bluuebunny/crossref_metadata_2025_split huggingface dataset:
HD_BPMDS: a curated binary pattern multitarget dataset of Huntington’s disease–targeting agents
Authors: Stefan Sven Marcel , Pahnke Jens , Namasivayam Vigneshwaran 
Published: November 2023

AbstractThe discovery of both distinctive lead molecules and novel drug targets is a great challenge in drug discovery, which particularly accounts for orphan diseases. Huntington’s disease (HD) is an orphan, neurodegenerative disease of which the pathology is well-described. However, its pathophysiological background and molecular mechanisms are poorly understood. To date, only 2 drugs have been approved on the US and European markets, both of which address symptomatic aspects of this disease only. Although several hundreds of agents were described with efficacy against the HD phenotype in in vitro and/or in vivo models, a successful translation into clinical use is rarely achieved. Two major impediments are, first, the lack of awareness and understanding of the interactome—the sum of key proteins, cascades, and mediators—that contributes to HD initiation and progression; and second, the translation of the little gained knowledge into useful model systems. To counteract this lack of data awareness, we manually compiled and curated the entire modulator landscape of successfully evaluated pre-clinical small-molecule HD-targeting agents which are annotated with substructural molecular patterns, physicochemical properties, as well as drug targets, and which were linked to benchmark databases such as PubChem, ChEMBL, or UniProt. Particularly, the annotation with substructural molecular patterns expressed as binary code allowed for the generation of target-specific and -unspecific fingerprints which could be used to determine the (poly)pharmacological profile of molecular-structurally distinct molecules.
Inhibitory potential of rutin and rutin nano-crystals against Helicobacter pylori, colon cancer, hemolysis and Butyrylcholinesterase in vitro and in silico
Authors: Qanash Husam , Al-Rajhi Aisha M. H. , Almashjary Majed N. , Basabrain Ammar A. , Hazzazi Mohannad S. , Abdelghany Tarek M. 
Published: November 2023

AbstractDespite the vital activity of many compounds, they lack that effectiveness due to their low solubility in water. Unfortunately, for this reason, rutin often leads to low tissue permeability and insufficient bioavailability, which has greatly limited its pharmacological utility. Therefore, the present investigation is designed to overcome this problem by formulating the rotin to rotin nanocrystals (RNCs) with studying their some pharmacological applications in vitro and in silico. RNCs were created via the ultrasonication approach and showed a spherical shape via Transmission electron microscopy with a mean particle size of 27 nm. RNCs reflected inhibitory action against Helicobacter pylori with an inhibition zone (IZ) of 22.67 mm compared to rutin (IZ of 18 mm) and standard control (IZ of 19.5 mm). RNCs exhibited less minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) (7.8 µg/mL) than rutin (62.5 µg/mL). The MBC/MIC index of rutin and RNCs indicated their bactericidal properties. RNCs were more acutely (92.12%) than rutin (85.43%) for inhibition the H. pylori biofilm formation. A promising half maximal inhibitory concentration (IC50) (6.85 µg/mL) was recorded using RNCs for urease inhibition compared to the IC50 value of rutin (97.8 µg/mL). The activity of rutin and RNCs was tested against cancer cells of human colon cancer (HT-29) and normal Vero cells. IC50 values of RNCs were less 168.23 ± 1.15 µg/mL and 297.69 ± 4.23 µg/mL than the IC50 values of rutin 184.96 ± 4.33 µg/mL and 335.31 ± 2.02 µg/mL against HT-29 cells and normal Vero cells, respectively. Different percentages (72.2, 77.3, and 81.9%) of hemolysis inhibition were recorded using RNCs, but 63.6, 68.9, 73.6, and 80.6% were obtained using rutin at 600, 800, and 1000 µg/mL, respectively. Butyrylcholinesterase (BChE) inhibition % was documented at a lower IC50 value for RNCs (12.74 µg/mL) than the IC50 of rutin (18.15 µg/mL). The target molecule underwent molecular docking research against H. pylori [Protein Data Bank (PDB) code: 4HI0], HT-29 cells (PDB code: 2HQ6), and BChE (PDB code: 6EMI) in order to enhance the interactions between rutin and the chosen receptors and to estimate its molecular operating environment (MOE) affinity scoring. Rutin has predicted strong binding interactions and potent activity against the examined proteins 4HI0, 2HQ6, and 6EMI with low binding scores of − 7.47778 kcal/mol, − 7.68511 kcal/mol, and − 9.50333 kcal/mol, respectively.
Aedes aegypti microbiome composition covaries with the density of Wolbachia infection
Authors: Pascar Jane , Middleton Henry , Dorus Steve 
Published: November 2023

