bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluating the efficacy of a priming dose of cyclophosphamide prior to pembrolizumab to treat metastatic triple negative breast cancer
Authors: Anders Carey K , Woodcock Mark G , Van Swearingen Amanda E D , Moore Dominic T , Sambade Maria J , Laurie Sonia , Robeson Alexander , Kolupaev Oleg , Cuaboy Luz A , Garrett Amy L , McKinnon Karen , Cowens Kristen , Bortone Dante , Calhoun Benjamin C , Wilkinson Alec D , Carey Lisa , Jolly Trevor , Muss Hyman , Reeder-Hayes Katherine , Kaltman Rebecca , Jankowitz Rachel , Gudena Vinay , Olajide Oludamilola , Perou Charles , Dees E Claire , Vincent Benjamin G , Serody Jonathan S 
Published: February 2022

PurposeTriple negative breast cancer (TNBC) is characterized by the presence of immune cells in the tumor microenvironment, however, the response to single-agent immune checkpoint inhibitor (ICI) therapy is modest. Preclinical models have demonstrated that intratumoral regulatory T cells (Tregs) dampen the antitumor response to ICI. We performed a single-arm phase II trial to evaluate the efficacy of a single low dose of cyclophosphamide (Cy) to deplete Tregsadministered before initiating pembrolizumab.Patients and methods40 patients with pretreated metastatic TNBC were enrolled. The primary endpoints were progression-free survival (PFS) and change in peripheral blood Tregsafter Cy. Secondary endpoints included overall response rate (ORR), duration of response, overall survival, treatment-related adverse events (AEs), and correlative evaluations.ResultsMedian PFS was 1.8 months, and the ORR was 21%. Tregswere not significantly decreased after Cy prior to ICI (−3.3%, p=0.19), and increased significantly after the first cycle of therapy (+21% between cycles 1 and 2, p=0.005). Immune-related AEs were similar to historical pembrolizumab monotherapy, and were associated with response to therapy (p=0.02). Patients with pretreatment tumors harboring increased expression of B cell metagene signatures and increased circulating B cell receptor repertoire diversity were associated with clinical response and immune-related toxicity (IRT).ConclusionsAmong patients with heavily pretreated TNBC, Cy prior to pembrolizumab did not significantly deplete Tregs, and in those with decreased numbers there was rapid recovery following therapy. Increased B cell gene expression in baseline samples was associated with clinical response and IRT.
Single-cell transcriptomics reveals a low CD8+T cell infiltrating state mediated by fibroblasts in recurrent renal cell carcinoma
Authors: Peng Yu-Lu , Xiong Long-Bin , Zhou Zhao-Hui , Ning Kang , Li Zhen , Wu Ze-Shen , Deng Min-Hua , Wei Wen-Su , Wang Ning , Zou Xiang-Peng , He Zhi-Song , Huang Ji-Wei , Luo Jun-Hang , Liu Jian-Ye , Jia Nan , Cao Yun , Han Hui , Guo Sheng-Jie , Dong Pei , Yu Chun-Ping , Zhou Fang-Jian , Zhang Zhi-Ling 
Published: February 2022

PurposeRecurrent renal cell carcinoma(reRCC) is associated with poor prognosis and the underlying mechanism is not yet clear. A comprehensive understanding of tumor microenvironment (TME) of reRCC may aid in designing effective anticancer therapies, including immunotherapies. Single-cell transcriptomics holds great promise for investigating the TME, however, this technique has not been used in reRCC. Here, we aimed to explore the difference in the TME and gene expression pattern between primary RCC (pRCC) and reRCC at single-cell level.Experimental designWe performed single-cell RNA sequencing analyses of 32,073 cells from 2 pRCC, 2 reRCC, and 3 adjacent normal kidney samples. 41 pairs of pRCC and reRCC samples were collected as a validation cohort to assess differences observed in single-cell sequencing. The prognostic significance of related cells and markers were studied in 47 RCC patients underwent immunotherapy. The function of related cells and markers were validated via in vitro and in vivo experiments.ResultsreRCC had reduced CD8+T cells but increased cancer-associated fibroblasts (CAFs) infiltration compared with pRCC. Reduced CD8+T cells and increased CAFs infiltration were significantly associated with a worse response from immunotherapy. Remarkably, CAFs showed substantial expression of LGALS1 (Gal1). In vitro, CAFs could induce CD8+T cells apoptosis via Gal1. In vivo, knockdown of Gal1 in CAFs suppressed tumor growth, increased CD8+T cells infiltration, reduced the proportion of apoptotic CD8+T cells and enhanced the efficacy of immunotherapy.ConclusionsWe delineated the heterogeneity of reRCC and highlighted an innovative mechanism that CAFs acted as a suppressor of CD8+T cells via Gal1. Targeting Gal1 combined with anti-PD1 showed promising efficacy in treating RCC.
Effectiveness of electronic drug monitoring feedback to increase adherence in patients with RA initiating a biological DMARD: a randomised clinical trial
Authors: Hebing Renske CF , Aksu Iremnur , Twisk Jos WR , Bos Wouter , Van den Bemt Bart , Nurmohamed Michael T 
Published: February 2022

