bluuebunny/crossref_metadata_2025_split huggingface dataset:
A highly annotated database of genes associated with platinum resistance in cancer
Authors: Huang Dongqing , Savage Sara R. , Calinawan Anna P. , Lin Chenwei , Zhang Bing , Wang Pei , Starr Timothy K. , Birrer Michael J. , Paulovich Amanda G. 
Published: October 2021

AbstractPlatinum-based chemotherapy, including cisplatin, carboplatin, and oxaliplatin, is prescribed to 10-20% of all cancer patients. Unfortunately, platinum resistance develops in a significant number of patients and is a determinant of clinical outcome. Extensive research has been conducted to understand and overcome platinum resistance, and mechanisms of resistance can be categorized into several broad biological processes, including (1) regulation of drug entry, exit, accumulation, sequestration, and detoxification, (2) enhanced repair and tolerance of platinum-induced DNA damage, (3) alterations in cell survival pathways, (4) alterations in pleiotropic processes and pathways, and (5) changes in the tumor microenvironment. As a resource to the cancer research community, we provide a comprehensive overview accompanied by a manually curated database of the >900 genes/proteins that have been associated with platinum resistance over the last 30 years of literature. The database is annotated with possible pathways through which the curated genes are related to platinum resistance, types of evidence, and hyperlinks to literature sources. The searchable, downloadable database is available online at http://ptrc-ddr.cptac-data-view.org.
Mitochondrial morphology is associated with respiratory chain uncoupling in autism spectrum disorder
Authors: Frye Richard E. , Lionnard Loïc , Singh Indrapal , Karim Mohammad A. , Chajra Hanane , Frechet Mathilde , Kissa Karima , Racine Victor , Ammanamanchi Amrit , McCarty Patrick John , Delhey Leanna , Tippett Marie , Rose Shannon , Aouacheria Abdel 
Published: October 2021

AbstractAutism spectrum disorder (ASD) is a neurodevelopmental disorder that is associated with unique changes in mitochondrial metabolism, including elevated respiration rates and morphological alterations. We examined electron transport chain (ETC) complex activity in fibroblasts derived from 18 children with ASD as well as mitochondrial morphology measurements in fibroblasts derived from the ASD participants and four typically developing controls. In ASD participants, symptoms severity was measured by the Social Responsiveness Scale and Aberrant Behavior Checklist. Mixed-model regression demonstrated that alterations in mitochondrial morphology were associated with both ETC Complex I+III and IV activity as well as the difference between ETC Complex I+III and IV activity. The subgroup of ASD participants with relative elevation in Complex IV activity demonstrated more typical mitochondrial morphology and milder ASD related symptoms. This study is limited by sample size given the invasive nature of obtaining fibroblasts from children. Furthermore, since mitochondrial function is heterogenous across tissues, the result may be specific to fibroblast respiration. Previous studies have separately described elevated ETC Complex IV activity and changes in mitochondrial morphology in cells derived from children with ASD but this is the first study to link these two findings in mitochondrial metabolism. The association between a difference in ETC complex I+III and IV activity and normal morphology suggests that mitochondrial in individuals with ASD may require ETC uncoupling to function optimally. Further studies should assess the molecular mechanisms behind these unique metabolic changes.Trial registration:Protocols used in this study were registered in clinicaltrials.gov as NCT02000284 and NCT02003170.
RETRACTED ARTICLE: METTL3 improves cardiomyocyte proliferation upon myocardial infarction via upregulating miR-17-3p in a DGCR8-dependent manner
Authors: Zhao Kun , Yang Chuanxi , Zhang Jing , Sun Wei , Zhou Bin , Kong Xiangqing , Shi Jing 
Published: October 2021

