI staining assay and cell cycle analysis. Western Blot analysis, Caspase enzyme activity test and DNA fragmentation assay were used to investigate the apoptosis. From the findings of the analysis, the F2 fraction had an outstanding anticancer effect on MCF-7 cells, with an IC50 value of 500 g/mL.
Influence of post-reformer temperature on the yields and qualities of the products from the TCR® process
Authors: Onyishi Hillary Onyebuchi , Neidel Johannes , Daschner Robert , Apfelbacher Andreas , Hornung Andreas 
Published: September 2023

Abstract
This work investigates the influence of the post-reformer temperature on the yield and quality of the products from the thermo-catalytic reforming (TCR®) process. It seeks to establish an optimisation methodology for achieving desired product yields and qualities by means of adjusting the post-reformer temperature. Five different feedstock materials are studied: straw, bio-stabilised compost, and three feedstock materials, which are mixtures of horse manure, straw, saw dust, and miscanthus in varying proportions. Two sets of experiments, one at a post-reformer temperature of 500°C and the other at 700°C, are carried out on all the feedstock materials. The results show that a greater biogas yield is achieved at the higher post-reformer temperature, but at the expense of the other products: biochar, process water, and biooil. As the post-reformer temperature increases, the carbon and energy yields generally increase for the biogas, but generally decrease for the other products. Moreover, the hydrogen fraction of the biogas is larger in the higher post-reformer temperature trials. In addition, the biooils and process waters produced at the higher post-reformer temperature of 700°C have less impurities, and the biooils are less acidic because of better reforming. However, there is no clear indication of any change in the calorific value of the biooil with increased post-reformer temperature. Conversely, the biochar produced from the lower post-reformer temperature trials have higher calorific values due to less thermal decomposition.
A Network Pharmacology Based Approach to Decipher the Pharmacological Mechanisms of Salvia officinalis in Neurodegenerative Disorders
Authors: Nazir Sheikh Sana , Goel Divya , Vohora Divya 
Published: September 2023

Abstract

The present study aimed to assess the pharmacological mechanism of Salvia officinalis in Neurodegenerative disorders using a network pharmacology approach followed by molecular docking analysis. Phytoconstituents of S.officinalis were obtained from various databases, followed by the screening of active ingredients using the Swiss ADME web tool. Potential targets of active ingredients were identified using PubChem & SwissTargetPrediction. Genes related to Alzheimer’s disease (AD), Parkinson’s disease (PD), and Huntington’s disease (HD) were gathered using online databases. Besides, the correlation between active ingredient targets and disease-associated genes was linked. Networks were constructed, visualized, and analyzed using Cytoscape. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway enrichment analysis were performed using DAVID database. Decisively, Autodock was used for molecular docking. The results of network analysis identified 9 key active ingredients based on topological analysis of the active ingredient - candidate targets network. Also, the analysis revealed a shared target of 9 key active ingredients of S. officinalis that interacted with 133 AD-related targets whereas only 6 active ingredients interacted with 85 and 58 targets of PD and HD respectively. The core genes from the network were AKT1, BACE1, CASP3, MAPK1, TNF, and IL6. Furthermore, GO and KEGG enrichment analysis showed that FOXO, TNF, MAPK, PI3K-Akt, Rap 1, and neurotrophin signalling pathways as enriched, which were further validated by molecular docking suggesting the protective role of S. officinalis in neurodegenerative diseases. Our research reveals the therapeutic benefits of S. officinalis, which might play a crucial role in modulating neurodegenerative diseases.