bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overcoming resistance to STING agonist therapy to incite durable protective antitumor immunity
Authors: Lemos Henrique , Ou Rong , McCardle Caroline , Lin Yijun , Calver Jessica , Minett Jack , Chadli Ahmed , Huang Lei , Mellor Andrew L 
Published: August 2020

BackgroundActivating the Stimulator of Interferon Genes (STING) adaptor incites antitumor immunity against immunogenic tumors in mice, prompting clinical trials to test STING activators. However, STING signaling in the tumor microenvironment (TME) during development of Lewis lung carcinoma (LLC) suppresses antitumor immunity to promote tumor growth. We hypothesized that local immune balance favoring suppression of antitumor immunity also attenuates antitumor responses following STING activation. The purpose of this study was to evaluate how STING activation impacts antitumor responses in mice bearing LLC tumors.MethodsMice bearing established LLC tumors were treated with synthetic cyclic diadenyl monophosphate (CDA) to activate STING. Mice were monitored to assess LLC tumor growth, survival and protective antitumor immunity. Transcriptional and metabolic analyses were used to identify pathways responsive to CDA, and mice were co-treated with CDA and drugs that disrupt these pathways.ResultsCDA slowed LLC tumor growth but most CDA-treated mice (77%) succumbed to tumor growth. No evidence of tumor relapse was found in surviving CDA-treated mice at experimental end points but mice were not immune to LLC challenge. CDA induced rapid increase in immune regulatory pathways involving programmed death-1 (PD-1), indoleamine 2,3 dioxygenase (IDO) and cyclooxygenase-2 (COX2) in the TME. PD-1 blockade enhanced antitumor responses to CDA and increased mouse survival but mice did not eliminate primary tumor burdens. Two IDO inhibitor drugs had little or no beneficial effects on antitumor responses to CDA. A third IDO inhibitor drug synergized with CDA to enhance tumor control and survival but mice did not eliminate primary tumor burdens. In contrast, co-treatments with CDA and the COX2-selective inhibitor celecoxib controlled tumor growth, leading to uniform survival without relapse, and mice acquired resistance to LLC re-challenge and growth of distal tumors not exposed directly to CDA. Thus, mice co-treated with CDA and celecoxib acquired stable and systemic antitumor immunity.ConclusionsSTING activation incites potent antitumor responses and boosts local immune regulation to attenuate antitumor responses. Blocking STING-responsive regulatory pathways synergizes with CDA to enhance antitumor responses, particularly COX2 inhibition. Thus, therapy-induced resistance to STING may necessitate co-treatments to disrupt regulatory pathways responsive to STING in patients with cancer.
Exposure to additives or multigrain flour is associated with high risk of work-related allergic symptoms among bakers
Authors: Olivieri Mario , Murgia Nicola , Spiteri Gianluca , Biscardo Carlo Alberto , Marchetti Pierpaolo , Folletti Ilenia , Verlato Giuseppe 
Published: August 2020

ObjectivesWheat flour exposure in bakers can elicit respiratory and skin symptoms. Scarce data are available on the prevalence of such conditions in bakers. We investigated the prevalence of work-related rhinitis, asthma-like symptoms and dermatitis in bakers according to job task and type of allergens involved.MethodsOf the 229 traditional bakeries in Verona area who were invited to participate in a cross-sectional survey, 211 (92%) accepted; 727 employees in these bakeries answered a modified version of a questionnaire on job tasks; allergen exposure within the bakery; and work-related nasal, asthma-like and skin symptoms during 2010–2014. Determinants of work-related nasal, asthma-like or skin disorders were separately evaluated using different logistic models.ResultsThe prevalence of work-related nasal and asthma-like symptoms was, respectively, 15.1% and 4.2% in bakery shop assistants, increasing to 25.7% and 9.5% in bakers using only wheat flour, and further to 31.8% and 13.6% in bakers using flour and additives, and then to 34.1% and 18.2% in bakers using flour with additives and multigrain (p<0.001). The risk of work-related asthma-like symptoms was more than doubled in bakers using additives without or with multigrain than in shop assistants (OR 2.3, 95% CI 1.0 to 5.5 and OR 3.4, 95% CI 1.1 to 10.8, respectively). Making bread with additives alone or with multigrain significantly increased the risk of work-related nasal symptoms in shop assistants, while the risk of skin symptoms was not significantly affected.ConclusionsBakers using additives alone or with multigrain are at a high risk of experiencing nasal and asthma-like symptoms.
Short-term effects of outdoor air pollution on acute ischaemic stroke occurrence: a case-crossover study in Tianjin, China
Authors: Qi Xuemei , Wang Zhongyan , Guo Xiaokun , Xia Xiaoshuang , Xue Juanjuan , Jiang Guojing , Gu Yumeng , Han Suqin , Yao Qing , Cai Ziying , Wang Xiaojia , Wang Lin , Leng Sean X , Li Xin 
Published: August 2020

