bluuebunny/crossref_metadata_2025_split huggingface dataset:
Virus‐triggered secondary hemophagocytic lymphohistiocytosis
Authors: Imashuku Shinsaku , Morimoto Akira , Ishii Eiichi 
Published: June 2021

AbstractPrimary (familial/hereditary) and secondary (non‐familial/hereditary) hemophagocytic lymphohistiocytosis (HLH) are hyperinflammatory and hypercytokinemic syndromes. Secondary HLH includes infection‐ (eg viral/bacterial/fungal/parasitic) and non–infection‐ (eg collagen disease or malignancy) related diseases. Viral HLH is the major type among all age groups. Secondary viral HLH and primary HLH must be differentiated carefully because primary HLH can be associated with viral infection(s), and the outcome is dismal without a timely diagnosis and hematopoietic stem cell transplantation (HSCT). Epstein‐Barr virus (EBV)‐related HLH (EBV‐HLH) is the most common type of viral HLH in childhood. For non–EBV‐HLH, appropriate treatment of viral infection, followed by immunomodulatory agent(s) such as corticosteroids, intravenous immunoglobulin or cyclosporine A, is usually successful; however, recent SARS‐CoV‐2‐related HLH may become life‐threatening. EBV‐HLH may occur heterogeneously associated with the primary infection, with chronic active EBV infection or with underlying primary HLH. Although immunomodulatory agent(s) are effective in the majority of EBV‐HLH cases, management differs from that of non–EBV‐HLH because severe and refractory cases may require etoposide‐containing HLH‐1994/2004 regimens or other experimental agents. The novel agent, emapalumab (an anti–IFN‐γ monoclonal antibody) can be used to treat EBV‐HLH cases to avoid the risk of secondary malignancy due to etoposide. Finally, HSCT is required for refractory EBV‐HLH cases and can also be curative in some other cases.
The impact of genetic risk on liver fibrosis in non‐alcoholic fatty liver disease as assessed by magnetic resonance elastography
Authors: Ajmera Veeral , Liu Amy , Bettencourt Ricki , Dhar Debanjan , Richards Lisa , Loomba Rohit 
Published: June 2021

SummaryBackgroundVariants in multiple genetic loci modify the risk of non‐alcoholic fatty liver disease (NAFLD) and cirrhosis but there are limited data on the quantitative impact of variant copies on liver fibrosis.AimTo investigate the effect of PNPLA3, TM6SF2, MBOAT7, GCKR and HSD17B13 genotype on liver fibrosis assessed by magnetic resonance elastography (MRE), a reproducible, accurate, continuous biomarker of liver fibrosis.MethodsThis is a cross‐sectional analysis derived from a well‐characterised cohort at risk for NAFLD who underwent genotyping and MRE assessment. Liver stiffness (LS) was estimated using MRE and advanced fibrosis was defined as liver stiffness ≥3.63 kilopascals (kPa). Univariable and multivariable linear and logistic regression analysis, were used to assess the association between genotype and MRE.ResultsTwo hundred sixty‐four patients (63% women) with a mean age 53 (±17) years, and 31% Hispanic ethnicity with genotyping and MRE were included. The odds of advanced fibrosis were 3.1 (95% CI: 1.1‐8.9, P = 0.04) for CG and 6.5 (95% CI: 2.2‐18.9, P < 0.01) for GG compared to CC PNPLA3 genotype. Each PNPLA3 risk variant copy was associated with 0.40 kPa (95% CI: 0.19‐0.61, P < 0.01) increase in LS on MRE in analysis adjusted for age, sex and BMI and there was significant genotype‐age interaction (P < 0.01). Conversely, the protective TA allele in HSD17B13 was associated with a −0.41 kPa (95% CI: −0.76 to −0.05, P = 0.03) decrease in liver stiffness on MRE multivariable analysis.ConclusionKnowledge of PNPLA3 and HSD17B13 genotype may assist in the non‐invasive risk stratification of NAFLD with closer monitoring recommended for those with high genetic risk.
Novel soluble guanylyl cyclase activators increase glomerular cGMP, induce vasodilation and improve blood flow in the murine kidney
Authors: Stehle Daniel , Xu Min Ze , Schomber Tibor , Hahn Michael G. , Schweda Frank , Feil Susanne , Kraehling Jan R. , Eitner Frank , Patzak Andreas , Sandner Peter , Feil Robert , Bénardeau Agnès 
Published: June 2021

