bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection and Neutralization of Unsymmetrical Dimethylhydrazine on the Surface of Construction Materials
Authors: Polunin K. E. , Ul’yanov A. V. , Polunina I. A. , Buryak A. K. 
Published: April 2021

Abstract
The construction materials that contacted with unsymmetrical dimethylhydrazine and the desorption solutions obtained when treating the contaminated surface of metals and alloys with water and reagents were studied by chromatography and mass spectrometry. Neutralization of unsymmetrical dimethylhydrazine was studied using ozone and shungite. Ozonation makes it possible to destroy the toxicant molecules chemically and physically adsorbed on the surface of metal constructions, due to which they can be reused and utilized. Shungite effectively adsorbs and catalytically decomposes not only unsymmetrical dimethylhydrazine and its transformation products, but also oligomer compounds formed during the storage of hydrazine fuel. Ozonation of spent shungite can increase the efficiency of destructive processes and completeness of its regeneration.
Longitudinal analyses of gender differences in first authorship publications related to COVID-19
Authors: Lerchenmüller Carolin , Schmallenbach Leo , Jena Anupam B , Lerchenmueller Marc J 
Published: April 2021

ObjectiveConcerns have been raised that the COVID-19 pandemic has shifted research productivity to the disadvantage of women in academia, particularly in early career stages. In this study, we aimed to assess the pandemic’s effect on women’s COVID-19-related publishing over the first year of the pandemic.Methods and resultsWe compared the gender distribution of first authorships for 42 898 publications on COVID-19 from 1 February 2020 to 31 January 2021 to 483 232 publications appearing in the same journals during the same period the year prior. We found that the gender gap—the percentage of articles on which men versus women were first authors—widened by 14 percentage points during the COVID-19 pandemic, despite many pertinent research fields showing near equal proportions of men and women first authors publishing in the same fields before the pandemic. Longitudinal analyses revealed that the significant initial expansions of the gender gap began to trend backwards to expected values over time in many fields. As women may have been differentially affected depending on their geography, we also assessed the gender distribution of first authorships grouped by countries and geographical areas. While we observed a significant reduction of the shares of women first authors in almost all countries, longitudinal analyses confirmed a resolving trend over time.ConclusionThe reduction in women’s COVID-19-related research output appears particularly concerning as many disciplines informing the response to the pandemic had near equal gender shares of first authorship in the year prior to the pandemic. The acute productivity drain with the onset of the pandemic magnifies deep-rooted obstacles on the way to gender equity in scientific contribution.
Vibro-fluidization of sand under coupled static loading and high-frequency cyclic loading
Authors: Dai Ning , Shan Yao , Fu Longlong , Ye Weitao , Guo Peijun , Zhou Shunhua , Rackwitz Frank , Stolle Dieter 
Published: April 2021

An increase in the operation speed of high-speed trains often leads to an increase in the loading frequency on subgrade soil. Hence, the long-term dynamic behavior of the subgrade and the service performance of high-speed tracks are affected. To determine the stress–strain characteristics of granular soil under high-frequency loading, a triaxial test setup was modified to investigate the effects of loading acceleration and duration, water content, vibration frequency, cell pressure, and initial soil density. The experimental results indicate that there are reductions in axial stress and volumetric strain during high-frequency loading. The reduction in axial stress is as high as 40%, and that of volumetric strain, which is permanent, could approach 0.1%. The stress reduction, strain compression, and excess pore pressure are found to vary linearly with vibration acceleration when a/g > 0.02, where a is vertical vibration acceleration and g is gravitational acceleration. The reduction in strength and strains are found to depend on the loading acceleration and effective cell pressure, but independent of the loading duration, water content, frequency, and initial density. A threshold acceleration a = 0.02g is observed, below which the changes in the shear strength and volumetric strain induced by vibration are negligible. At high vibration acceleration, the strain amplitude could increase, eventually leading to a collapse of the specimen.
SHP2-Mediated Inhibition of DNA Repair Contributes to cGAS–STING Activation and Chemotherapeutic Sensitivity in Colon Cancer
Authors: Wei Bin , Xu Lingyan , Guo Wenjie , Wang Yuanyuan , Wu Jingjing , Li Xiaofei , Cai Xiaomin , Hu Jinbo , Wang Meijing , Xu Qiang , Liu Wen , Gu Yanhong 
Published: April 2021

