bluuebunny/crossref_metadata_2025_split huggingface dataset:
Safety and efficacy of restarting immune checkpoint inhibitors after clinically significant immune-related adverse events in metastatic renal cell carcinoma
Authors: Abou Alaiwi Sarah , Xie Wanling , Nassar Amin H , Dudani Shaan , Martini Dylan , Bakouny Ziad , Steinharter John A , Nuzzo Pier Vitale , Flippot Ronan , Martinez-Chanza Nieves , Wei Xiao , McGregor Bradley A , Kaymakcalan Marina D , Heng Daniel Y C , Bilen Mehmet A , Choueiri Toni K , Harshman Lauren C 
Published: February 2020

BackgroundImmune checkpoint inhibitors (ICI) induce a range of immune-related adverse events (irAEs) with various degrees of severity. While clinical experience with ICI retreatment following clinically significant irAEs is growing, the safety and efficacy are not yet well characterized.MethodsThis multicenter retrospective study identified patients with metastatic renal cell carcinoma treated with ICI who had >1 week therapy interruption for irAEs. Patients were classified into retreatment and discontinuation cohorts based on whether or not they resumed an ICI. Toxicity and clinical outcomes were assessed descriptively.ResultsOf 499 patients treated with ICIs, 80 developed irAEs warranting treatment interruption; 36 (45%) of whom were restarted on an ICI and 44 (55%) who permanently discontinued. Median time to initial irAE was similar between the retreatment and discontinuation cohorts (2.8 vs 2.7 months, p=0.59). The type and grade of irAEs were balanced across the cohorts; however, fewer retreatment patients required corticosteroids (55.6% vs 84.1%, p=0.007) and hospitalizations (33.3% vs 65.9%, p=0.007) for irAE management compared with discontinuation patients. Median treatment holiday before reinitiation was 0.9 months (0.2–31.6). After retreatment, 50% (n=18/36) experienced subsequent irAEs (12 new, 6 recurrent) with 7 (19%) grade 3 events and 13 drug interruptions. Median time to irAE recurrence after retreatment was 2.8 months (range: 0.3–13.8). Retreatment resulted in 6 (23.1%) additional responses in 26 patients whose disease had not previously responded. From first ICI initiation, median time to next therapy was 14.2 months (95% CI 8.2 to 18.9) and 9.0 months (5.3 to 25.8), and 2-year overall survival was 76% (95%CI 55% to 88%) and 66% (48% to 79%) in the retreatment and discontinuation groups, respectively.ConclusionsDespite a considerable rate of irAE recurrence with retreatment after a prior clinically significant irAE, most irAEs were low grade and controllable. Prospective studies are warranted to confirm that retreatment enhances survival outcomes that justify the safety risks.
Propensity score–weighted analysis of chemotherapy after PD-1 inhibitors versus chemotherapy alone in patients with non–small cell lung cancer (WJOG10217L)
Authors: Kato Ryoji , Hayashi Hidetoshi , Chiba Yasutaka , Miyawaki Eriko , Shimizu Junichi , Ozaki Tomohiro , Fujimoto Daichi , Toyozawa Ryo , Nakamura Atsushi , Kozuki Toshiyuki , Tanaka Kentaro , Teraoka Shunsuke , Usui Kazuhiro , Nishino Kazumi , Hataji Osamu , Ota Keiichi , Ebi Noriyuki , Saeki Sho , Akazawa Yuki , Okuno Motoyasu , Yamamoto Nobuyuki , Nakagawa Kazuhiko 
Published: February 2020

