bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bilateral facial nerve palsy complicating Kawasaki disease: A case report and literature review
Authors: Ou Rong , Tan Zhongyou , Liu Ling 
Published: August 2024

Rationale:
Kawasaki disease (KD) manifests as an acute, self-limited vasculitis disease that constitutes the primary cause of acquired heart disease in children under 5 years of age. Facial nerve palsy (FNP) is a rare complication associated with coronary artery lesions (CALs) in patients with KD. Patients with KD and FNP usually present atypically, leading to a delayed diagnosis and treatment of KD.

Patient concerns:
A 4-month-old boy with fever, left FNP and bilateral conjunctival injection with spontaneous resolution, was admitted to the hospital, received a short course of intravenous dexamethasone, and experienced rapid FNP recovery on the first admission. The patient experienced a resurgence of fever, bilateral conjunctival injection, and right FNP, which led to readmission. Physical examination revealed redness at the site of Bacillus Calmette-Guérin inoculation, reddening of lips, and desquamation of the distal extremities. Echocardiography revealed right-sided CALs.

Diagnoses:
The patient initially missed KD on the first admission, and was later diagnosed with complete KD with FNP on the second admission.

Interventions and outcomes:
After a short course of intravenous dexamethasone, the left FNP resolved quickly. However, right FNP recurred after corticosteroids withdrawal. Meanwhile, more typical symptoms were observed, and KD was diagnosed. Treatment ensued with intravenous immunoglobulin (IVIG), aspirin, and dexamethasone. The patient achieved rapid remission, without recurrence. Echocardiography continued to show normal findings during 1-year follow-up after discharge.

Lessons:
The clinical symptoms of FNP complicating KD in children are atypical and can easily lead to delayed diagnosis and treatment. FNP in patients with KD may serve as a risk factor for CALs, which are more challenging to resolve than the FNP itself. Adding corticosteroids to IVIG may be recommended to reduce IVIG resistance, decrease the risk of developing CALs, and alleviate CALs.
Ceftriaxone-resistantNeisseria gonorrhoeaedetected in England, 2015 to 2024; an observational study
Authors: Fifer Helen , Doumith Michel , Rubinstein Luciana , Mitchell Laura , Wallis Mark , Singh Selena , Singh Gurmit Jagjit , Rayment Michael , Evans-Jones John , Blume Alison , Dosekun Olamide , Poon Kenny , Nori Achyuta , Day Michaela , Pitt Rachel , Sun Suzy , Narayanan Prarthana , Callan Emma , Vickers Anna , Minshull Jack , Bennet Kirsty , Johnson James E.C. , Saunders John , Alexander Sarah , Mohammed Hamish , Woodford Neil , Sinka Katy , Cole Michelle 
Published: August 2024

AbstractBackgroundSince June 2022, there has been a rise in the number of ceftriaxone resistantNeisseria gonorrhoeaecases detected in England (n = 15), of which one third were extensively-drug resistant (XDR). We describe the demographic and clinical details of the recent cases and investigate the phenotypic and molecular characteristics of the isolates. For a comprehensive overview, we also reviewed 16 ceftriaxone-resistant cases previously identified in England since December 2015 and performed a global genomic comparison of all publicly available ceftriaxone-resistantN. gonorrhoeaestrains with mosaicpenAalleles.MethodsAllN. gonorrhoeaeisolates resistant to ceftriaxone (MIC >0.125 mg/L) were whole-genome sequenced and compared with 142 global sequences of ceftriaxone-resistantN. gonorrhoeae. Demographic, behavioural, and clinical data were collected, including treatment and outcomes.ResultsAll cases were heterosexuals, and most infections were associated with travel to or from the Asia-Pacific region. However, some had not travelled outside England within the previous few months. There were no ceftriaxone genital treatment failures, but 3/5 pharyngeal infections and the only rectal infection failed treatment. The isolates represented 13 different multi-locus sequence types (MLSTs), and most had the mosaicpenA-60.001 allele. The global genomes clustered into eight major phylogroups, with regional associations. All XDR isolates belonged to the same phylogroup, represented by MLST 16406.ConclusionCeftriaxone resistance inN. gonorrhoeaecontinues to be associated with thepenA-60.001 allele within multiple genetic backgrounds and with widespread dissemination in the Asia-Pacific region. Heightened surveillance activities have been initiated to detect further cases with the aim of interrupting further transmission.
FEDKEA: Enzyme function prediction with a large pretrained protein language model and distance-weighted k-nearest neighbor
Authors: Zheng Lei , Li Bowen , Xu Siqi , Chen Junnan , Liang Guanxiang 
Published: August 2024

