bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of chemotherapy after anti‐PD‐1 blockade failure for relapsed and refractory Hodgkin lymphoma
Authors: Casadei Beatrice , Argnani Lisa , Morigi Alice , Lolli Ginevra , Broccoli Alessandro , Pellegrini Cinzia , Nanni Laura , Stefoni Vittorio , Coppola Paolo E. , Carella Matteo , Cavo Michele , Zinzani Pier Luigi 
Published: September 2020

AbstractProgrammed death‐1 (PD1) blockade is an efficient and safe therapeutic option in patients with relapsed/refractory (R/R) classical Hodgkin lymphoma (cHL). However, a substantial proportion of patients’ progresses or loses the response to anti‐PD1 treatment. We retrospectively investigated the effectiveness of salvage chemotherapies (CHT) for unsatisfactory response to anti‐PD1, in 25 R/R cHL patients. Twenty‐three patients (92%) were refractory to the last treatment before anti‐PD1. After a median of 14 cycles (range 3‐52), 68% (17/25) of patients had unsatisfactory responses to anti‐PD1 therapy, whereas 6 had a partial response (PR) and 2 patients achieved complete response (CR), with an overall response rate (ORR) of 32%. After a median time of 1.5 months, 15 patients received a single agent treatment and 10 had a multi‐agents regimen, due to the failure of PD1 blockade. The ORR was 60% (8 CR and 7 PR). Seven patients (3 in PR and 4 in CR) underwent a consolidation strategy with stem cell transplantation. Median progression‐free survival (PFS) with salvage treatment was reached at 19.1 months, while median PFS after anti‐PD1 has been reached at 8.2 months. After a median follow‐up of 32.4 months, 6 patients died while 13 are still in CR. The median overall estimated from the start of CHT was not reached. The efficacy of treatment following anti‐PD1 is not yet established, especially in lymphoma patients. To note, in our series, a subset of heavily pre‐treated and chemo‐refractory patients increased response rates to and survival with CHT given after exposure to immune‐checkpoint inhibitors.
Health‐related quality of life of patients with multiple myeloma: A real‐world study in China
Authors: Li Xiaozhe , Liu Junru , Chen Meilan , Gu Jingli , Huang Beihui , Zheng Dong , Li Juan 
Published: September 2020

AbstractPurposeThis study aimed to assess the health‐related quality of life (HRQOL) of Chinese patients with different stages of multiple myeloma (MM) who received various treatments and identify the factors associated with a lower quality of life in China.MethodsA cross‐sectional, anonymous questionnaire was distributed to adults with MM. The measures of quality of life included the European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ)‐C30, QLQ‐myeloma‐specific module 20 (MY20), and EuroQoL EQ‐5D. The data, including patient factors, difficulties experienced during the diagnosis and treatment processes, psychosocial factors and disease‐ or treatment‐related effects, were collected.ResultsFour hundred and thirty patients with MM were recruited from all 27 provinces of China, and their average age was 55.7 years. Many variables were significantly associated with the HRQOL of the patients with MM. In the multivariate analyses, performance status, psychosocial factors, disease phase, and an early diagnosis were significantly associated with the HRQOL. In the subgroup analysis, the HRQOL of the patients who underwent autologous stem cell transplantation (ASCT) was significantly higher than that of the non‐ASCT patients. Treatment‐related toxicities had a significant impact on the quality of life of the patients with MM, and 91.5% of the patients intended to stop the maintenance treatment.ConclusionsThe quality of life of patients with MM in China is affected by patient factors, difficulties experienced during the diagnosis and treatment processes, psychosocial factors, and disease‐ or treatment‐related effects. Efforts should be exerted to improve the overall quality of life of these patients in China.
A mediation analysis to explain socio‐economic differences in bladder cancer survival
Authors: Russell Beth , Hemelrijck Mieke V. , Gårdmark Truls , Holmberg Lars , Kumar Pardeep , Bellavia Andrea , Häggström Christel 
Published: September 2020