BackgroundStudies have suggested that chemotherapy after immune checkpoint inhibitors may confer an improved response for non–small cell lung cancer (NSCLC). However, potential selection bias in such studies has not been addressed. We therefore applied propensity score analysis to investigate the efficacy of chemotherapy after PD-1 inhibitor treatment (CAP) compared with chemotherapy alone.MethodsWe conducted a retrospective observational cohort study for patients treated at 47 institutions across Japan between April 1, 2014 and July 31, 2017. Eligible patients had advanced or recurrent NSCLC who have undergone chemotherapy. Patients subsequently treated with chemotherapy (docetaxel with or without ramucirumab, S-1 or pemetrexed) either after PD-1 inhibitor therapy (CAP cohort) or alone (control cohort) were included. The primary end point was objective response rate (ORR). Inverse probability weighting (IPW) was applied to adjust for potential confounding factors.ResultsA total of 1439 patients (243 and 1196 in the CAP and control cohorts, respectively) was available for unadjusted analysis. Several baseline characteristics—including age, histology,EGFRorALKgenetic alterations, and brain metastasis—differed significantly between the two cohorts. After adjustment for patient characteristics with the IPW method, ORR was 18.9% for the CAP cohort and 11.0% for the control cohort (ORR ratio 1.71; 95% CI 1.19 to 2.46; p=0.004). IPW-adjusted Kaplan-Meier curves showed that median progression-free survival (PFS) for the CAP and control cohorts was 2.8 and 2.7 months (IPW-adjusted HR 0.95; 95% CI 0.80 to 1.12; p=0.55), and median overall survival (OS) was 9.2 and 10.4 months (IPW-adjusted HR 1.05; 95% CI 0.86 to 1.28; p=0.63), respectively.ConclusionsAfter accounting for selection bias by propensity score analysis, CAP showed a significantly higher ORR compared with chemotherapy alone, with the primary end point of ORR being achieved. However, these results did not translate into a PFS or OS advantage, suggesting that prior administration of PD-1 inhibitors may result in a synergistic antitumor effect with subsequent chemotherapy, but that such an effect is transient. CAP therefore does not appear to achieve durable tumor control or confer a lasting survival benefit.
MicroRNA-4516-mediated regulation of MAPK10 relies on 3′ UTR cis-acting variants and contributes to the altered risk of Hirschsprung disease
Authors: Wang Yang , Jiang Qian , Chakravarti Aravinda , Cai Hao , Xu Ze , Wu Wenjie , Gu Beilin , Li Long , Cai Wei 
Published: February 2020

BackgroundHirschsprung disease (HSCR) is a life-threatening congenital disorder in which the enteric nervous system is completely missing from the distal gut. Recent studies have shown that miR-4516 markedly inhibits cell migration, and as one of its potential targets, MAPK10 functions as a modifier for developing HSCR. We thus aimed to evaluate the role of miR-4516 and MAPK10 in HSCR and how they contribute to the pathogenesis of HSCR.MethodsWe examined 13 genetic variants using the MassArray system in a case–control study (n=1015). We further investigated miR-4516-mediated regulation of MAPK10 in HSCR cases and human neural cells, the effects of cis-acting elements in MAPK10 on miR-4516-mediated modulation and cell migration process.ResultsThree positive 3′ UTR variants in MAPK10 were associated with altered HSCR susceptibility. We also showed that miR-4516 directly regulates MAPK10 expression, and this regulatory mechanism is significantly affected by the 3′ UTR cis-acting elements of MAPK10. In addition, knock-down of MAPK10 rescued the effect of miR-4516 on the migration of human neural cells.ConclusionOur findings indicate a key role of miR-4516 and its direct target MAPK10 in HSCR risk, and highlight the general importance of cis- and posttranscriptional modulation for HSCR pathogenesis.
Optical coherence tomography evaluation of vertebrobasilar artery stenosis: case series and literature review
Authors: Xu Xiaohui , Li Min , Liu Rui , Yin Qin , Shi Xuan , Wang Fang , Gao Jie , Xu Gelin , Ye Ruidong , Liu Xinfeng 
Published: February 2020

