bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clarifying the role of an unavailable distractor in human multiattribute choice
Authors: Cao Yinan , Tsetsos Konstantinos 
Published: August 2022

AbstractDecisions between two economic goods can be swayed by a thirdunavailable‘decoy’ alternative, which does not compete for choice, notoriously violating the principles of rational choice theory. Although decoy effects typically depend on the decoy’s position in a multiattribute choice space, recent studies using risky prospects (i.e., varying in reward and probability) reported a novel ‘positive’ decoy effect operating on a single ‘value’ dimension: the higher the ‘expected value’ of an unavailable (distractor) prospect was, the easier the discrimination between two available target prospects became, especially when their expected-value difference was small. Here we show that this unidimensional distractor effect affords alternative interpretations: it occurred because the distractor’s expected value covaried positively with the subjective utility difference between the two targets. Looking beyond this covariation, we report a modest ‘negative’ distractor effect operating on subjective utility, as well as classic multiattribute decoy effects. A normatively meaningful model (selective integration), in which subjective utilities are shaped by ‘intra-attribute’ information distortion, reproduces the multiattribute decoy effects, and as an epiphenomenon, the negative unidimensional distractor effect. These findings clarify the modulatory role of an unavailable distracting option, shedding fresh light on the mechanisms that govern multiattribute decisions.
A circuit mechanism for the coordinated actions of opposing neuropeptide and neurotransmitter signals
Authors: Soden Marta E. , Yee Joshua X. , Zweifel Larry S. 
Published: August 2022

SummaryFast-acting neurotransmitters and slow, modulatory neuropeptides are commonly co-released from neurons in the central nervous system (CNS), albeit from distinct synaptic vesicles1. The mechanisms of how co-released neurotransmitters and neuropeptides that have opposing actions, e.g., stimulatory versus inhibitory, work together to exert control of neural circuit output remain unclear. This question has been difficult to resolve due to the inability to selectively isolate these signaling pathways in a cell- and circuit-specific manner. To overcome these barriers, we developed a genetic-based anatomical disconnect procedure that utilizes distinct DNA recombinases to independently facilitate conditional in vivo CRISPR/Cas9 mutagenesis2 of neurotransmitter- and neuropeptide-related genes in distinct cell types in two different brain regions simultaneously. With this approach we demonstrate that the stimulatory neuropeptide neurotensin (Nts) and the inhibitory neurotransmitter γ-aminobutyric acid (GABA), which are co-released from neurons in the lateral hypothalamus (LH), work coordinately to activate dopamine neurons of the ventral tegmental area (VTA-DA). We show that GABA release from LH-Nts neurons acts on GABA neurons within the VTA to rapidly disinhibit VTA-DA neurons, while Nts signals through the Nts receptor 1 (Ntsr1) on VTA-DA neurons to promote a slow depolarization of these cells. Thus, these two signals act on distinct time scales through different cell types to enhance mesolimbic dopamine neuron activation, which optimizes behavioral reinforcement. These data demonstrate a circuit-based mechanism for the coordinated action of a neurotransmitter and neuropeptide with opposing effects on cell physiology.
Characterizing the genetic polymorphisms in 370 challenging medically relevant genes using long-read sequencing data from 41 human individuals among 19 global populations
Authors: Ji Yanfeng , Gong Jiao , Sedlazeck Fritz J , Fan Shaohua 
Published: August 2022

ABSTRACTNumerous challenging medically relevant genes (CMRGs) cannot be adequately investigated using next-generation sequencing, hindering the detection of functional variation among these genes. In this study, long-read sequencing data from 41 human individuals across 19 populations were analyzed using the current version of the human reference genome assembly (GRCh38) and a telomere-to-telomere assembly of the human genome (T2T-CHM13). After excluding 142 CMRGs containing windows with a depth of coverage (DoC) significantly deviating from the average DoC value of proteincoding regions in the GRCh38 (138) or T2T-CHM13 (47) assemblies, 179 and 263 CMRGs exhibited copy number variation (CNV) signal in GRCh38 and T2T-CHM13, respectively. In addition, 451 high-impact short variants were detected in 188 CMRGs. Further, some genetic alterations were individual- or continental-superpopulation-specific, suggesting a strong need to consider genetic background differences in future genetic testing and drug design studies. Finally, side-by-side comparisons of short variant calls in CMRGs using NGS and LRS data from 13 samples indicated that 15.79% to 33.96% of high-impact short variants in different individuals could only be detected using LRS data. The results described herein will be an important reference for future clinical and pharmacogenetic studies to further improve precision medicine.
Evaluation of a process to implement advance care planning conversations in primary care: uptake and patient experience
Authors: Arora Neha , Guenter Dale , Hafid Abe , Elston Dawn , Gallagher Erin , Winemaker Samantha , Hansen Nicolle , Waters Heather , Howard Michelle 
Published: August 2022

