bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inauthenticity aversion: Moral reactance toward tainted actors, actions, and objects
Authors: Silver Ike , Newman George , Small Deborah A. 
Published: December 2020

AbstractTheories of authenticity usually try to explain what leads consumers to see something as authentic. Here, we address the inverse question instead: What makes a brand, individual, or product seem inauthentic? This shift in focus reveals a distinct psychology that is more than just the absence or inverse of responses to authenticity. Whereas authenticity typically confers meaning and value, invoking inauthenticity typically implies the detection of a moral violation. Specifically, consumers judge an entity to be inauthentic if they perceive a mismatch between what that entity claims to be (e.g., a socially responsible apparel brand, 100% orange juice) and what it really is upon closer scrutiny. Such judgments give rise to a powerful, non‐compensatory reactance we term inauthenticity aversion. We segment inauthenticity violations into three principle types: deceptions, ulterior motives, and adulterations. This conceptualization allows us to capture a wide variety of inauthenticity cases and outline psychological commonalities across them. It also helps to explain the powerful outrage consumers display at perceived inauthenticity and illuminates potential hazards in common marketing approaches.
RTA‐408 protects against propofol‐induced cognitive impairment in neonatal mice via the activation of Nrf2 and the inhibition of NF‐κB p65 nuclear translocation
Authors: Zhang Ling , Zhou Qian , Zhou Chun‐Li 
Published: December 2020

AbstractObjectiveTo explore the effect of RTA‐408 on the propofol‐induced cognitive impairment of neonatal mice via regulating Nrf2 and NF‐κB p65 nuclear translocation.MethodsC57BL/6 neonatal mice were randomized into intralipid, propofol, vehicle + propofol, and RTA‐408 + propofol groups. The learning and memory ability was inspected by Morries water maze (MWM) test. TUNEL staining was performed to examine the apoptosis of neurons in hippocampus. The gene and protein expressions in hippocampus were detected by immunohistochemistry, qRT‐PCR, or Western blotting. The activities of glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) were tested by the corresponding kits.ResultsPropofol prolonged escape latency of mice, decreased the times of crossing the platform, and shortened the time of staying in the target quadrant, while RTA‐408 treatment improved the above‐mentioned situation. Besides, Nrf2 protein in hippocampus of mice induced by propofol was decreased with the increased NF‐κB p65 nuclear translocation, which was reversed by RTA‐408. Meanwhile, RTA‐408 decreased the apoptosis of neurons accompanying with the down‐regulation of Caspase‐3 and the up‐regulations of neuronal‐specific nuclear protein (NeuN), microtubule‐associated protein 2 (Map2), Ca2+/Calmodulin‐dependent Protein Kinase II (CaMKII), and parvalbumin (PV) immunostaining in hippocampus. Besides, propofol‐induced high levels of proinflammatory cytokines and antioxidase activities in hippocampus were reduced by RTA‐408.ConclusionRTA‐408 improved propofol‐induced cognitive impairment in neonatal mice via enhancing survival of neurons, reducing the apoptosis of hippocampal neurons, mitigating the inflammation and oxidative stress, which may be correlated with the activation of Nrf2 and the inhibition of NF‐κB p65 nuclear translocation.
The critical impact of tumor size in predicting cancer special survival for T3aM0M0 renal cell carcinoma: A proposal of an alternative T3aN0M0 stage
Authors: Li Luping , Shi Lei , Zhang Junjie , Fan Yingzhong , Li Qi 
Published: December 2020