AbstractRecent advancements in sequencing technologies have led to the identification of a vast number of hypothetical proteins, surpassing current experimental capabilities for annotation. Enzymes, crucial for diverse biological functions, have garnered significant attention; however, accurately predicting enzyme EC numbers for proteins with unknown functions remains challenging. Here, we introduce FEDKEA, a novel computational method that integrates ESM-2 and distance-weighted KNN (k-nearest neighbor) to enhance enzyme function annotation. FEDKEA first employs a fine-tuned ESM-2 model with four fully connected layers to distinguish from other proteins. For predicting EC numbers, it adopts a hierarchical approach, utilizing distinct models and training strategies across the four EC number levels. Specifically, the classification of the first EC number level utilizes a fine-tuned ESM-2 model with three fully connected layers, while transfer learning with embeddings from this model supports the second and third-level tasks. The fourth-level classification employs a distance-weighted KNN model. Compared to existing tools such as CLEAN and ECRECer, two state-of-the-art computational methods, FEDKEA demonstrates superior performance. We anticipate that FEDKEA will significantly advance the prediction of enzyme functions for uncharacterized proteins, thereby impacting fields such as genomics, physiology and medicine. FEDKEA is easy to install and currently available at:https://github.com/Stevenleizheng/FEDKEA
Co-release of GABA and ACh from medial olivocochlear neurons fine tunes cochlear efferent inhibition
Authors: Castagnola Tais , Castagna Valeria C , Kitcher Siân R. , Torres Cadenas Lester , Di Guilmi Mariano N , Gomez Casati Maria Eugenia , Buonfiglio Paula I , Dalamón Viviana , Katz Eleonora , Elgoyhen Ana Belén , Weisz Catherine J.C. , Goutman Juan D , Wedemeyer Carolina 
Published: August 2024

AbstractDuring development, inner hair cells (IHCs) in the mammalian cochlea are unresponsive to acoustic stimuli but instead exhibit spontaneous activity. During this same period, neurons originating from the medial olivocochlear complex (MOC) transiently innervate IHCs, regulating their firing pattern which is crucial for the correct development of the auditory pathway. Although the MOC-IHC is a cholinergic synapse, previous evidence indicates the widespread presence of gamma-aminobutyric acid (GABA) signaling markers, including presynaptic GABABreceptors (GABABR). In this study, we explore the source of GABA by optogenetically activating either cholinergic or GABAergic fibers. The optogenetic stimulation of MOC terminals from GAD;ChR2-eYFP and ChAT;ChR2-eYFP mice evoked synaptic currents in IHCs that were blocked by α-bungarotoxin. This suggests that GABAergic fibers release ACh and activate α9α10 nicotinic acetylcholine receptors (nAChRs). Additionally, MOC cholinergic fibers release not only ACh but also GABA, as the effect of GABA on ACh response amplitude was prevented by applying the GABAB-R blocker (CGP 36216). Using optical neurotransmitter detection and calcium imaging techniques, we examined the extent of GABAergic modulation at the single synapse level. Our findings suggest heterogeneity in GABA modulation, as only 15 out of 31 recorded synaptic sites were modulated by applying the GABABR specific antagonist, CGP (100-200 µM). In conclusion, we provide compelling evidence that GABA and ACh are co-released from at least a subset of MOC terminals. In this circuit, GABA functions as a negative feedback mechanism, locally regulating the extent of cholinergic inhibition at certain efferent-IHC synapses during an immature stage.Significance statementBefore hearing onset, the medial olivocochlear (MOC) efferent system of the mammalian cochlea regulates the pattern of IHC spontaneous firing rate through the activation of α9α10 nAChRs. However, GABA is also known to have a modulatory role at the MOC-IHC synapse. Our results show that GABA is co-released from at least a subset of MOC terminals, working as a precise regulatory mechanism for ACh release. Furthermore, we demonstrate that not all synaptic contacts within a single IHC are equally modulated by GABA.
Parvalbumin expression identifies subicular principal cells with high projection specificity
Authors: Baccini Gilda , Foggetti Angelica , Wernet Natalie , Engelhardt Karl-Alexander , Kronenbitter Kerstin , Michels Jan , Kulik Akos , Wozny Christian , Wulff Peer 
Published: August 2024

