bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advancing towards inclusive peace and security: Persons with disabilities and Security Council Resolution 2475
Authors: Ruminowicz Bogna 
Published: October 2022

AbstractPersons with disabilities are at higher risk of injury or death during an armed conflict, either as specific targets or through inability to protect themselves. Humanitarian responses concentrate on meeting the immediate basic needs of an average population. Yet historically, the situation of persons with disabilities during armed conflict, as well as peacebuilding processes, has been largely absent in the discussion at the Security Council. On 20 June 2019, the United Nations Security Council unanimously passed Resolution 2475. This groundbreaking text marks the first time the Council has dedicated an entire resolution to the situation of persons with disabilities in situations of armed conflict. The resolution has significantly raised the attention and understanding of the situation of persons with disabilities in the context of the armed conflict in the Security Council and beyond. This article details the process that led to Resolution 2475, as well as what has happened since.
Investigating Drivers of Particulate Matter Pollution Over India and the Implications for Radiative Forcing With GEOS‐Chem‐TOMAS15
Authors: Karambelas Alexandra , Fiore Arlene M. , Westervelt Daniel M. , McNeill V. Faye , Randles Cynthia A. , Venkataraman Chandra , Pierce Jeffrey R. , Bilsback Kelsey R. , Milly George P. 
Published: October 2022

AbstractAmbient fine particulate matter (PM2.5) concentrations in India frequently exceed 100 μg/m3 during fall and winter pollution episodes. We use the GEOS‐Chem chemical transport model with the TwO‐Moment Aerosol Sectional microphysics scheme with 15 size bins (TOMAS15) to assess PM2.5 composition and impacts on radiation and cloud condensation nuclei (CCN) during pollution episodes as compared to the seasonal (October‐December) average. We conduct high resolution (0.25° × 0.3125°) nested‐domain simulations over India for short‐duration, high‐PM2.5 episodes in the fall of 2015 and 2017. The simulations capture the magnitude and spatial patterns of pollution episodes measured by surface monitors (r2PM2.5 = 0.69) although aerosol optical depth is underestimated. During the episodes, near‐surface organic matter (OM), black carbon (BC), and secondary inorganic aerosol concentrations increase from seasonal averages by up to 36, 7, and 7 μg/m3, respectively. Episodic aerosol increases enhance cooling by lowering the top‐of‐atmosphere clear‐sky direct radiative effect (DRETOA) during the 2015 episode (−6 W/m2), with a smaller impact during the 2017 episode (−1 W/m2). Differences in DRETOA reflect larger increases in scattering aerosols in the column during the 2015 episode (+17 mg/m2) than in 2017 (+13 mg/m2), while absorbing aerosol column enhancements are smaller (+3 mg/m2) in both years. Changes in shortwave radiation at the surface (SWsfc) are spatially similar to DRETOA and mostly negative during both episodes. CCN enhancements (0.2% supersaturation) during these episodes occur across the western Indo‐Gangetic Plain, coincident with higher PM2.5 concentrations. Changes in DRETOA, SWsfc, and CCN during high‐PM2.5 episodes may have implications for crops, the hydrologic cycle, and surface temperature.
High Sensitivity of Compound Drought and Heatwave Events to Global Warming in the Future
Authors: Zhang Qin , She Dunxian , Zhang Liping , Wang Gangsheng , Chen Jie , Hao Zengchao 
Published: October 2022

AbstractCompound drought and heatwave (CDHW) events have received considerable attention in recent years due to their devastating effects on human society and ecosystem. In this study, we systematically investigated the changes of CDHW events in multi‐spatiotemporal scales for historical period (1951–2014) and four future scenarios (2020–2100) (SSP1‐2.6, SSP2‐4.5, SSP3‐7.0, and SSP5‐8.5) over global land by using Coupled Model Intercomparison Project Phase 6 (CMIP6) models. The responses of the CDHW events to the changes of maximum air temperature and the climatic water balance variable are also examined. The results show that the multi‐model ensembles project a significant increasing trend in CDHW characteristics over almost all global lands under SSP2‐4.5, SSP3‐7.0, and SSP5‐8.5, especially across northern North‐America, Caribbean, Mediterranean and Russian‐Arctic, there is a stronger increasing trend. A significantly increasing CDHW risk will occur across most global land for the medium to long term future without aggressive adaptation and mitigation strategies. The results of path analysis suggest that temperature is the dominant factor influencing CDHW events. Additionally, higher sensitivity of CDHW events to global warming will occur in the future. Particularly, each 1°C global warming increases the duration of the CDHW events by 3 days in the historical period, but by about 10 days in the future period. Overall, this study improves our understanding in the projection of CDHW events and the impacts of climate drivers to the CDHW events under various future scenarios, which could provide supports about the risk assessment, adaptation and mitigation strategies under climate change.
Precipitation Over Southern Africa: Moisture Sources and Isotopic Composition
Authors: Geppert M. , Hartmann K. , Kirchner I. , Pfahl S. , Struck U. , Riedel F. 
Published: October 2022

