bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Responsibility to Protect and its Critics: Explaining the Consensus
Authors: Serrano Mónica 
Published: December 2011

AbstractWhile critics have claimed that the Responsibility to Protect (R2P) is a North-South polarising issue and is therefore controversial, this is a deliberate misrepresentation in a rhetorical war led by a small minority of UN member states. The first section of this article briefly reviews the evolution of this emerging norm from its inception in the 2001 report by the International Commission on State Sovereignty and Intervention (ICISS), to its endorsement in 2005 by more than 150 heads of states in the 2005 World Summit Outcome Document, to its more recent configuration in a three-pillar structure. The next part seeks to identify the main criticisms that have been levelled at R2P. It touches on some of the myths and allegations that have long accompanied R2P, as well as on the chief legitimate concerns underlying the shift towards implementation. The third and concluding section briefly touches upon the impact of the interventions in Libya and Côte D'Ivoire upon the evolving R2P consensus, and critically assesses the implications of a normative strategy that has put a premium on unanimity and unqualified consensus.
Challenges and directions: an analysis of Genetic Analysis Workshop 17 data by collapsing rare variants within family data
Authors: Lin Peng , Hamm Michael , Hartz Sarah , Zhang Zhehao , Rice John P 
Published: December 2011

Abstract
Recent studies suggest that the traditional case-control study design does not have sufficient power to discover rare risk variants. Two different methods—collapsing and family data—are suggested as alternatives for discovering these rare variants. Compared with common variants, rare variants have unique characteristics. In this paper, we assess the distribution of rare variants in family data. We notice that a large number of rare variants exist only in one or two families and that the association result is largely shaped by those families. Therefore we explore the possibility of integrating both the collapsing method and the family data method. This combinational approach offers a potential power boost for certain causal genes, including VEGFA, VEGFC, SIRT1, SREBF1, PIK3R3, VLDLR, PLAT, and FLT4, and thus deserves further investigation.
Climate Change and Cardiovascular Health
Authors: Kazi Dhruv S. , Katznelson Ethan , Liu Chia-Liang , Al-Roub Nora M. , Chaudhary Richard S. , Young Diane E. , McNichol Megan , Mickley Loretta J. , Kramer Daniel B. , Cascio Wayne E. , Bernstein Aaron S. , Rice Mary B. 
Published: June 2024

ImportanceClimate change may increase the risk of adverse cardiovascular outcomes by causing direct physiologic changes, psychological distress, and disruption of health-related infrastructure. Yet, the association between numerous climate change–related environmental stressors and the incidence of adverse cardiovascular events has not been systematically reviewed.ObjectiveTo review the current evidence on the association between climate change–related environmental stressors and adverse cardiovascular outcomes.Evidence ReviewPubMed, Embase, Web of Science, and Cochrane Library were searched to identify peer-reviewed publications from January 1, 1970, through November 15, 2023, that evaluated associations between environmental exposures and cardiovascular mortality, acute cardiovascular events, and related health care utilization. Studies that examined only nonwildfire-sourced particulate air pollution were excluded. Two investigators independently screened 20 798 articles and selected 2564 for full-text review. Study quality was assessed using the Navigation Guide framework. Findings were qualitatively synthesized as substantial differences in study design precluded quantitative meta-analysis.FindingsOf 492 observational studies that met inclusion criteria, 182 examined extreme temperature, 210 ground-level ozone, 45 wildfire smoke, and 63 extreme weather events, such as hurricanes, dust storms, and droughts. These studies presented findings from 30 high-income countries, 17 middle-income countries, and 1 low-income country. The strength of evidence was rated as sufficient for extreme temperature; ground-level ozone; tropical storms, hurricanes, and cyclones; and dust storms. Evidence was limited for wildfire smoke and inadequate for drought and mudslides. Exposure to extreme temperature was associated with increased cardiovascular mortality and morbidity, but the magnitude varied with temperature and duration of exposure. Ground-level ozone amplified the risk associated with higher temperatures and vice versa. Extreme weather events, such as hurricanes, were associated with increased cardiovascular risk that persisted for many months after the initial event. Some studies noted a small increase in cardiovascular mortality, out-of-hospital cardiac arrests, and hospitalizations for ischemic heart disease after exposure to wildfire smoke, while others found no association. Older adults, racial and ethnic minoritized populations, and lower-wealth communities were disproportionately affected.Conclusions and RelevanceSeveral environmental stressors that are predicted to increase in frequency and intensity with climate change are associated with increased cardiovascular risk, but data on outcomes in low-income countries are lacking. Urgent action is needed to mitigate climate change–associated cardiovascular risk, particularly in vulnerable populations.
Updated Estimate of the Number of Extreme Risk Protection Orders Needed to Prevent 1 Suicide
Authors: Miller Matthew , Zhang Yifan , Studdert David M. , Swanson Sonja 
Published: June 2024

