bluuebunny/crossref_metadata_2025_split huggingface dataset:
CD137 Costimulation Counteracts TGFβ Inhibition of NK-cell Antitumor Function
Authors: Cabo Mariona , Santana-Hernández Sara , Costa-Garcia Marcel , Rea Anna , Lozano-Rodríguez Roberto , Ataya Michelle , Balaguer Francesc , Juan Manel , Ochoa Maria C. , Menéndez Silvia , Comerma Laura , Rovira Ana , Berraondo Pedro , Albanell Joan , Melero Ignacio , López-Botet Miguel , Muntasell Aura 
Published: September 2021

AbstractEnhancing natural killer (NK) cell–based cancer immunotherapy by overcoming immunosuppression is an area of intensive research. Here, we have demonstrated that the anti-CD137 agonist urelumab can overcome TGFβ-mediated inhibition of human NK-cell proliferation and antitumor function. Transcriptomic, immunophenotypic, and functional analyses showed that CD137 costimulation modified the transcriptional program induced by TGFβ on human NK cells by rescuing their proliferation in response to IL2, preserving their expression of activating receptors (NKG2D) and effector molecules (granzyme B, IFNγ) while allowing the acquisition of tumor-homing/retention features (CXCR3, CD103). Activated NK cells cultured in the presence of TGFβ1 and CD137 agonist recovered CCL5 and IFNγ secretion and showed enhanced direct and antibody-dependent cytotoxicity upon restimulation with cancer cells. Trastuzumab treatment of fresh breast carcinoma–derived multicellular cultures induced CD137 expression on tumor-infiltrating CD16+ NK cells, enabling the action of urelumab, which fostered tumor-infiltrating NK cells and recapitulated the enhancement of CCL5 and IFNγ production. Bioinformatic analysis pointed to IFNG as the driver of the association between NK cells and clinical response to trastuzumab in patients with HER2-positive primary breast cancer, highlighting the translational relevance of the CD137 costimulatory axis for enhancing IFNγ production. Our data reveals CD137 as a targetable checkpoint for overturning TGFβ constraints on NK-cell antitumor responses.
β2-Integrin Adhesion Regulates Dendritic Cell Epigenetic and Transcriptional Landscapes to Restrict Dendritic Cell Maturation and Tumor Rejection
Authors: Guenther Carla , Faisal Imrul , Fusciello Manlio , Sokolova Maria , Harjunpää Heidi , Ilander Mette , Tallberg Robert , Vartiainen Maria Kristina , Alon Ronen , Gonzalez-Granado Jose-Maria , Cerullo Vincenzo , Fagerholm Susanna Carola 
Published: September 2021

Abstract

Dendritic cells (DC), the classic antigen-presenting cells of the immune system, switch from an adhesive, phagocytic phenotype in tissues, to a mature, nonadhesive phenotype that enables migration to lymph nodes to activate T cells and initiate antitumor responses. Monocyte-derived DCs are used in cancer immunotherapy, but their clinical efficacy is limited. Here, we show that cultured bone marrow–derived DCs (BM-DC) expressing dysfunctional β2-integrin adhesion receptors displayed enhanced tumor rejection capabilities in B16.OVA and B16-F10 melanoma models. This was associated with an increased CD8+ T-cell response. BM-DCs expressing dysfunctional β2-integrins or manipulated to disrupt integrin adhesion or integrin/actin/nuclear linkages displayed spontaneous maturation in ex vivo cultures (increased costimulatory marker expression, IL12 production, and 3D migration capabilities). This spontaneous maturation was associated with an altered DC epigenetic/transcriptional profile, including a global increase in chromatin accessibility and H3K4me3/H3K27me3 histone methylation. Genome-wide analyses showed that H3K4me3 methylation was increased on DC maturation genes, such as CD86, Il12, Ccr7, and Fscn1, and revealed a role for a transcription factor network involving Ikaros and RelA in the integrin-regulated phenotype of DCs. Manipulation of the integrin-regulated epigenetic landscape in wild-type ex vivo–cultured BM-DCs enhanced their functionality in tumor rejection in vivo. Thus, β2-integrin–mediated adhesion to the extracellular environment plays an important role in restricting DC maturation and antitumor responses through regulation of the cellular epigenetic and transcriptional landscape. Targeting β2-integrins could therefore be a new strategy to improve the performance of current DC-based cancer immunotherapies.
An Onto-Hermeneutic Approach to Early Medieval Daoist Philosophy
Authors: Assandri Friederike 
Published: September 2021

