bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase II Randomized Trial of Rituximab Plus Cyclophosphamide Followed by Belimumab for the Treatment of Lupus Nephritis
Authors: Atisha‐Fregoso Yemil , Malkiel Susan , Harris Kristina M. , Byron Margie , Ding Linna , Kanaparthi Sai , Barry William T. , Gao Wendy , Ryker Kristin , Tosta Patti , Askanase Anca D. , Boackle Susan A. , Chatham W. Winn , Kamen Diane L. , Karp David R. , Kirou Kyriakos A. , Sam Lim S. , Marder Bradley , McMahon Maureen , Parikh Samir V. , Pendergraft William F. , Podoll Amber S. , Saxena Amit , Wofsy David , Diamond Betty , Smilek Dawn E. , Aranow Cynthia , Dall’Era Maria 
Published: August 2020

ObjectiveTo assess the safety, mechanism of action, and preliminary efficacy of rituximab followed by belimumab in the treatment of refractory lupus nephritis (LN).MethodsIn a multicenter, randomized, open‐label clinical trial, 43 patients with recurrent or refractory LN were treated with rituximab, cyclophosphamide (CYC), and glucocorticoids followed by weekly belimumab infusions until week 48 (RCB group), or treated with rituximab and CYC but no belimumab infusions (RC group). Patients were followed up until week 96. Percentages of total and autoreactive B cell subsets in the patients’ peripheral blood were analyzed by flow cytometry.ResultsTreatment with belimumab did not increase the incidence of adverse events in patients with refractory LN. At week 48, a complete or partial renal response occurred in 11 (52%) of 21 patients receiving belimumab, compared to 9 (41%) of 22 patients in the RC group who did not receive belimumab (P = 0.452). Lack of improvement in or worsening of LN was the major reason for treatment failure. B cell depletion occurred in both groups, but the percentage of B cells remained lower in those receiving belimumab (geometric mean number of B cells at week 60, 53 cells/μl in the RCB group versus 11 cells/μl in the RC group; P = 0.0012). Percentages of total and autoreactive transitional B cells increased from baseline to week 48 in both groups. However, percentages of total and autoreactive naive B cells decreased from baseline to week 48 in the belimumab group compared to the no belimumab RC group (P = 0.0349), a finding that is consistent with the observed impaired maturation of naive B cells and enhanced censoring of autoreactive B cells.ConclusionThe addition of belimumab to a treatment regimen with rituximab and CYC was safe in patients with refractory LN. This regimen diminished maturation of transitional to naive B cells during B cell reconstitution, and enhanced the negative selection of autoreactive B cells. Clinical efficacy was not improved with rituximab and CYC in combination with belimumab when compared to a therapeutic strategy of B cell depletion alone in patients with LN.
Residual disease after neoadjuvant chemoradiotherapy for oesophageal cancer: locations undetected by endoscopic biopsies in the preSANO trial
Authors: Wilk B J , Eyck B M , Doukas M , Spaander M C W , Schoon E J , Krishnadath K K , Oostenbrug L E , Lagarde S M , Wijnhoven B P L , Looijenga L H J , Biermann K , Lanschot J J B 
Published: August 2020

Abstract

Background
Active surveillance has been proposed for patients with oesophageal cancer in whom there is a complete clinical response after neoadjuvant chemoradiotherapy (nCRT). However, endoscopic biopsies have limited negative predictive value in detecting residual disease. This study determined the location of residual tumour following surgery to improve surveillance and endoscopic strategies.

Methods
The present study was based on patients who participated in the prospective preSANO trial with adenocarcinoma or squamous cell carcinoma of the oesophagus or oesophagogastric junction treated in four Dutch hospitals between 2013 and 2016. Resection specimens and endoscopic biopsies taken during clinical response evaluations after nCRT were reviewed by two expert gastrointestinal pathologists. The exact location of residual disease in the oesophageal wall was determined in resection specimens. Endoscopic biopsies were assessed for the presence of structures representing the submucosal layer of the oesophageal wall.

Results
In total, 119 eligible patients underwent clinical response evaluations after nCRT followed by standard surgery. Residual tumour was present in endoscopic biopsies from 70 patients, confirmed on histological analysis of the resected organ. Residual tumour was present in the resection specimen from 27 of the other 49 patients, despite endoscopic biopsies being negative. Of these 27 patients, residual tumour was located in the mucosa in 18, and in the submucosa beneath tumour-free mucosa in eight. One patient had tumour in muscle beneath tumour-free mucosa and submucosa.

