bluuebunny/crossref_metadata_2025_split huggingface dataset:
High tumor mutational burden predicts favorable response to anti-PD-(L)1 therapy in patients with solid tumor: a real-world pan-tumor analysis
Authors: Jung Jaeyun , Heo You Jeong , Park Sehhoon 
Published: April 2023

BackgroundTumor mutation burden (TMB) is an important biomarker to predict response to anti-PD-L1 treatment across cancer types. TruSight Oncology 500 (TSO500) is currently used globally as a routine assay for TMB.MethodsBetween 2019 and 2021, 1744 patients with cancer received TSO500 assay as part of a real-world clinical practice at the Samsung Medical Center, and 426 received anti-PD-(L)1 treatment. Correlations between TMB and clinical outcomes of anti-PD-(L)1 were analyzed. Digital spatial profiling (DSP) was used to investigate the tumor immune environment’s influence on the treatment response to anti-PD-(L)1 in high TMB (TMB-H) patients (n=8).ResultsThe incidence of TMB-H (≥10 mutations (mt)/megabase (Mb)) was 14.7% (n=257). Among TMB-H patients, the most common cancer type was colorectal cancer (n=108, 42.0%), followed by gastric cancer (GC; n=49, 19.1%), bladder cancer (n=21, 8.2%), cholangiocarcinoma (n=21, 8.2%), non-small cell lung cancer (n=17, 6.6%), melanoma (n=8, 3.1%), gallbladder cancer (GBC; n=7, 2.7%), and others (n=26, 10.1%). The response rate to anti-PD-(L)1 therapy was substantially higher in GC (71.4% vs 25.8%), GBC (50.0% vs 12.5%), head and neck cancer (50.0% vs 11.1%), and melanoma (71.4% vs 50.7%) among TMB-H patients when compared with low TMB (TMB-L) (<10 mt/Mb) patients with statistical significance. Additional analysis of patients with TMB ≥16 mt/Mb demonstrated prolonged survival after anti-PD-(L)1 therapy compared with patients with TMB-L (not reached vs 418 days, p=0.03). The benefit of TMB ≥16 mt/Mb was greater when combined with microsatellite status and PD-L1 expression profiles. Among the TMB-H patients, those who responded to anti-PD-L1 therapy had numerous active immune cells that infiltrated the tumor regions during the DSP analysis. Natural killer cells (p=0.04), cytotoxic T cells (p<0.01), memory T cells (p<0.01), naïve memory T cells (p<0.01), and proteins related to T-cell proliferation (p<0.01) were observed in a responder group compared with a non-responder group. In contrast, exhausted T-cell and M2 macrophage counts were increased in the non-responder group.ConclusionsThe overall incidence of TMB status was analyzed by the TSO500 assay, and TMB-H was observed in 14.7% of the pan-cancer population. In a real-world setting, TMB-H identified by a target sequencing panel seemed to predict response to anti-PD-(L)1 therapy, especially in patients with a higher proportion of immune cells enriched in the tumor region.
Safety and efficacy of the tumor-selective adenovirus enadenotucirev, in combination with nivolumab, in patients with advanced/metastatic epithelial cancer: a phase I clinical trial (SPICE)
Authors: Fakih Marwan , Harb Wael , Mahadevan Daruka , Babiker Hani , Berlin Jordan , Lillie Tom , Krige David , Carter Jo , Cox Chris , Patel Minesh , Parfitt Lola , Powell Mark , Rosen Lee 
Published: April 2023

