bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational Identification of Potential Inhibitors Targetingcdk1in Colorectal Cancer
Authors: Ogbodo Uchechukwu C. , Enejoh Ojochenemi A. , Okonkwo Chinelo H. , Gnanasekar Pranavathiyani , Gachanja Pauline W. , Osata Shamim , Atanda Halimat C. , Iwuchukwu Emmanuel A. , Achilonu Ikechukwu , Awe Olaitan I. 
Published: November 2023

AbstractDespite improved treatment options, colorectal cancer (CRC) remains a huge public health concern with a significant impact on affected individuals. Cell cycle dysregulation and overexpression of certain regulators and checkpoint activators are important recurring events in the progression of cancer. Cyclin-dependent kinase 1 (CDK1), a key regulator of the cell cycle component central to the uncontrolled proliferation of malignant cells, has been reportedly implicated in CRC. This study aimed to identify CDK1 inhibitors with potential for clinical drug research in CRC. Ten thousand (10,000) naturally occurring compounds were evaluated for their inhibitory efficacies against CDK1 through molecular docking studies. The stability of the lead compounds in complex with CDK1 was evaluated using molecular dynamics simulation for one thousand (1,000) nanoseconds. The top-scoring candidates’ ADME characteristics and drug-likeness were profiled using SwissADME. Four hit compounds namely spiraeoside, robinetin, 6-hydroxyluteolin, and quercetagetin were identified from molecular docking analysis to possess the least binding scores. Molecular dynamics simulation revealed that robinetin and 6-hydroxyluteolin complexes were stable within the binding pocket of the CDK1 protein. The findings from this study provide insight into novel candidates with specific inhibitory CDK1 activities that can be further investigated through animal testing, clinical trials, and drug development research for CRC treatment.
Machine Learning Approaches Reveal Future Harmful Algae Blooms in Jeju, Korea
Authors: Jang Huey 
Published: November 2023

ABSTRACTCyanobacterial algae blooms have proven to suppress diversity and abundance of other organisms while previous research shows the direct correlation between the growth of cyanobacteria and increasing global temperatures. Freshwater temperatures in Jeju island are most prone to climate change within the Korean peninsula, but research on Harmful Algae Blooms (HABs) in these environments has been scarcely conducted. The purpose of this study is to predict the cell numbers of the four HAB species in Jeju island’s four water supply sources in 2050 and 2100. Using the water quality data across the last 24 years, Scikit-learn GBM was developed to predict cell numbers of HAB based on four variables determined through multiple linear regression: temperature, pH, EC, and DO. Meanwhile, XGBoost was designed to predict four different levels of HAB bloom warnings. Future freshwater temperature was obtained through the linear relationship model between air and freshwater temperature. The performances of the Scikit-learn GBM on the cell numbers of each species were as follows (measured by MAE and R2): Microcystis (132.313; 0.857), Anabaena (36.567; 0.035), Oscillatoria (24.213; 0.672), and Apahnizomenon (65.716; 0.506). This model predicted that Oscillatoria would increase by 31.04% until 2100 and the total cell number of the four algeas would increase 376,414/ml until 2050 and reach 393,873/ml in 2100 (247.088; 0.617). The XGboost model predicted a 17% increase in the ‘Warning’ level of the Algae Alert System until 2100. The increase in HABs will ultimately lead to agricultural setbacks throughout Jeju; algae blooms in dams will produce neurotoxins and hapatotoxins, limiting the usage of agricultural water. Immediate solutions are required to suppress the growth rate of algae cells brought by global climate change in Jeju freshwaters.
A Pair of Cadmium-exposed Zebrafish Affect Boldness and Landmark use in the Un-exposed Majority
Authors: Shelton Delia S. , Suriyampola Piyumika S. , Dinges Zoe M. , Glaholt Stephen P. , Shaw Joseph R. , Martins Emília P. 
Published: November 2023