AbstractObjectiveBased on the eighth TNM staging system, T3a renal cell carcinoma (RCC) is identified as an anatomical extrarenal invasion and does not consider the size of the tumor; however, it may not fully predict the prognosis of the patient. The objective of this study was to evaluate the prognostic value of tumor size effects on prognosis in T3a RCC and propose an alternative tumor stage system combined with T1‐2.MethodsData relating to T1‐3aN0M0 RCC (n = 49586) were obtained from the Surveillance, Epidemiology, and End Results database (2004–2015). Survival analyses were conducted by Cox regression and Fine and Gray regression. Harrell's concordance index (c‐index) was used to assess the discriminatory ability of the prognostic factors.ResultsA 1‐cm increase in T3a RCC resulted in an 8% increase in all‐cause mortality (hazard ratio [HR]: 1.08; 95% confidence interval [CI]: 1.06–1.10, p < 0.001) and 14% increase in the risk of RCC‐specific mortality (sub‐distribution HR [sHR]: 1.14; 95% CI: 1.11–1.16, p < 0.001). T3a tumor size stratified by the cutoff of 4 cm and 7 cm showed a better prediction of RCC‐special survival (c‐index: 0.644), compared with a cutoff just by 4 cm (c‐index: 0.571) or by 7 cm (c‐index: 0.602). Compared with T1b tumors, T3a RCC ≤4 cm showed no differences in terms of all‐cause mortality (HR: 0.93; 95% CI: 0.79–1.09; p = 0.37) and mortality caused by RCC (sHR: 0.91; 95% CI: 0.70–1.19; p = 0.50). Last, the alternative T‐staging system (T1a, a combination of T1b and T3a [≤4 cm], T2a, T2b, T3a [4–7 cm], and T3a [>7] cm) demonstrated good RCC‐special survival predictive accuracy (c‐index: 0.729), which was higher than that shown by the current eighth edition T‐staging system (c‐index: 0.720).ConclusionTumor size should be taken into consideration for T3aN0M0 RCC rather than based on anatomical features alone.
Philadelphia‐negative myeloproliferative neoplasms among Kuwaiti Nationals
Authors: Alshemmari Salem , Almazyad Mazyad , Alwehaib Aisha , Ameen Reem 
Published: December 2020

AbstractThe epidemiology, genetics, and thrombosis risk of MPNs among Arabs are largely unknown. This may be attributed to scarce epidemiological data, particularly from our region. Our study included 381 Kuwaiti nationals with Ph‐negative MPNs and a confirmed driver mutation involving JAK2 (exon 12 14), CALR, or MPL. This first regional study examines the demographics, clinical parameters, and thrombosis‐related attributes of the participants. This study reported a median age of 58 years, with females and males representing 54.9% and 45.1%, respectively. ET was the most frequent subtype of Ph‐negative MPNs in our population, accounting for 52.0% of the cases, followed by PV, found in 34.6% of the participants, and PMF, found in 8.4% of participants. The crude annual cumulative incidence of Ph‐negative MPNs in Kuwait ranged from 0.674 to 3.177 per 100,000 population across the study period. The most common driver mutation was JAK2V617F, with a frequency of 89.5%. At diagnosis, 19.2% of the patients presented with unexplained thrombosis, and almost half were of arterial origins. Males were more likely to present with arterial thrombosis than females (61.5% vs. 35.3%), whereas venous thrombotic events were more common in females than in males (47.1% vs. 17.9%; p‐value = 0.025). Ph‐negative MPNs in Kuwait are rare; however, thrombosis is a frequent complication, being documented in up to 19.2% of cases at presentation, more commonly at arterial sites. These findings call for thorough evaluation of patients with unexplained derangements in their hematological parameters during follow‐ups.
Bone marrow mesenchymal stem cells‐derived exosomes reduce Aβ deposition and improve cognitive function recovery in mice with Alzheimer's disease by activating sphingosine kinase/sphingosine‐1‐phosphate signaling pathway
Authors: Wang Xinhui , Yang Guojie 
Published: December 2020

AbstractExosomes are associated with the development and progression of Alzheimer's disease (AD), although the impact of these extracellular vesicles in brain pathological condition remains incompletely understood. Therefore, this study aimed to investigate the role and mechanism of exosomes signaling in AD. Double transgenic APP/PS1 mice were injected with bone marrow mesenchymal stem cells (BM‐MSCs)‐derived exosomes or combined with SKI‐Ⅱ (sphingosine kinase [SphK] inhibitor) or VPC23019 (sphingosine‐1‐phosphate [S1P] 1 receptor blocker). We observed the spatial learning and memory ability of mice, and assessed the levels of amyloid and proteins. We found that exosomes improved spatial learning and memory ability of APP/PS1 mice, and enhanced the expression of SphK1 and S1P1. Moreover, exosomes inhibited the levels of amyloid and enhanced the expression of NeuN in cortex and hippocampus of APP/PS1 mice. Exosomes repressed the levels of Aβ1‐40, Aβ1‐42, BACE1, and PS1, and promoted the expression of neprilysin in APP/PS1 mice. The influence conferred by exosomes was abolished by SKI‐Ⅱ or VPC23019. In conclusion, our article confirms that BM‐MSCs‐derived exosomes reduce Aβ deposition and promote cognitive function recovery in AD mice by activating SphK/S1P signaling pathway. Thus, our data suggest that S1P/SphK‐containing exosomes should be explored as potential AD cure.
Structural and Electronic Control of the Bidentate 1‐(2‐pyridyl)benzotriazole Ligand in Copper Chemistry with Application to Catalysis in the A3 Coupling Reaction
Authors: Sampani Stavroula I. , Zdorichenko Victor , Devonport Jack , Rossini Gioia , Leech Matthew C. , Lam Kevin , Cox Brian , Abdul‐Sada Alaa , Vargas Alfredo , Kostakis George E. 
Published: December 2020