ABSTRACTObjectiveAdvance care planning (ACP) can support patients in achieving current and future medical care that aligns with their values and goals. In primary care, a lack of standardized processes hinders implementation of ACP conversations. This study reports a quality improvement process to identify and engage patients and clinicians in ACP.MethodsPrimary care clinicians received training in conversations based on the Serious Illness Conversation Guide and tools to support ACP. In December 2019, patients 65 years of age and older with chronic obstructive pulmonary disease were systematically identified, mailed ACP resources and telephoned by the clinic to invite them to an ACP appointment. We tracked the attendance of the patients and evaluated patient experience using a survey.ResultsOf the 91 patients telephoned, 50 were reached, and 27 attended the appointment. Further efforts were suspended in March 2020 due to the COVID-19 pandemic. Thirteen patients completed the survey. There were statistically significant increases in the patient’s perception of being heard and understood by their physician, feeling hopeful about quality of life and feeling peaceful.ConclusionThis study provides evidence that with training, tools and processes, patients and primary care clinicians can be effectively engaged in ACP conversations.KEY MESSAGESWhat was already known?Training resources exist for help clinicians enhance their advance care planning communication skillsBesides a need for skills, other practical challenges exist in implementing advance care planning in family practiceWhat are the new findings?Structured patient identification and preparation can facilitate advance care planning conversations in family practicePatients reported positive experiences of the conversationsWhat is their significance?Clinical: It is important to move beyond clinician training alone to implement processes in family practice to trigger advance care planning conversationsResearch: Further research to identify effective scalable approaches to triggering and implementing advance care planning conversations in family practice would be beneficial
A County-level Analysis of the Association Between Medicaid Expansion and Medicare Spending
Authors: El-Nahal Walid G. , Eisenberg Mattew D. 
Published: August 2022

AbstractBackgroundIf access to Medicaid improves health outcomes, it may also result in lower long-term spending, however the association between Medicaid expansion and Medicare spending is unknown. In this analysis we sought to investigate the association between Medicaid expansion and per capita Medicare spending at the county level.MethodsThis is an observational analysis of all U.S. counties in the ten years from 2010 to 2019. We used a difference-in-difference event study to investigate the difference in per capita Medicare spending between counties in states that expanded Medicaid and counties in states that did not expand Medicaid. The exposure was treatment year, which characterized whether a county was in an expansion state and when expansion occurred. In non-expansion counties, treatment year was assigned 0 for all observations. In expansion counties, treatment year ranged from -3 to +6, with treatment year 1 corresponding to the first full year of expansion. The primary outcome was fee-for-service Medicare spending per capita in each county. A secondary analysis investigated subcategories of per capita spending including inpatient, outpatient, skilled nursing care, inpatient rehabilitation, home health, and hospice care.ResultsWe analyzed 1,648 expansion and 1,494 non-expansion counties, with ten observations per county, one for each year between 2010 and 2019. In the adjusted event study analysis, the difference between expansion and non-expansion counties in expansion year 5 compared to pre-expansion was -200 [95% Confidence Interval (CI): -406, 6] dollars. In the subcategory analysis, the difference in inpatient care, skilled nursing care, outpatient care, and home health spending were -46 [95% CI: -103, 12], -92 [95% CI: -194, 11], 57 [95% CI: -67, 181], and 55 [95% CI: -17, 126] dollars per capita respectively.ConclusionsMedicaid expansion is not consistently significantly associated with lower Medicare spending compared to pre-expansion. However, observed trends towards lower spending and cost-shifting from inpatient to outpatient settings in expansion counties warrant additional investigation.
Circulating tumor DNA profiling approach based on in silico background elimination guides patient classification of multiple cancers
Authors: Li Ming , Xie Sisi , Hou Tao , Shao Tong , Kuang Jingyu , Lu Chenyu , Liu Xianling , Zhu Lingyun , Zhu Lvyun 
Published: August 2022

