bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linking objective measures of physical activity and capability with brain structure in healthy community dwelling older adults
Authors: Sanders Anne-Marthe , Richard Geneviève , Kolskår Knut , Ulrichsen Kristine M. , Kaufmann Tobias , Alnæs Dag , Beck Dani , Dørum Erlend S. , de Lange Ann-Marie G. , Nordvik Jan Egil , Westlye Lars T. 
Published: January 2021

AbstractMaintaining high levels of daily activity and physical capability have been proposed as important constituents to promote healthy brain and cognitive aging. Studies investigating the associations between brain health and physical activity in late life have, however, mainly been based on self-reported data or measures designed for clinical populations. In the current study, we examined cross-sectional associations between physical activity, recorded by an ankle-positioned accelerometer for seven days, physical capability (grip strength, postural control, and walking speed), and neuroimaging based surrogate markers of brain health in 122 healthy older adults aged 65-88 years. We used a multimodal brain imaging approach offering two complementary structural MRI based indicators of brain health: white matter diffusivity and coherence based on diffusion tensor imaging and subcortical and global brain age based on brain morphology inferred from T1-weighted MRI data. The analyses revealed a significant association between global white matter fractional anisotropy (FA) and walking speed, indicating higher white matter coherence in people with higher pace. We also found a significant interaction between sex and brain age on number of daily steps, indicating younger-appearing brains in more physically active women, with no significant associations among men. These results provide insight into the intricate associations between different measures of brain and physical health in old age, and corroborate established public health advice promoting physical activity.
Pre-existing cell subpopulations in primary prostate cancers display surface fingerprint of docetaxel-resistant cells
Authors: Drápela Stanislav , Kvokačková Barbora , Fedr Radek , Kurfürstová Daniela , Morong Martin , Študent Vladimír , van Weerden Wytske M. , Puhr Martin , Culig Zoran , Bouchal Jan , Souček Karel 
Published: January 2021

AbstractBackgroundDocetaxel resistance represents a leading obstacle in the therapy of prostate cancer (PCa), resulting in lethal disease. Intratumoral heterogeneity, which is frequently driven by epithelial-mesenchymal plasticity significantly contributes to the limited treatment response, chemoresistance, and subsequent poor prognosis of patients with lethal PCa.MethodsWe employed a high-throughput flow cytometry screening to identify cell surface fingerprint that associates with docetaxel resistance in PCa cells. Using patient-derived xenografts, we validated protein expression of the most robustly changed antigensin vivoand further assessed this 6-molecule surface fingerprint in primary PCa tumors.ResultsWe revealed the overexpression of SSEA-4 antigen in bothin vitroandin vivodocetaxel-resistant models and confirmed the SSEA-4 enrichment in a subpopulation of freshly isolated primary PCa tumors. The level of ST3GAL2, an enzyme that is critically involved in the SSEA-4 synthesis, correlated with increased expression of CD44, CD59, and CD95 and reduced expression of EpCAM and CD9. SSEA-4 was further directly linked to the antimicrotubule agent resistance and poor prognosis in PCa patients.ConclusionsWe propose that the 6-molecule surface fingerprint associates with docetaxel resistance and pre-exists in a cell subpopulation of primary PCa tumors even before docetaxel treatment.
Emergence of a smooth interface from growth of a dendritic network against a mechanosensitive contractile material
Authors: Sharma Medha , Jiang Tao , Jiang Zi Chen , Moguel-Lehmer Carlos E. , Harris Tony J. C. 
Published: January 2021