AbstractIntroductionThis study aims to disentangle heterogeneity in the survival of bladder cancer (BC) patients of different socioeconomic status (SES) by identifying potential mediators of the relationship.MethodsThe Bladder Cancer Database Sweden (BladderBaSe) was used to select patients diagnosed between 1997 and 2014 with Tis/Ta‐T4 disease. The education level was used as a proxy for SES. Accelerated failure time models were used to investigate the association between SES and survival. Mediation analysis was used to investigate potential mediators of the association also accounting for interaction.ResultsThe study included 37 755 patients from the BladderBaSe. Patients diagnosed with both non‐muscle invasive bladder cancer (NMIBC) and muscle‐invasive bladder cancer (MIBC) who had high SES were found to have increased overall and BC‐specific survival, when compared to those with low SES. In the NMIBC patients, Charlson Comorbidity Index was found to mediate this relationship by 10% (percentage of the total effect explained by the mediator) and hospital type by 4%. The time from referral to TURBT was a considerable mediator (14%) in the MIBC patients only.ConclusionsMediation analysis suggests that the association between SES and BC survival can be explained by several factors. The mediators identified were not, however, able to fully explain the theoretical causal pathway between SES and survival, therefore, future studies should also include the investigation of other possible mediators to help explain this relationship further. These results highlight the importance of standardization of clinical care across SES groups.
Real‐time suturing simulation for virtual reality medical training
Authors: Yu Peng , Pan Junjun , Qin Hong , Hao Aimin , Wang Haipeng 
Published: September 2020

AbstractAt present, virtual reality (VR) ‐based medical simulators provide an efficient and cost‐effective alternative without exposing risk to the traditional training approaches. As an essential and indispensable task in fundamental surgical skills training, the research of suturing simulation still remains insufficient in the field of virtual surgery. In this paper, we present a real‐time suturing simulation framework which can handle the complex interactions between surgical instruments and soft tissue. The simulation consists of two stages: external interaction and internal coupling. External interaction involves the interplay between needle/suture and the soft tissue, which are both deformed by position‐based dynamics (PBD) with different constraints. At the internal coupling stage, once the force exceeds a threshold, the needle tip will puncture and penetrate into the soft tissue and generate a path. To guarantee the needle/suture accurately following the path inside the soft tissue, we propose a novel coupling method by matching and generating the constraints among needle, suture, and penetration path. We have applied this suturing simulation into a VR laparoscopic surgery simulator with haptic force. Our experimental results demonstrate that our approach can achieve real‐time performance with a high degree of visual realism and haptic fidelity.
Resolving hand‐object occlusion for mixed reality with joint deep learning and model optimization
Authors: Feng Qi , Shum Hubert P. H. , Morishima Shigeo 
Published: September 2020

AbstractBy overlaying virtual imagery onto the real world, mixed reality facilitates diverse applications and has drawn increasing attention. Enhancing physical in‐hand objects with a virtual appearance is a key component for many applications that require users to interact with tools such as surgery simulations. However, due to complex hand articulations and severe hand‐object occlusions, resolving occlusions in hand‐object interactions is a challenging topic. Traditional tracking‐based approaches are limited by strong ambiguities from occlusions and changing shapes, while reconstruction‐based methods show a poor capability of handling dynamic scenes. In this article, we propose a novel real‐time optimization system to resolve hand‐object occlusions by spatially reconstructing the scene with estimated hand joints and masks. To acquire accurate results, we propose a joint learning process that shares information between two models and jointly estimates hand poses and semantic segmentation. To facilitate the joint learning system and improve its accuracy under occlusions, we propose an occlusion‐aware RGB‐D hand data set that mitigates the ambiguity through precise annotations and photorealistic appearance. Evaluations show more consistent overlays compared with literature, and a user study verifies a more realistic experience.
Ovarian cancer derived PKR1 positive exosomes promote angiogenesis by promoting migration and tube formation in vitro
Authors: Zhang XiaoYan , Sheng YouMing , Li BingWei , Wang Qin , Liu XueTing , Han JianQun 
Published: September 2020