AbstractSouthern Africa, with its vast arid to semiarid areas, is considered vulnerable to precipitation changes and amplifying weather extremes. However, during the last 100 ka, huge lakes existed in the currently dry central Kalahari. It has been suggested that these lakes could have existed due to altered atmospheric circulation pattern, leading to an increase in precipitation or to changes in the annual precipitation distribution. Past climate changes are recorded in paleo‐archives, yet, for a proper interpretation of paleo‐records, for example, from sedimentological archives or fossils, it is essential to put them in a context with recent observations. This study’s objective is, therefore, to analyze spatially differing annual precipitation distributions at multiple locations in southern Africa with respect to their stable water isotope composition, moisture transport pathways, and sources. Five different precipitation distributions are identified by end‐member modeling and respective rainfall zones are inferred, which differ significantly in their isotopic compositions. By calculating backward trajectories, different moisture source regions are identified for the rainfall zones and linked to typical circulation patterns. Our results furthermore show the importance of the seasonality, the amount effect, and the traveled distance of the moisture for the general isotopic composition over the entire southern Africa. The identified pattern and relationships can be useful in the evaluation of isotope‐enabled climate models for the region and are potentially of major importance for the interpretation of stable water isotope composition in paleo‐records in future research.
Characterization of Southern Ocean Boundary Layer Clouds Using Airborne Radar, Lidar, and In Situ Cloud Data: Results From SOCRATES
Authors: Schima Julian , McFarquhar Greg , Romatschke Ulrike , Vivekanandan Jothiram , D’Alessandro John , Haggerty Julie , Wolff Cory , Schaefer Ethan , Järvinen Emma , Schnaiter Martin 
Published: October 2022

AbstractClimate and numerical weather prediction models struggle to accurately predict radiative forcing over the Southern Ocean (SO), as the amount of clouds and their phases are poorly represented in such models due to a lack of observations upon which to base parameterizations. To address this, a novel particle identification (PID) scheme, based upon airborne radar and lidar data, was applied to data collected during the Southern Ocean Clouds, Aerosol, Radiation Transport Experimental Study (SOCRATES) to assess the vertical structure of SO boundary layer clouds. A comparison between the PID scheme and in situ phase data from SOCRATES showed relatively good agreement between the two data types. The convectivity of the clouds sampled during SOCRATES was determined using the novel Echo Classification from COnvectivity for Vertically pointing radars product. The PID and in situ data were then used synergistically to identify the following features of cloud vertical structure: (a) Supercooled liquid water was very common (Probability, P ∼ 80%) at cloud top for convective and stratiform clouds; (b) Supercooled large drops with maximum dimensions >95 μm frequently appear within a hundred meters below cloud top, particularly within convective clouds (Max P 35%–45%), but also within stratiform clouds (Max P 20%–30%); (c) Ice production was associated with convective activity, with P ∼ 20% at cloud top, increasing to 50%–70% 200 m below top, compared to P < 30% everywhere in stratiform clouds; (d) Convective clouds were found to be more vertically heterogeneous than stratiform clouds.
Controlled afterglow luminescent particles for photochemical tissue bonding
Authors: Kim Seong-Jong , Choi Minji , Hong Guosong , Hahn Sei Kwang 
Published: October 2022

