bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pancreatic enzymes digest obstructive meconium from cystic fibrosis pig intestines
Authors: Gangadharan Nambiar Gopinathan , Gonzalez Szachowicz Sussette , Zirbes Christian F. , Hill Jared J. , Powers Linda S. , Meyerholz David K. , Thornell Ian M. , Stoltz David A. , Fischer Anthony J. 
Published: April 2024

IntroductionMeconium ileus (MI) is a life-threatening obstruction of the intestines affecting ∼15% of newborns with cystic fibrosis (CF). Current medical treatments for MI often fail, requiring surgical intervention. MI typically occurs in newborns with pancreatic insufficiency from CF. Meconium contains mucin glycoprotein, a potential substrate for pancreatic enzymes or mucolytics. Our study aim was to determine whether pancreatic enzymes in combination with mucolytic treatments dissolve obstructive meconium using the CF pig model.MethodsWe collected meconium from CF pigs at birth and submerged it in solutions with and without pancreatic enzymes, including normal saline, 7% hypertonic saline, and the reducing agents N-acetylcysteine (NAC) and dithiothreitol (DTT). We digested meconium at 37 °C with agitation, and measured meconium pigment release by spectrophotometry and residual meconium solids by filtration.Results and discussionIn CF pigs, meconium appeared as a solid pigmented mass obstructing the ileum. Meconium microscopically contained mucus glycoprotein, cellular debris, and bile pigments. Meconium fragments released pigments with maximal absorption at 405 nm after submersion in saline over approximately 8 h. Pancreatic enzymes significantly increased pigment release and decreased residual meconium solids. DTT did not improve meconium digestion and the acidic reducing agent NAC worsened digestion. Pancreatic enzymes digested CF meconium best at neutral pH in isotonic saline. We conclude that pancreatic enzymes digest obstructive meconium from CF pigs, while hydrating or reducing agents alone were less effective. This work suggests a potential role for pancreatic enzymes in relieving obstruction due to MI in newborns with CF.
From desert flora to cancer therapy: systematic exploration of multi-pathway mechanisms using network pharmacology and molecular modeling approaches
Authors: Alblihy Adel 
Published: April 2024

Ovarian cancer, often labeled a “silent killer,” remains one of the most compelling and challenging areas of cancer research. In 2019 alone, a staggering 222,240 new cases of ovarian cancer were reported, with nearly 14,170 lives tragically lost to this relentless disease. The absence of effective diagnostic methods, increased resistance to chemotherapy, and the heterogeneous nature of ovarian cancer collectively contribute to the unfavorable prognosis observed in the majority of cases. Thus, there is a pressing need to explore therapeutic interventions that offer superior efficacy and safety, thereby enhancing the survival prospects for ovarian cancer patients. Recognizing this potential, our research synergizes bioinformatics with a network pharmacology approach to investigate the underlying molecular interactions of Saudi Arabian flora (Onopordum heteracanthum, Acacia ehrenbergiana, Osteospermum vaillantii, Cyperus rotundus, Carissa carandas, Carissa spinarum, and Camellia sinensis) in ovarian cancer treatment. At first, phytoconstituents of indigenous flora and their associated gene targets, particularly those pertinent to ovarian cancer, were obtained from open-access databases. Later, the shared targets of plants and diseases were compared to identify common targets. A protein–protein interaction (PPI) network of predicted targets was then constructed for the identification of key genes having the highest degree of connectivity among networks. Following that, a compound–target protein–pathway network was constructed, which uncovered that, namely, hispidulin, stigmasterol, ascorbic acid, octopamine, cyperene, kaempferol, pungenin, citric acid, d-tartaric acid, beta-sitosterol, (−)-epicatechin gallate, and (+)-catechin demonstrably influence cell proliferation and growth by impacting the AKT1 and VEGFA proteins. Molecular docking, complemented by a 20-ns molecular dynamic (MD) simulation, was used, and the binding affinity of the compound was further validated. Molecular docking, complemented by a 20-ns MD simulation, confirmed the binding affinity of these compounds. Specifically, for AKT1, ascorbic acid showed a docking score of −11.1227 kcal/mol, interacting with residues Ser A:240, Leu A:239, Arg A:243, Arg C:2, and Glu A:341. For VEGFA, hispidulin exhibited a docking score of −17.3714 kcal/mol, interacting with Asn A:158, Val A:190, Gln B:160, Ser A:179, and Ser B:176. To sum up, both a theoretical and empirical framework were established by this study, directing more comprehensive research and laying out a roadmap for the potential utilization of active compounds in the formulation of anti-cancer treatments.
Copaiba oil minimizes inflammation and promotes parenchyma re-epithelization in acute allergic asthma model induced by ovalbumin in BALB/c mice
Authors: Caputo Ludmila de Souza , Alves Carolina de Lima , Laranjeira Inês Martins , Fonseca-Rodrigues Diana , da Silva Filho Ademar Alves , Dias Alberto Carlos Pires , Pinto-Ribeiro Filipa , Pereira Junior Olavo dos Santos , de Paula Ana Claudia Chagas , Nagato Akinori Cardozo , Corrêa José Otávio do Amaral 
Published: April 2024

