bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reinduction therapy with everolimus in combination with dexamethasone, high‐dose cytarabin and cisplatinum in patients with relapsed or refractory classical Hodgkin lymphoma: an experimental phase I/II multicentre trial of the German Hodgkin Study Group (GHSG HD‐R3i)
Authors: Gillessen Sarah , Hüttmann Andreas , Vucinic Vladan , Müller Horst , Plütschow Annette , Viardot Andreas , Topp Max S. , Kobe Carsten , Böll Boris , Eichenauer Dennis A. , Sasse Stephanie , Haverkamp Heinz , Schmitz Christine , Borchmann Sven , Bröckelmann Paul J. , Heger Jan‐Michel , Fuchs Michael , Engert Andreas , Borchmann Peter , von Tresckow Bastian 
Published: November 2021

SummaryReinduction chemotherapy followed by high‐dose chemotherapy and autologous stem cell transplant (HDCT + ASCT) is second‐line standard of care for transplant‐eligible patients with relapsed/refractory classical Hodgkin lymphoma (r/r cHL) but has a high failure rate. Because response to reinduction is predictive of the outcome after HDCT + ASCT, we aimed to improve the standard dexamethasone, high‐dose cytarabine and cisplatinum (DHAP) reinduction regimen by addition of the oral mammalian target of rapamycin inhibitor everolimus (everDHAP). Transplant‐eligible patients aged 18–60 years with histologically confirmed r/r cHL were included in this experimental phase I/II trial. Everolimus (10 mg/day, determined in phase‐I‐part) was administered on day 0–13 of each DHAP cycle. From July 2014 to March 2018, 50 patients were recruited to the phase II everDHAP group; two were not evaluable, three discontinued due to toxicity. Randomization to a placebo group stopped in October 2015 due to poor recruitment after nine patients. The primary end‐point of computed tomography (CT)‐based complete remission (CR) after two cycles of everDHAP was expected to be ≥40%. With a CT‐based CR rate of 27% (n = 12/45) after two cycles of everDHAP the trial did not meet the primary end‐point. Adding everolimus to DHAP is thus feasible; however, the everDHAP regimen failed to show an improved efficacy.
An update on the US adult thalassaemia population: a report from the CDC thalassaemia treatment centres
Authors: Chapin John , Cohen Alan R. , Neufeld Ellis J. , Vichinsky Elliott , Giardina Patricia J. , Boudreaux Jeanne , Le Binh C. , Kenney Kristy , Trimble Sean , Thompson Alexis A. 
Published: November 2021

SummaryThalassaemia is caused by genetic globin defects leading to anaemia, transfusion‐dependence and comorbidities. Reduced survival and systemic organ disease affect transfusion‐dependent thalassaemia major and thalassaemia intermedia. Recent improvements in clinical management have reduced thalassaemia mortality. The therapeutic landscape of thalassaemia may soon include gene therapies as functional cures. An analysis of the adult US thalassaemia population has not been performed since the Thalassemia Clinical Research Network cohort study from 2000 to 2006. The Centers for Disease Control and Prevention supported US thalassaemia treatment centres (TTCs) to compile longitudinal information on individuals with thalassaemia. This dataset provided an opportunity to evaluate iron balance, chelation, comorbidities and demographics of adults with thalassaemia receiving care at TTCs. Two adult cohorts were compared: those over 40 years old (n = 75) and younger adults ages 18–39 (n = 201). The older adult cohort was characterized by higher numbers of iron‐related comorbidities and transfusion‐related complications. By contrast, younger adults had excess hepatic and cardiac iron and were receiving combination chelation therapy. The ethnic composition of the younger cohort was predominantly of Asian origin, reflecting the demographics of immigration. These findings demonstrate that comprehensive care and periodic surveys are needed to ensure optimal health and access to emerging therapies.
A novel HSF1 activator ameliorates non‐alcoholic steatohepatitis by stimulating mitochondrial adaptive oxidation
Authors: Rao Yong , Li Chan , Hu Yu‐Tao , Xu Yao‐Hao , Song Bing‐Bing , Guo Shi‐Yao , Jiang Zhi , Zhao Dan‐Dan , Chen Shuo‐Bin , Tan Jia‐Heng , Huang Shi‐Liang , Li Qing‐Jiang , Wang Xiao‐Jun , Zhang Ying‐Jun , Ye Ji‐Ming , Huang Zhi‐Shu 
Published: November 2021