Cancer cell derived exosomes play important roles in cancer progression and modulation of the tumour microenvironment. This study aims to investigate the role of prokineticin receptor 1 (PKR1) positive exosomes on angiogenesis. In the present study, PKR1 expression in tumour samples from ovarian cancer patients were examined firstly. Then, two ovarian cancer cell lines, namely A2780 and HO‐8910 cells, were used to isolate and obtain the PKR1 positive exosomes from the serum free medium. The function analysis of PKR1 positive exosomes on angiogenesis was conducted by cell proliferation and migration assay, tube formation analysis, and tumour volume assay. The results showed that PKR1 expression was down regulated in tumour samples of ovarian cancer patients compared with adjacent normal tissues. The intracellular expression of PKR1 could be detected in A2780 and HO‐8910 cells. And, the isolated exosomes from the serum free medium were confirmed by transmission electron microscopic and NTA analysis, as well as the co‐presence of PKR1 with exosome marker CD63. The function analysis of PKR1 positive exosomes on angiogenesis demonstrated the uptake of PKR1 positive exosomes by human umbilical vein endothelial cells through immunofluorescence staining. The angiogenesis assays in vitro indicated that PKR1 positive exosomes promoted migration and tube formation of HUVECs but not proliferation. The endogenous PKR1 was also verified to help to enhance migration and promote tube formation of vascular endothelial cells, which might involved in the phosphorylation of STAT3. Additionally, The tumour volume from exosomes treated A2780 tumour‐bearing mice was significantly increased compared with the control group, accompanied with the induced PKR1 expression and phosphorylation of STAT3 level.Significance of the StudyThis study proved the important role of PKR1 positive exosomes released from ovarian cancer cells on promoting angiogenesis. The data indicated that PKR1 derived from ovarian cancer cells could act as an important tumour associated antigen and biomolecular factor for cellular communication in tumour microenvironment.
The “Carbonyl Story” and Beyond; Experiences, Lessons and Implications
Authors: Alberto Roger 
Published: September 2020

AbstractThe complex [99mTc(OH2)3(CO)3]+ has become a versatile building block in radiopharmaceutical chemistry, applied by many groups worldwide. However, despite widespread efforts, only one compound has made it right the way through clinical trials. Along the way from its discovery to its development into an eventual product, the author experienced issues that he would handle differently in retrospect. In this article, these experiences are turned into “lessons” that might be helpful for young researchers finding themselves in similar situations. Beside issues with patenting and company strategies, the carbonyl story has provided scientific implications beyond its own story, and insights from which any future 99mTc‐based chemistry for radiopharmacy or molecular imaging might benefit.
Structural Cues for Understanding eEF1A2 Moonlighting
Authors: Carriles Alejandra A. , Mills Alberto , Muñoz‐Alonso María‐José , Gutiérrez Dolores , Domínguez Juan M. , Hermoso Juan A. , Gago Federico 
Published: September 2020

AbstractSpontaneous mutations in the EEF1A2 gene cause epilepsy and severe neurological disabilities in children. The crystal structure of eEF1A2 protein purified from rabbit skeletal muscle reveals a post‐translationally modified dimer that provides information about the sites of interaction with numerous binding partners, including itself, and maps these mutations onto the dimer and tetramer interfaces. The spatial locations of the side chain carboxylates of Glu301 and Glu374, to which phosphatidylethanolamine is uniquely attached via an amide bond, define the anchoring points of eEF1A2 to cellular membranes and interorganellar membrane contact sites. Additional bioinformatic and molecular modeling results provide novel structural insight into the demonstrated binding of eEF1A2 to SH3 domains, the common MAPK docking groove, filamentous actin, and phosphatidylinositol‐4 kinase IIIβ. In this new light, the role of eEF1A2 as an ancient, multifaceted, and articulated G protein at the crossroads of autophagy, oncogenesis and viral replication appears very distant from the “canonical” one of delivering aminoacyl‐tRNAs to the ribosome that has dominated the scene and much of the thinking for many decades.
The protective effects of umbilical cord‐derived endothelial colony forming cells on hepatic veno‐occlusive disease
Authors: Chen Lulu , Zhang Jingjing , Liu Xin , Yao Mingkang , Zhang Hao 
Published: September 2020

AbstractHepatic veno‐occlusive disease (HVOD) characterized by endothelial cell dysfunction is one of the serious complications after hematopoietic stem‐cell transplantation or chemotherapeutic drug application. The mortality of HVOD patients with multiorgan dysfunction is as high as 80%. The primary aim of this study was to evaluate whether the infusion of human umbilical cord‐derived endothelial colony forming cells (hUC‐ECFCs) could mitigate HVOD injury and investigate the underlying mechanism. We found that the expression of chemokine C–X–C chemokine ligand 12 (CXCL12) was markedly increased in the livers of HVOD mice. Meanwhile, hUC‐ECFCs infusion could significantly ameliorate liver injury in HVOD mice, which was accompanied by hUC‐ECFCs recruitment in the liver, reduced liver pathological alterations, and decreased serum alanine aminotransferase and aspartate aminotransferase activity. Besides, CXCL12‐induced migration in hUC‐ECFCs was partly impeded by chemokine receptor type 7 (CXCR7) silence or CXCR4 blockage. In conclusion, our results demonstrated that hUC‐ECFCs could mitigate HVOD through homing to the injured liver via the CXCL12‐CXCR4/CXCR7 signaling pathway.
Phenotypic drift in metastatic progression of breast cancer: A case report with histologically heterogeneous lesions that are clonally related
Authors: Kutasovic Jamie R. , McCart Reed Amy E. , Sokolova Anna , Jayanthan Janani , Da Silva Leonard , Simpson Peter T. , Lakhani Sunil R. 
Published: September 2020

