bluuebunny/crossref_metadata_2025 huggingface dataset:
Proteomics as a Metrological Tool to Evaluate Genome Annotation Accuracy Following De Novo Genome Assembly: A Case Study Using the Atlantic Bottlenose Dolphin (Tursiops truncatus)
Authors: Neely Benjamin A. , Ellisor Debra L. , Davis W. Clay
Published: August 2023

The last decade has witnessed dramatic improvements in whole-genome sequencing capabilities coupled to drastically decreased costs, leading to an inundation of high-quality de novo genomes. For this reason, the continued development of genome quality metrics is imperative. Using the 2016 Atlantic bottlenose dolphin NCBI RefSeq annotation and mass spectrometry-based proteomic analysis of six tissues, we confirmed 10,402 proteins from 4711 protein groups, constituting nearly one-third of the possible predicted proteins. Since the identification of larger proteins with more identified peptides implies reduced database fragmentation and improved gene annotation accuracy, we propose the metric NP10, which attempts to capture this quality improvement. The NP10 metric is calculated by first stratifying proteomic results by identifying the top decile (or 10th 10-quantile) of identified proteins based on the number of peptides per protein and then returns the median molecular weight of the resulting proteins. When using the 2016 versus 2012 Tursiops truncatus genome annotation to search this proteomic data set, there was a 21% improvement in NP10. This metric was further demonstrated by using a publicly available proteomic data set to compare human genome annotations from 2004, 2013 and 2016, which showed a 33% improvement in NP10. These results demonstrate that proteomics may be a useful metrological tool to benchmark genome accuracy, though there is a need for reference proteomic datasets across species to facilitate the evaluation of new de novo and existing genome.
Comparison of Growth Performance and Plasma Metabolomics between Two Sire-Breeds of Pigs in China
Authors: Xie Zhongwei , Gan Mailin , Du Junhua , Du Gao , Luo Yi , Liu Bin , Zhu Kangping , Cheng Wenqiang , Chen Lei , Zhao Ye , Niu Lili , Wang Yan , Wang Jingyong , Zhu Li , Shen Linyuan
Published: August 2023

The Yorkshire pigs, renowned for their remarkable growth rate, low feed conversion ratio (FCR), and high meat production, emerge as a novel preference for paternal breeding. In this study, we found that purebred paternal Yorkshire pigs (PY) surpass the purebred Duroc breed in terms of growth rate. Specifically, purebred PY attain a weight of 100 kg at an earlier age compared to purebred Duroc (Male, 145.07 vs. 162.91; Female, 145.91 vs. 167.57; p-value < 0.01). Furthermore, different hybrid combinations suggest that offspring involving purebred PY exhibit superior growth performance. Compared with purebred Duroc, the offspring of purebred PY have an earlier age in days (173.23 vs. 183.54; p-value < 0.05) at the same slaughter weight. The changes of plasma metabolites of 60-day-old purebred boars in the two sire-breeds showed that 1335 metabolites in plasma were detected. Compared with Duroc, 28 metabolites were down-regulated and 49 metabolites were up-regulated in PY. Principal component analysis (PCA) discerned notable dissimilarities in plasma metabolites between the two sire-breeds of pigs. The levels of glycerol 3-phosphate choline, cytidine, guanine, and arachidonic acid increased significantly (p-value < 0.05), exerting an impact on their growth and development. According to our results, PY could be a new paternal option as a terminal sire in three-way cross system.
Understanding Spatial Autocorrelation: An Everyday Metaphor and Additional New Interpretations
Authors: Griffith Daniel A.
Published: August 2023

An enumeration of spatial autocorrelation’s (SA’s) polyvalent forms occurred nearly three decades ago. Attempts to conceive and disseminate a clearer explanation of it employ metaphors seeking to better relate SA to a student’s or spatial scientist’s personal knowledge databank. However, not one of these uses the jigsaw puzzle metaphor appearing in this paper, which exploits an analogy between concrete visual content organization and abstract map patterns of attributes. It not only makes SA easier to understand, which furnishes a useful pedagogic tool for teaching novices and others about it, but also discloses that many georeferenced data should contain a positive–negative SA mixture. Empirical examples corroborate this mixture’s existence, as well as the tendency for marked positive SA to characterize remotely sensed and moderate (net) positive SA to characterize socio-economic/demographic, georeferenced data.
Potential Factors Associated with Healthcare Utilization for Balance Problems in Community-Dwelling Adults within the United States: A Narrative Review
Authors: Kapur Shweta , Sakyi Kwame S. , Lohia Prateek , Goble Daniel J.
Published: August 2023

Falls are the leading cause of mortality and chronic disability in elderly adults. There are effective fall prevention interventions available. But only a fraction of the individuals with balance/dizziness problems are seeking timely help from the healthcare system. Current literature confirms the underutilization of healthcare services for the management of balance problems in adults, especially older adults. This review article explores factors associated with healthcare utilization as guided by the Andersen Healthcare Utilization Model, a framework frequently used to explore the factors leading to the use of health services. Age, sex, race/ethnicity, BMI, and comorbidities have been identified as some of the potential predisposing factors; socioeconomic status, health insurance, and access to primary care are the enabling and disabling factors; and severity of balance problem, perceived illness, and its impact on daily activities are the factors affecting need for care associated with healthcare utilization for balance or dizziness problems. Knowledge about these barriers can help direct efforts towards improved screening of vulnerable individuals, better access to care, and education regarding effective fall prevention interventions for those who are at risk for underutilization. This can aid in timely identification and management of balance problems, thereby reducing the incidence of falls.
A Comparative Study on Deep Learning Models for COVID-19 Forecast
Authors: Guo Ziyuan , Lin Qingyi , Meng Xuhui
Published: August 2023