BackgroundIntracranial vertebrobasilar artery stenosis is an important cause of ischemic stroke. With its high resolution, intravascular optical coherence tomography (OCT) provides detailed assessment of vessel wall features. It is widely applied to identify high-risk plaque in the cardiovascular system, but its use in the intracranial artery has been limited.ObjectiveTo explore, in this pilot study, the usefulness of OCT in imaging of the intracranial artery wall.MethodsBetween November 2017 and July 2018, four patients with severe intracranial vertebrobasilar artery stenosis were enrolled for preintervention OCT evaluation of the lesion artery. Stenosis was present in the basilar artery in one case and in the intracranial vertebral artery in three cases.ResultsOCT images of the lesions showed various features of plaque vulnerability, such as intraluminal thrombus, lipid-rich plaque with plaque rupture, thin fibrous cap, macrophage accumulations, and a mixed lesion with dissecting aneurysm. In view of the OCT findings, all patients received balloon angioplasty and stent implantation.ConclusionsThese cases describe the successful implementation of OCT in intracranial vertebrobasilar artery stenosis. No side effects were seen during the OCT imaging. This technology may help in the diagnosis and treatment of cerebrovascular disease.
Spontaneous clearance ofChlamydia trachomatisaccounting for bacterial viability in vaginally or rectally infected women (FemCure)
Authors: Dukers-Muijrers Nicole H T M , Janssen Kevin J H , Hoebe Christian J P A , Götz Hannelore M , Schim van der Loeff Maarten F , de Vries Henry J C , Bruisten Sylvia M , Wolffs Petra F G 
Published: February 2020

ObjectivesSpontaneous clearance ofChlamydia trachomatis(CT) infections can occur between diagnosis and treatment. We followed CT patients to assess clearance using a conventional definition (no total CT-DNA, assessed by routine quantitative PCR methods) and a definition accounting for viability, assessed by viability PCR testing.MethodsThree outpatient STI clinics included CT-diagnosed women (The Netherlands, 2016–2017, FemCure study); participants had vaginal CT (vCT) and rectal CT (rCT) (group A: n=155), vCT and were rectally untested (group B: n=351), single vCT (group C: n=25) or single rCT (group D: n=29). Follow-up (median interval 9 days) vaginal and rectal samples underwent quantitative PCR testing (detecting total CT-DNA). When PCR positive, samples underwent V-PCR testing to detect ‘viable CT’ (CT-DNA from intact CT organisms; V-PCR positive). ‘Clearance’ was the proportion PCR-negative patients and ‘clearance of viable CT’ was the proportion of patients testing PCR negative or PCR positive but V-PCR negative. We used multivariable logistic regression analyses to assess diagnosis group (A–D), age, days since initial CT test (diagnosis) and study site (STI clinic) in relation to clearance and clearance of viable CT.ResultsClearance and clearance of viable CT at both anatomic sites were for (A) 0.6% and 3.9%; (B) 5.4% and 9.4%; (C) 32.0% and 52.0% and (D) 27.6% and 41.4%, respectively. In multivariate analyses, women with single infections (groups C and D) had higher likelihood of clearance than women concurrently infected with vCT and rCT (p<0.001).Of rectally untested women (group B), 76.9% had total CT-DNA and 46.7% had viable CT (V-PCR positive) at the rectal site.ConclusionsOf untreated female vCT patients who had CT also at the rectal site, or who were rectally untested, only a small proportion cleared CT (in fact many had viable CT) at their follow-up visit (median 9 days). Among single site infected women clearance was much higher.Trial registration numberNCT02694497.
Association between STI screening intensity in men who have sex with men and gonococcal susceptibility in 21 States in the USA: an ecological study
Authors: Van Dijck Christophe , Laumen Jolein , Zlotorzynska Maria , Manoharan-Basil Sheeba Santhini , Kenyon Chris 
Published: February 2020

