bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection ofMansonella ozzardiin patients with acute febrile illness in Colombia
Authors: Ciuoderis Karl A. , Zamanian Mostafa , Perez Laura , Patiño Claudia , Maya Maria Angelica , Chan John D. , Cloherty Gavin A. , Hernandez-Ortiz Juan P. , Osorio Jorge E. 
Published: February 2024

ABSTRACTMansonellosis is a vector-borne filariasis caused by parasitic nematodes of the genusMansonella. The prevalence and health impact of mansonellosis is largely unknown, and there are no control programmes targeting this neglected tropical disease. Mansonellosis is prevalent in certain regions of Colombia, and while infection is often thought to be asymptomatic it may be associated with underrecognized clinical manifestations. In this study, we analyzed biobanked specimens from 905 patients participating in a febrile syndrome surveillance program in Colombia for evidence ofMansonella ozzardiinfection, identifying four confirmed cases. While there have been prior reports on the incidence of mansonellosis in Colombia, this is the first report to our knowledge describingM. ozzardimicrofilariae occurring in febrile patients in the country. Additional studies are needed to better understand the clinical consequences of mansonellosis within the complex tropical environment of Colombia, which is endemic for numerous other blood-transmitted and other vector-borne pathogens.
The Ubiquitin Ligase RBX2/SAG Regulates Mitochondrial Ubiquitination and Mitophagy
Authors: Wang Wenjuan , Li Ermin , Zou Jianqiu , Qu Chen , Ayala Juan , Wen Yuan , Islam Md Sadikul , Weintraub Neal L. , Fulton David J. , Liang Qiangrong , Zhou Jiliang , Liu Jinbao , Li Jie , Sun Yi , Su Huabo 
Published: February 2024

ABSTRACTClearance of damaged mitochondria via mitophagy is crucial for cellular homeostasis. While the role of ubiquitin (Ub) ligase PARKIN in mitophagy has been extensively studied, increasing evidence suggests the existence of PARKIN-independent mitophagy in highly metabolically active organs such as the heart. Here, we identify a crucial role for Cullin-RING Ub ligase 5 (CRL5) in basal mitochondrial turnover in cardiomyocytes. CRL5 is a multi-subunit Ub ligase comprised by the catalytic RING box protein RBX2 (also known as SAG), scaffold protein Cullin 5 (CUL5), and a substrate-recognizing receptor. Analysis of the mitochondrial outer membrane-interacting proteome uncovered a robust association of CRLs with mitochondria. Subcellular fractionation, immunostaining, and immunogold electron microscopy established that RBX2 and Cul5, two core components of CRL5, localizes to mitochondria. Depletion of RBX2 inhibited mitochondrial ubiquitination and turnover, impaired mitochondrial membrane potential and respiration, and increased cell death in cardiomyocytes.In vivo, deletion of theRbx2gene in adult mouse hearts suppressed mitophagic activity, provoked accumulation of damaged mitochondria in the myocardium, and disrupted myocardial metabolism, leading to rapid development of dilated cardiomyopathy and heart failure. Similarly, ablation of RBX2 in the developing heart resulted in dilated cardiomyopathy and heart failure. Notably, the action of RBX2 in mitochondria is not dependent on PARKIN, and PARKIN gene deletion had no impact on the onset and progression of cardiomyopathy in RBX2-deficient hearts. Furthermore, RBX2 controls the stability of PINK1 in mitochondria. Proteomics and biochemical analyses further revealed a global impact of RBX2 deficiency on the mitochondrial proteome and identified several mitochondrial proteins as its putative substrates. These findings identify RBX2-CRL5 as a mitochondrial Ub ligase that controls mitophagy under physiological conditions in a PARKIN-independent, PINK1-dependent manner, thereby regulating cardiac homeostasis.
Mapping chromatin remodelling in glioblastoma identifies epigenetic regulation of key molecular pathways and novel druggable targets
Authors: Vinel Claire , Boot James , Jin Weiwei , Pomella Nicola , Mein Charles , Zabet Nicolae Radu , Marino Silvia 
Published: February 2024

