bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinal Thinning in People With Well-Controlled HIV Infection
Authors: Geannopoulos Katrina , McMahan Cynthia , Maldonado Ramiro S. , Abbott Akshar , Knickelbein Jared , Agron Elvira , Wu Tianxia , Snow Joseph , Nair Govind , Horne Elizabeth , Lau Chuen-Yen , Nath Avindra , Chew Emily Y. , Smith Bryan R. 
Published: June 2022

Background:
Retinal measurements correlate with disease progression in patients with multiple sclerosis; however, whether they associate with neurologic disease in people with controlled HIV is unknown. Using spectral domain optical coherence tomography, we evaluated retinal differences between people with HIV and HIV-negative controls and investigated clinical correlates of retinal thinning.

Methods:
People with HIV on antiretroviral therapy for at least 1 year and HIV-negative controls recruited from the same communities underwent spectral domain optical coherence tomography, ophthalmic examination, brain MRI, and neuropsychological testing. Retinal nerve fiber layer (RNFL) and ganglion cell inner plexiform layer (GC-IPL) thicknesses were compared between groups using analysis of covariance with relevant clinical variables as covariates. Linear regression was used to explore associations of HIV history variables, cognitive domain scores, and MRI volume measurements within the HIV group.

Results:
The HIV group (n = 69), with long-duration HIV infection (median time from diagnosis 19 years) and outstanding viral control have thinner retinal layers than HIV-negative controls (n = 28), after adjusting for covariates (GC-IPL: P = 0.002; RNFL: P = 0.024). The effect of HIV on GC-IPL thickness was stronger in women than in men (Women: P = 0.011; Men: P = 0.126). GC-IPL thickness is associated with information processing speed in the HIV group (P = 0.007, semipartial r = 0.309). No associations were found with retinal thinning and MRI volumes or HIV factors.

Conclusions:
People with HIV on antiretroviral therapy have thinning of the RNFL and GC-IPL of the retina, and women particularly are affected to a greater degree. This retinal thinning was associated with worse performance on tests of information processing speed.
Neurophysiological and Clinical Correlates of Acute Posthypoxic Myoclonus
Authors: Freund Brin E. , Kaplan Peter W. 
Published: June 2022

Summary:
Prognostication following cardiorespiratory arrest relies on the neurological examination, which is supported by neuroimaging and neurophysiological testing. Acute posthypoxic myoclonus (PHM) is a clinical entity that has prognostic significance and historically has been considered an indicator of poor outcome, but this is not invariably the case. “Malignant” and more “benign” forms of acute PHM have been described and differentiating them is key in understanding their meaning in prognosis. Neurophysiological tests, electroencephalogram in particular, and clinical phenotyping are crucial in defining subtypes of acute PHM. This review describes the neurophysiological and phenotypic markers of malignant and benign forms of acute PHM, a clinical approach to evaluating acute PHM following cardiorespiratory arrest in determining prognosis, and gaps in our understanding of acute PHM that require further study.
Biological Brain Age Prediction Using Machine Learning on Structural Neuroimaging Data: Multi-Cohort Validation Against Biomarkers of Alzheimer’s Disease and Neurodegeneration stratified by sex
Authors: Cumplido-Mayoral Irene , García-Prat Marina , Operto Grégory , Falcon Carles , Shekari Mahnaz , Cacciaglia Raffaele , Milà-Alomà Marta , Lorenzini Luigi , Ingala Silvia , Wink Alle Meije , Mutsaerts Henk JMM , Minguillón Carolina , Fauria Karine , Luis Molinuevo José , Haller Sven , Chetelat Gael , Waldman Adam , Schwarz Adam , Barkhof Frederik , Suridjan Ivonne , Kollmorgen Gwendlyn , Bayfield Anna , Zetterberg Henrik , Blennow Kaj , Suárez-Calvet Marc , Vilaplana Verónica , Gispert Juan Domingo ,   ALFA study,   EPAD study,   ADNI study,   OASIS study
Published: June 2022