Conclusion
Most residual disease after nCRT missed by endoscopic biopsies was located in the mucosa. Active surveillance could be improved by more sampling and considering submucosal biopsies.
Implementing the 3T‐approach for cervical cancer screening in Cameroon: Preliminary results on program performance
Authors: Levy Juliette , de Preux Marie , Kenfack Bruno , Sormani Jessica , Catarino Rosa , Tincho Eveline F. , Frund Chloé , Fouogue Jovanny T. , Vassilakos Pierre , Petignat Patrick 
Published: August 2020

AbstractOption recommended by World Health Organization (WHO) includes human papillomavirus (HPV) primary screening followed by visual inspection with acetic acid (VIA) triage. We implemented a program based on a 3T‐approach (Test‐Triage and Treat). Our objective was to verify the effectiveness of the program by defining a set of performance indices. A sensitization campaign was performed in Dschang (Cameroon) and women aged 30‐49 years were invited to participate for screening based on the 3T‐approach. Participants performed HPV self‐sampling (Self‐HPV), analyzed with the point‐of‐care Xpert HPV assay followed by VIA/VILI triage and treatment if required. Key performance indicators (KPIs) for screening, diagnosis, treatment and follow‐up were defined, and achievable targets were described for which the approach is likely to be running optimally. A total of 840 women with a mean age of 39.4±5.9 years participated. The KPIs included (i) the screening rate (8.4% at 7 months, target =20% at 12 months), (ii) HPV positivity rate (19.8%, expected range 18‐25%), (iii) compliance to referral to VIA/VILI and complete test (100%, target >90%), (iv) compliance to referral to thermal ablation (100%, target >90%), (v) VIA/VILI positivity rate (50.6%, expected range 45‐55%), (vi) a single visit from diagnostic to treatment (79.8%, target >80%), (vii) compliance to follow‐up at 1 month (96.4%, target >80%) and (viii) at 6 months (70.6%, target >80%). Program performance based on the single‐visit 3T‐approach corresponded to defined targets and preliminary results support adequateness of KPIs for periodic monitoring.
Circulating immune cell dynamics in patients with triple negative breast cancer treated with neoadjuvant chemotherapy
Authors: Talamantes Sarah , Xie Eric , Costa Ricardo L. B. , Chen Melissa , Rademaker Alfred , Santa‐Maria Cesar A. 
Published: August 2020

AbstractBackgroundLymphopenia has been associated with inferior cancer outcomes, but there is limited data in breast cancer. We describe the effects of neoadjuvant chemotherapy on circulating immune cells and its association with pathological complete response (pCR) rates in triple negative breast cancer (TNBC).MethodsWe constructed a database of patients with early stage TNBC treated with neoadjuvant chemotherapy. Circulating lymphocytes and monocytes were assessed before and after neoadjuvant chemotherapy. These were correlated with pCR rates and disease‐free survival (DFS) using Fisher's exact test, logistic regression, and the log‐rank test.ResultsFrom 2000 to 2015, we identified 95 eligible patients. Median age was 50; 29 (31%) were treated with platinum‐containing chemotherapy; and 66 (69%) with nonplatinum‐containing chemotherapy (anthracycline‐taxane, or either alone). About 32 (34%) patients achieved a pCR; and 33 (35%) had recurrence events. Median follow‐up time was 47 months. No significant associations were found between changes in lymphocytes and pCR or DFS. There was a correlation between lower monocyte levels after neoadjuvant chemotherapy and pCR (mean monocyte 0.56 in those with no‐pCR vs 0.46 in those with pCR, P = .049, multivariate P = .078) and DFS (median DFS in highest monocyte quartile was 30 vs 107 months in lowest quartile, P = .022, multivariate P = .023). In patients who received nonplatinum regimens, DFS was better among those who had larger decreases in monocytes.ConclusionsDevelopment of lymphopenia from neoadjuvant chemotherapy was not associated with pCR in patients with TNBC. However, lower absolute circulating monocytes after neoadjuvant chemotherapy was associated with improved outcomes.
Development of Gene‐Targeted Polypyridyl Triplex‐Forming Oligonucleotide Hybrids
Authors: Zuin Fantoni Nicolò , McGorman Bríonna , Molphy Zara , Singleton Daniel , Walsh Sarah , El‐Sagheer Afaf H. , McKee Vickie , Brown Tom , Kellett Andrew 
Published: August 2020

