bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of the HAS‐BLED versus ORBIT scores in predicting major bleeding among Asians receiving direct‐acting oral anticoagulants
Authors: Wattanaruengchai Phannita , Nathisuwan Surakit , Karaketklang Khemajira , Wongcharoen Wanwarang , Phrommintikul Arintaya , Lip Gregory Y. H. 
Published: November 2021

AimsThis study aimed to evaluate the performance of HAS‐BLED and ORBIT scores in predicting bleeding risk among Asian patients with nonvalvular atrial fibrillation (NVAF) using direct‐acting oral anticoagulants (DOACs).MethodsA retrospective chart review was conducted among adult patients receiving DOACs for ≥6 months during January 2013 to December 2017 in 10 tertiary care hospitals in Thailand. The area under the receiver operating curve (AUROC) method or C‐statistic was used to test the diagnostic accuracy for bleeding risk classification of HAS‐BLED and ORBIT scores. The predictive performances of the two scores were compared using DeLong's method.ResultsA total of 961 NVAF patients, 52.5% warfarin‐naïve and 47.5% warfarin‐experienced, with mean age of 74.25 ± 10.08 years, were included in the analysis. Mean HAS‐BLED and ORBIT scores of the cohort were 1.98 ± 1.10 and 2.37 ± 1.71, respectively. During the mean follow‐up time of 1.55 ± 1.13 years, 34 patients experienced major bleeding (2.28 events/100 patient‐year). For the overall cohort, both the HAS‐BLED and ORBIT scores showed similarly moderate predictive performance on bleeding with C‐statistic (95% confidence interval) of 0.65 (0.57‐0.74) and 0.64 (0.56‐0.71), respectively. There was no statistical significance between the two scores (P = .62). Analysis based on the status of previous warfarin use was consistent with the overall cohort. Based on the calibration analysis, both HAS‐BLED and ORBIT scores possessed moderate ability to identify those who experienced major bleeding from those who did not.ConclusionBoth HAS‐BLED and ORBIT bleeding risk scores had moderate predictive performance in Asian NVAF patients receiving DOACs.
Enhanced clot lysis by a single point mutation in a reteplase variant
Authors: Chen Shanli , Chen Dan , Liu Yurong , Xu Yanyan , Lin Huajian , Cheng Yuan , Li Jinyu , Meng Chun , Liang Mingli , Yuan Cai , Huang Mingdong 
Published: November 2021

SummaryRecombinant tissue‐type plasminogen activator (rtPA) is the clot lysis drug approved for clinical use, and is characterised by a short half‐life and substantial inactivation by plasminogen activator inhibitor‐1 (PAI‐1). We previously discovered that a tPA mutation (A419Y) at the protease domain led to enhanced fibrinolysis activity. In the present study, we studied the mechanism of such mutation in enhancing the proteolytic activity, and whether such enhancement persists in reteplase, an United States Food and Drug Administration‐approved tPA truncated variant. We constructed and expressed a series of reteplase‐based mutants, including rPAG (glycosylated rPA), rPAG‐Y (with A419Y mutant at rPAG), rPAG‐A4 (tetra‐alanine mutation at 37‐loop of rPAG), and rPAG‐A4/Y (with both) and evaluated their plasminogen activation and PAI‐1 resistance. Surface plasmon resonance analysis showed that the rPAG had fibrin affinity comparable to full‐length tPA. Moreover, rPAG‐Y had 8·5‐fold higher plasminogen activation and stronger tolerance to PAI‐1 compared to rPAG. We also found that the mutations containing tetra‐alanine (rPAG‐A4 and rPAG‐A4/Y) had dramatically reduced plasminogen activation and impaired clot lysis. In a pulmonary embolism murine model, rPAG‐Y displayed a more efficient thrombolytic effect than rPAG. These results identified a novel mutant reteplase variant of tPA with increased fibrinolytic activity, laying the foundation for the development of a new potent fibrinolytic agent.
Pharmacokinetics of adrenaline autoinjectors
Authors: Turner Paul J. , Muraro Antonella , Roberts Graham 
Published: November 2021