Abstract
This paper addresses the Buddhist terms and concepts in early medieval Daoist texts in the light of hermeneutic and onto-hermeneutic theory with an example from the Benji Jing. It argues that onto-hermeneutic strategies of interpretation allow us to understand Daoist texts with Buddhist terms and concepts as an expression of complex and creative philosophical thoughts without losing track of the essence of Daoism and thus as Daoist philosophy in its own right.
Comparison of traditional method and triple collocation analysis for evaluation of multiple gridded precipitation products across Germany
Authors: Duan Zheng , Duggan Edward , Chen Cheng , Gao Hongkai , Dong Jianzhi , Liu Junzhi 
Published: September 2021

AbstractEvaluating the accuracy of precipitation products is essential for many applications. The traditional method for evaluation is to calculate error metrics of products with gauge measurements that are considered as ground-truth. The multiplicative triple collocation (MTC) method has been demonstrated powerful in error quantification of precipitation products when ground-truth is not known. This study applied MTC to evaluate five precipitation products in Germany: two raw satellite-based (CMORPH and PERSIANN), one reanalysis (ERA-Interim), one soil moisture-based (SM2RAIN-ASCAT), and one gauge-based (REGNIE) products. Evaluation was performed at the 0.5° -daily spatial-temporal scales. MTC involves a log transformation of data, necessitating dealing with zero values in daily precipitation. Effects of 12 different strategies for dealing with zero value on MTC results were investigated. Seven different triplet combinations were tested to evaluate the stability of MTC. Results showed that different strategies for replacing zero values had considerable effects on MTC-derived error metrics particularly for root mean squared error (RMSE). MTC with different triplet combinations generated different error metrics for individual products. MTC-derived correlation coefficient (CC) was more reliable than RMSE. It is more appropriate to use MTC to compare the relative accuracy of different precipitation products. Based on CC with unknown truth, MTC with different triplet combinations produced the same ranking of products as the traditional method. A comparison of results from MTC and the classic TC with additive error model showed the potential limitation of MTC in arid area or dry time periods with large ratio of zero daily precipitation.
Food insecurity, morbidity, and susto: Factors associated with depression severity in Guatemala measured with the Personal Health Questionnaire 9
Authors: Maupin Jonathan , Hackman Joseph 
Published: September 2021

Background: Depression is the largest contributor to non-fatal health loss globally and the majority of this burden occurs in low- and middle-income countries. Yet, estimates of prevalence rates and severity in these contexts may be uncertain due to limited screening, lack of mental health providers, and stigma around mental disorders which may prevent individuals from seeking care. In Guatemala, estimates of depression vary, due in part to the range of screening and diagnostic instruments used and diversity of sample populations. Most studies emphasize personal experiences with violence as a predictor of depression in Guatemala, although high rates of inequality, discrimination, and resource scarcity in the country potentially play a role. Aims: In this study, we examine factors associated with depression severity categories measured with the Personal Health Questionnaire 9 (PHQ-9) among a random sample of women in a small urban community in the Central Highlands of Guatemala. Methods: Participants were recruited through a randomized sample of households in a small urban community. Participants completed a questionnaire which included questions on demographics, illness history, food insecurity, and the PHQ-9. In total, 101 women were included in the analysis. Results: Food insecurity, 2-week symptom reporting, and experiencing susto are associated with higher depression severity categories. Conclusion: This research highlights need for more research on factors related to the prevalence and severity of mental disorders, and the relationship between mental disorders and cultural constructs of distress, particularly in areas like Guatemala with limited mental health services.
Joint Provision of Non-audit Services to Audit Clients: Empirical Evidences from India
Authors: Tiwari Reshma Kumari , Debnath Jasojit 
Published: September 2021

