bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment with pembrolizumab in programmed death ligand 1–positive recurrent glioblastoma: Results from the multicohort phase 1 KEYNOTE‐028 trial
Authors: Reardon David A. , Kim Tae Min , Frenel Jean‐Sebastien , Simonelli Matteo , Lopez Juanita , Subramaniam Deepa S. , Siu Lillian L. , Wang Hui , Krishnan Suba , Stein Karen , Massard Christophe 
Published: January 2021

BackgroundCurrent treatments for recurrent glioblastoma offer limited benefit. The authors report the antitumor activity and safety of the anti–programmed death 1 (anti–PD‐1) immunotherapy, pembrolizumab, in programmed death ligand 1 (PD‐L1)–positive, recurrent glioblastoma.MethodsAdult patients with PD‐L1–positive tumors were enrolled in the recurrent glioblastoma cohort of the multicohort, phase 1b KEYNOTE‐028 study (ClinicalTrials.gov identifier, NCT02054806) and received pembrolizumab 10 mg/kg every 2 weeks for up to 2 years. The primary endpoint was investigator‐assessed overall response rate according to the Response Evaluation Criteria in Solid Tumors, version 1.1. Archival tumor samples were assessed for PD‐L1 expression levels (prospectively) and T‐cell–inflamed gene expression profile score (retrospectively).ResultsAfter a median follow‐up of 14 months (range, 2‐55 months) among the 26 enrolled patients, the overall response rate was 8% (95% CI, 1%‐26%). Two partial responses, lasting 8.3 and 22.8 months, occurred. Progression‐free survival (median, 2.8 months; 95% CI, 1.9‐8.1 months) rate at 6 months was 37.7%, and the overall survival (median, 13.1 months; 95% CI, 8.0‐26.6 months) rate at 12 months was 58%. Correlation of therapeutic benefit to level of PD‐L1 expression, gene expression profile score, or baseline steroid use could not be established. Treatment‐related adverse events occurred in 19 patients (73%), and 5 patients experienced grade 3 or 4 events (there were no grade 5 events). Immune‐mediated adverse events and infusion reactions occurred in 7 patients (27%).ConclusionsPembrolizumab monotherapy demonstrated durable antitumor activity in a subset of patients with manageable toxicity in this small, signal‐finding, recurrent glioblastoma cohort. Future studies evaluating rationally designed pembrolizumab combination regimens may improve outcomes in patients with recurrent glioblastoma.
SCR7, a potent cancer therapeutic agent and a biochemical inhibitor of nonhomologous DNA end‐joining
Authors: Manjunath Meghana , Choudhary Bibha , Raghavan Sathees C. 
Published: January 2021

AbstractBackgroundDNA double‐strand breaks (DSBs) are harmful to the cell as it could lead to genomic instability and cell death when left unrepaired. Homologous recombination and nonhomologous end‐joining (NHEJ) are two major DSB repair pathways, responsible for ensuring genome integrity in mammals. There have been multiple efforts using small molecule inhibitors to target these DNA repair pathways in cancers. SCR7 is a very well‐studied anticancer molecule that blocks NHEJ by targeting one of the critical enzymes, Ligase IV.Recent findingsIn this review, we have highlighted the anticancer effects of SCR7 as a single agent and in combination with other chemotherapeutic agents and radiation. SCR7 blocked NHEJ effectively both in vitro and ex vivo. SCR7 has been used for biochemical studies like chromosomal territory resetting and in understanding the role of repair proteins in cell cycle phases. Various forms of SCR7 and its derivatives are discussed. SCR7 is also used as a potent biochemical inhibitor of NHEJ, which has found its application in improving genome editing using a CRISPR‐Cas system.ConclusionSCR7 is a potent NHEJ inhibitor with unique properties and wide applications as an anticancer agent. Most importantly, SCR7 has become a handy aid for improving genome editing across different model systems.
Energetic Descriptors of Steric Hindrance in Real Space: An Improved IQA Picture**
Authors: Gallegos Miguel , Costales Aurora , Pendás Ángel Martín 
Published: January 2021

