bluuebunny/crossref_metadata_2025 huggingface dataset:
Circular RNA circFOXO3 regulates KDM2A by targeting miR‐214 to promote tumor growth and metastasis in oral squamous cell carcinoma
Authors: Ai Yilong , Wu Siyuan , Zou Chen , Wei Haigang
Published: June 2021

Oral squamous cell carcinoma (OSCC) is a pathological type of oral cancer, which accounts for over 90% of oral cancers. It has been widely shown that circRNA is involved in the regulation of multiple malignant oral diseases including OSCC. However, the mechanism underlying how circRNA regulates OSCC is still not clearly elucidated. In this article, we report circFOXO3 promotes tumor growth and invasion of OSCC by targeting miR‐214 which specifically degrades the lysine demethylase 2A (KDM2A). CircRNA sequencing was conducted in OSCC tumor and tumor‐side tissues, and the expression of circFOXO3 is found to be markedly increased in tumor tissues. CircFOXO3 is also highly expressed in several OSCC cell lines compared with human oral keratinocytes. Transwell assay and colony formation showed that knockdown of circFOXO3 prevents the invasion and proliferation of oral cancer cells. Via bioinformatic research, miR‐214 was found to be the target of circFOXO3 and correlate well with circFOXO3 both in vitro and in vivo. KDM2A was then validated by database analysis and luciferase assay to be the direct target of miR‐214. KDM2A helps to promote tumor invasiveness and proliferation of OSCC. Collectively, our results proved that circFOXO3 sponges miR‐214 to up‐regulate the expression of KDM2A, thus promotes tumor progression in OSCC.
MMP‐7 affects peritoneal ultrafiltration associated with elevated aquaporin‐1 expression via MAPK/ERK pathway in peritoneal mesothelial cells
Authors: Yin Yue , Zhang Fen , Zheng Zhuojun , Xiao Zhiwen , Yang Qiaomu , Gong Nirong , Zhou Jia , Zuo Daming , Ai Jun
Published: June 2021

Peritoneal membrane dysfunction and the resulting ultrafiltration failure are the major disadvantages of long‐term peritoneal dialysis (PD). It becomes increasingly clear that mesothelial cells play a vital role in the pathophysiological changes of the peritoneal membrane. Matrix metalloproteinases (MMPs) function in the extracellular environment of cells and mediate extracellular matrix turnover during peritoneal membrane homeostasis. We showed here that dialysate MMP‐7 levels markedly increased in the patients with PD, and the elevated MMP‐7 level was negatively associated with peritoneal ultrafiltration volume. Interestingly, MMP‐7 could regulate the cell osmotic pressure and volume of human peritoneal mesothelial cells. Moreover, we provided the evidence that MMP‐7 activated mitogen‐activated protein kinases (MAPKs)‐extracellular signal‐regulated kinase 1/2 (ERK) pathway and subsequently promoted the expression of aquaporin‐1 (AQP‐1) resulting in the change of cell osmotic pressure. Using a specific inhibitor of ERK pathway abrogated the MMP‐7‐mediating AQP‐1 up‐regulation and cellular homeostasis. In summary, all the findings indicate that MMP‐7 could modulate the activity of peritoneal cavity during PD, and dialysate MMP‐7 might be a non‐invasive biomarker and an alternative therapeutic target for PD patients with ultrafiltration failure.
PLAC8 promotes adriamycin resistance via blocking autophagy in breast cancer
Authors: Chen Yongxia , Jia Yunlu , Mao Misha , Gu Yifeng , Xu Chenpu , Yang Jingjing , Hu Wenxian , Shen Jun , Hu Dengdi , Chen Cong , Li Zhaoqing , Chen Lini , Ruan Jian , Shen Peng , Zhou Jichun , Wei Qun , Wang Linbo
Published: June 2021

Adriamycin (ADM) is currently one of the most effective chemotherapeutic agents in breast cancer treatment. However, growing resistance to ADM could lead to treatment failure and poor outcome. PLAC8 was reported as a novel highly conserved protein and functioned as an oncogene or tumour suppressor in various tumours. Here, we found higher PLAC8 expression was correlated with worse outcome and aggressive phenotype in breast cancer. Breast cancer patients with higher PLAC8 expression showed potential ADM resistance. In vitro experiments further confirmed that PLAC8 inhibited by siRNA or enforced overexpression by infecting pcDNA3.1(C)‐PLAC8 plasmid correspondingly decreased or increased ADM resistance. Subsequently, we demonstrated that ectopic PLAC8 expression in MCF‐7/ADMR cell blocked the accumulation of the autophagy‐associated protein LC3 and resulted in cellular accumulation of p62. Rapamycin‐triggered autophagy significantly increased cell response to ADM, while the autophagy inhibitor 3‐MA enhanced ADM resistance. 3‐MA and PLAC8 could synergistically cause ADM resistance via blocking the autophagy process. Additionally, the down‐regulation of p62 by siRNA attenuated the activation of autophagy and PLAC8 expression in breast cancer cells. Thus, our findings suggest that PLAC8, through the participation of p62, inhibits autophagy and consequently results in ADM resistance in breast cancer. PLAC8/p62 pathway may act as novel therapeutic targets in breast cancer treatment and has potential clinical application in overcoming ADM resistance.
The increased expression and aberrant methylation of SHC1 in non–small cell lung cancer: Integrative analysis of clinical and bioinformatics databases
Authors: Liang Yicheng , Lei Yangyang , Du Minjun , Liang Mei , Liu Zixu , Li Xingkai , Gao Yushun
Published: June 2021

