bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diagnosing Appendicitis with Precision: A Comparative Analysis of Modified Alvarado and RIPASA Scoring Systems in a Northern Divisional Hospital of Bangladesh
Authors: Naz Nafisa , Monower Md Mostafa , Shahid Shah Md Ahsan , Hossain Syeda Momena , Ahmad Tanvir , Islam Baharul 
Published: November 2024

AbstractObjectiveThis study aimed to evaluate the diagnostic efficacy of the Modified Alvarado Scoring System (MASS) and the Raja Isteri Pengiran Anak Saleha Appendicitis (RIPASA) scoring system, assessing their sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy.MethodsA cross-sectional analysis was conducted at the Department of General Surgery, Rajshahi Medical College Hospital, Bangladesh, from September to December 2020. The study included 138 purposively selected individuals aged 13 years and above, suspected of acute appendicitis. Data were collected through structured interviews, detailing socio-demographic characteristics, medical history, clinical examinations, and specific laboratory tests (CBC, Urine RE). Histopathology reports from post-operative cases were used as the gold standard for diagnosis. MASS and RIPASA scores, derived from their respective criteria, were analyzed using STATA.ResultsParticipants had a mean age of 26.2 years, with males constituting 55.0% of the sample. The MASS scoring system reported a sensitivity of 79.8%, specificity of 57.9%, PPV of 92.2%, NPV of 31.4%, and an overall diagnostic accuracy of 76.8%. In contrast, the RIPASA scoring system demonstrated a sensitivity of 96.6%, specificity of 73.7%, PPV of 95.8%, NPV of 77.8%, and a diagnostic accuracy of 93.5%. ROC AUC analysis yielded values of 0.6886 for MASS and 0.8516 for RIPASA, indicating a statistically significant difference (p<0.05).ConclusionThe findings highlight the superior clinical utility of the RIPASA scoring system over MASS, particularly in settings with limited access to advanced diagnostic facilities. Adopting the RIPASA scoring system could significantly enhance the diagnosis of acute appendicitis, suggesting its potential for improving clinical outcomes in similar healthcare environments.
An Accessible 3D HepG2/C3A Liver Spheroid Model Supporting the Complete Intrahepatocytic Lifecycle ofPlasmodium falciparum
Authors: Alqurashi Salwa Omar , Caygill Claire H , Adolfi Adriana , Carson Jessica , Sturm Angelika , Dechering Koen J , Reimer Lisa , Pennington Shaun H , Sharma Parveen , Ward Stephen A , Biagini Giancarlo A. 
Published: November 2024

AbstractCurrent liver-stagePlasmodium falciparummodels are complex, expensive, and largely inaccessible, hindering research progress. Here, we show that a 3D liver spheroid model grown from immortalized HepG2/C3A cells supports the complete intrahepatocytic lifecycle ofP. falciparum. Our results demonstrate sporozoite infection, development of exoerythrocytic forms, and breakthrough infection into erythrocytes. The 3D-grown spheroid hepatocytes are structurally and functionally polarised, displaying enhanced albumin and urea production and increased expression of key metabolic enzymes, mimickingin vivoconditions – relative to 2D cultures. This accessible, reproducible model lowers barriers to malaria research, promoting advancements in fundamental biology and translational research.
Electrical Coordinated Reset Stimulation Induces Network Desynchronization in an in Vivo Model of Status Epilepticus
Authors: Ehrens Daniel , Aeed Fadi , Otor Yara , Charu Vivek , Razavi Babak , Sarma Sridevi V. , Schiller Yitzhak , Tass Peter A. 
Published: November 2024

