bluuebunny/crossref_metadata_2025_split huggingface dataset:
Real‐World Comparative Effectiveness and Safety of Non‐Vitamin K Antagonist Oral Anticoagulants vs. Warfarin in a Developing Country
Authors: Mitsuntisuk Phatcharin , Nathisuwan Surakit , Junpanichjaroen Athirat , Wongcharoen Wanwarang , Phrommintikul Arintaya , Wattanaruengchai Phannita , Rattanavipanon Wipharak , Chulavatnatol Suvatna , Chaiyakunapruk Nathorn , Likittanasombat Khanchit , Lip Gregory Y. H. 
Published: October 2020

We aimed to compare effectiveness and safety of the non‐vitamin K antagonist oral anticoagulants (NOACs) vs. warfarin for stroke prevention in nonvalvular atrial fibrillation (NVAF) in a developing country where anticoagulation control with warfarin is suboptimal. A real‐world study was conducted among patients with NVAF in Thailand receiving NOACs and warfarin from 9 hospitals during January 2012 to April 2018. Propensity‐score weighting was used to balance covariates across study groups. Cox regression models were used to compare the risk of thromboembolism, major bleeding, and net adverse clinical events across matched cohorts. A total of 2,055 patients; 605, 604, 441, and 405 patients receiving warfarin, rivaroxaban, dabigatran, and apixaban, respectively, were included. Median (interquartile range) time in therapeutic range (TTR) for warfarin users was 49.5% (26.6%–70.3%). Compared with warfarin, NOACs were associated with a significant reduction in major bleeding either when analyzed as a group (adjusted hazard ratio (HR) (95% confidence interval (CI)) of 0.46 (0.34–0.62) or by each agent. Compared with warfarin users with poor TTR, apixaban (adjusted HR 0.48, 95% CI 0.26–0.86, P = 0.013) and dabigatran (adjusted HR 0.44, 95% CI 0.21–0.90, P = 0.025) were associated with a lower risk of thromboembolism, in addition to markedly lower risk of major bleeding. In a healthcare system where anticoagulation control with warfarin is suboptimal, use of NOACs was associated with a profound reduction in major bleeding. The effectiveness and safety advantages of NOACs were more pronounced compared with warfarin users with low TTR.
Countermeasures for Preventing and Treating Opioid Overdose
Authors: France Charles P. , Ahern Gerard P. , Averick Saadyah , Disney Alex , Enright Heather A. , Esmaeli‐Azad Babak , Federico Arianna , Gerak Lisa R. , Husbands Stephen M. , Kolber Benedict , Lau Edmond Y. , Lao Victoria , Maguire David R. , Malfatti Michael A. , Martinez Girardo , Mayer Brian P. , Pravetoni Marco , Sahibzada Niaz , Skolnick Phil , Snyder Evan Y. , Tomycz Nestor , Valdez Carlos A. , Zapf Jim 
Published: October 2020

The only medication available currently to prevent and treat opioid overdose (naloxone) was approved by the US Food and Drug Administration (FDA) nearly 50 years ago. Because of its pharmacokinetic and pharmacodynamic properties, naloxone has limited utility under some conditions and would not be effective to counteract mass casualties involving large‐scale deployment of weaponized synthetic opioids. To address shortcomings of current medical countermeasures for opioid toxicity, a trans‐agency scientific meeting was convened by the US National Institute of Allergy and Infectious Diseases/National Institutes of Health (NIAID/NIH) on August 6 and 7, 2019, to explore emerging alternative approaches for treating opioid overdose in the event of weaponization of synthetic opioids. The meeting was initiated by the Chemical Countermeasures Research Program (CCRP), was organized by NIAID, and was a collaboration with the National Institute on Drug Abuse/NIH (NIDA/NIH), the FDA, the Defense Threat Reduction Agency (DTRA), and the Biomedical Advanced Research and Development Authority (BARDA). This paper provides an overview of several presentations at that meeting that discussed emerging new approaches for treating opioid overdose, including the following: (1) intranasal nalmefene, a competitive, reversible opioid receptor antagonist with a longer duration of action than naloxone; (2) methocinnamox, a novel opioid receptor antagonist; (3) covalent naloxone nanoparticles; (4) serotonin (5‐HT)1A receptor agonists; (5) fentanyl‐binding cyclodextrin scaffolds; (6) detoxifying biomimetic “nanosponge” decoy receptors; and (7) antibody‐based strategies. These approaches could also be applied to treat opioid use disorder.
Biodegradable Plastics: Standards, Policies, and Impacts
Authors: Filiciotto Layla , Rothenberg Gadi 
Published: October 2020