Executive Summary The provision of non-audit services (NAS) by an incumbent auditor has remained a highly contentious issue. One school argues that the joint provision does not impair an auditor’s independence. Instead, it reduces total costs, enhances the ability to detect material misstatements, increases technical competence due to knowledge spillovers and leads to intense competition. However, a substantial tranche of an audit firms’ income is derived from NAS, and the joint provision increases economic ties with the client. Therefore, another school of thought perceives that the joint provision impairs auditor independence. It is also alleged that auditors expect non-audit work after finishing the auditing job. Their independence is also affected by the risks of self-review. Extant literature reveals that the majority of the studies on the issue are archival and experimental. The studies are concentrated in the US, UK, Australia, Malaysia, Nigeria, South Africa, China, and some of the European Union Nations. The article examines the perspective of chartered accountants (CAs) on the joint provision of NAS in India. The study samples 119 CAs. The reliability of the survey result was measured using Cronbach’s α, and a score of 0.77 indicated acceptable internal consistency reliability. The data were analysed using Wilcoxon signed-rank test and the Mann Whitney U test statistic. The summary of their suggestions for ensuring auditor independence is presented separately. The findings reflect that existing prohibitions imposed by the Companies Act, 2013, are not enough to ensure auditor independence, and the Management Services u/s 144 of the Act needs to be clearly defined. Practitioners do not support the proposition that joint provision should end and a separate category of professionals be mandated to render NAS. However, the recommendations include strengthening provisions to reduce the conflict of interest.
Validation of Skully Care as a Fast Method for Quantifying Positional Cranial Deformities
Authors: Van Adrichem Léon N.A. , Kronig Sophia A.J. , Kronig Otto D.M. 
Published: September 2021

Objective Craniofacial measuring is valuable for diagnosis and evaluation of growth and treatment of positional skull deformities. Plagiocephalometry (PCM) quantifies skull deformities and is proven to be reliable and valid. However, PCM needs direct skin contact with thermoplastic material, is laborious and time-consuming. Therefore, Skully Care (SC) was developed to measure positional skull deformities with a smartphone application. Design SC is retrospectively compared to PCM. Setting Pediatric physiotherapy centers. Patients Age ≤1 year, analyzed or treated for positional skull deformities. Interventions A total of 60 skull shape analyses were performed. Main Outcome Measures The main outcome measures employed are Pearson correlation coefficient between cranial vault asymmetry index (CVAI; in SC) and oblique diameter difference index (ODDI; in PCM) and between cranial index (CI; in SC) and cranial proportional index (CPI; in PCM). Mann–Whitney U test determined difference of time consumption between PCM and SC. Results High correlation was found between CVAI and ODDI ( r = 0.849; P < .01) in positional plagiocephaly and very high correlation between CI and CPI ( r  = 0.938; P < .01) in positional brachycephaly. SC is significantly faster than PCM ( P < .001). Conclusions SC is valid in analyzing positional skull deformities and strongly correlates to PCM, the gold standard in daily physiotherapy practice. The combination of simplicity, validity, speed, and user and child convenience makes SC a promising craniofacial measuring method in daily practice. SC has potential to be the modern successor for analyzing positional skull deformities.
Incidence and Demographics of Nasopharyngeal Carcinoma in Cheung Chau Island of Hong Kong—A Distinct Geographical Area With Minimal Residential Mobility and Restricted Public Healthcare Referral Network
Authors: Chan Sik-Kwan , Chau Sze-Chun , Chan Sum-Yin , Tong Chi-Chung , Lam Ka-On , Lai-Wan Kwong Dora , Leung To-Wai , Luk Mai-Yee , Lee Anne Wing-Mui , Choi Horace Cheuk-Wai , Lee Victor Ho-Fun 
Published: September 2021