ObjectiveAmbient air pollution is associated with ischaemic stroke incidence. However, most of the previous studies used stroke-related hospital admission rather than stroke onset itself. This study aimed to evaluate the relationship between ambient air pollutant exposures and acute ischaemic stroke based on the timing of symptom onset.MethodsA time-stratified, case-crossover analysis was performed among 520 patients who had ischaemic stroke admitted to the Second Hospital of Tianjin Medical University (Tianjin, China) between 1 April 2018 and 31 March 2019 (365 days). Daily air pollutant concentrations of particulate matter with aerodynamic diameter 2.5 µm, particulate matter with aerodynamic diameter 10 µm (PM10), sulfur dioxide, nitrogen dioxide, carbon monoxide and ozone were obtained from fixed-site monitoring stations. We used conditional logistic regression to estimate OR and 95% CI corresponding to an increase in IQR of each air pollutant after adjusting for the effects of temperature and relative humidity.ResultsOverall, a higher risk of ischaemic stroke was found between April and September. During this period PM10 was associated with an increased risk of ischaemic stroke (1-day lag: OR=1.49, 95% CI 1.09 to 2.02; 3-day mean: OR=1.58, 95% CI 1.09 to 2.29) among patients between 34 and 70 years old. Positive associations were also observed between PM10 (1-day lag: OR=1.51, 95% CI 1.10 to 2.07; 3-day mean: OR=1.57, 95% CI 1.08 to 2.29), ozone (1-day lag: OR=1.83, 95% CI 1.16 to 2.87; 3-day mean: OR=1.90, 95% CI 1.06 to 3.42) and ischaemic stroke occurrence among those with hyperlipidaemia.ConclusionOur results suggest that air pollution is associated with a higher risk of ischaemic stroke in younger people or people with hyperlipidemia. These findings still need to be further investigated.
The impact of the COVID-19 pandemic on cardiology services
Authors: Fersia Omar , Bryant Sue , Nicholson Rachael , McMeeken Karen , Brown Carolyn , Donaldson Brenda , Jardine Aaron , Grierson Valerie , Whalen Vanessa , Mackay Alistair 
Published: August 2020

ObjectiveThe COVID-19 pandemic resulted in prioritisation of National Health Service (NHS) resources to cope with the surge in infected patients. However, there have been no studies in the UK looking at the effect of the COVID-19 work pattern on the provision of cardiology services. We aimed to assess the impact of the pandemic on cardiology services and clinical activity.MethodsWe analysed key performance indicators in cardiology services in a single centre in the UK in the periods prior to and during lockdown to assess reduction or changes in service provision.ResultsThere has been a greater than 50% drop in the number of patients presenting to cardiology and those diagnosed with myocardial infarction. All areas of cardiology service provision sustained significant reductions, which included outpatient clinics, investigations, procedures and cardiology community services such as heart failure and cardiac rehabilitation.ConclusionsAs ischaemic heart disease continues to be the leading cause of death nationally and globally, cardiology services need to prepare for a significant increase in workload in the recovery phase and develop new pathways to urgently help those adversely affected by the changes in service provision.
Energy resolution and linearity of XENON1T in the MeV energy range
Authors: Aprile E. , Aalbers J. , Agostini F. , Alfonsi M. , Althueser L. , Amaro F. D. , Antochi V. C. , Angelino E. , Angevaare J. , Arneodo F. , Barge D. , Baudis L. , Bauermeister B. , Bellagamba L. , Benabderrahmane M. L. , Berger T. , Breur P. A. , Brown A. , Brown E. , Bruenner S. , Bruno G. , Budnik R. , Capelli C. , Cardoso J. M. R. , Cichon D. , Cimmino B. , Clark M. , Coderre D. , Colijn A. P. , Conrad J. , Cussonneau J. P. , Decowski M. P. , Depoian A. , Di Gangi P. , Di Giovanni A. , Di Stefano R. , Diglio S. , Elykov A. , Eurin G. , Ferella A. D. , Fulgione W. , Gaemers P. , Gaior R. , Rosso A. Gallo , Galloway M. , Gao F. , Garbini M. , Grandi L. , Hasterok C. , Hils C. , Hiraide K. , Hoetzsch L. , Hogenbirk E. , Howlett J. , Iacovacci M. , Itow Y. , Joerg F. , Kato N. , Kazama S. , Kobayashi M. , Koltman G. , Kopec A. , Landsman H. , Lang R. F. , Levinson L. , Lin Q. , Lindemann S. , Lindner M. , Lombardi F. , Lopes J. A. M. , Fune E. López , Macolino C. , Mahlstedt J. , Manenti L. , Manfredini A. , Marignetti F. , Undagoitia T. Marrodán , Martens K. , Masbou J. , Masson D. , Mastroianni S. , Messina M. , Miuchi K. , Molinario A. , Morå K. , Moriyama S. , Mosbacher Y. , Murra M. , Naganoma J. , Ni K. , Oberlack U. , Odgers K. , Palacio J. , Pelssers B. , Peres R. , Pienaar J. , Pizzella V. , Plante G. , Qin J. , Qiu H. , García D. Ramírez , Reichard S. , Rocchetti A. , Rupp N. , dos Santos J. M. F. , Sartorelli G. , Šarčević N. , Scheibelhut M. , Schindler S. , Schreiner J. , Schulte D. , Schumann M. , Lavina L. Scotto , Selvi M. , Semeria F. , Shagin P. , Shockley E. , Silva M. , Simgen H. , Takeda A. , Therreau C. , Thers D. , Toschi F. , Trinchero G. , Tunnell C. , Vargas M. , Volta G. , Wack O. , Wang H. , Wei Y. , Weinheimer C. , Xu M. Weiss , Wenz D. , Wittweg C. , Wulf J. , Xu Z. , Yamashita M. , Ye J. , Zavattini G. , Zhang Y. , Zhu T. , Zopounidis J. P. 
Published: August 2020