ABSTRACTSome individuals have a disproportionate effect on group responses. These individuals may possess distinct attributes that differentiate them from others. These characteristics may include susceptibility to contaminant exposure such as cadmium, a potent trace metal present in water and food. Here, we tested whether a pair of cadmium-exposed individuals could exert an impact on the behavior of the unexposed majority. We used behavioral assessments to characterize the extent of the effects of the cadmium-exposed pair on group boldness, cohesion, activity and responses to landmarks. We found that groups with a pair of cadmium-exposed fish approached and remained closer to novel stimuli and landmarks than did groups with pairs of fish treated with uncontaminated water (control). Shoals with cadmium and water treated fish exhibited similar levels of cohesion and activity. The results suggest that fish acutely exposed to environmentally-relevant cadmium concentrations can have profound effects on the un-exposed majority.
Correlative single molecule lattice light sheet imaging reveals the dynamic relationship between nucleosomes and the local chromatin environment
Authors: Daugird Timothy A. , Shi Yu , Holland Katie L. , Rostamian Hosein , Liu Zhe , Lavis Luke D. , Rodriguez Joseph , Strahl Brian D. , Legant Wesley R. 
Published: November 2023

SummaryIn the nucleus, biological processes are driven by proteins that diffuse through and bind to a meshwork of nucleic acid polymers. To better understand this interplay, we developed an imaging platform to simultaneously visualize single protein dynamics together with the local chromatin environment in live cells. Together with super-resolution imaging, new fluorescent probes, and biophysical modeling, we demonstrated that nucleosomes display differential diffusion and packing arrangements as chromatin density increases whereas the viscoelastic properties and accessibility of the interchromatin space remain constant. Perturbing nuclear functions impacted nucleosome diffusive properties in a manner that was dependent on local chromatin density and supportive of a model wherein transcription locally stabilizes nucleosomes while simultaneously allowing for the free exchange of nuclear proteins. Our results reveal that nuclear heterogeneity arises from both active and passive process and highlights the need to account for different organizational principals when modeling different chromatin environments.
Analysis of sugar-induced cell death dynamics in S. cerevisiae strains with deleted genes involved in several key metabolic processes
Authors: Valiakhmetov Airat Ya. 
Published: November 2023

AbstractBackgroundincubation of exponentially growing yeast S.cerevisiae with glucose in the absence of other nutrients results inSugarInducedCellDeath (SICD). SICD is accompanied by the accumulation of reactive oxygen species (ROS), has the nature of primary necrosis, affects cells in the S-phase of the cell cycle, and is completely suppressed by dissipation of ΔΨ. The specific mechanism linking the ΔΨ status to the induction of SICD remains unclear. This study aimed to attempt to identify the specific molecular mechanism responsible for ROS overproduction and the development of SICD.MethodsThe main method employed was the analysis of SICD development in a set of knockout mutants targeting key participants in metabolic processes.ResultsA statistically significant decrease in the number of cells with ROS overproduction was observed in the ΔAFO1, ΔPOX1, ΔYNO1, ΔTRK1, ΔTRK2, ΔVSB1, and ΔYPR003C strains. A significant decrease in the number of cells with SICD was shown in the ΔTRK1, ΔVSB1, and ΔYPR003C strains. The development of SICD is not due to the presence of a nitrogen reactive species (NRS). Deletion of certain genes expressed during the S-phase of the cell cycle did not alter the dynamics of ROS accumulation and the development of SICD. The presence of exogenous or endogenous glutathione significantly suppresses both processes studied, although not as effectively as ΔΨ dissipation.ConclusionsThe development of SICD is dependent on the presence of ROS, but is not strictly linked to it, as evidenced by the effects of glutathione and mutations related to its biosynthesis. In all strains tested, SICD was critically dependent on ΔΨ, although the nature of its generator remains unclear.
Single-cell spatial proteomics identifies the JAK/STAT pathway as an actionable therapeutic target in lethal cutaneous drug reactions
Authors: Nordmann Thierry M. , Anderton Holly , Hasegawa Akito , Schweizer Lisa , Zhang Peng , Stadler Pia-Charlotte , Sinha Ankit , Metousis Andreas , Rosenberger Florian A. , Zwiebel Maximillian , Satoh Takashi K. , Anzengruber Florian , Tanzer Maria C. , Saito Yuki , Gong Ting , Thielert Marvin , Kimura Haruna , Silke Natasha , Rodriguez Edwin H. , Gaetana Restivo , Nguyen Hong Ha , Gross Annette , Levesque Mitchell P. , Murray Peter J. , Ingen-Housz-Oro Saskia , Mund Andreas , Abe Riichiro , Silke John , Ji Chao , French Lars E. , Mann Matthias 
Published: November 2023