AbstractCirculating tumor DNA (ctDNA) analysis is increasingly providing a promising minimally invasive alternative to tissue biopsies in precision oncology. However, current methods of ctDNA mutation profiling have limited resolution because of the high background noise and false-positive rate caused by benign variants in plasma cell-free DNA (cfDNA), majorly generated during clonal hematopoiesis. Although personalized parallel white blood cell (WBC) genome sequencing suppresses the noise of clonal hematopoiesis variances observed in ctDNA based liquid biopsy, the system cost and complexity restrict its extensive application in clinical settings. To address this challenge, we describe a Matched WBC Genome sequencing Independent CtDNA profiling (MaGIC) approach, which enables the sensitive detection of recurrent tumor mutant information harbored by ctDNA from a bulk cfDNA background based on hybrid capture cfDNA deep sequencing, in silico background elimination, and a reliable readout measurement by the calculation the number of key mutated exons. Leveraging somatic mutation data from 10163 patients across 24 cancer types obtained from The Cancer Genome Atlas, we confirm that the MaGIC approaches are of ideal performance in prediction of prognosis by tissue biopsy samples of patients across multiple cancers. Meanwhile, MaGIC approaches enable the classification of prostate cancer patients from heathy cohorts by ctDNA sequencing data. We further profiled the ctDNAs of 80 plasma samples from 40 patients with nasopharyngeal carcinoma before and during chemotherapy by MaGIC approaches. The MaGICv2 can predict the chemosensitivity with high accuracy by simply using one liquid biopsy sample of each patient before a stereotypical treatment course. We anticipate that this new approach has the potential utility of ctDNA detection in multiple clinical cancer contexts, thus facilitating precise cancer therapy.TeaserA liquid biopsy analysis method for multifunctional patient classification such as diagnosis and chemosensitivity prediction.
Neutralization of Omicron BA.4/BA.5 and BA.2.75 by Booster Vaccination or BA.2 Breakthrough Infection Sera
Authors: Wang Xun , Ai Jingwen , Li Xiangnan , Zhao Xiaoyu , Wu Jing , Zhang Haocheng , He Xing , Zhao Chaoyue , Qiao Rui , Li Minghui , Cui Yuchen , Chen Yanjia , Yang Lulu , Hu Zixin , Xu Chenqi , Zhang Wenhong , Wang Pengfei 
Published: August 2022

AbstractMany new Omicron sub-lineages have been reported to evade neutralizing antibody response, including BA.2, BA.2.12.1, BA.4 and BA.5. Most recently, another emerging sub-lineage BA.2.75 has been reported in multiple countries. In this study, we constructed a comprehensive panel of pseudoviruses (PsVs), including wild-type, Delta, BA.1, BA.1.1, BA.2, BA.3, BA.2.3.1, BA.2.10.1, BA.2.12.1, BA.2.13, BA.2.75 and BA.4/BA.5, with accumulate coverage reached 91% according to the proportion of sequences deposited in GISAID database since Jan 1st, 2022. We collected serum samples from healthy adults at day14 post homologous booster with BBIBP-CorV, or heterologous booster with ZF2001, primed with two doses of BBIBP-CorV, or from convalescents immunized with three-dose inactivated vaccines prior to infection with Omicron BA.2, and tested their neutralization activity on this panel of PsVs. Our results demonstrated that all Omicron sub-lineages showed substantial evasion of neutralizing antibodies induced by vaccination and infection, although BA.2.75 accumulated the largest number of mutations in its spike, BA.4 and BA.5 showed the strongest serum escape. However, BA.2 breakthrough infection could remarkably elevated neutralization titers against all different variants, especially titers against BA.2 and its derivative sub-lineages.
Complex host/symbiont integration of a multi-partner symbiotic system in the eusocial aphid Ceratovacuna japonica
Authors: Yorimoto Shunta , Hattori Mitsuru , Maki Kondo , Shigenobu Shuji 
Published: August 2022

