bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the efficacy of 1-amino-cyclopropane-1-carboxylic acid (ACCA) as a natural compound in strengthening maize resistance against biotic and abiotic stressors: an empirical computational study
Authors: Debnath Sandip , Elgorban Abdallah M. , Bahkali Ali H. , Eswaramoorthy Rajalakshmanan , Verma Meenakshi , Tiwari Pragya , Wang Shifa , Wong Ling Shing , Syed Asad 
Published: August 2023

ObjectiveThis study aims to understand plant-bacteria interactions that enhance plant resistance to environmental stressors, with a focus on maize (Zea mays L.) and its vulnerability to various pathogenic organisms. We examine the potential of 1-amino-cyclopropane-1-carboxylic acid (ACCA) as a compound to boost maize’s resilience against stressors and pathogens.BackgroundWith the growing global population and increased food demand, the study of endophytes, comprising bacteria and fungi, becomes crucial. They reside within plant tissues, affecting their hosts either beneficially or detrimentally. Agrobacteria are of specific interest due to their potential to contribute to developing strategies for plant resistance enhancement.MethodsWe conducted exhaustive research on the defense-related proteins and mechanisms involved in maize-pathogen interactions. The efficacy of ACCA as a natural-compound that could enhance maize’s resistance was examined.ResultsOur research indicates that ACCA, having a binding energy of −9.98 kcal/mol, successfully strengthens maize resistance against pathogenic assaults and drought stress. It plays a crucial protective role in maize plants as they mature, outperforming other ligands in its effectiveness to improve productivity and increase yield.ConclusionApplying ACCA to maize plants has considerable potential in enhancing their resilience and tolerance to stress, proving to be an effective strategy to boost crop yield and productivity. This could help address the increasing global food demand. However, more research is needed to optimize ACCA application methods and to gain a comprehensive understanding of its long-term effects on maize cultivations and the environment.
Anti-quorum sensing potential of selenium nanoparticles against LasI/R, RhlI/R, and PQS/MvfR in Pseudomonas aeruginosa: a molecular docking approach
Authors: Kanak Kanak Raj , Dass Regina Sharmila , Pan Archana 
Published: August 2023

Pseudomonas aeruginosa is an infectious pathogen which has the ability to cause primary and secondary contagions in the blood, lungs, and other body parts of immunosuppressed individuals, as well as community-acquired diseases, such as folliculitis, osteomyelitis, pneumonia, and others. This opportunistic bacterium displays drug resistance and regulates its pathogenicity via the quorum sensing (QS) mechanism, which includes the LasI/R, RhlI/R, and PQS/MvfR systems. Targeting the QS systems might be an excellent way to treat P. aeruginosa infections. Although a wide array of antibiotics, namely, newer penicillins, cephalosporins, and combination drugs are being used, the use of selenium nanoparticles (SeNPs) to cure P. aeruginosa infections is extremely rare as their mechanistic interactions are weakly understood, which results in carrying out this study. The present study demonstrates a computational approach of binding the interaction pattern between SeNPs and the QS signaling proteins in P. aeruginosa, utilizing multiple bioinformatics approaches. The computational investigation revealed that SeNPs were acutely ‘locked’ into the active region of the relevant proteins by the abundant residues in their surroundings. The PatchDock-based molecular docking analysis evidently indicated the strong and significant interaction between SeNPs and the catalytic cleft of LasI synthase (Phe105-Se = 2.7 Å and Thr121-Se = 3.8 Å), RhlI synthase (Leu102-Se = 3.7 Å and Val138-Se = 3.2 Å), transcriptional receptor protein LasR (Lys42-Se = 3.9 Å, Arg122-Se = 3.2 Å, and Glu124-Se = 3.9 Å), RhlR (Tyr43-Se = 2.9 Å, Tyr45-Se = 3.4 Å, and His61-Se = 3.5 Å), and MvfR (Leu208-Se = 3.2 Å and Arg209-Se = 4.0 Å). The production of acyl homoserine lactones (AHLs) was inhibited by the use of SeNPs, thereby preventing QS as well. Obstructing the binding affinity of transcriptional regulatory proteins may cause the suppression of LasR, RhlR, and MvfR systems to become inactive, thereby blocking the activation of QS-regulated virulence factors along with their associated gene expression. Our findings clearly showed that SeNPs have anti-QS properties against the established QS systems of P. aeruginosa, which strongly advocated that SeNPs might be a potent solution to tackle drug resistance and a viable alternative to conventional antibiotics along with being helpful in therapeutic development to cure P. aeruginosa infections.
Pregnancy characteristics and adverse outcomes in offspring of women with epilepsy: a prospective registry study from Mainland China
Authors: Li Rui , Chen Qian , Cao Xing , Yan Hua , Wang Pei , Huang Qun , Li Xiaoyi , Chen Fang , Li Yangchao , Kong Qingxia , Guo Chonglun , Zhang Qi , Hong Qiulei , Liu Yong , Xiong Xiaoli , Han Yanbing , Xiao Xiaohua , Wang Kuiyun , Wu Xunyi , Zhu Xi , Zhang Qing , Chen Lei 
Published: August 2023