Abstract
Background
Wolbachia is a widespread bacterial endosymbiont that can inhibit vector competency when stably transinfected into the mosquito, Aedes aegypti, a primary vector of the dengue virus (DENV) and other arboviruses. Although a complete mechanistic understanding of pathogen blocking is lacking, it is likely to involve host immunity induction and resource competition between Wolbachia and DENV, both of which may be impacted by microbiome composition. The potential impact of Wolbachia transinfection on host fitness is also of importance given the widespread release of mosquitos infected with the Drosophila melanogaster strain of Wolbachia (wMel) in wild populations. Here, population-level genomic data from Ae. aegypti was surveyed to establish the relationship between the density of wMel infection and the composition of the host microbiome.

Results
Analysis of genomic data from 172 Ae. aegypti females across six populations resulted in an expanded and quantitatively refined, species-level characterization of the bacterial, archaeal, and fungal microbiome. This included 844 species of bacteria across 23 phyla, of which 54 species were found to be ubiquitous microbiome members across these populations. The density of wMel infection was highly variable between individuals and negatively correlated with microbiome diversity. Network analyses revealed wMel as a hub comprised solely of negative interactions with other bacterial species. This contrasted with the large and highly interconnected network of other microbiome species that may represent members of the midgut microbiome community in this population.

Conclusion
Our bioinformatic survey provided a species-level characterization of Ae. aegypti microbiome composition and variation. wMel load varied substantially across populations and individuals and, importantly, wMel was a major hub of a negative interactions across the microbiome. These interactions may be an inherent consequence of heightened pathogen blocking in densely infected individuals or, alternatively, may result from antagonistic Wolbachia-incompatible bacteria that could impede the efficacy of wMel as a biological control agent in future applications. The relationship between wMel infection variation and the microbiome warrants further investigation in the context of developing wMel as a multivalent control agent against other arboviruses.
Association between personality traits and smoking cessation among Chinese adults
Authors: Jin Weiyun , Xian Bensong , Zhao Longlong , Li Changle 
Published: November 2023

Abstract
Background
Although the tobacco epidemic is one of the greatest public health threats, the smoking cessation rate among Chinese adults is considerably lower. Personality information may indicate which treatments or interventions are more likely to be effective. China is the largest producer and consumer of tobacco worldwide. However, little is known about the association between smoking cessation and personality traits in China.

Aim
This study aimed to examine the association between successful smoking cessation and personality traits among Chinese adults.

Methods
This cross-sectional study used data from the 2018 China Family Panel Studies. Probit regression models were employed to analyze the association between successful smoking cessation and personality traits stratified by sex.

Results
Lower scores for neuroticism (Coef.=-0.055, p < 0.1), lower scores for extraversion (Coef.=-0.077, p < 0.05), and higher scores for openness to experience (Coef.=0.045, p < 0.1) predicted being a successful male quitter after adjusting for demographics. Moreover, lower scores for conscientiousness (Coef.=-0.150, p < 0.1) predicted being a successful female quitter after adjusting for demographics.

