bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dose intensity and treatment duration of bortezomib in transplant‐ineligible newly diagnosed multiple myeloma
Authors: Ibarra Gladys , Peña Marta , Abril Laura , Senín Alicia , Maluquer Clara , Clapés Victoria , Baca Cristina , Bustamante Gabriela , Sureda Anna , Oriol Albert 
Published: May 2021

AbstractBackgroundBortezomib‐related peripheral neuropathy (PN) affects a relevant proportion of multiple myeloma (MM) patients treated with melphalan, prednisone, and bortezomib (VMP). Empirical dose modifications have attempted to reduce toxicity without compromising efficacy.Patients and methodsWe retrospectively evaluated the dose‐response and dose‐toxicity relationships in 114 unselected untreated MM patients intended for treatment with VMP with subcutaneous bortezomib.ResultsSixty‐two patients (54%) completed the 9 scheduled cycles. Median treatment duration was 48 weeks (range 1‐57), cumulative bortezomib dose was 41.8 mg/m2 (2.6‐67.6) and median dose intensity was 1.0 mg/m2/wk (0.2‐2.6). Median progression‐free survival (PFS) and overall survival (OS) for the full cohort were 86 weeks (95%CI 77‐104) and 209 weeks (95% CI 157‐259) respectively. Patients who progressed <60 days after discontinuing bortezomib had received a significantly inferior mean cumulative dose, 34.6 mg/m2 than the remaining individuals, 45.5 (P = .023). PFS was significantly improved for patients achieving a very good partial response (VGPR) or better (P = .00007). Additional variables with a prognostic impact on PFS on univariate analysis included completion of the 9 scheduled cycles (P = .00002), patients with at least 50 weeks of treatment (P = .02) and patients receiving a cumulative dose of at least 49 mg/m2 (P = .05). Achievement of a VGPR (HR 0.23; 95%CI 0.12‐0.46; P = .00002) and a cumulative dose of 49 mg/m2 (HR 0.46, 95%CI 0.27‐0.78; P = .003) were statistically independent prognostic factors for PFS. Toxicity‐related treatment dose reductions occurred in 75 individuals (66%). PN was observed in 50 individuals (44.6%), grade 3 in 9 (8%). The only prognostic factor for emergence of PN in multivariate analysis was the presence of baseline PN.ConclusionsBiweekly full‐dose treatment in the first cycles has a major impact in depth of response. Depth of response, cumulative bortezomib dose, and treatment duration had an impact in prolongation of PFS.
GABAA receptor β1‐subunit knock‐out mice show increased delta power in NREM sleep and decreased theta power in REM sleep
Authors: Lie Maria Elena Klibo , Falk‐Petersen Christina Birkedahl , Piilgaard Louise , Griem‐Krey Nane , Wellendorph Petrine , Kornum Birgitte Rahbek 
Published: May 2021

Abstractγ‐Aminobutyric acid (GABA) acting through heteropentameric GABAA receptors plays a pivotal role in the sleep‐promoting circuitry. Whereas the role of the different GABAA receptor α‐subunits in sleep regulation and in mediating the effect of benzodiazepines for treatment of insomnia is well‐described, the β‐subunits are less studied. Here we report the first study characterizing sleep in mice lacking the GABAA receptor β1‐subunit (β1−/− mice). We show that β1−/− mice have a distinct and abnormal sleep phenotype characterized by increased delta power in non‐rapid eye movement (NREM) sleep and decreased theta activity in rapid eye movement (REM) sleep compared to β1+/+ mice, without any change in the overall sleep‐wake architecture. From GABAA receptor‐specific autoradiography, it is further demonstrated that functional β1‐subunit‐containing GABAA receptors display the highest binding levels in the hippocampus and frontal cortex. In conclusion, this study suggests that the GABAA receptor β1‐subunit does not play an important role in sleep initiation or maintenance but instead regulates the power spectrum and especially the expression of theta rhythm. This provides new knowledge on the complex role of GABAA receptor subunits in sleep regulation. In addition, β1−/− mice could provide a useful mouse model for future studies of the physiological role of delta and theta rhythms during sleep.
A group of ectomycorrhizal fungi restricts organic matter accumulation in boreal forest
Authors: Lindahl Björn D. , Kyaschenko Julia , Varenius Kerstin , Clemmensen Karina E. , Dahlberg Anders , Karltun Erik , Stendahl Johan 
Published: May 2021

