bluuebunny/crossref_metadata_2025_split huggingface dataset:
SRC family kinase (SFK) inhibitor dasatinib improves the antitumor activity of anti-PD-1 in NSCLC models by inhibiting Treg cell conversion and proliferation
Authors: Redin Esther , Garmendia Irati , Lozano Teresa , Serrano Diego , Senent Yaiza , Redrado Miriam , Villalba Maria , De Andrea Carlos E , Exposito Francisco , Ajona Daniel , Ortiz-Espinosa Sergio , Remirez Ana , Bertolo Cristina , Sainz Cristina , Garcia-Pedrero Juana , Pio Ruben , Lasarte Juan , Agorreta Jackeline , Montuenga Luis M , Calvo Alfonso 
Published: March 2021

IntroductionThe use of immune-checkpoint inhibitors has drastically improved the management of patients with non-small cell lung cancer (NSCLC), but innate and acquired resistances are hurdles needed to be solved. Immunomodulatory drugs that can reinvigorate the immune cytotoxic activity, in combination with antiprogrammed cell death 1 (PD-1) antibody, are a great promise to overcome resistance. We evaluated the impact of the SRC family kinases (SFKs) on NSCLC prognosis, and the immunomodulatory effect of the SFK inhibitor dasatinib, in combination with anti-PD-1, in clinically relevant mouse models of NSCLC.MethodsA cohort of patients from University Clinic of Navarra (n=116) was used to study immune infiltrates by multiplex immunofluorescence (mIF) and YES1 protein expression in tumor samples. Publicly available resources (TCGA, Km Plotter, and CIBERSORT) were used to study patient’s survival based on expression of SFKs and tumor infiltrates. Syngeneic NSCLC mouse models 393P and UNSCC680AJ were used for in vivo drug testing.ResultsAmong the SFK members, YES1 expression showed the highest association with poor prognosis. Patients with high YES1 tumor levels also showed high infiltration of CD4+/FOXP3+ cells (regulatory T cells (Tregs)), suggesting an immunosuppressive phenotype. After testing for YES1 expression in a panel of murine cell lines, 393P and UNSCC680AJ were selected for in vivo studies. In the 393P model, dasatinib+anti-PD-1 treatment resulted in synergistic activity, with 87% tumor regressions and development of immunological memory that impeded tumor growth when mice were rechallenged. In vivo depletion experiments further showed that CD8+ and CD4+ cells are necessary for the therapeutic effect of the combination. The antitumor activity was accompanied by a very significant decrease in the number of Tregs, which was validated by mIF in tumor sections. In the UNSCC680AJ model, the antitumor effects of dasatinib+anti-PD-1 were milder but similar to the 393P model. In in vitro assays, we demonstrated that dasatinib blocks proliferation and transforming growth factor beta-driven conversion of effector CD4+ cells into Tregs through targeting of phospholymphocyte-specific protein tyrosine kinase and downstream effectors pSTAT5 and pSMAD3.ConclusionsYES1 protein expression is associated with increased numbers of Tregs in patients with NSCLC. Dasatinib synergizes with anti-PD-1 to impair tumor growth in NSCLC experimental models. This study provides the preclinical rationale for the combined use of dasatinib and PD-1/programmed death-ligand 1 blockade to improve outcomes of patients with NSCLC.
Molecular correlates of response to nivolumab at baseline and on treatment in patients with RCC
Authors: Ross-Macdonald Petra , Walsh Alice M , Chasalow Scott D , Ammar Ron , Papillon-Cavanagh Simon , Szabo Peter M , Choueiri Toni K , Sznol Mario , Wind-Rotolo Megan 
Published: March 2021

