bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relationship between the efficacy of immunotherapy and characteristics of specific tumor mutation genes in non‐small cell lung cancer patients
Authors: Song Peng , Yang Dongliang , Wang Hanping , Cui Xiaoxia , Si Xiaoyan , Zhang Xiaotong , Zhang Li 
Published: April 2020

AbstractBackgroundImmune checkpoint inhibitors (ICIs) have greatly improved the prognosis and overall management of non‐small cell lung cancer (NSCLC) patients, but in the long term less than 20% of patients benefit from treatment with ICIs. Therefore, it is necessary to guide the choice of immunotherapy population through biomarkers in order to maximize the benefit for NSCLC patients. This article mainly explores the relationship between the efficacy of immunotherapy and specific tumor mutation gene characteristics in an NSCLC population.MethodsThis was a prospective analysis of patients with advanced NSCLC who visited the Department of Respiratory Medicine of Peking Union Medical College Hospital from March 2018 to June 2019 and were instructed to use PD‐1 inhibitors. The follow‐up deadline was 31 December 2019. The tumor pathological tissues were tested for tumor mutation genes, and the patients were evaluated for efficacy according to RECIST 1.1. The patients were divided into the durable benefit group (DCB) and the nonsustainable benefit group (NDB). DCB/NDB was used as the outcome variable. Various statistics methods were used to explore the independent predictors of long‐term benefits associated with immunotherapy and to draw a progression‐free survival curve for the relevant predictors.ResultsA total of 44 patients were examined for tumor mutation genes in pathological tissues; 20 in the DCB group and 24 in the NDB group. Specific gene mutations occurred in TP53 38.64%, KRAS 31.82%, EGFR 20.45%, BRCA 20.45%, ERBB (excluding EGFR) 18.18%, PTEN 15.91%, CDK4/6 13.64%, POLE 11.36%, MET 11.36%, PIK3CA 9.10%, FGFR 9.10%, BRAF 9.10%, JAK 9.10%, ALK 6.82%, POLD1 4.55%, BLM 4.55%. Chi‐square test results showed that there were statistically significant differences between DCB and NDB groups with eight mutations such as KRAS. Logistic regression showed that the KRAS mutation was statistically significant (P < 0.001). Two accuracy indicators, Random Forest Classification of Mean Decrease Gini and Mean Decrease Accuracy, evaluated the importance of the impact of different gene mutations on the outcome. Under two different measures, the variables were all KRAS mutations. It is suggested that the mutation of the KRAS gene is an independent predictor of the long‐term benefit of immunotherapy.ConclusionsThe mutation of KRAS gene in tumor tissues is an independent predictor of the long‐term benefit of immunotherapy, and the predictive ability is better.
Heteropaternal superfecundation frequently occurs in multiple‐bearing mob‐mated sheep
Authors: Berry D. P. , Bohan A. , O'Brien A. C. , Campion F. C. , McHugh N. , Wall E. 
Published: April 2020

SummaryHeteropaternal superfecundation may be defined as the fertilisation of two or more ova during the same oestrus cycle as a result of more than one coital act from different males; this results in foetuses being born in the same litter of the same age but different paternity. Heteropaternal superfecundation is more likely to occur in poly‐ovulatory species like sheep; moreover, female sheep are often mob‐mated with several rams concurrently, thus providing an opportunity for a given female to be served by multiple males during the same oestrus cycle. The objective of the present study was to determine the frequency of heteropaternal superfecundation in six sheep flocks where most of the ewes, lambs and rams were genotyped. A total of 685 multiple‐birth litters were available where the sire, dam and all lambs were genotyped. Of the 539 pairs of twins included in the analysis, 160 (i.e. 30%) were sired by two different rams. Of the 137 sets of triplets included in the analysis, 73 (i.e. 53%) were sired by more than one ram. Of the nine sets of quadruplets, eight were sired by two rams with the remaining litter being mono‐paternal. The overall incidence of heteropaternal superfecundation among litters was therefore 35%. Given that the incidence of multiple births in these flocks was 65%, heteropaternal superfecundation is expected to be relatively common in sheep; this is especially true as all but two of the litter‐mates were polyzygotic. Genotyping of progeny is one practical solution to identity such individuals.
Efficacy of quadruple treatment on different types of pre‐operative anaemia: secondary analysis of a randomised controlled trial
Authors: Rössler J. , Hegemann I. , Schoenrath F. , Seifert B. , Kaserer A. , Spahn G. H. , Falk V. , Spahn D. R. 
Published: April 2020