AbstractBoreal forest soils are important global carbon sinks, with significant storage in the organic topsoil. Decomposition of these stocks requires oxidative enzymes, uniquely produced by fungi. Across Swedish boreal forests, we found that local carbon storage in the organic topsoil was 33% lower in the presence of a group of closely related species of ectomycorrhizal fungi – Cortinarius acutus s.l.. This observation challenges the prevailing view that ectomycorrhizal fungi generally act to increase carbon storage in soils but supports the idea that certain ectomycorrhizal fungi can complement free‐living decomposers, maintaining organic matter turnover, nutrient cycling and tree productivity under nutrient‐poor conditions. The indication that a narrow group of fungi may exert a major influence on carbon cycling questions the prevailing dogma of functional redundancy among microbial decomposers. Cortinarius acutus s.l. responds negatively to stand‐replacing disturbance, and associated population declines are likely to increase soil carbon sequestration while impeding long‐term nutrient cycling.
Effect of dental malocclusion on cerebellar neuron activation via the dorsomedial part of the principal sensory trigeminal nucleus
Authors: Shi Minghong , Liu Xin , Zhang Chunkui , Zhang Hongyun , Liu Qian , Wang Dongmei , Liu Xiaodong , Li Jinlian , Wang Meiqing 
Published: May 2021

AbstractOcclusion has been proposed to play a role for body posture and balance, both of which are mediated mainly by the cerebellum. The dorsomedial part of the principal sensory trigeminal nucleus (Vpdm) has direct projection to the cerebellum. The experimental unilateral anterior crossbite (UAC) has an impact on the motor nuclei in the brain stem via trigeminal mesencephalic nucleus (Vme). The current aim was to explore whether UAC has an impact on Vpdm‐cerebellum circuit. The inferior alveolar nerve was injected into cholera toxin B subunit (CTb), the cerebellum was injected into fluoro‐gold (FG), and the Vpdm was injected into biotinylated dextran amine (BDA) to identify the activation of Vpdm‐cerebellum circuit by UAC. Data indicated that there were more neuronal nuclei (NeuN)/CTb/FG triple‐labelled neurons and NeuN/CTb/vesicular glutamate transporter 1(VGLUT1) triple‐labelled neurons in the Vpdm, and more NeuN/BDA/ VGLUT1 triple‐labelled neurons in the cerebellum of rats with UAC than in control rats. The VGLUT1 expression in the Vpdm and cerebellum in the UAC group was higher than that in control rats. These findings indicate an excitatory impact of UAC on the Vpdm‐cerebellum pathway and support the role of occlusion for body posture and balance.
Evaluation of diazepam nasal spray in patients with epilepsy concomitantly using maintenance benzodiazepines: An interim subgroup analysis from a phase 3, long‐term, open‐label safety study
Authors: Segal Eric B. , Tarquinio Daniel , Miller Ian , Wheless James W. , Dlugos Dennis , Biton Victor , Cascino Gregory D. , Desai Jay , Hogan R. Edward , Liow Kore , Sperling Michael R. , Vazquez Blanca , Cook David F. , Rabinowicz Adrian L. , Carrazana Enrique ,   The DIAZ.001.05 Study Group
Published: May 2021

AbstractObjectiveDiazepam nasal spray (Valtoco), indicated for acute treatment of frequent seizure activity (seizure clusters) in patients with epilepsy ≥6 years of age, is designed to be a rapid, noninvasive, socially acceptable route of administration. This interim analysis evaluated the safety profile of diazepam nasal spray in patients with and without concomitant use of benzodiazepines, with use of a second dose for a seizure cluster as a proxy for effectiveness.MethodsA long‐term, phase 3, open‐label safety study enrolled patients with epilepsy who had seizures despite a stable antiseizure medication regimen.ResultsAmong 175 patients enrolled by October 31, 2019, a total of 158 were treated with diazepam nasal spray (aged 6–65 years; 53.8% female). Of those, 119 (75.3%) received concomitant benzodiazepines (60, chronic; 59, intermittent); 39 (24.7%) did not. Use of a second dose was similar in patients using chronic concomitant benzodiazepines (second dose in 11.1% [144/1299]) and those with no concomitant benzodiazepines (second dose in 10.3% [41/398]). Treatment emergent adverse events (TEAEs) occurred for 80.0% with chronic use of concomitant benzodiazepines and 61.5% without. Cardiorespiratory depression was not reported, and no serious TEAEs were treatment related. Study retention was high: 83.3% in the chronic benzodiazepine group and 76.9% in the no‐benzodiazepine group. Findings were similar in a sub‐analysis of patients who were (n = 44) or were not (n = 75) taking clobazam.SignificanceThis analysis of patients from a long‐term study shows a similar safety profile of diazepam nasal spray in patients with and without concomitant benzodiazepines, and consistent with the established profile for diazepam. Use of a single dose of diazepam nasal spray and high study retention rates suggest the effectiveness of diazepam nasal spray in patients irrespective of chronic daily benzodiazepine use. Results were similar in the clobazam sub‐analysis. These results support the safety and effectiveness of diazepam nasal spray in patients with concomitant benzodiazepine use.
Regional microglial populations in central autonomic brain regions in SUDEP
Authors: Somani Alyma , El‐Hachami Hanna , Patodia Smriti , Sisodiya Sanjay , Thom Maria 
Published: May 2021