Despite the previous evidence showing that SHC adaptor protein 1 (SHC1) could encode three distinct isoforms (p46SHC, p52SHC and p66SHC) that function in different activities such as regulating life span and Ras activation, the precise underlying role of SHC1 in lung cancer also remains obscure. In this study, we firstly found that SHC1 expression was up‐regulated both in lung adenocarcinoma (LUAD) and in lung squamous cell carcinoma (LUSC) tissues. Furthermore, compared to patients with lower SHC1 expression, LUAD patients with higher expression of SHC1 had poorer overall survival (OS). Moreover, higher expression of SHC1 was also associated with worse OS in patients with stages 1 and 2 but not stage 3 lung cancer. Significantly, the analysis showed that SHC1 methylation level was associated with OS in lung cancer patients. It seemed that the methylation level at specific probes within SHC1 showed negative correlations with SHC1 expression both in LUAD and in LUSC tissues. The LUAD and LUSC patients with hypermethylated SHC1 at cg12473916 and cg19356022 probes had a longer OS. Therefore, it is reasonable to conclude that SHC1 has a potential clinical significance in LUAD and LUSC patients.
Evidence of a gabapentinoid and diuretic prescribing cascade among older adults with lower back pain
Authors: Read Stephanie H. , Giannakeas Vasily , Pop Paula , Bronskill Susan E. , Herrmann Nathan , Chen Simon , Luke Miles J. , Wu Wei , McCarthy Lisa M. , Austin Peter C. , Normand Sharon‐Lise , Gurwitz Jerry H. , Stall Nathan M. , Savage Rachel D. , Rochon Paula
Published: June 2021

Background/Objectives

Gabapentinoids are commonly prescribed to relieve pain. The development of edema, an established adverse effect of gabapentinoids, may lead to a potentially harmful prescribing cascade whereby individuals are subsequently prescribed diuretics and exposed to diuretic‐induced adverse events. The frequency of this prescribing cascade is unknown. Our objective was to measure the association between new dispensing of a gabapentinoid and the subsequent dispensing of a diuretic in older adults with new low back pain.

Design

Population‐based cohort study.

Setting

Ontario, Canada.

Participants

A total of 260,344 community‐dwelling adults aged 66 years or older, newly diagnosed with low back pain between April 1, 2011, and March 31, 2019.

Measurements

Exposure status was assigned using dispensed medications in the 1 week after low back pain diagnosis. Older adults newly dispensed a gabapentinoid (N = 7867) were compared with older adults who were not newly dispensed a gabapentinoid (N = 252,477). Hazard ratios (HRs) with 95% confidence intervals (CIs) for dispensing of a diuretic within 90 days of follow‐up among older adults prescribed gabapentin relative to those who were not.

Results

Older adults newly dispensed a gabapentinoid had a higher risk of being subsequently dispensed a diuretic within 90 days compared with older adults who were not prescribed a gabapentinoid (2.0% vs. 1.3%). After covariate adjustment, new gabapentinoid users had a higher rate of being dispensed a diuretic compared with those not prescribed a gabapentinoid (HR: 1.44, 95% CI: 1.23, 1.70). The rate of diuretic prescription among new gabapentinoid users increased with increasing gabapentinoid dosages.

Conclusions

We have demonstrated the presence of a potentially inappropriate and harmful prescribing cascade. Given the widespread use of gabapentinoids, the population‐based scale of this problem may be substantial. Increased awareness of this prescribing cascade is required to reduce the unnecessary use of diuretics and the exposure of patients to additional adverse drug events.
What matters to older adults? Exploring person‐centred care during and after transitions between hospital and home
Authors: Nilsen Elin Rogn , Hollister Brooke , Söderhamn Ulrika , Dale Bjørg
Published: June 2021

Aims and objectives

To explore person‐centred care provided to a group of older adults (65+) by understanding their experiences of care received, their participation in care and what matters to them during and after the transition process between hospital and home.

Background

Although facilitating person‐centred care (PCC) has gained increasing importance globally over the last few decades, its practical implementation has been challenging. This has caused difficulties in determining its core elements and best practices. Person‐centred care aims to deliver healthcare services based on individuals' preferences. Several approaches have been developed to better implement person‐centred care practices. The Norwegian transitional and follow‐up model, ‘Holistic Continuity of Patient Care’, chooses the ‘What Matters to You?’ approach. Other approaches include ‘Shared Decision Making’ and ‘Continuity of Care’.

Design

This study employed a qualitative design.

Methods

Individual repeated interviews were conducted among eight participants. A hermeneutic exploratory research method was chosen. The COREQ checklist was followed.

Results

Three main themes related to person‐centred care emerged: what matters in meetings with the individual healthcare worker, mobilising health‐promoting capabilities and resources and what matters when being in the organisational healthcare system.

Conclusion

To participate in their own health issues, older people need to be empowered and better informed about the importance and scope of person‐centred care. ‘What Matters to You?’ is a good focus for the direction of care but can lead to a simplified understanding of individuals' preferences. Increased focus on how care recipients' capabilities and resources affect their responding is needed.