AbstractXenon dual-phase time projection chambers designed to search for weakly interacting massive particles have so far shown a relative energy resolution which degrades with energy above $$\sim $$∼ 200 keV due to the saturation effects. This has limited their sensitivity in the search for rare events like the neutrinoless double-beta decay of $$^{136} \hbox {Xe}$$136Xe at its Q value, $$Q_{\beta \beta }\simeq 2.46\,\hbox {MeV}$$Qββ≃2.46MeV. For the XENON1T dual-phase time projection chamber, we demonstrate that the relative energy resolution at $$1\,\sigma /\mu $$1σ/μ is as low as ($$0.80 \pm 0.02$$0.80±0.02) % in its one-ton fiducial mass, and for single-site interactions at $$Q_{\beta \beta }$$Qββ. We also present a new signal correction method to rectify the saturation effects of the signal readout system, resulting in more accurate position reconstruction and indirectly improving the energy resolution. The very good result achieved in XENON1T opens up new windows for the xenon dual-phase dark matter detectors to simultaneously search for other rare events.
Dust content solutions for the Alcubierre warp drive spacetime
Authors: Santos-Pereira Osvaldo L. , Abreu Everton M. C. , Ribeiro Marcelo B. 
Published: August 2020

AbstractThe Alcubierre metric is a spacetime geometry where a massive particle inside a spacetime distortion, called warp bubble, is able to travel at velocities arbitrarily higher than the velocity of light, a feature known as the warp drive. This is a consequence of general relativity, which allows for global superluminal velocities but restricts local speeds to subluminal ones as required by special relativity. In this work we solved the Einstein equations for the Alcubierre warp drive spacetime geometry considering the dust matter distribution as source, since the Alcubierre metric was not originally advanced as a solution of the Einstein equations, but as a spacetime geometry proposed without a source gravity field. We found that all Einstein equations solutions of this geometry containing pressureless dust lead to vacuum solutions. We also concluded that these solutions connect the Alcubierre metric to the Burgers equation, which describes shock waves moving through an inviscid fluid. Our results also indicated that these shock waves behave as plane waves.
Static wormhole solutions and Noether symmetry in modified Gauss–Bonnet gravity
Authors: Sharif M. , Nawazish Iqra , Hussain Shahid 
Published: August 2020