AbstractSteric hindrance (SH) plays a central role in the modern chemical narrative, lying at the core of chemical intuition. As it however happens with many successfulchemical concepts, SH lacks an underlying physically sound root, and multiple mutually inconsistent approximations have been devised to relate this fuzzy concept to computationally derivable descriptors. We here argue that being SH related to spatial as well as energetic features of interacting systems, SH can be properly handled if we chose a real space energetic stance like the Interacting Quantum Atoms (IQA) approach. Drawing on previous work by Popelier and coworkers (ChemistryOpen8, 560, 2019) we build an energetic estimator of SH, referred to asEST. We show that the rise in the self‐energy of a fragment that accompanies steric congestion is a faithful proxy for the chemist's SH concept if we remove the effect of charge transfer. This can be done rigorously, and theESThere defined provides correct sterics even for hydrogen atoms, where the plain use of deformation energies leads to non‐chemical results. The applicability ofESTis validated in several chemical scenarios, going from atomic compressions to archetypalSN2reactions.ESTis shown to be a robust steric hindrance descriptor.
Abnormal glucose in pre‐school children and the association with obesity/physical activity: A large population‐based study
Authors: Wang Shuo , Li Weiqin , Qiao Yijuan , Wang Shuting , Zhang Tao , Liu Enqing , Pan Lei , Leng Junhong 
Published: January 2021

AbstractAimThe rise of diabetes mellitus (DM) and impaired fasting glucose (IFG) in children has become a worldwide challenge, but population‐based survey targeted on pre‐school children is lacking. The aim of the study was to determine the prevalence of DM and IFG in pre‐school children and their association with obesity and susceptible behaviours.MethodsA population‐based survey was conducted and 21,571 Chinese children aged 5–6 years were recruited from 66 kindergartens in Tianjin, China during the year of 2016–2018. Fasting glucose was measured for all participants. Children with fasting glucose over 7.0 mmol/L was defined as DM, and 5.6–6.9 mmol/L was defined as IFG.ResultsThe prevalence of DM and IFG in the current study among Chinese children aged 5–6 years old was 0.05% and 1.18%, respectively, with significant gender and regional disparities (p < 0.001). The risk of abnormal fasting glucose increased with obesity (OR 1.44, 95% CI 1.00–2.06, p < 0.05), especially with moderate/severe obesity (OR 1.84, 95% CI 1.10–3.10, p < 0.05). Further analyses found that as compared to children who had at least 2 h/day physical activity, physical activity <1 h/day increased the risk of abnormal fasting glucose independently of BMI z‐score (OR 1.79, 95% CI 1.10–2.91, p < 0.05).ConclusionsThe study was the first population‐based large‐scale survey of DM and IFG which targeted on pre‐school children, and demonstrated that moderate/severe obesity and inadequate physical activity raised the risk of DM and IFG early from pre‐school. The findings highlighted the necessity of early detection for abnormal glucose and control of obesity and susceptible behaviours.
Astrocytes as a target for Nogo‐A and implications for synapse formation in vitro and in a model of acute demyelination
Authors: Espírito‐Santo Sheila , Coutinho Vinícius G , Dezonne Rômulo S , Stipursky Joice , dos Santos‐Rodrigues Alexandre , Batista Carolina , Paes‐de‐Carvalho Roberto , Fuss Babette , Gomes Flávia Carvalho Alcantara 
Published: January 2021

AbstractCentral nervous system (CNS) function depends on precise synaptogenesis, which is shaped by environmental cues and cellular interactions. Astrocytes are outstanding regulators of synapse development and plasticity through contact‐dependent signals and through the release of pro‐ and antisynaptogenic factors. Conversely, myelin and its associated proteins, including Nogo‐A, affect synapses in a inhibitory fashion and contribute to neural circuitry stabilization. However, the roles of Nogo‐A‐astrocyte interactions and their implications in synapse development and plasticity have not been characterized. Therefore, we aimed to investigate whether Nogo‐A affects the capacity of astrocytes to induce synaptogenesis. Additionally, we assessed whether downregulation of Nogo‐A signaling in an in vivo demyelination model impacts the synaptogenic potential of astrocytes. Our in vitro data show that cortical astrocytes respond to Nogo‐A through RhoA pathway activation, exhibiting stress fiber formation and decreased ramified morphology. This phenotype was associated with reduced levels of GLAST protein and aspartate uptake, decreased mRNA levels of the synaptogenesis‐associated genes Hevin, glypican‐4, TGF‐β1 and BDNF, and decreased and increased protein levels of Hevin and SPARC, respectively. Corroborating these findings, conditioned medium from Nogo‐A‐treated astrocytes suppressed the formation of structurally and functionally mature synapses in cortical neuronal cultures. After cuprizone‐induced acute demyelination, we observed reduced immunostaining for Nogo‐A in the visual cortex accompanied by higher levels of Hevin expression in astrocytes and an increase in excitatory synapse density. Hence, we suggest that interactions between Nogo‐A and astrocytes might represent an important pathway of plasticity regulation and could be a target for therapeutic intervention in demyelinating diseases in the future.
Absence of CCR2 reduces spontaneous intestinal tumorigenesis in the ApcMin/+ mouse model
Authors: Jala Venkatakrishna Rao , Bodduluri Sobha Rani , Ghosh Sweta , Chheda Zinal , Singh Rajbir , Smith Michelle E. , Chilton Paula M. , Fleming Christopher J. , Mathis Steven Paul , Sharma Rajesh Kumar , Knight Rob , Yan Jun , Haribabu Bodduluri 
Published: January 2021