AbstractPlastics are ubiquitous in our society. They are in our phones, clothes, bottles, and cars. Yet having improved our lives considerably, they now threaten our environment and our health. The associated carbon emissions and persistency of plastics challenge the fragile balance of many ecosystems. One solution is using biodegradable plastics. Ideally, such plastics are easily assimilated by microorganisms and disappear from our environment. This can help reduce the problems of climate change, microplastics, and littering. However, biodegradable plastics are still only a tiny portion of the global plastics market and require further efforts in research and commercialization. Here, a critical overview of the state of the art of biodegradable plastics is given. Using a material flow analysis, the challenges of the plastic market are highlighted, and with it the large market potential of biodegradable plastics. The environmental and socio‐economic impact of plastics, government policies, standards and certifications, physico‐chemical properties, and analytical techniques are covered. The Review concludes with a personal outlook on the future of bioplastics, based on our own experience with their development and commercialization.
Resilient structure of nature‐based extension programs facilitates transition to online delivery and maintains participant satisfaction
Authors: Main Martin B. , Ober Holly K. , Johnson Shelly A. 
Published: October 2020

AbstractRestrictions on public gatherings in early 2020 due to the COVID‐19 pandemic resulted in cancelation of in‐person outreach programs offered by the Florida Master Naturalist Program and Natural Areas Training Academy, two successful University of Florida extension programs that provide natural history and resource management training to lay and professional audiences. In response, both programs rapidly transitioned to blended or 100% online educational methods to continue offering courses and maintain program operations. To assess participant responses to these changes, we used surveys and course registry data to evaluate and compare course enrollment, satisfaction, and outcomes among courses with new online formats to courses offered prior to the COVID‐19 pandemic. We also examined logistical challenges and key programmatic elements that facilitated the transition of both programs to increased reliance on online education. Course participants responded favorably to classes offered online. Our results revealed an audience exists for online programming, that satisfaction with online courses was high and comparable to that measured for in‐person courses, and that online approaches effectively transferred knowledge and promoted behavior change in participants. The transition to online programming required investments of time, energy, and in some cases, direct costs. However, this transition was greatly facilitated by the existence of well‐defined program protocols, educational curricula, strong partnerships, and feedback mechanisms for both programs. Long‐term investments in program structure, partnerships, and support systems enabled both programs to be resilient and adaptable and successfully implement online programming in response to the COVID‐19 pandemic.
Digital manikins to self‐report pain on a smartphone: A systematic review of mobile apps
Authors: Ali Syed Mustafa , Lau Wei J. , McBeth John , Dixon William G. , van der Veer Sabine N. 
Published: October 2020

AbstractBackgroundChronic pain is the leading cause of disability. Improving our understanding of pain occurrence and treatment effectiveness requires robust methods to measure pain at scale. Smartphone‐based pain manikins are human‐shaped figures to self‐report location‐specific aspects of pain on people's personal mobile devices.MethodsWe searched the main app stores to explore the current state of smartphone‐based pain manikins and to formulate recommendations to guide their development in the future.ResultsThe search yielded 3,938 apps. Twenty‐eight incorporated a pain manikin and were included in the analysis. For all apps, it was unclear whether they had been tested and had end‐user involvement in the development. Pain intensity and quality could be recorded in 28 and 13 apps, respectively, but this was location specific in only 11 and 4. Most manikins had two or more views (n = 21) and enabled users to shade or select body areas to record pain location (n = 17). Seven apps allowed personalising the manikin appearance. Twelve apps calculated at least one metric to summarise manikin reports quantitatively. Twenty‐two apps had an archive of historical manikin reports; only eight offered feedback summarising manikin reports over time.ConclusionsSeveral publically available apps incorporated a manikin for pain reporting, but only few enabled recording of location‐specific pain aspects, calculating manikin‐derived quantitative scores, or generating summary feedback. For smartphone‐based manikins to become adopted more widely, future developments should harness manikins’ digital nature and include robust validation studies. Involving end users in the development may increase manikins’ acceptability as a tool to self‐report pain.SignificanceThis review identified and characterised 28 smartphone apps that included a pain manikin (i.e. pain drawings) as a novel approach to measure pain in large populations. Only few enabled recording of location‐specific pain aspects, calculating quantitative scores based on manikin reports, or generating manikin feedback. For smartphone‐based manikins to become adopted more widely, future studies should harness the digital nature of manikins, and establish the measurement properties of manikins. Furthermore, we believe that involving end users in the development process will increase acceptability of manikins as a tool for self‐reporting pain.
Integration of 3D large‐scale earthquake simulations into the assessment of the seismic risk of Bogota, Colombia
Authors: Riaño Andrea C. , Reyes Juan C. , Yamín Luis E. , Bielak Jacobo , Taborda Ricardo , Restrepo Doriam 
Published: October 2020