Introduction: Asthma is a condition of airflow limitation, common throughout the world, with high mortality rates, especially as it still faces some obstacles in its management. As it constitutes a public health challenge, this study aimed to investigate the effect of copaiba oil (e.g., Copaifera langsdorffii), as a treatment resource, at doses of 50 and 100 mg/kg on certain mediators of acute lung inflammation (IL-33, GATA3, FOXP3, STAT3, and TBET) and early mechanisms of lung remodeling (degradation of elastic fiber tissues, collagen deposition, and goblet cell hyperplasia).Methods: Using an ovalbumin-induced acute allergic asthma model in BALB/c mice, we analyzed the inflammatory mediators through immunohistochemistry and the mechanisms of lung remodeling through histopathology, employing orcein, Masson’s trichrome, and periodic acid-Schiff staining.Results: Copaiba oil treatment (CO) reduced IL-33 and increased FOXP3 by stimulating the FOXP3/GATA3 and FOXP3/STAT3 pathways. Additionally, it upregulated TBET, suggesting an additional role in controlling GATA3 activity. In the respiratory epithelium, CO decreased the fragmentation of elastic fibers while increasing the deposition of collagen fibers, favoring epithelial restructuring. Simultaneously, CO reduced goblet cell hyperplasia.Discussion: Although additional research is warranted, the demonstrated anti-inflammatory and re-epithelializing action makes CO a viable option in exploring new treatments for acute allergic asthma.
The cardioprotective potential of selected species of mistletoe
Authors: Olas Beata 
Published: April 2024

Mistletoe is an evergreen woody shrub with stems measuring 30–100 cm. It has leathery, yellowish-green strap-shaped leaves, yellowish-green flowers, and bears typical berries. The most common species is Viscum album L., mainly present in Europe and Asia. It is commonly known as European mistletoe or simply, mistletoe. Scientific interest in mistletoe was awakened in the XX century. Mistletoe, especially V. album L., has historically been used in the treatment and prophylaxis of CVD, with its properties being confirmed in recent studies. This mini-review describes new aspects of the cardioprotective properties of various species of mistletoe, especially V. album L. The effect of oral and subcutaneous application of fresh V. album L. extracts on blood pressure has been studied in various models; while the data suggests that mistletoe may be a promising herbal extract with cardioprotective properties, the species has only been tested in vitro and in vivo, on animals. In addition, it is unclear whether the cardioprotective activity of mistletoe may be due to particular chemical components, as the chemical composition of mistletoe extracts can vary depending on inter alia the time of harvest, extraction method and plant part. Hence, this activity may instead result from synergistic interactions between various secondary metabolites. Therefore, further studies are needed to identify the mechanisms of action of mistletoe compounds on CVDs, and determine their interactions with other cardioprotective drugs, their metabolic mechanisms, pharamacokinetics and adverse effects. More research is also needed to determine the therapeutic doses of active ingredients for use in clinical trials; this would require an accurate understanding of the chemical composition of extracts from different species of mistletoe (not only V. album L.) and from various host trees.
Simulation of a synchronized methodology for MR-based electromechanical property imaging during transcranial electrical stimulation
Authors: Flé Guillaume , Van Houten Elijah , Gilbert Guillaume , Cloutier Guy 
Published: April 2024