Conclusion
The empirical findings suggested that among Chinese men, lower levels of neuroticism, lower levels of extraversion, and higher levels of openness to experience were associated with a higher likelihood of smoking cessation. Moreover, lower levels of conscientiousness were associated with successful smoking cessation among Chinese women. These results showed that personality information should be included in smoking cessation interventions.
Prenatal ethanol exposure and changes in fetal neuroendocrine metabolic programming
Authors: Liu Liang , Wen Yinxian , Ni Qubo , Chen Liaobin , Wang Hui 
Published: November 2023

AbstractPrenatal ethanol exposure (PEE) (mainly through maternal alcohol consumption) has become widespread. However, studies suggest that it can cause intrauterine growth retardation (IUGR) and multi-organ developmental toxicity in offspring, and susceptibility to various chronic diseases (such as neuropsychiatric diseases, metabolic syndrome, and related diseases) in adults. Through ethanol’s direct effects and its indirect effects mediated by maternal-derived glucocorticoids, PEE alters epigenetic modifications and organ developmental programming during fetal development, which damages the offspring health and increases susceptibility to various chronic diseases after birth. Ethanol directly leads to the developmental toxicity of multiple tissues and organs in many ways. Regarding maternal-derived glucocorticoid-mediated IUGR, developmental programming, and susceptibility to multiple conditions after birth, ethanol induces programmed changes in the neuroendocrine axes of offspring, such as the hypothalamus-pituitary-adrenal (HPA) and glucocorticoid-insulin-like growth factor 1 (GC-IGF1) axes. In addition, the differences in ethanol metabolic enzymes, placental glucocorticoid barrier function, and the sensitivity to glucocorticoids in various tissues and organs mediate the severity and sex differences in the developmental toxicity of ethanol exposure during pregnancy. Offspring exposed to ethanol during pregnancy have a “thrifty phenotype” in the fetal period, and show “catch-up growth” in the case of abundant nutrition after birth; when encountering adverse environments, these offspring are more likely to develop diseases. Here, we review the developmental toxicity, functional alterations in multiple organs, and neuroendocrine metabolic programming mechanisms induced by PEE based on our research and that of other investigators. This should provide new perspectives for the effective prevention and treatment of ethanol developmental toxicity and the early prevention of related fetal-originated diseases.
Use of patient-reported outcomes (PRO) data to complement exposure–response analysis in early clinical cancer drug development
Authors: Xia Huiming , Booth Brian P. , Wang Yaning , Fan Chunling , Bhatnagar Vishal , Kluetz Paul , Fourie Zirkelbach Jeanne 
Published: November 2023

Abstract
Background
This proof-of-concept retrospective case study investigated whether patient-reported outcomes (PRO) instruments, designed to capture symptomatic adverse event data, could identity a known exposure–response (ER) relationship for safety characterized in an original FDA analysis of an approved anti-cancer agent. PRO instruments have been designed to uniquely quantify the tolerability aspects of exposure-associated symptomatic adverse events. We explored whether standard ER analyses of clinician-reported safety data for symptomatic adverse events could be complemented by ER analysis using PRO data that capture and quantify the tolerability aspects of these same symptomatic adverse events.

Methods
Exposure-associated adverse event data for diarrhea were analyzed in parallel in 120 patients enrolled in a clinical trial using physician reported Common Terminology Criteria for Adverse Events (CTCAE) and patient-reported symptomatic adverse event data captured by the National Cancer Institute’s (NCI) PRO Common Terminology Criteria for Adverse Events (PRO-CTCAE) instrument. Comparative ER analyses of diarrhea were conducted using the same dataset. Results from the CTCAE and PRO-CTCAE ER analyses were assessed for consistency with the ER relationship for diarrhea established in the original NDA using a 750-patient dataset. The analysis was limited to the 120-patient subset with parallel CTCAE and PRO-CTCAE assessments.

Results
Within the same 120-patient dataset, ER analysis using dense, longitudinal PRO-CTCAE-derived data was sensitive to identify the known ER relationship for diarrhea, whereas the standard CTCAE based ER analysis was not.