AbstractIn the field of nucleic acid therapy there is major interest in the development of libraries of DNA‐reactive small molecules which are tethered to vectors that recognize and bind specific genes. This approach mimics enzymatic gene editors, such as ZFNs, TALENs and CRISPR‐Cas, but overcomes the limitations imposed by the delivery of a large protein endonuclease which is required for DNA cleavage. Here, we introduce a chemistry‐based DNA‐cleavage system comprising an artificial metallo‐nuclease (AMN) that oxidatively cuts DNA, and a triplex‐forming oligonucleotide (TFO) that sequence‐specifically recognises duplex DNA. The AMN‐TFO hybrids coordinate CuII ions to form chimeric catalytic complexes that are programmable – based on the TFO sequence employed – to bind and cut specific DNA sequences. Use of the alkyne‐azide cycloaddition click reaction allows scalable and high‐throughput generation of hybrid libraries that can be tuned for specific reactivity and gene‐of‐interest knockout. As a first approach, we demonstrate targeted cleavage of purine‐rich sequences, optimisation of the hybrid system to enhance stability, and discrimination between target and off‐target sequences. Our results highlight the potential of this approach where the cutting unit, which mimics the endonuclease cleavage machinery, is directly bound to a TFO guide by click chemistry.
Recent Perspectives on Rearrangement Reactions of Ylides via Carbene Transfer Reactions
Authors: Jana Sripati , Guo Yujing , Koenigs Rene M. 
Published: August 2020

AbstractAmong the available methods to increase the molecular complexity, sigmatropic rearrangements occupy a distinct position in organic synthesis. Despite being known for over a century sigmatropic rearrangement reactions of ylides via carbene transfer reaction have only recently come of age. Most of the ylide mediated rearrangement processes involve rupture of a σ‐bond and formation of a new bond between π‐bond and negatively charged atom followed by simultaneous redistribution of π‐electrons. This minireview describes the advances in this research area made in recent years, which now opens up metal‐catalyzed enantioselective sigmatropic rearrangement reactions, metal‐free photochemical rearrangement reactions and novel reaction pathways that can be accessed via ylide intermediates.
Crucial Role of Water in the Mechanosynthesis of CsPbI3 and Other ABX3 Halides
Authors: Tsvetkov Dmitry , Mazurin Maksim , Ivanov Ivan , Malyshkin Dmitry , Sereda Vladimir , Zuev Andrey 
Published: August 2020

AbstractMechanochemical synthesis of CsPbI3, as a model system for ABX3 halides, was studied. Water was shown to strongly promote the kinetics of formation of CsPbI3 from the CsI+PbI2 mixture through increased mobility of the constituting ionic species. Since many binary and ternary halides are hygroscopic, it was concluded that the presence of small, uncontrollable and unintentional additions of water should often occur in both precursor mixtures and synthesized complex halides boosting the kinetics of formation of many, if not all, ternary organic–inorganic hybrid halides such as, for example, MAPbX3 (X=Cl, Br, I). In addition, trace amounts of water should influence the transport characteristics of complex halides. Thus, the presence of water explains, at least partially, the huge scatter in both the reported mechanochemical reaction times necessary for obtaining single‐phase APbX3 perovskite halides and the activation energies of ionic diffusion in APbX3.
Application of Reclaimed Sodium Polyacrylate to Increase Soil Water Retention
Authors: Khodadadi Dehkordi Davoud , Shamsnia Seyed Amir 
Published: August 2020

AbstractThe aim of this study is to investigate the impacts of salt denseness, temperature, and pH on swelling capability and the water retention capability in loam soil treated by reclaimed hydrogel. In swelling dynamic and deswelling dynamic tests, a sample of reclaimed hydrogel (0.15 g) is applied. The bag (with polymer) is drowned in 110 mL distilled water in a vessel at lab temperature. For evaluating deswelling dynamic, the swollen superabsorbent polymer (after obtaining balance swelling) is set in a vessel in lab conditions. The influence of temperature is evaluated by conducting dynamic tests at 70 °C. The influence of pH on swelling capability is evaluated by providing solutions with different pH values. The results show that the reclaimed hydrogel has a large capability to take up and store moisture and is suitable in agricultural utilization. It is technically feasible to increase the water retention capability of soil, and therefore reduce irrigation cost. Moreover, the swelling capability rises with temperature, while it declines with the rise in salt or pH denseness. The results indicate that sodium polyacrylate achieved from used diapers can be reclaimed and applied as a moisture absorbing substance in agriculture for a superior irrigation administration.
Association between circulating tumor DNA burden and disease burden in patients with ALK‐positive lung cancer
Authors: Zhang Eric W. , Dagogo‐Jack Ibiayi , Kuo Anderson , Rooney Marguerite M. , Shaw Alice T. , Digumarthy Subba R. 
Published: August 2020

