bluuebunny/crossref_metadata_2025_split huggingface dataset:
Risk Analysis of COVID‐19 Infections in Kolkata Metropolitan City: A GIS‐Based Study and Policy Implications
Authors: Nath Bibhash , Majumder Santanu , Sen Jayanta , Rahman Mohammad Mahmudur 
Published: January 2021

AbstractThe COVID‐19 pandemic has affected daily lives of people around the world. People have already started to live wearing masks, keeping a safe distance from others, and maintaining a high level of hygiene. This paper deals with an in‐depth analysis of riskness associated with COVID‐19 infections in Kolkata Municipal Corporation (KMC) at the subcity (ward) level. Attempts have been made to identify the areas with high or low risk of infections using GIS‐based geostatistical approach. Cosine Similarity Index has been used to rank different wards of KMC according to the degree of riskness. Four indices were computed to address intervention objectives and to determine “Optimized Prevention Rank” of wards for future policy decisions. The highest risk areas were located in the eastern and western part of the city, to a great extent overlapped with wards containing larger share of population living in slums and/or below poverty level. On the other hand, highly infected areas lie in central Kolkata and in several wards at the eastern and northeastern periphery of the KMC. The “Optimized Prevention Rank” have indicated that the lack of social awareness along with lack of social distancing have contributed to the increasing number of containments of COVID‐19 cases. The rankings of the wards would no doubt provide the policy makers a basis to control further spread of the disease. Since effective antiviral drugs are already in the market, the best application of our research would be in the ensuing vaccination drive against further COVID‐19 infections.
Momentum Flux Balance at the Air‐Sea Interface
Authors: Qiao Wenli , Wu Lichuan , Song Jinbao , Li Xue , Qiao Fangli , Rutgersson Anna 
Published: January 2021

AbstractOcean waves can spatiotemporally redistribute the momentum flux at the air‐sea interface, which varies with the sea state. Traditional atmosphere‐ocean coupled systems assume the ocean‐side stress (τoc) to be identical to the air‐side stress (τa); consequently, the role of ocean waves is neglected. In this study, the wave impacts on the air‐sea momentum flux are investigated based on 1‐year high‐resolution model simulations in the Baltic Sea using an atmosphere‐wave coupled model (Uppsala University‐Coupled Model, UU‐CM). The simulation results show that τoc can differ significantly from τa in both direction and magnitude. The direction difference between τoc and τa (DD(τoc, τa)) and the normalized momentum flux () decrease with increasing inverse wave age. In general, and DD(τoc, τa) are pronounced under wind‐following swell and wind‐crossing swell conditions, respectively. The occurrence frequencies of large and DD(τoc, τa) are higher nearer the coast; statistically, both decrease significantly with increasing water depth because of the joint effect of dissipation processes. Based on four selected areas, we find that alongshore winds (winds blowing parallel to the coastline) are favorable for large angular differences between τoc and τa (DD(τoc, τa) > 5°). However, onshore winds predominate at . The τa in the wave model is generally less than that obtained from the atmospheric model under low‐moderate wind conditions if the wave model feeds only the Charnock coefficient (roughness length) back to the atmospheric model in coupled systems.
Extending Collaborative Care to Independent Primary Care Practices: A Chronic Care Model
Authors: Parkhurst John T. , Ballard Rachel R. , Lavigne John V. , Von Mach Tara , Romba Courtney , Perez-Reisler Marisa , Walkup John T. 
Published: January 2021

Objective: Collaborative approaches to pediatric primary care are increasingly recognized as a way to improve access to mental health care, but certain collaborative care models are not well suited for smaller, independent pediatric practices. We describe the development of the Mood, Anxiety, ADHD Collaborative Care (MAACC) program, based on the Chronic Care Model (CCM) and a hub-and-spoke organization for collaborating with such practices. Method: MAACC’s clinical team (coordinator, psychologist, psychiatrist) trained and collaborated with 46 pediatricians in 13 independent practices. Key services included a diagnostic evaluation by the psychologist, treatment planning for both psychotherapy and pharmacotherapy, tailored referrals to evidence-based therapy, pediatrician access to a psychiatrist for medication consultation, and centralized measurement-based progress monitoring. Results: During the 15-month start-up period, 234 patients were referred; 149 patients received an evaluation, 83 received a new referral for therapy, and 88 received medication recommendations for combined psychotherapy and medication. Patients experienced significant improvement in attention deficit/hyperactivity disorder and anxiety disorder symptoms. Pediatrician attitudes and access to care substantially improved. Conclusion: MAACC demonstrates the feasibility of implementing a CCM-derived model for collaborative care with independent pediatric practices. Implications for Impact Statement Collaboration among mental health and pediatric primary care providers is essential to addressing the substantial pediatric mental health burden. Financially sustainable extensions of collaborative care models to small, independent pediatric practices are needed. The Mood, Anxiety, ADHD Collaborative Care program is a high-quality collaborative model designed for pediatric primary care.
RETRACTED ARTICLE: PI3K/Akt pathway and Nanog maintain cancer stem cells in
sarcomas
Authors: Yoon Changhwan , Lu Jun , Yi Brendan C. , Chang Kevin K. , Simon M. Celeste , Ryeom Sandra , Yoon Sam S. 
Published: January 2021