AbstractUpconversion materials (UCMs) have been developed to convert tissue-penetrating near-infrared (NIR) light into visible light. However, the low energy conversion efficiency of UCMs has limited their further biophotonic applications. Here, we developed controlled afterglow luminescent particles (ALPs) of ZnS:Ag,Co with strong and persistent green luminescence for photochemical tissue bonding (PTB). The co-doping of Ag+ and Co2+ ions into ZnS:Ag,Co particles with the proper vacancy formation of host ions resulted in high luminescence intensity and long-term afterglow. In addition, the ALPs of ZnS:Ag,Co could be recharged rapidly under short ultraviolet (UV) irradiation, which effectively activated rose bengal (RB) in hyaluronate-RB (HA-RB) conjugates for the crosslinking of dissected collagen layers without additional light irradiation. The remarkable PTB of ZnS:Ag,Co particles with HA-RB conjugates was confirmed by in vitro collagen fibrillogenesis assay, in vivo animal wound closure rate analysis, and in vivo tensile strength evaluation of incised skin tissues. Taken together, we could confirm the feasibility of controlled ALPs for various biophotonic applications.
Fetuin-A is an immunomodulator and a potential therapeutic option in BMP4-dependent heterotopic ossification and associated bone mass loss
Authors: Kan Chen , Yang Jiazhao , Fan Haitao , Dai Yuanjuan , Wang Xingxing , Chen Rui , Liu Jia , Meng Xiangyue , Wang Wei , Li Guiling , Zhou Jiao , Zhang Ya , Zhu Wanbo , Fang Shiyuan , Wei Haiming , Zheng Hong , Wang Siying , Ni Fang 
Published: October 2022

AbstractHeterotopic ossification (HO) is the abnormal formation of bone in extraskeletal sites. However, the mechanisms linking HO pathogenesis with bone mass dysfunction remain unclear. Here, we showed that mice harboring injury-induced and BMP4-dependent HO exhibit bone mass loss similar to that presented by patients with HO. Moreover, we found that injury-induced hyperinflammatory responses at the injury site triggered HO initiation but did not result in bone mass loss at 1 day post-injury (dpi). In contrast, a suppressive immune response promoted HO propagation and bone mass loss by 7 dpi. Correcting immune dysregulation by PD1/PDL1 blockade dramatically alleviated HO propagation and bone mass loss. We further demonstrated that fetuin-A (FetA), which has been frequently detected in HO lesions but rarely observed in HO-adjacent normal bone, acts as an immunomodulator to promote PD1 expression and M2 macrophage polarization, leading to immunosuppression. Intervention with recombinant FetA inhibited hyperinflammation and prevented HO and associated bone mass loss. Collectively, our findings provide new insights into the osteoimmunological interactions that occur during HO formation and suggest that FetA is an immunosuppressor and a potential therapeutic option for the treatment of HO.
IKCa channels control breast cancer metabolism including AMPK-driven autophagy
Authors: Gross Dominic , Bischof Helmut , Maier Selina , Sporbeck Katharina , Birkenfeld Andreas L. , Malli Roland , Ruth Peter , Proikas-Cezanne Tassula , Lukowski Robert 
Published: October 2022

AbstractCa2+-activated K+ channels of intermediate conductance (IK) are frequently overexpressed in breast cancer (BC) cells, while IK channel depletion reduces BC cell proliferation and tumorigenesis. This raises the question, of whether and mechanistically how IK activity interferes with the metabolic activity and energy consumption rates, which are fundamental for rapidly growing cells. Using BC cells obtained from MMTV-PyMT tumor-bearing mice, we show that both, glycolysis and mitochondrial ATP-production are reduced in cells derived from IK-deficient breast tumors. Loss of IK altered the sub-/cellular K+- and Ca2+- homeostasis and mitochondrial membrane potential, ultimately resulting in reduced ATP-production and metabolic activity. Consequently, we find that BC cells lacking IK upregulate AMP-activated protein kinase activity to induce autophagy compensating the glycolytic and mitochondrial energy shortage. Our results emphasize that IK by modulating cellular Ca2+- and K+-dynamics contributes to the remodeling of metabolic pathways in cancer. Thus, targeting IK channel might disturb the metabolic activity of BC cells and reduce malignancy.
Limiting glutamine utilization activates a GCN2/TRAIL-R2/Caspase-8 apoptotic pathway in glutamine-addicted tumor cells
Authors: Yerbes Rosario , Mora-Molina Rocío , Fernández-Farrán F. Javier , Hiraldo Laura , López-Rivas Abelardo , Palacios Carmen 
Published: October 2022