AbstractIn this paper, we analyze static traversable wormholes via Noether symmetry technique in modified Gauss–Bonnet $$f(\mathcal {G})$$f(G) theory of gravity (where $$\mathcal {G}$$G represents Gauss–Bonnet term). We assume isotropic matter configuration and spherically symmetric metric. We construct three $$f(\mathcal {G})$$f(G) models, i.e, linear, quadratic and exponential forms and examine the consistency of these models. The traversable nature of wormhole solutions is discussed via null energy bound of the effective stress–energy tensor while physical behavior is studied through standard energy bounds of isotropic fluid. We also discuss the stability of these wormholes inside the wormhole throat and conclude the presence of traversable and physically stable wormholes for quadratic as well as exponential $$f(\mathcal {G})$$f(G) models.
Dairy Consumption and Risks of Colorectal Cancer Incidence and Mortality: A Meta-analysis of Prospective Cohort Studies
Authors: Jin Shaoyue , Kim Youngyo , Je Youjin 
Published: August 2020

AbstractBackground:Previous studies of dairy consumption and colorectal cancer incidence have shown inconsistent results, and there was no meta-analysis of association of dairy consumption with colorectal cancer mortality. Thus, we conducted a comprehensive analysis of prospective cohort studies to investigate these associations.Methods:PubMed and Web of Science databases were searched for eligible studies published up to July 2019, and a random effects model was used to estimate pooled RR.Results:We identified 31 prospective cohort studies, which included 24,964 and 2,302 cases for colorectal cancer incidence and mortality, respectively. The pooled RR of colorectal cancer incidence for the highest versus lowest categories of total dairy consumption was 0.79 [95% confidence interval (CI), 0.74–0.85]. For milk consumption, there was also a significant inverse association (RR, 0.81; 95% CI, 0.76–0.86). For cheese and fermented milk consumption, overall no association was found, but studies conducted in Europe showed a significant inverse association for cheese (RR, 0.87; 95% CI, 0.78–0.97) and fermented milk consumption (RR, 0.91; 95% CI, 0.85–0.98). For colorectal cancer mortality, we found 29% lower risk of death from colorectal cancer in subjects with high dairy consumption compared with those with low intakes of dairy products (RR, 0.71; 95% CI, 0.54–0.93), but each type of dairy consumption did not show a significant association.Conclusions:High dairy consumption was associated with lower colorectal cancer incidence and mortality.Impact:Our findings suggest that high dairy consumption may be associated with lower colorectal cancer incidence and mortality, but further studies are warranted.
The Gut Microbiome Is Associated with Clinical Response to Anti–PD-1/PD-L1 Immunotherapy in Gastrointestinal Cancer
Authors: Peng Zhi , Cheng Siyuan , Kou Yan , Wang Ziqi , Jin Rong , Hu Han , Zhang Xiaotian , Gong Ji-fang , Li Jian , Lu Ming , Wang Xicheng , Zhou Jun , Lu ZhiHao , Zhang Quan , Tzeng David T.W. , Bi Dongtao , Tan Yan , Shen Lin 
Published: August 2020

Abstract
We report on a comprehensive analysis of the gut microbiomes of patients with gastrointestinal (GI) cancer receiving anti–PD-1/PD-L1 treatment. The human gut microbiota has been associated with clinical responses to anti–PD-1/PD-L1 immunotherapy in melanoma, non–small cell lung cancer, and renal cell carcinoma. We aimed to investigate this association in GI cancers. We also identified bacterial taxa with patient stratification potential. We recruited 74 patients with advanced-stage GI cancer receiving anti–PD-1/PD-L1 treatment and collected their fecal samples prior to and during immunotherapy, along with clinical evaluations. Our 16S rRNA taxonomy survey on the fecal samples revealed an elevation of the Prevotella/Bacteroides ratio in patients, with a preferred response to anti–PD-1/PD-L1 treatment, and a particular subgroup of responders harboring a significantly higher abundance of Prevotella, Ruminococcaceae, and Lachnospiraceae. The shotgun metagenomes of the same samples showed that patients exhibiting different responses had differential abundance of pathways related to nucleoside and nucleotide biosynthesis, lipid biosynthesis, sugar metabolism, and fermentation to short-chain fatty acids (SCFA). Gut bacteria that were capable of SCFA production, including Eubacterium, Lactobacillus, and Streptococcus, were positively associated with anti–PD-1/PD-L1 response across different GI cancer types. We further demonstrated that the identified bacterial taxa were predictive of patient stratification in both our cohort and melanoma patients from two previously published studies. Our results thus highlight the impact of gut microbiomes on anti–PD-1/PD-L1 outcomes, at least in a subset of patients with GI cancer, and suggest the potential of the microbiome as a marker for immune-checkpoint blockade responses.
See articles by Tomita et al., p. 1236, and Hakozaki et al., p. 1243
Mendelian Randomization Analysis of Hemostatic Factors and Their Contribution to Peripheral Artery Disease—Brief Report
Authors: Small Aeron M. , Huffman Jennifer E. , Klarin Derek , Sabater-Lleal Maria , Lynch Julie A. , Assimes Themistocles L. , Sun Yan V. , Miller Donald , Freiberg Matthew S. , Morrison Alanna C. , Rader Daniel J. , Wilson Peter W.F. , Cho Kelly , Tsao Philip S. , Chang Kyong-Mi , Smith Nicholas L. , O’Donnell Christopher J. , de Vries Paul S. , Damrauer Scott M. ,   on behalf of the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Hemostasis Working Group and the VA Million Veteran Program
Published: August 2020