AbstractThe self-renewal transcription factor Nanog and the phosphoinositide
3-kinase (PI3K)–Akt pathway are known to be essential for maintenance of
mesenchymal stem cells. We evaluated their contribution to the maintenance of
CD133(+) cancer stem-like cells (CSCs) and spheroid-forming cells in
patient-derived cell lines from three human sarcoma subtypes: HT1080 fibrosarcoma,
SK-LMS-1 leiomyosarcoma, and DDLS8817 dedifferentiated liposarcoma. Levels of Nanog
and activated Akt were significantly higher in sarcoma cells grown as spheroids or
sorted for CD133 expression to enrich for CSCs. shRNA knockdown of Nanog decreased
spheroid formation 10- to 14-fold, and reversed resistance to both doxorubicin and
radiation in vitro and in H1080 flank xenografts. In the HT1080 xenograft model,
doxorubicin and Nanog knockdown reduced tumor growth by 34% and 45%, respectively,
and the combination reduced tumor growth by 74%. Using a human phospho-kinase
antibody array, Akt1/2 signaling, known to regulate Nanog, was found to be highly
activated in sarcoma spheroid cells compared with monolayer cells. Pharmacologic
inhibition of Akt using LY294002 and Akt1/2 knockdown using shRNA in sarcoma CSCs
decreased Nanog expression and spheroid formation and reversed chemotherapy
resistance. Akt1/2 inhibition combined with doxorubicin treatment of HT1080 flank
xenografts reduced tumor growth by 73%. Finally, in a human sarcoma tumor
microarray, expression of CD133, Nanog, and phospho-Akt were 1.8- to 6.8-fold higher
in tumor tissue compared with normal tissue. Together, these results indicate that
the Akt1/2–Nanog pathway is critical for maintenance of sarcoma CSCs and
spheroid-forming cells, supporting further exploration of this pathway as a
therapeutic target in sarcoma.
Necrotizing enterocolitis intestinal barrier function protection by antenatal dexamethasone and surfactant-D in a rat model
Authors: Lu Lei , Lu Jing , Yu Yueyue , Claud Erika 
Published: January 2021

AbstractBackgroundNecrotizing enterocolitis (NEC) is the most common gastrointestinal disorder in premature neonates. Possible therapeutic approaches are centered on promoting maturation of the gastrointestinal mucosal barrier. Studies have demonstrated that antenatal administration of corticosteroids can decrease NEC incidence and mortality.MethodsPregnant rat dams were administered dexamethasone 48 h prior to delivery. The pups were subjected to an experimental NEC-like injury protocol. Ileal tissues and sera were collected and evaluated for inflammatory cytokines, gut permeability and expressions and localizations of tight junction proteins, and surfactant protein-D by immunohistochemistry/immunofluorescent staining. Intestinal epithelial cells (IEC-6) were pretreated with SP-D to examine the effect of SP-D on tight junction protein expressions when challenged with platelet-activating factor and lipopolysaccharide to model proinflammatory insults.ResultsAntenatal dexamethasone reduced systemic inflammation, preserved intestinal barrier integrity, and stimulated SP-D expression on the intestinal mucosal surface in pups exposed to NEC-like injury. Pretreatment of SP-D blocked platelet-activating factor/lipopolysaccharide-induced tight junction disruption in IEC-6 cells in vitro.ConclusionsAntenatal dexamethasone preserves the development of intestinal mucosal barrier integrity and reduces incidence and morbidity from an experimental NEC-like injury model. Dexamethasone upregulation of intestinal SP-D-protective effects on tight junction proteins.ImpactAntenatal administration of dexamethasone can function in concert with intestinal surfactant protein-D to decrease systemic inflammatory responses, and protect intestinal barrier integrity in a neonatal rat model of NEC.A novel role of intestinal SP-D in preserving tight junction protein structures under inflammatory conditions.We describe the intestinal SP-D—an overlooked role of antenatal dexamethasone in neonatal NEC?
Inhibition of histone methyltransferase G9a attenuates liver cancer initiation by sensitizing DNA-damaged hepatocytes to p53-induced apoptosis
Authors: Nakatsuka Takuma , Tateishi Keisuke , Kato Hiroyuki , Fujiwara Hiroaki , Yamamoto Keisuke , Kudo Yotaro , Nakagawa Hayato , Tanaka Yasuo , Ijichi Hideaki , Ikenoue Tsuneo , Ishizawa Takeaki , Hasegawa Kiyoshi , Tachibana Makoto , Shinkai Yoichi , Koike Kazuhiko 
Published: January 2021

