bluuebunny/crossref_metadata_2025_split huggingface dataset:
Financial toxicity in hematological malignancies: a systematic review
Authors: Ouchveridze Evguenia , Banerjee Rahul , Desai Aakash , Aziz Muhammad , Lee-Smith Wade , Mian Hira , Berger Katherine , McClune Brian , Sborov Douglas , Qazilbash Muzaffar , Kumar Shaji , Mohyuddin Ghulam Rehman 
Published: April 2022

AbstractHematologic malignancy outcomes have remarkably improved in the past decade with further advancement expected in future years. However, the detrimental effects of financial toxicity (FT) on patients with hematologic malignancies, because of both diagnoses and subsequent treatments, have not been studied comprehensively. We performed a systematic review of all studies reporting FT as a primary or secondary outcome among adult or pediatric patients with hematological malignancies. A total of 55 studies met the inclusion criteria for analysis. Across studies, 20–50% of patients reported some form of FT, including loss of work productivity, food and transportation costs, and depletion of savings. Younger age, lower-income level, unemployment, and rural residence were the most commonly identified risk factors for FT. Two studies looked at survival outcomes, with one reporting improvement in survival with a decrease in financial toxicity. However, significant heterogeneity in FT definitions was found between countries and payor systems. Only half of the studies (51%, n = 28) used validated survey instruments such as the COST assessment. The present systematic review identified that FT is common in patients with hematological malignancies and may be associated with poorer outcomes. However, studies of FT generally use non-standardized methods with cross-sectional analyses rather than longitudinal, prospective assessments. Further work is needed to standardize FT reporting and investigate measures to alleviate FT among patients with hematologic malignancies.
p63, a key regulator of Ago2, links to the microRNA-144 cluster
Authors: Wang Benfan , Wu H. Helena , Abuetabh Yasser , Leng Sarah , Davidge Sandra T. , Flores Elsa R. , Eisenstat David D. , Leng Roger 
Published: April 2022

Abstract
As a key component of the RNA-induced silencing complex (RISC), Argonaute2 (Ago2) exhibits a dual function regulatory role in tumor progression. However, the mechanistic basis of differential regulation remains elusive. p63 is a homolog of the tumor suppressor p53. p63 isoforms play a critical role in tumorigenesis and metastasis. Herein, we show that p63 isoforms physically interact with and stabilize Ago2. Expression of p63 isoforms increases the levels of Ago2 protein, while depletion of p63 isoforms by shRNA decreases Ago2 protein levels. p63 strongly guides Ago2 dual functions in vitro and in vivo. Ectopic expression of the miR-144/451 cluster increases p63 protein levels; TAp63 transactivates the miR-144/451 cluster, forming a positive feedback loop. Notably, miR-144 activates p63 by directly targeting Itch, an E3 ligase of p63. Ectopic expression of miR-144 induces apoptosis in H1299 cells. miR-144 enhances TAp63 tumor suppressor function and inhibits cell invasion. Our findings uncover a novel function of p63 linking the miRNA-144 cluster and the Ago2 pathway.

Facts and questions

Identification of Ago2 as a p63 target.

Ago2 exhibits a dual function regulatory role in tumor progression; however, the molecular mechanism of Ago2 regulation remains unknown.

p63 strongly guides Ago2 dual functions in vitro and in vivo.

Unraveling a novel function of p63 links the miRNA-144 cluster and the Ago2 pathway.
Fragile, unfaithful and persistent Ys—on how meiosis can shape sex chromosome evolution
Authors: Ruiz-Herrera Aurora , Waters Paul D. 
Published: April 2022