BackgroundNovel combination therapies to overcome anti-PD-1 resistance are required. Enadenotucirev, a tumor-selective blood stable adenoviral vector, has demonstrated a manageable safety profile and ability to increase tumor immune-cell infiltration in phase I studies in solid tumors.MethodsWe conducted a phase I multicenter study of intravenous enadenotucirev plus nivolumab in patients with advanced/metastatic epithelial cancer not responding to standard therapy. Co-primary objectives were safety/tolerability and maximum tolerated dose and/or maximum feasible dose (MTD/MFD) of enadenotucirev plus nivolumab. Additional endpoints included response rate, cytokine responses, and anti-tumor immune responses.ResultsOverall, 51 heavily pre-treated patients were treated, 45/51 (88%) of whom had colorectal cancer (35/35 patients with information available were microsatellite instability-low/microsatellite stable) and 6/51 (12%) had squamous cell carcinoma of the head and neck. The MTD/MFD of enadenotucirev plus nivolumab was not reached, with the highest dose level tested (1×1012 vp day 1; 6×1012 vp days 3 and 5) shown to be tolerable. Overall, 31/51 (61%) patients experienced a grade 3–4 treatment-emergent adverse event (TEAE), most frequently anemia (12%), infusion-related reaction (8%), hyponatremia (6%), and large intestinal obstruction (6%). Seven (14%) patients experienced serious TEAEs related to enadenotucirev; the only serious TEAE related to enadenotucirev occurring in >1 patient was infusion-related reaction (n=2). Among the 47 patients included in efficacy analyses, median progression-free survival was 1.6 months, objective response rate was 2% (one partial response for 10 months), and 45% of patients achieved stable disease. Median overall survival was 16.0 months; 69% of patients were alive at 12 months. Persistent increases in Th1 and related cytokines (IFNγ, IL-12p70, IL-17A) were seen from ~day 15 in two patients, one of whom had a partial response. Among the 14 patients with matching pre-tumor and post-tumor biopsies, 12 had an increase in intra-tumoral CD8+T-cell infiltration and 7 had increased markers of CD8 T-cell cytolytic activity.ConclusionsIntravenously dosed enadenotucirev plus nivolumab demonstrated manageable tolerability, an encouraging overall survival and induced immune cell infiltration and activation in patients with advanced/metastatic epithelial cancer. Studies of next-generation variants of enadenotucirev (T-SIGn vectors) designed to further re-program the tumor microenvironment by expressing immune-enhancer transgenes are ongoing.Trial registration numberNCT02636036.
Global, regional and national burdens of gout in the young population from 1990 to 2019: a population-based study
Authors: Zhang Jing , Jin Chenye , Ma Bing , Sun Hao , Chen Yanmei , Zhong Ying , Han Cheng , Liu Tingting , Li Yongze 
Published: April 2023

ObjectiveTo use data from the Global Burden of Disease (GBD) Study 2019 to report the global, regional and national rates and trends of annual incidence, point prevalence and years lived with disability (YLD) for gout in adolescents and young adults aged 15–39 years.MethodsWe conducted a serial cross-sectional study of gout burden in the young population aged 15–39 years using data from GBD Study 2019. We extracted rates per 100 000 population of incidence, prevalence and YLD of gout, then calculated their average annual percentage changes (AAPCs) at the global, regional and national level between 1990 and 2019 by sociodemographic index (SDI).ResultsThe global gout prevalent cases in individuals aged 15–39 years was 5.21 million in 2019, with the annual incidence substantially increasing from 38.71 to 45.94 per 100 000 population during 1990–2019 (AAPC 0.61, 95% CI 0.57 to 0.65). This substantial increase was observed in all SDI quintiles (low, low-middle, middle, high-middle and high) and every age subgroup (15–19, 20–24, 25–29, 30–34 and 35–39 years). Males accounted for 80% of the gout burden. High-income North America and East Asia were facing a substantial increase in gout incidence and YLD simultaneously. Elimination of high body mass index can reduce 31.74% of the gout YLD globally in 2019, which varied from 6.97% to 59.31% regionally and nationally.ConclusionGout incidence and YLD in the young population grew simultaneously and substantially in both developed and developing countries. Improving representative national-level data on gout, interventions for obesity and awareness in young populations are strongly suggested.
Development of the Canadian Food Intake Screener to assess alignment of adults’ dietary intake with the 2019 Canada's Food Guide healthy food choices recommendations
Authors: Hutchinson Joy M. , Williams Tabitha E. , Westaway Ailish M. , Bédard Alexandra , Pitre Camille , Lemieux Simone , Dodd Kevin W. , Lamarche Benoît , Guenther Patricia M. , Haines Jess , Wallace Angela , Martin Alicia , Louzada Maria Laura da Costa , Jessri Mahsa , Olstad Dana Lee , Prowse Rachel , Simpson Janis Randall , Vena Jennifer E. , Kirkpatrick Sharon I. 
Published: April 2023