AbstractSome hemipteran insects rely on multiple endosymbionts for essential nutrients. However, the evolution of multi-partner symbiotic systems is not well-established. Here, we report a co-obligate symbiosis in the eusocial aphid, Ceratovacuna japonica. 16S rRNA amplicon sequencing unveiled co-infection with a novel Arsenophonus sp. symbiont and Buchnera aphidicola, a common obligate endosymbiont in aphids. Both symbionts were housed within distinct bacteriocytes and were maternally transmitted. The Buchnera and Arsenophonus symbionts had streamlined genomes of 432,286 bp and 853,149 bp, respectively, and exhibited metabolic complementarity in riboflavin and peptidoglycan synthesis pathways. These anatomical and genomic properties were similar to those of independently evolved multi-partner symbiotic systems, such as Buchnera–Serratia in Lachninae and Periphyllus aphids, representing remarkable parallelism. Furthermore, symbiont populations and bacteriome morphology differed between reproductive and soldier castes. Our study provides the first example of co-obligate symbiosis in Hormaphidinae and gives insight into the evolutionary genetics of this complex system.
Ranging patterns of the rainforest-adapted lion-tailed macaque Macaca silenus in a human-dominated landscape in the Anamalai hills of the Western Ghats, India
Authors: Dhawale Ashni Kumar , Sinha Anindya 
Published: August 2022

AbstractThe ranging patterns of five lion-tailed macaque Macaca silenus troops, forming the Puthuthottam sub-population, were studied over a three year period to determine road/habitation visitation rate, home ranges and habitat preference. Each troop visited the road or human habitation at varying rates, with the largest troop visiting most frequently. Home ranges sizes were observed to be highly reduced when compared to wild populations, and also greatly varied across troops, with relatively low overlap given the macaque density in the available area. All five macaque troops showed a preference for human-modified habitats such as roads and human settlements where anthropogenic food was easily available. Our study shows an increasing dependence amongst members of the Puthuthottam troops on anthropogenic foods, which has led to many threats faced by individuals including fatal collisions with vehicular traffic and electrocutions.
Systematic delineation of signaling and epigenomic mechanisms underlying microglia inflammatory activity in acute and chronic brain pathologies
Authors: Xavier Andre Machado , Distéfano-Gagné Félix , Belhamiti Nesrine , Belhocine Sarah , Bitarafan Sara , Falle Alexia , Fiola S. , Rivest Serge , Gosselin David 
Published: August 2022

AbstractMicroglia promptly mount an inflammatory response following detection of infectious agents or injuries in the central nervous system. Such function fundamentally depends upon dynamic modulation of gene expression. However, the signaling and epigenomic mechanisms that regulate the transcriptional process underlying microglial inflammatory activity are not well understood. To address this, we used RNA-seq, ChIP-seq and ATAC-seq to delineate gene signatures and activity across the repertoire of genomic regulatory elements of microglia engaged in acute and chronic neuroinflammatory activity. Systematic interrogations of the microglial population over time during a systemic inflammatory response revealed a coordinated, sequential activation of multiple gene programs associated with defense response, translation and cell cycling. Activation of these programs occurred in parallel with gain and loss of activity at 4,080 and 3,119 genomic cis-regulatory elements, respectively. Furthermore, computational analyses identified key transcriptional regulators, including Ets, AP-1, C/epb, Nf-κB, Irf, Runx, c-Myc and E2f family members, that display differential propensity for activity at gene promoters and promoter-distal cis-regulatory elements. Gene expression analyses also suggested that the transcriptional process likely contribute to the effective activity of numerous transcriptional regulators through the modulation of their mRNA levels. Finally, characterization of CD11c-positive microglia that emerge with chronic demyelinating brain lesions suggested that Egr2, Mef2 members and E-box-binding factors such as Tfeb and Mitf contribute to the enhanced phagosomal activity of this inflammatory subset. Loss-of-function experiments validated that Mef2a in microglia is necessary for the acquisition of the CD11c-positive phenotype. Collectively, these results demonstrate that the inflammatory activity of microglia arises through an intricate, ultimately context-dependent, interplay between signaling pathways, genomic regulatory elements and the transcriptional machinery.
Filming space-time changes of gene expression with expressyouRcell
Authors: Paganin Martina , Tebaldi Toma , Lauria Fabio , Viero Gabriella 
Published: August 2022