ObjectiveThis study aimed to explore the influencing factors of adverse outcomes in the offspring of women with epilepsy (WWE) and to analyze the changes brought about by the epilepsy knowledge popularization campaign in China (EKPCIC).MethodsThis nested case-control study focused on WWE and their offspring from a female epilepsy cohort in mainland China. From January 2009 to August 2022, WWE was prospectively enrolled in 32 study centers. This study aimed to observe the health outcomes of their offspring within 1 year of age. The main outcome measure assessed the health status of the offspring within their first year of age. We aimed to analyze the effects of seizures, anti-seizure medicines (ASMs), and a lack of folic acid supplementation on adverse outcomes in the offspring of WWE and to explore the changes in perinatal management and adverse outcomes of the offspring after dissemination of the EKPCIC in 2015. Additionally, subgroup analyses were conducted to compare seizure control during pregnancy between the valproate and non-valproate groups.ResultsIn total, 781 pregnancies in 695 WWE were included, of which 186 (23.69%) had adverse outcomes. The National Hospital Epilepsy Severity Scale score, number of seizures, status epilepticus, ASM type, and valproate and folic acid doses were associated with a high risk of adverse outcomes. After the EKPCIC, the use of ASMs (P = 0.013) and folic acid (P &lt; 0.001), the seizure-free rate during pregnancy (P = 0.013), and the breastfeeding rate (P &lt; 0.001) increased, whereas the incidence of complications during pregnancy decreased (P = 0.013). However, there was no significant difference in the incidence of adverse outcomes between the analyzed offspring pre-/post-EKPCIC. Additionally, there was no association between the frequency of seizures at different time points during pregnancy and the use of valproate (F = 1.514, P = 0.221).ConclusionPossible factors influencing adverse outcomes in the offspring of WWE include seizures, type and number of ASM usage, and a lack of folic acid supplementation. Although the management of WWE during pregnancy is now more standardized, further efforts are needed to reduce adverse outcomes in offspring.
Neuroinflammatory disorders of the brain and inner ear: a systematic review of auditory function in patients with migraine, multiple sclerosis, and neurodegeneration to support the idea of an innovative ‘window of discovery’
Authors: Di Stadio Arianna , De Luca Pietro , Koohi Nehzat , Kaski Diego , Ralli Massimo , Giesemann Anja , Hartung Hans-Peter , Altieri Marta , Messineo Daniela , Warnecke Athanasia , Frohman Teresa , Frohman Elliot M. 
Published: August 2023

BackgroundHearing can be impaired in many neurological conditions and can even represent a forme fruste of specific disorders. Auditory function can be measured by either subjective or objective tests. Objective tests are more useful in identifying which auditory pathway (superior or inferior) is most affected by disease. The inner ear’s perilymphatic fluid communicates with the cerebrospinal fluid (CSF) via the cochlear aqueduct representing a window from which pathological changes in the contents of the CSF due to brain inflammation could, therefore, spread to and cause inflammation in the inner ear, damaging inner hair cells and leading to hearing impairment identifiable on tests of auditory function.MethodsA systematic review of the literature was performed, searching for papers with case–control studies that analyzed the hearing and migraine function in patients with neuro-inflammatory, neurodegenerative disorders. With data extracted from these papers, the risk of patients with neurological distortion product otoacoustic emission (DPOAE) was then calculated.ResultsPatients with neurological disorders (headache, Parkinson’s disease, and multiple sclerosis) had a higher risk of having peripheral auditory deficits when compared to healthy individuals.ConclusionExisting data lend credence to the hypothesis that inflammatory mediators transmitted via fluid exchange across this communication window, thereby represents a key pathobiological mechanism capable of culminating in hearing disturbances associated with neuroimmunological and neuroinflammatory disorders of the nervous system.
What is the effect of benzodiazepines on deep brain activity? A study in pediatric patients with dystonia
Authors: Hernandez-Martin Estefania , Vidmark Jessica S. L. , MacLean Jennifer A. , Sanger Terence D. 
Published: August 2023

