bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomised clinical trial: Pemafibrate, a novel selective peroxisome proliferator‐activated receptor α modulator (SPPARMα), versus placebo in patients with non‐alcoholic fatty liver disease
Authors: Nakajima Atsushi , Eguchi Yuichiro , Yoneda Masato , Imajo Kento , Tamaki Nobuharu , Suganami Hideki , Nojima Toshiaki , Tanigawa Ryohei , Iizuka Masakazu , Iida Yuki , Loomba Rohit 
Published: September 2021

SummaryBackgroundPemafibrate is a novel, selective peroxisome proliferator‐activated receptor α modulator (SPPARMα). In mice, Pemafibrate improved the histological features of non‐alcoholic steatohepatitis (NASH). In patients with dyslipidaemia, it improved serum alanine aminotransferase (ALT).AimsTo evaluate the efficacy and safety of Pemafibrate in patients with high‐risk, non‐alcoholic fatty liver disease (NAFLD).MethodsThis double‐blind, placebo‐controlled, randomised multicentre, phase 2 trial randomised 118 patients (1:1) to either 0.2 mg Pemafibrate or placebo, orally, twice daily for 72 weeks. The key inclusion criteria included liver fat content of ≥10% by magnetic resonance imaging‐estimated proton density fat fraction (MRI‐PDFF); liver stiffness of ≥2.5 kPa, by magnetic resonance elastography (MRE); and elevated ALT levels. The primary endpoint was the percentage change in MRI‐PDFF from baseline to week 24. The secondary endpoints included MRE‐based liver stiffness, ALT, serum liver fibrosis markers and lipid parameters.ResultsThere was no significant difference between the groups in the primary endpoint (−5.3% vs −4.2%; treatment difference −1.0%, P = 0.85). However, MRE‐based liver stiffness significantly decreased compared to placebo at week 48 (treatment difference −5.7%, P = 0.036), and was maintained at week 72 (treatment difference −6.2%, P = 0.024), with significant reduction in ALT and LDL‐C. Adverse events were comparable between the treatment groups and therapy was well tolerated.ConclusionsPemafibrate did not decrease liver fat content but had significant reduction in MRE‐based liver stiffness. Pemafibrate may be a promising therapeutic agent for NAFLD/NASH, and also be a candidate for combination therapy with agents that reduce liver fat content. ClinicalTrials.gov, number: NCT03350165.
Radiographic and CT appearance of cavitary pulmonary lesions in a lamb
Authors: Kan J , Bauquier J , Tyrrell D , O'Byrne K , Stent AW , Brosnan B 
Published: September 2021

BackgroundPulmonary abscesses may be cavitary lesions on thoracic radiographs and computed tomography (CT).Case reportA 26‐day‐old, cross‐breed lamb presented for respiratory distress despite procaine penicillin treatment. Thoracic radiographs revealed several pulmonary ovoid thin‐walled gas and soft tissue opacity structures. CT showed that these gas‐filled structures enclosed mildly contrast enhancing soft tissue attenuating material and surrounded the lobar bronchus to the right middle and caudal lung lobes. Imaging revealed pulmonary cavitary lesions, and chronic pulmonary abscesses was confirmed with histopathology on samples obtained from a right caudal lung lobectomy.ConclusionTo the authors' knowledge, this is the first radiographic and CT report of cavitary pulmonary lesions in a lamb. The pulmonary abscesses in this case were suspected to be due aspiration pneumonia occurring during bottle feeding, along with the high possibility of failure of passive transfer from its orphan history.
Randomised trial: Peppermint oil (menthol) pharmacokinetics in children and effects on gut motility in children with functional abdominal pain
Authors: Shulman Robert J. , Chumpitazi Bruno P. , Abdel‐Rahman Susan M. , Garg Uttam , Musaad Salma , Kearns Gregory L. 
Published: September 2021