AbstractEpilepsy, a neurological disorder characterized by recurrent seizures, profoundly impacts individuals worldwide. Various electrical stimulation protocols have been investigated to mitigate epileptic seizures, among which Coordinated Reset (CR) stimulation may have potential for inducing long-lasting neural desynchronization. This study explores the acute effects of CR stimulation on synchronization dynamics during Status Epilepticus (SE) in an in vivo animal model. An electrographically sustained seizure-state was induced via 4-aminopyridine (4AP) administration to CA3. Custom-designed electrode probes were implanted to facilitate simultaneous recording and electrical stimulation. Analytical univariate and bivariate features were constructed from the LFP time-series recording. Feature metrics focused on spike synchronization metrics and continuous signal analysis of amplitude, spectral power and phase synchronization across electrode pairs and frequency bands. Significance of modulation was assessed through permutation testing of the observed differences between the CR-stimulated group (N=5) compared to the control (no stimulation) group (N=3) during SE. Results showed overall decrease in amplitude and power univariate features, and a significant modulation of bivariate synchronization and connectivity measures across the spectrum between the CR stimulation and control group. Our findings underscore the potential effectiveness of CR stimulation in attenuating excessive neural synchronization, paving the way for further exploration of CR stimulation as a viable intervention for network desynchronization of epileptiform activity and subsequently treatment of seizures.
Lack of functional polyester-biodegrading potential in marineversusterrestrial environments evidenced by an innovative airbrushing technique
Authors: Contreras-Moll Alberto , Obrador-Viel Theo , Molina Rocío Daniela Inés , Aguiló-Ferretjans Maria del Mar , Nogales Balbina , Bosch Rafael , Christie-Oleza Joseph A. 
Published: November 2024

ABSTRACTBiodegradable plastics, primarily aliphatic polyesters, degrade to varying extents in different environments. However, the absence of easily implementable techniques for screening microbial biodegradation potential —coupled with the limitations of non-functional omics analyses— has restricted comparative studies across diverse polymer types and ecosystems. In this study, we optimized a novel airbrushing method that facilitates functional analyses by simplifying the preparation of polyester-coated plates for biodegradation screening. By repurposing an airbrush kit, polyester microparticles (MPs) could be evenly sprayed onto solid media, enabling rapid detection of extracellular depolymerizing activity via clearing zone halos. This technique was effective in screening both isolated microbial cultures and natural environmental samples, demonstrating its versatility. The method was successfully applied across multiple environments, ranking the biodegradability of six polyesters, from most to least biodegradable: polycaprolactone (PCL), poly[(R)-3-hydroxybutyrate] (PHB), poly(butylene succinate) (PBS), poly(ethylene succinate) (PES), poly(lactic acid) (PLA), and poly(butylene adipate-co-terephthalate) (PBAT). Most notably, it revealed a consistent 1,000-fold higher biodegradation potential in terrestrial compared to marine environments. This approach offers a valuable tool for isolating novel polyester-degrading microbes with significant biotechnological potential, paving the way for improved plastic waste management solutions.SYNOPSISScreening polyester-degrading microbes has traditionally been challenging due to the difficulty of incorporating polyesters into solid media. This study introduces an innovative airbrush spraying method that simplifies the preparation of polyester MPs on solid media plates, making the screening process significantly more efficient. Using this method, we demonstrated the differential biodegradability of aliphatic polyesters across environments. The results revealed a stark contrast in biodegrading potential, with terrestrial ecosystems exhibiting substantially higher activity compared to marine environments.Abstract graphic
Antibacterial Compounds Against Non-Growing and Intracellular Bacteria
Authors: Kaldalu Niilo , Bērziņš Normunds , Fick Stina Berglund , Sharma Atin , Andersson Naomi Charlotta , Aedla Jüri , Hinnu Mariliis , Puhar Andrea , Hauryliuk Vasili , Tenson Tanel 
Published: November 2024

ABSTRACTSlow- and non-growing bacterial populations, along with intracellular pathogens, often evade standard antibacterial treatments and are linked to persistent and recurrent infections. This necessitates the development of therapies specifically targeting nonproliferating bacteria. To identify compounds active against non-growing uropathogenicEscherichia coli(UPEC) we performed a drug-repurposing screen of 6,454 approved drugs and drug candidates. Using dilution-regrowth assays, we identified 39 compounds that either kill non-growing UPEC or delay its regrowth post-treatment. The hits include fluoroquinolones, macrolides, rifamycins, biguanide disinfectants, a pleuromutilin, and anti-cancer agents. 29 of the hits have not previously been recognized as active against non-growing bacteria. The hits were further tested against non-growingPseudomonas aeruginosaandStaphylococcus aureus. Ten compounds – solithromycin, rifabutin, mitomycin C, and seven fluoroquinolones – have strong bactericidal activity against non-growingP. aeruginosa, killing >4 log10of bacteria at 2.5 µM. Solithromycin, valnemulin, evofosfamide, and satraplatin are unique in their ability to selectively target non-growing bacteria, exhibiting poor efficacy against growing bacteria. Finally, 31 hit compounds inhibit the growth of intracellularShigella flexneriin a human enterocyte infection model, indicating their ability to permeate the cytoplasm of host cells. The identified compounds hold potential for treating persistent infections, warranting further comparative studies with current standard-of-care antibiotics.
Growth dynamics and protein-expression ofEscherichia coliserotypes O26:H11, O111:H8 and O145:NM in the bovine rumen
Authors: Kudva Indira T. , Biernbaum Erika N. , Trachsel Julian M. 
Published: November 2024