Abstract
Myocardial infarction (MI), one of the most severe types of heart
attack, exerts a strong negative effect on heart muscle by causing a massive and
rapid loss of cardiomyocytes. However, the existing therapies do little to improve
cardiac regeneration. Due to the role of methyltransferase-like 3 (METTL3) in the
physiological proliferation of cardiomyocytes, we aimed to determine whether METTL3
could also promote cardiomyocyte proliferation under pathological conditions and to
elucidate the underlying mechanism. The effects of METTL3 on cardiomyocyte
proliferation and apoptosis were investigated in an in vivo rat model of MI and in
an in vitro model of neonatal rat cardiomyocytes (NRCMs) exposed to hypoxia. We
found that METTL3 expression was downregulated in hypoxia-exposed NRCMs and
MI-induced rats. Furthermore, METTL3 pretreatment enhanced cardiomyocyte
proliferation and inhibited cardiomyocyte apoptosis under hypoxic or MI conditions,
and silencing METTL3 had the opposite effects. Additionally, METTL3 overexpression
upregulated miR-17-3p expression. The miR-17-3p agomir mimicked the
pro-proliferative and antiapoptotic effects of METTL3 in hypoxia-exposed cells or
rats with MI, while the miR-17-3p antagomir blocked these effects. Additionally,
pretreatment with the RNA-binding protein DGCR8 also hampered the protective role of
METTL3 in hypoxia-exposed cells. Overall, the current study indicated that METTL3
could improve cardiomyocyte proliferation and subsequently ameliorate MI in rats by
upregulating proliferation-related miR-17-3p in a DGCR8-dependent
pri-miRNA-processing manner.
Characterization of SARS-CoV-2-specific humoral immunity and its potential applications and therapeutic prospects
Authors: Zheng Jiaxin , Deng Yingying , Zhao Zhenyu , Mao Binli , Lu Mengji , Lin Yong , Huang Ailong 
Published: October 2021

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing pandemic that poses a great threat to human health worldwide. As the humoral immune response plays essential roles in disease occurrence and development, understanding the dynamics and characteristics of virus-specific humoral immunity in SARS-CoV-2-infected patients is of great importance for controlling this disease. In this review, we summarize the characteristics of the humoral immune response after SARS-CoV-2 infection and further emphasize the potential applications and therapeutic prospects of SARS-CoV-2-specific humoral immunity and the critical role of this immunity in vaccine development. Notably, serological antibody testing based on the humoral immune response can guide public health measures and control strategies; however, it is not recommended for population surveys in areas with very low prevalence. Existing evidence suggests that asymptomatic individuals have a weaker immune response to SARS-CoV-2 infection, whereas SARS-CoV-2-infected children have a more effective humoral immune response than adults. The correlations between antibody (especially neutralizing antibody) titers and protection against SARS-CoV-2 reinfection should be further examined. In addition, the emergence of cross-reactions among different coronavirus antigens in the development of screening technology and the risk of antibody-dependent enhancement related to SARS-CoV-2 vaccination should be given further attention.
Exposure to 16 h of normobaric hypoxia induces ionic edema in the healthy brain
Authors: Biller Armin , Badde Stephanie , Heckel Andreas , Guericke Philipp , Bendszus Martin , Nagel Armin M. , Heiland Sabine , Mairbäurl Heimo , Bärtsch Peter , Schommer Kai 
Published: October 2021

AbstractFollowing prolonged exposure to hypoxic conditions, for example, due to ascent to high altitude, stroke, or traumatic brain injury, cerebral edema can develop. The exact nature and genesis of hypoxia-induced edema in healthy individuals remain unresolved. We examined the effects of prolonged, normobaric hypoxia, induced by 16 h of exposure to simulated high altitude, on healthy brains using proton, dynamic contrast enhanced, and sodium MRI. This dual approach allowed us to directly measure key factors in the development of hypoxia-induced brain edema: (1) Sodium signals as a surrogate of the distribution of electrolytes within the cerebral tissue and (2) Ktransas a marker of blood–brain–barrier integrity. The measurements point toward an accumulation of sodium ions in extra- but not in intracellular space in combination with an intact endothelium. Both findings in combination are indicative of ionic extracellular edema, a subtype of cerebral edema that was only recently specified as an intermittent, yet distinct stage between cytotoxic and vasogenic edemas. In sum, here a combination of imaging techniques demonstrates the development of ionic edemas following prolonged normobaric hypoxia in agreement with cascadic models of edema formation.
Clonal hematopoiesis is associated with risk of severe Covid-19
Authors: Bolton Kelly L. , Koh Youngil , Foote Michael B. , Im Hogune , Jee Justin , Sun Choong Hyun , Safonov Anton , Ptashkin Ryan , Moon Joon Ho , Lee Ji Yeon , Jung Jongtak , Kang Chang Kyung , Song Kyoung-Ho , Choe Pyoeng Gyun , Park Wan Beom , Kim Hong Bin , Oh Myoung-don , Song Han , Kim Sugyeong , Patel Minal , Derkach Andriy , Gedvilaite Erika , Tkachuk Kaitlyn A. , Wiley Brian J. , Chan Ireaneus C. , Braunstein Lior Z. , Gao Teng , Papaemmanuil Elli , Esther Babady N. , Pessin Melissa S. , Kamboj Mini , Diaz Luis A. , Ladanyi Marc , Rauh Michael J. , Natarajan Pradeep , Machiela Mitchell J. , Awadalla Philip , Joseph Vijai , Offit Kenneth , Norton Larry , Berger Michael F. , Levine Ross L. , Kim Eu Suk , Kim Nam Joong , Zehir Ahmet 
Published: October 2021