Abstract

As a cytoplasmic sensor of double-stranded DNA (dsDNA), the cyclic GMP-AMP synthase–stimulator of IFN genes (STING) pathway plays an important role in antitumor immunity. In this study, we investigated the effect of Src homology-2 domain-containing protein tyrosine phosphatase-2 (SHP2) on tumor cell–intrinsic STING pathway activity and DNA repair in colon cancer. SHP2 interacted with and dephosphorylated PARP1 after DNA damage. PARP1 inhibition by SHP2 resulted in reduced DNA repair and accumulation of dsDNA in cells, thus promoting hyperactivation of the STING pathway. The SHP2 agonist lovastatin was able to enhance SHP2 activity and promote STING pathway activation. Moreover, lovastatin significantly enhanced the efficacy of chemotherapy in colon cancer models, in part via STING pathway-mediated antitumor immunity. These findings suggest that SHP2 exacerbates STING pathway activation by restricting PARP1-mediated DNA repair in tumor cells, providing a basis for the combined use of lovastatin and chemotherapy in the treatment of colon cancer.

Significance:
Dephosphorylation of PARP1 by SHP2 simultaneously suppresses DNA repair and enhances STING pathway-mediated antitumor immunity, highlighting SHP2 activation as a potential therapeutic approach in colon cancer.
Sapanisertib Plus Exemestane or Fulvestrant in Women with Hormone Receptor–Positive/HER2-Negative Advanced or Metastatic Breast Cancer
Authors: Lim Bora , Potter David A. , Salkeni Mohamad A. , Silverman Paula , Haddad Tufia C. , Forget Frederic , Awada Ahmad , Canon Jean-Luc , Danso Michael , Lortholary Alain , Bourgeois Hugues , Tan-Chiu Elizabeth , Vincent Sylvie , Bahamon Brittany , Galinsky Kevin J. , Patel Chirag , Neuwirth Rachel , Leonard E. Jane , Diamond Jennifer R. 
Published: April 2021

AbstractPurpose:This open-label, multicenter, phase IB/II study evaluated sapanisertib, a dual inhibitor of mTOR kinase complexes 1/2, plus exemestane or fulvestrant in postmenopausal women with hormone receptor–positive (HR+)/HER2-negative (HER2−) advanced/metastatic breast cancer.Patients and Methods:Eligible patients had previously progressed on everolimus with exemestane/fulvestrant and received ≤3 (phase IB) or ≤1 (phase II) prior chemotherapy regimens. Patients received sapanisertib 3 to 5 mg every day (phase IB), or 4 mg every day (phase II) with exemestane 25 mg every day or fulvestrant 500 mg monthly in 28-day cycles. Phase II enrolled parallel cohorts based on prior response to everolimus. The primary objective of phase II was to evaluate antitumor activity by clinical benefit rate at 16 weeks (CBR-16).Results:Overall, 118 patients enrolled in phase IB (n = 24) and II (n = 94). Five patients in phase IB experienced dose-limiting toxicities, at sapanisertib doses of 5 mg every day (n = 4) and 4 mg every day (n = 1); sapanisertib 4 mg every day was the MTD in combination with exemestane or fulvestrant. In phase II, in everolimus-sensitive versus everolimus-resistant cohorts, CBR-16 was 45% versus 23%, and overall response rate was 8% versus 2%, respectively. The most common adverse events were nausea (52%), fatigue (47%), diarrhea (37%), and hyperglycemia (33%); rash occurred in 17% of patients. Molecular analysis suggested positive association between AKT1 mutation status and best treatment response (complete + partial response; P = 0.0262).Conclusions:Sapanisertib plus exemestane or fulvestrant was well tolerated and exhibited clinical benefit in postmenopausal women with pretreated everolimus-sensitive or everolimus-resistant breast cancer.
Standardized Uptake Value for 18F-Fluorodeoxyglucose Is a Marker of Inflammatory State and Immune Infiltrate in Cervical Cancer
Authors: Floberg John M. , Zhang Jin , Muhammad Naoshad , DeWees Todd A. , Inkman Matthew , Chen Kevin , Lin Alexander J. , Rashmi Ramachandran , Jayachandran Kay , Edelson Brian T. , Siegel Barry A. , Dehdashti Farrokh , Grigsby Perry W. , Markovina Stephanie , Schwarz Julie K. 
Published: April 2021

Abstract

Purpose:
Chemoradiotherapy for locally advanced cervical cancer fails in over a third of patients. Biomarkers with therapeutic implications are therefore needed. We investigated the relationship between an established prognostic marker, maximum standardized uptake value (SUVmax) on 18F-fluorodeoxyglucose positron emission tomography, and the inflammatory and immune state of cervical cancers.

