bluuebunny/crossref_metadata_2025_split huggingface dataset:
The genomic landscape of recurrent ovarian high grade serous carcinoma: the BriTROC-1 study
Authors: Smith P-S. , Bradley T. , Gavarró L. Morrill , Goranova T. , Ennis D. , Mirza H. , De Silva D. , Piskorz A.M. , Al-Khalidi S. , Sauer C. , Funingana I-G. , Reinius M. , Giannone G. , Lewsley L-A. , Stobo J. , McQueen J. , Bryson G. , Eldridge M. ,   The BriTROC Investigators, Macintyre G. , Markowetz F. , Brenton J.D. , McNeish I.A. 
Published: October 2022

AbstractThe drivers of recurrence and resistance in ovarian high grade serous carcinoma (HGSC) remain unclear. We established BriTROC-1 to investigate the acquisition of resistance by collecting tumour biopsies from women with recurrent ovarian HGSC that had relapsed following at least one line of platinum-based chemotherapy. Patients underwent biopsy or secondary debulking surgery, with tumour samples fixed in methanol-based fixative. Normal and tumour DNA samples underwent tagged-amplicon panel sequencing. Tumour DNA underwent shallow whole genome sequencing (sWGS). Tissue microarrays (TMA), created from diagnosis samples, were stained for CD3, CD8, CD20 and FoxP3. 276 patients were recruited (209 platinum-sensitive, 67 platinum-resistant). Panel sequencing showed close concordance between diagnosis and relapse, with only 4 discordant cases, and no revertant mutations inBRCA1orBRCA2were identified in relapse samples. CN signatures were strongly correlated with immune cell infiltration. There was very strong concordance in copy number (CN) between diagnosis and relapse, with no significant difference in purity, ploidy or focal somatic CN alterations, even when stratified by platinum sensitivity or prior chemotherapy lines. Small increases in CN signature 3 and 7 exposure were observed between diagnosis and relapse across the whole cohort but were not present in matched sample pairs. Diagnosis samples from patients with primary platinum resistance had increased rates ofCCNE1andKRASamplification and CN signature 6 exposure. The HGSC genome is remarkably stable between diagnosis and relapse and acquired chemotherapy resistance does not select for common copy number drivers. We have identified new genomic events at diagnosis, includingKRASamplification and CN signature 6 exposure, that are associated with primary platinum resistance.
Genomic epidemiology of Human Adenovirus F40 and F41 in Coastal Kenya: A retrospective hospital-based surveillance study (2013-2022)
Authors: Lambisia Arnold W. , Makori Timothy O. , Mutunga Martin , Cheruiyot Robinson , Murunga Nickson , Quick Joshua , Githinji George , Nokes D. James , Houldcroft Charlotte J. , Agoti Charles N. 
Published: October 2022

AbstractIntroductionHuman adenoviruses type F (HAdV-F) are leading cause of childhood diarrhoeal deaths. Genomic analysis would be key for understanding their potential drivers of disease severity, transmission dynamics, and for vaccine development. However, currently there is only limited data on HAdV-F genomes globally.MethodsHere, we sequenced and analysed HAdV-F from stool samples collected in coastal Kenya between 2013 and 2022. The samples were collected at Kilifi County Hospital in Kilifi, Kenya, from children < 13 years of age who reported a history of ≥ 3 loose stools in the previous 24hrs. The genomes were compared with data from the rest of the world by phylogenetic analysis and mutational profiling. Genotypes and lineages were assigned based on clustering on the global phylogenetic tree and from previously described nomenclature. Participant clinical and demographic data were linked to genotypic data.ResultsOf 91 cases identified using real-time PCR, 83 near-complete genomes were assembled, and these classified into HAdV-F40 and F41. These genotypes cocirculated throughout the study period. Three and four distinct lineages were observed for HAdV-F40 (Lineage 1-3) and F41 (Lineage 1, 2A, 3A, 3C and 3D). Genotype F40 and F41 coinfections were observed in five samples, and F41 and B7 in one sample. Two children with F40 and 41 coinfections were also infected with rotavirus and had moderate and severe disease, respectively. Intratypic recombination was found in 4 HAdV-F40 sequences occurring between lineages 1 and 3. None of the HAdV-F41 cases had jaundice.InterpretationThis study provides evidence of extensive genetic diversity, coinfections and recombination within HAdV-F40 in a high adenovirus transmission setting that will inform public health policy, vaccine development that includes the locally circulating lineages, and molecular diagnostic assay development. We recommend future comprehensive studies elucidating on HAdV-F genetic diversity and immunity for rational vaccine development.
Evidence for an Intricate Relationship Between Express Visuomotor Responses, Postural Control and Rapid Step Initiation in the Lower Limbs
Authors: Billen Lucas S. , Corneil Brian D. , Weerdesteyn Vivian 
Published: October 2022

