bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photopharmacological activation of adenosine A1receptor signaling suppresses seizures in a mouse model for temporal lobe epilepsy
Authors: Spanoghe Jeroen , Boon Paul , Vergaelen Marijke , Colvenaer Maren De , Mariman Tina , Vonck Kristl , Carrette Evelien , Wadman Wytse , Craey Erine , Larsen Lars E. , Sprengers Mathieu , Missinne Jeroen , Calenbergh Serge Van , Bundel Dimitri De , Smolders Ilse , Raedt Robrecht 
Published: July 2024

AbstractUp to 30% of epilepsy patients suffer from drug-resistant epilepsy (DRE). The search for innovative therapies is therefore important to close the existing treatment gap in these patients. The adenosinergic system possesses potent anticonvulsive effects, mainly through the adenosine A1receptor (A1R). However, clinical application of A1R agonists is hindered by severe systemic side effects. To achieve local modulation of A1Rs, we employed a photopharmacological approach using a caged version of the A1R agonist N6-cyclopentyladenosine, termed cCPA. We performed the firstin vivostudy with intracerebroventricularly (ICV) administered cCPA to investigate the potential to uncage sufficient amounts of cCPA in the hippocampus by local illumination in order to suppress hippocampal excitability and seizures in mice. Using hippocampal evoked potential recordings, we showed a reduction in hippocampal neurotransmission after photo-uncaging of cCPA, similar to that obtained with ICV injection of CPA. Furthermore, in the intrahippocampal kainic acid mouse model for DRE, photo-uncaging of CPA in the epileptic hippocampus resulted in a strong suppression of seizures. Finally, we demonstrated that intrahippocampal photo-uncaging of CPA resulted in less impairment of motor performance in the rotarod test compared to ICV administration of CPA. These results provide a proof of concept for photopharmacological A1R modulation as an effective precision treatment for DRE.
Synergically enhanced anti-tumor immunity ofin vivoCAR by circRNA vaccine boosting
Authors: Wang Yanyan , Lin Liangru , Wang Xinyue , Li Jing , Yin Jie , Gao Fei , Liao Xinyuan , Zhang Chenchen , Yin Qimeng , Zhao Chengzhi , Lin Jinzhong , Xu Yichi , Qiu Min , Luo Dan , Qu Liang 
Published: July 2024

AbstractChimeric Antigen Receptor (CAR) T cell therapy has shown promise in treating hematologic malignancies. However, it is limited to individualized cell therapy and faces challenges, including high costs, extended preparation time, and limited efficacy against solid tumors. Here, we generated circular RNAs (circRNAs) encoding Chimeric Antigen Receptor (CAR) transmembrane proteins, referred to as circRNACAR, which mediated remarkable tumor killing in both T cells and macrophages. In addition, macrophages exhibited efficient phagocytosis of tumor cells and pro-inflammatory polarization induced by circRNACARin vitro. We demonstrated that circRNACAR, delivered with immunocyte-tropic lipid nanoparticles (LNPs), significantly inhibited tumor growth, improved survival rates and induced a pro-inflammatory tumor microenvironment in mice. Importantly, the combination of circRNAAnti-HER2-CARand circRNA-based cancer vaccines encoding the corresponding transmembrane HER2 antigen, termed circRNAHER2, exhibited synergistically enhanced anti-tumor activity. This proof-of-concept study demonstrated that the combination of circRNA-basedin vivoCAR and vaccines, termedin vivoCAR-VAC, holds the potential to become an upgraded off-the-shelf immunotherapy.
Comparing Raman and NanoSIMS for heavy water labeling of single cells
Authors: Schaible George A. , Cliff John B. , Crandall Jennifer A. , Bougoure Jeremy J. , Atwood Joseph , Hatzenpichler Roland 
Published: July 2024