AbstractAcquired somatic mutations in hematopoietic stem and progenitor cells (clonal hematopoiesis or CH) are associated with advanced age, increased risk of cardiovascular and malignant diseases, and decreased overall survival. These adverse sequelae may be mediated by altered inflammatory profiles observed in patients with CH. A pro-inflammatory immunologic profile is also associated with worse outcomes of certain infections, including SARS-CoV-2 and its associated disease Covid-19. Whether CH predisposes to severe Covid-19 or other infections is unknown. Among 525 individuals with Covid-19 from Memorial Sloan Kettering (MSK) and the Korean Clonal Hematopoiesis (KoCH) consortia, we show that CH is associated with severe Covid-19 outcomes (OR = 1.85, 95%=1.15–2.99, p = 0.01), in particular CH characterized by non-cancer driver mutations (OR = 2.01, 95% CI = 1.15–3.50, p = 0.01). We further explore the relationship between CH and risk of other infections in 14,211 solid tumor patients at MSK. CH is significantly associated with risk of Clostridium Difficile (HR = 2.01, 95% CI: 1.22–3.30, p = 6×10−3) and Streptococcus/Enterococcus infections (HR = 1.56, 95% CI = 1.15–2.13, p = 5×10−3). These findings suggest a relationship between CH and risk of severe infections that warrants further investigation.
p107 mediated mitochondrial function controls muscle stem cell proliferative fates
Authors: Bhattacharya Debasmita , Shah Vicky , Oresajo Oreoluwa , Scimè Anthony 
Published: October 2021

AbstractMuscle diseases and aging are associated with impaired myogenic stem cell self-renewal and fewer proliferating progenitors (MPs). Importantly, distinct metabolic states induced by glycolysis or oxidative phosphorylation have been connected to MP proliferation and differentiation. However, how these energy-provisioning mechanisms cooperate remain obscure. Herein, we describe a mechanism by which mitochondrial-localized transcriptional co-repressor p107 regulates MP proliferation. We show p107 directly interacts with the mitochondrial DNA, repressing mitochondrial-encoded gene transcription. This reduces ATP production by limiting electron transport chain complex formation. ATP output, controlled by the mitochondrial function of p107, is directly associated with the cell cycle rate. Sirt1 activity, dependent on the cytoplasmic glycolysis product NAD+, directly interacts with p107, impeding its mitochondrial localization. The metabolic control of MP proliferation, driven by p107 mitochondrial function, establishes a cell cycle paradigm that might extend to other dividing cell types.
Humans monitor learning progress in curiosity-driven exploration
Authors: Ten Alexandr , Kaushik Pramod , Oudeyer Pierre-Yves , Gottlieb Jacqueline 
Published: October 2021

AbstractCuriosity-driven learning is foundational to human cognition. By enabling humans to autonomously decide when and what to learn, curiosity has been argued to be crucial for self-organizing temporally extended learning curricula. However, the mechanisms driving people to set intrinsic goals, when they are free to explore multiple learning activities, are still poorly understood. Computational theories propose different heuristics, including competence measures (e.g., percent correct) and learning progress, that could be used as intrinsic utility functions to efficiently organize exploration. Such intrinsic utilities constitute computationally cheap but smart heuristics to prevent people from laboring in vain on unlearnable activities, while still motivating them to self-challenge on difficult learnable activities. Here, we provide empirical evidence for these ideas by means of a free-choice experimental paradigm and computational modeling. We show that while humans rely on competence information to avoid easy tasks, models that include a learning-progress component provide the best fit to task selection data. These results bridge the research in artificial and biological curiosity, reveal strategies that are used by humans but have not been considered in computational research, and introduce tools for probing how humans become intrinsically motivated to learn and acquire interests and skills on extended time scales.
Learning non-stationary Langevin dynamics from stochastic observations of latent trajectories
Authors: Genkin Mikhail , Hughes Owen , Engel Tatiana A. 
Published: October 2021