ObjectivesAntimicrobial resistance is generally linked to antimicrobial selection pressure. Antimicrobial-resistantNeisseria gonorrhoeaeinfections frequently emerge in core groups. We hypothesised that these groups are more often exposed to antimicrobials as a consequence of the repeated treatment of both symptomatic and asymptomatic sexually transmitted infections (STIs) and that frequent STI screening in asymptomatic patients may contribute indirectly to antimicrobial exposure. In this study, we explored the ecological association between screening intensity in men who have sex with men and antimicrobial susceptibility inN. gonorrhoeaein the USA.MethodsData on STI screening intensity came from the American Men’s Internet Survey between October 2014 and March 2015. Data on gonococcal susceptibility to azithromycin, ceftriaxone and cefixime were used from the Gonococcal Isolate Surveillance Project in 2015. Spearman’s correlation was used to determine the association between these two variables.ResultsA positive ecological association was found between STI screening intensity and geometric mean gonococcal minimum inhibitory concentration for ceftriaxone (rho=0.42, p=0.031) and cefixime (rho=0.42, p=0.029), but not for azithromycin (rho=0.31, p=0.11). The above results must be interpreted with caution as many limitations apply.ConclusionsVariation in STI screening intensity may contribute to differences in gonococcal resistance between States in the USA.
Surveying bovine digital dermatitis and non‐healing bovine foot lesions for the presence of Fusobacterium necrophorum, Porphyromonas endodontalis and Treponema pallidum
Authors: Staton Gareth James , Sullivan Leigh Emma , Blowey Roger W , Carter Stuart D , Evans Nicholas James 
Published: February 2020

BackgroundNon‐healing bovine foot lesions, including non‐healing white line disease, non‐healing sole ulcer and toe necrosis, are an increasingly important cause of chronic lameness that are poorly responsive to treatment. Recent studies have demonstrated a high‐level association between these non‐healing lesions and the Treponema phylogroups implicated in bovine digital dermatitis (BDD). However, a polymicrobial aetiology involving other gram‐stain‐negative anaerobes is suspected.MethodsA PCR‐based bacteriological survey of uncomplicated BDD lesions (n=10) and non‐healing bovine foot lesions (n=10) targeting Fusobacterium necrophorum, Porphyromonas endodontalis, Dichelobacter nodosus and Treponema pallidum/T. paraluiscuniculi was performed.ResultsP. endodontalis DNA was detected in 80.0% of the non‐healing lesion biopsies (p=<0.001) but was entirely absent from uncomplicated BDD lesion biopsies. When compared to the BDD lesions, F. necrophorum was detected at a higher frequency in the non‐healing lesions (33.3% vs 70.0%, respectively), whereas D. nodosus was detected at a lower frequency (55.5% vs 20.0%, respectively). Conversely, T. pallidum/T. paraluiscuniculi DNA was not detected in either lesion type.ConclusionThe data from this pilot study suggest that P. endodontalis and F. necrophorum should be further investigated as potential aetiological agents of non‐healing bovine foot lesions. A failure to detect syphilis treponemes in either lesion type is reassuring given the potential public health implications such an infection would present.
Detecting Primordial Gravitational Waves: a forecast study on optimizing frequency distribution of next generation ground-based CMB telescope
Authors: Wu Deliang , Li Hong , Ni Shulei , Li Zheng-Wei , Liu Cong-Zhan 
Published: February 2020