Background and PurposeNon‐alcoholic steatohepatitis (NASH) is the more severe form of metabolic associated fatty liver disease (MAFLD) and no pharmacological treatment as yet been approved. Identification of novel therapeutic targets and their agents is critical to overcome the current inadequacy of drug treatment for NASH.Experimental ApproachThe correlation between heat shock factor 1 (HSF1) levels and the development of NASH and the target genes of HSF1 in hepatocyte were investigated by chromatin‐immunoprecipitation sequencing. The effects and mechanisms of SYSU‐3d in alleviating NASH were examined in relevant cell models and mouse models (the Ob/Ob mice, high‐fat and high‐cholesterol diet and the methionine‐choline deficient diet‐fed mice). The actions of SYSU‐3d in vivo were evaluated.Key ResultsHSF1 is progressively reduced with mitochondrial dysfunction in NASH pathogenesis and activation of this transcription factor by its newly identified activator SYSU‐3d effectively inhibited all manifestations of NASH in mice. When activated, the phosphorylated HSF1 (Ser326) translocated to nucleus and bound to the promoter of PPARγ coactivator‐1α (PGC‐1α) to induce mitochondrial biogenesis. Thus, increasing mitochondrial adaptive oxidation and inhibiting oxidative stress. The deletion of HSF1 and PGC‐1α or recovery of HSF1 in HSF1‐deficiency cells showed the HSF1/PGC‐1α pathway was mainly responsible for the anti‐NASH effects of SYSU‐3d independent of AMP‐activated protein kinase (AMPK).Conclusion and ImplicationsActivation of HSF1 is a practical therapeutic approach for NASH treatment via the HSF1/PGC‐1α/mitochondrial pathway and SYSU‐3d can be considered as a potential candidate for the treatment of NASH.
Basin modelling of a complex rift system: The Northern Vøring Volcanic Margin case example
Authors: Gac Sébastien , Abdelmalak Mansour M. , Faleide Jan Inge , Schmid Daniel W. , Zastrozhnov Dmitry 
Published: November 2021

AbstractExtensional processes can lead to complex crustal configuration depending on the mechanisms of lithospheric thinning and the impact of magmatic additions during rifting and breakup. In this context, we studied the Vøring volcanic passive margin offshore Norway. The evolution of the inner Vøring Margin is well explained by standard models of lithosphere extension. However, these models fail to reproduce key observations at the outer (volcanic) province such as regional uplift at the time of breakup and excess magmatism. Therefore, additional processes are required to explain these observations. Excess magmatism and uplift have been related to mantle processes such as the arrival of the hot Icelandic mantle ‘plume’ or small‐scale convection processes. Melt retention in the asthenosphere has also been proposed to explain uplift. At last, mantle phase transitions during extension may contribute to uplift. We present tectonic and thermal models of basin evolution along a seismic profile crossing the Northern Vøring Margin. The thermal and isostatic history of basins is constrained through time‐forward basin modelling based on an automated inverse basin reconstruction approach. Two scenarios are evaluated: The first one includes pronounced mantle stretching during the last late Cretaceous‐Paleocene rifting event, and the second one includes late Paleocene‐early Eocene mantle thinning, at the breakup time around 56–54 Ma. Models incorporating late Paleocene‐early Eocene mantle thinning and taking into account magmatic processes (melt retention and magmatic underplate) and mantle phase transitions satisfactorily reproduce the specific observations of the outer (volcanic) margin. This result supports the contribution of the hot Iceland plume on the evolution of the Vøring Margin. Our results also indicate that thin‐crust models can produce a partially serpentinized mantle beneath the highly extended parts of the Vøring Basin. However, this model fails to reproduce observations. This suggests that serpentinization can occur locally but could not explain the entire lower crustal body nature.
Psychosocial characteristics of patients evaluated for kidney transplant and associations with functional and frailty metrics at a veterans affairs hospital
Authors: Manay Priyadarshini , Ten Eyck Patrick , Siniff Erin , Binns Grace , Sanders M. Lee , Swee Melissa , Hornickel Jodell L. , Kalil Roberto , Katz Daniel A. 
Published: November 2021