Conclusions
ER analysis using PRO assessed symptomatic adverse event data may be a sensitive tool to complement traditional ER analysis. Improved identification of relationships for safety, by including quantification of the tolerability aspect of symptomatic adverse events using PRO instruments, may be useful to improve the sensitivity of exposure response analysis to support early clinical trial dosage optimization strategies, where decision making occurs within limited small patient datasets.
Antiviral activities of three Streptomyces spp. against Zucchini yellow mosaic virus (ZYMV) infecting squash (Cucurbita pepo L.) plants
Authors: Ghanem Gamal A. M. , Mahmoud Ahmed M. A. , Kheder Ahmed A. , Gebily Doha A. S. , Osamy Asmaa 
Published: November 2023

Abstract
Background
Zucchini yellow mosaic virus (ZYMV) is the major devastating disease worldwide, which leads to substantial economic losses (up to 100%) to yield and fruits quality produced of squash plants. Application of agro-pesticides is efficient and incompatible with organic agriculture and reportedly has harmful effects on human health and ecosystem. Nowadays, Streptomyces spp., a rich source of potential bioactive secondary metabolites, is extensively used to manage various biotic stresses for sustainable agriculture and considered to be eco-friendly.

Results
An isolate of ZYMV was isolated from squash plants and identified based on biological and molecular characterization using RT-PCR for several genes, i.e., coat protein gene (CP), DAG, P1 and P3 coding regions in the virus RNA, and then, nucleotide sequences were compared to other isolates submitted in GenBank having accession numbers, i.e., OM925548.1, OM925549.1, OM925550.1 and OM925551.1, respectively. Phylogenetic trees of CP, DAG, P1 and P3 sequences compared to other ZYMV nucleotide sequences presented in the GenBank. In order to determine new efficient substances elicitors derived from Streptomyces spp. to control ZYMV, greenhouse trials were designed with seven treatments including culture broth of three Streptomyces spp. (S. sampsonii, S. rochei and S. griseus) individually or in combinations. Early application of Streptomyces spp. revealed potent antiviral activity against ZYMV infection, inhibited virus replication and promoted plant growth as well as induced systemic resistance. Moreover, physiological stress markers as indicators for systemic acquired resistance were distinguished via significantly enhanced proline, phenols and defense-related enzymes, i.e., catalase, superoxide dismutase and glutathione peroxidase by culture broth treatments, despite the presence of infection. Real-time qPCR assay was a more reliable and accurate detection for quantification ZYMV than conventional PCR. The results revealed that the three Streptomyces spp. novel biocontrol agents produced Behenic alcohol (Docosanol) which provided clues to be potential antiviral mechanisms capable to down-regulate P1 gene expression responsible for virus replication and movement from cell to cell to induce systemic infection as well as safe eco-friendly candidates for the controlling approaches against plant viral pathogens.

Conclusion
Results suggest that the three Streptomyces spp. provided clues as a novel biocontrol agent having potential antiviral with protective activity and eco-friendly alternative pesticides for managing plant viruses.
Fully Endoscopic Microvascular Decompression for Trigeminal Neuralgia Caused by Vertebrobasilar Artery: A Case Series Review: 2-Dimensional Operative Video
Authors: Sun Jinxing , Wang Jiwei , Jia Junheng , Cao Zexin , Li Zhenke , Zhang Chao , Guo Xing , Wu Qianqian , Li Weiguo , Ma Xiangyu 
Published: November 2023

BACKGROUND AND OBJECTIVE:
Microvascular decompression (MVD) is the most definitive and preferred surgical treatment for trigeminal neuralgia (TN). Treatment of TN caused by the vertebrobasilar artery (VBA) has been reported to be challenging and less satisfactory in complications and recurrence. Endoscopy has been implemented to provide a comprehensive view of neurovascular conflicts and minimize brain tissue stretch injury while exploring the trigeminal nerve. However, there are few retrospective studies on the treatment of TN caused by VBA by fully endoscopic microvascular decompression (E-MVD). This article aimed to illustrate the safety and efficacy of E-MVD for TN caused by the VBA.

METHODS:
Clinical data for 26 patients with TN caused by the VBA who underwent E-MVD from 2019 to 2022 were retrospectively analyzed. The characteristics of vertebrobasilar-associated TN were summarized. The safety and efficacy of E-MVD for vertebrobasilar-associated TN were estimated based on the analysis of intraoperative manipulation, postoperative symptom relief, and complications.