ABSTRACTTo adapt to the ruminal environment, Shiga toxin-producingEscherichia coli(STEC) O157:H7 (O157) expresses proteins involved in survival rather than virulence. Additionally, STEC O157 strains exhibit distinctin vitrobut sharedin vivosurvival patterns in rumen fluids that sets them apart from non-STEC, commensalE. coli. To determine if similar responses would be observed with other STEC, we evaluated three non-O157 serotypes, O26:H11, O111:H8 and O145:NM, along with a non-STECE. coli, under the growth conditions used for STEC O157: (i) anaerobically,in vitro, in rumen fluid from cattle on a lactation (low fiber, high protein) or maintenance (high fiber, low protein) diet, at 39°C for 48 hr and (ii)in vivofor 48 hr within the rumen of cattle on the same diets using a non-terminal, rumen-fistulated animal model that allows for introduction of bacteria without ruminal contamination. On the lactation diet, the ruminal pH was acidic ranging from 5.2 - 6.0 and the total volatile fatty acids (VFA) concentration, 141 - 230 μM/ml. On the maintenance diet, the ruminal fluid pH was close to neutral ranging from 6.0 - 7.0, with a total VFA of 87 - 190 μM/ml. Unlike STEC O157, the three non-O157 serotypes demonstrated survival patterns similar to each other and the control non-STECE. coli.A greater reduction in viable STEC counts was observedin vitroin rumen fluid from cattle fed the lactation diet thanin vivo, corroborating previous reports thatin vitroconditions cannot mimic those observedin vivo. Like STEC O157, the non-O157 serotypes mainly expressed proteins supporting ruminal adaptation although not all proteins matched those expressed by STEC O157, and included the virulence protein, intimin. Explorative studies such as this could provide insights into common conditions/ targets that may have application in broader STEC control in cattle.Importance of this studyThis study demonstrates that non-O157 serotypes O26:H11, O111:H8, O145:NM have similar survival and protein expression patterns in rumen fluid with variations being influenced primarily by rumen fluid composition associated with diet. Unlike STEC O157, underin vivoconditions, the growth dynamics of the non-O157 serotypes were comparable to that of non-STEC, commensalE. coli. Hence, exploring bacterial protein expression within the host is critical in discerning therapeutic targets, unique to/shared between STEC, for broad control strategies. In addition, this study further validates the value of using a non-terminal animal model for rumen studies that reduces number of animals used for an experiment.
The MRAP2 accessory protein directly interacts with melanocortin-3 receptor to enhance signaling
Authors: Jamaluddin Aqfan , Wyatt Rachael A. , Lee Joon , Dowsett Georgina K.C. , Tadross John A. , Broichhagen Johannes , Yeo Giles S.H. , Levitz Joshua , Gorvin Caroline M. 
Published: November 2024