AbstractBackgroundThe effect of psychosocial problems on listing outcomes and potential interactions with functional metrics is not well‐characterized among Veteran transplant candidates.MethodsThe results from psychosocial evaluations, frailty metrics, and biochemical markers were collected on 375 consecutive Veteran kidney transplant candidates. Psychosocial diagnoses were compared between patients listed or denied for transplant. Functional abilities were compared among patients with or without psychosocial diagnoses and then evaluated based on reason for denial.ResultsEighty‐four percent of patients had a psychosocial diagnosis. Common issues included substance or alcohol abuse (62%), psychiatric diagnoses (50%), and poor adherence (25%). Patients with psychiatric diagnoses, cognitive impairments, and poor adherence were more likely to be denied for transplant (P < .05). Patients with depression, PTSD, and anxiety did not have worse functional ability, but experienced more exhaustion than patients without these problems. Patients denied for medical but not purely psychosocial reasons had worse troponin and functional metrics compared with listed patients.ConclusionOver 80% of patients with a psychosocial diagnosis were listed; however, poor adherence was a particularly important reason for denial for purely psychosocial reasons. Patients with psychosocial diagnoses generally were not more functionally limited than their counterparts without psychosocial diagnoses or those listed for transplant.
HIV prevalence among non‐injecting people who use drugs and related factors in Iran: A systematic review and meta‐analysis
Authors: Gholami Jaleh , Rostam‐Abadi Yasna , Rahimi Yekta , Fotouhi Akbar , Amin‐Esmaeili Masoumeh , Rahimi‐Movaghar Afarin 
Published: November 2021

AbstractIssuesThis systematic review aimed to provide an updated estimate on the prevalence of human immunodeficiency virus (HIV) infection among non‐injecting people who use drugs (PWUD) and the various subgroups and the odds of HIV infection in the injecting compared to non‐injecting PWUD.ApproachA comprehensive search of international, regional and national databases was performed from January 2005 to May 2020. We conducted backward citation tracking of the included studies and contacted experts for unpublished studies. Studies providing HIV prevalence among non‐injecting PWUD were included. Data were also drawn from a previous systematic review, covering 10 years from 1998 to 2007, and was added to the new database. The HIV prevalence was pooled for non‐injecting PWUD and other subgroups using the random‐effects model.Key FindingsSeventeen studies with a total sample of 9912 non‐injecting PWUD were found. The prevalence of HIV infection was 1.9% (95% confidence interval 0.9, 3.1) for 2007 and afterward (nine studies). It was not significantly different from the estimate for the years before 2007 (0.5%; 95% confidence interval 0.0, 2.0; eight studies). No significant difference was found among gender subgroups. The overall estimate of odds of HIV infection among injecting PWUD was 5.7 (95% confidence interval 3.2, 10.0) times higher than non‐injecting PWUD.Implications and ConclusionsThe HIV prevalence among the non‐injecting PWUD was higher than the general population in Iran. Targeting non‐injection PWUD by preventive measures such as harm reduction, drug and psychoeducation, and surveillance seem to be crucial in reducing HIV prevalence in this group.
Young children form generalized attitudes based on a single encounter with an outgroup member
Authors: Yu Chengfei , Qian Miao , Amemiya Jamie , Fu Genyue , Lee Kang , Heyman Gail D. 
Published: November 2021

AbstractThe goal of the present research was to assess whether children's first interaction with a single outgroup member can significantly impact their general attitudes toward the outgroup as a whole. In two preregistered studies, 5‐ to 6‐year‐old Chinese children (total N = 147) encountered a Black adult from another country for the very first time, and they played a game together. General attitudes toward the outgroup were assessed using both implicit and explicit measures. In both studies, the interaction resulted in less negative explicit attitudes toward Black people, but more negative implicit attitudes. The results demonstrate for the first time that one encounter with a single outgroup member can impact children's general attitudes toward that group, and that it can have differential effects on implicit and explicit attitudes.
Evaluating methods for estimating shark natural mortality rate and management reference points using life‐history parameters
Authors: Zhou Shijie , Deng Roy A. , Dunn Matthew R. , Hoyle Simon D. , Lei Yeming , Williams Ashley J. 
Published: November 2021