The COVID-19 pandemic has led to a global health crisis with significant morbidity, mortality, and socioeconomic disruptions. Understanding and predicting the dynamics of COVID-19 are crucial for public health interventions, resource allocation, and policy decisions. By developing accurate models, informed public health strategies can be devised, resource allocation can be optimized, and virus transmission can be reduced. Various mathematical and computational models have been developed to estimate transmission dynamics and forecast the pandemic’s trajectories. However, the evolving nature of COVID-19 demands innovative approaches to enhance prediction accuracy. The machine learning technique, particularly the deep neural networks (DNNs), offers promising solutions by leveraging diverse data sources to improve prevalence predictions. In this study, three typical DNNs, including the Long Short-Term Memory (LSTM) network, Physics-informed Neural Network (PINN), and Deep Operator Network (DeepONet), are employed to model and forecast COVID-19 spread. The training and testing data used in this work are the global COVID-19 cases in the year of 2021 from the Center for Systems Science and Engineering (CSSE) at Johns Hopkins University. A seven-day moving average as well as the normalization techniques are employed to stabilize the training of deep learning models. We systematically investigate the effect of the number of training data on the predicted accuracy as well as the capability of long-term forecast in each model. Based on the relative L2 errors between the predictions from deep learning models and the reference solutions, the DeepONet, which is capable of learning hidden physics given the training data, outperforms the other two approaches in all test cases, making it a reliable tool for accurate forecasting the dynamics of COVID-19.
A Cluster Randomised Control Trial of an SMS-Based Intervention to Promote Antenatal Health amongst Pregnant Women in a Remote, Highland Region of Vietnam
Authors: Dao Binh Thi Thanh , Trinh Huong Thi , Lai Phuong Hoai , Elsner Tahli , Kane Sumit , Nguyen Liem
Published: August 2023

Although Vietnam has achieved significant improvements in maternal, newborn, and children’s health, outcomes for ethnic minorities living in remote mountainous areas continue to lag. Interventions that leverage the extensive mobile networks in the country have been proposed as a way to overcome some of these challenges. A cluster randomised controlled trial (cRCT) was conducted to assess the effectiveness of an intervention comprising tailored SMS messages for promoting antenatal care knowledge and behaviours amongst ethnic minority (EM) pregnant women. The cRCT was implemented across eight intervention communes (640 women) and four control communes (315 women) in Northern Vietnam. Maternal health-related knowledge and behaviour outcomes and self-rated health status were assessed through questionnaires administered pre- and post-intervention. Difference-in-difference and logistic regression analysis found that the intervention group showed significant improvements in awareness about the danger signs of pregnancy and the importance of nutritional supplements. Significant improvements were seen in antenatal care-seeking behaviours and the intake of nutritional supplements. Mobile messaging-based behaviour change interventions can significantly improve maternal health-related knowledge and care-seeking amongst women residing in marginalised, hard-to-reach populations.
Knowledge about COVID-19 between Children and Adolescents with and without High Intellectual Abilities
Authors: López-Aymes Gabriela , Valadez Sierra María de los Dolores , Borges África , Ortiz Coronel Grecia Emilia , Flores-Bravo Juan Francisco , Rodríguez-Cervantes Celia Josefina , Ruvalcaba-Romero Norma A.
Published: August 2023

Among the characteristics within people with high intellectual abilities, some that stand out are a better handling of information, asynchronous development, high awareness, and sensibility. Therefore, our goal was to learn if, due to these characteristics, the children and adolescents with high intellectual abilities have a better understanding and comprehension about COVID-19 compared to those with average intellectual abilities. A qualitative study was conducted at the beginning of the lockdown with 649 children with and without high intellectual abilities. An online questionnaire was used and three open questions were analyzed with the ALCESTE software. The results showed that both groups had a similar handling of the information regarding COVID-19. Despite this, in the high ability group there is a greater social concern, which coincides with some characteristics associated with a more developed moral conscience. The results are then discussed in terms of the importance of designing actions that allow us to adequately follow the control and intervention strategies, as well as to propose improvements in the communication of relevant information before diverse crises to which the child population may be exposed.
Building an Electronic Medical Record System Exchanged in FHIR Format and Its Visual Presentation
Authors: Liu Tz-Jie , Lee Hsu-Ting , Wu Fan
Published: August 2023