ImportanceExtreme risk protection orders (ERPOs)—also known as red flag, risk warrant, and gun violence restraining orders—authorize law enforcement, family members, and sometimes others to petition a court to remove firearms from and prevent the acquisition of new firearms by a person judged to pose an immediate danger to themselves or others. Previous estimates suggest that 1 suicide is prevented for every 10 ERPOs issued, a number needed to treat that depends critically on the counterfactual estimate of the proportion of suicidal acts by ERPO respondents that would have involved firearms in the absence of ERPOs.ObjectiveTo empirically inform updated estimates of the number of ERPOs needed to prevent 1 suicide.Design, Setting, and ParticipantsThis cohort study used data from California for method-specific suicides by handgun ownership (October 18, 2004, to December 31, 2015). Handgun-owning suicide decedents in California were identified using individual-level registry data about lawful handgun ownership linked to cause-specific mortality for a cohort of more than 25 million adults. The study also used data from Connecticut for method-specific suicides among ERPO respondents who died by suicide, extracted from published data (October 1999 to June 2013). Data analysis was performed in December 2023.ExposureHandgun ownership.Main Outcomes and MeasuresThe primary outcomes were the number and distribution of suicidal acts by handgun owners in California, estimated using method-specific suicide mortality data and published case fatality ratios, and the counterfactual number and distribution of suicidal acts and deaths among ERPO respondents in Connecticut had no ERPOs been issued.ResultsA total of 1216 handgun owners (mean [SD] age, 50 [18] years; 1019 male [83.8%]) died by suicide during the study period. Among male handgun owners in California, 28% of suicidal acts involved firearms, 54% involved drug poisoning, 9% involved cutting or piercing, 3% involved hanging or suffocation, 2% involved poisoning with solids and/or liquids, and the remaining 4% involved other methods. Assuming this distribution approximates the counterfactual distribution among ERPO respondents in Connecticut in the absence of ERPOs, 1 suicide death was prevented for every 22 ERPOs issued.Conclusions and RelevanceThe estimates produced by this cohort study of California handgun owners suggest that ERPOs can play an important role in averting deaths among high-risk individuals.
Insurance Denials and Patient Treatment in a Large Academic Radiation Oncology Center
Authors: Shin Jacob Y. , Chino Fumiko , Cuaron John J. , Washington Charles , Jablonowski Margaret , McBride Sean , Gomez Daniel R. 
Published: June 2024

ImportanceInsurance barriers to cancer care can cause significant patient and clinician burden.ObjectiveTo investigate the association of insurance denial with changes in technique, dose, and time to delivery of radiation oncology treatment.Design, Setting, and ParticipantsIn this single-institution cohort analysis, data were collected from patients with payer-denied authorization for radiation therapy (RT) from November 1, 2021, to December 8, 2022. Data were analyzed from December 15, 2022, to December 31, 2023.ExposureInsurance denial for RT.Main Outcomes and MeasuresAssociation of these denials with changes in RT technique, dose, and time to treatment delivery was assessed using χ2 tests.ResultsA total of 206 cases (118 women [57.3%]; median age, 58 [range, 26-91] years) were identified. Most insurers (199 [96.6%]) were commercial payers, while 7 (3.4%) were Medicare or Medicare Advantage. One hundred sixty-one patients (78.2%) were younger than 65 years. Of 206 cases, 127 (61.7%) were ultimately authorized without any change to the requested RT technique or prescription dose; 56 (27.2%) were authorized after modification to RT technique and/or prescription dose required by the payer. Of 21 cases with required prescription dose change, the median decrease in dose was 24.0 (range, 2.3-51.0) Gy. Of 202 cases (98.1%) with RT delivered, 72 (34.9%) were delayed for a mean (SD) of 7.8 (9.1) days and median of 5 (range, 1-49) days. Four cases (1.9%) ultimately did not receive any authorization, with 3 (1.5%) not undergoing RT, and 1 (0.5%) seeking treatment at another institution.Conclusions and RelevanceIn this cohort study of patients with payer-denied cases, most insurance denials in radiation oncology were ultimately approved on appeal; however, RT technique and/or effectiveness may be compromised by payer-mandated changes. Further investigation and action to recognize the time and financial burdens on clinicians and clinical effects on patients caused by insurance denials of RT is needed.
Sodium-Glucose Cotransporter-2 Inhibitors and Nephritis Among Patients With Systemic Lupus Erythematosus
Authors: Yen Fu-Shun , Wang Shiow-Ing , Hsu Chih-Cheng , Hwu Chii-Min , Wei James Cheng-Chung 
Published: June 2024