Background and PurposeGeneration of cGMP via NO‐sensitive soluble guanylyl cyclase (sGC) has been implicated in the regulation of renal functions. Chronic kidney disease (CKD) is associated with decreased NO bioavailability, increased oxidative stress and oxidation of sGC to its haem‐free form, apo‐sGC. Apo‐sGC cannot be activated by NO, resulting in impaired cGMP signalling that is associated with chronic kidney disease progression. We hypothesised that sGC activators, which activate apo‐sGC independently of NO, increase renal cGMP production under conditions of oxidative stress, thereby improving renal blood flow (RBF) and kidney function.Experimental ApproachTwo novel sGC activators, runcaciguat and BAY‐543, were tested on murine kidney. We measured cGMP levels in real time in kidney slices of cGMP sensor mice, vasodilation of pre‐constricted glomerular arterioles and RBF in isolated perfused kidneys. Experiments were performed at baseline conditions, under L‐NAME‐induced NO deficiency, and in the presence of oxidative stress induced by ODQ.Key ResultsMouse glomeruli showed NO‐induced cGMP increases. Under baseline conditions, sGC activator did not alter glomerular cGMP concentration or NO‐induced cGMP generation. In the presence of ODQ, NO‐induced glomerular cGMP signals were markedly reduced, whereas sGC activator induced strong cGMP increases. L‐NAME and ODQ pretreated isolated glomerular arterioles were strongly dilated by sGC activator. sGC activator also increased cGMP and RBF in ODQ‐perfused kidneys.Conclusion and ImplicationsGC activators increase glomerular cGMP, dilate glomerular arterioles and improve RBF under disease‐relevant oxidative stress conditions. Therefore, sGC activators represent a promising class of drugs for chronic kidney disease treatment.LINKED ARTICLESThis article is part of a themed issue on cGMP Signalling in Cell Growth and Survival. To view the other articles in this section visithttp://onlinelibrary.wiley.com/doi/10.1111/bph.v179.11/issuetoc
Activation of Wnt signalling reduces the population of cancer stem cells in ameloblastoma
Authors: Kim Hyun‐Yi , Li Shujin , Lee Dong‐Joon , Park Jin Hoo , Muramatsu Takashi , Harada Hidemitsu , Jung Young‐Soo , Jung Han‐Sung 
Published: June 2021

AbstractObjectivesThe treatment of ameloblastoma, an odontogenic epithelial tumour destroying jawbone, mainly depends on radical destructive resections. Other therapeutic options are limited by the characteristics of ameloblastoma, such as high recurrence rates and resistance to radiation and chemotherapy, which implies possible existence of cancer stem cells (CSCs) in ameloblastoma. Here, we identified a putative CSC population in immortalized and primary human ameloblastoma cells and examined possible therapeutic reagents to reduce the CSC population.MethodsWe investigated subpopulations of AM‐1 cell line and human ameloblastoma cells using immunocytochemistry and flow cytometry and the effects of Wnt signalling activators on the 2‐ and 3‐dimensional cultured ameloblastoma cells using molecular biological analyses.ResultAmong heterogenous ameloblastoma cells, small‐sized and round‐shaped cells were found to be proliferative and expressed a marker of dental epithelial stem cells, SRY‐box 2 (Sox2). Exogenous activation of Wnt signalling using glycogen synthase kinase 3β inhibitors, lithium chloride (LiCl) and valproic acid (VPA), increased the cell size and decreased proliferation of cells and expression of Sox2 in 2 dimensionally cultured AM‐1 and human primary ameloblastoma cells. Furthermore, the growth of 3 dimensionally cultured AM‐1 cells as suspended or embedded in gel was suppressed by treatment with Wnt signalling activators, VPA and CHIR99021, or antibodies to sclerostin, an antagonist of Wnt signalling.ConclusionWe suggest that Wnt signalling activators are potential drug candidates to suppress CSCs in ameloblastoma.
Becoming society again: Reimagining new social contracts through Scandinavian creation theology
Authors: Gerle Elisabeth 
Published: June 2021