Relevance to clinical practice

Ensuring that person‐centred aspects are incorporated into the entire healthcare system requires better methods of engaging and empowering older adults in healthcare settings; more focus on PCC competence and skills of healthcare professionals as well as better integration of PCC practices into healthcare administration and policies.
Global value chain engagement and air pollution: Evidence from Chinese firms
Authors: Hua Yue , Lu Yue , Zhao Ruili
Published: June 2021

This paper studies the environmental consequences of firm's participation in the global value chain, based on a unique firm‐level data set from 2000 to 2007 by combining several large and representative databases in China. We propose a novel global value chain (GVC) engagement index that properly characterizes Chinese firm's importing patterns. By estimating fixed‐effects models with a rich set of firm‐level and industry‐level controls, our results robustly show that firm's engagement in GVC leads to decreased SO2 emission. The identified effects are stronger for firms with domestic ownership, firms of higher pollution intensity, and firms exposed to more stringent place‐based environmental regulation. We further demonstrate that the pollution reduction effects induced by firm's GVC engagement is attributable to lower SO2 intensity, which is likely to be achieved via the attenuated use of fossil fuels and the increased adoption of abatement devices.
Risk for hepatic and extra‐hepatic outcomes in nonalcoholic fatty liver disease
Authors: Hagström Hannes , Kechagias Stergios , Ekstedt Mattias
Published: June 2021

Nonalcoholic fatty liver disease (NAFLD) is defined by presence of steatosis in more than 5% of liver cells. The gold standard for diagnosis is liver biopsy, but this is seldom achieved due to costs and risk for side effects, and that is why the diagnosis is mostly made based on a combination of radiology and exclusion of other liver diseases. Disease severity staging can be noninvasively achieved with radiological exams such as elastography or blood‐based markers that usually have lower sensitivity and specificity. NAFLD is today the most common chronic liver disease globally with a prevalence estimated to be 25%. Fortunately, for many persons NAFLD is an incidental finding with a good prognosis. Whilst a major focus has been on liver‐related outcomes in NAFLD, there has recently been an increased interest in extrahepatic consequences of NAFLD. The most commonly studied outcomes include cardiovascular disease and cancer. The risk of adverse outcomes generally differs according to the baseline fibrosis stage. There is a five‐time higher risk of liver‐related events in NAFLD patients with fibrosis stage 3 as compared to those with no or little fibrosis. Meanwhile, the presence of nonalcoholic steatohepatitis (NASH) does not seem to influence prognosis in addition to fibrosis stage. Patients with NAFLD clearly have a higher risk for cardiovascular outcomes compared to the general population, with a recent meta‐analysis indicating a 37% increased hazard for cardiovascular events as opposed to individuals without NAFLD. The risk of liver cancer is increased, which is mostly driven by presence of cirrhosis, but the increased risk is present also in patients without cirrhosis, and to a greater extent than for other chronic liver disease. Around one‐third of patients with NAFLD and liver cancer do not have cirrhosis. Additionally, the risk of extrahepatic malignancies is thought to be moderately increased, with most evidence for a link between NAFLD and colorectal cancer where the risk is approximately 50% higher compared to patients without NAFLD. A particularly salient point is if NAFLD can be considered an independent risk factor for outcomes. Many studies have not been able to adjust for key confounders, or suffer from different forms of bias. The clinical problem is nevertheless to identify persons with an increased risk for adverse hepatic and extrahepatic outcomes. We here discuss the evidence linking NAFLD to severe hepatic and extrahepatic outcomes.
Letters of Conversion: Meta‐Alphabetic Discourse and Linguistic Participation in Colonial Highland Guatemala
Authors: Matsumoto Mallory E.
Published: June 2021

The alphabets that Spanish missionaries developed in the sixteenth century to record Amerindian languages were intimately tied to the evangelizing and civilizing projects of colonialism. This article highlights the consequences of missionaries’ alphabetic ideologies for engagement, in writing as well as speech, with native speakers of highland Mayan languages in Guatemala. In their alphabetic metadiscourse, missionaries juxtaposed Spanish‐speaking learners and indigenous speakers in different and unequal roles for linguistic participation. Through close examination of missionary sources, I demonstrate that missionary ideologies of written language not only articulated script with speech but also delineated knowledge circulation and shaped the power dynamics implicated in language’s actual use in colonial Guatemalan society.
Endogenous circadian regulation and phase resetting of clinical metabolic biomarkers
Authors: Grant Leilah K. , St Hilaire Melissa A. , Brainard George C. , Czeisler Charles A. , Lockley Steven W. , Rahman Shadab A.
Published: June 2021