AimsLittle is known regarding the pharmacokinetics and pharmacodynamics of menthol, the active ingredient in peppermint oil (PMO). Our aim was to investigate the pharmacokinetics of menthol at 3 dose levels in children and determine their effects on gut motility and transit.MethodsThirty children ages 7–12 years with functional abdominal pain underwent wireless motility capsule (WMC) testing. Approximately 1 week later they were randomized to 180, 360 or 540 mg of enteric coated PMO (10 participants per dose). Menthol pharmacokinetics were determined via blood sampling over 24 hours. They then took their respective dose of PMO (180 mg once, 180 mg twice or 180 mg thrice daily) for 1 week during which time the WMC test was repeated.ResultsEvaluable area under the plasma concentration vs. time curve (AUClast) data were available in 29 of 30 participants. A direct linear relationship (apparent dose‐proportionality for systemic menthol exposure) was observed between PMO dose and menthol systemic exposure with mean elimination half‐life 2.1, 3.5 and 4.6 hours for the 180, 360 and 540 mg doses, respectively. WMC technical issues precluded complete motility data in all participants. Colonic transit time was inversely related to AUClast (P = .003); transit time in other regions was not affected. In contrast, stomach, small bowel and whole gut (but not colonic) contractility positively correlated with menthol AUClast (P < .05).ConclusionPharmacokinetics and pharmacodynamics of menthol derived from PMO demonstrated apparent dose‐proportionality. A higher dose of PMO may be needed to achieve maximal gut response. www.clinicaltrials.gov NCT03295747.
Curcumin analog GO‐Y030 boosts the efficacy of anti‐PD‐1 cancer immunotherapy
Authors: MaruYama Takashi , Kobayashi Shuhei , Shibata Hiroyuki , Chen WanJun , Owada Yuji 
Published: September 2021

AbstractRegulatory T cells (Tregs) in the tumor microenvironment regulate tumor immunity. Programmed cell death protein 1 (PD‐1) is known to be expressed on Tregs and plays crucial roles in suppressing tumor immunity. However, the immune checkpoint inhibitor, anti‐PD‐1 antibody, is known to promote the proliferation of the Treg population in tumor‐infiltrating lymphocytes, thereby restricting the efficacy of cancer immunotherapy. In this study, we focused on the curcumin analog GO‐Y030, an antitumor chemical. GO‐Y030 inhibited the immune‐suppressive ability of Tregs via metabolic changes in vitro, even in the presence of immune checkpoint inhibitors. Mechanistically, GO‐Y030 inhibited the mTOR‐S6 axis in Tregs, which plays a pivotal role in their immune‐suppressive ability. GO‐Y030 also controlled the metabolism in cultured CD4+ T cells in the presence of TGF‐β + IL‐6; however, it did not prevent Th17 differentiation. Notably, GO‐Y030 significantly inhibited IL‐10 production from Th17 cells. In the tumor microenvironment, L‐lactate produced by tumors is known to support the suppressive ability of Tregs, and GO‐Y030 treatment inhibited L‐lactate production via metabolic changes. In addition, experiments in the B16‐F10 melanoma mouse model revealed that GO‐Y030 helped inhibit the anti‐PD‐1 immune checkpoint and reduce the Treg population in tumor‐infiltrating lymphocytes. Thus, GO‐Y030 controls the metabolism of both Tregs and tumors and could serve as a booster for anti‐immune checkpoint inhibitors.
The diagnostic trajectory of developmental coordination disorder in the Netherlands: Experiences of mothers
Authors: Lust Jessica M. , Adams Imke L. J. , Reinders‐Messelink Heleen A. , Luijckx Joli , Schoemaker Marina M. , Steenbergen Bert 
Published: September 2021