AbstractRecent work has described express visuomotor responses (EVRs) on the upper limb. EVRs are directionally-tuned bursts of muscle activity that occur within 100 ms of visual stimulus appearance, facilitating rapid reaching. Rapid stepping responses are also important in daily life, and while there is evidence of EVR expression on lower limbs, it is unknown whether lower-limb EVRs are influenced by increased postural demands. Here, we investigate the interaction between stepping-related EVRs and anticipatory postural adjustments (APAs) that typically precede step initiation.16 healthy young subjects rapidly stepped towards visual targets presented in front of the left or right foot. We recorded bilateral surface EMG of gluteus medius (GM), a muscle involved in both APAs and stepping, and bilateral ground reaction forces. Two conditions were introduced: an anterolateral or anteromedial stepping condition with reduced or increased postural demands, respectively. In the anterolateral stepping condition, EVRs were robustly and strongly present in stance-side GM, and ground reaction forces revealed strongly decreased expression of APAs. Larger EVRs preceded shorter RTs, consistent with EVRs facilitating step initiation. In contrast, in the anteromedial stepping condition, EVRs were largely absent, and ground reaction forces revealed the consistent expression of APAs. When occasionally present, EVRs in the anteromedial stepping condition preceded larger APAs and longer RTs. Thus, while EVRs in lower limbs can facilitate rapid stepping, their expression is normally suppressed when postural stability is low. Failing to appropriately suppress EVRs in such situations disrupts postural stability, necessitating larger compensatory APAs and leading to longer stepping RTs.Key PointsExpress visuomotor responses (EVRs) are directionally tuned bursts of muscle activity that aid the rapid initiation of a goal-directed movement. They are thought to be relayed to the motor periphery along a rapid subcortical pathway involving the superior colliculus.While EVRs have predominantly been studied in reaching, it is unclear whether EVRs extend to the lower extremities and if so, whether increasing the postural demands of a stepping task interfere with lower-limb EVR expression.We found that when postural demands were low, strong EVRs in the hip abductor muscle gluteus medius facilitated a rapid stepping response. Conversely, when postural demands were high, EVRs hindered a fast stepping response, as they necessitated larger, compensatory postural adjustments prior to step onset.These results help us better understand the interaction between ultra-rapid visuomotor transformations in the EVR network, the postural demands of a given stepping task, and subsequent step initiation.
Selective memory retrieval revealed by electroencephalographic (EEG) neural pattern reinstatement
Authors: Moccia Arianna , Plummer Matthew , Simpson Ivor , Morcom Alexa M. 
Published: October 2022

1.AbstractFor past experiences to guide our actions we need to retrieve the relevant memories. Here, we used electroencephalography (EEG) to investigate how memories are selected for retrieval from a large store of mnemonic traces, and to test how current goals and external retrieval cues drive selection during the retrieval cascade. We analysed data from two studies in which people studied objects in picture or auditory word formats, and later recalled them using either written words (Experiment 1, N=28) or line drawings (Experiment 2, N=28) as retrieval cues. We used multivariate decoding to quantify the reinstatement of study phase neural patterns when people successfully identified items that had been studied in the format currently designated as targets, versus non-targeted items. Neural reinstatement emerged at around 500 ms post-stimulus, as did the established left parietal event-related potential (ERP) signature of recollection. Reinstatement was also target-selective (greater for targets than non-targets) when test cues overlapped more with targets, a pattern previously shown for the left parietal ERP (Moccia & Morcom, 2021). In contrast, when cues overlapped more with non-targets, neural reinstatement was reversed – greater for non-targets – unlike the left parietal ERP. We also tested for goal-directed mental reinstatement proposed to guide selection prior to retrieval cues. When words were cues there was strong evidence of this proactive reinstatement, but it was not detected when pictures were cues. Together, the data suggest that selection can act at multiple stages of memory retrieval and depends on both external cues and goal-directed control.
The Genomic Diversity of theEliurusgenus in northern Madagascar with a Putative New Species
Authors: Sgarlata Gabriele Maria , Rasolondraibe Emmanuel , Salmona Jordi , Le Pors Barbara , Ralantoharijaona Tantely , Rakotonanahary Ando , Jan Fabien , Manzi Sophie , Iribar-Pelozuelo Amaya , Zaonarivelo John Rigobert , Andriaholinirina Nicole Volasoa , Rasoloharijaona Solofonirina , Chikhi Lounès 
Published: October 2022