Introduction: Recent investigations into the biomechanics of the brain have unveiled alteration in tissue stiffness triggered by external stimuli. For instance, visual stimulation effects can be measured in elasticity images of the cortex generated by functional magnetic resonance elastography (MRE). Such a mechanical characterization method combined with non-invasive brain stimulation (NIBS), a technique that seeks to selectively modulate particular parts of the brain using weak electrical currents, has the potential to influence research on various neurological disorders. In this in silico study, we aimed to elucidate individual and interdependent aspects related to a synchronized biomechanical imaging and non-invasive brain stimulation methodology. Magnetic resonance electrical impedance tomography (MREIT) was incorporated to the pipeline, providing a promising way of evaluating NIBS-induced electrical current patterns in the brain while leveraging MRE and transcranial alternating current stimulation (tACS) experimental settings.Methods: A mouse head model was assembled using open-access atlases to include five anatomical structures: skin/subcutaneous tissue, skull, cerebrospinal fluid (CSF), brain white and grey matters. MRE, tACS, and MREIT experiments were simulated using Comsol Multiphysics with Matlab Livelink. Synthetic MRE and MREIT data were processed using the subzone non-linear inversion and harmonic Bz algorithm, respectively, to reconstruct images of the distributed complex shear modulus and electrical conductivity.Results and Discussion: Lorentz body forces arising from simultaneous MRE and tACS elicited elastic waves of negligible amplitude compared with the extrinsic actuation levels reported in the literature, which allowed accurate reconstructions of the complex shear modulus. Qualitative electrical conductivity maps retrieved by MREIT accurately delineated anatomical regions of the brain model and could be used to recover reasonably accurate distributions of tACS-induced currents. This multi-physics approach has potential for translation to human brain imaging, and may provide more possibilities for the characterization of brain function together than in isolation.
Ensemble machine learning prediction of hyperuricemia based on a prospective health checkup population
Authors: Zhang Yongsheng , Zhang Li , Lv Haoyue , Zhang Guang 
Published: April 2024

Objectives: An accurate prediction model for hyperuricemia (HUA) in adults remain unavailable. This study aimed to develop a stacking ensemble prediction model for HUA to identify high-risk groups and explore risk factors.Methods: A prospective health checkup cohort of 40899 subjects was examined and randomly divided into the training and validation sets with the ratio of 7:3. LASSO regression was employed to screen out important features and then the ROSE sampling was used to handle the imbalanced classes. An ensemble model using stacking strategy was constructed based on three individual models, including support vector machine, decision tree C5.0, and eXtreme gradient boosting. Model validations were conducted using the area under the receiver operating characteristic curve (AUC) and the calibration curve, as well as metrics including accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and F1 score. A model agnostic instance level variable attributions technique (iBreakdown) was used to illustrate the black-box nature of our ensemble model, and to identify contributing risk factors.Results: Fifteen important features were screened out of 23 clinical variables. Our stacking ensemble model with an AUC of 0.854, outperformed the other three models, support vector machine, decision tree C5.0, and eXtreme gradient boosting with AUCs of 0.848, 0.851 and 0.849 respectively. Calibration accuracy as well as other metrics including accuracy, specificity, negative predictive value, and F1 score were also proved our ensemble model’s superiority. The contributing risk factors were estimated using six randomly selected subjects, which showed that being female and relatively younger, together with having higher baseline uric acid, body mass index, γ-glutamyl transpeptidase, total protein, triglycerides, creatinine, and fasting blood glucose can increase the risk of HUA. To further validate our model’s applicability in the health checkup population, we used another cohort of 8559 subjects that also showed our ensemble prediction model had favorable performances with an AUC of 0.846.Conclusion: In this study, the stacking ensemble prediction model for HUA was developed, and it outperformed three individual models that compose it (support vector machine, decision tree C5.0, and eXtreme gradient boosting). The contributing risk factors were identified with insightful ideas.
Effects of anodic transcranial direct current stimulation combined with physical training on the performance of elite swimmers
Authors: Yang Xipeng , Wu Jinlong , Tang Yucheng , Ren Zhanbing 
Published: April 2024

