bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating primary and booster vaccination prioritization strategies for COVID-19 by age and high-contact employment status using data from contact surveys
Authors: Roubenoff Ethan , Feehan Dennis , Mahmud Ayesha S. 
Published: December 2022

AbstractThe debate around vaccine prioritization for COVID-19 has revolved around balancing the benefits from: (1) the direct protection conferred by the vaccine amongst those at highest risk of severe disease outcomes, and (2) the indirect protection through vaccinating those that are at highest risk of being infected and of transmitting the virus. While adults aged 65+ are at highest risk for severe disease and death from COVID-19, essential service and other in-person workers with greater rates of contact may be at higher risk of acquiring and transmitting SARS-CoV-2. Unfortunately, there have been relatively little data available to understand heterogeneity in contact rates and risk across these demographic groups. Here, we retrospectively analyze and evaluate vaccination prioritization strategies by age and worker status. We use a mathematical model of SARS-CoV-2 transmission and uniquely detailed contact data collected as part of the Berkeley Interpersonal Contact Survey to evaluate five vaccination prioritization strategies: (1) prioritizing only adults over age 65, (2) prioritizing only high-contact workers, (3) splitting prioritization between adults 65+ and high-contact workers, (4) tiered prioritization of adults over age 65 followed by high-contact workers, and (5) tiered prioritization of high-contact workers followed by adults. We find that for the primary two-dose vaccination schedule, assuming 70% uptake, a tiered roll-out that first prioritizes adults 65+ averts the most deaths (31% fewer deaths compared to a no-vaccination scenario) while a tiered roll-out that prioritizes high contact workers averts the most number of clinical infections (14% fewer clinical infections compared to a no-vaccination scenario). We also consider prioritization strategies for booster doses during a subsequent outbreak of a hypothetical new SARS-CoV-2 variant. We find that a tiered roll-out that prioritizes adults 65+ for booster doses consistently averts the most deaths, and it may also avert the most number of clinical cases depending on the epidemiology of the SARS-CoV-2 variant and the vaccine efficacy.
A systematic review of interleukin-2-based immunotherapies in clinical trials for cancer and autoimmune diseases
Authors: Raeber Miro E. , Sahin Dilara , Karakus Ufuk , Boyman Onur 
Published: December 2022

AbstractBackgroundThe cytokine interleukin-2 (IL-2) can stimulate both effector immune cells and regulatory T (Treg) cells. The ability of selectively engaging either of these effects has spurred interest in using IL-2 for immunotherapy of cancer and autoimmune diseases. Thus, numerous IL-2-based biologic agents with improved bias or delivery toward effector immune cells or Treg cells have been developed. These improved IL-2-based compounds recently entered clinical trials.ObjectiveThis study systematically reviews clinical results of improved IL-2-based compounds for the treatment of cancer or autoimmune diseases.MethodsWe followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), searched theClinicalTrials.govdatabase for registered IL-2 trials using improved IL-2-based agents and different databases for available results of these studies.ResultsWe identified 547 registered clinical trials, of which we extracted 36 studies on improved IL-2-based compounds. Moreover, we assessed another 9 agents reported in two recent literature reviews and based on our knowledge, totaling in 45 improved IL-2-based compounds. A secondary search for registered clinical trials of each of these improved 45 compounds resulted in 139 clinical trials included in this systematic review, with 29 trials reporting clinical results.ConclusionsAs of yet, none of the improved IL-2-based compounds gained regulatory approval for the treatment of cancer or autoimmune diseases. Three compounds treating cancer have entered phase 3 trials with two studies still ongoing. NKTR-214 is the only compound that has completed phase 3 studies. The PIVOT IO-001 study testing the combination of NKTR-214 plus Pembrolizumab compared to Pembrolizumab monotherapy in metastatic melanoma missed its primary endpoint of superior objective response rate and progression-free survival. The PIVOT-09 study, combining NKTR-214 with Nivolumab compared to Sunitinib or Cabozantinib in advanced renal cell carcinoma, missed its primary endpoint of improved objective response rate. Trials in autoimmune diseases are currently in early stages, thus not allowing conclusions on efficacy. Results of ongoing trials will provide insight into which improved IL-2-based compounds will be beneficial for cancer and autoimmune diseases.
The Societal Value of Vaccines: Expert-Based Conceptual Framework and Methods Using COVID-19 Vaccines as A Case Study
Authors: Fusco Manuela Di , Mendes Diana , Steuten Lotte , Bloom David E , Drummond Michael , Hauck Katharina , Pearson-Stuttard Jonathan , Power Rachel , Salisbury David , Towse Adrian , Roiz Julie , Szabo Gabor , Yang Jingyan , Marczell Kinga 
Published: December 2022