Currently, the Taiwan Electronic Medical Record Exchange Center uses the Clinical Document Architecture (CDA) framework, which is based on the international medical standard. The CDA R2 standard, defined in 2005, is used for cross-institution retrieval of electronic medical records (Ministry of Health and Welfare, Information Department, 2021). However, CDA R2 only supports the exchange of clinical documents and is limited to the XML format. Due to the lack of a standardized framework for medical data exchange in Taiwan, different standards and specifications result in different data interface methods between systems, requiring customization for each system by healthcare institutions or the government. The inconsistency in data formats requires healthcare institutions and the government to spend more time on data parsing and mapping, resulting in slow integration of medical data. In this study, we simulated healthcare institutions using Fast Healthcare Interoperability Resources (FHIR) for medical information exchange and utilized the exchanged medical information to create a dynamic dashboard to assist healthcare professionals in making medical decisions. To ensure information security, we employed Hyper Text Transfer Protocol Secure (HTTPS) for secure transmission, which encrypts the transmitted medical record data using the Transport Layer Security (TLS) protocol, preventing deliberate interception and tampering of medical record data between the two systems. Finally, to test the load and performance of static and dynamic resources and web applications, we conducted a system performance evaluation using Apache JMeter. The results of this study demonstrate that replacing the gateway of the Electronic Medical Record Exchange Center with an FHIR server effectively reduces the time and cost spent by developers on data format conversion while also mitigating the information security risks associated with the previous VPN solution. Additionally, by utilizing dynamic charts, healthcare professionals are assisted in making medical decisions.
Identification of Loci for Four Important Agronomic Traits in Loose-Curd Cauliflower Based on Genome-Wide Association Studies
Authors: Zhang Xiaoli , Wen Zhenghua , Jiang Hanmin , Niu Guobao , Liu Lili , Yao Xingwei , Sun Deling , Shan Xiaozheng
Published: August 2023

Cauliflower is a nutritious vegetable with inflorescences that are specialized to form the edible organs called curds. Uncovering key genes underlying important traits is crucial for the genetic improvement of this important crop. However, the genetic basis of many important agronomic traits, including curd performance and plant architecture in cauliflower, remains unclear. GWASs have proved to be powerful tools to study agronomic traits in many crops. To reveal the genetic basis of four important agronomic traits, namely, the main stem height (MSH), purplish curd (PC), external leaf wing (ELW) and weight of a single curd (WSC), we selected 220 core accessions of loose-curd cauliflower for resequencing, phenotypic investigation and GWAS. The approach revealed significant novel loci. We detected several significant associations: on C02 for MSH and PC, on C06 for ELW and on C01 for WSC. More interestingly, we identified a significant single-peak signal for the weight of a single curd (WSC), an important yield trait, and within this signal interval, we identified the BOB01G136670 gene with five SNPs encoding nonsynonymous mutations in the CDS region; these mutations resulted in two haplotypes with significant differences in curd weight. The weight of a single curd was significantly increased in the varieties with the BOB01G136670 Hap1 allele compared to those with BOB01G136670 Hap2. BOB01G136670 was highly conserved with the homologous genes that encode serine carboxypeptidase and belong to the S10 family in other species, including GS5, which functions as a positive regulator of grain size in rice, wheat and maize. Additionally, BOB01G136670 was highly expressed specifically at the curd enlargement stage, with low or even no expression at all in other tissues and stages, indicating that BOB01G136670 is a plausible candidate gene for WSC. Overall, this study identified genomic loci for four important agronomic traits that are relevant for accelerating biological breeding and the improvement of cauliflower varieties.
Post-Natal Short-Term Home Visiting Programs: An Overview and a Volunteers-Based Program Pilot
Authors: Gross Manos Daphna , Bader Noha Gaber , Cohen Ayala
Published: August 2023

Post-natal home visits have been shown to be one of the most effective ways to prevent child maltreatment and reduce risks among children. Unfortunately, these programs tend to be expensive and thus not accessible or practical in many contexts. To address this problem, this paper reviews the literature on home visits conducted shortly after giving birth, considering different types of programs and their outcomes, while focusing on short-term and volunteer-based programs, two approaches that can answer the gap in accessibility. It then introduces a new, innovative, short-term, home visiting program that was developed in Israel. This post-natal program is uniquely structured as volunteer-based to allow it to be culturally informed and inexpensive and therefore accessible to municipalities. The paper describes how experts in the field developed the program and how the volunteers were trained. It elaborates on the protocol for the three defined home visits, each with a specific focus: (1) preventing risks at home, (2) providing parents with emotional support and tools to deal with stress, and (3) connecting them to community resources. We detail the pilot implementation process and some of the challenges that arise. Finally, we describe the design of the evaluation study that is currently collecting data in an Arab town in the north of Israel, with a final discussion on insights gained thus far from the overall process in light of the literature.
Mitigating Sarcopenia with Diet and Exercise
Authors: Shefflette Alex , Patel Neel , Caruso John
Published: August 2023

Sarcopenia is the loss of muscle mass and function from aging, inactivity, or disuse. It is a comorbidity to numerous conditions that exacerbates their severity and adversely impacts activities of daily living. While sarcopenia now receives more attention from the medical community, people with sarcopenia as a comorbidity nevertheless still sometimes receives less attention than other presenting diseases or conditions. Inevitable doctors’ visits or hospital stays for those with sarcopenia as a comorbidity have far higher healthcare costs than those without this condition, which imposes a greater financial burden on the medical insurance and healthcare industries. This review offers information and guidance on this topic. Treatments for sarcopenia include dietary, exercise, and pharmacological interventions. Yet, the latter treatment is only recommended in extreme cases as it may evoke numerous side effects and has little support in the scientific literature. Currently, a more holistic approach, with an emphasis on lifestyle modification, to reduce the likelihood of sarcopenia is examined. The current review discusses dietary and exercise interventions to limit the occurrence and severity of sarcopenia. References cited in this review conformed to the Declaration of Helsinki requirements for the use of human research subjects. Most of this review’s references (~97%) came from a PubMed search that spanned from 1997 to 2023. Search terms included “sarcopenia” OR “muscle wasting” OR “geriatrics”; OR “ageing”; and AND “diet” OR “exercise”. In addition, papers relevant or supportive of the topic as well as those considered seminal were included in the review. Over 96% of the references were peer-reviewed articles.
Dental Caries, Tooth Loss and Quality of Life of Individuals Exposed to Social Risk Factors in Northeast Brazil
Authors: de Albuquerque Luísa Simões , de Queiroz Raiana Gurgel , Abanto Jenny , Strazzeri Bönecker Marcelo José , Soares Forte Franklin Delano , Sampaio Fábio Correia
Published: August 2023