AbstractAnaphylaxis is a medical emergency with adrenaline acknowledged as the first‐line therapy. It is therefore important that patients have access to self‐injectable adrenaline in the community. Manufacturers have been requested by European Medicine Regulators to generate pharmacokinetic data for these autoinjector devices. For the first time, these data provide an insight into how individual devices work in different populations, and how they compare. We undertook a thorough literature search and also accessed grey literature, using searches of medicine regulators’ websites and freedom of information requests. The data demonstrate that it takes at least 5–10 min to achieve early peak plasma concentration for most devices. The specific autoinjector device seems to be the most important determinant of pharmacokinetics, with different devices giving rise to different plasma adrenaline profiles. Needle length does not seem to be the most important factor; rather, the force and speed of injection (which varies from one device to another) is likely to be of greater importance. In general, peak plasma adrenaline concentration is lower and time‐to‐peak concentration longer with increased skin‐to‐muscle depth. However, it is difficult to draw conclusions with the current available data, due to a lack of head‐to‐head comparisons, small numbers of study participants and the failure to acknowledge the biphasic nature of intramuscular adrenaline absorption for analysis purposes.
mTOR‐mediated autophagy in the hippocampus is involved in perioperative neurocognitive disorders in diabetic rats
Authors: Chen Xiaohui , Gao Fei , Lin Cuicui , Chen Andi , Deng Jianhui , Chen Pinzhong , Lin Mingxue , Xie Bingxin , Liao Yanling , Gong Cansheng , Zheng Xiaochun 
Published: November 2021

AbstractIntroductionPerioperative neurocognitive disorders (PND) are common neurological complications after surgery. Diabetes mellitus (DM) has been reported to be an independent risk factor for PND, but little is known about its mechanism of action. Mammalian target of rapamycin (mTOR) signaling is crucial for neuronal growth, development, apoptosis, and autophagy, but the dysregulation of mTOR signaling leads to neurological disorders. The present study investigated whether rapamycin can attenuate PND by inhibiting mTOR and activating autophagy in diabetic rats.MethodsMale diabetic Sprague‐Dawley rats underwent tibial fracture surgery under isoflurane anesthesia to establish a PND model. Cognitive functions were examined using the Morris water maze test. The levels of phosphorylated mTOR (p‐mTOR), phosphorylated tau (p‐tau), autophagy‐related proteins (Beclin‐1, LC3), and apoptosis‐related proteins (Bax, Bcl‐2, cleaved caspase‐3) in the hippocampus were examined on postoperative days 3, 7, and 14 by Western blot. Hippocampal amyloid β (Aβ) levels were examined by immunohistochemistry.ResultsThe data showed that surgical trauma and/or DM impaired cognitive function, induced mTOR activation, and decreased Beclin‐1 levels and the LC3‐II/I ratio. The levels of Aβ and p‐tau and the hippocampal apoptotic responses were significantly higher in diabetic or surgery‐treated rats than in control rats and were further increased in diabetic rats subjected to surgery. Pretreatment of rats with rapamycin inhibited mTOR hyperactivation and restored autophagic function, effectively decreasing tau hyperphosphorylation, Aβ deposition, and apoptosis in the hippocampus. Furthermore, surgical trauma‐induced neurocognitive disorders were also reversed by pretreatment of diabetic rats with rapamycin.ConclusionThe results demonstrate that mTOR hyperactivation regulates autophagy, playing a critical role in the mechanism underlying PND, and reveal that the modulation of mTOR signaling could be a promising therapeutic strategy for PND in patients with diabetes.
COVID‐19 pandemic: end‐of‐life experience in Australian residential aged care facilities
Authors: Hack Emma , Hayes Barbara , Radcliffe Nicholas , Monda Sally , Yates Paul 
Published: November 2021

AbstractBackgroundThe COVID‐19 pandemic has significantly impacted those in residential aged care facilities (RACF). This research was undertaken to explore and better understand the effects of the pandemic on the experience of next‐of‐kin and carers who encountered the death of a loved one who resided within a RACF during the pandemic.AimsTo explore end‐of‐life experiences for residents who die in RACF and their next‐of‐kin/carers during the COVID‐19 pandemic, to identify areas of concern and areas for improvement.MethodsProspective single‐centre mixed methods research was undertaken involving telephone interview with next‐of‐kin or carers of residents who died within 30 days of being referred to Austin Health Residential InReach Service during the ‘second wave’ of COVID‐19 in Melbourne, Australia, in 2020. Qualitative and quantitative data were collected. Qualitative description and aspects of grounded theory were used for analysing qualitative data. Thematic analysis of the interview transcripts used open and axial coding to identify initial themes and then to group these under major themes.ResultsForty‐one telephone interviews were analysed. Major themes identified included: COVID‐19 pandemic, communication and technology, death and dying experience, bereavement and grief, and social supports and external systems.ConclusionsFindings identify the many COVID‐19 pandemic‐related challenges faced by participants and their dying loved one in RACF. Access to palliative care and bereavement support is crucial for dying residents and for grieving that has been made more difficult by the pandemic.
Evaluation of composite restorations in primary molars subjected to selective caries removal associated with antimicrobial photodynamic therapy: A randomized controlled trial
Authors: Faria Laís Veiga , Antunes Leonardo Santos , Pio Luciana Ribeiro Reis , Dias Jessica Coelho , Pinheiro Liz Helena Moraes , Reis Caio Luiz Bitencourt , Fontes Karla Bianca Fernandes Costa , Cajazeira Marlus Roberto Rodrigues , Antunes Lívia Azeredo Alves 
Published: November 2021