The objective of this project was to develop a brief self-administered dietary screener, in English and French, to rapidly assess alignment of adults’ dietary intake with the 2019 Canada's Food Guide healthy food choices recommendations. In consultation with Health Canada and external advisors ( n = 15), guiding principles were defined. Existing screeners were scanned, and the healthy food choices recommendations were mapped to inform questions and response options. Cognitive interviews were conducted in English ( n = 17) and French ( n = 16) with adults aged 18–65 years from April to June 2021 to assess understanding of questions and face validity; recruitment emphasized variation in sociodemographic characteristics. Face and content validity were assessed with experts in nutrition, surveillance, and public health ( n = 13 English, 3 French) from April to May 2021. The testing indicated that the screener was well understood overall but informed refinements to improve comprehension of the questions and their alignment with the healthy food choices recommendations. The resulting Canadian Food Intake Screener/Questionnaire court canadien sur les apports alimentaires includes 16 questions to rapidly assess alignment of intake with the 2019 Canada's Food Guide healthy food choices recommendations, including healthy foods and foods to limit, in situations in which comprehensive dietary assessment is not feasible. Novelty The Canadian Food Intake Screener was developed to rapidly assess alignment of adults’ dietary intake over the past month with the Food Guide's healthy food choices recommendations. The screener was developed and evaluated through an iterative process that included three rounds of cognitive interviews in each of English and French, along with ongoing feedback from external advisors and face and content validity testing with a separate panel of content experts. The 16-question screener is intended for use with adults, aged 18–65 years, with marginal and higher health literacy in research and surveillance contexts in which comprehensive dietary assessment is not possible.
Complexity-free solution generated by gravitational decoupling for anisotropic self-gravitating star in symmetric teleparallel f(Q)-gravity theory
Authors: Maurya S. K. , Errehymy Abdelghani , Jasim M. K. , Daoud Mohammed , Al-Harbi Nuha , Abdel-Aty Abdel-Haleem 
Published: April 2023

AbstractIn this work, we attempt to find an anisotropic solution for a compact star generated by gravitational decoupling in f(Q)-gravity theory having a null complexity factor. To do this, we initially derive the complexity factor condition in f(Q) gravity theory using the definition given by Herrera (Phys Rev D 97:044010, 2018) and then derived a bridge equation between gravitational potentials by assuming complexity factor to be zero (Contreras and Stuchlik in Eur Phys J C 82:706, 2022). Next, we obtain two systems of equations using the complete geometric deformation (CGD) approach. The first system of equations is assumed to be an isotropic system in f(Q)-gravity whose isotropic condition is similar to GR while the second system is dependent on deformation functions. The solution of the first system is obtained by Buchdahl’s spacetime geometry while the governing equations for the second system are solved through the mimic constraint approach along with vanishing complexity condition. The novelty of our work is to generalize the perfect fluid solution into an anisotropic domain in f(Q)-gravity theory with zero complexity for the first time. We present the solution’s analysis to test its physical viability. We exhibit that the existence of pressure anisotropy due to gravitational within the self-gravitating bounded object plays a vital role to stabilize the f(Q) gravity system. In addition, we show that the constant involved in the solution controls the direction of energy flow between the perfect fluid and generic fluid matter distributions.
The One-Way Communication Complexity of Submodular Maximization with Applications to Streaming and Robustness
Authors: Feldman Moran , Norouzi-Fard Ashkan , Svensson Ola , Zenklusen Rico 
Published: April 2023

We consider the classical problem of maximizing a monotone submodular function subject to a cardinality constraint, which, due to its numerous applications, has recently been studied in various computational models. We consider a clean multiplayer model that lies between the offline and streaming model, and study it under the aspect of one-way communication complexity. Our model captures the streaming setting (by considering a large number of players), and, in addition, two-player approximation results for it translate into the robust setting. We present tight one-way communication complexity results for our model, which, due to the connections mentioned previously, have multiple implications in the data stream and robust setting.
Even for just two players, a prior information-theoretic hardness result implies that no approximation factor above 1/2 can be achieved in our model, if only queries to feasible sets (i.e., sets respecting the cardinality constraint) are allowed. We show that the possibility of querying infeasible sets can actually be exploited to beat this bound, by presenting a tight 2/3-approximation taking exponential time, and an efficient 0.514-approximation. To the best of our knowledge, this is the first example where querying a submodular function on infeasible sets leads to provably better results. Through the link to the (non-streaming) robust setting mentioned previously, both of these algorithms improve on the current state of the art for robust submodular maximization, showing that approximation factors beyond 1/2 are possible. Moreover, exploiting the link of our model to streaming, we settle the approximability for streaming algorithms by presenting a tight 1/2+ɛ hardness result, based on the construction of a new family of coverage functions. This improves on a prior 0.586 hardness and matches, up to an arbitrarily small margin, the best-known approximation algorithm.
De Diderot a Freud: o tear como metáfora e modelo
Authors: Delon Michel , Souza Maria das Graças de 
Published: April 2023