AbstractThis article focuses on bodily care as the basis of economy. Drawing on Luther and Scandinavian Creation Theology, with an emphasis on shared situatedness and society, I discuss contemporary threats to welfare states. Conservative arguments in favor of family and small communities, combined with charity, provide a cultural/religious alibi for a global “neoliberalism,” where citizens are replaced by customers, and where power and resources from professions are transferred to controllers, due to the logic of NPM. In a critical discussion with Hannah Arendt, I argue that we need a politics that reinforce and develop new social contracts, national as well as international, based on an inclusive demos. A pre‐political Lutheran ethos can give inspiration to act for the common good, transcending any homogenous ethnos. The local and national are crucial for sustaining body and mind. However, this is increasingly combined with global and planetary entanglements. Interdependency reveals itself as planetary, where disappearing rain forests, melting icebergs, and the ongoing extinction of species are threats to our shared future. Therefore, rather than emphasizing the individual as a consumer on a global market with neutral administrators administering control and obedience, new kinds of contracts are needed. Core values of the pre‐political, such as care for bodily life and minds, may, in collaboration with national and international political assemblies, develop a planetary consciousness able to act for the common good, for a global demos with structures of solidarity.
Quality appraisal of systematic reviews of interventions for children with cerebral palsy reveals critically low confidence
Authors: Kolaski Kat , Romeiser Logan Lynne , Goss Katherine D , Butler Charlene 
Published: June 2021

AimTo evaluate the methodological quality of recent systematic reviews of interventions for children with cerebral palsy in order to determine the level of confidence in the reviews’ conclusions.MethodA comprehensive search of 22 databases identified eligible systematic reviews with and without meta‐analysis published worldwide from 2015 to 2019. We independently extracted data and used A Measurement Tool to Assess Systematic Reviews‐2 (AMSTAR‐2) to appraise methodological quality.ResultsEighty‐three systematic reviews met strict eligibility criteria. Most were from Europe and Latin America and reported on rehabilitative interventions. AMSTAR‐2 appraisal found critically low confidence in 88% (n=73) because of multiple and varied deficiencies. Only 7% (n=6) had no AMSTAR‐2 critical domain deficiency. The number of systematic reviews increased fivefold from 2015 to 2019; however, quality did not improve over time.InterpretationMost of these systematic reviews are considered unreliable according to AMSTAR‐2. Current recommendations for treating children with CP based on these flawed systematic reviews need re‐evaluation. Findings are comparable to reports from other areas of medicine, despite the general perception that systematic reviews are high‐level evidence. The required use of current widely accepted guidance for conducting and reporting systematic reviews by authors, peer reviewers, and editors is critical to ensure reliable, unbiased, and transparent systematic reviews.
What this paper adds

Confidence was critically low in the conclusions of 88% of systematic reviews about interventions for children with cerebral palsy (CP).

Quality issues in the sample were not limited to systematic reviews of non‐randomized trials, or to those about certain populations of CP or interventions.

The inclusion of meta‐analysis did not improve the level of confidence in these systematic reviews.

Numbers of systematic reviews on this topic increased over the 5 search years but their methodological quality did not improve.
Adrenocortical dysfunction in rheumatoid arthritis: Α narrative review and future directions
Authors: Filippa Maria G. , Tektonidou Maria G. , Mantzou Aimilia , Kaltsas Gregory A. , Chrousos George P. , Sfikakis Petros P. , Yavropoulou Maria P. 
Published: June 2021

AbstractBackgroundIatrogenic adrenal insufficiency (AI) secondary to long‐term treatment with exogenous glucocorticoids (GC) is common in patients with systematic rheumatic diseases, including rheumatoid arthritis (RA). Moreover, a proportion of these patients is always in need of even small doses of glucocorticoids to maintain clinical remission, despite concomitant treatment with conventional and biologic disease‐modifying drugs.MethodsWe conducted a literature review up to December 2020 on (a) the incidence of AI in both long‐term GC‐treated and GC‐treatment naïve RA patients; (b) the potential effects of increased levels of circulating proinflammatory cytokines, as well as of chronic stress, in adrenocortical function in RA; (c) the circadian cortisol rhythm in RA; and (d) established and evolving methods of assessment of adrenocortical function.ResultsUp to 48% of RA patients develop glucocorticoid‐induced AI; however, predictors are not established, while adrenocortical dysfunction may also occur in GC‐treatment naïve RA patients. Experimental and clinical data have suggested that inadequate production of endogenous cortisol relative to enhanced clinical needs associated with the systemic inflammatory response, coined as the ‘disproportion principle’, may operate in RA. Although the underlying mechanisms are unknown, both proinflammatory cytokines and chronic stress may contribute the most in the adrenals hyporesponsiveness and the target tissue glucocorticoid resistance that have been described, but not systematically studied. A precise longitudinal assessment of endogenous cortisol production may be needed for optimal RA management.ConclusionApart from iatrogenic AI, an intrinsically compromised adrenal reserve in RA may have a pathogenetic role and interfere with effective management, thus deserving further research.
Experience‐related enhancements in striatal temporal encoding
Authors: Bruce Robert A. , Weber Matthew A. , Volkman Rachael A. , Oya Mayu , Emmons Eric B. , Kim Youngcho , Narayanan Nandakumar S. 
Published: June 2021