AbstractStable isotope probing (SIP) experiments in conjunction with Raman microspectroscopy (Raman) or nano-scale secondary ion mass spectrometry (NanoSIMS) are frequently used to explore single cell resolved metabolic activity in pure cultures as well as complex microbiomes. Despite the increasing popularity of these techniques, no study has yet compared results from isotope incorporation measurements using both Raman and NanoSIMS directly on the same cell. This knowledge gap creates uncertainty about the comparability of single cell SIP data generated independently using these techniques. In this study, we conducted a comparative analysis of 543Escherichia colicells grown in M9 minimal medium in the absence or presence of heavy water (2H2O) at single cell resolution using correlative Raman and NanoSIMS measurements. For the first time, we were able to establish the extent of data equivalence, allowing for comparisons between the two approaches. Utilizing the dataset from this study, we examined the effectiveness of preprocessing techniques and optimal wavenumbers for analyzing Raman spectra, along with identifying the ideal masses for NanoSIMS analysis of cells incubated in the presence of2H2O. We make recommendations for approaches to analyzing and comparing data using both or either of these techniques. We anticipate that the findings presented herein will enhance the comparability of studies employing either technique and ultimately contribute to the establishment of a standardized framework within the field.ImportanceAccurate and reliable measurements of cellular properties are fundamental to understanding the function and activity of microbes. This study addresses to what extent Raman microspectroscopy and nano-scale secondary ion mass spectrometry (NanoSIMS) measurements of single cell anabolic activity can be compared. For the first time, we study the relationship of the incorporation of a stable isotope (2H through incorporation of2H2O) as determined by the two techniques and calculate a correlation coefficient to support the use of either technique when analyzing cells incubated with2H2O. The ability to discern between the comparative strengths and limitations of these techniques is invaluable in refining experimental protocols, enhancing data comparability between studies, data interpretation, and ultimately advancing the quality and reliability of outcomes in microbiome research.
The regulatory functions of ESX-1 substrates, EspE and EspF, are separable from secretion
Authors: Prest Rebecca J. , Korotkov Konstantin V. , Champion Patricia A. 
Published: July 2024

AbstractPathogenic mycobacteria are a significant global health burden. The ESX-1 secretion system is essential for mycobacterial pathogenesis. The secretion of ESX-1 substrates is required for phagosomal lysis, which allows the bacteria to enter the macrophage cytoplasm, induce a Type I IFN response, and spread to new host cells. EspE and EspF are dual- functioning ESX-1 substrates. Inside the mycobacterial cell, they regulate transcription of ESX- 1-associated genes. Following secretion, EspE and EspF are essential for lytic activity. The link between EspE/F secretion and regulatory function has not been investigated. We investigated the relationship between EspE and EspF using molecular genetics inMycobacterium marinum,a non-tuberculous mycobacterial species that serves as an established model for ESX-1 secretion and function inM. tuberculosis.Our data support that EspE and EspF, which require each other for secretion, directly interact. Disruption of the predicted protein-protein interaction abrogates hemolytic activity and secretion but does not impact their gene regulatory activities in the mycobacterial cell. In addition, we predict a direct protein-protein interaction between the EsxA/EsxB heterodimer and EspF. Our data support that the EspF/EsxA interaction is also required for hemolytic activity and EspE secretion. Our study sheds light on the intricate molecular mechanisms governing the interactions between ESX-1 substrates, regulatory function and ESX-1 secretion, moving the field forward.ImportanceTuberculosis (TB), caused byMycobacterium tuberculosis,is a historical and pervasive disease responsible for millions of deaths annually. The rise of antibiotic and treatment-resistant TB, as well as the rise of infection by non-tuberculous mycobacterial species, calls for better understanding of pathogenic mycobacteria. The ESX-1 secreted substrates EspE and EspF are required for mycobacterial virulence, and may be responsible for phagosomal lysis. This study focuses on the mechanism of EspE and EspF secretion from the mycobacterial cell.
Multiple stressor effects on organic carbon degradation and microbial community composition in urban river sediments in a mesocosm experiment
Authors: Baikova Daria , Hadžiomerović Una , Pimentel Iris Madge , Buchner Dominik , Vermiert Anna-Maria , A.M.  , Rehsen Philipp M. , Brauer Verena S. , Meckenstock Rainer U. 
Published: July 2024