BackgroundPlasma genotyping is an emerging approach for the identification of genetic alterations mediating resistance to anaplastic lymphoma kinase (ALK)–targeted therapy. The authors reviewed plasma genotyping and imaging findings to assess the correlation between circulating tumor DNA (ctDNA) burden and disease burden in patients with ALK‐positive lung cancer.MethodsThe authors analyzed 97 plasma specimens from 75 patients with ALK‐positive lung cancer to identify ALK and non‐ALK alterations. Disease burden was estimated by tabulating lesions per organ and calculating lesion diameters, areas, and volumes. Disease burden was correlated with the allelic frequency (AF) of plasma alterations.ResultsThe mean interval between plasma collection and imaging was 8 days. ctDNA was detected in approximately 85% of plasma specimens. An ALK fusion and ALK mutation were detected in 79% and 76%, respectively, of plasma specimens. Using the maximum plasma alteration AF and maximum ALK alteration AF as independent surrogates of ctDNA burden, a higher disease burden measurement on imaging was found to be associated with higher ctDNA burden. Total body and extrathoracic tumor volume but not intrathoracic tumor volume correlated with ctDNA burden. Of all the disease sites assessed, the ctDNA burden correlated most with involvement of the liver, bones, and adrenal glands. Despite being the defining alteration in ALK‐positive lung cancer, isolated plasma ALK fusion AF did not perform as well as the maximum plasma alteration AF or maximum ALK alteration AF for correlating tumor burden.ConclusionsIn patients with ALK‐positive lung cancer, the maximum plasma alteration AF and maximum ALK alteration AF correlate with the extrathoracic burden of disease and are more predictive of tumor burden compared with the ALK fusion AF alone.Lay Summary

Analysis of genetic material shed from cancer cells into the circulation offers insights into the molecular composition of tumors. The circulating tumor DNA (ctDNA) varies over time and across individuals and is impacted by the distribution of disease.

Herein, the authors estimated tumor burden on imaging and correlated it with ctDNA by calculating the maximum allelic frequency.

The current study findings demonstrated that the greatest correlation exists between extrathoracic, extracranial tumor burden (particularly involvement of the liver, adrenal glands, or bones) and ctDNA burden, suggesting a biological basis for the interpatient and temporal intrapatient differences in ctDNA yield that have been described in previous studies.
A multiview approach based on naming behavioral modeling for aligning chinese user accounts across multiple networks
Authors: Zhu Junxing , Wang Xiang , Liu Qiang , Li Xiaoyong , Shao Chengcheng , Zhou Bin 
Published: August 2020

SummaryHundreds of millions of Chinese people have become social network users in recent years, and aligning the accounts of common Chinese users across multiple social networks is valuable to many inter‐network applications, for example, cross‐network recommendation and cross‐network link prediction. Many methods have explored the proper ways of utilizing account name information into aligning the common English users' accounts. However, how to properly utilize the account name information when aligning the Chinese user accounts remains to be detailedly studied. In this article, we first discuss the available naming behavioral models as well as the related features for different types of Chinese account name matchings. Second, we propose the framework of Multi‐View Cross‐Network User Alignment (MCUA) method, which uses a multi‐view framework to creatively integrate different models to deal with different types of Chinese account name matchings, and can consider all of the studied features when aligning the Chinese user accounts. Finally, we conduct experiments to prove that MCUA can outperform many existing methods on aligning Chinese user accounts between Sina Weibo and Twitter. Besides, we also study the best learning models and the top‐k valuable features of different types of name matchings for MCUA over our experimental datasets.
In Vitro Assays to Study PD‐1 Biology in Human T Cells
Authors: Tocheva Anna S. , Lerrer Shalom , Mor Adam 
Published: August 2020