AbstractBogotá, the capital city of Colombia, is mostly located on a lacustrine soil deposit surrounded by hills in a central plateau of the eastern cordillera of the Colombian Andes. This highly populated urban area is exposed to a significant seismic hazard from local and regional fault systems. In addition, the potential ground motion amplification during earthquakes due to the presence of soft soil deposits, along with the effects of the surface and subsurface topography, can strongly influence the seismic hazard and consequently the seismic risk to the city. This study aims to develop a physics‐based framework to generate synthetic ground records that can help better understand the seismic response of the basin and other amplification effects during strong earthquake shaking in the region, and to incorporate these effects into the estimation of seismic risk. To this end, a set of simulations were first conducted on Hercules, the wave propagation octree‐based finite element simulator developed by the Quake Group at Carnegie Mellon University, to identify the impacts of hypothetical strong earthquakes scenarios. Then, the results from these simulations were integrated with the exposure and vulnerability information previously developed for the main building constructions in the city to assess the seismic risk in the region under different conditions of analysis. Results from this more detailed model are compared with previously published results from simplified models. Sensitivity analyses help identify critical aspects that should be considered in the future to improve the seismic risk assessment of infrastructure.
Investigation of risk of dementia diagnosis and death in patients in older people's secondary care mental health services
Authors: Kershenbaum Anne , Cardinal Rudolf N. , Chen Shanquan , Underwood Benjamin R. , Seyedsalehi Aida , Lewis Jonathan , Rubinsztein Judy Sasha 
Published: October 2020

AbstractObjectivesPrevious studies have shown increased rates of death and dementia in older people in specific serious mental illnesses (SMI) such as bipolar disorder or depression. We examined the rates of death and dementia in older people referred into a secondary care psychiatric service across a range of SMIs.MethodsWe used an anonymised dataset across 6 consecutive years with 28,340 patients aged 65 years and older from a single secondary care psychiatric trust in the United Kingdom.We identified deaths and incident dementia in patients with bipolar disorder/mania, schizophrenia, recurrent depression and anxiety disorders. We compared mortality and dementia rates between these diagnostic groups and in different treatment settings. We also examined mortality rates and dementia rates compared with general population rates.ResultsPatients with schizophrenia showed the highest hazard rate for death compared to other groups with SMIs (hazard ratio, 1.58; 95% confidence interval (CI), 1.18–2.1, with anxiety group the reference). Survival was reduced in patients referred to liaison psychiatry services. There were no significant differences between the SMI groups in terms of rates of dementia. However, risks of death and dementia were significantly increased compared to the general population (standardized mortality rates with 95% CI, 2.6(2.0–3.3), 3.5(2.6–4.5), 2.5(2.0–3.0) and 1.8 (1.4–2.2) and standardized dementia incidence rates with 95% CI, 2.7(1.5–4.1), 2.9(1.5–4.7), 3.8(2.6–5.2) and 4.3 (3.0–5.7) for bipolar disorder/mania, schizophrenia, recurrent depression and anxiety disorders respectively.ConclusionsOlder adults referred into an old age psychiatry service show higher rates of dementia and death than those reported for the general population.
Approximation to pain‐signaling network in humans by means of migraine
Authors: Hosp Jonas Aurel , Reisert Marco , von Kageneck Charlotte , Rijntjes Michel , Weiller Cornelius 
Published: October 2020