ImportanceLupus nephritis is a major complication of systemic lupus erythematosus (SLE). Randomized clinical trials have shown nephroprotective and cardioprotective effects of sodium-glucose cotransporter-2 inhibitors (SGLT2is).ObjectiveTo investigate whether the use of SGLT2is is associated with the onset and progression of lupus nephritis and other kidney and cardiac outcomes in patients with SLE and type 2 diabetes.Design, Setting, and ParticipantsThis multicenter cohort study used the US Collaborative Network of the TriNetX clinical data platform to identify patients with SLE and type 2 diabetes from January 1, 2015, to December 31, 2022. Data collection and analysis were conducted in September 2023.ExposuresIndividuals were categorized into 2 groups by SGLT2i use or nonuse with 1:1 propensity score matching.Main Outcomes and MeasuresThe Kaplan-Meier method and Cox proportional hazards regression models were used to calculate the 5-year adjusted hazard ratios (AHRs) of lupus nephritis, dialysis, kidney transplant, heart failure, and mortality for the 2 groups.ResultsFrom 31 790 eligible participants, 1775 matched pairs of SGLT2i users and nonusers (N = 3550) were selected based on propensity scores. The mean (SD) age of matched participants was 56.8 (11.6) years, and 3012 (84.8%) were women. SGLT2i users had a significantly lower risk of lupus nephritis (AHR, 0.55; 95% CI, 0.40-0.77), dialysis (AHR, 0.29; 95% CI, 0.17-0.48), kidney transplant (AHR, 0.14; 95% CI, 0.03-0.62), heart failure (AHR, 0.65; 95% CI, 0.53-0.78), and all-cause mortality (AHR, 0.35; 95% CI, 0.26-0.47) than SGLT2i nonusers.Conclusions and RelevanceIn this cohort study of patients with SLE and type 2 diabetes, SGLT2i users had a significantly lower risk of lupus nephritis, dialysis, kidney transplant, heart failure, and all-cause mortality than nonusers. The findings suggest that SGLT2is may provide some nephroprotective and cardioprotective benefits.
Interconnection and damping assignment passivity‐based control for dynamic steering position stabilization of an underactuated AUV
Authors: Desai Ravishankar P. , Manjarekar Narayan S. 
Published: June 2024

AbstractSteering motion bestows autonomous underwater vehicles (AUVs) with the agility to navigate intricate paths and trajectories precisely. Ensuring effective steering position stabilization in underwater vehicles is paramount, as it enables precise navigation and enhances safety, efficiency, data accuracy, adaptability to changing conditions, and the overall success of diverse underwater missions. This article addresses the challenging task of steering position stabilization in underactuated AUVs. To achieve this, we employ an interconnection and damping assignment passivity‐based control method to design a control law tailored for steering position stabilization. Our approach considers the nonlinear dynamics of a six‐degrees‐of‐freedom steering motion in AUVs. The control objective involves assigning a suitable energy function and reshaping the interconnection and damping structure to render the closed‐loop system asymptotically stable at the desired equilibrium point. The robustness of our proposed control law is assessed rigorously, subjecting it to modeling uncertainties and underwater disturbances. Our findings are substantiated with simulation results that support the efficacy of the designed control law. Notably, we base our simulations on experimentally validated steering motion parameters obtained from the REMUS 100 AUV, enhancing the real‐world applicability of our research.
Physicochemical Cues Steering Spiky Mn/MoOx Nanocarriers to Mimic Oncolytic Virus for Potentiating Cancer Immunotherapy
Authors: Zhao Liying , Zhao Xiaomin , Zhang Wei , Miao Yuhang , Wang Xin , Deng Dawei 
Published: June 2024