IntroductionBenzodiazepines (BDZs) are commonly used to treat the symptoms of movement disorders; however, deep brain stimulation (DBS) has become a popular treatment for these disorders. Previous studies have investigated the effects of BDZ on cortical activity, no data are currently available on their effects on deep brain regions, nor on these regions’ responses to DBS. How the BDZ affects the thalamus and basal ganglia in dystonia patients remains unknown.MethodsDBS recordings were performed in ventral oralis anterior/posterior (VoaVop), ventral intermediate (VIM) and ventral anterior (VA) thalamic subnuclei, as well as globus pallidus interna (GPi) and subthalamic nucleus (STN). Evoked potentials (EP) and frequency domain analysis were performed to determine the BDZ effect on neural activities compared to the control condition (off-BDZ). Three male pediatric patients with dystonia treated with BDZ and undergoing depth electrode evaluation for clinical targeting were recruited for the study. Stimulation was administered at 25 and 55 Hz frequencies and recordings were simultaneously gathered through pairs of externalized stereoelectroencephalography (sEEG) electrodes. EP amplitude and the effect of stimulation on the frequency spectrum of activity were compared at baseline and following clinical administration of BDZ.ResultsFrequency analysis showed consistent reductions in activity during BDZ treatment in all studied brain regions for all patients. Evoked potential (EP) analysis showed increased subthalamic nucleus (STN) EP amplitude and decreased ventral intermediate (VIM) and STN EP amplitude during BDZ treatment.InterpretationBDZs reduce thalamic and basal ganglia activity in multiple regions and alter the efficacy of transmission between these regions. While the mechanism is unknown our results confirm the known widespread effects of this class of medications and identify specific areas within the motor system that are directly affected.
Ticagrelor versus clopidogrel after intracranial stent angioplasty: a real-world study
Authors: Sun Lili , Wang Shuzhen , Song Yun , Zhao Wei , Zheng Meimei , Yin Hao , Zhang Jun , Meng Yao , Wang Wei , Han Ju 
Published: August 2023

ObjectiveIt was unknown whether a regimen of aspirin plus ticagrelor (aspirin-ticagrelor) attenuates ischemic vascular events without increasing bleeding risk in patients who had undergone intracranial stenting compared with an aspirin plus clopidogrel (aspirin-clopidogrel) regimen. This article compares the efficacy and safety outcomes of the two double antibody regimens in patients undergoing intracranial stent and investigates whether aspirin-ticagrelor could be an alternative antiplatelet agent without increasing the risk of bleeding.MethodsWe conducted a retrospective analysis of our database for patients who had undergone intracranial stenting. From January 2017 to May 2021, consecutive patients treated with endovascular stenting were identified and dichotomized by whether aspirin-ticagrelor or aspirin-clopidogrel were used. The outcomes were compared by propensity score matching.ResultsA total of 340 patients treated with intracranial stent were included. Of all, 132 patients were matched. At 180 days, ischemic vascular events occurred in one patient (1.5%) in the aspirin-ticagrelor group and in six patients (9.1%) in the aspirin-clopidogrel group. Although the absolute incidence of ischemic vascular events [1.5% (1/66) vs. 9.1% (6/66), p = 0.125] was lower in the aspirin-ticagrelor group than in the aspirin-clopidogrel group, there were no statistical differences. There were no statistical differences in ischemic vascular events, ischemic stroke, or death up to 180 days between the two groups. In addition, the incidence of bleeding did not differ. No intracranial hemorrhage or mild bleeding occurred. No statistically significant difference was noted in restenosis and symptomatic restenosis at follow-up.ConclusionIn our study involving patients with acute ischemic stroke who had undergone intracranial stenting, aspirin-ticagrelor was not found to be superior to aspirin-clopidogrel in reducing the rate of ischemic vascular events. The risk of bleeding did not differ between the two groups. Aspirin-ticagrelor does not lower total restenosis and symptomatic restenosis risk at follow-up.
Metabolic syndrome in relation to dietary acid load: a dose–response meta-analysis of observational studies
Authors: Al-Hawary Sulieman Ibraheem Shelash , Mushabab Faris , Abullais Shahabe Saquib , Althomali Raed H. , Saleh Ebraheem Abdu Musad , Alnajjar Serar Nassir , Oudaha Khulood H. , Romero-Parra Rosario Mireya , Hussien Beneen M. , Garousi Nazila 
Published: August 2023