AbstractBreast cancer metastasis to the stomach is rare; invasive lobular carcinoma has a predilection to spread to the gastrointestinal system and is morphologically similar to primary diffuse gastric carcinoma. This case highlights heterogeneous metastatic progression and that documentation of heterogeneity is important for informing future treatment strategies and prognostication.
Cyclic Peptides as Drugs for Intracellular Targets: The Next Frontier in Peptide Therapeutic Development
Authors: Buckton Laura K. , Rahimi Marwa N. , McAlpine Shelli R. 
Published: September 2020

AbstractDeveloping macrocyclic peptides that can reach intracellular targets is a significant challenge. This review discusses the most recent strategies used to develop cell permeable cyclic peptides that maintain binding to their biological target inside the cell. Macrocyclic peptides are unique from small molecules because traditional calculated physical properties are unsuccessful for predicting cell membrane permeability. Peptide synthesis and experimental membrane permeability is the only strategy that effectively differentiates between cell permeable and cell impermeable molecules. Discussed are chemical strategies, including backbone N‐methylation and stereochemical changes, which have produced molecular scaffolds with improved cell permeability. However, these improvements often come at the expense of biological activity as chemical modifications alter the peptide conformation, frequently impacting the compound's ability to bind to the target. Highlighted is the most promising approach, which involves side‐chain alterations that improve cell permeability without impact binding events.
A Simple Method for Synthesizing Highly Active Amorphous Iridium Oxide for Oxygen Evolution under Acidic Conditions
Authors: Salimi Payam , Najafpour Mohammad Mahdi 
Published: September 2020

AbstractWater splitting for hydrogen production has been recognized as a promising approach to store sustainable energy. The performance of this method is limited by the oxygen‐evolution reaction. Herein, an approach for synthesizing a highly active oxygen‐evolving catalyst by a one‐step, low‐cost, environmentally friendly, and easy‐to‐perform method is presented, which works by using iridium metal as the anode at a relatively high potential. The obtained IrOx/Ir interface showed an overpotential of 250 mV at 10 mA cm−2 in 0.1 m HClO4 and remained stable under electrochemical conditions. The IrOx that was mechanically separated from the surface of IrOx/Ir metal after operation showed a threefold increase in activity compared to the current benchmark IrO2 catalyst. Various characterization analyses were used to identify the structure and morphology of the catalyst, which suggested nanosized, porous, and amorphous IrOx on the surface of metallic Ir. This synthetic approach can inspire a variety of opportunities to design and synthesize efficient metal oxide‐based electrocatalysts for sustainable energy conversion and utilization.
Phosphorescent Trinuclear Pt–Ir–Pt Complexes: Insights into the Photophysical and Electrochemical Properties and Interaction with Guanine Nucleobase
Authors: Das Bishnu , Borah Sakira Tabbasum , Ganguli Sagar , Gupta Parna 
Published: September 2020

AbstractIn this study we have analysed the comparative photophysical and electrochemical properties of two isomeric heterotrinuclear PtII–IrIII–PtII complexes 3 and 6 and the four corresponding intermediate isomeric homonuclear cyclometalated iridium(III) complexes 1, 2, 4 and 5. The isomerisation originates from positional differences in the formyl, di‐2‐picolylamine and Pt–di‐2‐picolylamine moieties appended to cyclometalated or ancillary ligands. The interaction of 5′‐GMP with the trinuclear complexes 3 and 6 shows that platinum centres appended to the cyclometalated ligand in 3 facilitate the binding of two 5′‐GMP units per PtII centre in preference to a single 5′‐GMP unit per PtII centre as observed in 6. The 1:2 and 1:1 PtII–5′‐GMP binding patterns probably arise from the convenient arrangements of the Pt–di‐2‐picolylamine units in different planes in complex 3, which is absent in complex 6.
Electrochemical Reduction of CO2 at Coinage Metal Nanodendrites in Aqueous Ethanolamine
Authors: Hossain M. Nur , Ahmad Syed , da Silva Iranaldo Santos , Kraatz Heinz‐Bernhard 
Published: September 2020