BackgroundNivolumab is an immune checkpoint inhibitor targeting the programmed death-1 receptor that improves survival in a subset of patients with clear cell renal cell carcinoma (ccRCC). In contrast to other tumor types that respond to immunotherapy, factors such as programmed death ligand-1 (PD-L1) status and tumor mutational burden show limited predictive utility in ccRCC. To address this gap, we report here the first molecular characterization of nivolumab response using paired index lesions, before and during treatment of metastatic ccRCC.MethodsWe analyzed gene expression and T-cell receptor (TCR) clonality using lesion-paired biopsies provided in the CheckMate 009 trial and integrated the results with their PD-L1/CD4/CD8 status, genomic mutation status and serum cytokine assays. Statistical tests included linear mixed models, logistic regression models, Fisher’s exact test, and Kruskal-Wallis rank-sum test.ResultsWe identified transcripts related to response, both at baseline and on therapy, including several that are amenable to peripheral bioassays or to therapeutic intervention. At both timepoints, response was positively associated with T-cell infiltration but not associated with TCR clonality, and some non-Responders were highly infiltrated. Lower baseline T-cell infiltration correlated with elevated transcription of Wnt/β-catenin signaling components and hypoxia-regulated genes, including the Treg chemoattractant CCL28. On treatment, analysis of the non-responding patients whose tumors were highly T-cell infiltrated suggests association of the RIG-I-MDA5 pathway in their nivolumab resistance. We also analyzed our data using previous transcriptional classifications of ccRCC and found they concordantly identified a molecular subtype that has enhanced nivolumab response but is sunitinib-resistant.ConclusionOur study describes molecular characteristics of response and resistance to nivolumab in patients with metastatic ccRCC, potentially impacting patient selection and first-line treatment decisions.Trial registration numberNCT01358721.
Effects of synthesizing time and Eu2+ concentration on photoluminescence properties of Ca2−xEuxMgSi2O7 phosphors
Authors: Fan Yu , Chen Chin-Ta , Wang Yen-Tsu , Yang Cheng-Fu 
Published: March 2021

Phosphors with the compositions of [Formula: see text] ([Formula: see text], 0.015, 0.025, 0.035, and 0.045) are synthesized in a reduction atmosphere (5% H2 + 95% N2) using a solid-state reaction method. At first, the [Formula: see text] powder is synthesized at 1350[Formula: see text]C with a duration of [Formula: see text] h to find the optimum synthesizing time. SEM images show that the particle sizes increase with synthesizing time and as the synthesizing time is more than 4 h, the abnormal particles appear and the intensities at the emission peaks of photoluminescence excitation (PLE) and photoluminescence emission (PL) spectra decrease. Next, 1350[Formula: see text]C and 4 h are used as synthesized parameters, which are used to find the concentration quench effect of [Formula: see text] phosphors. As the concentration of [Formula: see text] ions of [Formula: see text] phosphors increases, the intensities at the emission peaks of PLE and PL spectra first increase and reach the maximum values at [Formula: see text], and then they decrease as the concentration of [Formula: see text] ions further increases. These results prove that the synthesizing time and concentration of [Formula: see text] ions are two important factors to affect the photoluminescence properties of [Formula: see text] phosphors.
Development of the Elective Outpatient Percutaneous Coronary Intervention Episode–Based Cost Measure
Authors: Sandhu Alexander T. , Do Rose , Lam Joyce , Blankenship James , Van Decker William , Rich Jeffrey , Gonzalez Oscar , Wu Xiaolu , Pershing Suzann , Lin Eugene , MaCurdy Thomas E. , Bhattacharya Jay , Nagavarapu Sriniketh ,   on behalf of the Elective Outpatient PCI Cost Measure Writing Group
Published: March 2021

Background:
The Merit-Based Incentive Payment System adjusts clinician payments based on a performance score that includes cost measures. With the Centers for Medicare & Medicaid Services, we developed a novel cost measure that compared interventional cardiologists on a targeted set of costs related to elective percutaneous coronary intervention (PCI). We describe the measure and compare it to a hypothetical version including all expenditures post-PCI.

Methods:
Measure development was guided by 39 clinician experts. They identified services within 30 days of PCI that could be potentially affected by the interventional cardiologist. Expenditures for these PCI-related services were included as measure costs in a process termed service assignment. We used 1 year of Medicare claims to calculate clinician scores using the final measure that included only PCI-related costs (with service assignment) and a hypothetical version that included all costs post-PCI (without service assignment). We calculated reliability for both measures. This marker of precision breaks measure variance into signal (difference between clinicians) versus noise (difference between PCI episodes for a clinician). We also determined the change in clinician performance quintile between measures.