AbstractMany complex systems operating far from the equilibrium exhibit stochastic dynamics that can be described by a Langevin equation. Inferring Langevin equations from data can reveal how transient dynamics of such systems give rise to their function. However, dynamics are often inaccessible directly and can be only gleaned through a stochastic observation process, which makes the inference challenging. Here we present a non-parametric framework for inferring the Langevin equation, which explicitly models the stochastic observation process and non-stationary latent dynamics. The framework accounts for the non-equilibrium initial and final states of the observed system and for the possibility that the system’s dynamics define the duration of observations. Omitting any of these non-stationary components results in incorrect inference, in which erroneous features arise in the dynamics due to non-stationary data distribution. We illustrate the framework using models of neural dynamics underlying decision making in the brain.
PGRMC1 acts as a size-selective cargo receptor to drive ER-phagic clearance of mutant prohormones
Authors: Chen Yu-Jie , Knupp Jeffrey , Arunagiri Anoop , Haataja Leena , Arvan Peter , Tsai Billy 
Published: October 2021

AbstractThe reticulon-3 (RTN3)-driven targeting complex promotes clearance of misfolded prohormones from the endoplasmic reticulum (ER) for lysosomal destruction by ER-phagy. Because RTN3 resides in the cytosolic leaflet of the ER bilayer, the mechanism of selecting misfolded prohormones as ER-phagy cargo on the luminal side of the ER membrane remains unknown. Here we identify the ER transmembrane protein PGRMC1 as an RTN3-binding partner. Via its luminal domain, PGRMC1 captures misfolded prohormones, targeting them for RTN3-dependent ER-phagy. PGRMC1 selects cargos that are smaller than the large size of other reported ER-phagy substrates. Cargos for PGRMC1 include mutant proinsulins that block secretion of wildtype proinsulin through dominant-negative interactions within the ER, causing insulin-deficiency. Chemical perturbation of PGRMC1 partially restores WT insulin storage by preventing ER-phagic degradation of WT and mutant proinsulin. Thus, PGRMC1 acts as a size-selective cargo receptor during RTN3-dependent ER-phagy, and is a potential therapeutic target for diabetes.
MesoNet allows automated scaling and segmentation of mouse mesoscale cortical maps using machine learning
Authors: Xiao Dongsheng , Forys Brandon J. , Vanni Matthieu P. , Murphy Timothy H. 
Published: October 2021

AbstractUnderstanding the basis of brain function requires knowledge of cortical operations over wide spatial scales and the quantitative analysis of brain activity in well-defined brain regions. Matching an anatomical atlas to brain functional data requires substantial labor and expertise. Here, we developed an automated machine learning-based registration and segmentation approach for quantitative analysis of mouse mesoscale cortical images. A deep learning model identifies nine cortical landmarks using only a single raw fluorescent image. Another fully convolutional network was adapted to delimit brain boundaries. This anatomical alignment approach was extended by adding three functional alignment approaches that use sensory maps or spatial-temporal activity motifs. We present this methodology as MesoNet, a robust and user-friendly analysis pipeline using pre-trained models to segment brain regions as defined in the Allen Mouse Brain Atlas. This Python-based toolbox can also be combined with existing methods to facilitate high-throughput data analysis.
Breaking of Henry’s law for sulfide liquid–basaltic melt partitioning of Pt and Pd
Authors: Zhang Mingdong , Li Yuan 
Published: October 2021

AbstractPlatinum group elements are invaluable tracers for planetary accretion and differentiation and the formation of PGE sulfide deposits. Previous laboratory determinations of the sulfide liquid–basaltic melt partition coefficients of PGE ($${D}_{PGE}^{SL/SM}$$

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) yielded values of 102–109, and values of >105 have been accepted by the geochemical and cosmochemical society. Here we perform measurements of $${D}_{Pt,\,Pd}^{SL/SM}$$

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at 1 GPa and 1,400 °C, and find that $${D}_{Pt,\,Pd}^{SL/SM}$$

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increase respectively from 3,500 to 3.5 × 105 and 1,800 to 7 × 105, as the Pt and Pd concentration in the sulfide liquid increases from 60 to 21,000 ppm and 26 to 7,000 ppm, respectively, implying non-Henrian behavior of the Pt and Pd partitioning. The use of $${D}_{Pt,\,Pd}^{SL/SM}$$

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values of 2,000–6,000 well explains the Pt and Pd systematics of Earth’s mantle peridotites and mid-ocean ridge basalts. Our findings suggest that the behavior of PGE needs to be reevaluated when using them to trace planetary magmatic processes.
Superior robustness of anomalous non-reciprocal topological edge states
Authors: Zhang Zhe , Delplace Pierre , Fleury Romain 
Published: October 2021