AbstractBackgroundReceiving a diagnosis can have a major impact on the child and its family. Parental satisfaction concerning the diagnostic trajectory is important with regard to acceptance and coping with their child's problems. Our aim was to describe the diagnostic trajectory of developmental coordination disorder (DCD) in the Netherlands and identify factors that are related to parents' satisfaction.MethodMothers of 60 children with a DCD diagnosis completed an online survey concerning their experiences during and after the diagnostic trajectory of obtaining this diagnosis.ResultsForty percent of the mothers rated the diagnostic trajectory towards a DCD diagnosis as stressful and 47% rated the knowledgeability of the first professional they consulted (mostly a general practitioner, paediatric physical therapist, or youth health care physician) as having no or just superficial knowledge about DCD. Around 60% of the mothers described a lack of knowledge and support at their child's school after receiving the diagnosis. Notwithstanding this, the majority of the participating mothers was (very) satisfied with the diagnostic trajectory. Higher appreciation of both the manner of the diagnosing professional and the post‐diagnostic support provided were predictive of higher satisfaction.ConclusionsOur results underline the importance of improving the knowledgeability in primary schools and primary health care professionals with regard to DCD.
Aspirations and women's empowerment: Evidence from Kyrgyzstan
Authors: Kosec Katrina , Akramov Kamiljon , Mirkasimov Bakhrom , Song Jie , Zhao Hongdi 
Published: September 2021

AbstractThere is an enormous interest in development interventions aimed at reducing behavioural poverty traps, including by raising women's and girls' aspirations, or future‐oriented goals. However, little is known about how women's aspirations influence their gender attitudes, the marriages into which they select and their involvement in intra‐household decision‐making. We find that women in Kyrgyzstan with higher aspirations are more likely to espouse egalitarian gender attitudes, as are their husbands, and their husbands have higher aspirations. They also live in households in which women play a greater role in decision‐making, and in which spouses are more likely to agree about women's roles in decision‐making.
The effects of cerebral amyloidopathy on regional glucose metabolism in older adults with depression and mild cognitive impairment while performing memory tasks
Authors: Lee Eun Seong , Youn HyunChul , Hyung Won Seok William , Suh Sangil , Han Cheol E. , Eo Jae Seon , Jeong Hyun‐Ghang 
Published: September 2021

AbstractCo‐occurring depression and mild cognitive impairment (MCI) in older adults are important because they have a high risk of conversion to dementia. In the present study, task‐related F‐18 fluorodeoxyglucose positron emission tomography (FDG‐PET) was used to analyse older adults with concomitant depression and MCI. We recruited 20 older adults with simultaneous depression and MCI and 10 older adults with normal cognition (NC). The Verbal Paired Associates test and digit span test were used for the task‐related FDG‐PET. The 20 older adults with depression and MCI were classified into two groups based on the F‐18 florbetaben PET results: depressed MCI patients with (LLD‐MCI‐A[+]; n = 11) and without amyloid accumulation (LLD‐MCI‐A[−]; n = 9). Reduced regional cerebral glucose metabolism (rCMglc) in the left superior frontal region was observed in the LLD‐MCI‐A(−) group compared with the NC group. Analyses of the NC and LLD‐MCI‐A(+) groups showed significantly decreased rCMglc in the right inferior parietal and left middle frontal regions in the LLD‐MCI‐A(+) group. rCMglc in the left precuneus was lower in the LLD‐MCI‐A(+) group than in the LLD‐MCI‐A(−) group. Significant correlations between the rCMglc in the right inferior parietal/left precuneus regions and memory task scores were observed based on correlation analyses of NC and LLD‐MCI‐A(+) groups. The findings in the present study indicate the presence of amyloid accumulation influences glucose metabolism in depressed elderly subjects with MCI while performing cognitive tasks. Task‐related FDG‐PET examinations may help differentiate MCI associated with depression from comorbid depression in patients with prodromal Alzheimer's disease.
Do immortals need an eject button? Sartre and the importance of always having an exit
Authors: Buben Adam 
Published: September 2021

AbstractSartre directly addresses some of the core issues involved in the contemporary debate about the desirability of immortality. He thinks mortality can never be the source of life's meaning because death cuts us off before meaning can be determined, and because any meaning that survives is no longer our own. These claims already put Sartre at odds with immortality nay‐sayers who believe the limitations provided by our chronological finitude are essential to meaning, but he takes it further by arguing that the actual meaning‐generating limitations of our temporal situation would remain intact even if our lives never ended. Thus, Sartre seems like an obvious resource for anyone defending immortality. However, he does suggest one major reason to be wary. The possibility of ending up in a perpetually miserable situation makes truly indestructible immortality less attractive, and this diminished attractiveness suggests that we should not take the ability to die too lightly. With all of this in mind, I argue for a form of immortality involving indefinite life‐extension with the possibility to opt out in case existence becomes irreparably intolerable.
Synergistic associations of cognitive and motor impairments with functional outcome in covert cerebral small vessel disease
Authors: Jokinen Hanna , Laakso Hanna M. , Ahlström Matti , Arola Anne , Lempiäinen Juha , Pitkänen Johanna , Paajanen Teemu , Sikkes Sietske A. M. , Koikkalainen Juha , Lötjönen Jyrki , Korvenoja Antti , Erkinjuntti Timo , Melkas Susanna 
Published: September 2021

