bluuebunny/crossref_metadata_2025_split huggingface dataset:
How social engagement against Covid-19 in a Brazilian Slum helped mitigate rising statistics
Authors: Evangelista Heitor , Gonçalves Sérgio J. , Sodré Eduardo Delfino , Nogueira Juliana , Goldenberg-Barbosa Rodrigo , Magalhães Newton , dos Santos Angela M.G. , Godoi Ricardo H.M. , Amaral Cesar , da Silva Marcio Cataldo G. , de Oliveira Daniel A. Junger , Porto Luís Cristóvão 
Published: January 2021

AbstractObjectivesFor many underdeveloped countries, strategies implemented by social communities allied to scientific knowledge may be a rote to attenuate the rapid spread of Covid-19 cases and allow services to the population. This work presents a joint effort collaboration between scientists and underserved community groups from a Brazilian slum/Santa Marta in Rio de Janeiro City in the fight against Covid-19. Measurements of contamination in the air near the ground, georeferencing of data of infected people, were regressed with sanitization activities aiming at reducing the Covid-19 incidence.MethodsWe monitored aerosol containing SARS-Cov-2 virus in outdoor ambient air using various virus collection mediums (solid, liquid, and gelatinous substrates) at different aerodynamic sizes. We implemented a local statistics survey for the Covid-19 database correlated with varying sanitization levels between April 2020 and June 2021 developed in the Santa Marta slum.FindingsWe detected the SARS-CoV-2 virus in the air near the ground in diameters ranging from 0.25 to 0.5 µm, demonstrating that there is a circulation of the virus in the slum atmosphere. We demonstrate that Covid-19 cases for the Santa Marta slum were significatively lowered with improved sanitization levels (r = −0.74).ConclusionsDespite previous publications that discarded the use of sanitization as a relevant tool in the fight against Covid-19, our results suggest that profits can be achieved in mitigating Covid-19 in underserved community sites. Furthermore, a permanent sanitization activity may induce positive social behavior for the sake of combating Covid-19.
Single cell proteomics of tumor compartments identifies differential kinase activities defining sensitivity to mTOR-PI3-kinase inhibition
Authors: Karabacak Nezihi Murat , Zheng Yu , Dubash Taronish D. , Burr Risa , Micalizzi Douglas S. , Wittner Ben S. , Wiley Devon , Comaills Valentine , Emmons Erin , Niederhoffer Kira , Ho Uyen , Nieman Linda , Haas Wilhelm , Stott Shannon L. , Ting David T. , Miyamoto David T. , Haber Daniel A. , Toner Mehmet , Maheswaran Shyamala 
Published: January 2021

ABSTRACTCancer therapy often results in heterogeneous responses in different metastatic lesions in the same patient. Inter- and intra-tumor heterogeneity in proteomic signaling within the various tumor compartments and its impact on therapy are not well characterized due to the limited sensitivity of single cell proteomic approaches. To overcome this barrier, we applied single cell mass cytometry with a customized 29-antibody panel [against cell states, receptor tyrosine kinases (RTK) and phosphoinositide 3-kinase/mammalian target of rapamycin (PI3K/mTOR)-, mitogen-activated protein kinase (MAPK)-, and cytokine-signaling] to PTEN-deleted orthotopic prostate cancer xenograft models to measure the evolution of kinase activities in different tumor compartments during metastasis and upon drug treatment. Compared with primary tumors and circulating tumor cells (CTCs), bone metastases but not lung and liver metastases exhibited elevated PI3K/mTOR signaling and RTKs including c-Met protein, which, when suppressed, impaired tumor growth in the bone. Intra-tumoral heterogeneity within tumor compartments also arises from highly proliferative EpCAMhighepithelial cells with increased PI3K and mTOR kinase activities co-existing with poorly proliferating EpCAMlowmesenchymal populations with reduced kinase activities, findings recapitulated in epithelial and mesenchymal CTC populations in metastatic prostate and breast cancer patients. Increased kinase activity in EpCAMhighcells rendered them more sensitive to PI3K/mTOR inhibition and drug resistant EpCAMlowpopulations with reduced kinase activity emerged over time. Taken together, single cell proteomics identified microenvironment- and cell state-dependent activation of kinase networks creating heterogeneity and differential drug sensitivity among and within tumor populations across different sites, defining a new paradigm of drug responses to kinase inhibitors.
Role of T cells in intrauterine administration of activated peripheral blood mononuclear cells in recurrent implantation failure
Authors: Ricaud Guillaume , Vaillancourt Cathy , Blais Véronique , Disdier Marjorie , Joao Fabien , Johnson Bruno , Benkhalifa Moncef , Miron Pierre , Bernier Jacques 
Published: January 2021