This study aimed to investigate the impact of dental caries and tooth loss on oral health-related quality of life (OHRQoL) in socioeconomically disadvantaged people. A population-based, cross-sectional survey was conducted in 28 cities at social risk in Northeast Brazil. All permanent residents aged 12, 15–19, 35–44, and 65–74 years were eligible, and 3063 were included. Participants answered a questionnaire on socioeconomic status, beliefs, and behaviors. Trained local dentists performed oral clinical examinations during home visits. Caries and tooth loss were evaluated using the decayed, missing, and filled teeth (DMFT) index and OHRQoL was evaluated using the Oral Health Impact Profile-14 (OHIP-14). Poisson regression analysis was performed to assess the relationship between individual domains, OHIP-14 scores, dental caries, tooth loss, and socioeconomic/demographic characteristics. Mean DMFT (standard deviation) scores were 2.68 (4.01), 4.84 (4.30), 15.35 (7.26), and 26.72 (8.03) for groups aged 12, 15–19, 35–44, and 65–74 years, respectively. Most participants (70%) were partially edentulous and 13% were completely edentulous. Caries and tooth loss significantly increased with age and impacted OHRQoL. Physical pain (5.8%) and psychological discomfort (5.8%) were the most commonly reported on the OHIP-14. Untreated caries (prevalence ratio (PR), 1.54; 95% confidence interval (CI), 1.37–1.72) and edentulism (PR, 1.29; 95% CI, 1.08–1.53) had a significant negative impact on OHRQoL. Income, level of education, sex, age, and oral hygiene habits were also related to OHRQoL. There was a high prevalence of dental caries and edentulism in all age groups except 12-year-olds. OHRQoL was negatively impacted by these oral conditions across the lifespan, with a trend towards more negative scores and higher impact in older adults.
F-Actin Organization and Epidermal Cell Morphogenesis in the Brown Alga Sargassum vulgare
Authors: Panteris Emmanuel , Pappas Dimitris
Published: August 2023

The ordinary epidermal cells of various vascular plants are characterized by wavy anticlinal wall contours. This feature has not yet been reported in multicellular algal species. Here, we found that, in the leaf-like blades of the brown alga Sargassum vulgare, epidermal cells exhibit prominent waviness. Initially, the small meristodermal cells exhibit straight anticlinal contour, which during their growth becomes wavy, in a pattern highly reminiscent of that found in land plants. Waviness is restricted close to the external periclinal wall, while at inner levels the anticlinal walls become thick and even. The mechanism behind this shape relies on cortical F-actin organization. Bundles of actin filaments are organized, extending under the external periclinal wall and connecting its junctions with the anticlinal walls, constituting an interconnected network. These bundles define the sites of local thickening deposition at the anticlinal/periclinal wall junctions. These thickenings are interconnected by cellulose microfibril extensions under the external periclinal wall. Apart from the wavy anticlinal contour, outward protrusions also arise on the external periclinal wall, thus the whole epidermis exhibits a quilted appearance. Apart from highlighting a new role for F-actin in cell shaping, the comparison of this morphogenetic mechanism to that of vascular plants reveals a case of evolutionary convergence among photosynthetic organisms.
Circular RNA hsa_circ_0049657 as a Potential Biomarker in Non-Small Cell Lung Cancer
Authors: Ren Yihong , Zhao Yuxin , Shan Yanan , Li Sixuan , Su Nan , Cui Zhigang , Yin Zhihua
Published: August 2023

Non-small cell lung cancer (NSCLC) is a common lung disorder. In this study, we applied bioinformatics methods to analyze and investigate the role of the NFIX gene in NSCLC. Hsa_circ_0049657 is derived from the NFIX gene, this research aimed to verify the potential role of hsa_circ_0049657 in the development of NSCLC. The results suggested that NFIX was downregulated in most cancers. In addition, the NFIX expression in lung adenocarcinoma (LUAD) was associated with the clinicopathological stage. In LUAD, NFIX expression was associated with the degree of infiltration of most immune cells. The expression levels of hsa_circ_0049657 were significantly lower in cancerous tissues than in paracancerous tissues. Moreover, the results showed that hsa_circ_0049657 expression was downregulated in NSCLC cells. After overexpression of hsa_circ_0049657, the proliferation and migration ability of NSCLC cells were significantly inhibited and the level of apoptosis was increased. We could suppress the proliferation and invasion abilities and promote apoptosis of NSCLC cells by up-regulating hsa_circ_0049657, which might be a potential biomarker for NSCLC.
Hypertrophic Cardiomyopathy versus Storage Diseases with Myocardial Involvement
Authors: Burban Anna , Pucyło Szymon , Sikora Aleksandra , Opolski Grzegorz , Grabowski Marcin , Kołodzińska Agnieszka
Published: August 2023