ABSTRACTBrain-age can be inferred from structural neuroimaging and compared to chronological age (brain-age delta) as a marker of biological brain aging. Accelerated aging has been found in neurodegenerative disorders like Alzheimer’s disease (AD), but its validation against markers of neurodegeneration and AD is lacking. Here, imaging-derived measures from the UK Biobank dataset (N=22,661) were used to predict brain-age in 2,314 cognitively unimpaired (CU) individuals at higher risk of AD and mild cognitive impaired (MCI) patients from four independent cohorts with available biomarker data: ALFA+, ADNI, EPAD and OASIS. Brain-age delta was associated with abnormal amyloid-β, more advanced stages (AT) of AD pathology andAPOE-ε4 status. Brain-age delta was positively associated with plasma neurofilament light, a marker of neurodegeneration, and sex differences in the brain effects of this marker were found. These results validate brain-age delta as a non-invasive marker of biological brain aging related to markers of AD and neurodegeneration.
Subtyping of Small Cell Lung Cancer using plasma cell-free nucleosomes
Authors: Fialkoff Gavriel , Takahashi Nobuyuki , Sharkia Israa , Gutin Jenia , Hermoni Nadav , Kumar Rajesh , Pongor Lorinc , Nichols Samantha , Sciuto Linda , Graham Chante , Desai Parth , Nirula Micheal , Suresh Priya , Abel Melissa , Elmeskini Rajaa , Maoz Miriam , Rottenberg Yakir , Shoshan Nevo , Nechushtan Hovav , Peretz Tamar , Roame Diana , Carter Paula , Hubert Ayala , Cohen Jonathan E , Salah Azzam , Temper Mark , Grinshpun Albert , Weaver-Ohler Zoe , Rajan Arun , Figg William Douglas , Zick Aviad , Sadeh Ronen , Friedman Nir , Thomas Anish 
Published: June 2022

AbstractEmerging data on small cell lung cancer (SCLC), an aggressive malignancy with exceptionally poor prognosis, support subtypes driven by distinct transcription regulators, which engender unique therapeutic vulnerabilities. However, the translational potential of these observations is limited by access to tumor biopsies. Here, we leverage chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) on 442 plasma samples from individuals with advanced SCLC, neuroendocrine carcinomas (NEC), non-SCLC cancers, and healthy adults. Beyond providing reliable estimates of SCLC circulating free DNA tumor fraction, cfChIP-seq captures the unique epigenetic states of SCLC tissue- and cell-of-origin. Comparison of cfChIP-seq signals to matched tumor transcriptomes reveals genome-wide concordance, establishing a direct link between gene expression in the tumor and plasma cell-free nucleosomes. Exploiting this link, we develop a classifier that discriminates between SCLC lineage-defining transcription factor subtypes based on cfChIP-seq data. This work sets the stage to non-invasively profile SCLC transcriptomes using plasma cfDNA histone modifications.
Genotyping, sequencing and analysis of 140,000 adults from the Mexico City Prospective Study
Authors: Ziyatdinov Andrey , Torres Jason , Alegre-Díaz Jesús , Backman Joshua , Mbatchou Joelle , Turner Michael , Gaynor Sheila M. , Joseph Tyler , Zou Yuxin , Liu Daren , Wade Rachel , Staples Jeffrey , Panea Razvan , Popov Alex , Bai Xiaodong , Balasubramanian Suganthi , Habegger Lukas , Lanche Rouel , Lopez Alex , Maxwell Evan , Jones Marcus , García-Ortiz Humberto , Ramirez-Reyes Raul , Santacruz-Benítez Rogelio , Nag Abhishek , Smith Katherine R. ,   Regeneron Genetics Center, Reppell Mark , Zöllner Sebastian , Jorgenson Eric , Salerno William , Petrovski Slavé , Overton John , Reid Jeffrey , Thornton Timothy , Abecasis Goncalo , Berumen Jaime , Orozco-Orozco Lorena , Collins Rory , Baras Aris , Hill Michael R , Emberson Jonathan R , Marchini Jonathan , Kuri-Morales Pablo , Tapia-Conyer Roberto 
Published: June 2022