AbstractTemporal control of action is key for a broad range of behaviors and is disrupted in human diseases such as Parkinson's disease and schizophrenia. A brain structure that is critical for temporal control is the dorsal striatum. Experience and learning can influence dorsal striatal neuronal activity, but it is unknown how these neurons change with experience in contexts which require precise temporal control of movement. We investigated this question by recording from medium spiny neurons (MSNs) via dorsal striatal microelectrode arrays in mice as they gained experience controlling their actions in time. We leveraged an interval timing task optimized for mice which required them to “switch” response ports after enough time had passed without receiving a reward. We report three main results. First, we found that time‐related ramping activity and response‐related activity increased with task experience. Second, temporal decoding by MSN ensembles improved with experience and was predominantly driven by time‐related ramping activity. Finally, we found that a subset of MSNs had differential modulation on error trials. These findings enhance our understanding of dorsal striatal temporal processing by demonstrating how MSN ensembles can evolve with experience. Our results can be linked to temporal habituation and illuminate striatal flexibility during interval timing, which may be relevant for human disease.
A cross‐sectional, prospective ocular motor study in 72 patients with Niemann‐Pick disease type C
Authors: Bremova‐Ertl Tatiana , Abel Larry , Walterfang Mark , Salsano Ettore , Ardissone Anna , Malinová Věra , Kolníková Miriam , Gascón Bayarri Jordi , Reza Tavasoli Ali , Reza Ashrafi Mahmoud , Amraoui Yasmina , Mengel Eugen , Kolb Stefan A. , Brecht Andreas , Bardins Stanislavs , Strupp Michael 
Published: June 2021

AbstractObjectiveTo characterize ocular motor function in patients with Niemann‐Pick disease type C (NPC).MethodsIn a multicontinental, cross‐sectional study we characterized ocular‐motor function in 72 patients from 12 countries by video‐oculography. Interlinking with disease severity, we also searched for ocular motor biomarkers. Our study protocol comprised reflexive and self‐paced saccades, smooth pursuit, and gaze‐holding in horizontal and vertical planes. Data were compared with those of 158 healthy controls (HC).ResultsSome 98.2% of patients generated vertical saccades below the 95% CI of the controls’ peak velocity. Only 46.9% of patients had smooth pursuit gain lower than that of 95% CI of HC. The involvement in both downward and upward directions was similar (51°/s (68.9, [32.7–69.3]) downward versus 78.8°/s (65.9, [60.8–96.8]) upward). Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit correlated best to disease severity. Compensating strategies such as blinks to elicit saccades, and head and upper body movements to overcome the gaze palsy, were observed. Vertical reflexive saccades were more impaired and slower than self‐paced ones. Gaze‐holding was normal. Ocular‐motor performance depended on the age of onset and disease duration.ConclusionsThis is the largest cohort of NPC patients investigated for ocular‐motor function. Vertical supranuclear saccade palsy is the hallmark of NPC. Vertical upward and downward saccades are equally impaired. Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit can be used as surrogate parameters for clinical trials. Compensating strategies can contribute to establishing a diagnosis.
Measuring the intensive care experience: A cross‐sectional survey of patient and family experiences of critical care
Authors: Williams Helen , Gow Jeff , Rana Rezwanul , Rouse Alan , Chinthamuneedi Meher , Beccaria Gavin , Ralph Nicholas 
Published: June 2021