SummaryIn patients with pre‐operative anaemia undergoing cardiac surgery, combination treatment with intravenous iron, subcutaneous erythropoietin alpha, vitamin B12 and oral folic acid reduces allogeneic blood product transfusions. It is unclear if certain types of anaemia particularly benefit from this treatment. We performed a post‐hoc analysis of anaemic patients from a randomised trial on the ‘Effect of ultra‐short‐term treatment of patients with iron deficiency or anaemia undergoing cardiac surgery’. We used linear regression analyses to examine the efficacy of a combination anaemia treatment compared with placebo on the following deficiencies, each representing a part of the combination treatment: ferritin and transferrin saturation; endogenous erythropoietin; holotranscobalamine; and folic acid in erythrocytes. Efficacy was defined as change in reticulocyte count from baseline to the first, third and fifth postoperative days and represented erythropoietic activity in the immediate peri‐operative recovery phase. In all 253 anaemic patients, iron deficiency was the most common cause of anaemia. Treatment significantly increased reticulocyte count in all regression analyses on postoperative days 1, 3 and 5 (all p < 0.001). Baseline ferritin and endogenous erythropoietin were negatively associated with change in reticulocyte count on postoperative day 5, with an unstandardised regression coefficient B of −0.08 (95%CI −0.14 to −0.02) and −0.14 (95%CI −0.23 to −0.06), respectively. Quadruple anaemia treatment was effective regardless of the cause of anaemia and its effect manifested early in the peri‐operative recovery phase. The more pronounced a deficiency was, the stronger the subsequent boost to erythropoiesis may have been.
A non‐stationary bivariate INAR(1) process with a simple cross‐dependence: Estimation with some properties
Authors: Bakouch Hassan S. , Sunecher Y. , Mamode Khan N. , Jowaheer V. 
Published: April 2020

SummaryThis paper considers modelling of a non‐stationary bivariate integer‐valued autoregressive process of order 1 (BINAR(1)) where the cross‐dependence between the counting series is formed through the relationship of the current series with the previous‐lagged count series observations while the pair of innovations is independent and marginally Poisson. In addition, this paper proposes a generalised quasi‐likelihood (GQL) estimating equation based on the exact specification of the mean score and the auto‐covariance structure. The proposed approach is also compared with other popular techniques such as conditional maximum likelihood (CML), generalised least squares (GLS) and generalised method of moment (GMM) based on simulated data from the proposed BINAR(1). Moreover, the model is applied to weekly series of day and night road accidents arising in some regions of Mauritius and is compared with other existing BINAR(1) models.
nNOS‐CAPON blockers produce anxiolytic effects by promoting synaptogenesis in chronic stress‐induced animal models of anxiety
Authors: Zhu Li‐Juan , Shi Hu‐Jiang , Chang Lei , Zhang Cheng cheng , Si Meng , Li Na , Zhu Dong‐Ya 
Published: April 2020

Background and PurposeAnxiety disorder is a common mental health disorder. However, there are few safe and fast‐acting anxiolytic drugs available that can treat anxiety disorder. We previously demonstrated that the interaction of neuronal NOS (nNOS) with its carboxy‐terminal PDZ ligand (CAPON) is involved in regulating anxiety‐related behaviours. Here, we further investigated the anxiolytic effects of nNOS–CAPON disruptors in chronic stress‐induced anxiety in animals.Experimental ApproachMice were intravenously treated with nNOS–CAPON disruptors, ZLc‐002 or Tat‐CAPON12C, at the last week of chronic mild stress (CMS) exposure. We also infused corticosterone (CORT) into the hippocampus of mice to model anxiety behaviours and also delivered ZLc‐002 or Tat‐CAPON12C on the last week of chronic CORT treatment via pre‐implanted cannula. Anxiety‐related behaviours were examined using elevated plus maze, open field, novelty‐suppressed feeding and light–dark (LD) tests. The level of nNOS–CAPON interaction was determined by co‐immunoprecipitation (CO‐IP) and proximity ligation assay (PLA). The neural mechanisms underlying the behavioural effects of nNOS–CAPON uncoupling in anxiety animal models were assessed by western blot, immunofluorescence and Golgi‐Cox staining.Key ResultsZLc‐002 and Tat‐CAPON12C reversed CMS‐ or CORT‐induced anxiety‐related behaviours. ZLc‐002 and Tat‐CAPON12C increased synaptogenesis along with improved dendritic remodelling in CMS mice or CORT‐treated cultured neurons. Meanwhile, blocking nNOS–CAPON interaction significantly activated the cAMP response element‐binding protein (CREB)–brain‐derived neurotrophic factor (BDNF) pathway, which is associated with synaptic plasticity.Conclusion and ImplicationsCollectively, these results provide evidence for the anxiolytic effects of nNOS–CAPON uncouplers and their underlying mechanisms in anxiety disorders.
Extensional tectonics during the Tyrrhenian back‐arc basin formation and a new morpho‐tectonic map
Authors: Loreto Maria F. , Zitellini Nevio , Ranero César R. , Palmiotto Camilla , Prada Manel 
Published: April 2020