One of the main causes of heart failure is cardiomyopathies. Among them, the most common is hypertrophic cardiomyopathy (HCM), characterized by thickening of the left ventricular muscle. This article focuses on HCM and other cardiomyopathies with myocardial hypertrophy, including Fabry disease, Pompe disease, and Danon disease. The genetics and pathogenesis of these diseases are described, as well as current and experimental treatment options, such as pharmacological intervention and the potential of gene therapies. Although genetic approaches are promising and have the potential to become the best treatments for these diseases, further research is needed to evaluate their efficacy and safety. This article describes current knowledge and advances in the treatment of the aforementioned cardiomyopathies.
Multi-Omics Analysis of NCI-60 Cell Line Data Reveals Novel Metabolic Processes Linked with Resistance to Alkylating Anti-Cancer Agents
Authors: Rushing Blake R.
Published: August 2023

This study aimed to elucidate the molecular determinants influencing the response of cancer cells to alkylating agents, a major class of chemotherapeutic drugs used in cancer treatment. The study utilized data from the National Cancer Institute (NCI)-60 cell line screening program and employed a comprehensive multi-omics approach integrating transcriptomic, proteomic, metabolomic, and SNP data. Through integrated pathway analysis, the study identified key metabolic pathways, such as cysteine and methionine metabolism, starch and sucrose metabolism, pyrimidine metabolism, and purine metabolism, that differentiate drug-sensitive and drug-resistant cancer cells. The analysis also revealed potential druggable targets within these pathways. Furthermore, copy number variant (CNV) analysis, derived from SNP data, between sensitive and resistant cells identified notable differences in genes associated with metabolic changes (WWOX, CNTN5, DDAH1, PGR), protein trafficking (ARL17B, VAT1L), and miRNAs (MIR1302-2, MIR3163, MIR1244-3, MIR1302-9). The findings of this study provide a holistic view of the molecular landscape and dysregulated pathways underlying the response of cancer cells to alkylating agents. The insights gained from this research can contribute to the development of more effective therapeutic strategies and personalized treatment approaches, ultimately improving patient outcomes in cancer treatment.
Conservative Tryptophan Residue in the Vicinity of an Active Site of the M15 Family l,d-Peptidases: A Key Element in the Catalysis
Authors: Mikoulinskaia Galina V. , Prokhorov Dmitry A. , Chernyshov Sergei V. , Sitnikova Daria S. , Arakelian Arina G. , Uversky Vladimir N.
Published: August 2023

Bioinformatics analysis of the sequences of orthologous zinc-containing peptidases of the M15_C subfamily revealed the presence of a conserved tryptophan residue near the active site, which is not involved in the formation of the protein core. Site-directed mutagenesis of this Trp114/109 residue using two representatives of the family, l-alanoyl-d-glutamate peptidases of bacteriophages T5 (calcium-activated EndoT5) and RB49 (EndoRB49, without ion regulation) as examples, and further analysis of the 1H NMR spectra of the mutants showed that a decrease in the volume of the W → F → A residue leads to changes in the hydrophobic core and active center of the protein, and also decreases the affinity for regulatory Ca2+ in the EndoT5 mutants. The inactive T5W114A mutant lacks the ability to bind the substrate. In general, the conserved Trp114/109 residue, due to the spatial restrictions of its side chain, significantly affects the formation of the catalytically active form of the enzyme and is critical for catalysis.
Synthesis, X-ray Structure, Hirshfeld, DFT Conformational, Cytotoxic, and Anti-Toxoplasma Studies of New Indole-Hydrazone Derivatives
Authors: Hassan Eman M. , Soliman Saied M. , Moneer Esraa A. , Hagar Mohamed , Barakat Assem , Haukka Matti , Rasheed Hanaa
Published: August 2023

The hydrazones 3a–c, were synthesized from the reaction of indole-3-carbaldehyde and nicotinic acid hydrazide, isonicotinic acid hydrazide, and benzoic acid hydrazide, respectively. Their structures were confirmed using FTIR, 1HNMR, and 13CNMR spectroscopic techniques. Exclusively, hydrazones 3b and 3c were confirmed using single crystal X-ray crystallography to exist in the Eanti form. With the aid of DFT calculations, the most stable configuration of the hydrazones 3a–c in gas phase and in nonpolar solvents (CCl4 and cyclohexane) is the ESyn form. Interestingly, the DFT calculations indicated the extrastability of the EAnti in polar aprotic (DMSO) and polar protic (ethanol) solvents. Hirshfeld topology analysis revealed the importance of the N…H, O…H, H…C, and π…π intermolecular interactions in the molecular packing of the studied systems. Distribution of the atomic charges for the hydrazones 3a–c was presented. The hydrazones 3a–c showed a polar character where 3b has the highest polarity of 5.7234 Debye compared to the 3a (4.0533 Debye) and 3c (5.3099 Debye). Regarding the anti-toxoplasma activity, all the detected results verified that 3c had a powerful activity against chronic toxoplasma infection. Compound 3c showed a considerable significant reduction percent of cyst burden in brain homogenates of toxoplasma infected mice representing 49%.
Design of Cyclic Peptides Targeting Protein–Protein Interactions Using AlphaFold
Authors: Kosugi Takatsugu , Ohue Masahito
Published: August 2023