AbstractSharks (class Chondrichthyes, subclass Elasmobranchii) typically have a long lifespan, slow growth rate and low fecundity, leading to low productivity and hence relatively high vulnerability to fishing. Information for managing fisheries catches of elasmobranchs is often lacking, because elasmobranchs are usually non‐target species, often with low abundance. It is more feasible to develop management reference points for elasmobranchs based on their life‐history information than through traditional stock assessments. The natural mortality rate (M) is the leading life‐history parameter (LHP) required by many methods for developing reference points and is itself often derived indirectly from other LHPs. In this paper, we evaluate nineMestimators, using 15 shark stocks in the Western and Central Pacific Ocean as examples. We then compare four methods for developing fishing mortality reference pointsFmsy, including empirical modelling, the Euler‐Lotka equation, anM‐productivity‐based method and the spawning potential rate converted method. Our analyses show that popularMestimators developed mainly from teleost data resulted in large deviations from the average and were not suitable for elasmobranchs. All four methods for estimatingFmsyperformed similarly. However, the empirical method is very simple and cost‐effective and tended to produce smaller deviations from the average than the other three methods. Nonetheless, it is recommended that multiple methods should be used to minimize possible bias and reflect uncertainty, if the required LHPs are available.
Profiling insular vertebrates prone to biological invasions: What makes them vulnerable?
Authors: Marino Clara , Leclerc Camille , Bellard Céline 
Published: November 2021

AbstractInvasive alien species (IAS) are a major threat to insular vertebrates, although the ecological characteristics that make insular communities vulnerable to IAS are poorly understood. After describing the ecological strategies of 6015 insular amphibians, birds, lizards, and mammals, we assessed the functional and ecological features of vertebrates exposed to IAS. We found that at least 50% of insular amphibian functional richness was hosted by IAS‐threatened amphibians and up to 29% for birds. Moreover, all IAS‐threatened groups except birds harbored a higher functional richness than species groups threatened by other threats. Disentangling the ecological strategies threatened by IAS, compared to those associated with other threats, we showed that birds, lizards, and mammals were more likely to be terrestrial foragers and amphibians to have larval development. By contrast, large‐bodied species and habitat specialists were universally threatened. By considering the functional aspect of threatened insular diversity, our work improves our understanding of global IAS impacts. This new dimension proves essential for undertaking relevant and effective conservation actions.
Digital sovereignty–European Union's action plan needs a common understanding to succeed
Authors: Kaloudis Martin 
Published: November 2021

AbstractIn the states of the European Union (EU), the question currently raised is to what extent dependence on technologies from the USA and China will have a lasting impact on state sovereignty. The concept of digital sovereignty represents the EU's efforts to compensate for the deficits of the past decades caused by an inadequate positioning of Europe as a location for software and hardware development. Autocratic states use the path of digital autarky, the USA a path of liberalisation and high degrees of openness. In the EU, on the other hand, regulation, data protection and liberal values developed over centuries play a major role in the less pronounced IT development. The path of European states to more digital sovereignty has been addressed politically as an “action plan”, but there is still no common understanding or definition of what digital sovereignty exactly means, where the EU and thus also an individual European state stands. There is a lack of a target and a measurable index as well as evaluated measures derived from it. The present article articulates the basis, namely the common understanding and the definition of digital sovereignty. It places the concepts of digitalisation and state sovereignty in a historical framework and locates them in the current literature, then analyses digital sovereignty as a composite term and places it in the context of current research. Finally, a definition is proposed that can serve as the basis for further research to identify an index of digital sovereignty. This definition can also become the basis for EU legislation to implement the “action plan”.
Diverse myeloid cells are recruited to the developing and inflamed mammary gland
Authors: Wilson Gillian J. , Fukuoka Ayumi , Vidler Francesca , Graham Gerard J. 
Published: November 2021

AbstractThe immune system plays fundamental roles in the mammary gland, shaping developmental processes and controlling inflammation during infection and cancer.Here, we reveal unanticipated heterogeneity in the myeloid cell compartment duringdevelopment of virgin, pregnant, lactating and involuting mouse mammary glands,and in milk. We investigate the functional consequences of individual and compoundchemokine receptor deficiency on cell recruitment. Diverse myeloid cell recruitmentwas also shown in models of sterile inflammation and bacterial infection.Strikingly, we have shown that inflammation and infection can alter the abundanceof terminal end buds, a key developmental structure, within the pubertal mammarygland. This previously unknown effect of inflammatory burden during puberty couldhave important implications for understanding pubertal development.
Psychosocial interventions for older people with intellectual disabilities and the role of support staff: A systematic review
Authors: Thalen Marloes , Volkers Karin M. , van Oorsouw Wietske M. W. J. , Embregts Petri J. C. M. 
Published: November 2021