AbstractThe biological activities of chemokine (C‐C motif) ligand 2 (CCL2) are mediated via C‐C chemokine receptor‐2 (CCR2). Increased CCL2 level is associated with metastasis of many cancers. In our study, we investigated the role of the CCL2/CCR2 axis in the development of spontaneous intestinal tumorigenesis using the ApcMin/+ mouse model. Ablation of CCR2 in ApcMin/+ mice significantly increased the overall survival and reduced intestinal tumor burden. Immune cell analysis showed that CCR2−/−ApcMin/+ mice exhibited significant reduction in the myeloid cell population and increased interferon γ (IFN‐γ) producing T cells both in spleen and mesenteric lymph nodes compared to ApcMin/+ mice. The CCR2−/−ApcMin/+ tumors showed significantly reduced levels of interleukin (IL)‐17 and IL‐23 and increased IFN‐γ and Granzyme B compared to ApcMin/+ tumors. Transfer of CCR2+/+ApcMin/+ CD4+ T cells into Rag2−/− mice led to development of colitis phenotype with increased CD4+ T cells hyper proliferation and IL‐17 production. In contrast, adoptive transfer of CCR2−/−ApcMin/+ CD4+ T cells into Rag2−/− mice failed to enhance colonic inflammation or IL‐17 production. These results a suggest novel additional role for CCR2, where it regulates migration of IL‐17 producing cells mediating tumor‐promoting inflammation in addition to its role in migration of tumor associated macrophages.
Hedging against risks associated with travel and tourism stocks during COVID‐19 pandemic: The role of gold
Authors: Sikiru Abdulsalam Abidemi , Salisu Afees A. 
Published: January 2021

AbstractThe global lockdowns including movement restrictions during COVID‐19 pandemic impacted the hospitality business negatively and by extension the trading of related stocks such as travel & tourism stocks. Owing to the long standing hedging potential of gold, we examine whether this potential can be extended to the travel & tourism stocks in order to hedge against the associated risks caused by the current pandemic. Using daily data from January 2016 to July 2020 and constructing optimal portfolio strategies, we find that gold serves as a very strong hedge and safe haven for travel & tourism stocks, most especially in the pandemic period. This conclusion validates the inclusion of gold in the diversified portfolio of travel & tourism stocks in order to improve the risk‐adjusted return performance for investors in the sector particularly during COVID‐19 pandemic.
Machine learning in polymer informatics
Authors: Sha Wuxin , Li Yan , Tang Shun , Tian Jie , Zhao Yuming , Guo Yaqing , Zhang Weixin , Zhang Xinfang , Lu Songfeng , Cao Yuan‐Cheng , Cheng Shijie 
Published: January 2021

AbstractPolymers have been widely used in energy storage, construction, medicine, aerospace, and so on. However, the complexity of chemical composition and morphology of polymers has brought challenges to their development. Thanks to the integration of machine learning algorithms and large data resources, the data‐driven methods have opened up a new road for the development of polymer science and engineering. The emerging polymer informatics attempts to accelerate the performance prediction and process optimization of new polymers by using machine learning models based on reliable data. With the gradual supplement of currently available databases, the emergence of new databases and the continuous improvement of machine learning algorithms, the research paradigm of polymer informatics will be more efficient and widely used. Based on these points, this paper reviews the development trends of machine learning assisted polymer informatics and provides a simple introduction for researchers in materials, artificial intelligence, and other fields.image
Textile‐integrated microwave components based on artificial magnetic conductor
Authors: Kokolia Martin , Raida Zbynek 
Published: January 2021

AbstractIn the paper, we introduce a textile‐integrated waveguide (TIW) based on a novel artificial magnetic conductor (AMC), which consists of hexagonal elements. Thanks to the hexagonal shape of AMC elements, general TIW components (power‐dividers, waveguide bends, etc.) can be simply created. Since AMC replaces side walls of TIW, complicated manufacturing of vias can be eliminated. Due to the complex geometry of TIW, simulation of realistic models is not trivial. Attention is therefore turned to the combination of several computer‐oriented approaches (dispersive analysis, equivalent circuits, full wave models) to model AMC structures efficiently. Outputs of simulations are compared with measurements of components fabricated from self‐adhesive copper foil fixed to a three‐dimensional (3D) knitted substrate. Experiments show that simulations and measurements are in an acceptable agreement.
Surgical resection of early stage hepatocellular carcinoma improves patient survival at safety net hospitals
Authors: Vitiello Gerardo A. , Wang Annie , Lee Rachel M. , Russell Maria C. , Yopp Adam , Ryon Emily L. , Goel Neha , Luu Sommer , Hsu Cary , Silberfein Eric , Correa‐Gallego Camilo , Berman Russell S. , Lee Ann Y. 
Published: January 2021