AbstractWe present a new tectonic map focused upon the extensional style accompanying the formation of the Tyrrhenian back‐arc basin. Our basin‐wide analysis synthetizes the interpretation of vintage multichannel and single‐channel seismic profiles, integrated with modern seismic images, P‐wave velocity models, and high‐resolution morpho‐bathymetric data. Four distinct evolutionary phases of the Tyrrhenian back‐arc basin opening are further constrained, redefining the initial opening to Langhian/Serravallian time. Listric and planar normal faults and their conjugates bound a series of horst and graben, half‐graben and triangular basins. Distribution of extensional faults, active throughout the basin since Middle Miocene, allows us to define an arrangement of faults in the northern/central Tyrrhenian mainly related to a pure shear which evolved to a simple shear opening. At depth, faults accommodate over a Ductile‐Brittle Transitional zone cut by a low‐angle detachment fault. In the southern Tyrrhenian, normal, inverse and transcurrent faults appear to be related to a large shear zone located along the continental margin of the northern Sicily. Extensional style variation throughout the back‐arc basin combined with wide‐angle seismic velocity models allows to explore the relationships between shallow deformation, faults distribution throughout the basin, and crustal‐scale processes as thinning and exhumation.
Caspase‐1 inhibition prevents neuronal death by targeting the canonical inflammasome pathway of pyroptosis in a murine model of cerebral ischemia
Authors: Li Jia , Hao Jia‐Huan , Yao Di , Li Rong , Li Xue‐Fei , Yu Zhi‐Yuan , Luo Xiang , Liu Xing‐Hua , Wang Ming‐Huan , Wang Wei 
Published: April 2020

AbstractAimsThe involvement of pyroptosis in ischemic stroke remains to be established. Therefore, we used the specific pyroptosis inhibitor Vx765 as an experimental intervention target in a murine model of stroke.MethodsA total of 564 C57BL/6 mice were subjected to photothrombotic procedures and treated via gavage with Vx765 at 1‐hour post‐ischemia. We subsequently assessed the expression of Gasdermin D (GSDMD), inflammasomes, caspase‐1, and interleukin‐1β (IL‐1β) using immunofluorescence (IF) and Western blot (WB) analyses. We also examined ultrastructural changes of cortical neurons with transmission electron microscopy (TEM) and measured infarct volumes dynamically by magnetic resonance imaging (MRI). Moreover, we evaluated the neurologic deficits by modified neurological severity scores, the rotarod test, and Treadscan.ResultsElevated expression of GSDMD and GSDMD p30, the pore‐forming subunit, was evident in the peri‐ischemic region on days one and three post‐ischemia. The neuronal plasma, nuclear, and mitochondrial membranes showed ultrastructural damage at day three post‐stroke. Elevated expression of inflammasomes, caspase‐1, and IL‐1β was also present on days one and three post‐injury. There were significant differences between Vx765‐treated and vehicle groups in mean infarct volumes (14.36 vs 21.52 mm3; 12.34 vs 18.56 mm3; 4.13 vs 10.06 mm3; P < .05 at day one, three, and seven post‐surgery, respectively). Mice treated with Vx765 showed better motor recovery as assessed by serial behavior tests and had better neuronal survival, which was attributable to pyroptosis inhibition, as illustrated by downregulated expression of the effector protein GSDMD, inflammasomes, caspase‐1, and IL‐1β. Besides, treatment with Vx765 preserved neuronal membrane structures after the ischemic injury.ConclusionsPyroptosis emerges as an important pathway for neuronal death in an acute ischemic stroke. Vx765, a low molecular weight drug that has proven safe in clinical epilepsy trials, has potential therapeutic value for cerebral ischemia by targeting the canonical inflammasome pathway of pyroptosis.
Ultrasound image resolution influences analysis of skeletal muscle composition
Authors: Paris Michael T. , Bell Kirsten E. , Avrutin Egor , Mourtzakis Marina 
Published: April 2020