AbstractToxic epidermal necrolysis (TEN) is a fatal drug-induced skin reaction and an emerging public health issue. Triggered by common medications, TEN patients undergo severe and sudden epidermal detachment caused by keratinocyte cell death. Although molecular mechanisms driving keratinocyte cell death have been proposed, the main drivers remain unknown and no effective therapy exists. To systematically map molecular changes that are associated with TEN and identify potential druggable targets, we employed the single- cell spatial proteomics technique Deep Visual Proteomics. We analyzed formalin-fixed paraffin-embedded archived skin-tissue biopsies of three types of cutaneous drug reactions with varying severity and quantified over 5,000 proteins in keratinocytes and skin-infiltrating immune cells. Most strikingly, this revealed a robust enrichment of Type-I and -II interferon signature in the immune cell and keratinocyte compartment of TEN patients, along with a drastic activation of pSTAT1. Targeted inhibition with pan- JAK inhibitor (JAKi) tofacitinib reduced keratinocyte-directed cytotoxicity in a novel live-cell imaging assay, using patient-derived keratinocytes and peripheral blood mononuclear cells (PBMCs). Furthermore, oral administration of pan-JAKi tofacitinib or baricitinib ameliorated clinical and histological disease severity in two distinct mouse models of TEN. Lastly, JAKi treatment was safe and associated with rapid cutaneous re- epithelialization and recovery in four patients with TEN. This study uncovers the JAK- STAT and interferon signaling pathways as key pathogenic drivers of TEN and demonstrates the potential of targeted JAK inhibition as a curative therapy.
Travel surveillance uncovers dengue virus dynamics and introductions in the Caribbean
Authors: Taylor-Salmon Emma , Hill Verity , Paul Lauren M. , Koch Robert T. , Breban Mallery I. , Chaguza Chrispin , Sodeinde Afeez , Warren Joshua L. , Bunch Sylvia , Cano Natalia , Cone Marshall , Eysoldt Sarah , Garcia Alezaundra , Gilles Nicadia , Hagy Andrew , Heberlein Lea , Jaber Rayah , Kassens Elizabeth , Colarusso Pamela , Davis Amanda , Baudin Samantha , Rico Edhelene , Mejía-Echeverri Álvaro , Scott Blake , Stanek Danielle , Zimler Rebecca , Muñoz-Jordán Jorge L. , Santiago Gilberto A. , Adams Laura E. , Paz-Bailey Gabriela , Spillane Melanie , Katebi Volha , Paulino-Ramírez Robert , Mueses Sayira , Peguero Armando , Sánchez Nelissa , Norman Francesca F. , Galán Juan-Carlos , Huits Ralph , Hamer Davidson H. , Vogels Chantal B.F. , Morrison Andrea , Michael Scott F. , Grubaugh Nathan D. 
Published: November 2023

AbstractDengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean. To investigate this, we used travel surveillance and genomic epidemiology to reconstruct outbreak dynamics, DENV serotype turnover, and patterns of spread within the region from 2009-2022. We uncovered two recent DENV-3 introductions from Asia, one of which resulted in a large outbreak in Cuba, which was previously under-reported. We also show that while outbreaks can be synchronized between islands, they are often caused by different serotypes. Our study highlights the importance of surveillance of infected travelers to provide a snapshot of local introductions and transmission in areas with limited local surveillance and suggests that the recent DENV-3 introductions may pose a major public health threat in the region.
The maintenance of complex visual scenes in working memory may require activation of working memory manipulation circuits in the dlPFC
Authors: Nitchie Frederick , Casalvera Abigail , Teferi Marta , Patel Milan , Lynch Kevin , Makhoul Walid , Sheline Yvette , Balderston Nicholas L 
Published: November 2023

AbstractPast research has shown that the bilateral dorsolateral prefrontal cortices (dlPFC) are implicated in both emotional processing as well as cognitive processing,1,2,3in addition to working memory4, 5. Exactly how these disparate processes interact with one another within the dlPFC is less understood. To explore this, researchers designed an experiment that looked at working memory performance during fMRI under both emotional and non-emotional task conditions. Participants were asked to complete three tasks (letters, neutral images, emotional images) of the Sternberg Sorting Task under one of two trial conditions (sort or maintain). Regions of interest consisted of the left and right dlPFC as defined by brain masks based on NeuroSynth6. Results showed a significant main effect of the ‘sort’ condition on reaction speed for all three trial types, as well as a main effect of task type (letters) on accuracy. In addition, a significant interaction was found between trial type (sort) and task type (letters), but not for either of the picture tasks. These results reveal a discrepancy between BOLD signal and behavioral data, with no significant difference in BOLD activity during image trials being displayed, despite longer response times for every condition. While these results show that the dlPFC is clearly implicated in non-emotional cognitive processing, more research is needed to explain the lack of BOLD activation seen here for similar emotionally valanced tasks, possibly indicating involvement of other brain networks.
Prescription of nutritional interventions to HIV patients in Dar es Salaam, Tanzania
Authors: Abioye Ajibola I , Siril Hellen , Mhalu Aisa , Ulenga Nzovu , Fawzi Wafaie W 
Published: November 2023