More than 930,000 protein–protein interactions (PPIs) have been identified in recent years, but their physicochemical properties differ from conventional drug targets, complicating the use of conventional small molecules as modalities. Cyclic peptides are a promising modality for targeting PPIs, but it is difficult to predict the structure of a target protein–cyclic peptide complex or to design a cyclic peptide sequence that binds to the target protein using computational methods. Recently, AlphaFold with a cyclic offset has enabled predicting the structure of cyclic peptides, thereby enabling de novo cyclic peptide designs. We developed a cyclic peptide complex offset to enable the structural prediction of target proteins and cyclic peptide complexes and found AlphaFold2 with a cyclic peptide complex offset can predict structures with high accuracy. We also applied the cyclic peptide complex offset to the binder hallucination protocol of AfDesign, a de novo protein design method using AlphaFold, and we could design a high predicted local-distance difference test and lower separated binding energy per unit interface area than the native MDM2/p53 structure. Furthermore, the method was applied to 12 other protein–peptide complexes and one protein–protein complex. Our approach shows that it is possible to design putative cyclic peptide sequences targeting PPI.
Ganglionated Plexus Ablation Procedures to Treat Vasovagal Syncope
Authors: Yarkoni Merav , Rehman Wajeeh ur , Bajwa Ata , Yarkoni Alon , Rehman Afzal ur
Published: August 2023

Vasovagal syncope (VVS) refers to a heterogeneous group of conditions whereby the cardiovascular reflexes normally controlling the circulation are interrupted irregularly in response to a trigger, resulting in vasodilation, bradycardia, or both. VVS affects one-third of the population at least once in their lifetime or by the age of 60, reduces the quality of life, and may cause disability affecting certain routines. It poses a considerable economic burden on society, and, despite its prevalence, there is currently no proven pharmacological treatment for preventing VVS. The novel procedure of ganglionated plexus (GP) ablation has emerged rapidly in the past two decades, and has been proven successful in treating syncope. Several parameters influence the success rate of GP ablation, including specific ablation sites, localization and surgical techniques, method of access, and the integration of other interventions. This review aims to provide an overview of the existing literature on the physiological aspects and clinical effectiveness of GP ablation in the treatment of VVS. Specifically, we explore the association between GPs and VVS and examine the impact of GP ablation procedures as reported in human clinical trials. Our objective is to shed light on the therapeutic significance of GP ablation in eliminating VVS and restoring normal sinus rhythm, particularly among young adults affected by this condition.
Photocatalytic and Photothermal Antimicrobial Mussel-Inspired Nanocomposites for Biomedical Applications
Authors: Soto-Garcia Luis F. , Guerrero-Rodriguez Ingrid D. , Hoang Luu , Laboy-Segarra Samantha Lauren , Phan Ngan T. K. , Villafuerte Enrique , Lee Juhyun , Nguyen Kytai T.
Published: August 2023

Bacterial infection has traditionally been treated with antibiotics, but their overuse is leading to the development of antibiotic resistance. This may be mitigated by alternative approaches to prevent or treat bacterial infections without utilization of antibiotics. Among the alternatives is the use of photo-responsive antimicrobial nanoparticles and/or nanocomposites, which present unique properties activated by light. In this study, we explored the combined use of titanium oxide and polydopamine to create nanoparticles with photocatalytic and photothermal antibacterial properties triggered by visible or near-infrared light. Furthermore, as a proof-of-concept, these photo-responsive nanoparticles were combined with mussel-inspired catechol-modified hyaluronic acid hydrogels to form novel light-driven antibacterial nanocomposites. The materials were challenged with models of Gram-negative and Gram-positive bacteria. For visible light, the average percentage killed (PK) was 94.6 for E. coli and 92.3 for S. aureus. For near-infrared light, PK for E. coli reported 52.8 and 99.2 for S. aureus. These results confirm the exciting potential of these nanocomposites to prevent the development of antibiotic resistance and also to open the door for further studies to optimize their composition in order to increase their bactericidal efficacy for biomedical applications.
Hepatocellular Carcinoma: Past and Present Challenges and Progress in Molecular Classification and Precision Oncology
Authors: Coffin Philip , He Aiwu
Published: August 2023

Hepatocellular carcinoma (HCC) is one of the most common solid tumor malignancies in the world and represents roughly 90% of all primary malignancies of the liver. The most common risk factors for HCC include hepatitis B virus, hepatitis C virus, alcohol, and increasingly, fatty liver. Most HCC is diagnosed at advanced stages, excluding the possibility of curative resection, which leaves systemic therapy as the only treatment option. However, given the extreme mutational diversity and heterogenous nature of HCC, efforts to develop new targeted systemic therapies were largely unsuccessful until recently. HCC pathogenesis is thought to be a multistage process driven by a wide array of nonmutually exclusive driver mutations accompanied by many passenger mutations, with the average tumor possessing approximately 40 genomic aberrations. Over the past two decades, several efforts to categorize HCC prognostically and therapeutically according to different molecular subclassifications with the intent to guide treatment and identify drug targets have emerged, though, no single consensus has been reached. Recent breakthroughs in drug development have greatly expanded treatment options, but the ideal of uniting each patient’s unique HCC with a targeted systemic therapy remains elusive.
A Switch from Latent to Typical Infection during Pectobacterium atrosepticum—Tobacco Interactions: Predicted and True Molecular Players
Authors: Tsers Ivan , Parfirova Olga , Moruzhenkova Varvara , Petrova Olga , Gogoleva Natalia , Vorob’ev Vladimir , Gogolev Yuri , Gorshkov Vladimir
Published: August 2023