AbstractThe hybrid bidentate 1‐(2‐pyridyl)benzotriazole (pyb) ligand was introduced into 3d transition metal catalysis. Specifically, [CuII(OTf)2(pyb)2]⋅2 CH3CN (1) enables the synthesis of a wide range of propargylamines by the A3 coupling reaction at room temperature in the absence of additives. Experimental and high‐level theoretical calculations suggest that the bridging N atom of the ligand imposes exclusive trans coordination at Cu and allows ligand rotation, while the N atom of the pyridine group modulates charge distribution and flux, and thus orchestrates structural and electronic precatalyst control permitting alkyne binding with simultaneous activation of the C−H bond via a transient CuI species.
A short‐term deep learning model for urban pollution forecasting with incomplete data
Authors: Colorado Cifuentes Gerson Uriel , Flores Tlacuahuac Antonio 
Published: December 2020

AbstractA deep neural network model for the short term prediction of ozone, 10 μm particulate matter, and 2.5 μm particulate matter concentrations in a major northwestern metropolitan area of México is developed. In order to formulate such a model, the data available from the local air quality automatic network monitoring system are used for training, validation, and testing purposes. Such time series data are incomplete and a procedure of missing data imputation is carried out. The model predicts with high accuracy the concentration of the target pollutants, and the training procedure, performance metrics, and tools used are discussed in this work. Such a model can be deployed for the implementation and evaluation of public politics for improving population health, and reducing the potential negative impacts of harmful pollutants by issuing early warnings on dangerous pollution levels.
The phosphatase inhibitor Sds23 promotes symmetric spindle positioning in fission yeast
Authors: Schutt Katherine L. , Moseley James B. 
Published: December 2020

AbstractA hallmark of cell division in eukaryotic cells is the formation and elongation of a microtubule (MT)‐based mitotic spindle. Proper positioning of the spindle is critical to ensure equal segregation of the genetic material to the resulting daughter cells. Both the timing of spindle elongation and constriction of the actomyosin contractile ring must be precisely coordinated to prevent missegregation or damage to the genetic material during cellular division. Here, we show that Sds23, an inhibitor of protein phosphatases, contributes to proper positioning of elongating spindles in fission yeast cells. We found that sds23∆ mutant cells exhibit asymmetric spindles that initially elongate asymmetrically toward one end of the dividing cell. Spindle asymmetry in sds23∆ cells results from a defect that is distinct from previously identified mechanisms, including MT protrusions and enlarged vacuoles. Combined with our previous work, this study demonstrates that Sds23, an inhibitor of PP2A‐family protein phosphatases, promotes proper positioning of both the bipolar spindle and cytokinetic ring during fission yeast cell division. These two steps ensure the overall symmetry and fidelity of the cell division process.
The Question‐prompt list (QPL): Why it is needed in the Indian oncology setting?
Authors: Chawak Shweta , Chittem Mahati , Maya Sravannthi , Dhillon Haryana M. , Butow Phyllis N. 
Published: December 2020

AbstractBackgroundIn India, caregivers are an integral part of the illness experience, especially in cancer, to the extent that they can become proxy decision‐makers for the patient. Further, owing to acute resource constraints in the Indian healthcare system, it may be difficult for oncologists to assess and elicit questions from each patient/caregiver. Consequently, there is a need to address these unique aspects of oncology care in India to improve patient outcomes and understanding of their illness and treatment. This can be achieved through a Question Prompt List (QPL), a checklist used by care recipients during medical consultations.Recent FindingsThis narrative review will first introduce research on the development and effectiveness of the QPL, and then it will highlight current gaps in oncology care in India and explore how the QPL may aid in closing these gaps.A literature search of the empirical research focused on the development, feasibility and acceptability of the QPL in oncology settings was conducted. The final review included 40 articles pertaining to QPL research. Additionally, psycho‐oncology research in India centered on information needs and experiences was reviewed.Current Indian psycho‐oncology research reports patients' want to be actively involved in their cancer care and a need for more illness information. However, a high demand on physicians' resources and the family caregivers' interference can be barriers to meeting patients' information/communication needs. International research demonstrates that a QPL helps structure and decrease consultation time, improves patient satisfaction with care, and improves the quality of communication during medical encounters.ConclusionQPLs for Indian patients and caregivers may focus on the scope of medical consultations to address patient needs while influencing the course and content of the patient‐caregiver‐physician interactions. Further, it can address the resource constraints in Indian oncology care settings, thus reducing the physician's burden.
Developing and Validating a Clinical Warfarin Dose‐Initiation Model for Black‐African Patients in South Africa and Uganda
Authors: Asiimwe Innocent G. , Waitt Catriona , Sekaggya‐Wiltshire Christine , Hutchinson Claire , Okello Emmy , Zhang Eunice J. , Semakula Jerome R. , Mouton Johannes P. , Cohen Karen , Blockman Marc , Lamorde Mohammed , Jorgensen Andrea L. , Pirmohamed Munir 
Published: December 2020