ObjectiveAnodal transcranial direct current stimulation (a-tDCS) has been used to improve athletic performance in various populations; however, its role in improving performance in elite athletes is unclear. This study aimed to investigate the effects of a-tDCS on athletic performance in elite athletes.MethodsWe used a single-blind, randomized controlled experimental design and recruited 24 national-level freestyle swimmers from China. All athletes were randomly divided into two groups; the experimental group underwent a-tDCS (current 2 mA for 20 min) combined with physical training, and the control group underwent a-tDCS sham stimulation combined with physical training. The physical training program was identical in the experimental and control groups. The intervention period was 6 weeks, with five weekly sessions of 110 min each, consisting of 20 min of a-tDCS and 90 min of physical training. Base strength, explosive strength, aerobic endurance, and anaerobic endurance were measured in the athletes before and after the intervention.ResultsThe results were as follows. 1) Basic strength: There was a significant improvement in 5RM pull-ups in the experimental and control groups before and after the intervention (p &lt; 0.05). 2) Explosive strength: There was a significant improvement in vertical jump and swimming start distance into the water in the experimental and control groups before and after the intervention (p &lt; 0.05). 3) Aerobic endurance: There was no significant improvement in the experimental and control groups before and after the intervention. 4) Anaerobic endurance: There was a significant improvement in 400 m running performance in the experimental and control groups before and after the intervention (p &lt; 0.05).ConclusionCompared to physical training alone, a-tDCS combined with physical training can better improve the athletic performance of high-level swimmers, especially in basic strength, explosive strength, and aerobic endurance.
Coordination and modularization: the experience of the joint prevention and control mechanism to COVID emergencies in China
Authors: Yan Jingjing 
Published: April 2024

BackgroundThe integration of disparate emergency resources and the improvement of emergency response teamwork are the underlying trends and shared requirements for building resilience in an era of multiple global public health crises.ObjectiveThis study investigated the emergency response with emergency collaboration networks of each functional module and the overall Joint Epidemic Prevention and Control Mechanism (JPCM) network in China’s COVID outbreak prevention and control.MethodsThe study employed a scholarly framework of “the integration of JPCM coordination and emergency collaborative modularization” to explore the attributes of JPCM using social network analysis. The data were obtained from administrative records from JPCM’s official website, spanning January 2020 to December 2022.ResultsThe study examined the JPCM coordination and found several functional working modules of JPCM, such as Interrupt Spread, Manage Supply, Medical Rescue, Restore Work and Production, and Implement Responsibility modules. The network structure indicators showed that the Manage Supply module had the most extensive network connectivity, the shortest communication distance, and the most consistent collaboration. The E-I index of the overall JPCM network and the Manage Supply network were − 0.192 and − 0.452, respectively (at p &lt; 0.001 and p &lt; 0.05), indicating more internal relationships than external relationships. The E-I index of the Medical Rescue and Implement Responsibility collaboration networks were 0.122 and 0.147, respectively (at p &lt; 0.001 and p &lt; 0.05), indicating more external relationships than internal relationships. The QAP regression analysis showed that the most vital driver on the overall JPCM network was the Interrupt Spread module, followed by the Implement Responsibility and Medical Rescue modules.DiscussionThe Interrupt Spread module initiated emergency coordination with most departments and agencies. The Manage Supply module ensured the flow of medical supplies and survival essentials, while the Medical Rescue module addressed the core aspects of the health emergency response. The Restore Work and Production module repaired the halt in production and livelihoods caused by the outbreak, strengthening and developing emergency coordination and roles across emergency organizations. The Implement Responsibility module provided more heterogeneous emergency response resources for the overall JPCM coordination, complementing the COVID cross-organizational emergency response coordination.ConclusionThe study on the JPCM case in China improves public health emergency management and aids informed decision-making.
Blueprint for destigmatizing depression and increasing openness to treatment among adolescents using brief social contact-based videos: a qualitative study
Authors: DiGiovanni Madeline , Jankowski Samantha E. , Dixon Lisa B. , Martin Andrés , Amsalem Doron 
Published: April 2024

