bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electrical delays in quadripolar leads with cardiac resynchronization therapy
Authors: Koerber Scott M. , Field Michael E. , Cobb Daniel B. , Gregoski Mathew J. , Sturdivant John L. , Gold Michael R. 
Published: July 2021

AbstractBackgroundPacing at sites of late intraventricular activation (QLV) or long interventricular conduction (right ventricle [RV]‐left ventricular [LV]) have been associated with improved cardiac resynchronization therapy (CRT) outcomes. Quadripolar leads improve CRT outcomes by allowing for electrical repositioning to optimize pacing sites. However, little is known regarding the effect of such repositioning on electrical delay.ObjectiveDetermine the relationship between different electrical bipoles from a quadripolar lead and measures of electrical delay.MethodsForty‐six patients underwent CRT with a quadripolar lead. The RV‐LV and QLV intervals were measured for both the proximal and distal bipoles and the difference (Δ) between bipoles for each measure were calculated. Multivariate analyses were performed to identify predictors of electrical delays.ResultsThis was a typical CRT population with a mean age of 65 years and ejection fraction of 27%, with left bundle branch block (LBBB) present in 70%. The regression model for ΔQLV was significant (p = .05), with both gender (p = .008) and LBBB status (p = .020) significant predictors. The overall regression model for ΔRV‐LV was not significant. ΔQLV and ΔRV‐LV were significant among LBBB patients. Among non‐LBBB, only ΔRV‐LV was significant (mean: 7.2 ms, p = .006). ΔRV‐LV versus ΔQLV were strongly correlated in LBBB (R2 = .92) but not non‐LBBB (R2 = .06).ConclusionIn LBBB, ΔRV‐LV and ΔQLV are closely correlated suggesting that the proximal bipole and thus basal LV pacing sites should be selected when feasible. Greater variation in activation pattern is present in non‐LBBB, so pacing sites should be individualized.
Thickness of the left atrial wall surrounding the left atrial appendage orifice
Authors: Słodowska Katarzyna , Hołda Jakub , Dudkiewicz Damian , Malinowska Karolina , Bolechała Filip , Kopacz Paweł , Koziej Mateusz , Hołda Mateusz K. 
Published: July 2021

AbstractIntroductionThe aim of this study was to investigate the thickness of the left atrial wall surrounding the left atrial appendage (LAA) orifice.Methods and ResultsThe tissue thickness around the LAA orifice was measured at four points (superior, inferior, anterior, and posterior) in 200 randomly selected autopsied human hearts. The thickest tissue was observed at the anterior point (3.17 ± 1.41 mm), followed by the superior (2.47 ± 1.00 mm), inferior (2.22 ± 0.80 mm) and posterior (2.22 ± 0.83 mm). The chicken wing LAA type was associated with the lowest thickness at the superior point compared to the cauliflower and arrowhead shapes (p = .024). In hearts with an oval LAA orifice, the atrial wall was significantly thicker in all points than in specimens with a round LAA orifice (p > .05). Both the LAA orifice anteroposterior diameter and orifice surface area were negatively correlated with the tissue thickness in the anterior (r = −.22, p = .004 and r = −.23, p = .001) and posterior points (r = −.24, p = .001 and r = −.28, p = .005). Endocardial surface roughness was commonly in the inferior pole of the LAA orifice (75.5% of cases), while they are much less prevalent in other sectors around the orifice (anterior: 17.5%), superior: 4.0%, and posterior: 1.5%).ConclusionsAlthough a significant heterogeneity in the atrial wall thickness around the LAA orifice was observed, the thickness in the respective points is quite conservative and depends only on LAA orifice size and shape, as well as LAA body shape. Thin atrial wall and endocardial surface roughness might challenge invasive procedures within this region.
The inhibition of mammalian target of rapamycin (mTOR) in improving inflammatory response after traumatic brain injury
Authors: Campolo Michela , Casili Giovanna , Lanza Marika , Filippone Alessia , Cordaro Marika , Ardizzone Alessio , Scuderi Sarah Adriana , Cuzzocrea Salvatore , Esposito Emanuela , Paterniti Irene 
Published: July 2021