AbstractThe calcium-binding protein parvalbumin is an established marker for a subset of cortical inhibitory interneurons with similar biophysical features and connectivity. However, parvalbumin is also expressed in a small population of excitatory cells in layer 5 of the neocortex with specific sub-cortical projection targets. Parvalbumin may thus also in principal cells identify particular subclasses with distinct connectivity and function. Here we investigated whether parvalbumin is expressed in excitatory neurons of the hippocampal formation and if so, whether it delineated neurons with specific features. We report parvalbumin-expressing glutamatergic cells in the distal subiculum, which -based on location, connectivity and gene expression - separated into two subclasses: neurons in deep layers, which specifically project to the antero-ventral thalamus and neurons in superficial layers, which project to the mamillary bodies. Contrary to most adjacent pyramidal cells parvalbumin-positive neurons were non-bursting and displayed straight apical dendrites devoid of oblique dendrites. Functionally, the projections diverged from classical driver/modulator subdivisions. Parvalbumin expression thus marks two sub-types of subicular projection neurons with high target specificity and unique functional features.
Automated microinjection for zebrafish xenograft models
Authors: Ding Yi , van der Kolk Kees-Jan , van der Ent Wietske , Scotto di Mase Michele , Kowald Saskia , Huizing Jenny , Vidal Teuton Jana M , Mishra Gunja , Kempers Maxime , Almter Rusul , Kunz Sandra , Munier Laurine , Koschmann Carl , Waszak Sebastian M. , Di Donato Vincenzo , Dyballa Sylvia , Ten Dijke Peter , Esguerra Camila Vicencio , Jensen Lasse D. , de Sonneville Jan 
Published: August 2024

AbstractZebrafish xenograft models have been increasingly recognized for their ability to predict patient responses to cancer therapeutics, suggesting their potential as diagnostic tools in clinical settings. However, these models require the precise microinjection of cancer cell suspensions in many small and fragile zebrafish larvae. Manual injections are so challenging that, even after months of training, variability in experimental results persists among researchers. This limits the uptake and deployment of zebrafish xenograft models for clinical use and drug discovery. To address this challenge, we have designed, built, and validated an automated microinjection robot. Combined results of injections into the vasculature, perivitelline space, and hindbrain ventricle demonstrated an average injection success rate of approximately 60%, with a larvae survival rate exceeding 70%, comparable to manual injections using a traditional micromanipulator. Notably, the full automated mode was twice as fast as manual injections. This automation of the microinjection process significantly reduces the need for extensive personnel training while it enhances reproducibility, efficiency, and accuracy, paving the way for more extensive use of zebrafish xenograft models in drug discovery and patient diagnostics.
Neuronal progenitors suffer genotoxic stress in theDrosophilaclock mutantper0
Authors: Romano Nunzia Colonna , Marchetti Marcella , Marangoni Anna , Leo Laura , Retrosi Diletta , Rosato Ezio , Fanti Laura 
Published: August 2024

AbstractThe physiological role and the molecular architecture of the circadian clock in fully developed organisms are well established. Yet, we have a limited understanding about the function of the clock during ontogenesis. We have used a null mutant (per0) of the clock geneperiod(per) inDrosophila melanogasterto ask whether PER may play a role during normal brain development. In 3rdinstar larvae, we have observed that absence of functionalperresults in increased genotoxic stress compared to wild type controls. We have detected increased double strand DNA breaks in the central nervous system and chromosome aberrations in dividing neuronal precursor cells. We have demonstrated that reactive oxygen species (ROS) are causal to the genotoxic effect and that expression of PER in glia is necessary and sufficient to suppress such a phenotype. Finally, preliminary evidence indicates that absence of PER may result in less condensed chromatin, which may contribute to DNA damage.
Silver nanoparticle induced immunogenic cell death can improve immunotherapy
Authors: Sargsian Ara , Koutsoumpou Xanthippi , Girmatsion Hermon , Buttiens Kiana , Rios Luci Carla , Soenen Stefaan J. , Manshian Bella B. 
Published: August 2024