AbstractSex-linked inheritance is a stark exception to Mendel’s Laws of Heredity. Here we discuss how the evolution of heteromorphic sex chromosomes (mainly the Y) has been shaped by the intricacies of the meiotic programme. We propose that persistence of Y chromosomes in distantly related mammalian phylogroups can be explained in the context of pseudoautosomal region (PAR) size, meiotic pairing strategies, and the presence of Y-borne executioner genes that regulate meiotic sex chromosome inactivation. We hypothesise that variation in PAR size can be an important driver for the evolution of recombination frequencies genome wide, imposing constraints on Y fate. If small PAR size compromises XY segregation during male meiosis, the stress of producing aneuploid gametes could drive function away from the Y (i.e., a fragile Y). The Y chromosome can avoid fragility either by acquiring an achiasmatic meiotic XY pairing strategy to reduce aneuploid gamete production, or gain meiotic executioner protection (a persistent Y). Persistent Ys will then be under strong pressure to maintain high recombination rates in the PAR (and subsequently genome wide), as improper segregation has fatal consequences for germ cells. In the event that executioner protection is lost, the Y chromosome can be maintained in the population by either PAR rejuvenation (extension by addition of autosome material) or gaining achiasmatic meiotic pairing, the alternative is Y loss. Under this dynamic cyclic evolutionary scenario, understanding the meiotic programme in vertebrate and invertebrate species will be crucial to further understand the plasticity of the rise and fall of heteromorphic sex chromosomes.
Exploring dopant effects in stannic oxide nanoparticles for CO2 electro-reduction to formate
Authors: Ko Young-Jin , Kim Jun-Yong , Lee Woong Hee , Kim Min Gyu , Seong Tae-Yeon , Park Jongkil , Jeong YeonJoo , Min Byoung Koun , Lee Wook-Seong , Lee Dong Ki , Oh Hyung-Suk 
Published: April 2022

AbstractThe electrosynthesis of formate from CO2 can mitigate environmental issues while providing an economically valuable product. Although stannic oxide is a good catalytic material for formate production, a metallic phase is formed under high reduction overpotentials, reducing its activity. Here, using a fluorine-doped tin oxide catalyst, a high Faradaic efficiency for formate (95% at 100 mA cm−2) and a maximum partial current density of 330 mA cm−2 (at 400 mA cm−2) is achieved for the electroreduction of CO2. Furthermore, the formate selectivity (≈90%) is nearly constant over 7 days of operation at a current density of 100 mA cm−2. In-situ/operando spectroscopies reveal that the fluorine dopant plays a critical role in maintaining the high oxidation state of Sn, leading to enhanced durability at high current densities. First-principle calculation also suggests that the fluorine-doped tin oxide surface could provide a thermodynamically stable environment to form HCOO* intermediate than tin oxide surface. These findings suggest a simple and efficient approach for designing active and durable electrocatalysts for the electrosynthesis of formate from CO2.
Enabling reactive microscopy with MicroMator
Authors: Fox Zachary R. , Fletcher Steven , Fraisse Achille , Aditya Chetan , Sosa-Carrillo Sebastián , Petit Julienne , Gilles Sébastien , Bertaux François , Ruess Jakob , Batt Gregory 
Published: April 2022

AbstractMicroscopy image analysis has recently made enormous progress both in terms of accuracy and speed thanks to machine learning methods and improved computational resources. This greatly facilitates the online adaptation of microscopy experimental plans using real-time information of the observed systems and their environments. Applications in which reactiveness is needed are multifarious. Here we report MicroMator, an open and flexible software for defining and driving reactive microscopy experiments. It provides a Python software environment and an extensible set of modules that greatly facilitate the definition of events with triggers and effects interacting with the experiment. We provide a pedagogic example performing dynamic adaptation of fluorescence illumination on bacteria, and demonstrate MicroMator’s potential via two challenging case studies in yeast to single-cell control and single-cell recombination, both requiring real-time tracking and light targeting at the single-cell level.
Similarities and differences between nigral and enteric dopaminergic neurons unravel distinctive involvement in Parkinson’s disease
Authors: Chalazonitis Alcmène , Rao Meenakshi , Sulzer David 
Published: April 2022