Experimental Design:
An SUVmax most prognostic for freedom from progression (FFP) was identified and compared with known prognostic clinical variables in a cohort of 318 patients treated with definitive radiation with prospectively collected clinical data. Gene set enrichment analysis (GSEA) and CIBERSORT of whole-transcriptome data from 68 patients were used to identify biological pathways and immune cell subpopulations associated with high SUVmax. IHC using a tissue microarray (TMA, N = 82) was used to validate the CIBERSORT findings. The impact of macrophages on cervical cancer glucose metabolism was investigated in coculture experiments.

Results:
SUVmax &lt;11.4 was most prognostic for FFP (P = 0.001). The GSEA showed that high SUVmax is associated with increased gene expression of inflammatory pathways, including JAK/STAT3 signaling. CIBERSORT and CD68 staining of the TMA showed high SUVmax tumors are characterized by a monocyte-predominant immune infiltrate. Coculture of cervical cancer cells with macrophages or macrophage-conditioned media altered glucose uptake, and IL6 and JAK/STAT3 signaling contribute to this effect.

Conclusions:
SUVmax is a prognostic marker in cervical cancer that is associated with activation of inflammatory pathways and tumor infiltration of myeloid-derived immune cells, particularly macrophages. Macrophages contribute to changes in cervical cancer glucose metabolism.
See related commentary by Williamson et al., p. 4136
A Phase Ib/II Study of Pepinemab in Combination with Avelumab in Advanced Non–Small Cell Lung Cancer
Authors: Shafique Michael R. , Fisher Terrence L. , Evans Elizabeth E. , Leonard John E. , Pastore Desa Rae E. , Mallow Crystal L. , Smith Ernest , Mishra Vikas , Schröder Andreas , Chin Kevin M. , Beck Joseph T. , Baumgart Megan A. , Govindan Ramaswamy , Gabrail Nashat Y. , Spira Alexander I. , Seetharamu Nagashree , Lou Yanyan , Mansfield Aaron S. , Sanborn Rachel E. , Goldman Jonathan W. , Zauderer Maurice 
Published: April 2021

Abstract

Purpose:
The CLASSICAL-Lung clinical trial tested the combination of pepinemab, an IgG4 humanized mAb targeting semaphorin 4D, with the PD-L1 inhibitor avelumab to assess the effects of coupling increased T-cell infiltration and reversal of immune suppression via pepinemab with sustained T-cell activation via checkpoint inhibition.

Patients and Methods:
This phase Ib/II, single-arm study was designed to evaluate the safety, tolerability, and efficacy of pepinemab in combination with avelumab in 62 patients with advanced non–small cell lung cancer (NSCLC), including immunotherapy-naïve (ION) patients and patients whose tumors progressed following anti-PD-1/L1 monotherapy (IOF). The main objectives were to evaluate safety/tolerability, establish a recommended phase 2 dose (RP2D), obtain a preliminary evaluation of antitumor activity, and investigate candidate biomarker activity.

Results:
The combination was well tolerated with no major safety signals identified. Pepinemab, 10 mg/kg with avelumab, 10 mg/kg, every 2 weeks, was selected as the RP2D. Among 21 evaluable ION patients, 5 patients experienced partial responses (PR), 4 patients evidenced clinical benefit ≥1 year, and the disease control rate (DCR) was 81%. Notably, overall response rate with the combination therapy was higher than previously reported for single-agent avelumab in the PD-L1-negative/low population. Among 29 evaluable IOF patients, the combination resulted in a DCR of 59%, including 2 PR and 7 patients with durable clinical benefit of ≥23 weeks. Biomarker analysis of biopsies demonstrated increased CD8 T-cell density correlating with RECIST response criteria.

Conclusions:
The combination of pepinemab with avelumab was well tolerated in NSCLC and showed signs of antitumor activity in immunotherapy-resistant and PD-L1-negative/low tumors.
Cost Effectiveness of Interhospital Transfer for Mechanical Thrombectomy of Acute Large Vessel Occlusion Stroke
Authors: Schlemm Ludwig , Endres Matthias , Nolte Christian H. 
Published: April 2021

Background:
Emergency interhospital transfer of patients with stroke with large vessel occlusion to a comprehensive stroke center for mechanical thrombectomy is resource-intensive and can be logistically challenging. Imaging markers may identify patients in whom intravenous thrombolysis (IVT) alone is likely to result in thrombus resolution, potentially rendering interhospital transfers unnecessary. Here, we investigate how predicted probabilities to achieve IVT-mediated recanalization affect cost-effectiveness estimates of interhospital transfer.