AbstractBackgroundAntimicrobial photodynamic therapy (aPDT) has been used as an adjunct treatment of deep caries lesions; however, studies on the effects of aPDT on the longevity of restorations are still limited.AimTo evaluate the clinical performance of composite restorations in primary molars subjected to selective caries removal (SCR) associated with aPDT.DesignA randomized clinical trial was designed. Primary molars of patients (mean age 6.15 years) with deep caries lesions without signs and symptoms of pulpal involvement were selected. A total of 64 teeth were randomly divided into groups G1 (SCR, 32 teeth) and G2 (SCR + aPDT, 32 teeth) for treatment, restored with composite, and evaluated after a week (T0), 6 months (T1), and 12 months (T2) according to the criteria of FDI. Groups were compared using the Rao‐Scott chi‐squared test and the logistic regression analysis for complex designs to account for multiple observations per subject (alpha = 0.05).ResultsFrom all FDI criteria evaluated, the marginal adaptation for the SCR + aPDT group was significantly better in comparison with the SCR group at T0 and T2 in the logistic regression analysis (T0: OR = 0.151; 95% CI = 0.03‐0.068, P = .015; and T2: OR = 0.201; 95% CI = 0.05‐0.79, P = .022).ConclusionThe marginal adaptation of primary molar resin restorations was positively affected by aPDT after 12 months of follow‐up.
Effect of oxygen vacancy sites in exposed crystal facet on the gas sensing performance of ZnO nanomaterial
Authors: Kim Kyusung , Choi Pil Gyu , Itoh Toshio , Masuda Yoshitake 
Published: November 2021

AbstractThe development of a gas sensor for ppb‐level detection has been required for the industrial and medical fields. Exposed facet control is an effective way to improve gas sensing performance without novel metal catalysts. Herein, we investigated the change in gas sensitivity of ZnO nanostructures depending on the exposed surface. ZnO‐rod and ZnO‐whisker were synthesized using zinc nitrate hexahydrate, hexamethylenetetramine, and polyethyleneimine (PEI) via a low‐temperature aqueous solution process. As increasing the amount of PEI, the ZnO‐rod with (0001) facet was converted to the ZnO‐whisker with (101) facet by edge sharpening. Although both samples can detect acetone gas until 200 ppb, the ZnO‐whisker exhibited superior sensing performance in all ranges. Especially, the gas response of ZnO‐whisker was three times higher than that of ZnO‐rod at 5 ppm. The result was related to the difference in oxygen vacancy site where generate pre‐adsorbed oxygen species. In the analysis results of electron density distribution, two Zn atoms are associated with one oxygen vacancy site in (101) facet. On the other hand, one oxygen vacancy site was connected to only one Zn atom in the (0001) plane. Thus, electrons could be much easily provided to the oxygen vacancy site in (101) facet, and it causes the higher sensitivity of ZnO‐whisker.
Focus on blood pressure levels and variability in the early phase of acute ischemic stroke with hypertension and carotid stenosis
Authors: He Mingli , Cui Bing , Wang Jin'e , Xiao Xiao , Wu Taotao , Wang Mingyu , Yang Ru , Zhang Bo , Xu Bingchao , He Xiaobing , Zhang Guanghui , Niu Xiaoqin , Li Zaipo , Wang Bei , Xu Bei , Hui Rutai , Wang Yibo 
Published: November 2021