AbstractWhile the significance of acquired genetic abnormalities in the initiation of hepatocellular carcinoma (HCC) has been established, the role of epigenetic modification remains unknown. Here we identified the pivotal role of histone methyltransferase G9a in the DNA damage-triggered initiation of HCC. Using liver-specificG9a-deficient (G9aΔHep) mice, we revealed that loss of G9a significantly attenuated liver tumor initiation caused by diethylnitrosamine (DEN). In addition, pharmacological inhibition of G9a attenuated the DEN-induced initiation of HCC. After treatment with DEN, while the induction of γH2AX and p53 were comparable in theG9aΔHepand wild-type livers, more apoptotic hepatocytes were detected in theG9aΔHepliver. Transcriptome analysis identified Bcl-G, a pro-apoptotic Bcl-2 family member, to be markedly upregulated in theG9aΔHepliver. In human cultured hepatoma cells, a G9a inhibitor, UNC0638, upregulated BCL-G expression and enhanced the apoptotic response after treatment with hydrogen peroxide or irradiation, suggesting an essential role of the G9a-Bcl-G axis in DNA damage response in hepatocytes. The proposed mechanism was that DNA damage stimuli recruited G9a to the p53-responsive element of theBcl-Ggene, resulting in the impaired enrichment of p53 to the region and the attenuation of Bcl-G expression. G9a deletion allowed the recruitment of p53 and upregulated Bcl-G expression. These results demonstrate that G9a allows DNA-damaged hepatocytes to escape p53-induced apoptosis by silencing Bcl-G, which may contribute to the tumor initiation. Therefore, G9a inhibition can be a novel preventive strategy for HCC.
Autophagy augments the self-renewal of lung cancer stem cells by the degradation of ubiquitinated p53
Authors: Wang Jianyu , Liu Doudou , Sun Zhiwei , Ye Ting , Li Jingyuan , Zeng Bin , Zhao Qiting , Rosie Xing H. 
Published: January 2021

AbstractIt has been postulated that cancer stem cells (CSCs) are involved in all aspects of human cancer, although the mechanisms governing the regulation of CSC self-renewal in the cancer state remain poorly defined. In the literature, both the pro- and anti-oncogenic activities of autophagy have been demonstrated and are context-dependent. Mounting evidence has shown augmentation of CSC stemness by autophagy, yet mechanistic characterization and understanding are lacking. In the present study, by generating stable human lung CSC cell lines with the wild-type TP53 (A549), as well as cell lines in which TP53 was deleted (H1229), we show, for the first time, that autophagy augments the stemness of lung CSCs by degrading ubiquitinated p53. Furthermore, Zeb1 is required for TP53 regulation of CSC self-renewal. Moreover, TCGA data mining and analysis show that Atg5 and Zeb1 are poor prognostic markers of lung cancer. In summary, this study has elucidated a new CSC-based mechanism underlying the oncogenic activity of autophagy and the tumor suppressor activity of p53 in cancer, i.e., CSCs can exploit the autophagy-p53-Zeb1 axis for self-renewal, oncogenesis, and progression.
Direct control of store-operated calcium channels by ultrafast laser
Authors: Cheng Pan , Tian Xiaoying , Tang Wanyi , Cheng Juan , Bao Jin , Wang Haipeng , Zheng Sisi , Wang Youjun , Wei Xunbin , Chen Tunan , Feng Hua , Xue Tian , Goda Keisuke , He Hao 
Published: January 2021