Shiftwork and circadian disruption are associated with adverse metabolic effects. Therefore, we examined whether clinical biomarkers of metabolic health are under endogenous circadian regulation using a 40 hours constant routine protocol (CR; constant environmental and behavioral conditions) and evaluated the impact of typical daily conditions with periodic sleep and meals (baseline; 8 hours sleep at night, four meals during a 16 hour wake episode) on the phase and amplitude of these rhythms. Additionally, we tested whether these circadian rhythms are reset during simulated shiftwork. Under CR (n = 16 males, mean age ± SD = 23.4 ± 2.3 years), we found endogenous circadian rhythms in cholesterol, HDL and LDL, albumin and total protein, and VLDL and triglyceride. The rhythms were masked under baseline conditions except for cholesterol, which had near‐identical phases under both conditions. Resetting of the cholesterol rhythm and Dim Light Melatonin Onset (DLMO) was then tested in a study of simulated shiftwork (n = 25, 14 females, 36.3 ± 8.9 years) across four protocols; two with abrupt 8 hour delay shifts and exposure to either blue‐enriched or standard white light; and either an abrupt or gradual 8 hour advance (1.6 hours/day over 5 days) both with exposure to blue‐enriched white light. In the delay protocols, the cholesterol rhythm shifted later by −3.7 hours and −4.2 hours, respectively, compared to −6.6 hours and −4.7 hours, for DLMO. There was a significant advance in cholesterol in the abrupt (+5.1 hours) but not the gradual (+2.1 hours) protocol, compared to +3.1 hours and +2.8 hours in DLMO, respectively. Exploratory group analysis comparing the phases of all metabolic biomarkers under both studies showed evidence of phase shifts due to simulated shiftwork. These results show that clinical biomarkers of metabolic health are under endogenous circadian regulation but that the expression of these rhythms is substantially influenced by environmental factors. These rhythms can also be reset, which has implications for understanding how both behavioral changes and circadian shifts due to shiftwork may disrupt metabolic function.
Nicotinic acid supplementation at a supraphysiological dose increases the bioavailability of NAD+ precursors in mares
Authors: Pollard Charley‐Lea , Gibb Zamira , Swegen Aleona , Lawson Edwina F. , Grupen Christopher G.
Published: June 2021

NAD+ deficiency has recently been linked with increased occurrences of congenital abnormalities and embryonic death in human and animal subjects. Early embryonic death is a major component of pregnancy loss in mares and very little is known regarding the requirement for NAD+ in horses. The aim of this study was to quantify NAD+ and its metabolites in the plasma and urine of mares after orally administering an acute dose of nicotinic acid and determine the absorption, metabolism and excretion of this essential precursor for NAD+ biosynthesis. Nicotinic acid (5 g per os) was administered to four mares via a dosing syringe. Blood samples were collected at 0, 0.25, 0.5, 1, 2, 4, 6 and 22 h, and urine samples were collected at 0, 3, 6 and 22 h. The samples were processed and analysed by mass spectrometry. A general additive model was applied to all metabolite concentration values followed by a post‐hoc multiple comparisons test. Nicotinic acid was rapidly absorbed into peripheral blood within 15 min of administration and the concentrations of nicotinic acid, nicotinamide (NAM), nicotinuric acid, nicotinic acid mononucleotide and nicotinic acid adenine dinucleotide (NaAD) increased significantly in plasma at 30 min. The concentrations of NAM, nicotinic acid riboside and NaAD increased significantly in urine at 3 h. The levels of NAM and NaAD remained significantly elevated in plasma at 22 h, sixfold and ninefold greater, respectively, than the basal levels at 0 h. While the extracellular levels of NAD+ in the samples remained undetected, the large, sustained elevation of NaAD levels in plasma indicates that the NAD+ levels were boosted within the cellular compartments. The results show that nicotinic acid supplementation increases the bioavailability of NAD+ precursors in mares, which is proposed to be beneficial during periods of peak NAD+ demand, such as during early embryo development.
Pancreatic enzyme activity in the bile of healthy cats and its association with biliary morphology
Authors: Fujimoto Shinsuke , Torisu Shidow , Kaneko Yasuyuki , Mizutani Shinya , Yamamoto Shushi , Naganobu Kiyokazu , Nakamura Kensuke
Published: June 2021

Background

In human medicine, congenital maljunction of the common bile duct (CBD) and main pancreatic duct (MPD), or pancreatobiliary maljunction (PBM), is a known cause of cholecystitis.

Objective

Pancreatic enzyme activity in the bile (a diagnostic marker for PBM) of healthy cats was measured to determine normal values and evaluate its relationship with biliary morphology.

Animals

Fifty‐two healthy cats.

Methods

Cross‐sectional study of the biliary tracts of healthy cats during laparoscopic ovariohysterectomy and measurement of pancreatic enzyme activity in bile. The cats were divided into groups A and B based on the ratio of the diameter of the cystic duct (CD) to the CBD. The normal ratio was 3.4. Pancreatic enzyme activity in bile was compared between the groups.

Results

The CBDs were straight in all cases, whereas the CDs were variably tortuous or dilated. Amylase activity in the bile (median, <100 U/L; range, <100‐591 U/L) was lower than in serum in all cases, and group B, which had a CD/CBD ratio >3.4, had significantly higher amylase activity (median, 109 U/L; range, <100‐591 U/L) in the bile than did group A (median, <100 U/L; range, <100‐238 U/L), which had a CD/CBD ratio <3.4 (P = .0009).