AbstractHealth technology assessments (HTAs) of vaccines typically focus on the direct health benefits to individuals and healthcare systems. COVID-19 highlighted the widespread societal impact of infectious diseases and the value of vaccines in averting adverse clinical consequences and in maintaining or resuming social and economic activities. Using COVID-19 as a case study, this research work aimed to set forth a conceptual framework capturing the broader value elements of vaccines and to identify appropriate methods to quantify value elements not routinely considered in HTAs. A two-step approach was adopted combining a targeted literature review and three rounds of expert elicitation based on a modified Delphi method, leading to a conceptual framework of 30 value elements related to broader health effects, societal and economic impact, public finances, and uncertainty value. When applying the framework to COVID-19 vaccines in post-pandemic settings, 13 value elements were consensually rated highly important by the experts for consideration in HTAs. The experts reviewed over 10 methods that could be leveraged to quantify broader value elements and provided technical forward-looking recommendations. Limitations of the framework and the identified methods were discussed. This study supplements on-going efforts aimed towards a broader recognition of the full societal value of vaccines.
Danger changes the way the brain consolidates neutral information; and does so by interacting with processes involved in the encoding of that information
Authors: Qureshi Omar A. , Leake Jessica , Delaney Andrew J. , Killcross Simon , Westbrook R. Frederick , Holmes Nathan M. 
Published: December 2022

AbstractThis study examined the effect of danger on consolidation of neutral information in two regions of the rat (male and female) medial temporal lobe: the perirhinal cortex (PRh) and basolateral amygdala complex (BLA). The neutral information was the association that forms between an auditory stimulus and a visual stimulus (labelled S2 and S1) across their pairings in sensory preconditioning. We show that, when the sensory preconditioning session is followed by a shocked context exposure, the danger shifts consolidation of the S2-S1 association from the PRh to the BLA; and does so by interacting with processes involved in encoding of the S2-S1 pairings. Specifically, we show that the initial S2-S1 pairing in sensory preconditioning is encoded in the BLA and not the PRh; whereas the later S2-S1 pairings are encoded in the PRh and not the BLA. When the sensory preconditioning session is followed by a context alone exposure, the BLA-dependent trace of the early S2-S1 pairings decays and the PRh-dependent trace of the later S2-S1 pairings is consolidated in memory. However, when the sensory preconditioning session is followed by a shocked context exposure, the PRh-dependent trace of the later S2-S1 pairings is suppressed and the BLA-dependent trace of the initial S2-S1 pairing is consolidated in memory. These findings are discussed with respect to mutually inhibitory interactions between the PRh and BLA, and the way that these regions support memory in other protocols, including recognition memory in people.Significance StatementThe perirhinal cortex (PRh) and basolateral amygdala complex (BLA) process the pairings of neutral auditory and visual stimuli in sensory preconditioning. The involvement of each region in this processing is determined by the novelty/familiarity of the stimuli as well as events that occur immediately after the preconditioning session. Novel stimuli are represented in the BLA; however, as these stimuli are repeatedly presented without consequence, they come to be represented in the PRh. Whether the BLA- or PRh-dependent representation is consolidated in memory depends on what happens next. When nothing of significance occurs, the PRh-dependent representation is consolidated and the BLA-dependent representation decays; but when danger is encountered, the PRh-dependent representation is inhibited and the BLA-dependent representation is selected for consolidation.
Evaluating methods for measuring background connectivity in slow event-related functional MRI designs
Authors: Frank Lea E. , Zeithamova Dagmar 
Published: December 2022