AbstractCancer immunotherapy is often hindered by an immunosuppressive tumor microenvironment (TME). Various strategies are being evaluated to shift the TME from an immunologically ‘cold’ to ‘hot’ tumor and hereby improve current immune checkpoint blockades (ICB). One particular hot topic is the use of combination therapies. Here, we set out to screen a variety of metallic nanoparticles and explored their in-vitro toxicity against a series of tumor and non-tumor cell lines. For silver nanoparticles, we also explored the effects of core size and surface chemistry on cytotoxicity. Ag-citrate-5nm nanoparticles were found to induce high cytotoxicity in Renca cells through excessive generation of reactive oxygen species (ROS) and significantly increased cytokine production. The induced toxicity resulted in a shift of the immunogenic cell death (ICD) marker calreticulin to the cell surface in-vitro and in-vivo. Subcutaneous Renca tumors were treated with anti-PD1 or in combination with Ag-citrate-5nm. The combination group resulted in significant reduction in tumor size, increased necrosis, and immune cell infiltration at the tumor site. Inhibition of cytotoxic CD8+ T cells confirmed the involvement of these cells in the observed therapeutic effects. Our results suggest that Ag-citrate-5nm is able to promote immune cell influx and increase tumor responsiveness to ICB therapies.
High-fat diet exacerbates the loss of bone fracture toughness in aging for C57BL/6JN mice
Authors: Brown Kenna , Vahidi Ghazal , Hislop Brady D. , Moody Maya , Watson Steven , Welhaven Hope D. , Behzad Ramina , Paton Kat O. , Karim Lamya , June Ronald K. , Martin Stephen A. , Heveran Chelsea M. 
Published: August 2024

AbstractThe elderly are at increased risk of bone fracture and more often consume poor quality diets, such as high-fat diet (HFD). We hypothesized that HFD would exacerbate the loss of bone fracture resistance in aging. To test this hypothesis, we fed 5-month and 22-month C57BL/6JN mice of both sexes HFD or low-fat diet for 8 weeks. Aging and HFD lowered bone fracture toughness, while only aging reduced bone strength. At the tissue-scale, aging increased bone mineral maturity, while HFD altered bone mineralization and maturity as well as collagen structure. Cortical bone metabolism was also dysregulated with aging and HFD. Dysregulated pathways in aging and HFD were related to cellular function and viability, or glucose regulation, respectively. Aging with HFD also impacted osteoclast and adipocyte abundance and osteocyte viability. Together, these data demonstrate that HFD may exacerbate the loss of bone matrix quality and fracture resistance in aging.
Rhizosphere Microbiome Influence on Tomato Growth under Low-Nutrient Settings
Authors: Mejia Gerardo , Jara-Servin Angélica , Romero-Chora Luis , Hernández-Álvarez Cristóbal , Peimbert Mariana , Cruz-Ortega Rocío , Alcaraz Luis D. 
Published: August 2024

SummaryStudies have shown that reduced nutrient availability enhances microbial diversity around plant roots, positively impacting plant productivity. However, the specific contributions of rhizosphere microbiomes in nutrient-poor environments still need to be better understood. This study investigates the role of Plant Growth-Promoting Rhizobacteria (PGPR) in enhancing the growth ofSolanum lycopersicumunder hydroponic conditions. We hypothesised that nutrient limitation would increase the selection of beneficial bacterial communities, compensating for nutrient deficiencies. Our hydroponic system, with treatments consisting of 50% reduced fertiliser application supplemented with a soil-derived inoculum, exhibited greater bacterial diversity and biomass than controls, suggesting a successful enrichment of PGPR that compensates for nutrient deficiencies. Using 16S rRNA gene sequencing, we found a significant enrichment (p≤ 0.001) and correlation with beneficial plant traits (p≤ 0.05) of bacterial genera such asLuteolibacter,Sphingopyxis, andKaistia. Shotgun metagenomics identified the critical role ofMethyloversatilisin nitrogen fixation and other key taxa bacterial proteins in plant-bacteria interactions. Additionally, our findings identify core taxa across different cultivation systems. These results support the potential for microbiome engineering to enhance microbial diversity and plant productivity, offering a path to reduce fertiliser use in agriculture and improve sustainability.
SynDRep: A Knowledge Graph-Enhanced Tool based on Synergistic Partner Prediction for Drug Repurposing
Authors: Shalaby Karim S. , Rao Sathvik Guru , Schultz Bruce , Hofmann-Apitius Martin , Tom Kodamullil Alpha , Bharadhwaj Vinay Srinivas 
Published: August 2024