AbstractMicroorganisms in river sediments are the primarily responsible organisms for the turnover of dissolved organic carbon (DOC) in these systems and therefore are key players for river ecosystem functioning. Rivers are increasingly threatened by multiple stressors such as salinization and temperature rise, but little is known about how microbial DOC-degradation responds to these stressors and whether this function recovers after stressor release. Here, we investigated the direct and indirect effects of salinity and temperature increase and decrease on microbial communities and their ability to degrade DOC in river sediments using the outdoor experimental mesocosm systemExStream. Composition of sediment microbial communities was determined at the end of acclimatization, stressor, and recovery phase using 16S rRNA gene sequencing. At the same time points, DOC degradation rates were quantified in additional microcosm incubations based on isotopic changes of CO2 with the help of reverse stable isotope labelling. Our results showed that raising the salinity by 154.1 mg Cl-L-1and temperature by 3.5 °C did not affect DOC degradation during the stressor phase but significantly increased DOC degradation in the recovery phase after stressors were released. Likewise, microbial community composition stayed constant during acclimation and stressor phase, but became more diverse in the recovery phase. The results indicate that microbial community composition and functioning were resistant towards both stressors, but responded to stressor release due to indirect effects of stressor increase and release on the riverine food web.Graphical abstract
Plastid translocon recycling in dinoflagellates demonstrates the portability of complex plastids between hosts
Authors: Lewis William H , Paris Giulia , Beedessee Girish , Koreny Ludek , Flores Victor , Dendooven Tom , Gallet Benoit , Yee Daniel , Lam Simon , Decelle Johan , Luisi Ben F , Waller Ross F 
Published: July 2024

ABSTRACTThe plastids of photosynthetic organisms on land are predominantly ‘primary plastids’ derived from an ancient endosymbiosis of a cyanobacterium. Conversely, marine photosynthetic diversity is dominated by plastids gained by subsequent endosymbioses of photosynthetic eukaryotes, so-called ‘complex plastids’. The plastids of major eukaryotic lineages including cryptophytes, haptophytes, stramenopiles, dinoflagellates and apicomplexans, were originally all posited to derive from a single secondary endosymbiosis of a red alga—the ‘chromalveloate’ hypothesis1. Subsequent phylogenetic resolution of eukaryotes indicated that separate events of plastid acquisition must have occurred to account for this distribution of plastids2,3. The number of such events, however, and the donor organisms for the new plastid endosymbioses are still not resolved. A perceived bottleneck of endosymbiotic plastid gain is the development of protein targeting from the hosts into new plastids, and this supposition has often driven hypotheses towards minimising the number of plastid-gain events to explain plastid distribution in eukaryotes. But how plastid protein-targeting is established for new endosymbionts is often unclear, which makes it difficult to assess the likelihood of plastid transfers between lineages. Here we show that Kareniaceae dinoflagellates, that possess complex plastids known to be derived from haptophytes, acquired all the necessary protein import machinery from these haptophytes. Furthermore, cryo-electron tomography revealed that no additional membranes were added to the Kareniaceae complex plastid during serial endosymbiosis, suggesting that the haptophyte-derived import processes were sufficient. Our analyses suggests that complex red plastids are preadapted for horizontal transmission, potentially explaining their widespread distribution in aquatic algal diversity.
Effectiveness of integrating cervical cancer prevention strategies into HIV care programmes: A mixed-methods systematic review protocol
Authors: Govindsamy Kimeshnee , Noll Susanne , Blose Ntombifuthi , Amponsah-Dacosta Edina 
Published: July 2024