Phytopathogenic microorganisms, being able to cause plant diseases, usually interact with hosts asymptomatically, resulting in the development of latent infections. Knowledge of the mechanisms that trigger a switch from latent to typical, symptomatic infection is of great importance from the perspectives of both fundamental science and disease management. No studies to date have compared, at the systemic molecular level, the physiological portraits of plants when different infection types (typical and latent) are developed. The only phytopathogenic bacterium for which latent infections were not only widely described but also at least fluently characterized at the molecular level is Pectobacterium atrosepticum (Pba). The present study aimed at the comparison of plant transcriptome responses during typical and latent infections caused by Pba in order to identify and then experimentally verify the key molecular players that act as switchers, turning peaceful plant-Pba coexistence into a typical infection. Based on RNA-Seq, we predicted plant cell wall-, secondary metabolism-, and phytohormone-related genes whose products contributed to the development of the disease or provided asymptomatic plant—Pba interactions. By treatment tests, we confirmed that a switch from latent to typical Pba-caused infection is determined by the plant susceptible responses mediated by the joint action of ethylene and jasmonates.
Genetic Variation in miR-27a Is Associated with Fluoropyrimidine-Associated Toxicity in Patients with Dihydropyrimidine Dehydrogenase Variants after Genotype-Guided Dose Reduction
Authors: Medwid Samantha , Wigle Theodore J. , Ross Cameron , Kim Richard B.
Published: August 2023

Dihydropyrimidine dehydrogenase (DPYD) is the rate-limiting enzyme involved in the metabolism of fluoropyrimidine-based chemotherapy. However, single-nucleotide variants (SNVs) in DPYD only partially explain fluoropyrimidine-induced toxicity. The expression of DPYD has previously been shown to be regulated by microRNA-27a (miR-27a) and a common miR-27a SNV (rs895819) has been associated with an increased risk of toxicity in patients harboring a DPYD variant who received standard fluoropyrimidine dosing. We investigated if the miR-27a rs895819 SNV was associated with toxicity in DPYD wildtype patients and carriers of DPYD variants who received a reduced dose. The regulation of DPYD using miR-27a was investigated in HepG2 cells utilizing a miR-27a mimic. miR-27a overexpression decreased DPYD mRNA expression compared to control cells (p < 0.0001). In a cohort of patients that received pre-emptive DPYD genotyping, 45 patients had a DPYD variant and 180 were wildtype. Patients heterozygous for rs895819 had an increased risk of toxicity, which was seen in both patients who were wildtype for DPYD variants (OR (95%CI) = 1.99 (1.00–3.99)) and DPYD variant carriers (OR (95%CI) = 8.10 (1.16–86.21)). Therefore, miR-27a rs895819 may be a clinically relevant predictor of fluoropyrimidine-associated toxicities. Furthermore, toxicity was more profound in DPYD variant carriers, even after DPYD genotype-guided dose reduction. This suggests that patients may benefit from miR-27a genotyping to guide fluoropyrimidine dosing.
Clinical Application of In Vitro Tests for COVID-19 Vaccine Delayed Hypersensitivity Diagnostics
Authors: Romantowski Jan , Górska Aleksandra , Zieliński Maciej , Trzonkowski Piotr , Rucka Karolina , Niedoszytko Marek
Published: August 2023

Drug hypersensitivity reactions can be classified as immediate or delayed. While diagnostic options for immediate reactions are well developed and standardized, delayed reactions (in many cases type IV according to Gell and Coombs) are a challenge for allergy work-up. In recent years, some in vitro markers have been proposed and used for delayed reactions, such as contact dermatitis. Primary strategy: Avoidance is difficult to achieve, especially for COVID-19 vaccinations, when immunity against infection is extremely important. The aim of our study was to evaluate the application of in vitro delayed hypersensitivity tests in COVID-19 vaccines. Seven patients with a positive history of severe delayed drug allergy were enrolled. Vein blood was collected to stimulate cells with the tested vaccines (Comirnaty, Janssen, Spikevax) and excipients with the assessment of CD40L, CD69, IL-2, IL-4, IL-6, IL-10, IFNgamma, TNFalfa, and intracellular markers: granulysin and INFgamma. In addition, basophile activation tests, patch tests, skin prick tests, and intradermal tests were performed with the tested vaccine. Finally, the decision was made to either administer a vaccine or resign. Two out of seven patients were considered positive for drug hypersensitivity in the in vitro test according to the high vaccine stimulation index measured with CD69 (6.91 and 12.18) and CD40L (5.38 and 15.91). All patch tests, BATs, and skin tests were negative. Serum interleukin measurements were inconclusive as the impact of the vaccine itself on the immunity system was high. Intracellular markers gave uncertain results due to the lack of stimulation on the positive control. CD69 and CD40L could be reliable in vitro markers for delayed hypersensitivity to COVID-19 vaccines. Patch tests, skin tests, BATs, and serum interleukins did not confirm their usefulness in our study.
Role of Bacteria-Derived Flavins in Plant Growth Promotion and Phytochemical Accumulation in Leafy Vegetables
Authors: Ajeethan Nivethika , Yurgel Svetlana N. , Abbey Lord
Published: August 2023