AbstractThe approval of oncolytic viruses as antigen‐agnostic cancer vaccines provides a paradigm shift for immunotherapy. However, a delicate balance between safety and immunogenicity whether native or engineered oncolytic viruses remains elusive and further compounded by oncolysis‐induced immunosuppression. To address these dilemmas, the de novo design and synthesis of oncolytic viruses‐inspired nanoplatform are proposed by emulating desirable nanostructure and bioactivity for effective cancer immunotherapy. Initially, the influence of MoOx nanoparticles with varying physical morphologies on siRNA transfection are explored, wherein the virus‐inspired MoOx nanoparticles with spiky surfaces (Spi‐MoOx) are well positioned to serve as siRNA vectors to present the highest transfection efficacy. Given the preexisting immune suppression, defect engineering is incorporated into Spi‐MoOx through Mn dopants (Spi‐Mn/MoOx), in an effort to participate in tumor adaptation to hypoxia and maximize the oncolytic potency, while retaining favorable safety profiles. More importantly, the engineered oncolytic viruses hold considerable promise to function as a universal platform that enables any gene to be modulated precisely, allowing the selective activation of various pathways. Collectively, the study offers insights into the biomimetic synthesis and bioactivity of biological system through manipulating the physicochemical cues, while carrying significant implications to propel artificial oncolytic agents from the laboratory to clinical settings.
Post‐Assembled Alkylphosphonic Acids for Efficient and Stable Inverted Perovskite Solar Cells
Authors: Zhao Yan , Luan Xiangfeng , Han Liyuan , Wang Yanbo 
Published: June 2024

AbstractThe self‐assembled monolayer (SAM) is now widely applied at the hole‐selective interface of efficient inverted perovskite solar cells (PSCs). However, voids are unavoidable in SAMs due to the rough substrate and the deposition conditions, which lead to direct contact between the active layer and electrode, undermining the efficiency and stability of PSCs. Here, alkylphosphonic acids with different alkyl chain length are post‐assembled to fill the voids, thereby forming a compact po‐SAM layer. By further modifying the head group of alkylphosphonic acids, the efficiency and stability of PSCs are improved due to wetting and passivation. Finally, the po‐SAM layer formed by (2‐Bromoethyl) phosphonic acid and [4‐(3,6‐dimethyl‐9H‐carbazol‐9‐yl)butyl] phosphonic acid contributes to a champion device with the power conversion efficiency of 25.16% (certified 24.67%) and improved stability under operation or storage. This work demonstrates the advantages of po‐SAM layer in improving the performance of PSCs, offering ideas for SAM modification.
Tableting Engineering in Halide Gradient Perovskite: Energy Band Regulation and Design of Carrier Dynamics for THz Sensing
Authors: Li Junyu , Han Zeyao , Lu Xingyu , Li Xiaopeng , Liu Jiaxin , Zou Yousheng , Xu Xiaobao 
Published: June 2024

AbstractComponent regulation in perovskite single crystals (SCs) sets the precondition for designing energy band and carrier dynamics, which is essential for exploring functional optoelectronic devices. However, entropy‐driven ion diffusion in SCs leads to component homogenization in a few hours, while the gradient films exhibit long‐term gradient stability. Therefore, tableting engineering is proposed to introduce appropriate boundaries, ensuring good short‐range alignment within the grains and suppressed ion diffusion in the long range. With 6–10 MPa pressure, transverse/longitudinal gradient MAPbX3 (X = Cl, Br, I) tablets are constructed. Due to the alignment of the valence band maximum from MAPbCl3 to MAPbBr3 to MAPbI3, the hole extraction is significantly promoted. As well, different metal electrodes are utilized to regulate the main carrier types. Hole‐type Au/gradient tablet/Au devices show an obvious rectification effect, while electron‐type Ag/gradient tablet/Ag devices have near‐Ohmic contact. Compared to the electron‐type devices, Au/gradient tablet/Au devices show a 3.9‐fold improvement in terahertz responsivity to 3.51 µA W−1, a 2.6‐fold reduction in noise‐equivalent power to 2.22 × 10−8 W Hz−1/ 2; and a 2.6‐fold increase in specific detectivity to 1.89 × 107 Jones. This work demonstrates the tableting engineering to realize stable compositional gradients for energy band regulation in weak‐signal THz detection.
SOSTDC1 Nuclear Translocation Facilitates BTIC Maintenance and CHD1‐Mediated HR Repair to Promote Tumor Progression and Olaparib Resistance in TNBC
Authors: Deng Qiaodan , Qiang Jiankun , Liu Cuicui , Ding Jiajun , Tu Juchuanli , He Xueyan , Xia Jie , Peng Xilei , Li Siqin , Chen Xian , Ma Wei , Zhang Lu , Jiang Yi‐Zhou , Shao Zhi‐Ming , Chen Ceshi , Liu Suling , Xu Jiahui , Zhang Lixing 
Published: June 2024