AbstractCa2+ channels are essential to cell birth, life, and death. They can be externally activated by optogenetic tools, but this requires robust introduction of exogenous optogenetic genes for expression of photosensitive proteins in biological systems. Here we present femtoSOC, a method for direct control of Ca2+ channels solely by ultrafast laser without the need for optogenetic tools or any other exogenous reagents. Specifically, by focusing and scanning wavelength-tuned low-power femtosecond laser pulses on the plasma membrane for multiphoton excitation, we directly induced Ca2+ influx in cultured cells. Mechanistic study reveals that photoexcited flavins covalently bind cysteine residues in Orai1 via thioether bonds, which facilitates Orai1 polymerization to form store-operated calcium channels (SOCs) independently of STIM1, a protein generally participating in SOC formation, enabling all-optical activation of Ca2+ influx and downstream signaling pathways. Moreover, we used femtoSOC to demonstrate direct neural activation both in brain slices in vitro and in intact brains of living mice in vivo in a spatiotemporal-specific manner, indicating potential utility of femtoSOC.
Floquet spin states in OLEDs
Authors: Jamali S. , Mkhitaryan V. V. , Malissa H. , Nahlawi A. , Popli H. , Grünbaum T. , Bange S. , Milster S. , Stoltzfus D. M. , Leung A. E. , Darwish T. A. , Burn P. L. , Lupton J. M. , Boehme C. 
Published: January 2021

AbstractElectron and hole spins in organic light-emitting diodes constitute prototypical two-level systems for the exploration of the ultrastrong-drive regime of light-matter interactions. Floquet solutions to the time-dependent Hamiltonian of pairs of electron and hole spins reveal that, under non-perturbative resonant drive, when spin-Rabi frequencies become comparable to the Larmor frequencies, hybrid light-matter states emerge that enable dipole-forbidden multi-quantum transitions at integer and fractional g-factors. To probe these phenomena experimentally, we develop an electrically detected magnetic-resonance experiment supporting oscillating driving fields comparable in amplitude to the static field defining the Zeeman splitting; and an organic semiconductor characterized by minimal local hyperfine fields allowing the non-perturbative light-matter interactions to be resolved. The experimental confirmation of the predicted Floquet states under strong-drive conditions demonstrates the presence of hybrid light-matter spin excitations at room temperature. These dressed states are insensitive to power broadening, display Bloch-Siegert-like shifts, and are suggestive of long spin coherence times, implying potential applicability for quantum sensing.
Dynamical strengthening of covalent and non-covalent molecular interactions by nuclear quantum effects at finite temperature
Authors: Sauceda Huziel E. , Vassilev-Galindo Valentin , Chmiela Stefan , Müller Klaus-Robert , Tkatchenko Alexandre 
Published: January 2021

AbstractNuclear quantum effects (NQE) tend to generate delocalized molecular dynamics due to the inclusion of the zero point energy and its coupling with the anharmonicities in interatomic interactions. Here, we present evidence that NQE often enhance electronic interactions and, in turn, can result in dynamical molecular stabilization at finite temperature. The underlying physical mechanism promoted by NQE depends on the particular interaction under consideration. First, the effective reduction of interatomic distances between functional groups within a molecule can enhance the n → π* interaction by increasing the overlap between molecular orbitals or by strengthening electrostatic interactions between neighboring charge densities. Second, NQE can localize methyl rotors by temporarily changing molecular bond orders and leading to the emergence of localized transient rotor states. Third, for noncovalent van der Waals interactions the strengthening comes from the increase of the polarizability given the expanded average interatomic distances induced by NQE. The implications of these boosted interactions include counterintuitive hydroxyl–hydroxyl bonding, hindered methyl rotor dynamics, and molecular stiffening which generates smoother free-energy surfaces. Our findings yield new insights into the versatile role of nuclear quantum fluctuations in molecules and materials.
Uncomputability of phase diagrams
Authors: Bausch Johannes , Cubitt Toby S. , Watson James D. 
Published: January 2021

AbstractThe phase diagram of a material is of central importance in describing the properties and behaviour of a condensed matter system. In this work, we prove that the task of determining the phase diagram of a many-body Hamiltonian is in general uncomputable, by explicitly constructing a continuous one-parameter family of Hamiltonians H(φ), where $$\varphi \in {\mathbb{R}}$$
φ
∈
R
, for which this is the case. The H(φ) are translationally-invariant, with nearest-neighbour couplings on a 2D spin lattice. As well as implying uncomputablity of phase diagrams, our result also proves that undecidability can hold for a set of positive measure of a Hamiltonian’s parameter space, whereas previous results only implied undecidability on a zero measure set. This brings the spectral gap undecidability results a step closer to standard condensed matter problems, where one typically studies phase diagrams of many-body models as a function of one or more continuously varying real parameters, such as magnetic field strength or pressure.
Intratumoral IL-12 delivery empowers CAR-T cell immunotherapy in a pre-clinical model of glioblastoma
Authors: Agliardi Giulia , Liuzzi Anna Rita , Hotblack Alastair , De Feo Donatella , Núñez Nicolás , Stowe Cassandra L. , Friebel Ekaterina , Nannini Francesco , Rindlisbacher Lukas , Roberts Thomas A. , Ramasawmy Rajiv , Williams Iwan P. , Siow Bernard M. , Lythgoe Mark F. , Kalber Tammy L. , Quezada Sergio A. , Pule Martin A. , Tugues Sonia , Straathof Karin , Becher Burkhard 
Published: January 2021