AbstractMotivationDrug repurposing is gaining interest due to its high cost-effectiveness, low risks, and improved patient outcomes. However, most drug repurposing methods depend on drug-disease-target semantic connections of a single drug rather than insights from drug combination data. In this study, we propose SynDRep, a novel drug repurposing tool based on enriching knowledge graphs (KG) with drug combination effects. It predicts the synergistic drug partner with a commonly prescribed drug for the target disease, leveraging graph embedding and machine learning techniques. This partner drug is then repurposed as a single agent for this disease by exploring pathways between them in KG.ResultsHolE was the best-performing embedding model (with 84.58% of true predictions for all relations), and random forest emerged as the best ML model with an ROC-AUC value of 0.796. Some of our selected candidates, such as miconazole and albendazole for Alzheimer’s disease, have been validated through literature, while others lack either a clear pathway or literature evidence for their use for the disease of interest. Therefore, complementing SynDRep with more specialized KG, and additional training data, would enhance its efficacy and offer cost-effective and timely solutions for patients.Availability and ImplementationSynDRep is available as an open-source Python package athttps://github.com/SynDRep/SynDRepunder the Apache 2.0 License.
Self-assembly of mycolic acid in water: monolayer or bilayer
Authors: Kumar Yogendra , Basu Subhadip , Maiti Prabal Kumar 
Published: August 2024

AbstractThe enduring pathogenicity of Mycobacterium tuberculosis can be attributed to its lipid-rich cell wall, with mycolic acids (MAs) being a significant constituent. Different MAs’ fluidity and structural adaptability within the bacterial cell envelope significantly influence their physicochemical properties, operational capabilities, and pathogenic potential. Therefore, an accurate conformational representation of various MAs in aqueous media can provide insights into their potential role within the intricate structure of the bacterial cell wall. We have carried out the MD simulations of MAs in an aqueous solution and shed light on the various structural properties such as thickness, order parameters, area-per-MAs, conformational changes, and principle component (PC) in the single component and mixed MAs monolayer. The different conformational populations in the monolayer have been estimated using the distance-based analysis between the function groups represented as W, U, and Z-conformations that lead to the fold of the MAs chain in the monolayer. Additionally, we have also simulated the mixture of alpha-MA (α-MA or AMA), methoxy-MA (MMA), and keto-MA (KMA) with 56% AMA, 40 % MMA, and 14 % KMA composition. The thickness of the MAs monolayer was observed to range from 5 nm to 7 nm with an average 820 kg/m3density for α-MA, MMA, and KMA quantitative agreement with experimental results. The mero-chain (long chain), consisting of a functional group at the proximal and distal positions, tends to fold and exhibit a more disordered phase than the short chain. The keto-MA showed the greatest WUZ total conformations (35.32 %) with decreasing trend of eZ > eU > aU > aZ folds in both single component and mixture. Our results are in quantitative agreement with the experimental observations. The most minor population of sZ folds (0.75 % in a single component and 1.1 % in a mixture). However, eU and aU folds are most probable for the AMA and MMA. One striking observation is the abundance of MA conformers beyond the known WUZ convention because of the wide range distribution of intramolecular distances and change in dihedral angles. From the thermodynamic viewpoint, all monolayers were found to be stable in nature. The results from enhanced simulation revealed that changes in the magnitude of minimum free energy of the MAs are in order of KMA > AMA > MMA, and keto-MA exhibits more resistance (based on free energy values) for the drug molecules to permeate through the monolayer.