Diderot escreve, na Enciclopédia, um longo verbete, “Tear de meias”, no qual compara o tear a um raciocínio cuja conclusão seria o têxtil. Ele retoma esta comparação na Refutação de Helvétius: ali, é o próprio Leibniz que se torna uma máquina de reflexão, similar ao “tear de meias”. A opção materialista do homem máquina retoma uma tradição que assimila o texto ao tecido. Encontramos a mesma imagem no Fausto de Goethe, que é citado por Freud em A interpretação dos sonhos, e na novela de Henry James O motivo no tapete. A invenção é sempre cruzamento, tecelagem e mestiçagem, numa interação entre criação técnica e representação da atividade intelectual. O sistema de programação dos teares foi posteriormente adaptado às primeiras máquinas analíticas, ancestrais de nossos computadores atuais. A Enciclopédia teorizou esta interação, reabilitando os teares e concebendo o pensamento como um trabalho.
Consciência e reflexão no Ensaio de Locke
Authors: Freitas Vinícius França 
Published: April 2023

O artigo discute as noções de ‘consciência’ e ‘reflexão’ no Ensaio sobre o entendimento humano de John Locke. Apresentam-se dois critérios para se distinguir entre ambas as atividades mentais. Primeiramente, a consciência é uma atividade passiva, involuntária e não depende de atenção para ser exercida, diferentemente da reflexão, que, ao menos em um de seus graus – pois Locke concebe a existência de dois graus de reflexão –, é uma atividade ativa, voluntária e atenciosa da mente. Em segundo lugar, a consciência se distingue da reflexão na medida em que ela é uma atividade mental geradora de juízos / crenças, diferentemente da reflexão, cujas atividades apenas produzem ideias. Enquanto a consciência permite ao ser humano conhecer – julgar sobre e acreditar em suas atividades e estados mentais –, a reflexão é apenas uma capacidade mental de ter ideias e, enquanto tal, não é passível de ser verdadeira ou falsa.
Sensação inerte e sensação ativa em Diderot
Authors: Castro Clara 
Published: April 2023

Este artigo pretende estudar quatro princípios do movimento da matéria (força viva, força morta, força íntima da molécula e força vital) que aparecem no Sonho de d’Alembert (1769), nos Princípios filosóficos sobre a matéria e o movimento (1770) e nos Elementos de fisiologia (1782) de Diderot. Com tal estudo, gostaríamos de mostrar a possibilidade daquilo que chamamos de sensação inerte e de sensação ativa, com base num quinto princípio: a força neural. Nossa hipótese é que o raciocínio que fundamenta a teoria de Diderot sobre a sensibilidade universal da matéria desemboca nas ideias de sensação inerte e de sensação ativa.
Clastres contra Rousseau: a filosofia à luz da etnologia
Authors: Bandera Mauro Dela 
Published: April 2023

Leitor atento de Rousseau, embora raramente o citasse em seus textos, Clastres emprega o mesmo vocabulário que ganhou fama sob a pluma do cidadão de Genebra, tomando por vezes distância de suas reflexões: 1) alusão à vontade geral; 2) a encenação do gesto fundador da sociedade civil de cercar um terreno e o discurso possessivo que inaugura a propriedade privada e a acompanha (“isto é meu”); 3) e, por fim e mais importante, a crítica direcionada às duas frentes que compõem a narrativa de Rousseau sobre a origem do Estado: de um lado, a associação entre desejo de prestígio e vontade de poder; de outro, o fundamento econômico do poder político. Se é certo afirmar que a Arqueologia da violência é contra Hobbes ou uma inversão do argumento de Hobbes – pois aí Clastres politiza a guerra –, por sua vez, a Sociedade contra o Estado é em certa medida contra Rousseau ou, ainda, uma inversão do argumento de Rousseau, visto que se coloca contra a narrativa hipotética da história ocidental: não mais da economia e do prestígio para a política, mas da política para a economia, pois aí Clastres politiza a economia.
Flight from Urban Blight: Lead Poisoning, Crime, and Suburbanization
Authors: Curci Federico , Masera Federico 
Published: April 2023