AbstractResting-state functional MRI (fMRI) is widely used for measuring functional interactions between brain regions, significantly contributing to our understanding of large-scale brain networks and brain-behavior relationships. Furthermore, idiosyncratic patterns of resting-state connections can be leveraged to identify individuals and predict individual differences in clinical symptoms, cognitive abilities, and other individual factors. Idiosyncratic connectivity patters are thought to persist across task states, suggesting task-based fMRI can be similarly leveraged for individual differences analyses. Here, we tested the degree to which functional interactions occurring in the background of a task during slow event-related fMRI parallel or differ from those captured during resting-state fMRI. We compared two approaches for removing task- evoked activity from task-based fMRI: (1) applying a low-pass filter to remove task- related frequencies in the signal, or (2) extracting residuals from a general linear model (GLM) that accounts for task-evoked responses. We found that the organization of large-scale cortical networks and individual’s idiosyncratic connectivity patterns are preserved during task-based fMRI. In contrast, individual differences in connection strength can vary more substantially between rest and task. Compared to low-pass filtering, background connectivity obtained from GLM residuals produced idiosyncratic connectivity patterns and individual differences in connection strength that more resembled rest. However, all background connectivity measures were highly similar when derived from the low-pass filtered signal or GLM residuals, indicating that both methods are suitable for measuring background connectivity. Together, our results highlight new avenues for the analysis of task-based fMRI datasets and the utility of each background connectivity method.
COMPARATIVE RADIOPATHOLOGY OF MALE REPRODUCTIVE ORGANS IN SPRAGUE DAWLEY RATS ADMINISTERED WITHCurcuma longaANDOcimum sanctumAGAINST ACUTE GAMMA IRRADIATION
Authors: Thapru Meikunu , Nair Anirudh A , Hoque Rakibul , Namasudra Mousumi , De Arun Kumar , Pradhan Saktipada , Hansda Rabindra Nath , Mukhopadhayay S. K. , Mondal Samiran 
Published: December 2022

ABSTRACTObjectiveThe study was designed to evaluate the deleterious e□ects of acute lethal gamma irradiation on male reproductive organs of Sprague Dawley rats and the radioprotective potential byCurcuma longaandOcimum sanctumin experimental set up.Methods25 Male Spraque Dawley rats were taken and randomized into 5 groups (T1, T2, T3, T4, T5). Each group containing 5 animals. The groups were named as Group T1 (Negative Control), Group T2 (irradiation positive control), Group T3 (irradiation andCurcuma longa), Group T4 (irradiation andOcimum sanctum), Group T5 (irradiation,Curcuma longaandOcimum sanctum). The rats in groups T1 and T2 were given a daily dosage of normal saline for 14 days. Group T3 and T4 rats received aqueous extracts ofCurcuma longa(40 mg/kg) andOcimum sanctum(40 mg/kg), respectively, whereas group T5 rats received a combination of aqueous extracts ofCurcuma longa(40 mg/kg) andOcimum sanctum(40 mg/kg) for 14 days. prior to gamma irradiation. Animals of group T2, T3, T4, T5 were irradiated with 10 Gy of γ – radiation on 15th day.ResultsExposure of animals to 10 Gy gamma radiation resulted in significant decrease in body weight and testicular weight. Histopathological observations revealed testicular degenerative changes in the seminiferous tubules with primary spermatocytes being most affected and epididymis showed decreased spermatids density with cell debris in the lumen. Pretreatment withCurcuma longaat 40mg/kg for 14 days alleviated the radiation induced pathological changes in testis and epididymis.Curcuma longademonstrated much better protective effect in combination withOcimum sanctumin alleviating the radio pathological changes showing the possibility of synergistic effect. However, administration ofOcimum sanctumalone at 40mg/kg for 14 days did not reveal any significant radioprotective property after histomorphological evaluation.ConclusionGamma irradiation of 10 Gy induces severe radio pathological damage to organs of male reproductive system of Spraque Dawley rats. Pre-treatment withCurcuma longaprior to radiotherapy may be effective in preventing radiation-induced damage in the male reproductive organs. Better radioprotection can be achieved with the combination ofCurcuma longaandOcimum sanctumthan using alone.
Regression convolutional neural network models implicate peripheral immune regulatory variants in the predisposition to Alzheimer’s disease
Authors: Ramamurthy Easwaran , Agarwal Snigdha , Toong Noelle , Kaplow Irene M. , Phan BaDoi , Pfenning Andreas R. 
Published: December 2022