AbstractIn addition to the well-known degeneration of midbrain dopaminergic neurons, enteric neurons can also be affected in neurodegenerative disorders such as Parkinson’s disease (PD). Dopaminergic neurons have recently been identified in the enteric nervous system (ENS). While ENS dopaminergic neurons have been shown to degenerate in genetic mouse models of PD, analyses of their survival in enteric biopsies of PD patients have provided inconsistent results to date. In this context, this review seeks to highlight the distinctive and shared factors and properties that control the evolution of these two sets of dopaminergic neurons from neuronal precursors to aging neurons. Although their cellular sources and developmental times of origin differ, midbrain and ENS dopaminergic neurons express many transcription factors in common and their respective environments express similar neurotrophic molecules. For example, Foxa2 and Sox6 are expressed by both populations to promote the specification, differentiation, and long-term maintenance of the dopaminergic phenotype. Both populations exhibit sustained patterns of excitability that drive intrinsic vulnerability over time. In disorders such as PD, colon biopsies have revealed aggregation of alpha-synuclein in the submucosal plexus where dopaminergic neurons reside and lack blood barrier protection. Thus, these enteric neurons may be more susceptible to neurotoxic insults and aggregation of α-synuclein that spreads from gut to midbrain. Under sustained stress, inefficient autophagy leads to neurodegeneration, GI motility dysfunction, and PD symptoms. Recent findings suggest that novel neurotrophic factors such as CDNF have the potential to be used as neuroprotective agents to prevent and treat ENS symptoms of PD.
Autonomous quantum error correction in a four-photon Kerr parametric oscillator
Authors: Kwon Sangil , Watabe Shohei , Tsai Jaw-Shen 
Published: April 2022

AbstractAutonomous quantum error correction has gained considerable attention to avoid complicated measurements and feedback. Despite its simplicity compared with the conventional measurement-based quantum error correction, it is still a far from practical technique because of significant hardware overhead. We propose an autonomous quantum error correction scheme for a rotational symmetric bosonic code in a four-photon Kerr parametric oscillator. Our scheme is the simplest possible error correction scheme that can surpass the break-even point—it requires only a single continuous microwave tone. We also introduce an unconditional reset scheme that requires one more continuous microwave tone in addition to that for the error correction. The key properties underlying this simplicity are protected quasienergy states of a four-photon Kerr parametric oscillator and the degeneracy in its quasienergy level structure. These properties eliminate the need for state-by-state correction in the Fock basis. Our schemes greatly reduce the complexity of autonomous quantum error correction and thus may accelerate the use of the bosonic code for practical quantum computation.
An adjuvanted zoster vaccine elicits potent cellular immune responses in mice without QS21
Authors: Nam Hyo Jung , Hong Sung Jun , Lee Ara , Kim Jiyeon , Lee Sangho , Casper Corey , Carter Darrick , Reed Steven G. , Simeon George , Shin Eui-Cheol 
Published: April 2022

AbstractHerpes zoster (HZ) is caused by reactivation of latent varicella-zoster virus (VZV) when VZV-specific cellular immunity is insufficient to control reactivation. Currently, Shingrix, which contains the VZV gE protein and GSK’s AS01Badjuvant composed of liposomes formulated with cholesterol, monophosphoryl lipid A (MPL) and QS21, is used for prevention of HZ. However, reactogenicity to Shingrix is common leading to poor patient compliance in receiving one or both shots. Here, we evaluated the immunogenicity of a newly formulated gE protein-based HZ vaccine containing Second-generation Lipid Adjuvant (SLA), a synthetic TLR4 ligand, formulated in an oil-in-water emulsion (SLA-SE) without QS21 (gE/SLA-SE). In VZV-primed mouse models, gE/SLA-SE-induced gE-specific humoral and cellular immune responses at comparable levels to those elicited by Shingrix in young mice, as both gE/SLA-SE and Shingrix induce polyfunctional CD4+T-cell responses. In aged mice, gE/SLA-SE elicited more robust gE-specific T-cell responses than Shingrix. Furthermore, gE/SLA-SE-induced T-cell responses were sustained until 5 months after immunization. Thus, QS21-free, gE/SLA-SE is a promising candidate for development of gE-based HZ vaccines with high immunogenicity—particularly when targeting an older population.
S-Nitrosylated hemoglobin predicts organ yield in neurologically-deceased human donors
Authors: Nazemian Ryan , Matta Maroun , Aldamouk Amer , Zhu Lin , Awad Mohamed , Pophal Megan , Palmer Nicole R. , Armes Tonya , Hausladen Alfred , Stamler Jonathan S. , Reynolds James D. 
Published: April 2022