Abstract
In this paper we study the effect of violent crime on residential and firms location decisions and their implications for segregation in cities. We do so by proposing a new instrument to exogenously predict violent crime in city centers. We base our instrument on chemical and medical evidence that links local characteristics of the soil to lead poisoning and aggression. We show that the increase in violent crime between 1960 and 1990 due to lead poisoning moved almost 8 million people to the suburbs. Firms followed by leaving the city centers. We then show that the suburbanization process was characterized by “white flight”.
Family Support during Hard Times: Dynamics of Intergenerational Exchange after Adverse Events
Authors: Schaller Jessamyn , Eck Chase 
Published: April 2023

Abstract
We use event studies to examine changes in intergenerational financial transfers and informal care within families following wealth loss, job exit, widowhood, and health shocks. We find sharp reductions in giving to adult children following negative shocks to parents' wealth and earned income, particularly in low-wealth households. Giving also decreases with some health shocks and increases following spousal death. Meanwhile, children of low-wealth households increase financial transfers to parents following adverse shocks in parental households and children of both high- and low-wealth households sharply increase their provision of informal care to parents following a wide range of adverse shocks.
Impact of ENSO on Wintertime Land Surface Variables in Northern Hemisphere Extratropics: Role of Atmospheric Moisture Processes
Authors: Sun Linyuan , Yang Xiu-Qun , Tao Lingfeng 
Published: April 2023

Abstract
El Niño–Southern Oscillation (ENSO) is the strongest interannual signature in the tropical air–sea system and can affect global atmospheric variables, but ENSO’s climatic impact on land surface variables such as skin temperature, snow cover, and soil moisture that can serve as seasonal climate predictors remains relatively little known. Here we examine ENSO’s impact on the three land surface variables in Northern Hemisphere extratropics by regression analysis, using a combination of ERA5 reanalysis, GLDAS, satellite-based observations, and CESM2 simulations. Our results show that during El Niño winters anomalous land surface warming occurs in Northern Hemisphere midlatitudes, accompanied by snow cover reduction, especially in northern North America and eastern Europe, while anomalous cooling occurs in southern North America and the Tibetan Plateau, accompanied by increased snow cover. Meanwhile, increased soil moisture is observed in southern North America, central Asia, and southeast China. Further analysis indicates that atmospheric moisture processes dominate the formation of the land surface anomalies, for which the changes in water vapor and precipitation induced by the ENSO-related large-scale atmospheric teleconnection are critical. The anomalous land surface warming in midlatitudes mainly results from the increased downward longwave radiation due to the increase of water vapor, whereas the physical pathway causing water vapor anomalies is different over North America and Eurasia. Controlled by ENSO-induced changes in atmospheric circulation and moisture transport, anomalous precipitation explains most of the snow cover and soil moisture anomalies, which play a certain role in shaping the skin temperature anomalies in some regions through snow–albedo feedback and evaporation, respectively.
Perceived stress, anxiety and depression : Living along the border in Jammu and Kashmir
Authors: Pandey Shreyashee , Saxena Sakshi , Joshi Pooran C , Mahajan Chakraverti 
Published: April 2023

Background: Conflicts adversely affect psychological well-being and are associated with mental disorders. Aim: The study aims to assess the levels of perceived stress, anxiety and depression and their association with demographic factors among the youth in the border villages of Jammu and Kashmir (J&K). Methods: A cross-sectional study was conducted among youth aged 18 to 25 years. The sample consisted of 300 individuals from the border villages of J&K. Of these, 150 individuals were from the villages located near the International Border (IB) in the Jammu district, and 150 individuals were from the villages near the Line Of Control (LOC) in the Rajouri district. Perceived Stress scale (PSS), Generalised Anxiety Disorder (GAD7), and Public Health Questionnaire (PHQ9) scales were used to determine the levels of perceived stress, depression, and anxiety. Mann Whitney, Chi-square and Odds ratio analysis were performed to assess the levels of the indicators and their association with demographic factors. Results: 94% of the respondents had perceived stress, 34.46% anxiety and 31% depression. Perceived stress, anxiety and depression were significantly higher among the LOC youth than IB youth ( p < .00*). The LOC youth with an educational status below graduation level were found to be more anxious ( p = .034) and more depressed ( p = .003) than those with the educational status of graduation and above. The youth whose main activity was that of a student were found to be more depressed than the employed and unemployed youth ( p = .000). Conclusion: Perceived stress, anxiety, and depression were prevalent among the youth in border villages. These were found to be significantly higher among youth in border villages on the LOC. The findings suggest that education level has a significant impact on the mental health of the youth.