AbstractOver the last few years, intrauterine administration of autologous peripheral blood mononuclear cells (PBMC) has been proposed as new immunotherapy for patients with unexplained recurrent implantation failure (RIF). In these patients, administration of activated PBMC before embryo transfer results in a 2-fold increase in live birth rates(Yang et al., 2020). In this study we evaluated the role of T cells to promotes human endometrial receptivity. On the day of ovulation, PBMC were isolated from and activated with T cells mitogen, the phytohemagglutinin (PHA) and hCG for 48-h in a conditioned culture medium. Distributions of CD4+T cells were characterized in 157 patients by flow cytometry before and after PHA/hCG activation. Cytokine production was analyzed by cytometric beads array. We observed in RIF patients a significant decrease in Th2 and natural Treg cells before activation with PHA/hCG and an increase of Th17 cells after activation compared to intrauterine sperm insemination (IUI) and in vitro fertilization (IVF) groups. Furthermore, the hCG/PHA treatment increases anti-inflammatory T cells (Th2 and Treg cells) compared to non-treated T cells. Principal component analysis (PCA) performed on CD4 T cell subtypes revealed a different cellular profile in the RIF compared to the IUI and IVF groups. This inflammatory state change could explain how endometrium immunomodulation by hCG-activated PBMC helps patients with unexplained RIF to reach implantation.
Multiplexed Imaging Analysis of the Tumor-Immune Microenvironment Reveals Predictors of Outcome in Triple-Negative Breast Cancer
Authors: Patwa Aalok , Yamashita Rikiya , Long Jin , Angelo Michael , Keren Leeat , Rubin Daniel L. 
Published: January 2021

AbstractTriple-negative breast cancer, the poorest-prognosis breast cancer subtype, lacks clinically approved biomarkers for patient risk stratification and treatment management. Prior literature has shown that interrogation of the tumor-immune microenvironment may be a promising approach for the discovery of methods to fill these gaps. Recently developed high-dimensional tissue imaging technology, such as multiplexed ion beam imaging, provide spatial context to protein expression in the microenvironment, allowing in-depth characterization of cellular processes. We demonstrate that profiling the functional proteins involved in cell-to-cell interactions in the microenvironment can predict recurrence and overall survival. We highlight the immunological relevance of the immunoregulatory proteins PD-1, PD-L1, IDO, and Lag3 by tying interactions involving them to recurrence and survival. Multivariate analysis reveals that our methods provide additional prognostic information compared to clinical variables. In this work, we present a computational pipeline for the examination of the tumor-immune microenvironment using multiplexed ion-beam imaging that produces interpretable results, and is generalizable to other cancer types.
Barth syndrome cellular models have dysregulated respiratory chain complex I and mitochondrial quality control due to abnormal cardiolipin
Authors: Anzmann Arianna F. , Sniezek Olivia L. , Pado Alexandra , Busa Veronica , Vaz Frédéric Maxime , Kreimer Simion D. , Cole Robert Norman , Le Anne , Kirsch Brian James , Claypool Steven M. , Vernon Hilary J. 
Published: January 2021