AbstractThe Mexico City Prospective Study (MCPS) is a prospective cohort of over 150,000 adults recruited two decades ago from the urban districts of Coyoacán and Iztapalapa in Mexico City. We generated genotype and exome sequencing data for all individuals, and whole genome sequencing for 10,000 selected individuals. We uncovered high levels of relatedness and substantial heterogeneity in ancestry composition across individuals. Most sequenced individuals had admixed Native American, European and African ancestry, with extensive admixture from indigenous groups in Central, Southern and South Eastern Mexico. Native Mexican segments of the genome had lower levels of coding variation, but an excess of homozygous loss of function variants compared with segments of African and European origin. We estimated population specific allele frequencies at 142 million genomic variants, with an effective sample size of 91,856 for Native Mexico at exome variants, all available via a public browser. Using whole genome sequencing, we developed an imputation reference panel which outperforms existing panels at common variants in individuals with high proportions of Central, South and South Eastern Native Mexican ancestry. Our work illustrates the value of genetic studies in populations with diverse ancestry and provides foundational imputation and allele frequency resources for future genetic studies in Mexico and in the United States where the Hispanic/Latino population is predominantly of Mexican descent.
Probabilistic embedding, clustering, and alignment for integrating spatial transcriptomics data with PRECAST
Authors: Liu Wei , Liao Xu , Luo Ziye , Yang Yi , Lau Mai Chan , Jiao Yuling , Shi Xingjie , Zhai Weiwei , Ji Hongkai , Yeong Joe , Liu Jin 
Published: June 2022

AbstractSpatially resolved transcriptomics involves a set of emerging technologies that enable the transcriptomic profiling of tissues with the physical location of expressions. Although a variety of methods have been developed for data integration, most of them are for single-cell RNA-seq datasets without consideration of spatial information. Thus, methods that can integrate spatial transcriptomics data from multiple tissue slides, possibly from multiple individuals, are needed. Here, we present PRECAST, a data integration method for multiple spatial transcriptomics datasets with complex batch effects and/or biological effects between slides. PRECAST unifies spatial factor analysis simultaneously with spatial clustering and embedding alignment, while requiring only partially shared cell/domain clusters across datasets. Using both simulated and four real datasets, we show improved cell/domain detection with outstanding visualization, and the estimated aligned embeddings and cell/domain labels facilitate many downstream analyses. We demonstrate that PRECAST is computationally scalable and applicable to spatial transcriptomics datasets from different platforms.
Repeat controlled human malaria infection of healthy UK adults with blood-stagePlasmodium falciparum: safety and parasite growth dynamics
Authors: Salkeld Jo , Themistocleous Yrene , Barrett Jordan R. , Mitton Celia H. , Rawlinson Thomas A. , Payne Ruth O. , Hou Mimi M. , Khozoee Baktash , Edwards Nick J. , Nielsen Carolyn M. , Sandoval Diana Muñoz , Bach Florian A. , Nahrendorf Wiebke , Ramon Raquel Lopez , Baker Megan , Ramos-Lopez Fernando , Folegatti Pedro M. , Quinkert Doris , Ellis Katherine J. , Poulton Ian D. , Lawrie Alison M. , Cho Jee-Sun , Nugent Fay L. , Spence Philip J. , Silk Sarah E. , Draper Simon J. , Minassian Angela M. 
Published: June 2022

AbstractIn endemic settings it is known that natural malaria immunity is gradually acquired following repeated exposures. Here we sought to assess whether similar acquisition of blood-stage malaria immunity would occur following repeated parasite exposure by controlled human malaria infection (CHMI). We report the findings of a repeat homologous blood-stagePlasmodium falciparum(3D7 clone) CHMI study (VAC063C;ClinicalTrials.govNCT03906474). In total, 24 healthy, unvaccinated, malaria-naïve UK adult participants underwent primary CHMI followed by drug treatment. Ten of these then underwent secondary CHMI in the same manner, and then six of these underwent a final tertiary CHMI. As with primary CHMI, malaria symptoms were common following secondary and tertiary infection, however, most resolved within a few days of treatment and there were no long term sequelae or serious adverse events related to CHMI. Despite detectable induction and boosting of anti-merozoite serum IgG antibody responses following each round of CHMI, there was no clear evidence of anti-parasitic immunity (manifest as reduced parasite growthin vivo) conferred by repeated challenge with the homologous parasite in the majority of volunteers. However, three volunteers showed some variation in parasite growth dynamicsin vivofollowing repeat CHMI that were either modest or short-lived. We also observed no major differences in clinical symptoms or laboratory markers of infection across the primary, secondary and tertiary challenges. However, there was a trend to more severe pyrexia after primary CHMI and the absence of a detectable transaminitis post-treatment following secondary and tertiary infection. We hypothesize that this could represent the initial induction of disease tolerance or clinical malaria immunity. Repeat homologous blood-stage CHMI is thus safe and provides a model with the potential to further the understanding of the acquisition of blood-stage immunity in a highly controlled setting.
A Dense sub-graph based approach for Automatic detection of Optic Disc
Authors: Jana Subrata , Banerjee Tribeni Prasad , Mitra Thakur Gour Sundar , Mitra Pabitra 
Published: June 2022