AbstractNociceptive signals are processed within a pain‐related network of the brain. Migraine is a rather specific model to gain insight into this system. Brain networks may be described by white matter tracts interconnecting functionally defined gray matter regions. Here, we present an overview of the migraine‐related pain network revealed by this strategy. Based on diffusion tensor imaging data from subjects in the Human Connectome Project (HCP) database, we used a global tractography approach to reconstruct white matter tracts connecting brain regions that are known to be involved in migraine‐related pain signaling. This network includes an ascending nociceptive pathway, a descending modulatory pathway, a cortical processing system, and a connection between pain‐processing and modulatory areas. The insular cortex emerged as the central interface of this network. Direct connections to visual and auditory cortical association fields suggest a potential neural basis of phono‐ or photophobia and aura phenomena. The intra‐axonal volume (Vintra) as a measure of fiber integrity based on diffusion microstructure was extracted using an innovative supervised machine learning approach in form of a Bayesian estimator. Self‐reported pain levels of HCP subjects were positively correlated with tract integrity in subcortical tracts. No correlation with pain was found for the cortical processing systems.
MGMT promoter methylation analysis for allocating combined CCNU/TMZ chemotherapy: Lessons learned from the CeTeG/NOA‐09 trial
Authors: Tzaridis Theophilos , Schäfer Niklas , Weller Johannes , Steinbach Joachim‐Peter , Schlegel Uwe , Seidel Sabine , Sabel Michael , Hau Peter , Seidel Clemens , Krex Dietmar , Goldbrunner Roland , Tonn Jörg‐Christian , Grauer Oliver , Kebir Sied , Schneider Matthias , Schaub Christina , Vatter Hartmut , Coch Christoph , Glas Martin , Fimmers Rolf , Pietsch Torsten , Reifenberger Guido , Herrlinger Ulrich , Felsberg Jörg 
Published: October 2020

AbstractThe CeTeG/NOA‐09 trial showed a survival benefit for combined CCNU/TMZ therapy in MGMT‐promoter‐methylated glioblastoma patients (quantitative methylation‐specific PCR [qMSP] ratio > 2). Here, we report on the prognostic value of the MGMT promoter methylation ratio determined by qMSP and evaluate the concordance of MGMT methylation results obtained by qMSP, pyrosequencing (PSQ) or DNA methylation arrays (MGMT‐STP27). A potential association of qMSP ratio with survival was analyzed in the CeTeG/NOA‐09 trial population (n = 129; log‐rank tests, Cox regression analyses). The concordance of MGMT methylation assays (qMSP, PSQ and MGMT‐STP27) was evaluated in 76 screened patients. Patients with tumors of qMSP ratio > 4 showed superior survival compared to those with ratios 2‐4 (P = .0251, log‐rank test). In multivariate analysis, the qMSP ratio was not prognostic across the study cohort (hazard ratio [HR] = 0.88; 95% CI: 0.72‐1.08). With different cutoffs for qMSP ratio (4, 9, 12 or 25), the CCNU/TMZ benefit tended to be larger in subgroups with lower ratios (eg, for cutoff 9: HR 0.32 for lower subgroup, 0.73 for higher subgroup). The concordance rates with qMSP were 94.4% (PSQ) and 90.2% (MGMT‐STP27). Discordant results were restricted to tumors with qMSP ratios ≤4 and PSQ mean methylation rate ≤25%. Despite a shorter survival in MGMT‐promoter‐methylated patients with lower methylation according to qMSP, these patients had a benefit from combined CCNU/TMZ therapy, which even tended to be stronger than in patients with higher methylation rates. With acceptable concordance rates, decisions on CCNU/TMZ therapy may also be based on PSQ or MGMT‐STP27.
Regulation of ferroptosis by ncRNA: A new direction
Authors: Li Yujia , Shen Min , Jin Chun , Gao Liyuan , Liang Baoyu , Wang Zhenyi , Tan Shanzhong , Chen Anping , Zhang Feng , Zhang Zili , Zheng Shizhong 
Published: October 2020