AbstractBackgroundCognitive and motor impairments are the key clinical manifestations of cerebral small vessel disease (SVD), but their combined effects on functional outcome have not been elucidated. This study investigated the interactions and mediating effects of cognitive and motor functions on instrumental activities of daily living (IADL) and quality of life in older individuals with various degrees of white matter hyperintensities (WMH).MethodsParticipants of the Helsinki Small Vessel Disease Study (n = 152) were assessed according to an extensive clinical, physical, neuropsychological and MRI protocol. Volumes of WMH and gray matter (GM) were obtained with automated segmentation.ResultsCognitive (global cognition, executive functions, processing speed, memory) and motor functions (gait speed, single‐leg stance, timed up‐and‐go) had strong interrelations with each other, and they were significantly associated with IADL, quality of life as well as WMH and GM volumes. A consistent pattern on significant interactions between cognitive and motor functions was found on informant‐evaluated IADL, but not on self‐evaluated quality of life. The association of WMH volume with IADL was mediated by global cognition, whereas the association of GM volume with IADL was mediated by global cognition and timed up‐and‐go performance.ConclusionThe results highlight the complex interplay and synergism between motor and cognitive abilities on functional outcome in SVD. The combined effect of motor and cognitive disturbances on IADL is likely to be greater than their individual effects. Patients with both impairments are at disproportionate risk for poor outcome. WMH and brain atrophy contribute to disability through cognitive and motor impairment.
Adult‐onset idiopathic dystonia: A national data‐linkage study to determine epidemiological, social deprivation, and mortality characteristics
Authors: Bailey Grace A. , Rawlings Anna , Torabi Fatemeh , Pickrell Owen , Peall Kathryn J. 
Published: September 2021

AbstractBackground and purposeAccurate epidemiological information is essential for the improved understanding of dystonia syndromes, as well as better provisioning of clinical services and providing context for diagnostic decision‐making. Here, we determine epidemiological, social deprivation, and mortality characteristics of adult‐onset idiopathic dystonia in the Welsh population.MethodsA retrospective population‐based cohort study using anonymized electronic health care data in Wales was conducted to identify individuals with dystonia between 1 January 1994 and 31 December 2017. We developed a case‐ascertainment algorithm to determine dystonia incidence and prevalence, as well as characterization of the dystonia cohort, based on social deprivation and mortality.ResultsThe case‐ascertainment algorithm (79% sensitivity) identified 54,966 cases; of these cases, 41,660 had adult‐onset idiopathic dystonia (≥20 years). Amongst the adult‐onset form, the median age at diagnosis was 41 years, with males significantly older at time of diagnosis compared to females. Prevalence rates ranged from 0.02% in 1994 to 1.2% in 2017. The average annual incidence was 87.7/100,000/year, increasing from 49.9/100,000/year (1994) to 96.21/100,000/year (2017). In 2017, people with dystonia had a similar life expectancy to the Welsh population.ConclusionsWe have developed a case‐ascertainment algorithm, supported by the introduction of a neurologist‐reviewed validation cohort, providing a platform for future population‐based dystonia studies. We have established robust population‐level prevalence and incidence values for adult‐onset idiopathic forms of dystonia, with this reflecting increasing clinical recognition and identification of causal genes. Underlying causes of death mirrored those of the general population, including circulatory disorders, respiratory disorders, cancers, and dementia.
We are not all the same: The importance of perceived difference in racial ideology and Afrocentricity for African American relationships
Authors: Parsons Aleja , Scott Shelby B. , Knopp Kayla , Nguyen Phuong Linh L. , Markman Howard J. , Stanley Scott M. 
Published: September 2021