AbstractTraumatic brain injury (TBI) provokes primary and secondary damage on endothelium and brain parenchyma, leading neurons die rapidly by necrosis. The mammalian target of rapamycin signalling pathway (mTOR) manages numerous aspects of cellular growth, and it is up‐regulated after moderate to severe traumatic brain injury (TBI). Currently, the significance of this increased signalling event for the recovery of brain function is unclear; therefore, we used two different selective inhibitors of mTOR activity to discover the functional role of mTOR inhibition in a mouse model of TBI performed by a controlled cortical impact injury (CCI). Treatment with KU0063794, a dual mTORC1 and mTORC2 inhibitor, and with rapamycin as well‐known inhibitor of mTOR, was performed 1 and 4 hours subsequent to TBI. Results proved that mTOR inhibitors, especially KU0063794, significantly improved cognitive and motor recovery after TBI, reducing lesion volumes. Also, treatment with mTOR inhibitors ameliorated the neuroinflammation associated with TBI, showing a diminished neuronal death and astrogliosis after trauma. Our findings propose that the involvement of selective mTORC1/2 inhibitor may represent a therapeutic strategy to improve recovery after brain trauma.
LncRNA PAXIP1‐AS1 fosters the pathogenesis of pulmonary arterial hypertension via ETS1/WIPF1/RhoA axis
Authors: Song Rong , Lei Si , Yang Song , Wu Shang‐Jie 
Published: July 2021

AbstractPulmonary arterial hypertension (PAH) is a life‐threatening disease featured with elevated pulmonary vascular resistance and progressive pulmonary vascular remodelling. It has been demonstrated that lncRNA PAXIP1‐AS1 could influence the transcriptome in PAH. However, the exact molecular mechanism of PAXIP1‐AS1 in PAH pathogenesis remains largely unknown. In this study, in vivo rat PAH model was established by monocrotaline (MCT) induction and hypoxia was used to induce in vitro PAH model using human pulmonary artery smooth muscle cells (hPASMCs). Histological examinations including H&E, Masson's trichrome staining and immunohistochemistry were subjected to evaluate the pathological changes of lung tissues. Expression patterns of PAXIP1‐AS1 and RhoA were assessed using qRT‐PCR and Western blotting, respectively. CCK‐8, BrdU assay and immunofluorescence of Ki67 were performed to measure the cell proliferation. Wound healing and transwell assays were employed to evaluate the capacity of cell migration. Dual‐luciferase reporter assay, co‐immunoprecipitation, RIP and CHIP assays were employed to verify the PAXIP1‐AS1/ETS1/WIPF1/RhoA regulatory network. It was found that the expression of PAXIP1‐AS1 and RhoA was remarkably higher in both lung tissues and serum of MCT‐induced PAH rats, as well as in hypoxia‐induced hPASMCs. PAXIP1‐AS1 knockdown remarkably suppressed hypoxia‐induced cell viability and migration of hPASMCs. PAXIP1‐AS1 positively regulated WIPF1 via recruiting transcriptional factor ETS1, of which knockdown reversed PAXIP1‐AS1‐mediated biological functions. Co‐immunoprecipitation validated the WIPF1/RhoA interaction. In vivo experiments further revealed the role of PAXIP1‐AS1 in PAH pathogenesis. In summary, lncRNA PAXIP1‐AS1 promoted cell viability and migration of hPASMCs via ETS1/WIPF1/RhoA, which might provide a potential therapeutic target for PAH treatment.
Pharmacokinetic and pharmacodynamic studies of CD19 CAR T cell in human leukaemic xenograft models with dual‐modality imaging
Authors: Wu Qiong , Wang Yan , Wang Xinyu , Liang Ningxia , Liu Jingjing , Pan Donghui , Xu Yuping , Wang Lizhen , Yan Junjie , Wang Guangji , Miao Liyan , Yang Min 
Published: July 2021