AbstractBreast tumor‐initiating cells (BTICs) of triple‐negative breast cancer (TNBC) tissues actively repair DNA and are resistant to treatments including chemotherapy, radiotherapy, and targeted therapy. Herein, it is found that a previously reported secreted protein, sclerostin domain containing 1 (SOSTDC1), is abundantly expressed in BTICs of TNBC cells and positively correlated with a poor patient prognosis. SOSTDC1 knockdown impairs homologous recombination (HR) repair, BTIC maintenance, and sensitized bulk cells and BTICs to Olaparib. Mechanistically, following Olaparib treatment, SOSTDC1 translocates to the nucleus in an importin‐α dependent manner. Nuclear SOSTDC1 interacts with the N‐terminus of the nucleoprotein, chromatin helicase DNA‐binding factor (CHD1), to promote HR repair and BTIC maintenance. Furthermore, nuclear SOSTDC1 bound to β‐transducin repeat‐containing protein (β‐TrCP) binding motifs of CHD1 is found, thereby blocking the β‐TrCP‐CHD1 interaction and inhibiting β‐TrCP‐mediated CHD1 ubiquitination and degradation. Collectively, these findings identify a novel nuclear SOSTDC1 pathway in regulating HR repair and BTIC maintenance, providing insight into the TNBC therapeutic strategies.
Burst firing in Output‐Defined Parallel Habenula Circuit Underlies the Antidepressant Effects of Bright Light Treatment
Authors: Liu Xianwei , Li Han , Ma Ruijia , Tong Xiaohan , Wu Jijin , Huang Xiaodan , So Kwok‐Fai , Tao Qian , Huang Lu , Lin Song , Ren Chaoran 
Published: June 2024

AbstractResearch highlights the significance of increased bursting in lateral habenula (LHb) neurons in depression and as a focal point for bright light treatment (BLT). However, the precise spike patterns of LHb neurons projecting to different brain regions during depression, their roles in depression development, and BLT's therapeutic action remain elusive. Here, LHb neurons are found projecting to the dorsal raphe nucleus (DRN), ventral tegmental area (VTA), and median raphe nucleus (MnR) exhibit increased bursting following aversive stimuli exposure, correlating with distinct depressive symptoms. Enhanced bursting in DRN‐projecting LHb neurons is pivotal for anhedonia and anxiety, while concurrent bursting in LHb neurons projecting to the DRN, VTA, and MnR is essential for despair. Remarkably, reducing bursting in distinct LHb neuron subpopulations underlies the therapeutic effects of BLT on specific depressive behaviors. These findings provide valuable insights into the mechanisms of depression and the antidepressant action of BLT.
Identification and Characterization of Metastasis‐Initiating Cells in ESCC in a Multi‐Timepoint Pulmonary Metastasis Mouse Model
Authors: Wong Ching Ngar , Zhang Yu , Ru Beibei , Wang Songna , Zhou Hongyu , Lin Jiarun , Lyu Yingchen , Qin Yanru , Jiang Peng , Lee Victor Ho‐Fun , Guan Xin‐Yuan 
Published: June 2024

AbstractMetastasis is the biggest obstacle to esophageal squamous cell carcinoma (ESCC) treatment. Single‐cell RNA sequencing analyses are applied to investigate lung metastatic ESCC cells isolated from pulmonary metastasis mouse model at multiple timepoints to characterize early metastatic microenvironment. A small population of parental KYSE30 cell line (Cluster S) resembling metastasis‐initiating cells (MICs) is identified because they survive and colonize at lung metastatic sites. Differential expression profile comparisons between Cluster S and other subpopulations identified a panel of 7 metastasis‐initiating signature genes (MIS), including CD44 and TACSTD2, to represent MICs in ESCC. Functional studies demonstrated MICs (CD44high) exhibited significantly enhanced cell survival (resistances to oxidative stress and apoptosis), migration, invasion, stemness, and in vivo lung metastasis capabilities, while bioinformatics analyses revealed enhanced organ development, stress responses, and neuron development, potentially remodel early metastasis microenvironment. Meanwhile, early metastasizing cells demonstrate quasi‐epithelial‐mesenchymal phenotype to support both invasion and anchorage. Multiplex immunohistochemistry (mIHC) staining of 4 MISs (CD44, S100A14, RHOD, and TACSTD2) in ESCC clinical samples demonstrated differential MIS expression scores (dMISs) predict lymph node metastasis, overall survival, and risk of carcinothrombosis.