AbstractAnalysis of chromatin remodelling in neoplastic stem cells as compared to ontogenetically related neural stem cells, reveals multifactorial epigenetic regulation of signalling pathways known to contribute to glioblastoma development. It also identifies novel epigenetically regulated druggable target genes on a patient-specific level, including SMOX and GABBR2 which could be further developed for future translational approaches to more effectively treat this neoplasm.
Imaging brain vascular function in Cystic Fibrosis: an MRI study of cerebral blood flow and brain oxygenation
Authors: Chandler HL , Germuska M , Lancaster TM , Xanthe C , O’leary C , Stirk S , Murphy K , Metzler-Baddeley C , Wise RG , Duckers J 
Published: February 2024

AbstractCystic fibrosis (CF) is a progressive inherited disorder that primarily affects the lungs. With recent breakthroughs in effective treatments for CF that increase life-expectancy, a higher prevalence of age-related comorbidities have been reported including cardiovascular disease, stroke and cognitive decline. Despite the known relationship between cardiovascular health and cerebrovascular function, very little is known about brain blood flow and oxygen metabolism in patients with CF (PwCF). In 14 PwCF and 56 healthy age / sex matched controls, we used pseudo-continuous arterial spin labelling (pCASL) to quantify cerebral perfusion in grey-matter and T2-Relaxation-Under-Spin-Tagging (TRUST) to estimate global oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen consumption (CMRO2). Compared to healthy controls, PwCF showed elevated CMRO2(p =0.015). There were no significant between-group differences in grey-matter CBF (p =0.342), or whole brain OEF (p =0.091). However, regional analysis showed certain areas with higher CBF in PwCF (p< .05, FDR). This is the first study to characterise cerebrovascular function and brain oxygen metabolism in PwCF. Our findings highlight the need for early cardiovascular monitoring procedures to help maintain cerebrovascular function and combat accelerated aging effects in the brains of PwCF.
Quantification of metabolic activity from isotope tracing data using automated methodology
Authors: Liu Shiyu , Liu Xiaojing , Locasale Jason W. 
Published: February 2024

SUMMARYIsotope tracing is a widely used technique to study metabolic activities by introducing heavy labeled nutrients into living cells and organisms. However, interpreting isotope tracing data is often heuristic, and application of automated methods using artificial intelligence is limited due to the paucity of evaluative knowledge. Our study developed a new pipeline that efficiently predicts metabolic activity in expansive metabolic networks and systematically quantifies flux uncertainty of traditional computational methods. We further developed an algorithm adept at significantly reducing this uncertainty, enabling robust evaluations of metabolic activity with limited data. Using this technology, we discovered highly reprogrammed mitochondria-cytosol exchange cycles in tumor tissue of patients, and observed similar metabolic patterns influenced by nutritional conditions in cancer cells. Thus, our refined methodology provides robust automated quantification of metabolism allowing for new insight into metabolic network activity.
Volitional control of movement interacts with proprioceptive feedback in motor cortex during brain-computer interface control in humans
Authors: Liu Monica F. , Gaunt Robert A. , Collinger Jennifer L. , Downey John E. , Batista Aaron P. , Boninger Michael L. , Weber Douglas J. 
Published: February 2024