AbstractIntroductionCervical cancer, which is the fourth most frequently diagnosed cancer among women globally, remains a significant health burden despite being preventable and treatable, exposing gaps in accessing prevention and control services. Adolescent girls and young women (AGYW) face heightened risk of persistent HPV infection, a primary cause of cervical cancer. The overlap of cervical cancer and HIV exacerbates public health challenges, especially in resource-limited areas, urging intensified efforts in bolstering prevention and control measures. Integrating HPV vaccination, cervical cancer screening, treatment of precancerous lesions and educational interventions into HIV care programs shows promise in effectively addressing this dual burden.MethodsTo evaluate the effectiveness of integrating cervical cancer prevention strategies within HIV care programs, a mixed-methods systematic review will be conducted. A comprehensive Boolean search for literature published between 2006 to present and indexed in PubMed, Cochrane Library, EBSCO Host, Web of Science, Scopus, and Google Scholar will be conducted, without imposing any language restrictions. This review will be conducted in alignment with the Joanna Briggs guidelines on systematic reviews together with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data from eligible studies will be extracted and synthesized, and their quality assessed.DiscussionThere is limited understanding of the effectiveness of integrating cervical cancer prevention and HIV care in the real-world setting. While some studies touch on integration, focus tends to be on cervical cancer screening alone, neglecting vaccination, treatment of precancerous lesions, and education programs. Previous reviews on this focus are outdated, surpassing six years. This systematic review aims to fill these evidence gaps by thoroughly evaluating the challenges and opportunities associated with integrating the full complement of HPV prevention strategies and HIV care programs. The anticipated findings could enhance service delivery models aimed at reducing cervical cancer incidence and mortality among AGYW living with HIV.Trial registrationSystematic review registration: PROSPERO registration number: CRD42024535821.
Anti-integrin αvβ6 antibodies predict pouchitis in patients with ulcerative colitis after restorative proctocolectomy with ileal pouch-anal anastomosis
Authors: Nakanishi Risa , Kuwada Takeshi , Shiokawa Masahiro , Nishikawa Yoshihiro , Ota Sakiko , Yamazaki Hajime , Yanaidani Takafumi , Sawada Kenji , Hirata Ayako , Yasuda Muneji , Takimoto Ikuhisa , Chikugo Koki , Yokode Masataka , Muramoto Yuya , Matsumoto Shimpei , Matsumori Tomoaki , Uza Norimitsu , Chiba Tsutomu , Seno Hiroshi 
Published: July 2024

AbstractBackgroundPouchitis is the most common complication of restorative proctocolectomy (RPC) with ileal pouch-anal anastomosis (IPAA) in patients with ulcerative colitis (UC). We previously reported the presence of anti-integrin αvβ6 antibodies in the serum of patients with UC. This study investigated the association between anti-integrin αvβ6 antibodies and the development of pouchitis in patients with UC.MethodsSerum levels of anti-integrin αvβ6 antibodies were measured by enzyme-linked immunosorbent assay in 16 patients with UC who underwent RPC with IPAA. Integrin αvβ6 expression in the colonic, terminal ileal, and pouch epithelium was examined using immunohistochemistry and western blot analysis.ResultsAnti-integrin αvβ6 antibody levels in patients with UC were significantly decreased at 3, 9, and 12 months after RPC (P < 0.05). However, in patients who developed pouchitis, antibody levels remained high. The antibody levels at the time of RPC were significantly higher in patients who developed pouchitis compared to those who did not. Kaplan–Meier analysis revealed a significantly higher incidence of pouchitis in patients with antibody levels above the cutoff at the time of RPC. Although integrin αvβ6 was not expressed in the terminal ileal epithelium at the time of RPC, expression became positive in the pouch epithelium of patients with pouchitis.ConclusionsThe anti-integrin αvβ6 antibody levels in patients with UC were decreased after RPC, but remained high in patients who developed pouchitis. The antibody levels at the time of RPC may serve as a potential prognostic biomarker for predicting the risk of pouchitis in patients with UC.
Antimicrobial resistance ofStaphylococcusspp. from human specimens submitted to diagnostic laboratories in South Africa, 2012–2017
Authors: Sigudu Themba Titus , Qekwana Daniel Nenene , Oguttu James Wabwire 
Published: July 2024