BackgroundDepression is a major public health concern for adolescents, who exhibit low rates of connection to care despite significant needs. Although barriers to help-seeking such as stigma are well documented, interventions to address stigma and to increase help-seeking behavior are insufficient. Dissemination of short videos in social media offer a promising approach, but designing effective stimuli requires better insight into adolescents’ perspectives of their own experiences, barriers, and possible interventions.MethodsWe conducted 20 semi-structured interviews with adolescents recruited online via RecruitMe, a Columbia University clinical research registry, to explore their perceptions of depression stigma, barriers to care, the role of schools, and the role of brief video interventions. Thematic analysis guided our analytic approach.ResultsWe developed a model consisting of three major domains: (1) Barriers to Help-Seeking, which depicts participants debating their locus of control, naming social, parental, and peer stigma, and acknowledging systemic barriers; (2) Importance of School Systems, in which participants elaborated on the role of schools filling unmet needs and the importance of being taken care of; and (3) Role of Social Media Videos, characterized by adolescents who are seeking legitimacy, finding cultural authenticity, and working towards creating an accessible blueprint for better mental healthcare.DiscussionWe provide insights into adolescents’ perceptions of help-seeking for depression and what nuances they would hope to see reflected in future interventions, most notably school-based interventions and peer social media videos. Our study offers a steppingstone towards the creation of brief, social contact-based video interventions focused on destigmatizing depression and promoting openness to treatment among adolescents.
Re-evaluating the gender gap: a cross-sectional analysis of accepted American Academy of Neurology annual meeting abstracts in 2020 and 2021
Authors: Kim Minseon , Kim Youngran , Sharrief Anjail Z. , Nguyen Thy P. 
Published: April 2024

Background and objectivePrior studies reveal that invited speaker panels, editorial boards, authors of practice guidelines, and senior authors of published articles are disproportionately male in the neurology field. We aimed to analyze a gender gap in authorship of accepted abstracts to the American Academy of Neurology annual meetings in 2020 and 2021.Design/methodsThis is a cross-sectional study evaluating the proportions of female first and senior abstract authors in 2020 and 2021. Abstracts were reviewed manually (n = 3,211 in 2020; n = 2,178 in 2021). Data were collected regarding the gender of first and senior authors, subspecialties, and origin of research (USA, international, or corporate-affiliated). Then, we compared the percentages of female first and senior authors in the 2 years to assess for any short-term effects of the COVID-19 pandemic.ResultsAccepted abstracts with female first and senior authors comprised 46%, 34% in 2020, and the same in 2021, without change. Female senior authors had a significantly higher proportion of female first authors than their male senior author counterparts. The analysis of subspecialties with more than 100 abstracts showed the lowest percentages of female senior authors was oncology (24.7%), sleep (25.5%), headache (28.7%), and cerebrovascular disease (29%) in 2020. Cerebrovascular disease (29%) and behavioral neurology (24.7%) had the lowest percentage of female senior authors in 2021. In the analysis of the origin of research, corporate-affiliated authors had the lowest percentages of female first (34 and 36%) and senior authors (22.6 and 27.6%).ConclusionThe gender gap in neurology was reaffirmed in regards to female senior authorship overall and in subgroups of abstracts including cerebrovascular disease, headache, behavioral neurology, sleep, oncology, and corporate-affiliated research.