AbstractOncogenic transformation leads to changes in glutamine metabolism that make transformed cells highly dependent on glutamine for anabolic growth and survival. Herein, we investigated the cell death mechanism activated in glutamine-addicted tumor cells in response to the limitation of glutamine metabolism. We show that glutamine starvation triggers a FADD and caspase-8-dependent and mitochondria-operated apoptotic program in tumor cells that involves the pro-apoptotic TNF-related apoptosis-inducing ligand receptor 2 (TRAIL-R2), but is independent of its cognate ligand TRAIL. In glutamine-depleted tumor cells, activation of the amino acid-sensing general control nonderepressible-2 kinase (GCN2) is responsible for TRAIL-R2 upregulation, caspase-8 activation, and apoptotic cell death. Interestingly, GCN2-dependent ISR signaling induced by methionine starvation also leads to TRAIL-R2 upregulation and apoptosis. Moreover, pharmacological inhibition of transaminases activates a GCN2 and TRAIL-R2-dependent apoptotic mechanism that is inhibited by non-essential amino acids (NEAA). In addition, metabolic stress upon glutamine deprivation also results in GCN2-independent FLICE-inhibitory protein (FLIP) downregulation facilitating caspase-8 activation and apoptosis. Importantly, downregulation of the long FLIP splice form (FLIPL) and apoptosis upon glutamine deprivation are inhibited in the presence of a membrane-permeable α-ketoglutarate. Collectively, our data support a model in which limiting glutamine utilization in glutamine-addicted tumor cells triggers a previously unknown cell death mechanism regulated by GCN2 that involves the TRAIL-R2-mediated activation of the extrinsic apoptotic pathway.
Liquid biopsy in gastric cancer: predictive and prognostic biomarkers
Authors: Zhang Zihao , Wu Hao , Chong Wei , Shang Liang , Jing Changqing , Li Leping 
Published: October 2022

AbstractGastric cancer (GC) is a high-incidence cancer worldwide. Most patients are diagnosed at an advanced stage, by which time they have limited treatment options and poor prognosis. Early diagnosis and precise treatment are important. In the past few years, emerging research has been conducted on the use of non-invasive liquid biopsy, with its advantages of minimal invasiveness and repeated sampling, to monitor tumor occurrence and recurrence in real time and to evaluate prognosis and treatment response. Many studies have demonstrated the potential of liquid biopsy in GC, and the detection of circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), circulating free DNA (cfDNA), and exosomes has achieved gratifying results. In this review, we summarize evolving technologies for and information regarding liquid biopsy, the most recently discovered GC liquid biopsy biomarkers, and ongoing clinical trials and discuss the challenges and application prospects of liquid biopsy in GC.
Extracellular vesicles microRNA-592 of melanoma stem cells promotes metastasis through activation of MAPK/ERK signaling pathway by targeting PTPN7 in non-stemness melanoma cells
Authors: Zhang Yuhan , Chen Yan , Shi Lei , Li Jie , Wan Wenjuan , Li Bowen , Liu Doudou , Li Xiaoshuang , Chen Yuting , Xiang Meng , Chen Hao , Zeng Bin , Xing H. Rosie , Wang Jianyu 
Published: October 2022

AbstractMelanoma, one of the most aggressive malignancies, its high mortality and low survival rates are associated with effective metastatic colonization. Melanoma metastasis hinges on the bidirectional cell-cell communication within the complex metastatic microenvironments (MME). Extracellular vesicles (EVs) are recognized as a new class of molecular mediator in MME programing. Published studies show that melanoma EVs can educate MME stromal cells to acquire the pro-metastatic phenotype to enhance metastatic colonization. Whether EVs can mediate the interactions between heterogenous cancer cells within the MME that alter the course of metastasis has not been investigated at the mechanistic level. In this study, melanoma parental cells (MPCs) and paired derivative cancer stem cell line melanoma stem cells (MSCs) that were derived from melanoma cell line M14 were used. We demonstrate that the EVs-mediated crosstalk between the MSCs and the MPCs is a novel mechanism for melanoma metastasis. We characterized miR-592, a relatively novel microRNA of prognostic potential, in mediation of such intercellular crosstalk. EVs can encapsulate and deliver miR-592 to target MPCs. Upon entering, miR-592 inhibits the expression of its gene target protein tyrosine phosphatase non-receptor type7 (PTPN7), a phosphatase targeting MAPKs. This leads to the relief of the inhibitory effect of PTPN7 on MAPK/ERK signaling and consequently the augmentation of metastatic colonization of MPCs. Thus, via the extracellular vesicle miR-592/PTPN7/MAPK axis, melanoma-CSCs can transfer their metastatic ability to the low-metastatic non-CSC melanoma cells.
Somatic genetic variation in healthy tissue and non-cancer diseases
Authors: Solís-Moruno Manuel , Batlle-Masó Laura , Bonet Núria , Aróstegui Juan I. , Casals Ferran 
Published: October 2022