Sinorhizobium meliloti 1021 bacteria secretes a considerable amount of flavins (FLs) and can form a nitrogen-fixing symbiosis with legumes. This strain is also associated with non-legume plants. However, its role in plant growth promotion (PGP) of non-legumes is not well understood. The present study evaluated the growth and development of lettuce (Lactuca sativa) and kale (Brassica oleracea var. acephala) plants inoculated with S. meliloti 1021 (FL+) and its mutant 1021ΔribBA, with a limited ability to secrete FLs (FL−). The results from this study indicated that inoculation with 1021 significantly (p < 0.05) increased the lengths and surface areas of the roots and hypocotyls of the seedlings compared to 1021ΔribBA. The kale and lettuce seedlings recorded 19% and 14% increases in total root length, respectively, following inoculation with 1021 compared to 1021ΔribBA. A greenhouse study showed that plant growth, photosynthetic rate, and yield were improved by 1021 inoculation. Moreover, chlorophylls a and b, and total carotenoids were more significantly (p < 0.05) increased in kale plants associated with 1021 than non-inoculated plants. In kale, total phenolics and flavonoids were significantly (p < 0.05) increased by 6% and 23%, respectively, and in lettuce, the increments were 102% and 57%, respectively, following 1021 inoculation. Overall, bacterial-derived FLs enhanced kale and lettuce plant growth, physiological indices, and yield. Future investigation will use proteomic approaches combined with plant physiological responses to better understand host-plant responses to bacteria-derived FLs.
Role of the Nrf2 Signaling Pathway in Ovarian Aging: Potential Mechanism and Protective Strategies
Authors: Gao Xiaofan , Wang Bo , Huang Yibao , Wu Meng , Li Yuting , Li Yinuo , Zhu Xiaoran , Wu Mingfu
Published: August 2023

The ovary holds a significant role as a reproductive endocrine organ in women, and its aging process bears implications such as menopause, decreased fertility, and long-term health risks including osteoporosis, cardiovascular disorders, and cognitive decline. The phenomenon of oxidative stress is tightly linked to the aging metabolic processes. More and more studies have demonstrated that oxidative stress impacts both physiologic and pathologic ovarian aging, and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway plays a crucial role in regulating the antioxidant response. Furthermore, various therapeutic approaches have been identified to ameliorate ovarian aging by modulating the Nrf2 pathway. This review summarizes the important role of the Nrf2/ Kelch-like ECH-associated protein 1 (Keap1) signaling pathway in regulating oxidative stress and influencing ovarian aging. Additionally, it highlights the therapeutic strategies aimed at targeting the Nrf2/Keap1 pathway.
Striking Neurochemical and Behavioral Differences in the Mode of Action of Selegiline and Rasagiline
Authors: Harsing Laszlo G. , Timar Julia , Miklya Ildiko
Published: August 2023

Selegiline and rasagiline are two selective monoamine oxidase B (MAO-B) inhibitors used in the treatment of Parkinson’s disease. In their clinical application, however, differences in L-dopa-sparing potencies have been observed. The aim of this study was to find neurochemical and behavioral explanations for the antiparkinsonian effects of these drugs. We found that selegiline possesses a dopaminergic enhancer effect: it stimulated the electrically induced [3H]dopamine release without influencing the resting [3H]dopamine release from rat striatal slices in 10−10–10−9 mol/L concentrations. Rasagiline added in 10−13 to 10−5 mol/L concentrations did not alter the resting or electrically stimulated [3H]dopamine release. Rasagiline (10−9 mol/L), however, suspended the stimulatory effect of selegiline on the electrically induced [3H]dopamine release. The trace amine-associated receptor 1 (TAAR1) antagonist EPPTB (10−8–10−7 mol/L) also inhibited the stimulatory effect of selegiline on [3H]dopamine release. The effect of selegiline in its enhancer dose (5.33 nmol/kg) against tetrabenazine-induced learning deficit measured in a shuttle box apparatus was abolished by a 5.84 nmol/kg dose of rasagiline. The selegiline metabolite (−)methamphetamine (10−9 mol/L) also exhibited enhancer activity on [3H]dopamine release. We have concluded that selegiline acts as an MAO-B inhibitor and a dopaminergic enhancer drug, and the latter relates to an agonist effect on TAAR1. In contrast, rasagiline is devoid of enhancer activity but may act as an antagonist on TAAR1.
A Novel Hardware Architecture for Enhancing the Keccak Hash Function in FPGA Devices
Authors: Sideris Argyrios , Sanida Theodora , Dasygenis Minas
Published: August 2023

Hash functions are an essential mechanism in today’s world of information security. It is common practice to utilize them for storing and verifying passwords, developing pseudo-random sequences, and deriving keys for various applications, including military, online commerce, banking, healthcare management, and the Internet of Things (IoT). Among the cryptographic hash algorithms, the Keccak hash function (also known as SHA-3) stands out for its excellent hardware performance and resistance to current cryptanalysis approaches compared to algorithms such as SHA-1 and SHA-2. However, there is always a need for hardware enhancements to increase the throughput rate and decrease area consumption. This study specifically focuses on enhancing the throughput rate of the Keccak hash algorithm by presenting a novel architecture that supplies efficient outcomes. This novel architecture achieved impressive throughput rates on Field-Programmable Gate Array (FPGA) devices with the Virtex-5, Virtex-6, and Virtex-7 models. The highest throughput rates obtained were 26.151 Gbps, 33.084 Gbps, and 38.043 Gbps, respectively. Additionally, the research paper includes a comparative analysis of the proposed approach with recently published methods and shows a throughput rate above 11.37% Gbps in Virtex-5, 10.49% Gbps in Virtex-6 and 11.47% Gbps in Virtex-7. This comparison allows for a comprehensive evaluation of the novel architecture’s performance and effectiveness in relation to existing methodologies.