AbstractMadagascar exhibits extraordinarily high level of species richness and endemism, while being severely threatened by habitat loss and fragmentation (HL&F). In front of such threat to biodiversity, conservation effort can be directed, for instance, in the documentation of species that are still unknown to science, or in investigating how species respond to HL&F. The tufted-tail rats genus (Eliurusspp.) is the most speciose genus of endemic rodents in Madagascar, with 13 described species, which occupy two major habitat types: dry or humid forests. The large species diversity and association to specific habitat types make theEliurusgenus a suitable model for investigating species adaptation to new environments, as well as response to HL&F (dryvshumid). In the present study, we investigatedEliurusspp. genomic diversity across northern Madagascar, a region covered by both dry and humid fragmented forests. From the mitochondrial DNA (mtDNA) and nuclear genomic (RAD-seq) data of 124Eliurusindividuals sampled in poorly studied forests of northern Madagascar, we identified an undescribedEliurustaxon (Eliurus sp. nova). We tested the hypothesis of a newEliurusspecies using several approaches: i) DNA barcoding; ii) phylogenetic inferences; iii) species delimitation tests based on the Multi-Species Coalescent (MSC) model, iv) genealogical discordance index (gdi); v) thead-hoctest of isolation-by-distance withinversusbetween sister-taxa, vi) comparisons of %GC content patterns and vii) morphological analyses. All analyses support the recognition of the undescribed lineage as a distinct species. In addition, we show thatEliurus myoxinus, a species known from the dry forests of western Madagascar, is, surprisingly, found mostly in humid forests in northern Madagascar. In conclusion, we discuss the implications of such findings in the context ofEliurusspecies evolution and diversification, and use the distribution of northernEliurusspecies as a proxy for reconstructing past changes in forest cover and vegetation type in northern Madagascar.
A positive statistical benchmark to assess network agreement
Authors: Hao Bingjie , Kovács István A. 
Published: October 2022

AbstractAs the current best practice, an experimental network dataset is validated by showing significant overlap with a gold standard network. Significance is assessed by comparison to a negative benchmark, often a randomized version of the same gold standard. While such analysis can reliably indicate the presence of signal, it is illsuited to assess how much signal there is. As an alternative, here we introduce a positive statistical benchmark corresponding to the best-case scenario, capturing the maximum possible overlap between two networks. Such a positive benchmark can be efficiently generated in a maximum entropy framework and opens the way to assess if the observed overlap is significantly different from the best-case scenario. In combination with the negative benchmark, we provide a normalized overlap score (Normlap). As an application, we compare molecular and functional networks, resulting in anagreement networkof human as well as yeast network datasets. Although the number of shared interactions between most networks within the same organism is relatively small, we find that it is typically close to the best-case scenario. This paradox is resolved by the underlyingdegree inconsistency, meaning that highly connected hubs in one network often have small degrees in another, limiting the potential overlap. Furthermore, we illustrate how Normlap improves the quality assessment of experimental networks, fostering the creation of future high-quality networks.
Smart Glasses for Gait Analysis in Parkinson’s Disease: A preliminary study
Authors: Kiprijanovska Ivana , Stankoski Simon , Gjoreski Martin , William Archer James Archer , Broulidakis John , Mavridou Ifigeneia , Hayes Bradley , Nduka Charles , Gjoreski Hristijan 
Published: October 2022