AbstractGlioblastoma multiforme (GBM) is the most common and aggressive form of primary brain cancer, for which effective therapies are urgently needed. Chimeric antigen receptor (CAR)-based immunotherapy represents a promising therapeutic approach, but it is often impeded by highly immunosuppressive tumor microenvironments (TME). Here, in an immunocompetent, orthotopic GBM mouse model, we show that CAR-T cells targeting tumor-specific epidermal growth factor receptor variant III (EGFRvIII) alone fail to control fully established tumors but, when combined with a single, locally delivered dose of IL-12, achieve durable anti-tumor responses. IL-12 not only boosts cytotoxicity of CAR-T cells, but also reshapes the TME, driving increased infiltration of proinflammatory CD4+ T cells, decreased numbers of regulatory T cells (Treg), and activation of the myeloid compartment. Importantly, the immunotherapy-enabling benefits of IL-12 are achieved with minimal systemic effects. Our findings thus show that local delivery of IL-12 may be an effective adjuvant for CAR-T cell therapy for GBM.
Environmental signals rather than layered ontogeny imprint the function of type 2 conventional dendritic cells in young and adult mice
Authors: Papaioannou Nikos E. , Salei Natallia , Rambichler Stephan , Ravi Kaushikk , Popovic Jelena , Küntzel Vanessa , Lehmann Christian H. K. , Fiancette Remi , Salvermoser Johanna , Gajdasik Dominika W. , Mettler Ramona , Messerer Denise , Carrelha Joana , Ohnmacht Caspar , Haller Dirk , Stumm Ralf , Straub Tobias , Jacobsen Sten Eirik W. , Schulz Christian , Withers David R. , Schotta Gunnar , Dudziak Diana , Schraml Barbara U. 
Published: January 2021

AbstractConventional dendritic cells (cDC) are key activators of naive T cells, and can be targeted in adults to induce adaptive immunity, but in early life are considered under-developed or functionally immature. Here we show that, in early life, when the immune system develops, cDC2 exhibit a dual hematopoietic origin and, like other myeloid and lymphoid cells, develop in waves. Developmentally distinct cDC2 in early life, despite being distinguishable by fate mapping, are transcriptionally and functionally similar. cDC2 in early and adult life, however, are exposed to distinct cytokine environments that shape their transcriptional profile and alter their ability to sense pathogens, secrete cytokines and polarize T cells. We further show that cDC2 in early life, despite being distinct from cDC2 in adult life, are functionally competent and can induce T cell responses. Our results thus highlight the potential of harnessing cDC2 for boosting immunity in early life.
Choroid plexus NKCC1 mediates cerebrospinal fluid clearance during mouse early postnatal development
Authors: Xu Huixin , Fame Ryann M. , Sadegh Cameron , Sutin Jason , Naranjo Christopher , Della Syau  , Cui Jin , Shipley Frederick B. , Vernon Amanda , Gao Fan , Zhang Yong , Holtzman Michael J. , Heiman Myriam , Warf Benjamin C. , Lin Pei-Yi , Lehtinen Maria K. 
Published: January 2021

AbstractCerebrospinal fluid (CSF) provides vital support for the brain. Abnormal CSF accumulation, such as hydrocephalus, can negatively affect perinatal neurodevelopment. The mechanisms regulating CSF clearance during the postnatal critical period are unclear. Here, we show that CSF K+, accompanied by water, is cleared through the choroid plexus (ChP) during mouse early postnatal development. We report that, at this developmental stage, the ChP showed increased ATP production and increased expression of ATP-dependent K+transporters, particularly the Na+, K+, Cl−, and water cotransporter NKCC1. Overexpression of NKCC1 in the ChP resulted in increased CSF K+clearance, increased cerebral compliance, and reduced circulating CSF in the brain without changes in intracranial pressure in mice. Moreover, ChP-specific NKCC1 overexpression in an obstructive hydrocephalus mouse model resulted in reduced ventriculomegaly. Collectively, our results implicate NKCC1 in regulating CSF K+clearance through the ChP in the critical period during postnatal neurodevelopment in mice.