AbstractVision and proprioception regulate motor output during reaching. To study the effects of sensory input on motor control, brain computer interfaces (BCIs) offer particular advantages. As part of a long-term clinical BCI trial, we implanted two 96-channel microelectrode arrays into M1 of a person who was completely paralyzed below the neck but retained intact somatosensation. Neural recordings from M1 were transformed into a 2-dimensional velocity control signal for a robotic arm using an optimal linear estimator decoder that was calibrated while the participant imagined performing movements demonstrated by a virtual arm. Once the decoder was calibrated, we asked the participant to move the robotic arm left and right past a pair of lines as many times as possible in one minute. We examined how visual and proprioceptive feedback were incorporated into BCI control during this task by providing the participant with either visual or proprioceptive feedback, both, or neither. Proprioceptive feedback was provided by moving the participant’s own arm to match the movement of the robotic arm. Task performance with vision or proprioception alone was better than when neither were provided. However, providing proprioceptive feedback impaired performance relative to visual feedback alone, unless the decoder was calibrated with neural data collected while both visual and proprioceptive feedback were provided. Providing proprioceptive feedback during decoder calibration rescued performance because it better captured M1’s neural activity during BCI control with proprioceptive feedback. In general, BCI performance was positively correlated with how well the decoder captured variance in neural activity during the task. In summary, we found that while the BCI participant was able to use proprioceptive feedback regardless of whether the decoder was trained with vision only or vision and proprioception, training the decoder with both visual and proprioceptive feedback made performance more robust to the addition or removal of visual or proprioceptive feedback. This was because training a decoder with proprioceptive feedback allows the decoder to take advantage of proprioception-driven activity in M1. Overall, we demonstrated that natural sensation can be effectively combined with BCI to improve performance in humans.
Post-peak mpox in England: epidemiology, reinfection, and vaccine effectiveness – data from 2023
Authors: Charles Hannah , Thorley Katie , Turner Charlie , Bennet Kirsty F. , Andrews Nick , Bertran Marta , Mandal Sema , Amirthalingam Gayatri , Ramsay Mary E. , Mohammed Hamish , Sinka Katy 
Published: February 2024

AbstractEngland, like other countries that experienced a large outbreak of emergent mpox in 2022, continued to record cases during 2023 at a low but steady frequency. Comprehensive national surveillance shows that cases continue to occur primarily among gay, bisexual and other men who have sex with men mostly in London. Of 137 cases in 2023, around half were acquired overseas, half were vaccinated, and one case of reinfection was reported. Eleven people required hospital care. High vaccination uptake, during 2022, has provided good coverage of those at higher risk of mpox. Using the screening method, vaccine effectiveness of one dose was estimated at 84%. None of the vaccinated cases in 2023 were hospitalised.
Statistical pitfalls of multiple exposures in causal observational studies and tools to address them
Authors: McIntyre Kevin J , Wiener Joshua C , Davies Smith Emma 
Published: February 2024

ABSTRACTThe Table 2 Fallacy is an interpretation error commonly encountered in medical literature. This fallacy occurs when coefficient estimates in multivariable regression models, apart from that of the primary exposure, are interpreted as total effects on the outcome. Causal diagrams can be used to identify sets of covariates that, when adjusted for, allow for unbiased estimation and correct interpretation of multiple total effects of interest. However, proper investigation of multiple total effects requires fitting several regression models and conducting multiple inferences. As the number of inferences increases, so does the rate of a false positive finding, a phenomenon known as multiplicity. While multiple comparison procedures are recognized as a critical consideration of randomized controlled trials, opinion remains divided on their use within observational studies. This commentary highlights how multiplicity may arise alongside the Table 2 Fallacy, and how causal diagrams can be used in conjunction with multiple comparison procedures to simultaneously avoid this fallacy, control the risk of spurious findings, and further align the best practices of experimental and observational studies.
Knowledge, Perception, and Preventive Practices of Livestock Workers and Household Animal Owners Regarding Anthrax in Nigeria
Authors: Cadmus E. , Adesokan H.K. , Awosanya E.J. , Iziomo P.M. , Akinseye V.O. , Besong M.A. , Jolaoso A.O. , Bida A. Nma , Akangbou J.P. , Nwanga E. , Orum G T. , Omileye A.O , Adeleye A.A. , Owoicho S. , Taiwo O.J. , Ansumana R. , Vakuru C. , Cadmus S.I. 
Published: February 2024