AbstractGlaucoma is a situation of greater than normal intraocular pressure surrounded by the eyes. This explains the harm to the optic nerves as the limb passes in sequence to the brain. The graph base is used in this paper for automatic localization of the optic disc. This paper proposed and modified a new dense sub - graph approach to locate the affected optic disc by using DRIVE, STAIR, and Drishti -GS1 databases. This model has proved to be more accurate when compared with other standard models representing the concert’s progress. This method provides a new idea for the location of the optic disc with a system accuracy of 93%.
Theta oscillations in the human hippocampus normalize the information content of episodic memory
Authors: Santos-Pata D. , Zucca R. , Fernandez Amil A. , Principe A. , Pérez-Enríquez C. , Rocamora R. , Kwok S. C. , Verschure P. 
Published: June 2022

AbstractThe principles governing the formation of episodic memories from the continuous stream of sensory stimuli are not fully understood. Theoretical models of the hippocampus propose that the representational format of episodic memories comprise oscillations in the theta frequency band (2-8 Hz) that set the time boundaries in which discrete events are bound encoded in the gamma frequency range (>30 Hz). We investigated this temporal segmentation and binding process by analyzing the intracranial EEG (iEEG) of surgically implanted epileptic patients performing a virtual-navigation task. We found a positive correlation between sensory information density encountered by the subject and hippocampal theta-frequency, suggesting that the human hippocampus normalizes the information content of episodic memories relative to the density of sensory information. This interpretation is further supported by the observation that as a marker of mnemonic encoding, i.e. the amount of persistent gamma events, directly correlates with sensory information density, gamma-frequency power and the phase relation between theta and gamma oscillations remain constant. Using a theoretical model of the hippocampus, we build a model that analogously displays a similar normalization of gamma episodes per theta cycle relative to information density by accounting for the physiological signatures of theta-gamma coding through combining fast and slow inhibitory feedback. We propose that this intrinsic normalization mechanism optimizes the trade-off between the discretization and compression of continuous experience relative to the limited capacity of episodic memory.SummaryWe move in continuous time and space, yet we can encode and recall discrete episodes from our past experiences. The neural mechanism behind this discretization is not fully understood. It has been previously observed that rodent locomotion modulates ongoing hippocampal theta rhythms. Thus, raising the question of whether these slow rhythms bind events together during a single oscillatory cycle relative to the movement speed or overall information density.We quantified the effects of increasing locomotion and sensory information in modulating theta oscillations during virtual navigation with intracranial hippocampal activity from human epileptic patients.. We observed hippocampal theta waves increased with higher speed and higher sensory demands, thereby maintaining constant information per oscillatory cycle.These results highlight the role of hippocampal theta oscillations in discretizing ongoing experience relative to the available information and explain how episodic memory integrates a fixed number of items per oscillatory theta cycle irrespective of richness of the external world.
Global worming: massive invasion of North America by earthworms revealed
Authors: Mathieu Jérôme , Reynolds John Warren , Fragoso Carlos , Hadly Elizabeth 
Published: June 2022

AbstractHuman activities cause major ecological changes by reshuffling the spatial distribution of species. The extent to which this process affects belowground biota is a critical issue because soil organisms play a key role in ecosystem functioning and maintenance. However, the magnitude of the reshuffling of soil species remains unknown so far because of the lack of a historic baseline. Here, we begin to fill this gap with the largest spatiotemporal database of native and alien earthworms in North America. Our results reveal that the entire continent is being invaded by non-native earthworms through a variety of pathways. We show that these aliens bring novel ecological functions in most regions and thus represent a major threat to native ecosystems. Our findings demonstrate that earthworms, and most likely other soil organisms, represent a major but overlooked pool of invasive species with strong ecological impact. They need to be better integrated in control and mitigation strategies.
Viral diversity and zoonotic risk in endangered species
Authors: Nikc Kayla , Albery Gregory F. , Becker Daniel J. , Eskew Evan A. , Fagre Anna C. , Ryan Sadie J. , Carlson Colin J. 
Published: June 2022