AbstractBackgroundAnemia and micronutrient deficiencies are common among people living with HIV (PLHIV). There are no current guidelines from the World Health Organization (WHO) regarding whether supplements are recommended or not. We sought to assess the practices with respect to nutritional supplementation among clinicians providing care to people living with HIV in Dar es Salaam, Tanzania.MethodsWe conducted a cross-sectional survey at clinics providing care to PLHIV in Dar es Salaam, Tanzania. All healthcare workers with prescribing responsibility were invited. Self-administered questionnaires were used to collect information about participants’ demographic and professional characteristics, and their approach to making decisions regarding the prescription of nutritional interventions. Descriptive analyses regarding prescribing patterns and associated factors were done.ResultsTwo hundred and fifty-four clinicians participated in the survey. They were clinical officers (65%), medical assistants (21%) or medical doctors (13%), and attended to 30 patients (IQR: 10, 100) on average, per week. While the majority usually prescribed iron and multivitamin supplements (79% and 76%, respectively), only 33% usually prescribed ready-to-use therapeutic foods (RUTF). The decision to prescribe nutritional supplements were typically guided by patients’ clinical condition and laboratory test results. Pallor was the most commonly considered clinical feature across patient subgroups. Most participants commenced supplementation when hemoglobin concentration was ≤10g/dl. Clinicians who attended to between 10 and <100 patients or believed in the need for universal iron supplementation for pregnant PLHIV were more likely to prescribe iron supplements compared to counterparts who attended to <10 patients weekly or who did not believe in the need for universal iron supplementation for pregnant PLHIV respectively.ConclusionClinicians frequently prescribe nutritional supplements, with considerable variation in how they decide whether and how to.
A Systematic Review evaluating the role of the 7 T MRI in Neurosurgery: Unveiling Trends in the Literature So Far after Clinical Approval in 2017
Authors: Perera Molligoda Arachchige Arosh S. 
Published: November 2023

AbstractAims(1) To assess the impact of 7-Tesla Magnetic Resonance Imaging (7T MRI) on neurosurgery, focusing on its applications in diagnosis, treatment planning, and post-operative assessment. (2) To systematically analyze and identify patterns and trends in the existing literature related to the utilization of 7T MRI in neurosurgical contexts.MethodsSystematic search of PubMed for studies published between January 1, 2017, and December 31, 2021, using MeSH terms related to 7T MRI and neurosurgery. Inclusion criteria: Studies involving patients of all ages, meta-analyses, systematic reviews, and original research. Exclusion criteria: Pre-prints, studies with insufficient data eg: case reports, letters, etc., non-English publications, and studies involving animal subjects. Data synthesis involved standardized extraction forms, and a narrative synthesis was performed.ResultsIdentified 83 records from PubMed, screened for inclusion criteria, resulting in 48 studies included in the systematic review. Most common neurosurgical procedures using 7T MRI: endoscopic neurosurgery, resective epilepsy surgery, and deep brain stimulation surgery. Commonly treated pathologies: cerebrovascular diseases, epilepsy, pituitary adenoma, and gliomas. USA, Netherlands, and Germany had the highest absolute number of publications, but the Netherlands showed the highest research productivity per 7T MRI available. A decline in research output in 2018 followed by an increase in subsequent years. Could not conduct a meta-analysis due to insufficient studies for each pathology.Conclusions7T MRI holds great potential in improving the characterization and understanding of various neurological and psychiatric conditions. Superiority of 7T MRI over lower field strengths demonstrated in terms of image quality, lesion detection, and tissue characterization. Applications in epilepsy, pituitary adenoma, Parkinson’s disease, cerebrovascular diseases, trigeminal neuralgia, traumatic head injury, multiple sclerosis, glioma, and psychiatric disorders. Limitations include database selection, research productivity metrics, and study inclusion criteria. Findings suggest the need for accelerated global distribution of 7T MR systems and increased training for radiologists to ensure safe and effective integration into routine clinical practice.
Monitoring ESBL-Escherichia coliin Swiss wastewater between November 2021 and November 2022: insights into population carriage
Authors: Conforti Sheena , Holschneider Aurélie , Sylvestre Émile , Julian Timothy R. 
Published: November 2023