AbstractBackground and ObjectivesSurgical resection is indicated for hepatocellular carcinoma (HCC) patients with Child A cirrhosis. We hypothesize that surgical intervention and survival are limited by advanced HCC presentation at safety net hospitals (SNHs) versus academic medical centers (AMCs).MethodsPatients with HCC and Child A cirrhosis in the US Safety Net Collaborative (2012–2014) were evaluated. Demographics, clinicopathologic features, operative characteristics, and outcomes were compared between SNHs and AMCs. Liver transplantation was excluded. Kaplan–Meier and Cox proportional‐hazards models were used to identify the effect of surgery on overall (OS).ResultsA total of 689 Child A patients with HCC were identified. SNH patients frequently presented with T3/T4 stage (35% vs. 24%) and metastases (17% vs. 8%; p < .05). SNH patients were as likely to undergo surgery as AMC patients (17% vs. 18%); however, SNH patients were younger (56 vs. 64 years), underwent minor hepatectomy (65% vs. 38%), and frequently harbored well‐differentiated tumors (23% vs. 2%; p < .05). On multivariate analysis, surgical resection and stage, but not hospital type, were associated with improved OS.ConclusionsAlthough SNH patients present with advanced HCC, survival outcomes for early stage HCC are similar at SNHs and AMCs. Identifying barriers to early diagnosis at SNH may increase surgical candidacy and improve outcomes.
Thirty‐day complication rates do not differ by race among patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma
Authors: Mitsakos Anastasios T. , Dennis Samuel O. , Parikh Alexander A. , Snyder Rebecca A. 
Published: January 2021

AbstractBackground and ObjectivesBlack patients with pancreatic ductal adenocarcinoma (PDAC) are less likely to receive multimodality treatment and have worse survival compared to White patients. However, little is known regarding racial differences in postoperative outcomes. The primary aim of this study was to determine if 30‐day complication rates following pancreaticoduodenectomy (PD) differ by race.MethodsA retrospective cohort study of patients who underwent PD for PDAC from 2014 to 2016 within the ACS‐NSQIP pancreatectomy‐specific data set was performed. Primary outcomes were 30‐day pancreas‐specific and overall major complications.ResultsA total of 6936 patients were identified, including 91.4% (N = 6337) White and 8.6% (N = 599) Black. Pathologic stage and rates of neoadjuvant therapy were similar among Whites and Blacks. Rates of pancreas‐specific (23.9% vs. 23.1%, p = .88) and major postoperative complications (39.2% vs. 39.9%, p = .55) were similar between Whites and Blacks. By multivariable regression analysis, there was no association between race and odds of pancreas‐specific complications (odds ratio [OR] 1.10, 95% confidence interval [CI] 0.89–1.37) or overall major complications (OR 1.13, 95% CI 0.95–1.36).ConclusionsAmong patients undergoing PD for PDAC, Black race is not associated with increased pancreas‐specific or overall 30‐day postoperative complications. Short‐term postoperative outcomes do not appear to explain the increase in pancreatic cancer mortality among Black patients.
Autophagy modulation as a potential targeted cancer therapy: From drug repurposing to new drug development
Authors: Lin Chia‐Jung , Tsao Yuan‐Ni , Shu Chih‐Wen 
Published: January 2021

AbstractAutophagy is an evolutionarily conserved signaling pathway to deliver dysfunctional proteins or organelles into lysosomes for degradation and recycling, which is an important pathway for normal homeostasis. Autophagy dysfunction can lead to various diseases, particularly cancer. Autophagy not only plays a role in tumor suppression, but it also serves as a tumor promoter in cancer malignancy. In this review, we summarize the involvement of autophagy‐related (ATG) proteins in autophagy signaling and the role of autophagy in cancer progression. The effectiveness of US Food and Drug Administration‐approved drugs in regulating autophagic flux and suppressing cancer cells is also discussed. Moreover, since clinically available drugs do not specifically target ATG proteins, there is little doubt that their cancer suppression function is autophagy dependent. Therefore, this review also discusses several inhibitors against ATG proteins, such as ULK1/2, ATG4, and VPS34 to suppress cancer cells. Autophagy modulators can be either used alone or combined with chemotherapy or radiation therapy to enhance the efficacy of current treatments for certain types of cancer. This review summarizes current autophagy modulation used as a potential strategy for targeted cancer therapy.
Selection criteria for prison locations: Key study of Turkey
Authors: Uzuner Ahmet Tuğcin , Geyikçi Umut Burak 
Published: January 2021