AbstractIntroductionAnalysis of muscle composition using ultrasound requires standardization of several equipment settings (i.e. gain). However, the influence of image resolution, which is altered by imaging depth, on measures of muscle composition is unknown.MethodsWe analysed rectus femoris muscle composition using ultrasound images captured from 32 males and females (aged 28 ± 5 years) at depths of 9.0, 7.3, 5.9 and 4.7 cm. The transducer's orientation was fixed using a clamp during image acquisition to minimize movement. Across each image resolution, a region of interest encompassing the same anatomical area within the muscle was used for muscle composition analysis. Muscle composition was analysed using a combination of first‐, second‐ and higher‐order texture features. Muscle composition agreement across image resolutions was evaluated using a one‐way ANOVA and intraclass correlation coefficients (ICC).ResultsMost muscle composition features displayed differences due to image resolution (p < .05). ICCs demonstrated poor‐to‐good agreement across different image resolutions. In general, higher resolution images (i.e. shallower imaging depth) demonstrated better agreement (ICC > 0.90) compared to lower resolution images.ConclusionsUltrasound image resolution influences muscle composition analysis. Image resolution should be fixed within and between individuals when evaluating muscle composition using ultrasound.
Storage of an avulsed tooth prior to replantation: A systematic review and meta‐analysis
Authors: De Brier Niels , O Dorien , Borra Vere , Singletary Eunice M. , Zideman David A. , De Buck Emmy ,   the International Liaison Committee on Resuscitation First Aid Task Force
Published: April 2020

AbstractBackground/AimIt is crucial to store an avulsed tooth appropriately to preserve the viability of the periodontal ligament cells prior to replantation. The aim of this systematic review was to identify the best available evidence for the effectiveness of any technique available to laypeople for storing an avulsed tooth compared with storage in milk or saliva.MethodsThe following databases were searched (September 2019): Cochrane Library, MEDLINE, and Embase. Two reviewers independently considered trial eligibility, then extracted and analyzed data, and assessed the risk of bias. The certainty of the body of evidence was appraised according to the GRADE methodology.ResultsOut of 4118 references, 33 studies were included and reported 23 comparisons of which 10 were synthesized in a meta‐analysis. The limited evidence available favors storing an avulsed tooth in Hank's balanced salt solution (pooled SMD 2.47, 95% CI [1.59;3.34], P < .00001), propolis solution (pooled SMD 1.73, 95% CI [1.12;2.33], P < .00001), oral rehydration salts (pooled SMD 4.16, 95% CI [2.10;6.23], P < .0001), rice water, and cling film compared with storage in milk. The cell viability rate was significantly lower in teeth stored in saline solutions (pooled SMD −4.35, 95% CI [−7.55;−1.14], P = .008), tap water, buttermilk, castor oil, GC Tooth Mousse, and turmeric extract than those stored in milk. There is insufficient evidence to recommend for or against temporary storage of an avulsed tooth in saliva compared with alternative solutions. The certainty of evidence was considered low to very low due to limitations in study design, indirect study populations and outcome measures, and imprecision.ConclusionAlthough milk was shown to extend the periodontal ligament cell viability before replantation compared with saline or tap water, the following media have also demonstrated efficacy at preserving the cell viability: Hank's balanced salt solution, propolis, oral rehydration salts, rice water, and cling film.
Informed feature regularization in voxelwise modeling for naturalistic fMRI experiments
Authors: Yılmaz Özgür , Çelik Emin , Çukur Tolga 
Published: April 2020

AbstractVoxelwise modeling is a powerful framework to predict single‐voxel functional selectivity for the stimulus features that exist in complex natural stimuli. Yet, because VM disregards potential correlations across stimulus features or neighboring voxels, it may yield suboptimal sensitivity in measuring functional selectivity in the presence of high levels of measurement noise. Here, we introduce a novel voxelwise modeling approach that simultaneously utilizes stimulus correlations in model features and response correlations among voxel neighborhoods. The proposed method performs feature and spatial regularization while still generating single‐voxel response predictions. We demonstrated the performance of our approach on a functional magnetic resonance imaging dataset from a natural vision experiment. Compared to VM, the proposed method yields clear improvements in prediction performance, together with increased feature coherence and spatial coherence of voxelwise models. Overall, the proposed method can offer improved sensitivity in modeling of single voxels in naturalistic functional magnetic resonance imaging experiments.
No association between migraine frequency, white matter lesions and silent brain infarctions: a study in a series of women with chronic migraine
Authors: Meilán A. , Larrosa D. , Ramón C. , Cernuda‐Morollón E. , Martínez‐Camblor P. , Saiz A. , Santamarta E. , Pérez‐Pereda S. , Pascual J. 
Published: April 2020