Results:
We identified 100 992 elective outpatient PCI episodes from May 2, 2016, to May 1, 2017. Total Medicare expenditures within 30 days of PCI averaged $13 234. After excluding costs unrelated to PCI, average cost was $10 966. For individual clinicians, mean reliability for the hypothetical measure without service assignment was 0.36. After service assignment, final measure reliability increased to 0.53. When evaluated as clinician groups, reliability increased from 0.43 to 0.73 following service assignment. Approximately 66% (2340 of 3527) of clinicians were reclassified into a different performance quintile after excluding unrelated costs.

Conclusions:
The elective outpatient PCI cost measure had increased precision and reclassified clinician performance relative to a hypothetical version that included total expenditures.
Neural Decoding Reveals Concurrent Phonemic and Subphonemic Representations of Speech Across Tasks
Authors: Beach Sara D. , Ozernov-Palchik Ola , May Sidney C. , Centanni Tracy M. , Gabrieli John D. E. , Pantazis Dimitrios 
Published: March 2021

Abstract
Robust and efficient speech perception relies on the interpretation of acoustically variable phoneme realizations, yet prior neuroimaging studies are inconclusive regarding the degree to which subphonemic detail is maintained over time as categorical representations arise. It is also unknown whether this depends on the demands of the listening task. We addressed these questions by using neural decoding to quantify the (dis)similarity of brain response patterns evoked during two different tasks. We recorded magnetoencephalography (MEG) as adult participants heard isolated, randomized tokens from a /ba/-/da/ speech continuum. In the passive task, their attention was diverted. In the active task, they categorized each token as ba or da. We found that linear classifiers successfully decoded ba vs. da perception from the MEG data. Data from the left hemisphere were sufficient to decode the percept early in the trial, while the right hemisphere was necessary but not sufficient for decoding at later time points. We also decoded stimulus representations and found that they were maintained longer in the active task than in the passive task; however, these representations did not pattern more like discrete phonemes when an active categorical response was required. Instead, in both tasks, early phonemic patterns gave way to a representation of stimulus ambiguity that coincided in time with reliable percept decoding. Our results suggest that the categorization process does not require the loss of subphonemic detail, and that the neural representation of isolated speech sounds includes concurrent phonemic and subphonemic information.
Revision of Myceporthus Skelley & Powell, 2018 (Coleoptera: Erotylidae: Erotylinae: Tritomini)
Authors: Powell Gareth S. , Skelley Paul E. 
Published: March 2021

Abstract
Myceporthus Skelley & Powell, 2018 (Coleoptera: Erotylidae: Tritomini) is revised. Species currently in the genus, M. pauperculus (Lacordaire, 1842) and M. vernix (Casey, 1916), are reviewed. Five new species are described: M. careorufus sp. nov., M. melinatrum sp. nov., M. rubeus sp. nov., M. rubicundus sp. nov., and M. rufus sp. nov., with a dichotomous key to members of the genus also provided.
From order to approval
Authors: Shefer Hagit 
Published: March 2021

Abstract
The article discusses the development of the Hebrew polysemous construction bɛsɛdɛr (the prefixed preposition bɛ ‘in’ + the noun sɛdɛr ‘order’). An analysis within the framework of Construction Grammar (Traugott & Trousdale, 2013) as well as tendencies of (inter)subjectification (Traugott, 2010, 2012) suggest that the construction developed through fusion and host-class expansion from an objective meaning of concrete and abstract order into an adverb, and later into a fully substantive lexical construction conveying subjective positive evaluation and to an intersubjectified discourse function expressing agreement and approval. The article further supports the proposal that both processes of grammatical and lexical constructionalization are evident in the constructionalization of beseder. Moreover, the analysis suggests that the different meanings which developed are interrelated, as they all derive from the original concept of order and organization, which at some point began to be desirable and appreciated, leading eventually to the development of discourse functions of approval and consent.
Detection and Tracking of Tropical Convective Storms Based on Globally Gridded Precipitation Measurements: Algorithm and Survey over the Tropics
Authors: Takahashi Hanii , Lebsock Matthew , Luo Zhengzhao Johnny , Masunaga Hirohiko , Wang Cindy 
Published: March 2021