AbstractRobustness against disorder and defects is a pivotal advantage of topological systems1, manifested by the absence of electronic backscattering in the quantum-Hall2 and spin-Hall effects3, and by unidirectional waveguiding in their classical analogues4,5. Two-dimensional (2D) topological insulators4–13, in particular, provide unprecedented opportunities in a variety of fields owing to their compact planar geometries, which are compatible with the fabrication technologies used in modern electronics and photonics. Among all 2D topological phases, Chern insulators14–25 are currently the most reliable designs owing to the genuine backscattering immunity of their non-reciprocal edge modes, brought via time-reversal symmetry breaking. Yet such resistance to fabrication tolerances is limited to fluctuations of the same order of magnitude as their bandgap, limiting their resilience to small perturbations only. Here we investigate the robustness problem in a system where edge transmission can survive disorder levels with strengths arbitrarily larger than the bandgap—an anomalous non-reciprocal topological network. We explore the general conditions needed to obtain such an unusual effect in systems made of unitary three-port non-reciprocal scatterers connected by phase links, and establish the superior robustness of anomalous edge transmission modes over Chern ones to phase-link disorder of arbitrarily large values. We confirm experimentally the exceptional resilience of the anomalous phase, and demonstrate its operation in various arbitrarily shaped disordered multi-port prototypes. Our results pave the way to efficient, arbitrary planar energy transport on 2D substrates for wave devices with full protection against large fabrication flaws or imperfections.
Analysis of parental abnormal chromosomal karyotype and subsequent live births in Chinese couples with recurrent pregnancy loss
Authors: Li Shan , Chen Mei , Zheng Peng-Sheng 
Published: October 2021

AbstractThe frequency and distribution of chromosomal abnormalities and the impact of parental chromosomal aberration on the pregnancy outcomes of couples with recurrent pregnancy loss remains controversial. 3235 RPL couples who experienced two or more miscarriages before 20 weeks were diagnosed in our tertiary referral hospital during 2008–2018 and included in the single-center retrospective cohort study covering a 10-year period. Chromosome aberration was detected in 121 (3.74%) among 3235 RPL couples which included 75 female and 46 male cases at an individual level. 101 cases were structural aberrations including balanced translocations in 46(38.0%) cases, Robertsonian translocations in 13(10.7%) cases, inversions in 42(34.7%) cases and 20(16.5%) cases were numerical aberrations. 121 carriers and 428 non-carriers were followed up for two years, 55 carriers and 229 non-carriers were subsequent pregnant after diagnosis by natural conception or intrauterine insemination. The frequency of carriers to have a health newborn was not significantly different with non-carriers (72.7% vs. 71.2%, adjusted P = 0.968). This study described the majority of carriers were balanced translocations and chromosome aberrations had a limited influence on live birth rate from the present data. The results of the study also remind us that natural conception may be also a good alternative rather than PGD (Pre-implantation Genetic Diagnosis) which is common in many other reproductive centers for such patients.
Ionospheric perturbation during the South American total solar eclipse on 14th December 2020 revealed with the Chilean GPS eyeball
Authors: Shrivastava Mahesh N. , Maurya Ajeet Kumar , Kumar Kondapalli Niranjan 
Published: October 2021

AbstractThe influence of the South American total solar eclipse of 14th December 2020 on the ionosphere is studied by using the continuous Chilean Global Positioning System (GPS) sites across the totality path. The totality path with eclipse magnitude 1.012 passed through the Villarrica (Lon. 72.2308°W and Lat. 39.2820°S) in south Chile during 14:41:02.0 UTC to 17:30:58.1 UTC and maximum occurred ~ 16:03:49.5 UTC around the local noon. The vertical total electron content (VTEC) derived by GPS sites across the totality path for two PRN’s 29 and 31 show almost 20–40% of reduction with reference to ambient values. The percentage reduction was maximum close to totality site and decreases smoothly on both sides of totality sites. Interestingly, the atmospheric gravity waves (AGWs) with a period ~ 30–60 min obtained using wavelet analysis of VTEC timeseries show the presence of strong AGWs at the GPS sites located north of the totality line. But the AGWs do not show any significant effect on the VTEC values to these sites. Our analysis suggests, possibly an interplay between variability in the background plasma density and eclipse-generated AGWs induced plasma density perturbation could explain the observations.