AbstractIn recent years, chimeric antigen receptor T (CAR T)‐cell therapy has shown great potential in treating haematologic disease, but no breakthrough has been achieved in solid tumours. In order to clarify the antitumour mechanism of CAR T cell in solid tumours, the pharmacokinetic (PK) and pharmacodynamic (PD) investigations of CD19 CAR T cell were performed in human leukaemic xenograft mouse models. For PK investigation, we radiolabelled CD19 CAR T cell with 89Zr and used PET imaging in the CD19‐positive and the CD19‐negative K562‐luc animal models. For PD evaluation, optical imaging, tumour volume measurement and DNA copy‐number detection were performed. Unfortunately, the qPCR results of the DNA copy number in the blood were below the detection limit. The tumour‐specific uptake was higher in the CD19‐positive model than in the CD19‐negative model, and this was consistent with the PD results. The preliminary PK and PD studies of CD19 CAR T cell in solid tumours are instructive. Considering the less efficiency of CAR T‐cell therapy of solid tumours with the limited number of CAR T cells entering the interior of solid tumours, this study is suggestive for the subsequent CAR T‐cell design and evaluation of solid tumour therapy.
Process effectiveness assessment by modeling the kinetics of lotus seed drying combining air‐borne ultrasound and microwave vacuum
Authors: Wang Weiwei , Lei Yanping , Lo Y. Martin , Han Yinjie , Zheng Baodong , Tian Yuting 
Published: July 2021

AbstractThis study presents the effects of ultrasound (US) on the drying kinetics of lotus seeds in a hybrid dryer equipped with constant microwave power in combination with airborne US at vacuum degree (USMVD) and atmospheric pressure (USMD) from 120 to 440 W of five US power levels. Water‐borne US pretreatment before microwave drying (US + MD) or microwave vacuum drying (US + MVD) was simultaneously performed to compare their effectiveness in drying lotus seeds under the same US power. USMD and USMVD techniques reduced the drying time up to 26.19% and 14.29% while reducing energy consumption by up to 10.42% and 23.02% when compared with MVD and MD (without US), respectively, and with relatively high ultrasonic power density. The US + MD and US + MVD drying also reduced the processing time and energy consumption compared to MD and MVD process, respectively, but was less effective than USMVD and USMD. In addition, with higher US power applied, drying occurred more rapidly with less energy consumption. The newly proposed model showed the best fit to the drying curve based on model with the highest regression coefficient, lowest root mean square error, sum square error, and chi‐square. Furthermore, the enhanced effectiveness by USMVD and USMD could be attributed to the respective “heating” and “synergistic” effects generated by microwave and US. Therefore, US in combination with MVD or MD could be used jointly owing to the enhanced process effectiveness.Practical applicationsDrying process is one of the most complex and energy‐consuming processes. The drying kinetics model was applied in drying equipment engineering. The drying kinetic model studies the law of moisture changes during the drying process and provides a theoretical basis for the adjustment of the lotus seed drying equipment parameters. In order to improve the quality of drying products and optimize the drying process, it is necessary to use mathematical model to simulate the drying process under different drying conditions. This study provides data support for equipment selection, energy saving, and consumption reduction and industrial design of lotus seeds drying process.
Honor killings in Muslim and Western countries in modern times: A critical literature review and definitional implications
Authors: Ne'eman‐Haviv Vered 
Published: July 2021

AbstractHonor killings are an ancient phenomenon that has been widely discussed in the professional literature. This article reviews the current literature in the field, using a socio‐cultural theoretical framework, and critically examines the effect of modernization processes on the phenomenon, distinguishing between Arab and Muslim countries and Western countries. The review shows that despite modernization processes, and at times owing to concerns about these processes, the use of honor killings as a tool to strengthen patriarchal control seems to be widening. The impact of these trends on the definition of honor killings is discussed. An up‐to‐date literature review is necessary to raise awareness of this phenomenon of violence and to establish effective prevention programs. Directions for future research are also discussed.
Participation of persons with dementia and their caregivers in research
Authors: Frank Lori , Jennings Lee A. , Petersen Ronald C. , Majid Tabassum , Gilmore‐Bykovskyi Andrea , Schicker Lonni , Karlawish Jason 
Published: July 2021