AbstractCurrent human donor care protocols following death by neurologic criteria (DNC) can stabilize macro-hemodynamic parameters but have minimal ability to preserve systemic blood flow and microvascular oxygen delivery. S-nitrosylated hemoglobin (SNO-Hb) within red blood cells (RBCs) is the main regulator of tissue oxygenation (StO2). Based on various pre-clinical studies, we hypothesized that brain death (BD) would decrease post-mortem SNO-Hb levels to negatively-impact StO2and reduce organ yields. We tracked SNO-Hb and tissue oxygen in 61 DNC donors. After BD, SNO-Hb levels were determined to be significantly decreased compared to healthy humans (p = 0·003) and remained reduced for the duration of the monitoring period. There was a positive correlation between SNO-Hb and StO2(p < 0.001). Furthermore, SNO-Hb levels correlated with and were prognostic for the number of organs transplanted (p < 0.001). These clinical findings provide additional support for the concept that BD induces a systemic impairment of S-nitrosylation that negatively impacts StO2and reduces organ yield from DNC human donors. Exogenous S-nitrosylating agents are in various stages of clinical development. The results presented here suggest including one or more of these agents in donor support regimens could increase the number and quality of organs available for transplant.
No evidence for disruption of reconsolidation of conditioned threat memories with a cognitively demanding intervention
Authors: Jaswetz Lars , de Voogd Lycia D. , Becker Eni S. , Roelofs Karin 
Published: April 2022

AbstractSimultaneous execution of memory retrieval and cognitively demanding interventions alter the subjective experience of aversive memories. This principle can be used in treatment to target traumatic memories. An often-used interpretation is that cognitive demand interferes with memory reconsolidation. Laboratory models applying this technique often do not meet some important procedural steps thought necessary to trigger reconsolidation. It remains therefore unclear whether cognitively demanding interventions can alter the reconsolidation process of aversive memories. Here, 78 (41 included) healthy participants completed an established 3-day threat conditioning paradigm. Two conditioned stimuli were paired with a shock (CS+ s) and one was not (CS-). The next day, one CS+ (CS+ R), but not the other (CS+), was presented as a reminder. After 10 min, participants performed a 2-back working memory task. On day three, we assessed retention. We found successful acquisition of conditioned threat and retention (CS+ s > CS-). However, SCRs to the CS+ R and the CS+ during retention did not significantly differ. Although threat conditioning was successful, the well-established cognitively demanding intervention did not alter the reconsolidation process of conditioned threat memories. These findings challenge current views on how cognitively demand may enhance psychotherapy-outcome.
Latent state-trait structure of BPRS subscales in clinical high-risk state and first episode psychosis
Authors: Hochstrasser Lisa , Studerus Erich , Riecher-Rössler Anita , Schimmelmann Benno G. , Lambert Martin , Lang Undine E. , Borgwardt Stefan , Stieglitz Rolf-Dieter , Huber Christian G. 
Published: April 2022

AbstractTo investigate the longitudinal latent state-trait structure of the different dimensions of psychosis symptoms in clinical high-risk state (CHRS) and first episode psychosis (FEP) individuals over a one year time-span. This paper examines if the symptom clusters Positive Symptoms, Negative Symptoms, Affectivity, Resistance, Activation, and Excitement according to the Brief Psychiatric Rating Scale (BPRS) differ in their trait and state characters in 196 CHRS and 131 FEP individuals. Statistical analysis was performed using latent state-trait analysis. On average, trait differences accounted for 72.2% of Positive Symptoms, 81.1% of Negative Symptoms, 57.0% of Affectivity, and 69.2% of Activation, whereas 15.0% of the variance of Resistance and 13.2% of the variance of Excitement were explained by trait differences. Explorative analyses showed a trait components’ increase of 0.408 in Positive Symptoms from baseline up to the 9th month and an increase of 0.521 in Affectivity from baseline up to the 6th month. Negative Symptoms had the highest trait component levels of all subscales between baseline and 6 months. The finding that an increasing proportion of psychosis symptoms is persisting over time underlines the importance of early intervention programs in individuals with psychotic disorders.
Characterization of transcriptome diversity and in vitro behavior of primary human high-risk breast cells
Authors: Alothman Sahar J. , Kang Keunsoo , Liu Xuefeng , Krawczyk Ewa , Azhar Redha I. , Hu Rong , Goerlitz David , Kallakury Bhaskar V. , Furth Priscilla A. 
Published: April 2022