AbstractElectrocatalytic reduction of CO2 into usable chemicals is a promising path to address climate change and energy challenges. Herein, we demonstrate the synthesis of unique coinage metal (Cu, Ag, and Au) nanodendrites (NDs) via a facile galvanic replacement reaction (GRR), which can be effective electrocatalysts for the reduction of CO2 in an ethanolamine (EA) solution. Each metal ND surface was directly grown on glassy‐carbon (GC) substrates from a mixture of Zn dust and the respective precursor solution. The electrocatalytic activities of the synthesized ND surfaces were optimized for CO2 reduction in EA solution by varying their composition. It was determined that a 0.05 mol fraction of EA exhibited the highest catalytic activity for all metal NDs. Linear sweep voltammetry (LSV) and electrochemical impedance spectroscopy (EIS) techniques showed that metal‐ND electrodes possessed higher current densities, lower onset potentials and lower charge‐transfer resistances for CO2 reduction than their smooth polycrystalline electrode counterparts, indicating improved CO2 reduction catalytic activity. It was determined, using FTIR and NMR spectroscopy, that formate was produced as a result of the CO2 reduction.
Cyclic Bis‐alkylidene Complexes of Titanium and Zirconium: Synthesis, Characterization, and Reaction
Authors: Zhang Yongliang , Wu Botao , Zhong Mingdong , Zhang Wen‐Xiong , Xi Zhenfeng 
Published: September 2020

AbstractTransition‐metal alkylidenes have exhibited wide applications in organometallic chemistry and synthetic organic chemistry, however, cyclic Schrock‐carbene‐like bis‐alkylidenes of group 4 metals with a four‐electron donor from an alkylidene have not been reported. Herein, the synthesis and characterization of five‐membered cyclic bis‐alkylidenes of titanium (4 a,b) and zirconium (5 a,b) are reported, as the first well‐defined group 4 metallacyclopentatrienes, by two‐electron reduction of their corresponding titana‐ and zirconacyclopentadienes. DFT analyses of4 ashow a four‐electron donor (σ‐donation and π‐donation) from an alkylidene carbon to the metal center. The reaction of4 awithN,N′‐diisopropylcarbodiimide (DIC) leads to the [2+2]‐cycloaddition product 6. Compound4 areacted with CO, affording the oxycyclopentadienyl titanium complex 7. These reactivities demonstrate the multiple metal–carbon bond character. The reactions of4 aor5 awith cyclooctatetraene (COT) or azobenzene afforded sandwich titanium complex 8or diphenylhydrazine‐coordinated zirconacyclopentadiene9, respectively, which exhibit two‐electron reductive ability.
A Stable Primary Phosphane Oxide and Its Heavier Congeners
Authors: Horký Filip , Císařová Ivana , Štěpnička Petr 
Published: September 2020

Abstract(Ferrocenylmethyl)phosphane (1) oxidation with hydrogen peroxide, elemental sulfur and grey selenium produced (ferrocenylmethyl)phosphane oxide 1O, sulfide 1S and selenide 1Se, respectively, as the first isolable primary phosphane chalcogenides lacking steric protection. At elevated temperatures, compound 1O disproportionated into 1 and (ferrocenylmethyl)phosphinic acid. In reactions with [(η6‐mes)RuCl2]2, 1O underwent tautomerization into a phosphane complex [(η6‐mes)RuCl2{FcCH2PH(OH)‐κP}], whereas 1S and 1Se lost their P‐bound chalcogen atoms, giving rise to the phosphane complex [(η6‐mes)RuCl2(FcCH2PH2‐κP)] (Fc=ferrocenyl, mes=mesitylene). No tautomerization was observed in the reaction of 1O with B(C6F5)3, which instead produced a Lewis pair FcCH2P(O)H2‐B(C6F5)3. Phosphane oxide 1O added to C=O bonds of aldehydes and ketones and even to cumulenes PhNCE (E=O and S). However, both PH hydrogens were only employed in the reactions with aldehydes and cyanates.