ABSTRACTAlzheimer’s disease (AD) involves aggregation of amyloid β and tau, neuron loss, cognitive decline, and neuroinflammatory responses. Both resident microglia and peripheral immune cells have been associated with the immune component of AD. However, the relative contribution of resident and peripheral immune cell types to AD predisposition has not been thoroughly explored due to their similarity in gene expression and function. To study the effects of AD associated variants oncis-regulatory elements, we train convolutional neural network (CNN) regression models that link genome sequence to cell type-specific levels of open chromatin, a proxy for regulatory element activity. We then usein silicomutagenesis of regulatory sequences to predict the relative impact of candidate variants across these cell types. We develop and apply criteria for evaluating our models and refine our models using massively parallel reporter assay (MPRA) data. Our models identify many AD-associated variants with a greater predicted impact in peripheral cells relative to microglia or neurons but few with greater predicted impact in microglia and neurons. Our results suggest that peripheral immune cells themselves may mediate a component of AD predisposition and support their use as models to study the effects of AD associated variants. We make our library of CNN models and predictions available as a resource for the community to study immune and neurological disorders.
Optical-quality assessment of a miniaturized intraocular telescope
Authors: Nepita Irene , Raimondi Raffaele , Piazza Simonluca , Diaspro Alberto , Vidal-Aroca Faustino , Surdo Salvatore , Romano Mario R. 
Published: December 2022

AbstractPurposeEvaluating the optical transmission and geometrical aberrations of an intraocular device, namely, the Small-Incision New Generation Implantable Miniature Telescope (SING IMT™, Samsara Vision), designed to correct age-related macular degeneration.MethodsOptical transmission in the spectral range 350-750 nm of the implantable optics was recorded with a fiber-optic spectrometer. Geometrical aberrations were studied by measuring the wavefront of a laser beam after passing through the implantable optics and performing an expansion of the measured wavefront into a Zernike polynomial basis. The study was conducted underin-vitroexperimental conditions. A second monofocal intraocular lens (SY60WF, Alcon) was tested and used as reference for assessing the optical quality of the SING IMT™ device.ResultsSpectroscopy measurements revealed that the SING IMT™ and monofocal IOL element feature UV-rejection and blue-rejection capabilities, respectively. Wavefront concavity indicated that the SING IMT™ behaves as a diverging lens with a focal length of approximately -100 mm; Zernike analysis showed that SING IMT™ has negligible coma, trefoil, astigmatism, and spherical aberrations of any order and along any direction.ConclusionsThe SING IMT™ exhibited even optical transmission in the whole visible spectrum and curvature capable of magnifying the retinal images without introducing geometrical aberrations, which proves the feasibility of this device as high-quality optical element for imaging. The rigidity of the compound lens of the SING IMT™ prevents mechanically-induced distortions, an issue encountered with polymeric lenses.Translational RelevanceSpectrometry andin vitrowavefront analysis provide evidence supporting the new generation miniaturized telescopic intraocular lens as a favorable option to intraocular implant in age-related macular degeneration.
Plant architecture is correlated with variation in cannabinoid concentration and biomass production inCannabis sativa
Authors: Stack George M. , Carlson Craig H. , Toth Jacob A. , Philippe Glenn , Crawford Jamie L. , Hansen Julie L. , Viands Donald R. , Rose Jocelyn K. C. , Smart Lawrence B. 
Published: December 2022