Background and purposeIt has been suggested that silent infarctions (SIs) and hyperintense white matter lesions (WMLs) are related to migraine frequency. We studied their prevalence and anatomical distribution in patients with chronic migraine (CM).MethodsA total of 96 women with CM [mean age 43 (range 16–65) years] and 29 women with episodic migraine (EM) [mean age 36 (range 16–58) years] underwent 1.5‐T magnetic resonance imaging following the CAMERA protocol. The number, size and location of SIs and deep WMLs were recorded and a modified Fazekas scale was applied to assess periventricular WMLs.ResultsWhite matter lesions were found in 59 (61.5%) women with CM and 17 (58.6%) women with EM (odds ratio, 1.13; 95% confidence intervals, 0.48–2.62; P = 0.784). The majority (63% CM and 71% EM) were small deep WMLs. Exclusive periventricular WMLs were exceptional. Of the 739 WMLs seen in patients with CM, 734 (99.3%) were hemispheric and mostly frontal (81%). Posterior fossa WMLs were seen in only five (5.2%) women with CM (always in the pons) and two (6.9%) women with EM. Age >45 years was the only vascular risk factor associated with a higher WML number (median: 0 < 45 years and 3 > 45 years; P = 0.004). We found seven SIs in six women with CM (6.3%).ConclusionsAs compared with the expected prevalence at this age, this study confirms that the prevalence of WMLs, in most cases small, deep and frontal, was increased in CM and EM. However, our results do not support an association of WMLs or SIs with a higher frequency of attacks, but with the presence of vascular risk factors and mainly age >45 years.
Early data on long‐term efficacy and safety of inotersen in patients with hereditary transthyretin amyloidosis: a 2‐year update from the open‐label extension of the NEURO‐TTR trial
Authors: Brannagan T. H. , Wang A. K. , Coelho T. , Waddington Cruz M. , Polydefkis M. J. , Dyck P. J. , Plante‐Bordeneuve V. , Berk J. L. , Barroso F. , Merlini G. , Conceição I. , Hughes S. G. , Kwoh J. , Jung S. W. , Guthrie S. , Pollock M. , Benson M. D. , Gertz M. ,   for the NEURO‐TTR open‐label extension investigators
Published: April 2020

Background and purposeHereditary transthyretin (hATTR) amyloidosis causes progressive polyneuropathy resulting from transthyretin (TTR) amyloid deposition throughout the body, including the peripheral nerves. The efficacy and safety of inotersen, an antisense oligonucleotide inhibitor of TTR protein production, were demonstrated in the pivotal NEURO‐TTR study in patients with hATTR polyneuropathy. Here, the long‐term efficacy and safety of inotersen are assessed in an ongoing open‐label extension (OLE) study.MethodsPatients who completed NEURO‐TTR were eligible to enroll in the OLE (NCT02175004). Efficacy assessments included the modified Neuropathy Impairment Score plus seven neurophysiological tests composite score (mNIS + 7), the Norfolk Quality of Life – Diabetic Neuropathy (Norfolk QOL‐DN) questionnaire total score and the Short‐Form 36 Health Survey (SF‐36) Physical Component Summary (PCS) score. Safety and tolerability were also assessed.ResultsOverall, 97% (135/139) of patients who completed NEURO‐TTR enrolled in the OLE. Patients who received inotersen for 39 cumulative months in NEURO‐TTR and the OLE continued to show benefit; patients who switched from placebo to inotersen in the OLE demonstrated improvement or stabilization of neurological disease progression by mNIS + 7, Norfolk QOL‐DN and SF‐36 PCS. No new safety concerns were identified. There was no evidence of increased risk for grade 4 thrombocytopenia or severe renal events with increased duration of inotersen exposure.ConclusionInotersen slowed disease progression and reduced deterioration of quality of life in patients with hATTR polyneuropathy. Early treatment with inotersen resulted in greater long‐term disease stabilization than delayed initiation. Routine platelet and renal safety monitoring were effective; no new safety signals were observed.