Conclusions and Clinical Importance

The results suggest that a dilated CD is associated with reflux of pancreatic juice. In the future, it will be necessary to examine the clinical usefulness of these findings by measuring pancreatic enzyme activity in the bile of cats with cholangitis.
Habitat‐mediated reef fish assemblages in coral reef tidal pools
Authors: dos Santos Crislaine Morais , Santana Virginia , Bastos Alice , Teixeira Jessyca Luana , Gama Mateus Alexander Campeche , Kennedy Sara Buttrose , Félix‐Hackradt Fabiana Cézar , Hackradt Carlos Werner
Published: June 2021

Tide pools are important environments for several fish species, as they offer essential resources such as shelter and food. Thus, understanding the relationships of the ichthyofauna with the habitat structural characteristics in tide pools is important to understand the distribution patterns of fish assemblages in shallow environments. This study investigated how the habitat structure in tide pools influences the reef fish assemblages in Southwestern Atlantic (Bahia, Brazil). During 17 months, tidal pools were evaluated through visual censuses aiming to sampling the ichthyofauna, and additionally, variables of the structural characteristics of the pools (depth, area, volume, rugosity, etc.) were measured. By using multiple statistical modeling approaches, we found that there were significant differences in diversity, abundance, and species richness at the interaction between time and space factors, with higher averages of the three variables during the warmer months across all reef banks. Moreover, at local spatial scale, greater coral‐dominated and complex pools harbored higher fish species and diversity, while algae cover was most important in shaping fish numbers. The most important variables in the structuring of the fish assemblages were the pool volume, distance from the edge of the reef, and habitat complexity, confirming our hypothesis. Resident fish species were found in pools near the out reef edge, while occasional and transient species were found in pools closer to the inland sea. Our study highlights the multi‐scale role of habitat characteristics as predictors of the fish assemblage structure in these extremely variable environments and emphasizes the need to protect these fragile and overexploited tidal pools.
Efficient simulation of wind fields based on the factorization of wavenumber‐frequency joint spectrum
Authors: Yang Xiongjun , Lei Ying
Published: June 2021

The fast Fourier transform (FFT) technique is usually adopted in the wind field simulation based on the wavenumber‐frequency joint spectrum. However, inefficient multi‐dimensional FFT in both frequency and wavenumber domains are directly implemented in the existing literature. In this paper, a novel factorization method of wavenumber‐frequency joint spectrum is proposed to enhance efficiency. For the one‐spatial dimension wind field, the wavenumber‐frequency joint spectrum is decoupled by employing the proper orthogonal decomposition technology, and it is proposed to factorize the double‐index random phase angle into two independent random phase angles. Then, the previous 2D FFT can be replaced by 1D FFT. Furthermore, the proposed factorization method is extended to the two‐spatial dimension wind field, considering two wavenumbers and triple‐index random phase angle are introduced, the wavenumber‐frequency spectrum and triple‐index random phase angle are decomposed twice in succession. Thus, the undesired 3D FFT can be avoided. Simulations of a one‐spatial dimension and a two‐spatial dimension wind fields are used to demonstrate the accuracy and efficiency of the proposed method by comparing it with the existing method involved in multi‐dimensional FFT.
Factors predicting coping in older people with dementia: A cross‐sectional study
Authors: Leecharoen Phanit , Pothiban Linchong , Chintanawat Rojanee , Khampolsiri Totsaporn
Published: June 2021

Coping can buffer the effect of stress on well‐being. Information about factors predicting coping is essential knowledge for developing programs to promote effective coping among older people with dementia and serves as basic knowledge for further study. A cross‐sectional study design was employed to investigate the associated and predictive factors of coping. The factors were derived from the Stress Process Model for people with dementia. A group of 364 participants was determined by power analysis and purposively selected from out‐patient dementia clinics of hospitals in Thailand. Data were collected from interviews using questionnaires and were analyzed using Spearman's rank correlation coefficient and the enter method of multiple regression analysis. With reference to the conceptual framework of the Stress Process Model, the results revealed that three background and context factors (gender, personal income, and relationships with family members), two stressor factors (cognitive ability, and self‐esteem), and four mediator factors (optimism, hope, hardiness, and perceived social support) were significantly related to coping. Of the variation in coping scores, 47% could be explained by hope, perceived social support, cognitive ability, and gender.
Genome‐wide association analysis of agronomical and physiological traits linked to drought tolerance in a diverse potatoes (Solanum tuberosum) panel
Authors: Tagliotti Martin Enrique , Deperi Sofia Irene , Bedogni Maria Cecilia , Huarte Marcelo Atilio
Published: June 2021

Potatoes is often considered a drought‐sensitive crop and its sustainable production is threatened due to frequent drought episodes. Drought tolerance is a complex trait of increasing importance in potatoes therefore its yield is threatened. The differential response of several physiological and agronomical traits was evaluated in a diverse potatoes panel under contrasting water regimes to identify quantitative trait loci (QTL) associated with drought tolerance using genome‐wide association analysis with 4859 high‐quality SNP markers. Phenotypic data were collected from multiple environments and years. QTL with diverse linkage disequilibrium blocks for proline concentration, water consumption and yield were detected on chromosomes 1, 4 and 10. These QTL detected were associated with known gene functions. The current study provides insights into the putative genes that controlled the responses to the drought tolerance in potatoes at physiological and agronomical levels. The QTL described in this work might be included in future marker‐assisted selection programmes linked with drought tolerance in potatoes.
Changing light promotes isoflavone biosynthesis in soybean pods and enhances their resistance to mildew infection
Authors: Li Xiaoman , Yang Caiqiong , Chen Jianhua , He Yuanyuan , Deng Juncai , Xie Congwei , Xiao Xinli , Long Xiyang , Wu Xiaoling , Liu Weiguo , Du Junbo , Yang Feng , Wang Xiaochun , Yong Taiwen , Zhang Jing , Wu Yushan , Yang Wenyu , Liu Jiang
Published: June 2021