ObjectiveMedication non-adherence in rheumatoid arthritis (RA) is associated with disease flares, increased disability and increased costs. This study assessed the effectiveness of electronic monitoring feedback (EMF) on medication adherence in patients with RA starting with or switching to a new biological disease-modifying antirheumatic drug (bDMARD).MethodsIn this randomised controlled trial, bDMARD starters were assigned to the intervention or control group and followed for 1 year. The intervention group received a needle container with a Medication Event Monitoring System (MEMS) cap registering patient’s adherence to injections. Scores were calculated every 3 months with MEMS and motivational interviewing feedback was given. The control group received usual care. Effectiveness of EMF on adherence was measured with the medication possession ratio (MPR).Results104 consecutive intervention patients were included and 102 controls. MPR was 0.95 (SD: 0.10) and 0.90 (0.16) after 12 months (B: 0.036, 95% CI: 0.001 to 0.007, p=0.045). bDMARD-naive patients receiving EMF achieved low disease activity (LDA) sooner compared with the control group, adjusted for baseline DAS (HR: 1.68, 95% CI: 1.00 to 2.81, p=0.050). Side effects and DAS28 were similar.ConclusionEMF increased adherence for patients with RA starting with or switching to a bDMARD. Especially bDMARD-naive patients achieved LDA sooner compared with the control group, which holds promise for the future.
Long-term safety and efficacy of upadacitinib or adalimumab in patients with rheumatoid arthritis: results through 3 years from the SELECT-COMPARE study
Authors: Fleischmann Roy , Mysler Eduardo , Bessette Louis , Peterfy Charles G , Durez Patrick , Tanaka Yoshiya , Swierkot Jerzy , Khan Nasser , Bu Xianwei , Li Yihan , Song In-Ho 
Published: February 2022

ObjectivesTo assess the long-term safety and efficacy of the Janus kinase inhibitor upadacitinib versus adalimumab over 3 years in the ongoing long-term extension (LTE) of SELECT-COMPARE, a randomised controlled phase 3 trial of patients with active rheumatoid arthritis and inadequate response to methotrexate (MTX).MethodsPatients on stable background MTX were randomised 2:2:1 to upadacitinib 15 mg, placebo or adalimumab 40 mg. Patients with an insufficient response were switched by week 26 from placebo to upadacitinib, upadacitinib to adalimumab or adalimumab to upadacitinib. Patients who completed the 48-week double-blind period could enter an LTE for up to 10 years. Safety and efficacy results were analysed here through 3 years. Treatment-emergent adverse events (AEs) were summarised based on exposure to upadacitinib and adalimumab. Efficacy was analysed by original randomised groups (non-responder imputation), as well as separately by treatment sequence (as observed).ResultsRates of several AEs were generally comparable between upadacitinib and adalimumab, including AEs leading to discontinuation, serious infections and serious AEs, malignancies, major adverse cardiac events, venous thromboembolism and deaths. Consistent with earlier results, herpes zoster, lymphopaenia, hepatic disorder and CPK elevation were reported at higher rates with upadacitinib versus adalimumab. In terms of efficacy, upadacitinib continued to show numerically better clinical responses than adalimumab over 3 years across all endpoints, including low disease activity and remission.ConclusionThe safety profile of UPA 15 mg was consistent with previous study-specific and integrated safety reports. Higher levels of clinical response continued to be observed with upadacitinib versus adalimumab through 3 years of treatment.
Development of radiographic classification criteria for hand osteoarthritis: a methodological report (Phase 2)
Authors: Haugen Ida K , Felson David , Abhishek Abhishek , Berenbaum Francis , Edwards John James , Herrero Beaumont Gabriel , Hermann-Eriksen Merete , Hill Catherine L , Ishimori Mariko , Jonsson Helgi , Karjalainen Teemu , Leung Ying Ying , Maheu Emmanuel , Mallen Christian D , Moe Rikke Helene , Ramonda Roberta , Ritschl Valentin , Stamm Tanja A , Szekanecz Zoltan , van der Giesen Florus J , Ritt Marco J P F , Wittoek Ruth , Kjeken Ingvild , Osteras Nina , van de Stadt Lotte A , Englund Martin , Dziedzic Krysia S , Marshall M , Bierma-Zeinstra Sita , Hansen Paul , Greibrokk Elsie , Smeets Wilma , Kloppenburg Margreet 
Published: February 2022