Background Nasopharyngeal carcinoma (NPC) is endemic in Hong Kong with a skewed geographical and ethnic distribution. We performed an epidemiological study of NPC in Cheung Chau Island, a fishing village with very minimal residential mobility, and compared its demographics and survival with the rest of Hong Kong. Methods NPC data in Cheung Chau and non–Cheung Chau residents between 2006 and 2017 treated in our tertiary center were collected. The incidence, stage distribution, and mortality of Cheung Chau NPC residents were compared with those of their counterparts in the whole Hong Kong obtained from the Hong Kong Cancer Registry. Propensity score matching (PSM) was performed between Cheung Chau and non–Cheung Chau cases in a 1:4 ratio. Overall survival (OS), progression-free survival (PFS), and cancer-specific survival (CSS) were compared between these two cohorts by product limit estimation and log-rank tests. Results Sixty-one patients residing in Cheung Chau were identified between 2006 and 2017. There was a significantly higher NPC incidence ( P < .001) but an insignificant difference in the mortality rate in Cheung Chau compared to the whole Hong Kong data. After PSM with 237 non–Cheung Chau patients, the Cheung Chau cohort revealed a stronger NPC family history ( P < .001). However, there were no significant differences in OS ( P = .170), PFS ( P = .053), and CSS ( P = .160) between these two cohorts. Conclusion Our results revealed that Cheung Chau had a higher NPC incidence but similar survival outcomes compared to the whole of Hong Kong. Further prospective studies are warranted to verify this finding and to explore the possible underlying mechanisms.
Shaking table test of acceleration response of surrounding rock of the 3D cross tunnel under earthquake
Authors: Pai Lifang , Wu Honggang , Lei Hao 
Published: September 2021

Taking the 3D cross-engineering of Caomeigou No.1 Tunnel and Pandaoling Tunnel as an example, a shaking table test was carried out to study the effect of tunnel spatial position on seismic wave propagation characteristics and acceleration response of surrounding rock under earthquake seismic excitation. Based on the influence of the spatial position of the tunnel, the characteristic form of the surrounding rock between the cross section and non-cross section is divided, and the accelerometer layout scheme is designed. Based on statistical probability, the ratio of peak ground velocity to peak ground acceleration (PGA) was introduced to quantitatively characterize the characteristics of seismic wave propagation spectrum. Furthermore, the SPECTR calculation was used to obtain the regional difference in the seismic wave propagation potential damage potential displacement parameter ( P d). Under the influence of the spatial location of the 3D cross tunnel, the peak acceleration and motion duration of the seismic wave are mainly reflected in the variation of the section along the elevation direction. Low-frequency (≤20 Hz) seismic waves have a greater impact on the tunnel structure, and peak ground velocity/peak ground acceleration ratio has a positive correlation with the peak input energy of ground motion. The ultra-small net-spacing cross tunnel has a spatially distributed coupling deformation effect. The crown of the upper-span tunnel is highly sensitive to earthquakes and becomes a weak link in seismic design. These results help us provide a theoretical basis for the seismic design of the cross-tunnel.
Mindfulness-based cognitive therapy for depression in people with dementia: A qualitative study on participant, carer and facilitator experiences
Authors: Douglas Sarah , Stott Josh , Spector Aimee , Brede Janina , Hanratty Éanna , Charlesworth Georgina , Noone Deirdre , Payne Jacob , Patel Mina , Aguirre Elisa 
Published: September 2021

Background Depression in dementia is common and associated with negative health outcomes. Mindfulness-based cognitive therapy is a recommended treatment of choice for recurrent depression, but its use for depression in dementia is yet to be assessed. Objective This study aimed to investigate the experiences of people with depression and dementia who participated in the mindfulness-based cognitive therapy intervention and those of their carers and facilitators. Methods This qualitative study was nested within a randomised controlled feasibility study. Semi-structured interviews were conducted with 18 people (eight people with dementia and depression, six carers and four course facilitators). Thematic analysis was used to analyse the data. Findings Several beneficial effects of mindfulness-based cognitive therapy were described. These were a sense of shared suffering among the group, greater present moment focus and awareness, various positive emotional changes, including greater self-compassion, and benefits for carers, such as the reduction of anxiety. Specific aspects of the programme were identified as particularly useful, including facilitator characteristics and certain mindfulness practices. Carer involvement, cognitive difficulties and barriers to home practice influenced engagement with the course. Facilitators described adaptations made to mindfulness-based cognitive therapy and suggested additional modifications for future groups. Conclusion Results of this process evaluation suggest that mindfulness-based cognitive therapy is a potentially useful intervention for people with depression in dementia, but that further adaptation of the intervention is required to make the programme suitable for this clinical population.
Cast-OFF Trial: One Versus 4 to 5 Weeks of Plaster Cast Immobilization for Nonreduced Distal Radius Fractures: A Randomized Clinical Feasibility Trial
Authors: Boersma Emily Z. , Hekma Edo J. , Kraaijvanger Nicole , Mollen Roland M. H. G. , Nijhuis-van der Sanden Maria W. G. , Edwards Michael J. R. 
Published: September 2021