AbstractAnthrax disease outbreak is a significant public health and socioeconomic problem, especially in low and middle-income countries (LMIC) like Nigeria. Inadequate knowledge and poor preventive practices against the disease among livestock workers and household animal owners remain important for disease transmission. Following the recent outbreaks in Nigeria, a cross-sectional study was carried out to assess the knowledge, perception and preventive practices of livestock workers and household animal owners regarding anthrax and the associated socioeconomic implications in Nigeria.A pretested, semi-structured, interviewer-administered questionnaire was used to elicit relevant information from the respondents (n=1025) in seven of the 36 states in Nigeria. Data were analysed using SPSS version 29. Univariate analysis was done and Chi-square test statistics was test for association between the knowledge/perception and other variables.Of the 1025 respondents, 58.6% and 79.9% demonstrated good knowledge and positive perception towards anthrax. However, there were important exposure practices, including a lack of preventive measures against anthrax infection (22.0%). Besides, only 27.7% of the respondents knew about the anthrax vaccination programme for livestock in the study area. With respect to the socioeconomic effects of the disease outbreak, 23.8% of the respondents indicated that the regulations imposed during an anthrax outbreak affect their livestock-related activities, while 40.6% were worried they might go out of business due to the anthrax outbreak. The respondents’ knowledge of anthrax was significantly associated with higher education (p=0.000), level of awareness (p=0.000) and perception of risk (p=0.000).The study reveals a relatively high level of perception but an average knowledge level regarding anthrax with associated socioeconomic impacts among livestock workers and household animal owners in Nigeria. An important knowledge gap includes the poor knowledge of the routine annual vaccination of animals. Hence, mitigation strategies should include educational programmes targeting this gap.
A Randomized, Controlled Clinical Trial Demonstrates Improved Cognitive Function in Senior Dogs Supplemented with a Senolytic and NAD+ Precursor Combination
Authors: Simon Katherine E. , Russell Katharine , Mondino Alejandra , Yang Chin-Chieh , Case Beth C , Anderson Zachary , Whitley Christine , Griffith Emily , Gruen Margaret E. , Olby Natasha J. 
Published: February 2024

AbstractAge-related decline in mobility and cognition are associated with cellular senescence and NAD+ depletion in dogs and people. A combination of a novel NAD+ precursor and senolytic, LY-D6/2 was examined in this randomized controlled trial. Seventy dogs were enrolled and allocated into placebo, low or full dose groups. Primary outcomes were change in cognitive impairment measured with the owner-reported Canine Cognitive Dysfunction Rating (CCDR) scale and change in activity measured with physical activity monitors. Fifty-nine dogs completed evaluations at the three-month primary endpoint, and 51 reached the six-month secondary endpoint. There was a significant difference in CCDR score across treatment groups from baseline to the primary endpoint (p=0.02) with the largest decrease in the full dose group. There were no significant differences between groups in changes in measured activity. However, the proportion of dogs that improved in frailty and owner-reported activity levels and happiness was higher in the full dose group than other groups. Adverse events occurred equally across groups. All groups showed improvement in cognition, frailty, and activity suggesting placebo effect and benefits of trial participation. We conclude that LY-D6/2 significantly improves owner-assessed cognitive function and may have broader effects on frailty, activity and happiness as reported by owners.
The transcriptional response of cortical neurons to concussion reveals divergent fates after injury
Authors: Alkaslasi Mor R. , Lloyd Eliza Y. H. , Gable Austin S. , Silberberg Hanna , Yarur Hector E. , Tsai Valerie S. , Sohn Mira , Margolin Gennady , Tejeda Hugo A. , Le Pichon Claire E. 
Published: February 2024

AbstractTraumatic brain injury (TBI) is a risk factor for neurodegeneration, however little is known about how different neuron types respond to this kind of injury. In this study, we follow neuronal populations over several months after a single mild TBI (mTBI) to assess long ranging consequences of injury at the level of single, transcriptionally defined neuronal classes. We find that the stress responsive Activating Transcription Factor 3 (ATF3) defines a population of cortical neurons after mTBI. We show that neurons that activate ATF3 upregulate stress-related genes while repressing many genes, including commonly used markers for these cell types. Using an inducible reporter linked to ATF3, we genetically mark damaged cells to track them over time. Notably, we find that a population in layer V undergoes cell death acutely after injury, while another in layer II/III survives long term and retains the ability to fire action potentials. To investigate the mechanism controlling layer V neuron death, we genetically silenced candidate stress response pathways. We found that the axon injury responsive kinase MAP3K12, also known as dual leucine zipper kinase (DLK), is required for the layer V neuron death. This work provides a rationale for targeting the DLK signaling pathway as a therapeutic intervention for traumatic brain injury. Beyond this, our novel approach to track neurons after a mild, subclinical injury can inform our understanding of neuronal susceptibility to repeated impacts.
Modeling cancer dependency with deep graph models
Authors: Fu Hengyi , Zhao Bojin , Wang Peng 
Published: February 2024