AbstractAims and ObjectivesTo report patient and family intensive care experiences using the Measuring the Intensive Care Experience (MICE) tool across two intensive care units (ICU).BackgroundThe patient and family experience of care is an important indicator for quality improvement of ICUs, yet few studies evaluate both patient and family experiences in relation to overall care quality as well as specifically measuring quality of medical care, nursing care and organisational care as well as overall experience of the quality of intensive care.DesignA cross‐sectional survey.MethodsA 23 item survey was administered to ICU patients and their family members across two ICUs, a regional 189‐bed hospital and a metropolitan 227‐bed hospital in Queensland, Australia. The response rate was 272 of 394 ICU patients (36.4%). STROBE guidelines were used in reporting this study.ResultsFindings indicate a highly positive overall experience of ICU care among patients and families. However, patients reported areas of unmet needs following their stay in ICU broadly related to (1) symptom management, education and information support, and (2) improving the incorporation of patient and family care ICU‐related shared decision‐making.ConclusionsSupportive interventions are needed that target improve symptom management and inform and education ICU patients.Relevance to clinical practiceThe MICE survey facilitated the identification of a range of areas requiring quality improvement. Improving the integration of patients and families into shared decision‐making and support is a key aspect for quality improvement.
‘What matters to you?'—a qualitative study on the views of nursing home residents with dementia regarding the health care they receive
Authors: Nygaard Agnete , Halvorsrud Liv , Grov Ellen Karine , Bergland Astrid 
Published: June 2021

AbstractAims and ObjectiveThis study's aim is to examine what matters to nursing home residents with dementia by exploring their perceptions of nursing home health care through the conceptual lens of person‐centred care.BackgroundDementia is a major contributor to nursing home placement. To understand the meaning of living with dementia, the inclusion of persons with dementia in research studies is essential.MethodsIn total, 35 in‐depth qualitative interviews were conducted with people who have dementia and live in nursing homes. A thematic analysis was applied to analyse the data. Checklist for qualitative studies: Consolidated Criteria for Reporting Qualitative Research (COREQ) https://www.equator‐network.org/reporting‐guidelines/coreq/ResultsThe analysis revealed one overarching theme with four sub‐themes. Different matchings of person‐centred care and routines in health care being the overarching theme. The four sub‐themes were as follows: (a) understanding of the interplay between disabilities and ageing; (b) participating based on one's own preferences and needs; (c) incongruence between the person with dementia's preferences and needs and health‐care support; and (d) working conditions: the relationship between residents and health‐care providers. Despite the substantive focus of researchers on person‐centred care and the positive impact on the nursing home health care of those who receive it, the results showed that nursing home residents still want more person‐centred care.ConclusionsThe results indicate that the incongruence between general routines and individual preferences and needs, as well as the demand to operationalise the person‐centred dimensions of health‐care behaviour in nursing homes, must be resolved. Health care in nursing homes must focus on enabling residents to participate in daily activities and sustain their personhood and sense of self.Relevance to clinical practiceBased on the residents' statements, the results contribute to the fields of dementia education, health‐care provision and policy‐making and may be used to achieve person‐centredness and governance.
COVID‐19 risk mitigation behaviors among rural and urban community‐dwelling older adults in summer, 2020
Authors: Probst Janice C. , Crouch Elizabeth L. , Eberth Jan M. 
Published: June 2021

AbstractPurposeRisk mitigation behaviors are important for older adults, who experience increased mortality risk from COVID‐19. We examined these reported behaviors among rural and urban community‐dwelling adults aged 65 and older.MethodsWe analyzed public use files from the National Health and Aging Trends Study, which fielded a COVID survey from June to October, 2020, restricted to community‐dwelling adults (n = 2,982). Eight behaviors were studied: handwashing, avoid touching face, mask wearing, limiting shopping, avoiding restaurants or bars, limiting gatherings, avoiding contact with those outside the household, and distancing. Residence was defined as urban (metropolitan county) or rural (nonmetropolitan county). Difference testing used Chi Square tests, with an alpha level of P = .05. Multivariable logistic regression was used to calculate adjusted odds ratios.ResultsRural residents constituted 18.8% (± Standard Error 3.6%) of the study population. In bivariate comparisons, rural older adults were less likely to report 5 of 8 studied behaviors: keep 6‐foot distance (rural: 88.3% ±1.0%, urban 93.2% ±.08%), limit gatherings (rural 87.5% ±1.8%; urban 91.6% ±0.8%), avoid restaurants/bars (rural 85.3% ±1.9%, urban 89.6% ±0.8%), avoid touching face (rural 83.1% ±2.3%, urban 88.6%, 0.8%), and avoid contact with those outside the household (rural 80.4% ±2.4%, urban 86.2% ±1.0%). After adjusting for demographic characteristics, only maintaining a 6‐foot distance remained lower among rural older adults (AOR 0.58, 95% CI: 0.42‐0.81).ConclusionsWithin older adults, reported compliance with recommended behaviors to limit the spread of COVID‐19 was high. Nonetheless, consistent rural shortfalls were noted. Findings highlight the need for rural‐specific messaging strategies for future public health emergencies.