AbstractObjectiveSudden unexpected death in epilepsy (SUDEP) may arise as a result of autonomic dysfunction during a seizure. The central autonomic networks (CANs) modulate brainstem cardiorespiratory regulation. Recent magnetic resonance imaging (MRI) studies in SUDEP have shown cortical and subcortical volume changes and altered connectivity between CAN regions, but the pathological correlate is unknown. Because neuroinflammation is both a cause and a consequence of seizures and may relate to regional brain pathology, our aim was to evaluate microglial populations in CANs in SUDEP.MethodsIn 55 postmortem cases, including SUDEP, epilepsy controls without SUDEP and nonepilepsy controls, we quantified Iba1‐expressing microglia in 14 cortical and thalamic areas that included known CAN regions.ResultsMean Iba1 labeling across all brain regions was significantly higher in SUDEP cases compared to epilepsy and nonepilepsy controls. There was significant regional variation in Iba1 labeling in SUDEP cases only, with highest labeling in the medial thalamus. Significantly higher labeling in SUDEP cases than epilepsy and nonepilepsy controls was consistently noted in the superior temporal gyrus. In cases with documented seizures up to 10 days prior to death, significantly higher mean Iba1 labeling was observed in SUDEP compared to epilepsy controls.SignificanceOur findings support microglial activation in SUDEP, including cortical and subcortical regions with known autonomic functions such as the thalamus and superior temporal gyrus. This may be relevant to cellular pathomechanisms underlying cardioregulatory failure during a seizure.
Selection on fish personality differs between a no‐take marine reserve and fished areas
Authors: Thorbjørnsen Susanna Huneide , Moland Even , Villegas‐Ríos David , Bleeker Katinka , Knutsen Halvor , Olsen Esben Moland 
Published: May 2021

AbstractMarine reserves can protect fish populations by increasing abundance and body size, but less is known about the effect of protection on fish behaviour. We looked for individual consistency in movement behaviours of sea trout in the marine habitat using acoustic telemetry to investigate whether they represent personality traits and if so, do they affect survival in relation to protection offered by a marine reserve. Home range size had a repeatability of 0.21, suggesting that it represents a personality trait, while mean swimming depth, activity and diurnal vertical migration were not repeatable movement behaviours. The effect of home range size on survival differed depending on the proportion of time fish spent in the reserve, where individuals spending more time in the reserve experienced a decrease in survival with larger home ranges while individuals spending little time in the reserve experienced an increase in survival with larger home ranges. We suggest that the diversity of fish home range sizes could be preserved by establishing networks of marine reserves encompassing different habitat types, ensuring both a heterogeneity in environmental conditions and fishing pressure.
The value of recreational fishing in Sweden – Estimates based on a nationwide survey
Authors: Carlén Ola , Bostedt Göran , Brännlund Runar , Persson Lars 
Published: May 2021