Parkinson’s disease (PD) is one of the most common neurodegenerative disorders of the central nervous system, which predominantly affects patients’ motor functions, movement, and stability. Monitoring movement in patients with PD is crucial for inferring motor state fluctuations throughout daily life activities, which aids in disease progression analysis and assessing how patients respond to medications over time. In recent years, there has been an increase in the usage of wearable sensors for PD symptom monitoring. In this study, we present a preliminary analysis of smart glasses equipped with IMU sensors to provide objective information on the motor state in patients with PD. Data were collected from seven Parkinson’s patients with varying levels of symptom severity. The patients performed the Timed-Up-and-Go (TUG) Test while wearing IMU-equipped glasses. Our analysis indicates that smart glasses can provide information about patients’ gait that can be used to assess the severity level of the PD as measured by two standardized questionnaires. Furthermore, patient-specific clusters can be easily detected in the sensor data, hinting at the development of personalized models for patient-specific monitoring of symptom progression. Therefore, smart glasses have the potential to be used as an unobtrusive and continuous screening tool for PD patients’ gait, enhancing medical assessment and treatment.CCS CONCEPTS • Applied computing • Life and medical sciences • Health informaticsACM Reference FormatFirst Author’s Name, Initials, and Last Name, Second Author’s Name, Initials, and Last Name, and Third Author’s Name, Initials, and Last Name. 2022. The Title of the Paper: ACM Conference Proceedings Manuscript Submission Template: This is the subtitle of the paper, this document both explains and embodies the submission format for authors using Word. In Woodstock ‘18: ACM Symposium on Neural Gaze Detection, June 03–05, 2018, Woodstock, NY. ACM, New York, NY, USA, 10 pages. NOTE: This block will be automatically generated when manuscripts are processed after acceptance.
Hemochromatosis Neural Archetype Reveals Iron Disruption in Motor Circuits
Authors: Loughnan Robert , Ahern Jonathan , Boyle Mary , Jernigan Terry L. , Hagler Donald J. , Iversen John R. , Frei Oleksandr , Smith Diana M. , Andreassen Ole , Zaitlen Noah , Sugrue Leo , Thompson Wesley K. , Dale Anders , Schork Andrew J. , Fan Chun Chieh 
Published: October 2022

AbstractOur understanding of brain iron regulation and its disruption in disease is currently lacking. We previously found that motor circuitry is susceptible to the cumulative neurotoxic effects of excessive iron, leading to the manifestation of Parkinson’s disease. However, beyond a few well-known genes involved in peripheral iron metabolism, the underlying molecular mechanisms regulating central iron levels remain unclear. To bridge this gap, we generated scores in neurotypical individuals based on the archetypal brain iron accumulation observed in magnetic resonance imaging scans of individuals who exhibit excessive absorption of dietary iron and hemochromatosis risk. Genome-wide analysis, using common-variant SNP-array and rare-variant exome data, demonstrated this archetypal brain iron accumulation pattern is highly heritable, revealing both known and novel loci associated with iron homeostasis, and causally driven by peripheral iron levels. Our score predicted abnormalities in gait and revealed a U-shape relationship with PD risk - identifying a group of individuals with a 3-fold increased risk for this disorder. Taken together these results establish a hormetic relationship between brain iron and PD risk, in which central iron levels are strongly determined by genetics via peripheral iron. We believe this framework combining forward and reverse genetics represents a powerful new study design to understand genomic drivers underlying high dimensional phenotypes.
Pod-based e-cigarette use among college-aged adults in the United States: A survey on the perception of health effects, sociodemographic correlates, and interplay with other tobacco products
Authors: Obisesan Olufunmilayo H. , Uddin S.M. Iftekhar , Boakye Ellen , Osei Albert D. , Mirbolouk Mohammadhassan , Orimoloye Olusola A. , Dzaye Omar , Shahawy Omar El , Stokes Andrew , DeFilippis Andrew P. , Benjamin Emelia J. , Blaha Michael J. 
Published: October 2022