AbstractBarth syndrome (BTHS) is an X-linked genetic condition caused by defects inTAZ, which encodes a transacylase involved in the remodeling of the inner mitochondrial membrane phospholipid, cardiolipin (CL). As such, CL has been implicated in numerous mitochondrial functions, and the role of defective CL in the clinical pathology of BTHS is under intense investigation. We used untargeted proteomics, shotgun lipidomics, gene expression analysis, and targeted metabolomics to identify novel areas of mitochondrial dysfunction in a new model of TAZ deficiency in HEK293 cells. Functional annotation analysis of proteomics data revealed abnormal regulation of mitochondrial respiratory chain complex I (CI), driven by the reduced abundance of 6 CI associated proteins in TAZ-deficient HEK293 cells: MT-ND3, NDUFA5, NDUFAB1, NDUFB2, NDUFB4, and NDUFAF1. This resulted in reduced assembly and function of CI in TAZ-deficient HEK293 cells as well as BTHS patient derived lymphoblast cells. We also identified increased abundance of PARL, a rhomboid protein involved in the regulation of mitophagy and apoptosis, and abnormal downstream processing of PGAM5, another mediator of mitochondrial quality control, in TAZ-deficient cells. Lastly, we modulated CL via the phospholipase inhibitor bromoenol lactone and the CL targeted SS-peptide, SS-31, and showed that each is able to remediate abnormalities in CI abundance as well as PGAM5 processing. Thus, mitochondrial respiratory chain CI and PARL/PGAM5 regulated mitochondrial quality control, both of whose functions localize to the inner mitochondrial membrane, are dysregulated due to TAZ deficiency and are partially remediated via modulation of CL.
Onset of sexual maturity of sexually propagated and wildFavites abditacolonies in northwestern Philippines
Authors: Bonilla KG , Guest JR , dela Cruz DW , Baria-Rodriguez MV 
Published: January 2021

AbstractScleractinian corals are modular colonial organisms and are the main framework builders of coral reefs. Most corals reproduce by broadcast spawning with external fertilization and these processes are essential to replenish reef coral populations. Despite decades of research, many aspects of coral reproductive biology remain poorly studied. For example, two important reproductive life history traits, colony size and age at the onset of sexual maturity, are mostly unknown for many reef-building corals. In this study, wild colonies of different size classes and colonies of a known age (i.e. colonies sexually cultured and reared from larvae to adults) of the massive scleractinianFavites abditawere examined for the presence or absence of mature oocytes to determine size and age at the onset of sexual reproduction. Fecundity at the onset of reproductive maturity across size classes of wild colonies was also determined. Surveyed and sampled colonies were grouped into three size classes based on maximum colony diameter (A = 0.1-4.0 cm, B = 4.1-8.0 cm, and C = >8.1 cm). For both wild and sexually propagated colonies, the smallest colonies containing gametes were 1.8 cm in diameter, suggesting that this is the minimum colony size at onset of sexual maturity. Colonies of size class A had lower mean oocyte counts per polyp (44 ± 6.08; mean ± SE) compared to colonies of classes B and C (469 ± 62.41, 278 ± 57.15, respectively). However, mean oocyte geometric mean diameter of size class A colonies was greater (340.38 ± 7.68 μm) than classes B and C (283.96 ± 6.94 μm, 317.57 ± 9.18 μm, respectively). Results of this study bring in to question the widely applied operational definition of coral juveniles being colonies ≤4.0 cm diameter and suggest that even quite small colonies may play a role in contributing to the natural larval pool on reefs than previously thought.
Frog nest foams exhibit pharmaceutical foam-like properties
Authors: Brozio Sarah , O’Shaughnessy Erin M. , Woods Stuart , Hall-Barrientos Ivan , Martin Patricia E. , Kennedy Malcolm W. , Lamprou Dimitrios A. , Hoskisson Paul A. 
Published: January 2021

AbstractFoams have frequently been used as systems for the delivery of cosmetic and therapeutic molecules; however, there is high variability in the foamability and long-term stability of synthetic foams. The development of pharmaceutical foams that exhibit desirable foaming properties, delivering appropriate amounts of the active pharmaceutical ingredient (API) and that have excellent biocompatibility is of great interest. The production of stable foams is rare in the natural world; however, certain species of frogs have adopted foam production as a means of providing a protective environment for their eggs and larvae from a predators and parasites, to prevent desiccation, to control gaseous exchange, temperature extremes, and to reduce UV damage. These foams show great stability (up to 10 days in tropical environments) and are highly biocompatible due to the sensitive nature of amphibian skin. This work demonstrates for the first time, that nests of the Túngara frog (Engystomops pustulosus) is stableex situwith useful physiochemical and biocompatible properties and is capable of encapsulating a range of compounds, including antibiotics. These protein foam mixtures share some properties with pharmaceutical foams and may find utility in a range of pharmaceutical applications such as a topical drug delivery systems (DDS).
Structural Brain Correlates of Creative Personality
Authors: Sadana Divya , Gupta Rajnish K. , Kumaran S. S. , Jain Sanjeev , Rajeswaran Jamuna 
Published: January 2021