ObjectivesIn Phase 1 of developing new hand osteoarthritis (OA) classification criteria, features associated with hand OA were identified in a population with hand complaints. Radiographic findings could better discriminate patients with hand OA and controls than clinical examination findings. The objective of Phase 2 was to achieve consensus on the features and their weights to be included in three radiographic criteria sets of overall hand OA, interphalangeal OA and thumb base OA.MethodsMultidisciplinary, international expert panels were convened. Patient vignettes were used to identify important features consistent with hand OA. A consensus-based decision analysis approach implemented using 1000minds software was applied to identify the most important features and their relative importance influencing the likelihood of symptoms being due to hand OA. Analyses were repeated for interphalangeal and thumb base OA. The reliability and validity of the proposed criteria sets were tested.ResultsThe experts agreed that the criteria sets should be applied in a population with pain, aching or stiffness in hand joint(s) not explained by another disease or acute injury. In this setting, five additional criteria were considered important: age, morning stiffness, radiographic osteophytes, radiographic joint space narrowing and concordance between symptoms and radiographic findings. The reliability and validity were very good.ConclusionRadiographic features were considered critical when determining whether a patient had symptoms due to hand OA. The consensus-based decision analysis approach in Phase 2 complemented the data-driven results from Phase 1, which will form the basis of the final classification criteria sets.
Effect of parthenolide, an NLRP3 inflammasome inhibitor, on insulin resistance in high-fat diet-obese mice
Authors: Chinta Pavan Kumar , Tambe Suhas , Umrani Dhananjay , Pal Ajay Kumar , Nandave Mukesh 
Published: February 2022

The activation of Nod-like receptor proteins (NLRP3) containing the pyrin domain inflammasome is a hallmark of the pathogenesis of metabolic disorders. Inhibition of the NLRP3 inflammasome by phytoconstituents has been attempted as a strategy to mitigate these disorders. Therefore, the present study aimed to evaluate the efficacy of an NLRP3 inflammasome inhibitor, parthenolide (PN; 5 mg/kg i.p.) against inflammation and insulin resistance in high-fat diet (HFD) – obese mice. Treatment with PN and pioglitazone (PIO; 30 mg/kg p.o.) attenuated lipopolysaccharide (LPS; 1 ng/ml) – induced elevation of tumor necrosis factor-α and interleukin-1β in mouse peritoneal macrophages in a dose-dependent manner. Sixty days of PN and PIO treatment marginally reduced obesity-induced insulin resistance in HFD-obese mice. PN treatment also decreased blood glucose from 14th to 60th day, supporting the hypothesis of simultaneous attenuation of inflammation and insulin resistance in obese mice. Thus, PN treatment was also evident with significant improvement in glucose tolerance and peripheral insulin resistance validated through the respective tolerance tests. Therefore, the present study suggests that PN, an NLRP3 inflammasome inhibitor, could be a possible therapeutic agent for attenuating obesity-induced insulin resistance.
Measuring the electron Yukawa coupling via resonant s-channel Higgs production at FCC-ee
Authors: d’Enterria David , Poldaru Andres , Wojcik George 
Published: February 2022

AbstractThe Future Circular Collider (FCC-ee) offers the unique opportunity of studying the Higgs Yukawa coupling to the electron, $$y_\mathrm {e}$$

y
e

, via resonant s-channel production, $$\mathrm {e^+e^-}\rightarrow \mathrm {H}$$

e
+

e
-

→
H

, in a dedicated run at $$\sqrt{s} = m_\mathrm {H}$$

s

=

m
H

. The signature for direct Higgs production is a small rise in the cross sections for particular final states, consistent with Higgs decays, over the expectations for their occurrence due to Standard Model (SM) background processes involving $$\mathrm {Z}^*$$

Z

∗

, $$\gamma ^*$$

γ
∗

, or t-channel exchanges alone. Performing such a measurement is remarkably challenging for four main reasons. First, the low value of the e$$^\pm $$

±

mass leads to a tiny $$y_\mathrm {e}$$

y
e

coupling and correspondingly small cross section: $$\sigma _\mathrm {ee\rightarrow H} \propto m_\mathrm {e}^2 = 0.57$$

