bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined inhibition of Ref‐1 and STAT3 leads to synergistic tumour inhibition in multiple cancers using 3D and in vivo tumour co‐culture models
Authors: Caston Rachel A. , Shah Fenil , Starcher Colton L. , Wireman Randall , Babb Olivia , Grimard Michelle , McGeown Jack , Armstrong Lee , Tong Yan , Pili Roberto , Rupert Joseph , Zimmers Teresa A. , Elmi Adily N. , Pollok Karen E. , Motea Edward A. , Kelley Mark R. , Fishel Melissa L. 
Published: December 2020

AbstractWith a plethora of molecularly targeted agents under investigation in cancer, a clear need exists to understand which pathways can be targeted simultaneously with multiple agents to elicit a maximal killing effect on the tumour. Combination therapy provides the most promise in difficult to treat cancers such as pancreatic. Ref‐1 is a multifunctional protein with a role in redox signalling that activates transcription factors such as NF‐κB, AP‐1, HIF‐1α and STAT3. Formerly, we have demonstrated that dual targeting of Ref‐1 (redox factor‐1) and STAT3 is synergistic and decreases cell viability in pancreatic cancer cells. Data presented here extensively expands upon this work and provides further insights into the relationship of STAT3 and Ref‐1 in multiple cancer types. Using targeted small molecule inhibitors, Ref‐1 redox signalling was blocked along with STAT3 activation, and tumour growth evaluated in the presence and absence of the relevant tumour microenvironment. Our study utilized qPCR, cytotoxicity and in vivo analysis of tumour and cancer‐associated fibroblasts (CAF) response to determine the synergy of Ref‐1 and STAT3 inhibitors. Overall, pancreatic tumours grown in the presence of CAFs were sensitized to the combination of STAT3 and Ref‐1 inhibition in vivo. In vitro bladder and pancreatic cancer demonstrated the most synergistic responses. By disabling both of these important pathways, this combination therapy has the capacity to hinder crosstalk between the tumour and its microenvironment, leading to improved tumour response.
Naringin attenuates cisplatin‐ and aminoglycoside‐induced hair cell injury in the zebrafish lateral line via multiple pathways
Authors: Li Ming , Liu Jingwen , Liu Dong , Duan Xuchu , Zhang Qingchen , Wang Dawei , Zheng Qingyin , Bai Xiaohui , Lu Zhiming 
Published: December 2020

AbstractExposure to ototoxic drugs is a significant cause of hearing loss that affects about 30 thousand children with potentially serious physical, social and psychological dysfunctions every year. Cisplatin (CP) and aminoglycosides are effective antineoplastic or bactericidal drugs, and their application has a high probability of ototoxicity which results from the death of hair cells (HCs). Here, we describe the therapeutic effect of the flavonoid compound naringin (Nar) against ototoxic effects of cisplatin and aminoglycosides include gentamicin (GM) and neomycin (Neo) in zebrafish HCs. Animals incubated with Nar (100‐400 μmol/L) were protected against the pernicious effects of CP (150‐250 μmol/L), GM (50‐150 μmol/L) and Neo (50‐150 μmol/L). We also provide evidence for the potential mechanism of Nar against ototoxicity, including antioxidation, anti‐apoptosis, promoting proliferation and hair cell regeneration. We found that mRNA levels of the apoptotic‐ and pyroptosis‐related genes are regulated by Nar both in vivo and in vitro. Finally, by proving that Nar does not affect the anti‐tumour efficacy of CP and antibacterial activity of aminoglycosides in vitro, we highlight its value in clinical application. In conclusion, these results unravel a novel therapeutic role for Nar as an otoprotective drug against the adverse effects of CP and aminoglycosides.
Experimental evaluation of nickel and cobalt release from tools and self‐reported prevalence of nickel and cobalt allergy in the German hairdressing trade
Authors: Symanzik C. , Skudlik C. , John S.M. 
Published: December 2020