Background and Objective:
Peripheral artery disease (PAD) is the third most common form of atherosclerotic vascular disease and is characterized by significant functional disability and increased cardiovascular mortality. Recent genetic data support a role for a procoagulation protein variant, the factor V Leiden mutation, in PAD. The role of other hemostatic factors in PAD remains unknown. We evaluated the role of hemostatic factors in PAD using Mendelian randomization.

Approach and Results:

Two-sample Mendelian randomization to evaluate the roles of FVII (factor VII), FVIII (factor VIII), FXI (factor XI), VWF (von Willebrand factor), and fibrinogen in PAD was performed using summary statistics from GWAS for hemostatic factors performed within the Cohorts for Heart and Aging Research in the Genome Epidemiology Consortium and from GWAS performed for PAD within the Million Veteran Program. Genetically determined FVIII and VWF, but not FVII, FXI, or fibrinogen, were associated with PAD in Mendelian randomization experiments (FVIII: odds ratio, 1.41 [95% CI, 1.23–1.62],
P
=6.0×10
−7
, VWF: odds ratio, 1.28 [95% CI, 1.07–1.52],
P
=0.0073). In single variant sensitivity analysis, the
ABO
locus was the strongest genetic instrument for both FVIII and VWF.

Conclusions:
Our results suggest a role for hemostasis, and by extension, thrombosis in PAD. Further study is warranted to determine whether VWF and FVIII independently affect the biology of PAD.
Noninvasive Assessment of Cardiac Output: Accuracy and Precision of the Closed‐Circuit Acetylene Rebreathing Technique for Cardiac Output Measurement
Authors: Hardin E. Ashley , Stoller Douglas , Lawley Justin , Howden Erin J. , Hieda Michinari , Pawelczyk James , Jarvis Sara , Prisk Kim , Sarma Satyam , Levine Benjamin D. 
Published: August 2020

Background

Accurate assessment of cardiac output is critical to the diagnosis and management of various cardiac disease states; however, clinical standards of direct Fick and thermodilution are invasive. Noninvasive alternatives, such as closed‐circuit acetylene (C
2
H
2
) rebreathing, warrant validation.

Methods and Results

We analyzed 10 clinical studies and all available cardiopulmonary stress tests performed in our laboratory that included a rebreathing method and direct Fick or thermodilution. Studies included healthy individuals and patients with clinical disease. Simultaneous cardiac output measurements were obtained under normovolemic, hypovolemic, and hypervolemic conditions, along with submaximal and maximal exercise. A total of 3198 measurements in 519 patients were analyzed (mean age, 59 years; 48% women). The C
2
H
2
method was more precise than thermodilution in healthy individuals with half the typical error (TE; 0.34 L/min [
r
=0.92] and coefficient of variation, 7.2%) versus thermodilution (TE=0.67 [
r
=0.70] and coefficient of variation, 13.2%). In healthy individuals during supine rest and upright exercise, C
2
H
2
correlated well with thermodilution (supine:
r
=0.84, TE=1.02; exercise:
r
=0.82, TE=2.36). In patients with clinical disease during supine rest, C
2
H
2
correlated with thermodilution (
r
=0.85, TE=1.43). C
2
H
2
was similar to thermodilution and nitrous oxide (N
2
O) rebreathing technique compared with Fick in healthy adults (C
2
H
2
rest:
r
=0.85, TE=0.84; C
2
H
2
exercise:
r
=0.87, TE=2.39; thermodilution rest:
r
=0.72, TE=1.11; thermodilution exercise:
r
=0.73, TE=2.87; N
2
O rest:
r
=0.82, TE=0.94; N
2
O exercise:
r
=0.84, TE=2.18). The accuracy of the C
2
H
2
and N
2
O methods was excellent (
r
=0.99, TE=0.58).

Conclusions

The C
2
H
2
rebreathing method is more precise than, and as accurate as, the thermodilution method in a variety of patients, with accuracy similar to an N
2
O rebreathing method approved by the US Food and Drug Administration.