ABSTRACTThe last decade has witnessed massive advancements in high-throughput techniques capable of producing quantifications of transcript and protein levels across time and space, and at high resolution. Yet, the large volume of big data available and the complexity of experimental designs hamper an easy understanding and effective communication of the results.Here we present expressyouRcell, a unique and easy-to-use R package to map the multi-dimensional variations of transcript and protein levels in cell-pictographs. These variations are outcomes of differential and gene set enrichment analysis across space and time. Our tool directly associates these results with up to twenty specific cellular compartments, visualising them as pictographic representations of four different cellular thematic maps. expressyouRcell visually reduces the complexity of displaying gene expression and protein level changes across multiple time-points by generating dynamic representations of cellular pictographs.We applied expressyouRcell to six datasets, demonstrating its flexibility and usability in the visualization of simple and highly effective static and dynamic representations of time course variations in gene expression. Our approach complements classical plot-based methods for visualization and exploitation of biological data, improving the standard quantitative interpretation and communication of relevant results.
Tensorial Independent Component Analysis Reveals Social and Reward Networks Associated with Major Depressive Disorder
Authors: Dennison Jeff B. , Tepfer Lindsey J. , Smith David V. 
Published: August 2022

AbstractMajor depressive disorder (MDD) has been associated with changes in functional brain connectivity. Yet, typical analyses of functional connectivity, such as spatial ICA for resting-state data, often ignore sources of between-subject variability, which may be crucial for identifying functional connectivity patterns associated with MDD. Typically, methods like spatial ICA will identify a single component to represent a network like the default mode network (DMN), even if groups within the data show differential DMN coactivation. To address this gap, this project applies a tensorial extension of ICA (tensorial ICA)—which explicitly incorporates between-subject variability—to identify functionally connected networks using fMRI data from the Human Connectome Project (HCP). Data from the HCP included individuals with a diagnosis of MDD, a family history of MDD, and healthy controls performing a gambling and social cognition task. Based on evidence associating MDD with blunted neural activation to rewards and social stimuli, we predicted that tensorial ICA would identify networks associated with reduced spatio-temporal coherence and blunted social and reward-based network activity in MDD. Across both tasks, tensorial ICA identified three networks showing decreased coherence in MDD. All three networks included ventromedial prefrontal cortex (vmPFC), striatum, and cerebellum and showed different activation across the conditions of their respective tasks. However, MDD was only associated with differences in task-based activation in one network from the social task. Additionally, these results suggest that tensorial ICA could be a valuable tool for understanding clinical differences in relation to network activation and connectivity.
The Nested Hierarchy of Overt, Mouthed, and Imagined Speech Activity Evident in Intracranial Recordings
Authors: Soroush Pedram Z. , Herff Christian , Ries Stephanie K. , Shih Jerry J. , Schultz Tanja , Krusienski Dean J. 
Published: August 2022

AbstractRecent studies have demonstrated that it is possible to decode and synthesize various aspects of acoustic speech directly from intracranial measurements of electrophysiological brain activity. In order to continue progressing toward the development of a practical speech neuroprosthesis for the individuals with speech impairments, better understanding and modeling of imagined speech processes are required. The present study uses intracranial brain recordings from participants that performed a speaking task with trials consisting of overt, mouthed, and imagined speech, representing various degrees of decreasing behavioral output. Speech activity detection models are constructed using spatial, spectral, and temporal brain activity features, and the features and model performances are characterized and compared across the three degrees of behavioral output. The results indicate there is a hierarchy in which the relevant channels for the lower behavioral output modes form nested subsets of the relevant channels from the higher behavioral output modes. This provides important insights for the elusive goal of developing more effective imagined speech decoding models with respect to the better-established overt speech decoding counterparts.