AbstractBackgroundNickel release from some metal tools in the hairdressing trade has been sporadically evidenced, whereas data about cobalt release from metal tools in the hairdressing trade are lacking.ObjectivesTo screen metal tools for nickel and cobalt release and to estimate the prevalence of nickel allergy and cobalt allergy in the German hairdressing trade.MethodsFour hundred seventy‐five metal tools in the hairdressing trade were tested in three North German states with a nickel spot test for nickel release and with a cobalt spot test for cobalt release. Seventy hairdressers were surveyed with a standardized questionnaire to collect data about the tested metal tools as well as the prevalence of nickel allergy and cobalt allergy.ResultsOne hundred thirty‐one of 475 metal tools (27.6%) – 60 of 60 hair clips (100%), five of five crochet hooks (100%), 24 of 40 tweezers (60.0%), 33 of 75 sectioning clips (44.0%), five of 32 straight razors (15.6%), and four of 45 tail combs (8.9%) – released nickel and 10 of 475 metal tools (2.1%) – three of 40 tweezers (7.5%), four of 60 hair clips (6.7%), one of 32 straight razors (3.1%), and two of 75 sectioning clips (2.7%) – released cobalt. Eight of 63 female hairdressers (12.7%) suffered from nickel allergy and two of 63 female hairdressers (3.2%) suffered from cobalt allergy.ConclusionsMetal tools in the German hairdressing trade – with which a prolonged skin contact is intended – release nickel and cobalt in allergologically relevant amounts and thus should be taken into account as occupational sources of exposure to nickel and cobalt.
Professional judgement in clinical practice (part 3): A better alternative to strong evidence‐based medicine
Authors: Mugerauer Robert 
Published: December 2020

AbstractParts 1 and 2 in this series of three articles have shown that and how strong evidence‐based medicine has neither a coherent theoretical foundation nor creditable application to clinical practice. Because of its core commitment to the discredited positivist tradition it holds both a false concept of scientific knowledge and misunderstandings concerning clinical decision‐making. Strong EBM continues attempts to use flawed adjustments to recover from the unsalvageable base view. Paper three argues that a promising solution is at hand if we can manage several modes of inclusion. A modified original, moderate version of EBM continues though usually overshadowed. As definitively laid out by Sackett in the 1990s, clinical decision making is intended to be person‐centered, recognizing and integrating multiple modes of evidence and knowledge that have been marginalized: professional experience, illness narratives, and individual patients' values and preferences. Complementary resources are at hand: interpretative understanding and practice, such as philosophical anthropology, hermeneutical phenomenology, complexity theory, and phronetic practices respond to the major problems and open new possibilities. Phronesis is especially important in regard to public decision making. Within part 3 an additional tone necessarily occurs. While most of papers 1, 2, and 3 are written in the classical mode of contrasting the theoretical‐logical and empirical evidence offered by contending positions bearing on the decision making and judgement in clinical practice, a shift occurs when considerations move beyond what is possible for clinical practitioners to accomplish. A different, discontinuous level of power operates in the trans‐personal realm of instrumental policy, insurance, and hospital management practices. In this social‐economic‐political‐ethical realm what happens in clinical practice today increasingly becomes a matter of what is “done unto” clinical practitioners, of what hampers their professional action and thus care of individual patients and clients.
Case definitions for skin lesion syndromes in chinook salmon farmed in Marlborough Sounds, New Zealand
Authors: Johnston Hazel , Symonds Jane , Walker Seumas , Preece Mark , Lopez Cesar , Nowak Barbara 
Published: December 2020

AbstractSkin lesions are commonly reported in farmed salmonids. Chinook salmon (Oncorhynchus tshawytscha), introduced from California USA, is the only salmonid species commercially farmed in New Zealand, although trout are cultured for release by Fish and Game New Zealand. There are several farming areas in New Zealand, including Marlborough Sounds, Canterbury and Stewart Island. While the industry has not been affected by any of the major production diseases seen internationally, skin lesions have been recorded with an increase in prevalence from 2012 onwards in the Marlborough Sounds and were associated with elevated summer mortalities on farms in 2015. Here we are proposing case definitions for different types of skin lesions for future monitoring and research. Based on our current understanding of the above skin conditions, we developed case definitions for spots, spreading spots, ulcerated spreading spots and Regular Outline Flank Ulcers defining a positive case for three study units, including individual fish, pen/unit and farm.
ISO order imbalances and individual stock returns
Authors: Cox Justin 
Published: December 2020