Mildew severely reduces soybean yield and quality, and pods are the first line of defence against pathogens. Maize‐soybean intercropping (MSI) reduces mildew incidence on soybean pods; however, the mechanism remains unclear. Changing light (CL) from maize shading is the most important environmental feature in MSI. We hypothesized that CL affects isoflavone accumulation in soybean pods, affecting their disease resistance. In the present study, shading treatments were applied to soybean plants during different developmental stages according to various CL environments under MSI. Chlorophyll fluorescence imaging (CFI) and classical evaluation methods confirmed that CL, especially vegetative stage shading (VS), enhanced pod resistance to mildew. Further metabolomic analyses and exogenous jasmonic acid (JA) and biosynthesis inhibitor experiments revealed the important relationship between JA and isoflavone biosynthesis, which had a synergistic effect on the enhanced resistance of CL‐treated pods to mildew. VS promoted the biosynthesis and accumulation of constitutive isoflavones upstream of the isoflavone pathway, such as aglycones and glycosides, in soybean pods. When mildew infects pods, endogenous JA signalling stimulated the biosynthesis of downstream inducible malonyl isoflavone (MIF) and glyceollin to improve pod resistance.
Sugar‐sweetened beverage consumption and overweight and obesity in adolescents in Ho Chi Minh City, Vietnam: a population‐based analysis
Authors: Nguyen Ngoc‐Minh , K Tang Hong , Dibley Michael John , Alam Ashraful
Published: June 2021

Background

The aim of this research was to describe the patterns of consumption of multiple sugar‐sweetened beverages (including modern and traditional ones) among adolescents in Ho Chi Minh City and to identify a possible relationship between this consumption and overweight, obesity, and other factors.

Methods

A secondary analysis from a cross‐sectional study of 11–15‐year‐old students from 31 junior high schools across Ho Chi Minh City was used. We measured the students’ anthropometric status and assessed beverage consumption using a validated Food Frequency Questionnaire. Multivariate logistic regression models were used to identify the association between the consumption of sugar‐sweetened beverages, obesity and other factors.

Results

The sugar‐sweetened beverages (SSB) ranged widely from modern soft drinks and powdered drinks to traditional sugar‐added fruit and leaf juices, and milk‐based drinks. These beverages were very popular among 2,660 participants with 36% consuming at least one variety daily. Factors positively associated with sugar‐sweetened beverage consumption included a higher level of physical activity, higher consumption of fast foods, and daily fruit and vegetable consumption. We found a negative association between milk‐based SSBs and the overweight and obesity status of the students, i.e. every kcal more of fresh milk with sugar and condensed milk can reduce an obesity odd of 0.005 (95% CI [0.002–0.008], p < 0.001) and 0.004 (95% CI [0.002–0.010], p = 0.044) consecutively. None of the other SSBs was significantly related to adolescent overweight and obesity.

Conclusions

Milk‐based drinks potentially protect adolescents against overweight and obesity. Further research to assess this protection is needed.
Algorithmic bias: Senses, sources, solutions
Authors: Fazelpour Sina , Danks David
Published: June 2021

Data‐driven algorithms are widely used to make or assist decisions in sensitive domains, including healthcare, social services, education, hiring, and criminal justice. In various cases, such algorithms have preserved or even exacerbated biases against vulnerable communities, sparking a vibrant field of research focused on so‐called algorithmic biases. This research includes work on identification, diagnosis, and response to biases in algorithm‐based decision‐making. This paper aims to facilitate the application of philosophical analysis to these contested issues by providing an overview of three key topics: What is algorithmic bias? Why and how can it occur? What can and should be done about it? Throughout, we highlight connections—both actual and potential—with philosophical ideas and concerns.
Practical Wisdom, Well‐Being, and Success
Authors: Tsai Cheng‐hung
Published: June 2021

What is practical wisdom? What does a practically wise person know? It is widely held that a person is practically wise if and only if the person knows how to live well, and that a person knows how to live well only if the person knows what is good or important for well‐being. The question is: What is it that contributes to or constitutes well‐being known by a wise person? A theory of wisdom without a substantive answer to this question can never be seriously tested and used in practice. In this paper, I propose a fully articulated theory of wisdom by integrating the skill theory of wisdom with the success theory of well‐being, arguing that practical wisdom is a skill conducive to well‐being conceived as attitude success.
The Unity of Normative Thought
Authors: Fix Jeremy David
Published: June 2021

Practical cognitivism is the view that practical reason is our will, not an intellectual capacity whose exercises can influence those of our will. If practical reason is our will, thoughts about how I am to act have an essential tie to action. They are intentions. Thoughts about how others are to act, though, lack such a tie to action. They are beliefs, not intentions. How, then, can these thoughts form a unified class? I reject two answers which deny the differences between such thoughts about myself and those about others, one of which says that all such thoughts are intentions, the other that all are beliefs. I then reject a shared assumption which says that a class of those is unified only if all its elements are all of one type of thought. I instead argue that this class is unified even though some elements are intentions, others beliefs, because such beliefs depend on those intentions in various ways.
Humility for Everyone: A No‐Distraction Account
Authors: Callahan Laura Frances
Published: June 2021

This paper attempts to motivate and reconcile two thoughts about humility that are in tension. First, the experiences of oppressed people matter a great deal to the question of whether humility is a virtue. Second, prima facie anyway, there still seems reason to think humility is a virtue, and an ‘inclusive’ virtue at that, i.e. a virtue for all people. I attempt to reconcile these two thoughts by suggesting a new account of humility, which I call the no‐distraction account. Humility is just the disposition to be free from distracting pride.
The Mind’s Presence to Itself: In Search of Non‐intentional Awareness
Authors: Mitchell Jonathan
Published: June 2021