AbstractStructures and machines require smoothening of raw materials. Self-organized smoothening guides cell and tissue morphogenesis, and is relevant to advanced manufacturing. Across the syncytial Drosophila embryo surface, smooth interfaces form between expanding Arp2/3-based actin caps and surrounding actomyosin networks, demarcating the circumferences of nascent dome-like compartments used for pseudo-cleavage. We found that smoothening of the actomyosin interfaces requires Arp2/3 in vivo. To dissect the physical basis of this requirement, we reconstituted the interacting networks using node-based models. When actomyosin networks were simulated with clearances instead of Arp2/3 networks, rough boundaries persisted with low levels of myosin contractility. With addition of expanding Arp2/3 networks, network-network interfaces failed to smoothen, but accumulated myosin nodes and tension. After incorporating actomyosin mechanosensitivity, Arp2/3 network growth induced local contractility and smoothening of the interfaces, effects also evident in vivo. In this way, a smooth structure can emerge from the lateral interaction of irregular starting materials.
mTOR repression in response to amino acid starvation promotes ECM degradation through MT1-MMP endocytosis arrest
Authors: Colombero Cecilia , Remy David , Antoine Sandra , Macé Anne-Sophie , Monteiro Pedro , ElKhatib Nadia , Fournier Margot , Dahmani Ahmed , Montaudon Elodie , Montagnac Guillaume , Marangoni Elisabetta , Chavrier Philippe 
Published: January 2021

AbstractUnder conditions of starvation, normal and tumor epithelial cells can rewire their metabolism towards the consumption of extracellular matrix-derived components as nutrient sources. The mechanism of pericellular matrix degradation by starved cells has been largely overlooked. Here we show that matrix degradation by breast and pancreatic tumor cells and patient-derived xenograft explants increases by one order of magnitude upon amino acid and growth factor deprivation. In addition, we found that collagenolysis requires the invadopodia components, TKS5 and the transmembrane metalloproteinase, MT1-MMP, which are key to the tumor invasion program. Increased collagenolysis is controlled by mTOR repression upon nutrient depletion or pharmacological inhibition by rapamycin. Our results reveal that starvation hampers clathrin-mediated endocytosis, resulting in MT1-MMP accumulation in arrested clathrin-coated pits. Our study uncovers a new mechanism whereby mTOR repression in starved cells leads to the repurposing of abundant plasma membrane clathrin-coated pits into robust ECM-degradative assemblies.
The SARS-CoV-2 Y453F mink variant displays a striking increase in ACE-2 affinity but does not challenge antibody neutralization
Authors: Bayarri-Olmos Rafael , Rosbjerg Anne , Johnsen Laust Bruun , Helgstrand Charlotte , Bak-Thomsen Theresa , Garred Peter , Skjoedt Mikkel-Ole 
Published: January 2021

AbstractSARS-CoV-2 transmission from humans to animals has been reported for many domesticated species, including cats, dogs and minks. Identification of novel spike gene mutations appearing in minks has raised major concerns about potential immune evasion and challenges for the global vaccine strategy. The genetic variant, known as “cluster-five”, arose among farmed minks in Denmark and resulted in a complete shutdown of the world’s largest mink production. However, the functional properties of this new variant are not established. Here we present functional data on the Y453F cluster-five receptor-binding domain (RBD) and show that it does not decrease established humoral immunity or affect the neutralizing response in a vaccine model based on wild-type RBD or spike. However, it binds the human ACE-2 receptor with a four-fold higher affinity suggesting an enhanced transmission capacity and a possible challenge for viral control.
Impact of a commercial accountable care organization on prescription drugs
Authors: Zhang Hui , Cowling David W. , Graham Joanne M. , Taylor Erik 
Published: January 2021

AbstractObjectiveTo determine the long‐run impact of a commercial accountable care organization (ACO) on prescription drug spending, utilization, and related quality of care.Data Sources/Study SettingCalifornia Public Employees' Retirement System (CalPERS) health maintenance organization (HMO) member enrollment data and pharmacy benefit claims, including both retail and mail‐order generic and brand‐name prescription drugs.Study DesignWe applied a longitudinal retrospective cohort study design and propensity‐weighted difference‐in‐differences regression models. We examined the relative changes in outcome measures between two ACO cohorts and one non‐ACO cohort before and after the ACO implementation in 2010. The ACO directed provider prescribing patterns toward generic substitution for brand‐name prescription drugs to maximize shared savings in pharmacy spending.Data Collection/Extraction MethodsThe study sample included members continuously enrolled in a CalPERS commercial HMO from 2008 through 2014 in the Sacramento area.Principal FindingsThe cohort differences in baseline characteristics of 40 483 study participants were insignificant after propensity‐weighting adjustment. The ACO enrollees had no significant differential changes in either all or most of the five years of the ACO operation for the following measures: (1) average total spending and (2) average total scripts filled and days supplied on either generic or brand‐name prescription drugs, or the two combined; (3) average generic shares of total prescription drug spending, scripts filled or days supplied; (4) annual rates of 10 outpatient process quality of care metrics for medication prescribing or adherence.ConclusionsParticipation in the commercial ACO was associated with negligible differential changes in prescription drug spending, utilization, and related quality of care measures. Capped financial risk‐sharing and increased generics substitution for brand names are not enough to produce tangible performance improvement in ACOs. Measures to increase provider financial risk‐sharing shares and lower brand‐name drug prices are needed.
Delineating the relationship between immune system aging and myogenesis in muscle repair
Authors: Tobin Stephanie W. , Alibhai Faisal J. , Wlodarek Lukasz , Yeganeh Azadeh , Millar Sean , Wu Jun , Li Shu‐hong , Weisel Richard D. , Li Ren‐Ke 
Published: January 2021