AbstractProbing primordial gravitational waves is one of the core scientific objectives of the next generation CMB polarization experiment. Integrating more detector modules on the focal plane and performing high accurate observations are the main directions of the next generation CMB polarization telescope, like CMB S4. Also, multi-band observation is required by foreground analysis and reduction, as it is understood that foregrounds have become the main obstacles of CMB polarization measurements. However, ground observation is limited by the atmospheric window and can be usually carried out in one or two bands, like what BICEP or Keck array have done in the south pole. In this paper, we forecast the sensitivity of tensor-to-scalar ratio r that may be achieved by a multi-frequency CMB polarization experiment, basing on which to provide guidance for further expanding frequency bands and optimize the focal plane of a telescope. At the same time, the realization of having two frequency bands in one atmospheric window is discussed. With fixed number of detectors, the simulation results show that, in order to get a good limit, more frequency bands are needed. Better constraints can be obtained when it includes at least three bands, i.e., one CMB channel (95 GHz) + one dust channel (high frequency) and one synchrotron channel (low frequency). For example, 41 + 95 + 220 GHz, which is better than only focusing around the CMB band, like 85 + 105 + 150 GHz, and 95 + 135 + 155 GHz, and this frequency combination is even better than the combination of 41 + 95 + 150 + 220 GHz. As CMB S4 plans to consider two frequency bands in each atmospheric window, and along this way, we find that one CMB band and more bands in synchrotron and dust channels are helpful, for example, 2 bands in lower frequency, 30 + 41 GHz, 2 bands in higher frequency, 220 + 270 GHz, i.e. 30 + 41 + 95 + 220 + 270 GHz, can get better constraints, and in this case, more detectors are asked to be assigned in the CMB channel.
Entanglement dynamics for static two-level atoms in cosmic string spacetime
Authors: He Pingyang , Yu Hongwei , Hu Jiawei 
Published: February 2020

AbstractWe study the entanglement dynamics of two static atoms coupled with a bath of fluctuating scalar fields in vacuum in the cosmic string spacetime. Three different alignments of atoms, i.e. parallel, vertical, and symmetric alignments with respect to the cosmic string are considered. We focus on how entanglement degradation and generation are influenced by the cosmic string, and find that they are crucially dependent on the atom-string distance r, the interatomic separation L, and the parameter $$\nu $$ν that characterizes the nontrivial topology of the cosmic string. For two atoms initially in a maximally entangled state, the destroyed entanglement can be revived when the atoms are aligned vertically to the string, which cannot happen in the Minkowski spacetime. When the symmetrically aligned two-atom system is initially in the antisymmetric state, the lifetime of entanglement can be significantly enhanced as $$\nu $$ν increases. For two atoms which are initially in the excited state, when the interatomic separation is large compared to the transition wavelength, entanglement generation cannot happen in the Minkowski spacetime, while it can be achieved in the cosmic string spacetime when the position of the two atoms is appropriate with respect to the cosmic string and $$\nu $$ν is large enough.
Study on $$\Xi _{cc}\rightarrow \Xi _c$$ and $$\Xi _{cc}\rightarrow \Xi '_c$$ weak decays in the light-front quark model
Authors: Ke Hong-Wei , Lu Fang , Liu Xiao-Hai , Li Xue-Qian 
Published: February 2020

AbstractIn this work we study the weak decays of $$\Xi _{cc}\rightarrow \Xi _c$$Ξcc→Ξc and $$\Xi _{cc}\rightarrow \Xi '_c$$Ξcc→Ξc′ in the light-front quark model. Generally, a naive, but reasonable conjecture suggests that the cc subsystem in $$\Xi _{cc}$$Ξcc ( us pair in $$\Xi ^{(')}_c$$Ξc(′)) stands as a diquark with definite spin and color assignments. During the concerned processes, the diquark of the initial state is not a spectator, namely must be broken. A Racah transformation would decompose the original (cc)q into a combination of c(cq) components. Thus we may deal with the decaying c quark alone while keeping the (cq) subsystem as a spectator. With the re-arrangement of the inner structure we calculate the form factors numerically and then obtain the rates of semi-leptonic decays and non-leptonic decays, which will be measured in the future.
Indirect measurement of triple-Higgs coupling at an electron–positron collider with polarized beams
Authors: Rindani Saurabh D. , Singh Balbeer 
Published: February 2020