AbstractA growing body of evidence links zoonotic disease risk, including pandemic threats, to biodiversity loss and other upstream anthropogenic impacts on ecosystem health. However, there is little current research assessing viral diversity in endangered species. Here, combining IUCN Red List data on 5,876 mammal species with data on host-virus associations for a subset of 1,273 extant species, we examine the relationship between endangered species status and viral diversity, including the subset of viruses that can infect humans (zoonotic viruses). We show that fewer total viruses and fewer zoonotic viruses are known to infect more threatened species. After correcting for sampling effort, zoonotic virus diversity is mostly independent of threat status, but endangered species—despite a higher apparent research effort—have a significantly lower diversity of viruses, a property that is not explained by collinearity with host phylogeography or life history variation. Although this pattern could be generated by real biological processes, we suspect instead that endangered species may be subject to additional sampling biases not captured by the total volume of scientific literature (e.g., lower rates of invasive sampling may decrease viral discovery). Overall, our findings suggest that endangered species are no more or less likely to host viruses that pose a threat to humans, but future zoonotic threats might remain undiscovered in these species. This may be concerning, given that drivers of endangered species’ vulnerability such as habitat disturbance, wildlife trade, or climate vulnerability may increase virus prevalence in reservoirs and risk of spillover into humans.
Characterization of a KDM5 Small Molecule Inhibitor with Antiviral Activity against Hepatitis B Virus
Authors: Gilmore Sarah A. , Tam Danny , Cheung Tara L. , Snyder Chelsea , Farand Julie , Dick Ryan , Matles Mike , Feng Joy Y. , Ramirez Ricardo , Li Li , Yu Helen , Xu Yili , Barnes Dwight , Czerwieniec Gregg , Brendza Katherine M. , Appleby Todd C. , Birkus Gabriel , Willkom Madeleine , Kobayashi Tetsuya , Paoli Eric , Labelle Marc , Boesen Thomas , Tay Chin H. , Delaney William E. , Notte Gregory T. , Schmitz Uli , Feierbach Becket 
Published: June 2022

AbstractChronic hepatitis B (CHB) is a global health care challenge and a major cause of liver disease. To find new therapeutic avenues with a potential to functionally cure chronic Hepatitis B virus (HBV) infection, we performed a focused screen of epigenetic modifiers to identify replication inhibitors. From this work we identified isonicotinic acid inhibitors of the histone lysine demethylase 5 (KDM5) with potent anti-HBV activity. To enhance the cellular permeability and liver accumulation of the most potent KDM5 inhibitor identified (GS-080) an ester prodrug was developed (GS-5801) that resulted in improved bioavailability and liver exposure as well as an increased H3K4me3:H3 ratio on chromatin. GS-5801 treatment of HBV-infected primary human hepatocytes inhibited HBV replication and antigen levels. Evaluation of GS-5801 antiviral activity in a humanized mouse model of HBV infection, however, did not result in antiviral efficacy, despite achieving pharmacodynamic levels of H3K4me3:H3 predicted to be efficacious from the in vitro model. Here we discuss potential reasons for the disconnect between in vitro and in vivo efficacy, which highlight the translational difficulties of epigenetic targets for viral diseases.
Safety and uptake of fully oxidized β-carotene
Authors: Burton Graham W. , Mogg Trevor J. , Stupak Jacek , Stark Felicity C. , Twine Susan M. , Li Jianjun 
Published: June 2022

AbstractSpontaneous oxidation of β-carotene yields a polymer-rich product (OxBC) also containing small amounts of many apocarotenoids. OxBC extends β-carotene’s benefits beyond vitamin A, finding utility in supporting health in livestock, pets, and humans. Although naturally occurring OxBC is consumed in foods and feeds, a direct demonstration here of safety of synthetic OxBC supports its increasing usage. A toxicological study in rats showed a maximum tolerated single oral dose, an LD50, and a NOAEL of 5,000, 30,079 and 1875 mg/kg body weight, respectively. The repeat-dose 90-day oral toxicity study showed no adverse physiological or pathological effects. A first study of OxBC uptake by mice over 2-5 days into a select set of tissues showed OxBC already was naturally present. The highest levels were in liver, lung, and hamstring. Despite dosing, no net increases occurred in liver, kidney, lung, and muscle. Net increases occurred in urine, intestinal content, plasma, feces, spleen, and cecum, consistent with processing of OxBC and preferential elimination of polymer. Compared to the 4:1 polymer: apocarotenoid ratio of OxBC, polymer was enriched in liver and spleen and depleted in lung, kidney, hamstring, and abdominal muscle. The apparent control of OxBC in major tissues further supports its safety.