AbstractBackgroundThe life expectancy of people with intellectual disabilities has increased. The implications of ageing have resulted in changes in their support needs and challenges to support staff. Access to evidence based strategies for support staff providing care to elderly with intellectual disabilities remains scarce. A systematic review was conducted to provide an overview of available psychosocial interventions.MethodsFour databases were searched and assessed according to the PRISMA guidelines. A narrative, integrative method of analysis was conducted to synthesise quantitative and qualitative data.ResultsThe 36 studies included in the review reported on interventions aimed at either identifying and meeting the needs or perceptions of older individuals or at improving their behaviour and skills. Furthermore, the role of support staff in the implementation of interventions was either active, assisting or undefined.ConclusionsThis overview of studies could contribute to the existing body of knowledge and help to optimise psychosocial support for a growing population.
Persistent left superior vena cava transvenous lead extraction: A European experience
Authors: Akhtar Zaki , Sohal Manav , Starck Christoph T. , Mazzone Patrizio , Melillo Francesco , Gonzalez Elkin , Al‐Razzo Omar , Richter Sergio , Breitenstein Alexander , Steffel Jan , Rinaldi Christopher A. , Mehta Vishal , Zuberi Zia , Zaidi Amir , Gallagher Mark M. 
Published: November 2021

AbstractBackgroundTransvenous lead extraction (TLE) is rising in parallel to cardiac implantable electronic device implantations. Persistent left side superior vena cava (PLSVC) is a relatively common anatomical variant in the healthy population; TLE in patients with a PLSVC is rare.MethodData were collated from 6 European TLE institutes of 10 patients who had undergone lead extraction with a PLSVC. Patient demographics, procedural challenges and outcomes were reported.ResultsTen patients aged 73.4 ± 7.8 years (60% male) underwent TLE of 20 leads (3 left ventricle, 10 right ventricle, 7 right atrium) with dwell time of 82.95 ± 39.1 months. Of the 10 cases, 4 had an infection indication and 5 were biventricular system extractions; 25% of the extracted leads were defibrillator leads. The majority of the procedures were completed in the cardiac catheterization suite (80%) under general anaesthesia (60%) by cardiologists (80%) using a rotational powered sheath (65%). The Tandem approach was used successfully in 3 cases. Complete procedural success was obtained in 100% of cases in the absence of complications within 127.4 ± 74.7 min. There was no 30‐day mortality.ConclusionTLE in PLSVC is feasible albeit rare. Standard extraction techniques in experienced hands are associated with favorable outcomes; the Tandem procedure may be an additional technique to improve the safety and efficacy of TLE in PLSVC.
The Sigma‐2 Receptor/TMEM97 Agonist PB28 Suppresses Cell Proliferation and Invasion by Regulating the PI3K‐AKT‐mTOR Signalling Pathway in Renal Cancer
Authors: Zhan Bo , Zhang Zhe , Piao Chiyuan , Dong Xiao , Du Yang , Kong Chuize , Jiang Yuanjun 
Published: November 2021

AbstractSigma‐2 receptor/TMEM97 is overexpressed in many tumours, and sigma‐2 receptor ligands are under investigation for cancer therapy. We intended to evaluate the effect of PB28 on renal cancer in proliferation, migration and invasion in vitro and in vivo. Invasive renal cancer cell lines treated with PB28 (or sigma‐2 receptor antagonist 1) were subjected to cell proliferation, migration and invasion assays. The therapeutic effect of PB28 was performed on nude mice. Western blot for proteins in the PI3K‐AKT‐mTOR signalling pathway was conducted. A CCK‐8 assay was used to examine the effect of the combination of PB28 and cisplatin on renal cancer cells. Significant inhibitory effects were observed on proliferation, migration and invasion of 786‐O and ACHN cells after culturing with PB28. But, the outcomes of sigma‐2 receptor antagonist 1 presented the opposite tendency. PB28 significantly inhibited the proliferative and invasive ability of OS‐RC‐2 cells in vivo. Treatment resulted in decreased phosphorylation of constituents of the PI3K‐AKT‐mTOR pathway. The combination of PB28 and cisplatin showed enhanced efficacy in the inhibition of renal cancer cell proliferation. Taken together, PB28 inhibited the tumorigenic behaviours of renal cancer cells by regulating the PI3K‐AKT‐mTOR signalling pathway and was expected to be a sensitizer of cisplatin.