σ

ee
→
H

∝

m

e

2

=
0.57

fb accounting for initial-state $$\gamma $$
γ
radiation. Second, the $$\mathrm {e^+e^-}$$

e
+

e
-

beams must be monochromatized such that the spread of their centre-of-mass (c.m.) energy is commensurate with the narrow width of the SM Higgs boson, $$\varGamma _\mathrm {H} = 4.1$$

Γ
H

=
4.1

MeV, while keeping large beam luminosities. Third, the Higgs mass must also be known beforehand with a few-MeV accuracy in order to operate the collider at the resonance peak, $$\sqrt{s} = m_\mathrm {H}$$

s

=

m
H

. Last but not least, the cross sections of the background processes are many orders-of-magnitude larger than those of the Higgs decay signals. A preliminary generator-level study of 11 Higgs decay channels using a multivariate analysis, which exploits boosted decision trees to discriminate signal and background events, identifies two final states as the most promising ones in terms of statistical significance: $$\mathrm {H}\rightarrow gg$$

H
→
g
g

and $$\mathrm {H}\rightarrow \mathrm {W}\mathrm {W}^*\!\rightarrow \ell \nu $$

H
→
W

W

∗

→
ℓ
ν

+ 2 jets. For a benchmark monochromatization with 4.1-MeV c.m. energy spread (leading to $$\sigma _\mathrm {ee\rightarrow H} = 0.28$$

σ

ee
→
H

=
0.28

fb) and 10 ab$$^{-1}$$

-
1

of integrated luminosity, a $$1.3\sigma $$

1.3
σ

signal significance can be reached, corresponding to an upper limit on the e$$^\pm $$

±

Yukawa coupling at 1.6 times the SM value: $$|y_\mathrm {e}|<1.6|y^\mathrm {\textsc {sm}}_\mathrm {e}|$$

|

y
e

|
<
1.6
|

y
e

S
M

|

at 95% confidence level, per FCC-ee interaction point per year. Directions for future improvements of the study are outlined.
ASSESSMENT OF FUTURE CLIMATE PROJECTIONS IN ALGERIA USING STATISTICAL DOWNSCALING MODEL
Authors: SAHABI-ABED SALAH 
Published: February 2022

In this study, we assess the future changes in minimum temperature (T-min), maximum temperature (T-max), and precipitation (PRCP) for the three periods the 2020s (2011–2040), the 2050s (2041–2070), and the 2080s (2071–2100), with respect to the reference period 1981–2010 over Algeria focusing on a validation of the Statistical DownScaling Model (SDSM). In this approach, to underpin our analysis, we evaluate statistically the SDSM performance by simulating the historical temperatures and precipitation. The NCEP reanalysis data and CanESM2 predictors of three future scenarios, RCP2.6, RCP4.5, and RCP8.5 are used for model calibration and future projection, respectively. The projected climate changes resulting from the application of SDSM show a convincing consistency with those unveiled in previous studies over Algeria based on dynamical regional climate model outputs conducted in the context of Middle East-North Africa region. By the end of the century, the results exhibit strong warming for both extreme temperatures under the worst-case scenario (RCP 8.5), it is more pronounced for the T-max and over the Algerian Sahara region. Under the optimistic scenario (RCP2.6), the strength of the warming is expected to increase for both extreme temperatures. The projected changes of precipitation revealed for all scenarios several discrepancies with significant decrease over the northwest region and central Sahara, while nonsignificant change is projected for the center and eastern coastal regions. Our findings corroborate previous studies using sophisticated tools by demonstrating that Algeria’s climate is expected to warm further in the future. These primary findings could give an overview of the application of the statistical modeling approach using SDSM over a semi-arid and arid vulnerable region like Algeria and would extend our knowledge in the climate-modelling field for the North Africa zone by providing an added value to the existing GCMs and regional climate projections. In addition, reliable information regarding the magnitude of future changes at local scale may be used in impact models to assess changes of other key economic sector variables such as water resources management, energy and agriculture.
ASHRAY: Enhancing Water-usage Comfort in Developing Regions using Data-driven IoT Retrofits
Authors: Abbas Samar , Ehsan Ahmed , Ahmed Saad , Khan Sheraz Ali , Jadoon Tariq M. , Alizai Muhammad Hamad 
Published: February 2022