AbstractTo investigate the optimal blood pressure (BP) levels and relative importance of BP and BP variability in the early phase of acute ischemic stroke (AIS) for hypertensive patients with carotid artery stenosis (CAS). A single‐center cohort study included 750 AIS patients with hypertension and tests were performed for CAS. Participants were categorized to Group 1 (SBP < 140 mm Hg and DBP < 90 mm Hg), Group 2: (SBP: 140–159 mm Hg and or DBP: 90–99 mm Hg), and Group 3: (SBP ≥160 mm Hg and/or DBP ≥100 mm Hg) according to the guidelines. The associations of mean BP levels and variability with outcomes (recurrent stroke, all‐cause death and the composite cardiovascular events) at 6 months were analyzed by Cox proportional hazard models. The associations of BP variability with BP levels and cerebral blood flow (CBF) were analyzed by linear regression and generalized additive models. Both for primary and secondary outcome, more events occurred in Group 1 compared with Group 2, while no significant difference was found in Group 3 with higher BP levels. Lower systolic BP variability showed better prognosis and higher CBF. The associations were more significant in patients with CAS ≥50%. BP variability exhibited a linear negative relationship with BP levels. In the early phase of AIS with hypertension and CAS, maintaining low blood pressure variability may be important to improve outcomes while low BP levels (SBP/DBP < 140/90 mm Hg) were harmful, especially in those patients with CAS ≥ 50%.
MicroRNA‐411‐3p inhibits bleomycin‐induced skin fibrosis by regulating transforming growth factor‐β/Smad ubiquitin regulatory factor‐2 signalling
Authors: Zhang Ziyan , Gao Xuemin , He Yang , Kang Yumeng , Jin Fuyu , Li Yaqian , Li Tian , Wei Zhongqiu , Li Shifeng , Cai Wenchen , Mao Na , Wang Shan , Liu Heliang , Yang Fang , Xu Hong , Yang Jie 
Published: November 2021

AbstractSkin fibrosis, which is characterized by fibroblast proliferation and increased extracellular matrix, has no effective treatment. An increasing number of studies have shown that microRNAs (miRNAs/miRs) participate in the mechanism of skin fibrosis, such as in limited cutaneous systemic sclerosis and pathological scarring. The objective of the present study was to determine the role of miR‐411‐3p in bleomycin (BLM)‐induced skin fibrosis and skin fibroblast transformation. Using Western blot analysis and real‐time quantitative polymerase chain reaction assess the expression levels of miR‐411‐3p, collagen (COLI) and transforming growth factor (TGF)‐β/Smad ubiquitin regulatory factor (Smurf)‐2/Smad signalling factors both in vitro and in vivo with or without BLM. To explore the regulatory relationship between miR‐411‐3p and Smurf2, we used the luciferase reporter assay. Furthermore, miR‐411‐3p overexpression was identified in vitro and in vivo via transfection with Lipofectamine 2000 reagent and injection. Finally, we tested the dermal layer of the skin using haematoxylin and eosin and Van Gieson's staining. We found that miR‐411‐3p expression was decreased in bleomycin (BLM)‐induced skin fibrosis and fibroblasts. However, BLM accelerated transforming growth factor (TGF)‐β signalling and collagen production. Overexpression of miR‐411‐3p inhibited the expression of collagen, F‐actin and the TGF‐β/Smad signalling pathway factors in BLM‐induced skin fibrosis and fibroblasts. In addition, miR‐411‐3p inhibited the target Smad ubiquitin regulatory factor (Smurf)‐2. Furthermore, Smurf2 was silenced, which attenuated the expression of collagen via suppression of the TGF‐β/Smad signalling pathway. We demonstrated that miR‐411‐3p exerts antifibrotic effects by inhibiting the TGF‐β/Smad signalling pathway via targeting of Smurf2 in skin fibrosis.
A theory of maximalist luxury
Authors: Liu Zhenqi (Jessie) , Yildirim Pinar , Zhang Z. John 
Published: November 2021

AbstractThe availability of high‐quality, low‐price counterfeits in many luxury markets threatens the role of luxury goods as a status symbol. If those counterfeits look and feel the same as the authentic counterparts, as many professional authenticators observe, and they are available at a fraction of the price of authentic goods, why would self‐interested consumers purchase authentic luxury goods? Then, the future of luxury goods is called into question. In this paper, we propose that the presence of high‐quality, low‐price counterfeits can, surprisingly, motivate the wealthy consumers to pursue what we term as the “maximalist luxury” strategy. In the presence of these counterfeits, the wealthy can resort to signaling their status by purchasing the maximum number of luxury goods available and put their copious consumption on display, while in the absence of such counterfeits, the wealthy consumers only need to purchase the minimum number of luxury goods to stand out. This new signaling mechanism then highlights the importance of product line decisions by a luxury brand in combating counterfeits and provides a number of managerial insights about how to maintain the role of luxury goods as a status symbol through pricing, adjusting the product line, and limiting its products' functionality.
Loss of Gn1a/OsCKX2 confers heavy‐panicle rice with excellent lodging resistance
Authors: Tu Bin , Tao Zhang , Wang Shiguang , Zhou Lei , Zheng Ling , Zhang Chun , Li Xinzi , Zhang Xiaoyu , Yin Junjie , Zhu Xiaobo , Yuan Hua , Li Ting , Chen Weilan , Qin Peng , Ma Bingtian , Wang Yuping , Li Shigui 
Published: November 2021