AbstractI examine the relation between intermarket sweep order (ISO) order imbalances and the daily returns of individual stocks. First, I show that ISO order imbalances are positively related to contemporaneous returns. Second, I find that price pressures emanating from ISO imbalances are persistent and predict cumulative abnormal returns up to 2 months. The predictive power of ISO order imbalances on contemporaneous and future abnormal returns is strongest for firms in the smallest firm size quintile. Finally, I analyze herding among ISO order imbalances and find strong commonality. My results indicate that ISOs contribute to both short‐ and long‐term return formation.
Microwave vacuum drying of Pereskia aculeata Miller leaves: Powder production and characterization
Authors: Monteiro Ricardo Lemos , Garcia Analiz Hüntemann , Tribuzi Giustino , Mattar Carciofi Bruno Augusto , Laurindo João Borges 
Published: December 2020

AbstractPereskia aculeata Miller (PAM) is a non‐conventional leaf vegetable that has drawn attention due to its remarkable nutritional quality, such as a high protein, carotenoids, and vitamin content. This study aimed to produce dehydrated PAM‐leaves by air‐drying (AD), freeze‐drying (FD), and microwave vacuum drying (MWVD), and evaluate the quality and physicochemical properties (moisture, aw, bulk density, particle density, bed porosity, apparent solubility, dispersion time, and β‐carotene content) of the dried powdered leaves. To produce powders with aw lower than 0.4 and moisture content below 6%, MWVD showed a drying time of 1.3 and 0.8 hr using the input power of 300 W and 500 W, respectively; besides, the final drying time for AD and FD was around 10 and 16 hr, respectively. MWVD dried powder showed bed porosity of ~67% and solubility around 30%, slightly less porous, and with a similar solubility to the FD‐powder. PAM powder dehydrated by MWVD preserved about 66% of the original content of β‐carotene equivalent for both microwave power, which is only 15% lower of the content in the FD‐powder, and twice bigger than AD‐powder. The MWVD of PAM allowed obtaining high‐quality powders comparable to the freeze‐dried PAM.Practical ApplicationsAs Pereskia aculeata Miller (PAM) is a leaf vegetable with high protein, carotenoids, and vitamin contents, its powders can be a suitable and stable presentation for a new proteinaceous product. This use of PAM as a powder with high protein concentration is in agreement with the global trend that seeks new plant‐based protein sources. In this way, the study of drying processes that result in PAM powders with suitable properties is of interest to researchers and food industries.
Utilization and Functional Outcomes Among Medicare Home Health Recipients Varied Across Living Situations
Authors: Wang Jinjiao , Ying Meiling , Temkin‐Greener Helena , Shang Jingjing , Caprio Thomas V. , Li Yue 
Published: December 2020

BACKGROUND/OBJECTIVESHome health (HH) is a major type of home‐based skilled care available to Medicare beneficiaries. We examined the association between living situation (home alone, home with others, and assisted living (AL) residence) and utilization and functional outcomes among Medicare HH recipients.DESIGNAnalysis of national data from the Outcome and Assessment Information Set, HH Compare, Medicare claims, and Area Health Resource Files.SETTINGMedicare‐certified HH agencies in the United States.PARTICIPANTSNational population of Medicare beneficiaries ≥65 years old who received HH care in CY 2017 (N = 6,637,496).MEASUREMENTSOutcomes included time‐to‐event measures of hospitalization and emergency department (ED) visits, and improvement in activities of daily living (ADL) from the start to the end of the HH admission.RESULTSAL residents (12%) and patients living alone at home (24%) had longer survival time without hospitalization and ED visits than patients living with others at home (64%). Adjusting for covariates and HH agency‐level random effects, and compared with patients living with others, AL residents had lower risk of hospitalization (hazard ratio (HR) = 0.85, P < .001) and ED visit (HR = 0.92, P < .001); however, less ADL improvement (β = 0.29 (29% less of total independence in one ADL)); and patients living alone had lower risk of hospitalization (HR = 0.94, P < .001) and ED visit (HR = 0.93, P < .001), yet more ADL improvement (β = −0.15 (15% more of total independence in one ADL)).CONCLUSIONIn the national population of Medicare HH recipients, patients living with others at home had the highest risk of hospitalization and ED visits, whereas AL residents had the lowest risk of hospitalization and patients living alone at home had the lowest risk of ED visits, meaning that combined support from HH and AL reduces acute care admissions. Evidence‐based interventions are needed for HH patients living with others at home to avoid unnecessary acute care use.
Hippocampal hyperglutamatergic signaling matters: Early targeting glutamate neurotransmission as a preventive strategy in Alzheimer's disease
Authors: Gulyaeva Natalia V. 
Published: December 2020