Warfarin remains the oral anticoagulant of choice in sub‐Saharan Africa. However, dosing is challenging due to a highly variable clinical response for a given dose. This study aimed to develop and validate a clinical warfarin dose‐initiation model in sub‐Saharan Black‐African patients. For the development cohort, we used data from 364 patients who were recruited from 8 outpatient clinics and hospital departments in Uganda and South Africa (June 2018–July 2019). Validation was undertaken using the International Warfarin Pharmacogenetics Consortium (IWPC) dataset (690 black patients). Four predictors (age, weight, target International Normalized Ratio range, and HIV status) were included in the final model, which achieved mean absolute errors (MAEs; mean of absolute differences between true dose and dose predicted by the model) of 11.6 (95% confidence interval (CI) 10.4–12.8) and 12.5 (95% CI 11.6–13.4) mg/week in the development and validation cohorts, respectively. Two other clinical models, IWPC and Gage, respectively, obtained MAEs of 12.5 (95% CI 11.3–13.7) and 12.7 (95% CI 11.5–13.8) mg/week in the development cohort, and 12.1 (95% CI 11.2–13.0) and 12.2 (95% CI 11.4–13.1) mg/week in the validation cohort. Compared with fixed dose‐initiation, our model decreased the percentage of patients at high risk of suboptimal anticoagulation by 7.5% (1.5–13.7%) and 11.9% (7.1–16.8%) in the development and validation cohorts, respectively. The clinical utility of this model will be tested in a prospective study.
Study Highlights

WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

☑ Warfarin dosing remains challenging due to a highly variable clinical response for a given dose.

WHAT QUESTION DID THIS STUDY ADDRESS?
☑ Can a clinical dose‐initiation model be developed and validated for sub‐Saharan Black‐African patients?

WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
☑ We have developed the first warfarin dose‐initiation clinical model for Black‐African patients in Uganda and South Africa.

HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
☑ We will be implementing and validating this model in a prospective cohort to inform future large‐scale implementation. More optimized dosing should improve the quality of warfarin anticoagulation in these two developing countries.
Thromboembolic and Hemorrhagic Outcomes in the Direct Oral Anticoagulant Trials Across the Spectrum of Kidney Function
Authors: Limdi Nita A. , Beasley Timothy Mark , Sun Jielin , Stockbridge Norman , Pacanowski Michael , Florian Jeffry 
Published: December 2020