AbstractThe central melanocortin system links nutrition to energy expenditure, with melanocortin-4 receptor (MC4R) controlling appetite and food intake, and MC3R regulating timing of sexual maturation, rate of linear growth and lean mass accumulation. Melanocortin-2 receptor accessory protein-2 (MRAP2) is a single transmembrane protein that interacts with MC4R to potentiate it’s signalling, and human mutations in MRAP2 cause obesity. Previous studies have been unable to consistently show whether MRAP2 affects MC3R activity. Here we used single-molecule pull-down (SiMPull) to confirm that MC3R and MRAP2 interact in HEK293 cells. Analysis of fluorescent photobleaching steps showed that MC3R and MRAP2 readily form heterodimers most commonly with a 1:1 stoichiometry. Human single-nucleus and spatial transcriptomics show MRAP2 is co-expressed with MC3R in hypothalamic neurons with important roles in energy homeostasis and appetite control. Functional analyses showed MRAP2 enhances MC3R cAMP signalling, impairs β-arrestin recruitment, and reduces internalization in HEK293 cells. Structural homology models revealed putative interactions between the two proteins and alanine mutagenesis of five MRAP2 and three MC3R transmembrane residues significantly reduced MRAP2 effects on MC3R signalling. Finally, we showed genetic variants in MRAP2 that have been identified in individuals that are overweight or obese prevent MRAP2’s enhancement of MC3R-driven signalling. Thus, these studies reveal MRAP2 as an important regulator of MC3R function and provide further evidence for the crucial role of MRAP2 in energy homeostasis.
Long-term effects of psilocybin on dynamic and effectivity connectivity of fronto-striatal-thalamic circuits
Authors: Pasquini Lorenzo , Vohryzek Jakub , Escrichs Anira , Sanz Perl Yonatan , Ponce-Alvarez Adrian , Idesis Sebastian , Girn Manesh , Roseman Leor , Mitchell Jennifer M. , Gazzaley Adam , Kringelbach Morten , Nutt David J. , Lyons Taylor , Carhart-Harris Robin L. , Deco Gustavo 
Published: November 2024

AbstractPsilocybin has been shown to induce fast and sustained improvements in mental well-being across various populations, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed behavior and motivational states. Here, we apply empirical methods and computational modeling to resting-state fMRI data from a within-subject longitudinal psilocybin trial in psychedelic-naïve healthy volunteers. We first show increases in FST dynamic activity four weeks after a full dose of psilocybin. We then proceed to mechanistically account for these increased dynamics, by showing that reduced structural constraints underlie increased FST dynamic activity post psilocybin. Further, we show that these reduced structural constraints come along with increased bottom-up and reduced top-down modulation of FST circuits. While cortical reductions in top-down modulation are linked to regional 5-HT2A receptor availability, increased information outflow via subcortical and limbic regions relate to local D2 receptor availability. Together, these findings show that increased FST flexibility weeks after psilocybin administration is linked to serotonergic-mediated decreases in top-down information flow and dopaminergic-mediated increases in bottom-up information flow. This long-term functional re-organization of FST circuits may represent a common mechanism underling the potential clinical efficacy of psilocybin across various neuropsychiatric disorders including substance abuse, major depression, and anorexia.Significance StatementFronto-striatal-thalamic systems, which underlie motivation and reward, go through profound functional and structural changes following psilocybin administration. We leveraged longitudinal fMRI data from a within-subject psilocybin trial in psychedelic-naïve healthy participants to show that psilocybin increases fronto-striatal-thalamic dynamic activity as well as flexibility four weeks after dosing. Computational modeling revealed that this increased flexibility is mechanistically caused by reduced structural constraints on functional dynamics. Further long-term changes included increased bottom-up and reduced top-down information flow mediated by the serotonergic and dopaminergic systems. This long-term functional re-organization of fronto-striatal-thalamic circuits may reflect a common mechanism underlying clinical symptoms improvements across diagnostic groups, such as increased openness, improved well-being, and reductions in anhedonia, apathy, and substance craving.
TIA1 Mediates Divergent Inflammatory Responses to Tauopathy in Microglia and Macrophages
Authors: Webber Chelsea J. , van de Spek Sophie J. F. , Cruz Anna Lourdes , Puri Sambhavi , Zhang Cheng , Aw Jacqueline T. M. , Papadimitriou Georgia-Zeta , Roberts Rebecca , Jiang Kiki , Tran Thuc Nhan , Zhang Lushuang , Taylor Alexandria , Wang Zihan , Porter Jacob , Sotiropoulos Ionnis , Emili Andrew , Silva Joana , Li Hu , Wolozin Benjamin 
Published: November 2024