AbstractThis Editorial highlights a remarkable study in the current issue of the Journal of Neurochemistry in which Hascup and coworkers provide novel data showing that riluzole, an anti‐glutamatergic drug, may be a promising early intervention strategy for Alzheimer's disease (AD), aimed at restoring glutamate neurotransmission prior to amyloid beta (Aβ) plaque accumulation and cognitive decline. The mice APP/PS1, a model of AD, initially are cognitively normal but have elevated glutamate release in the hippocampus at 2–4 months of age. They begin showing cognitive decline and Aβ plaque accumulation at approximately 6–8 months of age, and show obvious AD neuropathology and cognitive impairment at 10–12 months. The riluzole treatment over 4 months (at 2–6 months of age) targeting early changes in glutamatergic neurotransmission prevents cognitive decline observed at 12 months of age and restores glutamatergic neurotransmission. This is one of the most convincing preclinical evidence supporting the idea of targeting glutamate neurotransmission in patients at risk for AD and to use riluzole for this purpose.
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Mutual Fund Holdings of Credit Default Swaps: Liquidity, Yield, and Risk
Authors: JIANG WEI , OU JITAO , ZHU ZHONGYAN 
Published: December 2020

ABSTRACTThis study analyzes the motivations for and consequences of funds' credit default swap (CDS) investments using mutual funds' quarterly holdings from pre‐ to postfinancial crisis. Funds invest in CDS when facing unpredictable liquidity needs. Funds sell more in reference entities when the CDS is liquid relative to the underlying bonds and buy more when the CDS‐bond basis is more negative. To enhance yield, funds engage in negative basis trading and sell CDS with the highest spreads within rating categories, and with spreads higher than those of their bond portfolios. Funds with superior portfolio returns also demonstrate more skill in CDS trading.
Quantifying CD138+ cells in the endometrium to assess chronic endometritis in women at risk of recurrent pregnancy loss: A prospective cohort study and rapid review
Authors: Rimmer Michael P. , Fishwick Katherine , Henderson Ian , Chinn David , Al Wattar Bassel H. , Quenby Siobhan 
Published: December 2020

AbstractObjectiveTo determine the value of uterine CD138+ cells, as a marker of chronic endometritis, in predicting subsequent reproductive outcome in women with history of recurrent pregnancy loss.DesignA prospective longitudinal study.SettingTertiary specialized clinic.PatientsWomen with history of recurrent pregnancy loss or implantation failure over a 12‐months follow‐up period.InterventionWe quantified the CD138+ cells/high powered field (hpf) using immunohistochemistry and image analysis of endometrial biopsies obtained during the secretory stage post ovulation.Main outcome measuresLive birth and subsequent pregnancy loss. We calculated the receiver operator curve for predicting subsequent pregnancy loss and reported using relative risk (RR) and 95% confidence intervals (CI).ResultsWe enrolled 344 women of whom 88 became pregnant (88/344, 25.5%). Half of them had a subsequent live birth (47/88, 53%) and the rest lost their pregnancy (41/88, 46%). The median CD138+ score was significantly lower in the live birth group (P < 0.005) and women with a CD138+ score ≥ 16/hpf had a higher risk of subsequent miscarriage (RR 10.0, 95% CI 2.78–36.02). CD138+ cells count showed a good prediction for subsequent pregnancy loss in high‐risk women with an area under the curve of 0.75 (95% CI 0.59–0.82, P = 0.01). A cut‐off value of 4–6 cells/hpf offered the best predictive accuracy with higher scores predicting worse reproductive outcome. Our findings are limited by the small event rate and the sample size of our cohort.ConclusionQuantifying CD138+ cells by immunohistochemistry in women with a history of recurrent pregnancy loss is helpful to diagnose chronic endometritis and predict subsequent reproductive outcome.
Transthyretin amyloid deposits in lumbar spinal stenosis and assessment of signs of systemic amyloidosis
Authors: Eldhagen P. , Berg S. , Lund L.H. , Sörensson P. , Suhr O.B. , Westermark P. 
Published: December 2020