In developing countries, majority of the households use overhead water tanks to have running water. These water tanks are exposed to the elements, which usually render the tap water uncomfortable to use, given the extreme subtropical weather conditions. Externally weatherproofing these tanks to maintain the groundwater temperature is short-lived, and only results in a marginal (0.5°C–1°C) improvement in tap water temperature. We propose
Ashray
, an IoT-inspired, intelligent system to minimize the exposure of water to the elements thereby maintaining its temperature close to that of the groundwater.
Ashray
learns the water demand patterns of a household and pumps water into the overhead tank only when necessary. The predictive, machine learning based, approach of
Ashray
improves water comfort by up to 8°C in summers and 3°C in winters, on average.
Ashray
is retrofitted into existing infrastructure with a hardware prototyping cost of $27, whereas it can save up to 16% on water heating costs, through reduction in natural gas consumption, by leveraging groundwater temperature. Moreover, we also consider a transiently-powered
Ashray
, which uses the energy harvested from the ambient environment, and propose an intermittent data pipeline to improve its prediction accuracy. The transiently-powered
Ashray
is suitable for long-term deployment, requires minimal maintenance and delivers approximately the same performance.
Ashray
has the potential to improve the thermal comfort and reduce energy costs for millions of households in developing countries.
Toward Scalable and Privacy-preserving Deep Neural Network via Algorithmic-Cryptographic Co-design
Authors: Zhou Jun , Zheng Longfei , Chen Chaochao , Wang Yan , Zheng Xiaolin , Wu Bingzhe , Chen Cen , Wang Li , Yin Jianwei 
Published: February 2022

Deep Neural Networks (DNNs) have achieved remarkable progress in various real-world applications, especially when abundant training data are provided. However, data isolation has become a serious problem currently. Existing works build privacy-preserving DNN models from either
algorithmic
perspective or
cryptographic
perspective. The former mainly splits the DNN computation graph between data holders or between data holders and server, which demonstrates good scalability but suffers from accuracy loss and potential privacy risks. In contrast, the latter leverages time-consuming cryptographic techniques, which has strong privacy guarantee but poor scalability. In this article, we propose SPNN—a Scalable and Privacy-preserving deep Neural Network learning framework, from an algorithmic-cryptographic co-perspective. From algorithmic perspective, we split the computation graph of DNN models into two parts, i.e., the private-data-related computations that are performed by data holders and the rest heavy computations that are delegated to a semi-honest server with high computation ability. From cryptographic perspective, we propose using two types of cryptographic techniques, i.e., secret sharing and homomorphic encryption, for the isolated data holders to conduct private-data-related computations privately and cooperatively. Furthermore, we implement SPNN in a decentralized setting and introduce user-friendly APIs. Experimental results conducted on real-world datasets demonstrate the superiority of our proposed SPNN.
Federated Social Recommendation with Graph Neural Network
Authors: Liu Zhiwei , Yang Liangwei , Fan Ziwei , Peng Hao , Yu Philip S. 
Published: February 2022

Recommender systems have become prosperous nowadays, designed to predict users’ potential interests in items by learning embeddings. Recent developments of the Graph Neural Networks (GNNs) also provide recommender systems (RSs) with powerful backbones to learn embeddings from a user-item graph. However, only leveraging the user-item interactions suffers from the cold-start issue due to the difficulty in data collection. Hence, current endeavors propose fusing social information with user-item interactions to alleviate it, which is the social recommendation problem. Existing work employs GNNs to aggregate both social links and user-item interactions simultaneously. However, they all require centralized storage of the social links and item interactions of users, which leads to privacy concerns. Additionally, according to strict privacy protection under General Data Protection Regulation, centralized data storage may not be feasible in the future, urging a decentralized framework of social recommendation.As a result, we design a federated learning recommender system for the social recommendation task, which is rather challenging because of its heterogeneity, personalization, and privacy protection requirements. To this end, we devise a novel frameworkFedratedSocial recommendation withGraph neural network (FeSoG). Firstly,FeSoGadopts relational attention and aggregation to handle heterogeneity. Secondly,FeSoGinfers user embeddings using local data to retain personalization. Last but not least, the proposed model employs pseudo-labeling techniques with item sampling to protect the privacy and enhance training. Extensive experiments on three real-world datasets justify the effectiveness ofFeSoGin completing social recommendation and privacy protection. We are the first work proposing a federated learning framework for social recommendation to the best of our knowledge.
Microenvironment Is a Key Determinant of Immune Checkpoint Inhibitor Response
Authors: Cho Shih-Feng , Anderson Kenneth C. , Tai Yu-Tzu 
Published: February 2022

SummaryUtilizing advanced RNA-sequencing techniques and rigorous bioinformatics analysis, this study identified gene signatures predicting responsiveness to pembrolizumab monotherapy. T-cell–inflamed gene expression profile was predictive for better treatment response, while angiogenesis, monocytic myeloid–derived suppressor cell, and stroma/epithelial–mesenchymal transition/TGFβ gene signatures were associated with lower treatment response.See related article by Cristescu et al., p. 1680