AbstractThe theory of public finance suggests that public sector intervention in the economy primarily concerns the efficient allocation of resources, equal distribution of wealth, and stabilization of economic activity throughout the operating cycle. Given that prisons are a public investment, this study identified the criteria involved in selecting the location of prisons in Turkey, a topic that has not been discussed before. The criteria for locating these establishments were analysed using an analytical network process in which the weight of each criterion in the total was determined by conducting a face‐to‐face survey with officials in the justice system who are difficult to access. The results show that political factors (50.89%) had the biggest influence on the location selection of a prison, and the positive impact on economic development of the selected region was only 13.56%. In contrast to the existing literature, location selection in Turkey does not follow the theory of public finance: the economic impacts are not considered, and decisions are taken politically.
Interfacial Sites in Ag Supported Layered Double Oxide for Dehydrogenation Coupling of Ethanol to n‐Butanol
Authors: Zhang Jian , Shi Kai , Zhu Yanru , An Zhe , Wang Wanning , Ma Xiaodan , Shu Xin , Song Hongyan , Xiang Xu , He Jing 
Published: January 2021

AbstractUpgrading of ethanol to n‐butanol through dehydrogenation coupling has received increasing attention due to the wide application of n‐butanol. But the enhancement of ethanol dehydrogenation and followed coupling to produce high selectivity to n‐butanol is still highly desired. Our previous work has reported an acid‐base‐Ag synergistic catalysis, with Ag particles supported on Mg and Al‐containing layered double oxides (Ag/MgAl‐LDO). Here, Ag‐LDO interfaces have been manipulated for dehydrogenation coupling of ethanol to n‐butanol by tailoring the size of Ag particles and the interactions between Ag and LDO. It has been revealed that increasing the population of surface Ag sites at Ag‐LDO interfaces promotes not only the dehydrogenation of ethanol to acetaldehyde but also the subsequent aldol condensation of generated acetaldehyde. A selectivity of up to 76 % to n‐butanol with an ethanol conversion of 44 % has been achieved on Ag/LDO with abundant interfacial Ag sites, much superior to the state‐of‐the‐art catalysts.
Fibrous Bundles in Biomorph Systems: Surface‐Specific Growth and Interaction with Microposts
Authors: Knoll Pamela , D'Silva Denvert S. , Adeoye Damilola I. , Roper Michael G. , Steinbock Oliver 
Published: January 2021

AbstractBiomorphs are polycrystalline assemblies that form when barium, silicate, and carbonate ions react in basic solutions. Their micrometer‐scale morphologies include leaf‐like sheets, helices, and cones, while their nanoscale architecture is based on co‐aligned witherite nanorods. We report a biomorph shape that resembles hair strands that smoothly curl into spirals or twisting fiber ribbons. They can thicken through continuous fractal‐like branching or abrupt events in which fibers split simultaneously. Raman and energy dispersive X‐ray spectroscopy as well as optical polarization microscopy reveal that their composition is very similar to classical biomorphs. They are most abundant in the absence of glass substrates and at high pH values. However, if a glass surface is covered by a thin SU‐8 resin layer, their growth is observed and photolithographically produced SU‐8 posts serve as nucleation sites. The hair‐like structures can detach resin posts from the glass surface and reposition them due to continued growth at the hair‐resin interface. Collisions of growing biomorph sheets with SU‐8 posts result in overgrowth or a sheet‐to‐hair transition.
Refinement and modularity of immortal dyons
Authors: Alexandrov Sergei , Nampuri Suresh 
Published: January 2021

Abstract
Extending recent results in $$ \mathcal{N} $$
N
= 2 string compactifications, we propose that the holomorphic anomaly equation satisfied by the modular completions of the generating functions of refined BPS indices has a universal structure independent of the number $$ \mathcal{N} $$
N
of supersymmetries. We show that this equation allows to recover all known results about modularity (under SL(2, ℤ) duality group) of BPS states in $$ \mathcal{N} $$
N
= 4 string theory. In particular, we reproduce the holomorphic anomaly characterizing the mock modular behavior of quarter-BPS dyons and generalize it to the case of non-trivial torsion invariant.