Methods:
We performed a health economic analysis comparing emergency interhospital transfer of patients with acute large vessel occlusion stroke after administration of IVT with a scenario in which patients also receive IVT but remain at the primary hospital. Results were stratified by clinical parameters, treatment delays, and the predicted probability to achieve IVT-mediated recanalization. Estimated 3-month outcomes were combined with a long-term probabilistic model to yield quality-adjusted life years (QALYs) and costs. Uncertainty was quantified in probabilistic sensitivity analyses.

Results:
Depending on input parameters, marginal costs of interhospital transfer ranged from USD −61 366 (cost saving) to USD +20 443 and additional QALYs gained from 0.1 to 3.0, yielding incremental cost-effectiveness ratios of <USD 0 (dominant) to USD 310 000 per QALY. For some elderly patients with moderate or severe stroke symptoms treated in a remote primary stroke center, transfer was unlikely to be cost effective at a willingness-to-pay threshold of USD 100 000 and 50 000 per QALY (20% and 1%, respectively) if the predicted probability to achieve IVT-related recanalization was high. On the other hand, in some younger patients, the analysis yielded incremental cost-effectiveness ratio estimates below USD 20 000 per QALY independent of the predicted recanalization rate.

Conclusions:
Predicted probabilities to achieve IVT-mediated recanalization significantly affect the cost-effectiveness of interhospital transfer for MT, in particular in elderly patients with moderate or severe stroke symptoms. However, high predicted recanalization rates alone do not generally imply that patients should not be considered for transfer.
Interdecadal Shift of the Relationship between ENSO and Winter Synoptic Temperature Variability over the Asian–Pacific–American Region in the 1980s
Authors: Jian Yuntao , Leung Marco Y. T. , Zhou Wen , Jian Maoqiu , Yang Song , Lin Xiaoxia 
Published: April 2021

AbstractIn this study, the interdecadal variability of the relationship between ENSO and winter synoptic temperature variability (STV) over the Asian–Pacific–American region is investigated based on observational data from 1951 to 2018. An interdecadal shift in the ENSO–STV relationship occurred in the 1980s over Eastern China, changing from significant in period 1 (P1; 1951–87) to insignificant in period 2 (P2; 1988–2018). But the ENSO–STV relationship is significantly stable over North America for the whole period. In addition, a possible reason for this interdecadal shift in the ENSO–STV relationship over Eastern China is also investigated. During P1, the ENSO pattern is significantly correlated to the temperature gradient over Northeast Asia, which is the key region influencing the intensification of extratropical eddies. The intensification of extratropical eddies over Northeast Asia is directly associated with the magnitude of STV over Eastern China. But in P2, the ENSO pattern is not related to the temperature over Northeast Asia. Therefore, the change in the ENSO pattern from P1 to P2 contributes to the interdecadal shift in the ENSO–STV relationship in the 1980s over Eastern China by influencing the temperature gradient over Northeast Asia, while ENSO can influence the temperature gradient over North America for the whole period. Furthermore, the possible role of the ENSO patterns in P1 and P2 is also examined by using an atmospheric general circulation model, highlighting that the pattern of SST variation is a determining factor in regulating STV in different regions.
Biphenotypic Sinonasal Sarcoma: A Case Report and Review of Literature
Authors: Kominsky Evan , Boyke Andre E. , Madani Daniel , Kamat Ameet , Schiff Bradley A. , Agarwal Vijay 
Published: April 2021