AbstractSignificant achievements have been made in breeding programs for the heavy‐panicle‐type (HPT) rice (Oryza sativa) in Southwest China. The HPT varieties now exhibit excellent lodging resistance, allowing them to overcome the greater pressures caused by heavy panicles. However, the genetic mechanism of this lodging resistance remains elusive. Here, we isolated a major quantitative trait locus, Panicle Neck Diameter 1 (PND1), and identified the causal gene as GRAIN NUMBER 1A/CYTOKININ OXIDASE 2 (Gn1A/OsCKX2). The null gn1a allele from rice line R498 (gn1aR498) improved lodging resistance through increasing the culm diameter and promoting crown root development. Loss‐of‐function of Gn1a/OsCKX2 led to cytokinin accumulation in the crown root tip and accelerated the development of adventitious roots. Gene pyramiding between the null gn1aR498 allele with two gain‐of‐function alleles, STRONG CULM 2 (SCM2) and SCM3, further improved lodging resistance. Moreover, Gn1a/OsCKX2 had minimal influence on overall rice quality. Our research thus highlights the distinct genetic components of lodging resistance of HPT varieties and provides a strategy for tailor‐made crop improvement of both yield and lodging resistance in rice.
Evidence base review of couple‐ and family‐based psychosocial interventions to promote infant and early childhood mental health, 2010–2019
Authors: Kaminski Jennifer W. , Robinson Lara R. , Hutchins Helena J. , Newsome Kimberly B. , Barry Caroline M. 
Published: November 2021

AbstractInfant and early childhood mental health (IECMH) has been defined as the capacity of infants and young children to regulate their emotions, form secure relationships, and explore their environments. For this special issue, we conducted a review of IECMH outcomes from evaluations of couple‐ and family‐based psychosocial interventions not explicitly designed for trauma exposure published from 2010 through 2019, following Evidence Base Update criteria and the current convention of classifying general categories of intervention approaches rather than the former practice of evaluating specific brand‐name packaged programs. Full‐text review of 695 articles resulted in 39 articles eligible for categorization into intervention approaches, taking into consideration the theoretical orientation of the treatment, the population served, the intervention participants, the target outcomes, the treatment theory of change, and the degree to which the intervention was standardized across participants. Four intervention approaches were identified in this review as Probably Efficacious: Behavioral Interventions to Support Parents of Toddlers, Interventions to Support Adolescent Mothers, Tiered Interventions to Provide Support Based on Assessed Risk, and Home Visiting Interventions to Provide Individualized Support to Parents. Other intervention approaches were classified as Possibly Efficacious, Experimental, or did not have sufficient evidence in this time period to classify under these criteria. Further research could explore how to ensure that all families who need support can receive it, such as by increasing the reach of effective programs and by decreasing the number of families needing additional support.
How Do Financial Constraints Affect Product Pricing? Evidence from Weather and Life Insurance Premiums
Authors: GE SHAN 
Published: November 2021

ABSTRACTI identify the effects of financial constraints on firms' product pricing decisions, using insurance groups containing both life and property & casualty (P&C) divisions. Following P&C divisions' losses, life divisions change prices in a manner that can generate more immediate financial resources: premiums fall (rise) for life policies that immediately increase (decrease) insurers' financial resources. Premiums change more in groups that are more constrained. Life divisions increase transfers to P&C divisions, suggesting P&C divisions' shocks are transmitted to life divisions. Results hold when instrumenting for P&C divisions' losses with exposure to unusual weather damages, implying that the effects are causal.
Pursuing Gains or Avoiding Losses: The Contingent Effect of Transgenerational Intentions on Innovation Investments
Authors: Bammens Yannick , Hünermund Paul , Andries Petra 
Published: November 2021

AbstractMany business‐owning families aspire to someday transfer their firm to the next family generation. Controversy surrounds the question of how these transgenerational intentions affect risky growth strategies such as investments in innovation: some emphasize the positives of a transgenerational time horizon for investments in future growth, others highlight the negatives of a more conservative mindset with amplified concern for stability and risk avoidance. Using regulatory focus theory, we resolve this long‐standing controversy about the impact of transgenerational intentions by theorizing how they can trigger a promotion focus with increased innovation spending or a prevention focus with reduced innovation spending, depending on the firm’s survival hazard. Based on a sample of around 3,900 German firms using OLS and 2SLS estimation, we find empirical support for our predictions. This study extends the mixed gamble lens on family firm decision‐making with insights from regulatory focus theory to build consensus on the role of transgenerational intentions while shifting consensus on the role of family ownership in relation to the innovation spending decision.