AbstractBackgroundAntimicrobial resistance (AMR) poses a global health threat, causing millions of deaths annually, with expectations of increased impact in the future. Wastewater surveillance offers a cost-effective, non-invasive tool to understand AMR carriage trends within a population.AimWe monitored extended-spectrum β-lactamase producingEscherichia coli(ESBL-E. coli) weekly in influent wastewater from six wastewater treatment plants (WWTPs) in Switzerland (November 2021 to November 2022) to investigate spatio-temporal variations, explore correlations with environmental variables, develop a predictive model for ESBL-E. colicarriage in the community, and detect the most prevalent ESBL-genes.MethodsWe cultured total and ESBL-E. coliin 300 wastewater samples to quantify daily loads and percentage of ESBL-E. coli. Additionally, we screened 234 ESBL-E. coliisolates using molecular-methods for the presence of 18 ESBL-gene families.ResultsWe found a population-weighted mean percentage of ESBL-E. coliof 1.9% (95%CI 1.8%, 2%) across all sites and weeks, which can inform ESBL-E. colicarriage. Concentrations of ESBL-E. colivaried across WWTPs and time, with higher values observed in WWTPs serving larger populations. Recent precipitations (previous 24-/96-hours) showed no significant association with ESBL-E. coli, while temperature occasionally had a moderate impact (p<0.05, correlation coefficients approximately 0.40) in some locations. We identifiedblaCTX-M-1,blaCTX-M-9andblaTEMas the predominant ESBL-gene families.ConclusionsOur study demonstrates that wastewater-based surveillance of culturable ESBL-E. coliprovides insights into AMR trends in Switzerland and may also inform resistance. These findings establish a foundation for long-term, nationally established monitoring protocols and provide information that may help inform targeted public health interventions.
Investigation of contributions from cortical and subcortical brain structures for speech decoding
Authors: Wu Hemmings , Cai Chengwei , Ming Wenjie , Chen Wangyu , Zhu Zhoule , Feng Chen , Jiang Hongjie , Zheng Zhe , Sawan Mohamad , Wang Ting , Zhu Junming 
Published: November 2023

AbstractLanguage impairments often arise from severe neurological disorders, prompting the development of neural prosthetics based on electrophysiological signals for the restoration of comprehensible language information. Previous decoding efforts have focused mainly on signals from the cerebral cortex, neglecting the potential contributions of subcortical brain structures to speech decoding in brain-computer interfaces (BCIs). This study aims to explore the role of subcortical structures for speech decoding by utilizing stereotactic electroencephalography (sEEG). Two native Mandarin Chinese speakers, who underwent sEEG implantation for pharmaco-resistant epilepsy, participated in this study. sEEG contacts were primarily located in the superior temporal gyrus, middle temporal gyrus, inferior temporal gyrus, thalamus, hippocampus, insular gyrus, amygdala, and parahippocampal gyrus. The participants were asked to read Chinese text, which included 407 Chinese characters (covering all Chinese syllables), displayed on a screen after receiving prompts. 1-30, 30-70 and 70-150 Hz frequency band powers of sEEG signals were used as key features. A deep learning model based on long short-term memory (LSTM) was developed to evaluate the contribution of different brain structures during encoding of speech. Prediction of speech characteristics of consonants (articulatory place and manner) and tone within single words based on the selected features and electrode contact locations was made. Cortical signals were generally better at articulatory place prediction (86.5% accuracy, chance level = 12.5%), while cortical and subcortical signals predicted articulatory manner at similar level (51.5% vs 51.7% accuracy, respectively, chance level = 14.3%). Subcortical signals generated better prediction for tone (around 58.3% accuracy, chance level = 25%). Superior temporal gyrus remains highly relevant during speech decoding for both consonants and tone. Prediction reached the highest level when cortical and subcortical inputs were combined, especially for tone prediction. Our findings indicate that both cortical and subcortical structures can play crucial roles for speech decoding, each contributing to different aspects of speech.