Objectives: Biphenotypic sinonasal sarcoma (BSNS), previously low-grade sinonasal sarcoma with neural and myogenic features, is a rare tumor of the sinonasal tract first described in 2012. Due to its rarity, limited literature is available in providing clinicians with a standardized treatment regimen, particularly in cases of positive surgical margins. This article aims to provide a clinical review of the currently available reported cases of BSNS, as well as presenting clinical, radiologic, and pathologic details of 2 novel cases. Methods: Online electronic databases include PubMed and Embase where queried for reports of biphenotypic sinonasal sarcoma or low-grade sinonasal sarcoma with neural and myogenic features. Two previously unpublished cases were included in the results. Data including clinical presentation, epidemiologic data, radiologic evaluation, intraoperative details, histopathology, treatment modality, and postoperative follow-up information were included. Results: A total of 100 previously published cases were identified in 12 prior articles. Mean age at presentation was 52.9 years. Extrasinonasal extension was observed in 27.4% of cases with most common site of extension being cribriform plate. Forty-seven cases included treatment details with surgical excision being the most common modality. Recurrence rates were identical for both surgical excision alone and surgical excision with adjuvant radiotherapy (33.3%). Conclusions: Biphenotypic sinonasal sarcoma is a slow-growing tumor that is amenable to surgical resection. Recurrence rates are similar between surgical excision and surgical excision with adjuvant radiation therapy, but limited data in reported cases preclude a determination of treatment superiority.
Adjuvant radiofrequency thermocoagulation improves the outcome of liquid sclerotherapy in the treatment of spider veins of the leg: A pilot study
Authors: Diken Adem İlkay , Alemdaroğlu Utku , Özyalçın Sertan , Hafez İzzet , Tünel Hüseyin A , Yalçınkaya Adnan , Ecevit Ata N 
Published: April 2021

Objective This study evaluated the effect of low-energy radiofrequency thermocoagulation added to standard liquid sclerotherapy on clinical outcomes of patients with venous insufficiency. Patients and method We included 111 patients with spider veins CEAP/C1 stage. The patients were randomized into sclerotherapy (Group 1) and sclerotherapy + sclerotherapy immediately followed by low energy percutaneous RF thermocoagulation (Group 2) groups and followed up with same protocols prospectively. Results The study groups did not differ in terms of the mean age, body mass index, the number of spider veins and pre-interventional venous clinical severity scores (VCSS). Patients' self-assessed satisfaction ratings of cosmetic outcomes were found to be higher compared to the baseline (p = 0.001). While both techniques caused a significant decline in VCSS at postprocedural third month, it was observed that the type of applied intervention did not affect the VCSS (p = 0.43 and p = 0.93, respectively). There was a significant difference in hyperpigmentation and trapped blood between the two groups after the procedure (p = 0.009 and p = 0.02, respectively), there was no statistically significant difference in terms of skin necrosis (p = 0.52). A significant difference in the self-assessed cosmetic outcomes was observed in patients treated with sclerotherapy followed by low energy percutaneous RF thermocoagulation compared with patients whom sclerotherapy performed alone (p = 0.001). Discussion This study suggests that radiofrequency thermocoagulation added to the sclerotherapy provides better cosmetic outcomes with less treatment sessions and no additional complication rates.
Modeling Diagnostic Strategies to Manage Toxic Adverse Events following Cancer Immunotherapy
Authors: van Delft Frederik , Muller Mirte , Langerak Rom , Koffijberg Hendrik , Retèl Valesca , van den Broek Daan , IJzerman Maarten 
Published: April 2021

Background Although immunotherapy (IMT) provides significant survival benefits in selected patients, approximately 10% of patients experience (serious) immune-related adverse events (irAEs). The early detection of adverse events will prevent irAEs from progressing to severe stages, and routine testing for irAEs has become common practice. Because a positive test outcome might indicate a clinically manifesting irAE that requires treatment to (temporarily) discontinue, the occurrence of false-positive test outcomes is expected to negatively affect treatment outcomes. This study explores how the UPPAAL modeling environment can be used to assess the impact of test accuracy (i.e., test sensitivity and specificity), on the probability of patients entering palliative care within 11 IMT cycles. Methods A timed automata-based model was constructed using real-world data and expert consultation. Model calibration was performed using data from 248 non–small-cell lung cancer patients treated with nivolumab. A scenario analysis was performed to evaluate the effect of changes in test accuracy on the probability of patients transitioning to palliative care. Results The constructed model was used to estimate the cumulative probabilities for the patients’ transition to palliative care, which were found to match real-world clinical observations after model calibration. The scenario analysis showed that the specificity of laboratory tests for routine monitoring has a strong effect on the probability of patients transitioning to palliative care, whereas the effect of test sensitivity was limited. Conclusion We have obtained interesting insights by simulating a care pathway and disease progression using UPPAAL. The scenario analysis indicates that an increase in test specificity results in decreased discontinuation of treatment due to suspicion of irAEs, through a reduction of false-positive test outcomes.