AbstractBiology and transcriptomes of non-cancerous human mammary epithelial cells at risk for breast cancer development were explored following primary isolation utilizing conditional reprogramming cell technology from mastectomy tissue ipsilateral to invasive breast cancer. Cultures demonstrated consistent categorizable behaviors. Relative viability and mammosphere formation differed between samples but were stable across three different mammary-specific media. E2F cell cycle target genes expression levels were positively correlated with viability and advancing age was inversely associated. Estrogen growth response was associated with Tissue necrosis factor signaling and Interferon alpha response gene enrichment. Neoadjuvant chemotherapy exposure significantly altered transcriptomes, shifting them towards expression of genes linked to mammary stem cell formation. Breast cancer prognostic signature sets include genes that in normal development are limited to specific stages of pregnancy or the menstrual cycle. Sample transcriptomes were queried for stage specific gene expression patterns. All cancer samples and a portion of high-risk samples showed overlapping stages reflective of abnormal gene expression patterns, while other high-risk samples exhibited more stage specific patterns. In conclusion, at-risk cells preserve behavioral and transcriptome diversity that could reflect different risk profiles. It is possible that prognostic platforms analogous to those used for breast cancer could be developed for high-risk mammary cells.
Self-esteem depends on beliefs about the rate of change of social approval
Authors: Low Alexis An Yee , Hopper William John Telesfor , Angelescu Ilinca , Mason Liam , Will Geert-Jan , Moutoussis Michael 
Published: April 2022

AbstractA major challenge in understanding the neurobiological basis of psychiatric disorders is rigorously quantifying subjective metrics that lie at the core of mental illness, such as low self-esteem. Self-esteem can be conceptualized as a ‘gauge of social approval’ that increases in response to approval and decreases in response to disapproval. Computational studies have shown that learning signals that represent the difference between received and expected social approval drive changes in self-esteem. However, it is unclear whether self-esteem based on social approval should be understood as a value updated through associative learning, or as a belief about approval, updated by new evidence depending on how strongly it is held. Our results show that belief-based models explain self-esteem dynamics in response to social evaluation better than associative learning models. Importantly, they suggest that in the short term, self-esteem signals the direction and rate of change of one’s beliefs about approval within a group, rather than one’s social position.
Carry-over effects of dry period heat stress on the mammary gland proteome and phosphoproteome in the subsequent lactation of dairy cows
Authors: Skibiel Amy L. , Koh Jin , Zhu Ning , Zhu Fanchao , Yoo Mi-Jeong , Laporta Jimena 
Published: April 2022

AbstractExposure to heat stress during a cow’s dry period disrupts mammary gland remodeling, impairing mammary function and milk production during the subsequent lactation. Yet, proteomic changes in the mammary gland underlying these effects are not yet known. We investigated alterations in the mammary proteome and phosphoproteome during lactation as a result of dry period heat stress using an isobaric tag for relative and absolute quantitation (iTRAQ)-based approach. Cows were cooled (CL;n = 12) with fans and water soakers in a free stall setting or were heat stressed through lack of access to cooling devices (HT;n = 12) during the entire dry period (approximately 46 days). All cows were cooled postpartum. Mammary biopsies were harvested from a subset of cows (n = 4 per treatment) at 14, 42, and 84 days in milk. Overall, 251 proteins and 224 phosphorylated proteins were differentially abundant in the lactating mammary gland of HT compared to CL cows. Top functions of differentially abundant proteins and phosphoproteins affected were related to immune function and inflammation, amino acid metabolism, reactive oxygen species production and metabolism, tissue remodeling, and cell stress response. Patterns of protein expression and phosphorylation are indicative of increased oxidative stress, mammary gland restructuring, and immune dysregulation due to prior exposure to dry period heat stress. This study provides insights into the molecular underpinnings of disrupted mammary function and health during lactation arising from prior exposure to dry period heat stress, which might have led to lower milk yields.