Background Distal radius fracture is a common fracture of which the incidence appears to be increasing worldwide. This pilot study investigated whether 1 week of plaster cast is feasible for nonreduced (stable fractures including nondisplaced and displaced fractures) distal radius fractures. Methods The study was a multicenter randomized clinical feasibility trial including patients from regional acute care providers. Patients with a nonreduced distal radius fracture were included in the study. Nonreduced fractures meant intra-articular or extra-articular fractures and including nondisplaced and minimal displaced fractures (dorsal angulation less than 5°-10°, maximum radial shortening of 2 mm, and maximum radial shift of 2 mm) not needing a reduction. Forty Patients were included and randomized. After 1 week of plaster cast, patients were randomized to 1 of the 2 treatment groups: plaster cast removed (intervention group) versus 4 to 5 weeks of plaster cast (control group). Results The analysis shows no significant differences between the 2 groups in having less pain, better function after 6 weeks, and better overall patient satisfaction. No difference was shown in secondary displacement between the 2 groups (control 1 vs intervention 0) Conclusion One week of plaster cast treatment for nonreduced distal radius fracture is feasible, preferred by patients, with at least the same functional outcome and pain scores. Level of Evidence According to the Oxford 2011 level of evidence, the level of evidence of this study is 2.
Impact of renal impairment on short-term outcomes following endovascular thrombectomy for acute ischemic stroke: A systematic review and meta-analysis
Authors: Jeon Jin Pyeong , Chen Chih-Hao , Tsuang Fon-Yih , Liu Jianmin , Hill Michael D , Zhang Lei , Yang Pengfei , Wang Guoping , Cho Bang-Hoon , Kim Joon-Tae , Goyal Mayank , Cho Yong Jun , Chai Chung Liang 
Published: September 2021

Background The impact of renal impairment on the outcomes of patients with acute ischemic stroke treated with endovascular thrombectomy was relatively limited and contradictory. We performed a systematic review and meta-analysis to investigate this. Aims We registered a protocol in September 2020 and searched MEDLINE, EMBASE, and Google Scholar accordingly. Renal impairment was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2. Predefined outcomes included functional independence (defined as a modified Rankin Scale of 0, 1, or 2) at three months, successful reperfusion, mortality, and symptomatic intracerebral hemorrhage. Summary of review Eleven studies involving 3453 patients were included. For the unadjusted outcomes, renal impairment was associated with fewer functional independence (odds ratio (OR), 0.49; 95% confidence interval (CI), 0.39–0.62) and higher mortality (OR, 2.55; 95% CI, 2.03–3.21). Renal impairment was not associated with successful reperfusion (OR, 0.80; 95% CI 0.63–1.00) and symptomatic intracerebral hemorrhage (OR, 1.41; 95% CI, 0.95–2.10). For the adjusted outcomes, results derived from a multivariate meta-analysis were consistent with the respective unadjusted outcomes: functional independence (OR, 0.59; 95% CI, 0.45–0.77), mortality (OR, 2.23, 95% CI, 1.45–3.43), and symptomatic intracerebral hemorrhage (OR, 1.34; 95% CI, 0.85–2.10). Conclusions We presented the first systematic review to demonstrate that renal impairment is associated with fewer functional independence and higher mortality. Future endovascular thrombectomy studies should publish complete renal estimated glomerular filtration rate data to facilitate prognostic studies and permit estimated glomerular filtration rate to be analyzed in a continuous variable. Systematic Review Registration: PROSPERO CRD42020191309