AbstractRecruited immune cells play a critical role in muscle repair, in part by interacting with local stem cell populations to regulate muscle regeneration. How aging affects their communication during myogenesis is unclear. Here, we investigate how aging impacts the cellular function of these two cell types after muscle injury during normal aging or after immune rejuvenation using a young to old (Y‐O) or old to old (O‐O) bone marrow (BM) transplant model. We found that skeletal muscle from old mice (20 months) exhibited elevated basal inflammation and possessed fewer satellite cells compared with young mice (3 months). After cardiotoxin muscle injury (CTX), old mice exhibited a blunted inflammatory response compared with young mice and enhanced M2 macrophage recruitment and IL‐10 expression. Temporal immune and cytokine responses of old mice were partially restored to a young phenotype following reconstitution with young cells (Y‐O chimeras). Improved immune responses in Y‐O chimeras were associated with greater satellite cell proliferation compared with O‐O chimeras. To identify how immune cell aging affects myoblast function, conditioned media (CM) from activated young or old macrophages was applied to cultured C2C12 myoblasts. CM from young macrophages inhibited myogenesis while CM from old macrophages reduced proliferation. These functional differences coincided with age‐related differences in macrophage cytokine expression. Together, this study examines the infiltration and proliferation of immune cells and satellite cells after injury in the context of aging and, using BM chimeras, demonstrates that young immune cells retain cell autonomy in an old host to increase satellite cell proliferation.
Similar topologies of individual‐based plant‐herbivorous networks in forest interior and anthropogenic edges
Authors: Carvalho Raquel L , Anjos Diego V , Fagundes Roberth , Luna Pedro , Ribeiro Sérvio Pontes 
Published: January 2021

AbstractUnderstanding the impacts of edge effects on ecological interactions plays an integral role in planning ecosystem recovery from human perturbations, as well as conservation of habitats. Edge effects related to forest fragmentation cause changes in species diversity that can disrupt ecological networks. Here, we evaluated how the diversity of, and interactions between, herbivorous insects associated with individuals of a pioneer plant species, Mabea fistulifera (Euphorbiaceae) are affected by the disturbances related to edge effects. We addressed two specific questions: (i) How do the forest edges affect species richness, abundance and composition of herbivorous interacting with M. fistulifera? (ii) Do different disturbances related to edge effects affect the topology of individual‐based plant‐herbivorous networks? Herbivorous insects were sampled from three population patches of M. fistulifera in Brazilian Atlantic forest areas: two areas were subjected to distinct intensities of anthropogenic disturbances (firebreak and park access road, considered edges of low‐ and high‐impact, respectively), and one in the forest interior (control). We expected a lower species richness and abundance of herbivorous interacting with plants in forest edges than in the forest interior apart from to differences in the species composition. Therefore, based on these predictions, we expected that the various disturbances related to edge effects may change the topology of individual‐based plant‐herbivorous networks. We observed that species richness and abundance of herbivorous in high‐impact environments decreased in relation to forest interior, as well the species composition differed between these areas. Disturbance jeopardised network specialisation but did not change the topology of individual‐based networks, which presented a modular pattern. Edges affected herbivorous diversity and decreased the interaction overlap as individual‐based networks became highly specialised with increasing disturbance. These results enhance the understanding of edge effects and resilience of plant‐herbivorous interactions in regularly disturbed tropical environments.
Outcomes of extracorporeal membrane oxygenation in adults with active hematologic and nonhematologic malignancy
Authors: Park Chul , Ko Ui Won , Ko Ryoung‐Eun , Na Soo Jin , Yang Jeong Hoon , Jeon Kyeongman , Suh Gee Young , Sung Kiick , Cho Yang Hyun 
Published: January 2021