We examine the possibility of using single-Higgs production at an [Formula: see text] collider with polarized beams to measure, or constrain, indirectly a possible anomalous triple-Higgs coupling, which can contribute to the process via one-loop diagrams. In the dominant process [Formula: see text], longitudinally polarized beams can lead to an improvement in the cross-section by 50% for [Formula: see text] and [Formula: see text] polarizations of [Formula: see text] and [Formula: see text], respectively. This corresponds to an improvement in the sensitivity to the triple-Higgs coupling of about 18% for a center-of-mass energy of 250 GeV and an integrated luminosity of 2 ab[Formula: see text], making a strong case of beam polarization. This also implies that with polarized beams, the luminosity needed to get a particular sensitivity is less by about 33% as compared to that needed with unpolarized beams. Even when only the [Formula: see text] beam is polarized [Formula: see text], the improvement in the sensitivity is about 8%. We also study the effect of longitudinal beam polarization on the sensitivity to the triple-Higgs coupling of Higgs production through the subdominant process [Formula: see text] occurring through [Formula: see text] fusion.
Epidemiologic Risk Factors in a Comparison of a Barrett Esophagus Registry (BarrettNET) and a Case–Control Population in Germany
Authors: Schmidt Melissa , Ankerst Donna P. , Chen Yiyao , Wiethaler Maria , Slotta-Huspenina Julia , Becker Karl-Friedrich , Horstmann Julia , Kohlmayer Florian , Lehmann Andreas , Linkohr Birgit , Strauch Konstantin , Schmid Roland M. , Quante Anne S. , Quante Michael 
Published: February 2020

AbstractEndoscopic screening for Barrett's esophagus as the major precursor lesion for esophageal adenocarcinoma is mostly offered to patients with symptoms of gastroesophageal reflux disease (GERD). However, other epidemiologic risk factors might affect the development of Barrett's esophagus and esophageal adenocarcinoma. Therefore, efforts to improve the efficiency of screening to find the Barrett's esophagus population “at risk” compared with the normal population are needed. In a cross-sectional analysis, we compared 587 patients with Barrett's esophagus from the multicenter German BarrettNET registry to 1976 healthy subjects from the population-based German KORA cohort, with and without GERD symptoms. Data on demographic and lifestyle factors, including age, gender, smoking, alcohol consumption, body mass index, physical activity, and symptoms were collected in a standardized epidemiologic survey. Increased age, male gender, smoking, heavy alcohol consumption, low physical activity, low health status, and GERD symptoms were significantly associated with Barrett's esophagus. Surprisingly, among patients stratified for GERD symptoms, these associations did not change. Demographic, lifestyle, and clinical factors as well as GERD symptoms were associated with Barrett's esophagus development in Germany, suggesting that a combination of risk factors could be useful in developing individualized screening efforts for patients with Barrett's esophagus and GERD in Germany.
Breaking barriers: Iberian Lynx Lynx pardinus Temminck, 1827 (Mammalia: Carnivora: Felidae) colonizing Olive groves
Authors: Garrote Germán , Bueno José Francisco , Ruiz Manuel , De Lillo Santiago , Martin José Manuel , Moral Manuel , Simón Miguel Angel 
Published: February 2020

In recent years, the Andújar-Cardeña Iberian Lynx Lynx pardinus population has grown both in number and in occupied surface area. This feline has spread into areas surrounding existing population nuclei and occupied new habitats including human-dominated areas and tree crops. Here we describe this colonization process and the evolution of the Iberian Lynx populations in the Olive Olea europaea groves that surround typical Lynx scrub habitats in Andújar-Cardeña. Our findings were obtained through radio-tracking, camera trapping and European Rabbit Oryctolagus cuniculus monitoring. Two colonized areas—Zocueca and Marmolejo-Montoro—were identified in which Olive cultivation is predominant. Since 2011, a total of 45 and 50 different individuals have been detected in Zocueca and Marmolejo-Montoro, respectively. At present, 19 individuals are known to live in Zocueca and 29 in Marmolejo-Montoro. The main cause of mortality is road-kills. Our results suggest that the Iberian Lynx is capable of colonizing human-modified areas such as agricultural land provided that they can support high-density Rabbit populations and the causes of non-natural mortality are minimized.