AbstractThis paper is the first attempt to document a simple convection-tracking method based on the IMERG precipitation product to generate an IMERG-based Convection Tracking (IMERG-CT) dataset. Up to now, precipitation datasets have been Eulerian accumulations. Now with IMERG-CT, we can estimate total rainfall based on Lagrangian accumulations, which is a very important step in diagnosing cloud-precipitation process following the evolution of air masses. Convection-tracking algorithms have traditionally been developed on the basis of brightness temperature (Tb) from satellite infrared (IR) retrievals. However, vigorous rainfall can be produced by warm-topped systems in a moist environment; this situation cannot be captured by traditional IR-based tracking but is observed in IMERG-CT. Therefore, an advantage of IMERG-CT is its ability to include the previously missing information of shallow clouds that grow into convective storms, which provides us more-complete life cycle records of convective storms than traditional IR-based tracking does. This study also demonstrates the utility of IMERG-CT through investigating various properties of convective systems in terms of the evolution before and after peak precipitation rate and amount. For example, composite analysis reveals a link between evolution of precipitation and convective development: the signature of stratiform anvils remaining after the storm has produced the maximum rainfall, as average Tb stays almost constant for 5 h after the peak of precipitation. Our study highlights the importance of joint analysis of cloud and precipitation data in time sequence, which helps to elucidate the underlying dynamic processes producing tropical rainfall and its resultant effects on the atmospheric thermodynamics.
Thoracic duct injury after decortication of lung, new technique to repair thoracic duct in this challenging situation: A case report
Authors: Kapadia Nandkishore , Jenasamant Saumya Sekhar , Rawat Ganesh Sohan Singh , Kamkhedkar Shailesh , Shah Pratik , Kapadia Parnal 
Published: March 2021

Background Chylothorax is a rare form of pleural effusion that can be associated with both traumatic and non-traumatic causes. Very few patients respond to conservative line of therapy. Thoracic duct ligation is often the treatment of choice in post-surgical patients; however, the optimal treatment of this disease process after traumatic injury remains unclear. Case presentation: We present the case of a 46-year-old woman with thoracic duct injury secondary to decortication for post-pneumonic empyema. Conservative therapy and pleurodesis done twice failed. She developed severe cachexia losing 15 kg in 30 days. She was referred to our center for ligation of thoracic duct. Preoperative lymphangiography located the duct injury in upper part of mediastinum. Computerized tomography scan of chest showed collapse of left lower lobe and thickened left pleura, indicating a significant pericardial effusion. She underwent decortication of left lung, pericardial window, and native pericardial patch repair of thoracic duct. Results and Conclusions: In this unusual and complex case, successful resolution of the chyle leak was achieved with new surgical technique of patch repair. The patient recovered well and was now on a normal diet. She has put on 12 kg in four months. We have avoided late complications of thoracic duct ligation by this technique. This nouvelle technique may be recommended as it is simple and effective. Ligation of thoracic duct carries late complications. Isolating right lung by double lumen tube may cause severe hypoxia as left-sided lung is not expanded as in this case.
Extracorporeal membrane oxygenation outcomes in children with Williams syndrome: a review of the ELSO registry
Authors: Martin Amarilis , Rycus Peter T , Farooqi Ahmad , Dentel John , Cashen Katherine 
Published: March 2021