AbstractBackgroundAntimicrobial drug resistance is of public health importance due to its potential to reduce treatment options and increase healthcare expenditure. There is, however, a paucity of studies that have examined antimicrobial resistance in countries with poor to moderate income. The present study examined the patterns and predictors of antimicrobial resistance in Staphylococcus isolates collected from humans at diagnostic laboratories in South Africa between 2012 and 2017.Method and materialsA cross-sectional study design using retrospective data of 404 217 diagnostic laboratory records of staphylococcal isolates collected between 2012 and 2017 was adopted in this study. Isolates were assessed for antimicrobial drug resistance against 24 antimicrobials. Descriptive statistics, and binary logistic regression models were used to analyse the data. Significance was assessed at < 0.05.ResultsThe highest resistance was observed against Cloxacillin (70.3%), while the lowest resistance was against Colistin (0.1%). A significant (p < 0.05) decreasing trend in AMR was observed over the study period, while a significant increasing temporal trend (p < 0.05) was observed for MDR over the same period. A Significant (p < 0.05) association was observed between specimen type, species of organism, and year of isolation with AMR outcome. Significant (p < 0.05) associations were observed between specimen type and season, with MDR.Discussion and recommendationsThe observed high levels of AMR and the increasing temporal trend in MDR is of public health concern. Clinicians should consider these findings when deciding on therapeutic options. Continued monitoring of AMR amongStaphylococcusspp. and judicious use of antimicrobials in human medicine should be promoted.
Using a mixed-reality headset to elicit and track clinically relevant movement in the clinic
Authors: Calame Dylan , Lester Evan , Chiu Phil , Seeberger Lauren 
Published: July 2024

AbstractBackground21st century neurology will require scalable and quantitative tools that can improve neurologic evaluations over telehealth and expand access to care. Commercially available mixed-reality headsets allow for simultaneous presentation of stimuli via holograms projected into the real world and objective and quantitative measurement of hand movement, eye movement, and phonation.MethodsWe created 6 tasks designed to mimic standard neurologic assessments and administered them to a single participant via the Microsoft HoloLens 2 mixed-reality headset. The tasks assessed postural hand tremor, finger tapping, pronation and supination of hands, hand and eye tracking of a center-out task, hand and eye tracking of a random motion task, and vocal assessment.FindingsWe show the utility of the HoloLens for commonly used neurological exams. First, we demonstrate that headset-derived holograms can project hand movements and objects in 3D space, providing a method to accurately and reproducibly present test stimuli to reduce test-test variability. Second, we found that participant hand movements closely matched holographic stimuli using a variety of metrics calculated on recorded movement data. Third, we showed that the HoloLens can record and playback exam tasks for visual inspection, sharing with other medical providers, and future analysis. Fourth, we showed that vocal recordings and analysis could be used to profile vocal characteristics over time. Together, this demonstrates the versatility of mixed reality headsets and possible applications for neurological assessment.InterpretationAdministering components of the neurologic exam via a self-contained and commercially available mixed-reality headset has numerous benefits including detailed kinematic quantification, reproducible stimuli presentation from test to test, and can be self-administered expanding access to neurological care and saving hospital time and money.FundingThis work was supported by grants from the National Institutes of Health (NIH) (F30AG063468) (E.L.), (F31NS113395) (D.J.C), and the Pilot Grant Award from the University of Colorado Movement Disorders Center (D.J.C).
The Association of NICU Strain with Neonatal Mortality and Morbidity
Authors: Salazar Elizabeth G. , Passarella Molly , Formanowski Brielle , Rogowski Jeannette , Edwards Erika , Phibbs Ciaran , Lorch Scott A. 
Published: July 2024

AbstractObjectiveTo examine the association of admission NICU strain with neonatal mortality and morbidity.Study Design2008-2021 South Carolina cohort using linked vital statistics and discharge data of 22-44 weeks GA infants, born at hospitals with ≥ level 2 unit and ≥5 births of infants <34 weeks GA/year. The exposure was tertiles of admission NICU strain, defined as the sum of infants <44 weeks GA with a congenital anomaly plus all infants born <33 weeks GA at midnight on the day of birth. We used Poisson generalized linear mixed models to examine the association of exposure to strain with the primary outcome of a composite of mortality and term and preterm morbidities adjusting for patient and hospital characteristics.ResultsWe studied 64,647 infants from 30 hospitals. High strain was associated with increased risk of mortality and morbidity adjusting for patient/hospital factors (aIRR 1.07, 95% CI 1.01 – 1.12).ConclusionNICU strain is associated with increased adverse outcomes.