AbstractA nationwide recreational fishing survey in Sweden was used to estimate the benefits of recreational fishing in Sweden. The survey targeted the Swedish population and, consequently, the sample contained a large fraction of zero fishing days. To consider this, a zero‐inflated Poisson model was used in the estimations. Swedes fished about 15.6 million days in 2013, of which two‐thirds were spent on inland fishing, and one‐third on marine and coastal fishing. Expected consumer surplus per fishing day varied with the season; SEK 193 for winter fishing, SEK 787 for summer fishing and SEK 95 for autumn fishing. Although about 70 per cent of total fishing days were spent on inland fishing, the weighted consumer surplus per fishing day in marine and coastal areas were higher. The results also demonstrated strong positive effects of increases in expected catch per day on number of fishing days demanded and consumer surplus, which have important implications for fishery policies directed at recreational fishing.
The Recreational value of Atlantic salmon angling under different fishing regulations
Authors: Stensland Stian , Dugstad Anders , Navrud Ståle 
Published: May 2021

AbstractAtlantic salmon,SalmosalarL., stocks worldwide have dwindled, and stricter recreational fishing regulations have been implemented. This study estimates the recreational value of salmon fishing under different regulatory schemes and identifies factors explaining changes in net economic value of sport fishing. A Contingent Valuation mail survey in the Verdal River, Norway, asked anglers their willingness‐to‐pay for increased fishing expenditures or willingness‐to‐accept compensation in reduced fishing expenditures, to estimate recreational value. The average annual recreational value per angler decreased under stricter regulations from about €420 (in 2007–2009) to €280 (2010–2012) to €180 for the future scenario (2013–2015). Although an overall net decline in recreational value was found with stricter regulations, anglers have heterogeneous preferences. Anglers with non‐catch motives or high place attachment have higher recreational value with stricter regulations than others. If stricter regulations remain over time, younger, less consumptive‐oriented anglers would probably dominate the fishery.
Unusual characteristics of the carbon cycle during the 2015−2016 El Niño
Authors: Wang Kai , Wang Xuhui , Piao Shilong , Chevallier Frédéric , Mao Jiafu , Shi Xiaoying , Huntingford Chris , Bastos Ana , Ciais Philippe , Xu Hao , Keeling Ralph F. , Pacala Stephen W. , Chen Anping 
Published: May 2021

AbstractThe 2015−2016 El Niño was one of the strongest on record, but its influence on the carbon balance is less clear. Using Northern Hemisphere atmospheric CO2 observations, we found both detrended atmospheric CO2 growth rate (CGR) and CO2 seasonal‐cycle amplitude (SCA) of 2015−2016 were much higher than that of other El Niño events. The simultaneous high CGR and SCA were unusual, because our analysis of long‐term CO2 observations at Mauna Loa revealed a significantly negative correlation between CGR and SCA. Atmospheric inversions and terrestrial ecosystem models indicate strong northern land carbon uptake during spring but substantially reduced carbon uptake (or high emissions) during early autumn, which amplified SCA but also resulted in a small anomaly in annual carbon uptake of northern ecosystems in 2015−2016. This negative ecosystem carbon uptake anomaly in early autumn was primarily due to soil water deficits and more litter decomposition caused by enhanced spring productivity. Our study demonstrates a decoupling between seasonality and annual carbon cycle balance in northern ecosystems over 2015−2016, which is unprecedented in the past five decades of El Niño events.
The urban governance configuration: A conceptual framework for understanding complexity and enhancing transitions to greater sustainability in cities
Authors: Baud Isa , Jameson Shazade , Peyroux Elisabeth , Scott Dianne 
Published: May 2021

AbstractThis article proposes a conceptual framework for analysing and comparing urban governance configurations and their dynamics in the context of sustainability transitions. Our contribution to the debates consists of drawing on a literature review to develop a conceptual framework with the dimensions necessary for understanding urban governance processes and their dynamics; an urban governance configuration framework. We argue that this framework allows us to combine important dimensions (discourses, actor networks, knowledge and material processes) shaping urban development decision‐making and outcomes in their social, economic and environmental domains, in a complex world. The main advantages of this approach are: first, it enables the analysis how complex decision‐making is combined in a particular time and space, generating decisions and outcomes based on a variety of knowledge; second, it allows a comparative analysis of governance configurations across different places within the same city and between cities; and third, provides lessons on how urban governance could shift to more inclusive, sustainable forms of urban development.
Health‐care professionals’ assessment of a person‐centred intervention to empower self‐management and health across chronic illness: Qualitative findings from a process evaluation study
Authors: Heggdal Kristin , Mendelsohn Joshua B. , Stepanian Natalie , Oftedal Bjørg Frøysland , Larsen Marie Hamilton 
Published: May 2021