AbstractOur understanding of programmed cell death 1 (PD‐1) biology is limited due to technical difficulties in establishing reproducible, yet simple, in vitro assays to study PD‐1 signaling in primary human T cells. The protocols in this article were refined to test the consequences of PD‐1 ligation on short‐term T cell signaling, long‐term T cell function, and the structural consequences of PD‐1 ligation with PD‐1 ligands. Basic Protocol 1 addresses the need for a robust and reproducible short‐term assay to examine the signaling cascade triggered by PD‐1. We describe a phospho flow cytometry method to determine how PD‐1 ligation alters the level of CD3ζ phosphorylation on Tyr142, which can be easily applied to other proximal signaling proteins. Basic Protocol 2 describes a plate‐bound assay that is useful to examine the long‐term consequences of PD‐1 ligation such as cytokine production and T cell proliferation. Complementary to that, Basic Protocol 3 describes an in vitro superantigen‐based assay to evaluate T cell responses to therapeutic agents targeting the PD‐1/PD‐L axis, as well as immune synapse formation in the presence of PD‐1 engagement. Finally, in Basic Protocol 4 we outline a tetramer‐based method useful to interrogate the quality of PD‐1/PD‐L interactions. These protocols can be easily adapted for mouse studies and other inhibitory receptors. They provide a valuable resource to investigate PD‐1 signaling in T cells and the functional consequences of various PD‐1‐based therapeutics on T cell responses. © 2020 Wiley Periodicals LLC.Basic Protocol 1: PD‐1 crosslinking assay to determine CD3ζ phosphorylation in primary human T cellsBasic Protocol 2: Plate‐based ligand binding assay to study PD‐1 function in human T cellsSupport Protocol 1: T cell proliferation assay in the presence of PD‐1 ligationBasic Protocol 3: In vitro APC/T cell co‐culture system to evaluate therapeutic interventions targeting the PD‐1/PD‐L1 axisSupport Protocol 2: Microscopy‐based approach to evaluate the consequences of PD‐1 ligation on immune synapse formationBasic Protocol 4: Tetramer‐based approach to study PD‐1/PD‐L1 interactions
Boost Selectivity of HCOO−Using Anchored Bi Single Atoms towards CO2Reduction
Authors: Yang Xupeng , Chen Yuliang , Qin Lang , Wu Xiaonan , Wu Yuting , Yan Tao , Geng Zhigang , Zeng Jie 
Published: August 2020

AbstractSingle atoms have been widely applied as efficient catalysts in various catalytic systems due to its high selectivity for certain products, which is induced by a uniform coordinate environment of active sites. Herein, it is demonstrated that Bi single atoms anchored on carbon black (Bi SAs/C) can serve as an efficient catalyst for CO2electroreduction into formate (HCOO−). During CO2electroreduction, Bi SAs/C achieved a faradaic efficiency for HCOO−of 83.6 % at−1.1 Vversus reversible hydrogen electrode (V vs. RHE). Notably, the selectivity for HCOO−of Bi SAs/C was always higher than 95 % at all applied potentials. In addition, at−1.2 Vvs.RHE, the current density for HCOO−formation in thepresence of Bi SAs/C reached−12.0 mA cm−2, which was 3.4 times as high as that (−3.5 mA cm−2) of BiOxclusters on carbon black (BiOx/C). Mechanistic studies revealed that Bi SAs/C facilitated the faradaic process and accelerated reaction kinetics in comparison with BiOx/C.
Smoking and COVID‐19: Similar bronchial ACE2 and TMPRSS2 expression and higher TMPRSS4 expression in current versus never smokers
Authors: Voinsky Irena , Gurwitz David 
Published: August 2020

AbstractUncertainties remain concerning the pathophysiology, epidemiology, and potential therapeutics for COVID‐19. Among unsettled controversies is whether tobacco smoking increases or protects from severe COVID‐19. Several epidemiological studies reported reduced COVID‐19 hospitalizations among smokers, while other studies reported the opposite trend. Some authors assumed that smokers have elevated airway expression of ACE2, the cell recognition site of the SARS‐Cov‐2 spike protein, but this suggestion remains unverified. We therefore performed data mining of two independent NCBI GEO genome‐wide RNA expression files (GSE7894 and GSE994) and report that in both data sets, current smokers and never smokers have, on average, closely similar bronchial epithelial cell mRNA levels of ACE2, as well as TMPRSS2, coding for a serine protease priming SARS‐Cov‐2 for cell entry, and ADAM17, coding for a protease implicated in ACE2 membrane shedding. In contrast, the expression levels of TMPRSS4, coding for a protease that primes SARS‐CoV‐2 for cell entry similarly to TMPRSS2, were elevated in bronchial epithelial cells from current smokers compared with never smokers, suggesting that higher bronchial TMPRSS4 levels in smokers might put them at higher SARS‐Cov‐2 infection risk. The effects of smoking on COVID‐19 severity need clarification with larger studies. Additionally, the postulated protective effects of nicotine and nitric oxide, which may presumably reduce the risk of a “cytokine storm” in infected individuals, deserve assessment by controlled clinical trials.