AbstractThe RNA binding protein TIA1 is known to regulate stress responses. Here we show that TIA1 plays a much broader role in inflammatory cells, being required for the microglial sensome. We crossed TIA1 cKO mice (using a CX3CR1 driven cre element) to PS19 MAPT P301S tauopathy mice. The peripheral macrophages of TIA1 cKO mice exhibited a hyper-inflammatory phenotype with increased cytokine signaling, as expected. Surprisingly, the brains of these mice showed striking reductions in inflammation, including decreases in microglial inflammatory cytokines (TNFα and IL-1β) and sensome markers (CLEC7A, TREM2, ITGAX); these reductions were accompanied by corresponding decreases in tau pathology. Analysis of the brain TIA1 protein interactome identified brain selective TIA1 protein mediated pathways, including strong interactions with the microglial protein C1q, which directs pruning of dystrophic neurons. These results uncover a previously unknown regulatory role for TIA1 in microglial activation in the context of neurodegenerative disease and highlights the divergent regulation of two mononuclear phagocytic lineages: microglia and macrophages.
Daily ultrastructural remodeling of clock neurons
Authors: Ispizua JI , Rodríguez-Caron M , Tassara FJ , Kim KY , Insussarry Perkins C , Barzi M , Carpio-Romero C , Vasquez MF , Hansen CN , Gargiulo J , Rosato E , de la Iglesia H , Ellisman MH , Ceriani MF 
Published: November 2024

AbstractInDrosophila,about 250 clock neurons in the brain form a network that orchestrates circadian rhythmicity. Among them, eight small Lateral ventral Neurons (s-LNvs) play a critical role, synchronizing the circadian ensembleviathe neuropeptide Pigment-Dispersing Factor (PDF). Moreover, their neurites show daily variations in morphology, PDF levels, synaptic markers and connectivity. This process, called circadian structural plasticity, is ill-defined at the subcellular level. Here, we present 3D volumes of the s-LNv terminals generated by Serial Block-face Scanning Electron Microscopy (SBEM) at three key time points, two hours before lights-ON, two hours after lights-ON, and two hours after lights-OFF. We report a reduction in the number of neuronal varicosities at night, which reflects (and probably regulates) the cycling of the components we found therein. Indeed, in the morning we observed more presynaptic sites and increased accumulation and release of dense core vesicles. These rhythms were paralleled by periodic changes in mitochondrial structure that suggest daily modulation of their activity. We propose that circadian plasticity of the functionally relevant structures within presynaptic varicosities cyclically modulates the influence of the s-LNvs on the clock network.
Resting-state connectivity modifies the effects of amyloid on cognitive and physical function: evidence for network-based cognitive reserve
Authors: Laurienti Paul J. , Kritchevsky Stephen B. , Lyday Robert G. , Miller Michael E. , Lockhart Samuel N. , Rundle Melissa M. , Hugenschmidt Christina E. , Burdette Jonathan H. , Shappell Heather M. , Chen Haiying , Baker Laura D , Neyland Blake R. , Holtzer Roee 
Published: November 2024

AbstractCognitive and physical function are interrelated in aging co-occurring impairments in both domains can be debilitating and lead to increased risk of developing dementia. Amyloid beta (Aβ) deposition in the brain is linked to cognitive decline and is also associated with poorer physical function in older adults. However, significant inter-individual variability exists with respect to the influence of increased brain Aβ concentrations on cognitive and physical outcomes. Identifying factors that explain inter-individual variability in associations between Aβ and clinical outcomes could inform interventions designed to delay declines in both cognitive and physical function. Cognitive reserve (CR) is considered a buffer that allows for cognitive performance that is better than expected for a given level of brain injury or pathology. Although the neural mechanisms underlying CR remain unknown, there is growing evidence that resting-state brain networks may serve as a neural surrogate for CR. The currently study evaluated whether functional brain networks modified associations between brain Aβ and cognitive and physical function in community-dwelling older adults from the Brain Networks and Mobility (B-NET) study. We found that the integrity of the central executive and basal ganglia networks modified associations of Aβ with cognitive and physical performance. Associations between brain Aβ and cognitive and physical function were less pronounced when brain network integrity was high. The current study introduces novel evidence for brain networks underlying CR as a buffer against the influence of Aβ accumulation on cognitive and physical function.Significance StatementThere is a growing number of medications targeting beta amyloid for the treatment of Alzheimer’s disease. The treatments effectively lower brain amyloid but do not have as robust of an effect on clinical outcomes. The current study introduces novel evidence for brain networks as a buffer against the influence of Aβ accumulation on cognitive and physical function in older adults with normal cognition. Future studies should examine if brain network integrity underlies the variability in treatment response to amyloid-lowering drugs in patients with cognitive decline.