Background and aimSeveral studies have identified that dietary acid load (DAL) may be associated with the odds of metabolic syndrome (MetS); however, the evidence is inconclusive. This dose–response meta-analysis aimed to examine the relation of DAL to MetS.MethodsA systematic literature search was carried out in PubMed and Scopus up to April 2023 for pertinent studies evaluating the relation of DAL scores, including potential renal acid load (PRAL) and net endogenous acid production (NEAP), to the odds of MetS. The odds ratios (OR) with 95% confidence intervals (CI) were pooled using a random-effects meta-analysis to test the association.ResultsEight studies, with an overall sample size of 31,351 participants, were included in this meta-analysis. Higher DAL scores were significantly related to the elevated odds of MetS (NEAP: OR = 1.42, 95%CI = 1.12–1.79; PRAL: OR = 1.76, 95%CI = 1.11–2.78), with significant evidence of heterogeneity across studies. The linear dose–response analysis proposed that a 10 mEq/day elevation in NEAP and PRAL was linked to a 2% (OR = 1.02, 95%CI = 1.001–1.05) and 28% (OR = 1.28, 95%CI = 1.11–1.47) increased odds of MetS, respectively. No non-linear association was observed between MetS and NEAP (P-non-linearity = 0.75) and PRAL (P-non-linearity = 0.92).ConclusionThis study revealed a significant direct relationship between DAL and MetS. Therefore, lower acidogenic diets are suggested for the prevention of MetS.
Proposal for a new N-stage classification system for intrahepatic cholangiocarcinoma
Authors: Liao Shan , Liao Ruizhe , Wu Huaxing , Wang Shijie , Zhou Yanming 
Published: August 2023

BackgroundThe number of metastatic lymph nodes (MLNs) is not considered in the nodal status (N classification) of intrahepatic cholangiocarcinoma (ICC) in the current 8thEdition of the American Joint Committee on Cancer (AJCC) staging system. The aim of this study was to find out the optimal cut-off point based on the number of MLNs and establish a modified AJCC staging system for ICC according to the new N categoryMethodsA total of 675 ICC patients diagnosed between 2004 and 2015 were retrieved from the Surveillance, Epidemiology and End Results (SEER) database. The optimal cut-off value of MLNs affecting survival was determined by X-tile software. The relative discriminative power was assessed by Harrell’s concordance index (C-index) and Akaike information criterion (AIC).ResultsThe proposed new nodal category subdivided patients into three groups (N0, no MLN; N1, 1–3 MLNs; and N2, ≥ 4 MLNs) with significantly different overall survival (P &lt; 0.001). Multivariable analysis revealed that the new nodal category was an independent prognostic factor (P &lt; 0.001). Both the C-index and AIC for our modified staging system were better than those for the 8th AJCC edition (0.574 [95% confidence interval 0.533-0.615] versus 0.570 [95% confidence interval 0.527-0.613], and 853.30 versus 854.21, respectively).ConclusionThe modified AJCC staging system based on the number of MLNs may prove to be a useful alternative for predicting survival of ICC patients in clinical practice.
Clinical features of COVID-19 in Italian outpatient children and adolescents during Parental, Delta, and Omicron waves: a prospective, observational, cohort study
Authors: Di Chiara Costanza , Boracchini Riccardo , Sturniolo Giulia , Barbieri Alessia , Costenaro Paola , Cozzani Sandra , De Pieri Marica , Liberati Cecilia , Zin Annachiara , Padoan Andrea , Bonfante Francesco , Kakkar Fatima , Cantarutti Anna , Donà Daniele , Giaquinto Carlo 
Published: August 2023

IntroductionCOVID-19 features changed with the Omicron variant of SARS-CoV-2 in adults. This study aims to describe COVID-19 symptoms in children and adolescents during the Parental, Delta, and Omicron erasMethodsA single-centre, prospective observational study was conducted on individuals aged 0–20 years attending the University Hospital of Padua (Italy) from April 2020 to December 2022. COVID-19 cases were defined by positive SARS-CoV-2 molecular detection and/or serology; patient/family symptoms and virological positivity were considered to determine the infection onset. Variables were summarized and compared using appropriate tests of descriptive statisticsResultsA total of 509 cases [46% female, median age eight years (IQR: 4–12)] were studied. Three-hundred-eighty-seven (76%), 52 (10%), and 70 (14%) subjects experienced COVID-19 during the Parental, Delta, and Omicron waves, respectively. All subjects developed an asymptomatic/mild COVID-19. Overall, the most frequent symptoms were fever (47%) and rhinitis (21%), which showed a significant increasing incidence from the Parental to Omicron waves (p &lt; 0.001). Conversely, diarrhea was most common during the pre-Omicron eras (p = 0.03). Stratifying symptoms according to the age group, fever, rhinitis, and skin rashes were observed more frequently among infants/toddlers; conversely, fatigue was more common in children older than five years. The duration of symptoms was similar across different SARS-CoV-2 variants of concern (VOCs); conversely, the number of symptoms varied according to the age group (p &lt; 0.0001)DiscussionThis study showed differences in COVID-19 clinical presentation among infants, children, and adolescents and confirmed Omicron infection is more likely to be associated with upper respiratory symptoms. However, further population-based studies are needed to support these findings. In addition, active surveillance will play a crucial role in assessing the disease severity of future VOCs.
Clinical efficacy of IgM-enriched immunoglobulin as adjunctive therapy in neonatal and pediatric sepsis: a systematic review and meta-analysis
Authors: Dinleyici Ener Cagri , Frey Georg , Kola Ermira , Wippermann Ulrike , Bauhofer Artur , Staus Alexander , Griffiths Peter , Azharry Muhamad , Rohsiswatmo Rinawati 
Published: August 2023