AbstractBackgroundThe National Institute on Aging, in conjunction with the Department of Health and Human Services as part of the National Alzheimer's Project Act, convened a 2020 National Research Summit on Care, Services, and Supports for Persons with Dementia and their Caregivers. This review article addresses research participation by persons living with dementia (PLWD) and their care partners in two different ways: as research participants with input on outcomes studied and as engaged research partners.ResultsThis article summarizes each of the topics presented at this Summit session, followed by reflection from the session panelists. Lee Jennings examined collection of outcomes directly from PLWD and the potential for individualized outcomes to enhance measurement in intervention trials. Ron Petersen discussed the impact of nomenclature on research and clinical care, and how and why investigators should be mindful of the connection between dementia nomenclature and the conduct of dementia research. Tabassum Majid examined strategies for engagement in research, including specific examples of involving PLWD and their care partners (including staff in assisted living and skilled nursing facilities), and the potential for this research engagement to improve our understanding of interventions in dementia.ConclusionsResearch participation by PLWD and their care partners is evolving. This review summarizes three areas of opportunity and steps for researchers to work with PLWD and their care partners to design and conduct research that enhances knowledge based on what we learn from PLWD and their care partners, and creates knowledge with them.
Emerging topics in dementia care and services
Authors: Wolff Jennifer L. , Benge Jared F. , Cassel Christine K. , Monin Joan K. , Reuben David B. 
Published: July 2021

AbstractBackgroundThe National Institute on Aging (NIA), in conjunction with the Department of Health and Human Services as part of the National Alzheimer's Project Act (NAPA), convened a 2020 Dementia Care, Caregiving, and Services Research Summit Virtual Meeting Series. This review article summarizes three areas of emerging science that are likely to grow in importance given advances in measurement, technologies, and diagnostic tests that were presented at the Summit.ResultsDr. Cassel discussed novel ethical considerations that have resulted from scientific advances that have enabled early diagnosis of pre‐clinical dementia. Dr. Monin then summarized issues regarding emotional experiences in persons with dementia and their caregivers and care partners, including the protective impact of positive emotion and heterogeneity of differences in emotion by dementia type and individual characteristics that affect emotional processes with disease progression. Finally, Dr. Jared Benge provided an overview of the role of technologies in buffering the impact of cognitive change on real‐world functioning and their utility in safety and monitoring of function and treatment adherence, facilitating communication and transportation, and increasing access to specialists in underserved or remote areas.ConclusionsNational policy initiatives, supported by strong advocacy and increased federal investments, have accelerated the pace of scientific inquiry and innovation related to dementia care and services but have raised some new concerns regarding ethics, disparities, and attending to individual needs, capabilities, and preferences.
Design, implement, and diffuse scalable and sustainable solutions for dementia care
Authors: Boustani Malaz , Unützer Jürgen , Leykum Luci K. 
Published: July 2021

AbstractMost innovations developed to reduce the burden of Alzheimer disease and other related dementias (ADRD) are difficult to implement, diffuse, and scale. The consequences of such challenges in design, implementation, and diffusion are suboptimal care and resulting harm for people living with ADRD and their caregivers. National experts identified four factors that contribute to our limited ability to implement and diffuse of evidence‐based services and interventions for people living with ADRD: (1) limited market demand for the implementation and diffusion of effective ADRD interventions; (2) insufficient engagement of persons living with ADRD and those caring for them in the development of potential ADRD services and interventions; (3) limited evidence and experience regarding scalability and sustainability of evidence‐based ADRD care services; and (4) difficulties in taking innovations that work in one context and successfully implementing them in other contexts. New investments in the science of human‐centered design, implementation, and diffusion are crucial for meeting the goals of the National Plan to Address Alzheimer's Disease under the auspices of the National Alzheimer's Project Act.
Telehealth was beneficial during COVID‐19 for older Americans: A qualitative study with physicians
Authors: Goldberg Elizabeth M. , Jiménez Frances N. , Chen Kevin , Davoodi Natalie M. , Li Melinda , Strauss Daniel H. , Zou Maria , Guthrie Kate , Merchant Roland C. 
Published: July 2021