AbstractSomatic genetic variants have been studied for several years mostly concerning cancer, where they contribute to its origin and development. It is also clear that the somatic variants load is greater in aged individuals in comparison to younger ones, pointing to a cause/consequence of the senescence process. More recently, researchers have focused on the role of this type of variation in healthy tissue and its dynamics in cell lineages and different organs. In addition, somatic variants have been described to contribute to monogenic diseases, and the number of evidences of their role in complex disorders is also increasing. Thanks to recent advances in next-generation sequencing technologies, this type of genetic variation can be now more easily studied than in the past, although we still face some important limitations. Novel strategies for sampling, sequencing and filtering are being investigated to detect these variants, although validating them with an orthogonal approach will most likely still be needed. In this review, we aim to update our knowledge of somatic variation detection and its relation to healthy tissue and non-cancer diseases.
Emergent helical edge states in a hybridized three-dimensional topological insulator
Authors: Chong Su Kong , Liu Lizhe , Watanabe Kenji , Taniguchi Takashi , Sparks Taylor D. , Liu Feng , Deshpande Vikram V. 
Published: October 2022

AbstractAs the thickness of a three-dimensional (3D) topological insulator (TI) becomes comparable to the penetration depth of surface states, quantum tunneling between surfaces turns their gapless Dirac electronic structure into a gapped spectrum. Whether the surface hybridization gap can host topological edge states is still an open question. Herein, we provide transport evidence of 2D topological states in the quantum tunneling regime of a bulk insulating 3D TI BiSbTeSe2. Different from its trivial insulating phase, this 2D topological state exhibits a finite longitudinal conductance at ~2e2/h when the Fermi level is aligned within the surface gap, indicating an emergent quantum spin Hall (QSH) state. The transition from the QSH to quantum Hall (QH) state in a transverse magnetic field further supports the existence of this distinguished 2D topological phase. In addition, we demonstrate a second route to realize the 2D topological state via surface gap-closing and topological phase transition mechanism mediated by a transverse electric field. The experimental realization of the 2D topological phase in a 3D TI enriches its phase diagram and marks an important step toward functionalized topological quantum devices.
Distinct organization of two cortico-cortical feedback pathways
Authors: Shen Shan , Jiang Xiaolong , Scala Federico , Fu Jiakun , Fahey Paul , Kobak Dmitry , Tan Zhenghuan , Zhou Na , Reimer Jacob , Sinz Fabian , Tolias Andreas S. 
Published: October 2022

AbstractNeocortical feedback is critical for attention, prediction, and learning. To mechanically understand its function requires deciphering its cell-type wiring. Recent studies revealed that feedback between primary motor to primary somatosensory areas in mice is disinhibitory, targeting vasoactive intestinal peptide-expressing interneurons, in addition to pyramidal cells. It is unknown whether this circuit motif represents a general cortico-cortical feedback organizing principle. Here we show that in contrast to this wiring rule, feedback between higher-order lateromedial visual area to primary visual cortex preferentially activates somatostatin-expressing interneurons. Functionally, both feedback circuits temporally sharpen feed-forward excitation eliciting a transient increase–followed by a prolonged decrease–in pyramidal cell activity under sustained feed-forward input. However, under feed-forward transient input, the primary motor to primary somatosensory cortex feedback facilitates bursting while lateromedial area to primary visual cortex feedback increases time precision. Our findings argue for multiple cortico-cortical feedback motifs implementing different dynamic non-linear operations.