AbstractCannabis sativais cultivated for multiple uses including the production of cannabinoids. In developing improved production systems for high-cannabinoid cultivars, scientists and cultivators must consider the optimization of complex and interacting sets of morphological, phenological, and biochemical traits, which have historically been shaped by natural and anthropogenic selection. Determining factors that modulate cannabinoid variation within and among genotypes is fundamental to developing efficient production systems and understanding the ecological significance of cannabinoids. Thirty-two high-cannabinoid hemp cultivars were characterized for traits including flowering date and shoot-tip cannabinoid concentration.Additionally, a set of plant architecture traits, as well as wet, dry, and stripped inflorescence biomass were measured at harvest. One plant per plot was partitioned post-harvest to quantify intra-plant variation in inflorescence biomass production and cannabinoid concentration. Some cultivars showed intra-plant variation in cannabinoid concentration, while many had a consistent concentration regardless of canopy position. There was both intra- and inter-cultivar variation in architecture that correlated with intra-plant distribution of inflorescence biomass, and concentration of cannabinoids sampled from various positions within a plant. These relationships among morphological and biochemical traits will inform future decisions by cultivators, regulators, and plant breeders as well as our broader understanding of intra-plant variation of specialized biochemicals.HighlightIn-season hemp plant architecture measurements can predict post-harvest traits related to the distribution of biomass and concentration of cannabinoids.
Single-Cell Transcriptional and Epigenetic Profiles of Male Breast Cancer Nominate Salient Cancer-Specific Enhancers
Authors: Kim Hyunsoo , Wisniewska Kamila , Regner Matthew J. , Spanheimer Philip M. , Franco Hector L. 
Published: December 2022

ABSTRACTMale breast cancer represents about 1% of all breast cancer diagnoses and, although there are some similarities between male and female breast cancer, the paucity of data available on male breast cancer makes it difficult to establish targeted therapies. To date, most male breast cancers (MBC) are treated according to protocols established for female breast cancer (FBC). Thus, defining the transcriptional and epigenetic landscape of MBC with improved resolution is critical for developing better avenues for therapeutic intervention. In this study, we present matched transcriptional (scRNA-seq) and epigenetic (scATAC-seq) profiles at single-cell resolution of two treatment naïve MBC tumors processed immediately after surgical resection. These data enable the detection of differentially expressed genes between male and female breast tumors across immune, stromal, and malignant cell types, to highlight several genes that may have therapeutic implications. Notably,MYCtarget genes andmTORC1signaling genes were significantly upregulated in the malignant cells of MBC compared to the female counterparts. To understand how the regulatory landscape of MBC give rise to these male-specific gene expression patterns, we leveraged the scATAC-seq data to systematically link changes in chromatin accessibility to changes in gene expression within each cell type. We observed cancer-specific rewiring of several salient enhancers and posit that these enhancers have a higher regulatory load than lineage specific enhancers. We highlight two examples of previously unannotated cancer-cell specific enhancers ofANXA2andPRDX4gene expression and show evidence for super-enhancer regulation ofLAMB3andCD47in male breast cancer cells. Overall, this dataset annotates clinically relevant regulatory networks in male breast tumors, providing a useful resource that expands our current understanding of the gene expression programs that underlie the biology of MBC.
Mathematical modeling of mechanosensing and contact-dependent motility coordination inMyxococcus xanthus
Authors: Chen Yirui , Chen Jing 
Published: December 2022

AbstractSensing and responding to mechanical cues in the environment are important for the survival and propagation of bacteria. A ‘social’ bacterium,Myxococcus xanthus, which exhibits periodic cell reversals, modulates its reversal frequency in response to environmental mechanical cues, such as substrate stiffness and cell-cell contact. InM. xanthuspopulations, the cell-cell contact-dependent reversal control is particularly important for formation of complex multicellular patterns and structures during the cooperative ‘social’ behaviors. Here we hypothesize that the gliding motility machinery ofM. xanthuscan sense the environmental mechanical cues during force generation and modulate the timing and frequency of cell reversal through signaling the cell’s reversal control pathway. To examine our hypothesis, we extend an existing mathematical model for periodic polarity switching (which mediates periodic cell reversal) inM. xanthus, and incorporate the experimentally suggested (i) intracellular dynamics of the gliding motors and (ii) interactions between the gliding motors and reversal regulators. The model results suggest the proper mode of interaction between the gliding motors and reversal regulators that can generate the observed increase of cell reversal frequency on stiffer substrates. Furthermore, the selected model predicts a cell reversal response to cell-cell contact, which is sufficient for generating the rippling wave, an important multicellular pattern inM. xanthuspopulations. Our model highlights a potential role of the gliding machinery ofM. xanthusas a ‘mechanosensor’ that transduces mechanical cues into a reversal control signal.