According to some philosophers, the mind enjoys a form of presence to itself. That is to say, in addition to being aware of whatever objects it is aware of, it is also (co‐presently) aware of itself. This paper explores the proposal that we should think about this kind of experiential‐presence in terms of a form of non‐intentional awareness. Various candidates for the relevant form of awareness, as constituting supposed non‐intentional experiential‐presence, are considered and are shown to encounter significant problems. The fact that a plausible account of the non‐intentional awareness which experience putatively has of itself cannot be framed with reference to such forms of awareness is grounds for scepticism concerning the cogency of non‐intentional experiential presence.
AI Automation and Retailer Regret in Supply Chains
Authors: Li Meng , Li Tao
Published: June 2021

Artificial intelligence (AI) has significantly changed the supply chain process. In this study, we study the effects associated with AI automation of the retailer's order decision in a decentralized supply chain comprising one supplier and one regretful retailer. In the absence of AI automation, the retailer has a regret bias in that it behaves as though considering the deviation between the realized demand and order quantity, when making an ex ante inventory decision. We find that if profit margins of the supply chain are high, regret bias drives the retailer to decline the supplier's contract, whereas, if profit margins are low, regret drives retailers to order more from the supplier. As a result, although the automation of retailer decision leads to a higher expected profit for a retailer that operates in a centralized vacuum, it nevertheless can be a negative force for a decentralized supply chain with either high or low profit margins. Perhaps more interestingly, as a retailer's decision becomes automatic, it is not destined to earn a higher expected profit. In the extreme, a lose‐lose outcome can prevail in which automation potentially leaves both the retailer and supplier worse off.
Consumer Choice Models and Estimation: A Review and Extension
Authors: Feng Qi , Shanthikumar J. George , Xue Mengying
Published: June 2021

Choice models are widely applied in psychology, economics, transportation, marketing, and operations studies. We review the existing developments on the modeling of consumers’ choices, including the attraction model, the utility‐based model, the temporal model, and the rank‐based model. The relationships among different classes of structural models are established and analyzed. Moreover, an operational data analytics (ODA) framework is presented to estimate the general consumer choice model using data. This framework, generalizing the existing estimation methods for specific structural models, strikes a delicate balance between the (likely imprecise) structural knowledge and the data. This is achieved by articulating the domain of validation through extending the structural knowledge and by formulating the data‐integration model based on the associated structural properties. We demonstrate the implementation of the ODA framework to identify the appropriate consumer choice models. The ODA estimate outperforms the existing parametric and nonparametric methods, particularly over the choice sets that are not covered in the data. We also discuss potential future research of developing ODA approaches to study the related aspects of consumer choice models.
Add‐On Pricing in a Distribution Channel
Authors: Yin Qianbo , Huang Kwei‐Long , Kuo Chia‐Wei , Zhou Sean X.
Published: June 2021

We consider add‐on pricing in a distribution channel where a retailer sells a base good and an add‐on, supplied by two manufacturers, respectively, to consumers. The retailer decides whether to sell the two products through either bundling or add‐on pricing and sets the corresponding retail prices. Under add‐on pricing, the add‐on price is unobservable to consumers when they make the purchase decision of the base good. Each manufacturer, if independent of the retailer, sets the wholesale price. Under four channel structures differed by whether either manufacturer is independent of the retailer, we specify the scenario that is optimal for the retailer to adopt add‐on pricing and show the contrasting impact from the two manufacturers. When all three firms are integrated, the retailer in general prefers add‐on pricing to bundling when the cost of base good is low and the cost of add‐on is high. Using this case as the benchmark, we show that add‐on pricing is more (less) likely to be adopted when the add‐on (base) manufacturer is independent, and add‐on pricing is again more likely to be adopted when all three firms are independent. In addition to the demand smoothing effect of bundling, we identify two drivers from the supply side: the margin squeezing effect of bundling from the add‐on manufacturer and the margin smoothing effect of bundling from the base manufacturer, where the former encourages add‐on pricing whereas the latter discourages it. The interplay of these drivers largely influences the retailer's add‐on strategy and renders the preceding results. Several extensions are discussed, including correlated consumer valuations of base good and add‐on, an alternate decision sequence, knowledgeable consumers (about add‐on price), simultaneous offering of bundling and add‐on pricing, and bilateral monopoly.
Timing the Price Agreement in High‐Tech Component Procurement
Authors: Zhang Wei , Wang Jingqi , Ahmadi Reza , Dasu Sriram
Published: June 2021