Introduction: Williams syndrome (WS) results from a microdeletion that usually involves the elastin gene, leading to generalized arteriopathy. Cardiovascular anomalies are seen in 80% of WS patients, including supravalvular aortic stenosis (SVAS), pulmonary artery stenosis (PAS), and pulmonary stenosis (PS). Sudden death associated with procedural sedation and in the perioperative period in WS children have been reported. This study aims to describe extracorporeal membrane oxygenation (ECMO) use in WS children, identify risk factors for hospital mortality of WS patients, and compare outcomes between WS children and non-WS children with SVAS, PAS, and PS. Methods: Children 0–18 years-old in the Extracorporeal Life Support Organization (ELSO) Registry with a primary or secondary diagnosis of WS, SVAS, PAS, or PAS were included. Results: Included were 50 WS children and 1222 non-WS children with similar cardiac diagnoses. ECMO use increased over time in both groups (p = 0.93), with most cases occurring in the current era. WS children were younger (p = 0.004), weighed less (p = 0.048), had a pulmonary indication for ECMO (50% vs 10%, p < 0.001), and were placed more on high frequency ventilation (p < 0.001) than non-WS patients. Despite reporting a respiratory indication, most (84%) WS patients were placed on VA-ECMO. There were no significant differences between the two groups in terms of pre-ECMO cardiac arrest, ECMO duration, or reason for ECMO discontinuation. Both groups had a mortality rate of 48% (p = 1.00). No risk factors for WS mortality were identified.
Role of TLR-4/IL-6/TNF-α, COX-II and eNOS/iNOS pathways in the impact of carvedilol against hepatic ischemia reperfusion injury
Authors: Hassan Mohamed IA , Ali Fares EM , Shalkami Abdel-Gawad S 
Published: March 2021

Aim: Hepatic ischemia/reperfusion (I/R) injury is a syndrome involved in allograft dysfunction. This work aimed to elucidate carvedilol (CAR) role in hepatic I/R injury. Methods: Male rats were allocated to Sham group, CAR group, I/R group and CAR plus I/R group. Rats subjected to hepatic ischemia for 30 minutes then reperfused for 60 minutes. Oxidative stress markers, inflammatory cytokines and nitric oxide synthases were measured in hepatic tissues. Results: Hepatocyte injury following I/R was confirmed by a marked increase in liver enzymes. Also, hepatic I/R increased the contents of malondialdehyde however decreased glutathione contents and activities of antioxidant enzymes. Furthermore, hepatic I/R caused elevation of toll-like receptor-4 (TLR-4) expression and inflammatory mediators levels such as tumor necrosis factor-α, interleukin-6 and cyclooxygenase-II. Hepatic I/R caused down-regulation of endothelial nitric oxide synthase and upregulation of inducible nitric oxide synthase expressions. CAR treatment before hepatic I/R resulted in the restoration of liver enzymes. Administration of CAR caused a significant correction of oxidative stress and inflammation markers as well as modulates the expression of endothelial and inducible nitric oxide synthase. Conclusions: CAR protects liver from I/R injury through reduction of the oxidative stress and inflammation, and modulates endothelial and inducible nitric oxide synthase expressions.
Psoriatic arthritis and the association with cardiometabolic disease: a narrative review
Authors: Karmacharya Paras , Ogdie Alexis , Eder Lihi 
Published: March 2021

Psoriatic arthritis (PsA) is associated with a higher burden of cardiometabolic disorders, such as hypertension, dyslipidemia, diabetes, obesity, and cardiovascular disease (CVD), compared with the general population. These comorbidities are associated with the severity of disease, and adversely affect treatment outcomes in PsA. Comorbidities lead to increased physician visits and medications for patients and make the selection and maintenance of therapies challenging for physicians. Moreover, CVD is a leading cause of mortality in PsA. Therefore, optimal management of PsA should include not only treating the skin and joint disease, but also identifying comorbidities early, and managing them to improve long-term outcomes. Further studies are needed to understand the complex mechanisms, interactions, and trajectories of cardiometabolic comorbidities in psoriatic disease. Plain Language Summary Psoriatic arthritis and the association with cardiometabolic disease Psoriatic arthritis (PsA) is associated with a higher incidence and prevalence of cardiometabolic comorbidities compared with the general population, and higher than psoriasis and other inflammatory arthritides, such as rheumatoid arthritis and other spondyloarthritides. Obesity and hyperlipidemia are associated with an increased risk of developing PsA. Cardiometabolic comorbidities in PsA are associated with more severe disease and a lower likelihood of response to therapy. Suggested approaches to improve screening and management of CVD in PsA include education of family physicians and relevant specialists, development of mechanisms to improve communication between the rheumatologists and primary care providers, and novel models of care, including interdisciplinary cardio-rheumatology clinics.