AbstractBackgroundPerson‐centred care (PCC) empowers patients to manage their chronic illness and promote their health in accordance with their own beliefs, values and preferences. Drawing on health‐care professional's (HCP’s) experiences implementing an empowerment‐focused, person‐centred intervention called the Bodyknowledging Program (BKP), we undertook a process evaluation that aimed to assess the impact on patient health and well‐being.MethodsWe used individual in‐depth interviews and semi‐structured focus groups comprising n = 8 interprofessional HCP who facilitated intervention sessions with n = 58 patients situated in Norwegian specialist care sites. Content analysis was used to analyse the data and summarize major themes.ResultsHealth‐care professional interviews revealed four main ways in which the intervention operated in support of health‐related patient outcomes: (i) addressing the whole person; (ii) hope and affirmation; (iii) expanding recovery; and (iv) social support and revitalized relationships. The intervention provided new tools for patients to understand the social, emotional and physical impact of their illness. Health‐care professional reported new insights to facilitate patient engagement and to promote patients’ health.ConclusionsThe Bodyknowledging Program facilitated patient engagement through the promotion of patient‐centred care while developing the patients’ ability to exploit their own resources for effectively managing their health within illness. The process evaluation supported the underlying theoretical basis of the intervention and was suggestive of its potential transferability elsewhere.
Partial replacement of fat and salt in liver pâté by addition of Agaricus bisporus and Pleurotus ostreatus flour
Authors: Cerón‐Guevara Magdalena I. , Santos Eva M. , Lorenzo José M. , Pateiro Mirian , Bermúdez‐Piedra Roberto , Rodríguez José A. , Castro‐Rosas Javier , Rangel‐Vargas Esmeralda 
Published: May 2021

SummaryThe effect of incorporation of 7.5% (hydrated 50/50 w/w) and 10% (hydrated 70/30 w/w) of Agaricus bisporus (Ab) and Pleurotus ostreatus (Po) flours as partial replacers of fat and salts (sodium chloride and phosphates) on physicochemical properties, microbiological and sensory properties of pâté was studied during cold storage. Mushroom flours increased moisture, dietary fibre and protein contents improving the nutritional value of pâtés. Mushroom flour influenced the colour parameters, especially Ab, and gave harder pâtés in 10% mushroom flour addition. Sensorially, the odour and taste of 7.5% of mushroom flour were considered acceptable, and its addition hydrated in a ratio 50/50 w/w should be the most suitable to improve the nutritional value of this product without significantly affecting the sensory properties. The addition of Ab and Po flours was a feasible strategy to replace fat and salts in pâté.
Association between ectopic pancreatic and hepatic fat and metabolic risk factors in children with non‐alcoholic fatty liver disease
Authors: Lee Eun Hye , Kim Ji Young , Yang Hye Ran 
Published: May 2021

SummaryBackgroundFew studies have reported an association between ectopic pancreatic and hepatic fat and metabolic factors in children with non‐alcoholic fatty liver disease (NAFLD).ObjectivesWe investigated this association and also the factors associated with pancreatic and hepatic fat deposition in children with NAFLD.MethodsThis cross‐sectional study investigated 65 children with NAFLD (49 boys, 13.0 ± 3.2 years, mean body mass index z‐score 2.5 ± 1.2), who underwent liver biopsy and magnetic resonance imaging–based proton density fat fraction, as well as anthropometry, laboratory tests, body composition analysis, and hepatic fat fraction (HFF) and pancreatic fat fraction (PFF) measurements.ResultsHFF and PFF were 4.2%–49.9% (median 24.3) and 0.4%–26.9% (median 3.8), respectively. HFF was not significantly correlated with PFF. HFF was correlated with total body fat% (r = 0.329, p = 0.010) and γ‐glutamyl transpeptidase (GGT) (r = 0.260, p = 0.040), while PFF was correlated with the diastolic blood pressure (r = 0.253, p = 0.045), GGT (r = 0.335, p = 0.007) and fasting plasma glucose (r = 0.417, p = 0.001). Multiple linear regression analysis showed that HFF was significantly associated with sex, age, body fat% and GGT, whereas PFF was associated with hypertension and fasting plasma glucose levels but not insulin resistance.ConclusionsHFF was associated with sex, age and body fat in children with NAFLD, while PFF was associated with hypertension and increased fasting plasma glucose, which suggests that the pathophysiology of ectopic fat accumulation varies across organs in children with NAFLD.