We consider a high‐technology supply chain wherein a manufacturer is sourcing a new component from a monopolistic supplier who has limited production capacity. We focus on a setting wherein the manufacturer has decided to adopt the component but has not introduced the end product to the market and the manufacturer's task is to negotiate with the supplier for the procurement price before a deadline. The only uncertainty is the number of manufacturers adopting this component, which determines the supplier's outside option. With this uncertainty, delaying the agreement could be preferable because the manufacturer may receive a price cut if the supplier's outside option turns out to be weak. However, delay could also be costly as the supplier may refuse to sell or ask for a high price if many adopters show up. Thus, the timing of agreement for the manufacturer is a trade‐off between the benefit of collecting more information and the risk of losing the limited supply (or paying a high price). Given that the firms are rational, information is symmetric, and the manufacturer's outside option is to use older technologies, we derive the manufacturer's optimal timing strategy—how to set the deadline and whether to delay the agreement. Interestingly, we find that the manufacturer can benefit more from waiting when there is a greater chance that other higher‐value buyers exist. Furthermore, in certain circumstances, we find that the manufacturer should commit to a tighter deadline, even though it is optimal to delay the agreement.
Group classification and analytical solutions of a radially symmetric avascular cancer model
Authors: Bortuli Altemir , Freire Igor Leite , Maidana Norberto Anibal
Published: June 2021

We consider a system of partial differential equations modeling tumors. The system under consideration describes the spatial dynamics of the tumor cells, extracellular matrix, and matrix degrading enzymes. We first carry out a complete group classification of the Lie point symmetries of this model. Next, we use symmetry techniques to construct invariant solutions for it. In addition, we consider a second system of partial differential equations, coupling to the original one the concentration of oxygen, and we find several analytical solutions to this system. Most of the solutions are biologically relevant and consistent with the evolution of such tumors.
Objective and quantitative measurement of skin micro‐relief by image analysis and application in age‐dependent changes
Authors: Wu Yue , Tanaka Toshiyuki
Published: June 2021

Background

Skin micro‐relief has been researched by a variety of devices and methods, which usually are expensive or complicated. On the other hand, skin micro‐relief relates to quite a few parameters, and it is hard to evaluate all of them at the same time. In the study, all parameters related to skin micro‐relief are extracted and evaluated by image analysis.

Materials and Methods

Skin micro‐relief evaluation was divided into four aspects: (a) Tamura features method was used to evaluate skin surface. (b) Morphological transform was applied to extract skin pores. (c) Watershed transform was applied to extract skin furrows. (d) labeling operation was used to evaluate the number, area and average area of skin closed polygons. Then, cheek images from 163 healthy Japanese females (0‐70 years old) are analyzed to explore the age‐dependent changes.

Results

Most parameters increased as age went on with significant differences, such as skin surface coarseness, contrast, skin pore number, area, average area, skin furrow width, skin closed polygon area and skin closed polygon average area. Skin coarseness has a strong correlation with pore area.

Conclusion

The method proposed in the study provided a comprehensive and effective assessment of skin micro‐relief.
Variable accuracy, precision, and consistency of compounded famciclovir formulated for management of feline herpesvirus‐1 in cats
Authors: O'Leary Louise M. , Allbaugh Rachel A. , Schrunk Dwayne E. , Olsen Thomas E. , Sebbag Lionel
Published: June 2021

Objective

To evaluate compounded famciclovir suspensions for accuracy, precision, and consistency in drug content.

Procedures

Two compounded famciclovir concentrations were evaluated (250 and 400 mg/mL, 30 preparations total from nine 503A compounding pharmacies) with U.S. Food and Drug Administration (FDA)‐approved famciclovir tablets as control. Drug quantification via high‐performance liquid chromatography (with famciclovir reference standard and pramipexole internal standard) was performed at 0, 14, and 28 days with concentrations of 90%–110% of labeled dose considered acceptable (US Pharmacopoeia standards).

Results

FDA‐approved tablets from three different manufacturers were found to be accurate and precise with acceptable drug content. A significantly greater mean deviation from labeled content was noted for 400 mg/mL suspensions (–52.9%) compared to 250 mg/mL suspensions (–18.0%). When assessing time points separately, 15/63 (24%) samples of 250 mg/mL and 0/27 (0%) samples of 400 mg/mL suspensions met the acceptance standards. Coefficients of variation (CV) in drug content among pharmacy batches ranged from 0.5% to 29%, with 5/10 formulations having significantly lower CV% compared to control (decreased precision). Similarly, drug content changed over time (0–28 days) in all compounded formulations, with both downward and upward trends observed (variable consistency).

Conclusions

Most compounded famciclovir formulations were inaccurate, imprecise, and inconsistent. FDA‐approved famciclovir tablets may be preferred over compounded famciclovir formulations for the management of feline herpesvirus‐1. If compounded famciclovir is used in practice, a concentration of 250 mg/mL is preferred over 400 mg/mL given the lower accuracy of the higher concentration.
Myofibroblast fate plasticity in tissue repair and fibrosis: Deactivation, apoptosis, senescence and reprogramming
Authors: Merkt Wolfgang , Zhou Yan , Han Hongwei , Lagares David
Published: June 2021

In response to tissue injury, fibroblasts differentiate into professional repair cells called myofibroblasts, which orchestrate many aspects of the normal tissue repair programme including synthesis, deposition and contraction of extracellular matrix proteins, leading to wound closure. Successful tissue repair responses involve termination of myofibroblast activities in order to prevent pathologic fibrotic scarring. Here, we discuss the cellular and molecular mechanisms limiting myofibroblast activities during physiological tissue repair, including myofibroblast deactivation, apoptosis, reprogramming and immune clearance of senescent myofibroblasts. In addition, we summarize pathological mechanisms leading to myofibroblast persistence and survival, a hallmark of fibrotic diseases. Finally, we discuss emerging anti‐fibrotic therapies aimed at targeting myofibroblast fate such as senolytics, gene therapy, cellular immunotherapy and CAR‐T cells.