AbstractA fundamental premise for precision oncology is a catalog of diverse actionable targets that could enable personalized treatment. Large scale Genome-wide lost-of-function screens such as cancer dependency map have systematically identified single gene vulnerabilities in numerous cell lines. However, it remains challenging to scale such analyses to many clinical samples and untangle molecular networks underlying observed vulnerabilities. We developed a deep learning framework, DepGPS, combing graph neural networks with transformers to model the network interactions underlying tumor vulnerabilities. Our model demonstrated an improved ability to predict context-specific vulnerabilities over existing models and showed a higher responsiveness in perturbation analysis. Furthermore, perturbation induced dependency changes by our model demonstrated utility to support context-aware identification of synthetic lethal genes. Overall, our model represents a valuable tool to extend tumor vulnerability analyses to broader range of subjects and could help to decipher molecular networks dictating context-specific tumor vulnerabilities.
CTFFIND5 provides improved insight into quality, tilt and thickness of TEM samples
Authors: Elferich Johannes , Kong Lingli , Zottig Ximena , Grigorieff Nikolaus 
Published: February 2024

AbstractImages taken by transmission electron microscopes are usually affected by lens aberrations and image defocus, among other factors. These distortions can be modeled in reciprocal space using the contrast transfer function (CTF). Accurate estimation and correction of the CTF is essential for restoring the high-resolution signal in cryogenic electron microscopy (cryoEM). Previously, we described the implementation of algorithms for this task in thecisTEM software package (Grant et al., 2018). Here we show that taking sample characteristics, such as thickness and tilt, into account can improve CTF estimation. This is particularly important when imaging cellular samples, where measurement of sample thickness and geometry derived from accurate modeling of the Thon ring pattern helps judging the quality of the sample. This improved CTF estimation has been implemented in CTFFIND5, a new version of thecisTEM program CTFFIND. We evaluated the accuracy of these estimates using images of tilted aquaporin crystals and eukaryotic cells thinned by focused ion beam milling. We estimate that with micrographs of sufficient quality CTFFIND5 can measure sample tilt with an accuracy of 3° and sample thickness with an accuracy of 5 nm.
The 5-HT7receptor antagonist SB 269970 ameliorates maternal fluoxetine exposure-induced impairment of synaptic plasticity in the prefrontal cortex of the offspring female mice
Authors: Bobula Bartosz , Kusek Magdalena , Hess Grzegorz 
Published: February 2024

AbstractBackgroundAlthough the use of a selective serotonin reuptake inhibitor fluoxetine in depression during pregnancy is considered safe, it might increase the risk of affective disorders and cognitive symptoms in progeny. In animal models, maternal exposure to fluoxetine throughout gestation and lactation negatively affects the behavior of the offspring. Little is known about the effects of maternal fluoxetine on synaptic transmission and plasticity in the offspring cerebral cortex.MethodsDuring pregnancy and lactation C57BL/6J mouse dams received fluoxetine (7.5 mg/kg/day) with drinking water. Female offspring mice received intraperitoneal injections of the selective 5-HT7receptor antagonist SB 269970 (2.5 mg/kg) for 7 days. Whole-cell and field potential electrophysiological recordings were performed in the medial prefrontal cortex (mPFC)ex vivobrain slices.ResultsPerinatal exposure to fluoxetine resulted in decreased field potentials and impaired long-term potentiation (LTP) in layer II/III of the mPFC of female young adult offspring. Neither the intrinsic excitability nor spontaneous excitatory postsynaptic currents were altered in layer II/III mPFC pyramidal neurons. In mPFC slices obtained from fluoxetine-treated mice that were administered SB 269970 both field potentials and LTP magnitude were restored and did not differ from controls.ConclusionsTreatment of fluoxetine-exposed mice with a selective 5-HT7receptor antagonist, SB269970, normalizes synaptic transmission and restores the potential for plasticity in the mPFC of mice exposedin uteroand postnatally to fluoxetine.