AbstractIntroductionE-cigarette use among youth and young adults remains of public health concern. Pod-based e-cigarettes, including JUUL, significantly changed the e-cigarette landscape in the United States (US). Using an online survey, we aimed to explore the socio-behavioral correlates, predisposing factors, and addictive behaviors among young adult pod-mod users within a University in Maryland, USA.Methods112 eligible college students aged 18-24 years recruited from a University in Maryland who reported using pod-mods were included in this study. Participants were categorized into current/non-current users based on past-30-day use. Descriptive statistics were used to analyze participants’ responses.ResultsOf the 112 participants with mean age 20.5±1.2 years, 56.3% were female, 48.2% White, and 40.2% reported past-30-day (current) use of pod-mods. The mean age of first experimentation with pod-mods was 17.8±1.4 years, while the mean age of regular use was 18.5±1.4 years, with the majority (67.9%) citing social influence as the reason for initiation. Of current users, 62.2% owned their own devices, and 82.2% predominantly used JUUL and menthol flavor (37.8%). A significant proportion of current users (73.3%) reported buying pods in person, 45.5% of whom were below the age of 21. Among all participants, 67% had had a past serious quit attempt. Among them, 89.3% neither used nicotine replacement therapy nor prescription medications. Finally, current use (adjusted odds ratio (aOR):4.52; 95%CI:1.76,11.64), JUUL use (aOR:2.56; 95%CI:1.08,6.03), and menthol flavor (aOR:6.52; 95%CI:1.38,30.89) were associated with reduced nicotine autonomy, a measure of addiction.ConclusionOur findings provide specific data to inform the development of public health interventions targeted at college youth, including the need for more robust cessation support for pod-mod users.
Advancing Post-Traumatic Seizure Classification and Biomarker Identification: Information Decomposition Based Multimodal Fusion and Explainable Machine Learning with Missing Neuroimaging Data
Authors: Akbar Md Navid , Ruf Sebastian F. , Singh Ashutosh , Faghihpirayesh Razieh , Garner Rachael , Bennett Alexis , Alba Celina , La Rocca Marianna , Imbiriba Tales , Erdoğmuş Deniz , Duncan Dominique 
Published: October 2022

ABSTRACTA late post-traumatic seizure (LPTS), a consequence of traumatic brain injury (TBI), can potentially evolve into a lifelong condition known as post-traumatic epilepsy (PTE). Presently, the mechanism that triggers epileptogenesis in TBI patients remains elusive, inspiring the epilepsy community to devise ways to predict which TBI patients will develop PTE and to identify potential biomarkers. In response to this need, our study collected comprehensive, longitudinal multimodal data from 48 TBI patients across multiple participating institutions. A supervised binary classification task was created, contrasting data from LPTS patients with those without LPTS. To accommodate missing modalities in some subjects, we took a two-pronged approach. Firstly, we extended a graphical model-based Bayesian estimator to directly classify subjects with incomplete modality. Secondly, we explored conventional imputation techniques. The imputed multimodal information was then combined, following several fusion and dimensionality reduction techniques found in the literature, and subsequently fitted to a kernel- or a tree-based classifier. For this fusion, we proposed two new algorithms: recursive elimination of correlated components (RECC) that filters information based on the correlation between the already selected features, and information decomposition and selective fusion (IDSF), which effectively recombines information from decomposed multimodal features. Our cross-validation findings showed that the proposed IDSF algorithm delivers superior performance based on the area under the curve (AUC) score. Ultimately, after rigorous statistical comparisons and interpretable machine learning examination using Shapley values of the most frequently selected features, we recommend the two following magnetic resonance imaging (MRI) abnormalities as potential biomarkers: the left anterior limb of internal capsule in diffusion MRI (dMRI), and the right middle temporal gyrus in functional MRI (fMRI).
Meta-analysis of preclinical pharmacogenomic studies to discover robust and translatable biomarkers of drug response
Authors: Smirnov Petr , Nair Sisira Kadambat , Abbas-Aghababazadeh Farnoosh , Feizi Nikta , Smith Ian , Pugh Trevor J. , Haibe-Kains Benjamin 
Published: October 2022

AbstractPreclinical pharmacogenomic studies provide an opportunity to discover novel biomarkers for drug response. However, pharamcogenomic studies linking gene expression profiles to drug response do not always agree on the significance or strength of biomarkers. We apply a statistical meta-analysis approach to 7 large independent pharmacogenomic studies, testing for tissue-specific gene expression markers predictive of response among cancer cell lines. We found 4,338 statistically-significant biomarkers across 8 tissue types and 34 drugs. Significant biomarkers were found to be closer than random to drug targets in a gene network built on pathway co-membership (average distance of 2 vs 2.9). However, functional relationships with the drug target did not predict reproducibility across studies. To validate these biomarkers, we utilized 10 clinical datasets, allowing 42/4338 biomarkers to be assessed for clinical translation. Of the 42 candidate biomarkers, the expression ofODC1was found to be significantly predictive of Paclitaxel response as a neoadjuvant treatment of breast carcinoma across 2 independent clinical studies of>200 patients each. We expect that as more clinical transcriptomics data matched with response are available, our results can be used to prioritize which genes to evaluate as clinical biomarkers of drug response.