BackgroundSepsis is a major cause of mortality and morbidity globally, with around one-quarter of all sepsis-related deaths occurring in children under the age of 5. We conducted a meta-analysis and systematic review of the literature to evaluate the clinical effectiveness of an IgM-enriched immunoglobulin preparation in pediatrics patients and neonates with sepsis.MethodsSystematic searches of PubMed, the Cochrane Library and Embase databases were performed in November 2022, with no date limitations, to identify studies in which IgM-enriched immunoglobulin was used as adjunctive therapy in neonatal and pediatric patients with sepsis.ResultsIn total, 15 studies fulfilled the eligibility criteria, 13 neonatal studies and 2 pediatric studies. Pooled estimates from all studies indicated that mortality rates were significantly lower in patients who received treatment with the IgM-enriched immunoglobulin compared with controls (OR 0.41; 95% CI 0.32–0.55). Further analyses in neonatal studies, alone, showed a significant benefit with longer treatment durations (&gt;3 days) vs. the recommended treatment duration (3 days) (OR 0.32; 95% CI 0.22–0.47) vs. (OR 0.61; 95% CI 0.41–0.92). Treatment with IgM-enriched immunoglobulin was associated with a lower mortality risk compared with controls in prospective studies vs. retrospective analyses (OR 0.37; 95% CI 0.27–0.51) vs. (OR 0.73; 95% CI 0.41–1.30).ConclusionsThis systematic review suggests that adjunctive treatment with IgM-enriched immunoglobulin may reduce the risk of mortality in neonatal and pediatric populations. However, large randomized controlled trials are required to further substantiate and evaluate these findings.
Cost-effectiveness analysis of selexipag for the combined treatment of pulmonary arterial hypertension
Authors: Dong Wenxing , Zhang Zhe , Chu Mingming , Gu Peng , Hu Min , Liu Lulu , Huang Jingbin , Zhang Rong 
Published: August 2023

Objective: Adding selexipag to the combined treatment of endothelin receptor antagonists (ERA) and phosphodiesterase 5 inhibitor (PDE5i) reduces the risk of clinical worsening events in patients with pulmonary arterial hypertension (PAH) but at a considerably higher cost. This study evaluated the cost-effectiveness of adding selexipag to the combined treatment of ERA and PDE5i in patients with PAH from a Chinese healthcare system perspective.Methods: A Markov model was developed to assess costs and quality-adjusted life years (QALYs) of macitentan + tadalafil + selexipag vs. macitentan + tadalafil for the treatment of PAH. Markov states included WHO Functional Class (FC) (I–IV) and death. Transition probabilities were based on data from the TRITON trial. Mortality rates, costs, and utilities were obtained from published literature and public databases.Results: In the base case analysis, compared with macitentan + tadalafil, selexipag + macitentan + tadalafil increased costs ($357,807.588 vs. $116,534.543, respectively) and QALYs (7.234 QALYs vs. 6.666 QALYs, respectively). The resulting incremental cost-effectiveness ratio was $424,746.070 per QALY, which was higher than the willingness-to-pay (WTP) of $38,223.339 per QALY. The results were most sensitive to HR for mortality of patients with FC IV relative to the general population, discount rate, and the cost of selexipag. The probability was greater than 50% for the selexipag + macitentan + tadalafil only if the WTP was more significant than $426,019.200 per QALY.Conclusion: In China, adding selexipag may not be cost-effective for patients with PAH who failed to control their condition after combined treatment of ERA and PDE5i. Results of the analysis can aid discussions on the value and position of selexipag for the combined treatment of PAH.