Chronic kidney disease is a common comorbidity among patients taking direct‐acting oral anticoagulants (DOACs). Herein, we evaluate the influence of kidney function on stroke or systemic embolism (SEE), hemorrhage, and composite end points (stroke/SEE/hemorrhage/death and stroke/SEE/death) among patients on DOACs and warfarin. Baseline kidney function was categorized as glomerular filtration rate (GFR) ≥ 60 (reference), 45–59, and < 45mL/min/1.73 m2 for participants in the Randomized Evaluation of Long‐Term Anticoagulant Therapy (RE‐LY) (n = 18,049), Apixaban for Reduction in Stroke and Other Thromboembolic Events (ARISTOTLE) (n = 18,187), and The Effective Anticoagulation with Factor Xa Next Generation in AF (ENGAGE AF) (n = 20,798) trials. Incidence of events was compared across GFR categories. Hazard ratios for events were estimated using Cox regression using intention‐to‐treat analysis adjusting for known predictors. A large proportion of participants had GFR < 60 (25–29% had 45 ≤ GFR < 60 and 9.5–12.6% with GFR < 45). Compared with patients with GFR ≥ 60, warfarin users across the trials with GFR ≥ 45–59 and GFR < 45 had a higher incidence of hemorrhage (P values < 0.0001) and warfarin users in the ARISTOTLE and ENGAGE trials had higher incidence of stroke/SEE (P values ≤ 0.05). Compared with patients with GFR ≥ 60, dabigatran users with GFR ≥ 45–59 and GFR < 45 had a higher incidence of stroke/SEE (P ≤ 0.02), hemorrhage (P < 0.001), and both composite end points (P < 0.0001). Compared with patients with GFR ≥ 60, apixaban and edoxaban users with GFR ≥ 45–59 and GFR < 45 had a higher incidence of hemorrhage (P values ≤ 0.05) and composite end points (P values ≤ 0.05). After adjustment, compared with patients with GFR ≥ 60, warfarin users with GFR < 60 in the ARISTOTLE and RE‐LY trials had a higher risk of hemorrhage (P < 0.05), as did dabigatran (P < 0.001) and edoxaban (P ≤ 0.005) users, while apixaban users did not exhibit an increased risk (P = 0.08 GFR ≥ 45–59; P = 0.71 GFR < 45). Kidney function significantly influences the safety and efficacy of oral anticoagulants.
Identification of tumor‐associated macrophage subsets that are associated with breast cancer prognosis
Authors: Strack Elisabeth , Rolfe P. Alexander , Fink Annika F. , Bankov Katrin , Schmid Tobias , Solbach Christine , Savai Rajkumar , Sha Weixiao , Pradel Leon , Hartmann Sylvia , Brüne Bernhard , Weigert Andreas 
Published: December 2020

AbstractBackgroundBreast cancer is the leading cause of cancer‐related deaths in women, demanding new treatment options. With the advent of immune checkpoint blockade, immunotherapy emerged as a treatment option. In addition to lymphocytes, tumor‐associated macrophages exert a significant, albeit controversial, impact on tumor development. Pro‐inflammatory macrophages are thought to hinder, whereas anti‐inflammatory macrophages promote tumor growth. However, molecular markers to identify prognostic macrophage populations remain elusive.MethodsWe isolated two macrophage subsets, from 48 primary human breast tumors, distinguished by the expression of CD206. Their transcriptomes were analyzed via RNA‐Seq, and potential prognostic macrophage markers were validated by PhenOptics in tissue microarrays of patients with invasive breast cancer.ResultsNormal human breast tissue contained mainly CD206+ macrophages, while increased relative amounts of CD206− macrophages were observed in tumors. The presence of CD206+ macrophages correlated with a pronounced lymphocyte infiltrate and subsets of CD206+ macrophages, expressing SERPINH1 and collagen 1, or MORC4, were unexpectedly associated with improved survival of breast cancer patients. In contrast, MHCIIhi CD206− macrophages were linked with a poor survival prognosis.ConclusionOur data highlight the heterogeneity of tumor‐infiltrating macrophages and suggest the use of multiple phenotypic markers to predict the impact of macrophage subpopulations on cancer prognosis. We identified novel macrophage markers that correlate with the survival of patients with invasive mammary carcinoma.
Little to no expression of angiotensin‐converting enzyme‐2 on most human peripheral blood immune cells but highly expressed on tissue macrophages
Authors: Song Xiang , Hu Wei , Yu Haibo , Zhao Laura , Zhao Yeqian , Zhao Xin , Xue Hai‐Hui , Zhao Yong 
Published: December 2020

AbstractAngiotensin‐converting enzyme‐2 (ACE2) has been recognized as the binding receptor for the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Flow cytometry demonstrated that there was little to no expression of ACE2 on most of the human peripheral blood‐derived immune cells including CD4+ T, CD8+ T, activated CD4+/CD8+ T, Tregs, Th17, NKT, B, NK cells, monocytes, dendritic cells, and granulocytes. There was no ACE2 expression on platelets and very low level of ACE2 protein expression on the surface of human primary pulmonary alveolar epithelial cells. The ACE2 expression was markedly upregulated on the activated type 1 macrophages (M1). Immunohistochemistry demonstrated high expressions of ACE2 on human tissue macrophages, such as alveolar macrophages, Kupffer cells within livers, and microglial cells in brain at steady state. The data suggest that alveolar macrophages, as the frontline immune cells, may be directly targeted by the SARS‐CoV‐2 infection and therefore need to be considered for the prevention and treatment of COVID‐19.