AbstractAlthough the number of cancer patients admitted to the intensive care unit is increasing, the data on the use of extracorporeal membrane oxygenation in patients with malignancy are limited. We applied extracorporeal membrane oxygenation to carefully selected patients with active hematologic malignancy or nonhematologic malignancy who experienced respiratory or cardiac failure despite maximal conventional therapy. Patients with active malignancy who underwent extracorporeal membrane oxygenation in our institution between January 2012 and December 2016 were included in this study. The primary outcome of this study was defined as survival to hospital discharge. We also investigated the factors associated with survival to hospital discharge. There were 30 (30.6%) and 68 (69.4%) patients in the hematologic malignancy group and the nonhematologic malignancy group, respectively. Patients in the hematologic malignancy group were younger, more neutropenic, more hypotensive, had a lower Charlson Comorbidity Index, higher sequential organ failure assessment score, and lower platelet count than those in the nonhematologic malignancy group. Forty‐six (46.9%) patients were successfully weaned off extracorporeal membrane oxygenation, and 30 (30.6%) patients survived until hospital discharge. Hospital survival rate and survival status 6 months after hospital discharge were significantly lower in patients with hematologic malignancy than in those with nonhematologic malignancy (13.3% vs. 38.2%, P = .026 and 3.3% vs. 26.5%, P = .017, respectively). Multivariate analysis identified an active hematologic malignancy, older age, acidosis, thrombocytopenia, high vasoactive‐inotrope score, and respiratory failure as the risk factors for in‐hospital death. Patients with hematologic malignancy requiring extracorporeal membrane oxygenation support had significantly lower rates of hospital survival and 6‐month survival after discharge than patients with nonhematologic malignancy. Therefore, extracorporeal membrane oxygenation for treating cardiac or respiratory failure should only be considered in highly selected patients with hematologic malignancy.
HIF‐1α downregulation of miR‐433‐3p in adipocyte‐derived exosomes contributes to NPC progression via targeting SCD1
Authors: Yin Haimeng , Qiu Xiaoxia , Shan Ying , You Bo , Xie Lixiao , Zhang Panpan , Zhao Jianmei , You Yiwen 
Published: January 2021

AbstractResident adipocytes under a hypoxic tumor microenvironment exert an increasingly important role in cell growth, proliferation, and invasion in cancers. However, the communication between adipocytes and cancer cells during nasopharyngeal carcinoma (NPC) progression is poorly understood. Here, we demonstrate that hypoxic adipocyte‐derived exosomes are key information carriers that transfer low expression of miR‐433‐3p into NPC cells. In addition, luciferase reporter assays detected that hypoxia inducible factor‐1α (HIF‐1α) induced miR‐433‐3p transcription through five binding sites at its promoter region. Concordantly, the low expression of miR‐433‐3p promoted proliferation, migration, and lipid accumulation in NPC cells via targeting stearoyl‐CoA desaturase 1 (SCD1) are suggested by functional studies. Consistent with these findings, in tumor‐bearing mice, NPC cells with low HIF‐1α expression, high miR‐433‐3p expression, and low SCD1 expression were equally endowed with remarkably reduced potential of tumorigenesis. Collectively, our study highlights the critical role of the HIF‐1α‐miR‐433‐3p‐SCD1 axis in NPC progression, which can serve as a mechanism‐based potential therapeutic approach.
Partitioning cash flows to overcome retailer aversion to stocking new products
Authors: Devlin Anna G. , Elmaghraby Wedad J. , Hamilton Rebecca W. 
Published: January 2021