ABSTRACTCreative individuals and their enigmatic personalities have always been a subject of fascination. The current study explored the neuroanatomical basis of creative personality using voxel-based morphometry. The sample comprised of two groups - Creative (CR) group (professional creative artists) and matched controls with no demonstrated artistic creativity (NC) with 20 participants in each group, in the age range of 20-40 years, right-handed, and had minimum average intelligence (IQ > 90). Participants in CR were selected using the creativity achievement questionnaire, creativity was assessed using the Wallach & Kogan test of creativity, and personality was administered using NEO-FFI. Results indicated significantly higher openness to new experiences in CR which positively correlates with the right middle frontal gyrus. An increased grey matter volume in the inferior frontal gyrus, anterior cingulate gyrus in CR, pointing towards the integration of cognitive and imaginative processes that might be implicated in creative personality.
Stability and folding pathways of tetra-nucleosome from six-dimensional free energy surface
Authors: Ding Xinqiang , Lin Xingcheng , Zhang Bin 
Published: January 2021

AbstractThe three-dimensional organization of chromatin is expected to play critical roles in regulating genome functions. High-resolution characterization of its structure and dynamics could improve our understanding of gene regulation mechanisms but has remained challenging. Using a near-atomistic model that preserves the chemical specificity of protein-DNA interactions at residue and base-pair resolution, we studied the stability and folding pathways of a tetra-nucleosome. Dynamical simulations performed with an advanced sampling technique uncovered multiple pathways that connect open chromatin configurations with the zigzag crystal structure. Intermediate states along the simulated folding pathways resemble chromatin configurations reported fromin situexperiments. We further determined a six-dimensional free energy surface as a function of the inter-nucleosome distances via a deep learning approach. The zigzag structure can indeed be seen as the global minimum of the surface. However, it is not favored by a significant amount relative to the partially unfolded,in situconfigurations. Chemical perturbations such as histone H4 tail acetylation and thermal fluctuations can further tilt the energetic balance to stabilize intermediate states. Our study provides insight into the connection between various reported chromatin configurations and has implications on thein siturelevance of the 30nm fiber.
Network Analysis Reveals Synergistic Genetic Dependencies for Rational Combination Therapy in Philadelphia Chromosome-like Acute Lymphoblastic Leukemia
Authors: Ding Yang-Yang , Kim Hannah , Madden Kellyn , Loftus Joseph P , Chen Gregory M , Allen David Hottman , Zhang Ruitao , Xu Jason , Hu Yuxuan , Tasian Sarah K , Tan Kai 
Published: January 2021

ABSTRACTSystems biology approaches can identify critical targets in complex cancer signaling networks to inform therapy combinations and overcome conventional treatment resistance. Herein, we developed a data-driven, network controllability-based approach to identify synergistic key regulator targets in Philadelphia chromosome-like B-acute lymphoblastic leukemia (Ph-like B-ALL), a high-risk leukemia subtype associated with hyperactive signal transduction and chemoresistance. Integrated analysis of 1,046 childhood B-ALL cases identified 14 dysregulated network nodes in Ph-like ALL involved in aberrant JAK/STAT, Ras/MAPK, and apoptosis pathways and other critical processes. Consistent with network controllability theory, combination small molecule inhibitor therapy targeting a pair of key nodes shifted the transcriptomic state of Ph-like ALL cells to become less like kinase-activatedBCR-ABL1-rearranged (Ph+) B-ALL and more similar to prognostically-favorable childhood B-ALL subtypes. Functional validation experiments further demonstrated enhanced anti-leukemia efficacy of combining the BCL-2 inhibitor venetoclax with tyrosine kinase inhibitors ruxolitinib or dasatinibin vitroin human Ph-like ALL cell lines andin vivoin multiple patient-derived xenograft models. Our study represents a broadly-applicable conceptual framework for combinatorial drug discovery, based on systematic interrogation of synergistic vulnerability pathways with pharmacologic targeted validation in sophisticated preclinical human leukemia models.
A Processed EEG based Brain Anesthetic Resistance Index Predicts Postoperative Delirium in Older Adults: A Dual Center Study
Authors: Cooter Mary , Bunning Thomas , Eleswarpu Sarada S. , Heflin Mitchell T. , McDonald Shelley , Lagoo-Deenadalayan Sandhya , Whitson Heather , Deiner Stacie G , Berger Miles 
Published: January 2021