AbstractA large body of existing research on African American relationships perpetuates a deficit model that assumes Eurocentric norms and emphasizes between‐group differences (e.g., cross‐racial comparisons with the majority group—European Americans). The current study examined within‐group variability and the influence of culturally unique factors, Afrocentricity, racial ideology, and perceived discrepancy between self and partner on African American relationship processes. Data were collected from 137 self‐identified African American adults in same‐race, cross‐gender relationships. Consistent with the literature on protective values of Afrocentricity, there was an association between reported relationship quality and high levels of one's own and perceived partner's Afrocentricity. Discrepancies between self and partner Afrocentricity were not associated with relationship processes, but higher perceived discrepancies across all four subscales of racial ideology were associated with lower relationship dedication. Higher perceived discrepancies on the humanist and assimilationist subscales were also related to higher levels of conflict. These findings have important clinical implications and demonstrate a need for further research into the nuances of individual factors and dyadic processes that are unique to African American couples.
Moving on up: Vertical distribution shifts in rocky reef fish species during climate‐driven decline in dissolved oxygen from 1995 to 2009
Authors: Meyer‐Gutbrod Erin , Kui Li , Miller Robert , Nishimoto Mary , Snook Linda , Love Milton 
Published: September 2021

AbstractAnthropogenic climate change has resulted in warming temperatures and reduced oxygen concentrations in the global oceans. Much remains unknown on the impacts of reduced oxygen concentrations on the biology and distribution of marine fishes. In the Southern California Channel Islands, visual fish surveys were conducted frequently in a manned submersible at three rocky reefs between 1995 and 2009. This area is characterized by a steep bathymetric gradient, with the surveyed sites Anacapa Passage, Footprint and Piggy Bank corresponding to depths near 50, 150 and 300 m. Poisson models were developed for each fish species observed consistently in this network of rocky reefs to determine the impact of depth and year on fish peak distribution. The interaction of depth and year was significant in 23 fish types, with 19 of the modelled peak distributions shifting to a shallower depth over the surveyed time period. Across the 23 fish types, the peak distribution shoaled at an average rate of 8.7 m of vertical depth per decade. Many of the species included in the study, including California sheephead, copper rockfish and blue rockfish, are targeted by commercial and recreational fisheries. CalCOFI hydrographic samples are used to demonstrate significant declines in dissolved oxygen at stations near the survey sites which are forced by a combination of natural multidecadal oscillations and anthropogenic climate change. This study demonstrates in situ fish depth distribution shifts over a 15‐year period concurrent with oxygen decline. Climate‐driven distribution shifts in response to deoxygenation have important implications for fisheries management, including habitat reduction, habitat compression, novel trophic dynamics and reduced body condition. Continued efforts to predict the formation and severity of hypoxic zones and their impact on fisheries dynamics will be essential to guiding effective placement of protected areas and fisheries regulations.
High temperature mechanical behavior of low stiffness Al2TiO5 and Al2TiO5–3Al2O3.2SiO2–ZrTiO4 composite materials
Authors: Violini María Agustina , Hernández María Florencia , Gass Sebastian Emiliano , Tomba Martinez Analía Gladys , Rendtorff Nicolás Maximiliano 
Published: September 2021

AbstractThe mechanical behavior of low (and negative) thermal expansion and low stiffness Al2TiO5 materials and Al2TiO5–3Al2O3.2SiO2–ZrTiO4 composite materials was studied by diametral compression test at room temperature 400 and 800°C. The effect of both temperature and composition was analyzed. Stress–strain curves were obtained and, from them, apparent elastic modulus (Eapp) and mechanical strength (σF) were determined. Fracture mechanisms and fracture patterns were also analyzed. All materials showed a brittle behavior up to 800°C. The thermal variation of σF, that was even higher as testing temperature increased, was interpreted based on the microcracks behavior. A double linear correlation of Eapp was found with temperature (T) and zircon content ([Z]), with a fitting coefficient > .9. The particular low stiffness and the mechanical and thermal behavior of the studied materials suggest that they would be able to withstand thermal stresses.