AbstractBecause decision makers tend to dislike ambiguity, the uncertainty surrounding new products can act as a barrier to retailer acceptance. We propose that by changing the structure of cash flows in the contract offered to a retailer (keeping net payments constant), a manufacturer can shift a retailer from making ambiguity‐averse to ambiguity‐neutral choices, thereby increasing the retailer's willingness to stock new products. In a series of studies, we demonstrate that contracts structured to provide positive cash flows after ambiguity has been resolved can increase the retailer's willingness to choose products with an unknown demand distribution. Thus, contracts with positive postdemand payments to the retailer have the potential to increase acceptance of new products.
A randomized, placebo‐controlled study to evaluate the efficacy and safety of adding omarigliptin to insulin therapy in Japanese patients with type 2 diabetes and inadequate glycaemic control
Authors: Kadowaki Takashi , Seino Yutaka , Kaku Kohei , Okamoto Taro , Kameya Miho , Sato Asako , Hirano Tomona , Oshima Nobuyuki , Gantz Ira , O'Neill Edward A. , Engel Samuel S. ,   the Omarigliptin Study 039 Group
Published: January 2021

AbstractAimTo evaluate the efficacy and safety of adding the once‐weekly oral dipeptidyl peptidase‐4 inhibitor omarigliptin to treatment of Japanese patients with type 2 diabetes and inadequate glycaemic control on insulin monotherapy.Materials and MethodsIn a 52‐week clinical trial, Japanese patients on insulin monotherapy were randomized to once‐weekly omarigliptin 25 mg (N = 123) or placebo (N = 61) for a 16‐week, double‐blind, placebo‐controlled period. After Week 16, patients continued or switched to omarigliptin for a 36‐week open‐label period.ResultsFrom a mean baseline of approximately 8.8%, the Week 16 least squares mean changes in HbA1c were −0.61% (omarigliptin) and 0.29% (placebo); the between‐group difference was −0.90% (p < .001). At Week 52, the mean change from baseline in HbA1c was −0.57% in both the group on omarigliptin for 52 weeks and the group on omarigliptin for 36 weeks (switched from placebo at Week 16). During the first 16 weeks of treatment, the incidences of adverse events (AEs), serious AEs, drug‐related AEs and discontinuation from trial medication because of an AE were similar in both groups. A slight increase in incidence of symptomatic hypoglycaemia was observed in the omarigliptin group (n = 13 [10.6%]) compared with placebo (n = 4 [6.6%]). No severe hypoglycaemia was reported during the study. No new safety signals emerged with treatment beyond Week 16 through Week 52.ConclusionThe addition of once‐weekly omarigliptin to insulin therapy for up to 52 weeks was generally well tolerated and provided clinically meaningful improvement in glycaemic control throughout the trial period. ClinicalTrials.gov: NCT02906709
Bilateral subthalamic nucleus deep brain stimulation is an effective treatment for diphasic dyskinesia
Authors: Kim Ahro , Kim Han‐Joon , Kim Aryun , Kim Yoon , Jang Mihee , Paek Sun Ha , Jeon Beomseok 
Published: January 2021

AbstractBackground and purposeThe purpose was to assess the effect of bilateral subthalamic nucleus deep brain stimulation (STN DBS) on diphasic dyskinesia in patients with Parkinson disease (PD) and to assess the factors associated with the remission of diphasic dyskinesia.MethodsMedical records for PD patients who underwent bilateral STN DBS at the Movement Disorder Center of Seoul National University Hospital from March 2005 to November 2016 were reviewed. Patients were evaluated preoperatively and at 3, 6 and 12 months after surgery, and annually thereafter. The presence of peak‐dose dyskinesia and diphasic dyskinesia is based on the interview and examination of patients at baseline and at each follow‐up.ResultsAmongst 202 patients who underwent STN DBS, 66 patients who had diphasic dyskinesia preoperatively were included in the analysis. Diphasic dyskinesia disappeared in 49 (74%) after surgery. In 27 (55.1%) patients whose diphasic dyskinesia disappeared after DBS, peak‐dose and diphasic dyskinesia disappeared persistently from as early as 3 months postoperatively. Age at onset was younger and disease duration at surgery was longer in patients whose diphasic dyskinesia persisted compared with patients whose diphasic dyskinesia disappeared. Multivariate Cox regression analysis demonstrated that patients with greater postoperative decrease of dopaminergic medications were more likely to have remission of diphasic dyskinesia.ConclusionThis study showed that bilateral STN DBS is effective in controlling diphasic dyskinesia and should be considered in PD patients with diphasic dyskinesia.