AbstractBackgroundWild‐type transthyretin (ATTRwt) amyloidosis is the most common systemic amyloidosis in Western countries and manifests mainly as progressive restrictive cardiomyopathy.ObjectiveTo study the prevalence of ATTR deposits in ligament tissue in patients undergoing surgery for lumbar spinal stenosis and to assess whether these deposits are associated with cardiac amyloidosis.Materials and methodsA total of 250 patients, aged 50–89 (57% women), none with known cardiovascular disease, were included. Ligaments were investigated microscopically for amyloid. ATTR type was determined by immunohistochemistry and fibril type by Western blot. The amount of amyloid was graded 0‐4. All patients with grade 3‐4 ATTR deposits were offered cardiac investigation including ECG, cardiac ultrasound, plasma NT‐proBNP and cardiac magnetic resonance (CMR), including modern tissue characterization.ResultsAmyloid was identified in 221 of the samples (88.4%). ATTR appeared in 93 samples (37%) of whom 42 (17 women and 25 men) were graded 3‐4; all had fibril type A (mixture of full‐length TTR and fragmented TTR). Twenty‐nine of 42 patients with grade 3‐4 ATTR deposits accepted cardiovascular investigations; none of them had definite signs of cardiac amyloidosis, but five men had a history of carpal tunnel syndrome.ConclusionsThe prevalence of ATTR deposits in ligamentum flavum in patients with lumbar spinal stenosis was high but not associated with manifest ATTR cardiac amyloidosis. However, the findings of fibril type A, the prevalence of previous carpal tunnel syndrome and ATTR amyloid in surrounding adipose and vascular tissue indicate that amyloid deposits in ligamentum flavum may be an early manifestation of systemic ATTR disease.
An intersectional perspective on the intergenerational transmission of trauma and state‐perpetrated violence
Authors: Heberle Amy E. , Obus Elsia A. , Gray Sarah A. O. 
Published: December 2020

AbstractWe utilize intersectionality as the framework for analyzing and critiquing the literature on the intergenerational transmission of trauma in early childhood. In particular, we assess the extent to which the literature replicates the oppression of marginalized and minoritized children and families by deemphasizing traumas and traumatic processes that are attributable to interlocking systems of oppression. In addition, building on the emphasis on systems that is central to intersectionality, we assess the degree to which the literature engages with trauma perpetrated through formal social systems. We assert that an intersectional lens demands acknowledgement of state‐perpetrated violence and that this acknowledgment is absent from the extant literature. To illustrate our argument, we present three structural analyses (“cases”) of state‐perpetrated violence, leveraging life course theory and theories of historical and cultural trauma in addition to intersectionality theory to draw inferences about the intergenerational impacts of these cases. Through our analysis, we demonstrate how efforts to reduce contemporary state‐perpetrated violence and repair the effects of historical state‐perpetrated violence are well aligned with ongoing efforts in the public policy arena at promoting early childhood mental health and family thriving. We close with a proposed agenda for better integrating such efforts into research and policy.
A qualitative study of service users’ experiences of mental health nurses’ knowledge and skills in relation to medication
Authors: Pearson Mark , Sibson Tara , Carter Timothy 
Published: December 2020

AbstractIntroductionThe role of the mental health nurse in relation to medications remains complex. Despite an increasing focus on pharmacology within pre‐registration nurse education, there is limited research exploring how mental health service users experience mental health nurses’ knowledge and skills in relation to medication.AimTo explore the experiences of service users working with mental health nurses, in relation to the nurses’ knowledge and skills associated with medicines management.MethodThe research prioritized the principles of co‐production and was undertaken collaboratively with a researcher with lived experience. Data were collected via semi‐structured interviews with individuals who have accessed UK mental health services. Interviews were audio‐recorded, transcribed verbatim and subjected to thematic analysis.ResultsThree themes were generated from the data: inconsistencies in knowledge and practice, holistic therapeutic engagement and dialogical approach to medicines.DiscussionService users may have a sense of uncertainty around the role of the nurse, potentially resulting in frustration and anxiety. However, mental health nurses also possess unique skills in relation to medicines management.Implications for practiceThe findings emphasize that service users value not only pharmacological knowledge but also unique skills in facilitating dialogue, prioritising shared decision‐making and practical support in medicines optimization.