AbstractFerroptosis is a metabolic disorder of lipid oxides in cells, which leads to abnormal metabolism under the catalysis of iron, which produces an expansive number of lipids, wrecks the redox in cells, attacks biological macromolecules and triggers cell death. This death process was marked by the increase of cytoplasmic and lipid reactive oxygen species, the decrease of mitochondria and the higher density of mitochondrial membrane. Non‐coding RNA (ncRNA) is a kind of small RNA molecules found in recent years, which can transcribe but do not encode proteins and have specific functions. These ncRNAs play a key role in controlling gene expression by combining with proteins or other molecules to turn genes on or off. Ferroptosis is viewed as a leap forward in the medication of tumors and some intractable maladies. Under the circumstances that there are still many mysteries in the study of ferroptosis, the research on the role of ncRNAs in ferroptosis is even less. By consulting the pertinent literature, this article reviews the research advance about ncRNAs on ferroptosis, which provides a new research direction and ideas for the study of ferroptosis.
An in vitro assessment of the response of THP‐1 macrophages to varying stiffness of a glycol‐chitosan hydrogel for vocal fold tissue engineering applications
Authors: Coburn Patrick Thomas , Herbay Alexandre Camille , Berrini Mattia , Li‐Jessen Nicole Y. K. 
Published: October 2020

AbstractThe physical properties of a biomaterial play an essential role in regulating immune and reparative activities within the host tissue. This study aimed to evaluate the immunological impact of material stiffness of a glycol‐chitosan hydrogel designed for vocal fold tissue engineering. Hydrogel stiffness was varied via the concentration of glyoxal cross‐linker applied. Hydrogel mechanical properties were characterized through atomic force microscopy and shear plate rheometry. Using a transwell setup, macrophages were co‐cultured with human vocal fold fibroblasts that were embedded within the hydrogel. Macrophage viability and cytokine secretion were evaluated at 3, 24, and 72 hr of culture. Flow cytometry was applied to evaluate macrophage cell surface markers after 72 hr of cell culture. Results indicated that increasing hydrogel stiffness was associated with increased anti‐inflammatory activity compared to relevant controls. In addition, increased anti‐inflammatory activity was observed in hydrogel co‐cultures. This study highlighted the importance of hydrogel stiffness from an immunological viewpoint when designing novel vocal fold hydrogels.
The phytoestrogen glabrene prevents osteoporosis in ovariectomized rats through upregulation of the canonical Wnt/β‐catenin signaling pathway
Authors: Liu Jun , Deng Xinchang , Liang Xiao , Li Longying 
Published: October 2020

AbstractThis study systematically investigated the effects of phytoestrogen glabrene on postmenopausal osteoporosis in an ovariectomy (OVX) rat model. Glabrene administration (25, 50, and 100 mg/kg) for 13 weeks can significantly slow down the body weight gain and slightly increase the uterus weight of OVX rats. The increased levels of U‐Ca, U‐P levels, urine DPD/creatinine, serum ALP, OCN, triglycerides, and total cholesterol induced by OVX were dramatically inhibited in rats, whereas no difference occurred for S‐Ca and S‐P in all groups. Furthermore, glabrene can enhance bone mineral density of the right femur, fourth‐lumbar vertebra and tibia and improve biomechanical parameters, such as femoral neck loading force, three‐point bending of the tibia, and vertebral compression in OVX rats. Moreover, glabrene greatly suppressed the expression of TRAP protein but increased OPG and BGP protein expression in tibia tissue of OVX rats. In addition, OVX‐induced reduction of Lrp‐5, β‐catenin, Runx2, and Osx protein expression was all restored by glabrene treatment. The present study indicated that glabrene might be a potential alternative medicine for the prevention and treatment of postmenopausal osteoporosis via activation of the Wnt/β‐catenin signaling pathway.
SP3 is associated with migration, invasion, and Akt/PKB signalling in MDA‐MB‐231 breast cancer cells
Authors: Mansour Mohammed A. 
Published: October 2020

AbstractSpecificity proteins (SPs) have pro‐oncogenic functions in cancer cells, ranging from cancer cell proliferation, migration, invasion, and angiogenesis. There is strong evidence that several antineoplastic drugs target depletion of SP proteins via different pathways. However, the mode of action of SP3 and the underlying consequences of its depletion are not well understood. Here, we demonstrate that SP3 is overexpressed in invasive breast cancer cells vs normal counterparts. The gene expression analysis from The Cancer Genome Atlas datasets indicated that SP3 is strongly correlated with Akt signalling‐related proteins, G protein subunit alpha 13, and RAB33B (RAB33B, member RAS oncogene family). RNA interference of SP3 decreased active phosphorylation of Akt at serine and threonine sites. These findings indicate that SP3 exhibits a pro‐oncogenic function, which clearly fits the description of an nononcogene addiction gene. Future analyses are prompted to uncover the SP3 gene regulation function and to reveal downstream targets of SP3 in breast cancer.