AbstractBackgroundIndividuals aged 65 and older face unique barriers to adoption of telehealth, and the coronavirus disease 2019 pandemic has provided a “natural experiment” in how to meet the health needs of older patients remotely. Physician perspectives on practical considerations surrounding telehealth adoption, motivations of use, and reasons for nonuse are necessary to inform the future of healthcare delivery. The objective is to understand the experiences of physicians using telemedicine for older patients.MethodsFrom September to November 2020, we conducted 30‐min semi‐structured interviews using purposeful sampling to identify and enroll participants from diverse settings. We included 48 U.S.‐based physicians (geriatrician, n = 18, primary care, n = 15, emergency, n = 15) from all geographic regions, rural–urban and academic/community settings. Audio‐recorded interviews were professionally transcribed and analyzed using framework analysis. Major themes and subthemes were identified.ResultsParticipants had a median (interquartile range) age of 37.5 (34–44.5), 27 (56%) were women. Five major themes emerged: (1) telehealth uptake was rapid and iterative, (2) telehealth improved the safety of medical care, (3) use cases were specialty‐specific (for geriatricians and primary care physicians telehealth substituted for in‐person visits; for emergency physicians it primarily supplemented in‐person visits), (4) physicians altered clinical care to overcome older patient barriers to telehealth use, and (5) telehealth use among physicians declined in mid‐April 2020, due primarily to patient needs and administrator preferences, not physician factors.ConclusionIn this qualitative analysis, physicians reported a rapid, iterative uptake of telehealth and attenuation of use as coronavirus disease 2019 prevalence declined. Physician experiences during the pandemic can inform interventions and policies to help buoy telehealth for ongoing healthcare delivery and ensure its accessibility for older Americans.
Mass spectrometry‐based methods for robust measurement of Alzheimer's disease biomarkers in biological fluids
Authors: Korecka Magdalena , Shaw Leslie M. 
Published: July 2021

AbstractAlzheimer's disease (AD) is the most common form of dementia affecting 60%–70% of people afflicted with this disease. Accurate antemortem diagnosis is urgently needed for early detection of AD to enable reliable estimation of prognosis, intervention, and monitoring of the disease. The National Institute on Aging/Alzheimer's Association sponsored the ‘Research Framework: towards a biological definition of AD’, which recommends using different biomarkers in living persons for a biomarker‐based definition of AD regardless of clinical status. Fluid biomarkers represent one of key groups of them. Since cerebrospinal fluid (CSF) is in direct contact with brain and many proteins present in the brain can be detected in CSF, this fluid has been regarded as the best biofluid in which to measure AD biomarkers. Recently, technological advancements in protein detection made possible the effective study of plasma AD biomarkers despite their significantly lower concentrations versus to that in CSF. This and other challenges that face plasma‐based biomarker measurements can be overcome by using mass spectrometry. In this review, we discuss AD biomarkers which can be reliably measured in CSF and plasma using targeted mass spectrometry coupled to liquid chromatography (LC/MS/MS). We describe progress in LC/MS/MS methods’ development, emphasize the challenges, and summarize major findings. We also highlight the role of mass spectrometry and progress made in the process of global standardization of the measurement of Aβ42/Aβ40. Finally, we briefly describe exploratory proteomics which seek to identify new biomarkers that can contribute to detection of co‐pathological processes that are common in sporadic AD.image
Refining the amyloid β peptide and oligomer fingerprint ambiguities in Alzheimer’s disease: Mass spectrometric molecular characterization in brain, cerebrospinal fluid, blood, and plasma
Authors: Michno Wojciech , Blennow Kaj , Zetterberg Henrik , Brinkmalm Gunnar 
Published: July 2021

AbstractSince its discovery, amyloid‐β (Aβ) has been the principal target of investigation of in Alzheimer's disease (AD). Over the years however, no clear correlation was found between the Aβ plaque burden and location, and AD‐associated neurodegeneration and cognitive decline. Instead, diagnostic potential of specific Aβ peptides and/or their ratio, was established. For instance, a selective reduction in the concentration of the aggregation‐prone 42 amino acid‐long Aβ peptide (Aβ42) in cerebrospinal fluid (CSF) was put forward as reflective of Aβ peptide aggregation in the brain. With time, Aβ oligomers—the proposed toxic Aβ intermediates—have emerged as potential drivers of synaptic dysfunction and neurodegeneration in the disease process. Oligomers are commonly agreed upon to come in different shapes and sizes, and are very poorly characterized when it comes to their composition and their “toxic” properties. The concept of structural polymorphism—a diversity in conformational organization of amyloid aggregates—that depends on the Aβ peptide backbone, makes the characterization of Aβ aggregates and their role in AD progression challenging. In this review, we revisit the history of Aβ discovery and initial characterization and highlight the crucial role mass spectrometry (MS) has played in this process. We critically review the common knowledge gaps in the molecular identity of the Aβ peptide, and how MS is aiding the characterization of higher order Aβ assemblies. Finally, we go on to present recent advances in MS approaches for characterization of Aβ as single peptides and oligomers, and convey our optimism, as to how MS holds a promise for paving the way for progress toward a more comprehensive understanding of Aβ in AD research.
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