ABSTRACTBackgroundSome older adults show exaggerated responses to drugs that act on the brain, such as increased delirium risk in response to anticholinergic drugs. The brain’s response to anesthetic drugs is often measured clinically by processed electroencephalogram (EEG) indices. Thus, we developed a processed EEG based-measure of the brain’s neurophysiologic resistance to anesthetic dose-related changes, and hypothesized that it would predict postoperative delirium.MethodsWe defined the Duke Anesthesia Resistance Scale (DARS) as the average BIS index divided by the quantity 2.5 minus the average age-adjusted end-tidal MAC (aaMAC) inhaled anesthetic fraction. The relationship between DARS and postoperative delirium was analyzed in derivation (Duke; N=69), validation (Mt Sinai; N=70), and combined estimation cohorts (N=139) of older surgical patients (age ≥65). In the derivation cohort, we identified a threshold relationship between DARS and for delirium and identified an optimal cut point for prediction.ResultsIn the derivation cohort, the optimal DARS threshold for predicting delirium was 27.0. The delirium rate was 11/49 (22.5%) vs 11/20 (55.0%) and 7/57 (12.3%) vs 6/13 (46.2%) for those with DARS ≥ 27 vs those with DARS < 27 in the derivation and validation cohorts respectively. In the combined estimation cohort, multivariable analysis found a significant association of DARS <27.0 with postoperative delirium (OR=4.7; 95% CI: 1.87, 12.0; p=0.001). In the derivation cohort, the DARS had an AUC of 0.63 with sensitivity of 50%, specificity of 81%, positive predictive value of 0.55, and negative predictive value of 0.78. The DARS remained a significant predictor of delirium after accounting for opioid, midazolam, propofol, non-depolarizing neuromuscular blocker, phenylephrine and ketamine dosage, and for nitrous oxide and epidural usage.ConclusionsThese results suggest than an intraoperative processed EEG-based measure of lower brain anesthetic resistance (i.e. DARS <27) could be used in older surgical patients as an independent predictor of postoperative delirium risk.
Epidemiological differences in the impact of COVID-19 vaccination in the United States and China
Authors: Makhoul Monia , Chemaitelly Hiam , Ayoub Houssein H. , Seedat Shaheen , Abu-Raddad Laith J. 
Published: January 2021

AbstractBackgroundThe objective of this study was to forecast the impact of COVID-19 vaccination in the United States (US) and China, two countries at different epidemic phases.MethodsA mathematical model describing SARS-CoV-2 transmission and disease progression was used to investigate vaccine impact. Impact was assessed both for a vaccine that prevents infection (VES = 95%) and a vaccine that prevents only disease (VEP = 95%).ResultsFor VES = 95% and gradual easing of restrictions, vaccination in the US reduced the peak incidence of infection, disease, and death by >55% and cumulative incidence by >32%, and in China by >77% and >65%, respectively. Nearly three vaccinations were needed to avert one infection in the US, but only one was needed in China. For VEP = 95%, benefits of vaccination were half those for VES = 95%. In both countries, the impact of vaccination was substantially enhanced with rapid scale-up, vaccine coverage >50%, and slower or no easing of restrictions, particularly in the US.ConclusionsCOVID-19 vaccination can flatten, delay, and/or prevent future epidemic waves. However, vaccine impact is destined to be heterogeneous across countries because of an underlying “epidemiologic inequity” that reduces benefits for countries already at high incidence, such as the US. Despite 95% efficacy, actual vaccine impact could be meager in such countries, if vaccine scale-up is slow, acceptance of the vaccine is poor, or restrictions are eased prematurely.One Sentence SummaryVaccine impact will be heterogeneous across countries disadvantaging countries at high incidence. This heterogeneity can be alleviated with rapid vaccination scale-up and limited easing of restrictions.