RESULTS:
Intraoperatively, the vertebrobasilar artery was regarded as a direct offending vessel in all 26 patients with TN, the vertebral artery in 18 (69.23%) and the basilar artery in 10 (38.46%). In addition to the vertebrobasilar artery, other vessels involved included the superior cerebellar artery in 12 patients, anterior inferior cerebellar artery in 9, posterior inferior cerebellar artery in 1, and veins in 4. All patients underwent E-MVD, and TN was entirely resolved in 26 (100%) patients immediately postoperatively. During the follow-up period of 12–45 months, no recurrence or serious complications were found. There were no serious postoperative complications, such as cerebellar swelling, intracranial hemorrhage, or death.

CONCLUSION:
E-MVD for vertebrobasilar-associated TN is effective and safe.
Got (Optimal) Milk? Pooling Donations in Human Milk Banks with Machine Learning and Optimization
Authors: Chan Timothy C. Y. , Mahmood Rafid , O’Connor Deborah L. , Stone Debbie , Unger Sharon , Wong Rachel K. , Zhu Ian Yihang 
Published: November 2023

Problem definition: Human donor milk provides critical nutrition for millions of infants who are born preterm each year. Donor milk is collected, processed, and distributed by milk banks. The macronutrient content of donor milk is directly linked to infant brain development and can vary substantially across donations, which is why multiple donations are typically pooled together to create a final product. Approximately half of all milk banks in North America do not have the resources to measure the macronutrient content of donor milk, which means pooling is done heuristically. For these milk banks, an approach is needed to optimize pooling decisions. Methodology/results: We propose a data-driven framework combining machine learning and optimization to predict macronutrient content of donations and then optimally combine them in pools, respectively. In collaboration with our partner milk bank, we collect a data set of milk to train our predictive models. We rigorously simulate milk bank practices to fine-tune our optimization models and evaluate operational scenarios such as changes in donation habits during the COVID-19 pandemic. Finally, we conduct a year-long trial implementation, where we observe the current nurse-led pooling practices followed by our intervention. Pools created by our approach meet clinical macronutrient targets approximately 31% more often than the baseline, although taking 60% less recipe creation time. Managerial implications: This is the first paper in the broader blending literature that combines machine learning and optimization. We demonstrate that such pipelines are feasible to implement in a healthcare setting and can yield significant improvements over current practices. Our insights can guide practitioners in any application area seeking to implement machine learning and optimization-based decision support. History: This paper has been accepted as part of the 2023 Manufacturing & Service Operations Management Practice-Based Research Competition. Supplemental Material: The e-companion is available at https://doi.org/10.1287/msom.2022.0455 .
The role of the clinical nurse specialist in stoma care: a scoping review
Authors: Bird Andrew , Burch Jennie , Thorpe Gabrielle 
Published: November 2023

Aim: Rapidly evolving roles in nursing require exploration and description. This review aims to examine the role of the clinical nurse specialist (CNS) in stoma care from the UK perspective. Design: A scoping review was undertaken using the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Data were synthesised using content analysis to derive meaning units and themes. Data sources: Three electronic databases were used to conduct the search: Embase, AMED and Ovid Medline. Additional sources identified through the reference lists of included studies and guidelines were also included. Methods: Two reviewers undertook the search for articles that described the role of the stoma care CNS in the UK. Any disagreements were to be resolved through discussion. Results: Seven papers met the eligibility criteria. Analysis resulted in 184 unique meaning units. Meaning units were grouped into themes reflecting the four pillars of advanced practice: advanced clinical practice; leadership; facilitation of education and learning; and evidence, research and development. The fewest meaning units were attributed to the evidence theme (n=13) and the most related to advanced clinical practice (n=107) such as having specialist knowledge and skills to manage complications. Conclusion: The stoma care CNS role reflects the four pillars of advanced practice. These practitioners are valuable, carrying out a complex role that involves high-level, specialist decision-making skills. The results from this scoping review could be useful in service development; they will be used to inform the Association of Stoma Care Nurses UK modified Delphi consensus to examine the views of stoma care CNS practitioners.