bluuebunny/crossref_metadata_2025 huggingface dataset:
CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 contributes to prostate carcinogenesis
Authors: Qi Jin-Chun , Yang Zhan , Lin Tao , Ma Long , Wang Ya-Xuan , Zhang Yong , Gao Chun-Cheng , Liu Kai-Long , Li Wei , Zhao An-Ning , Shi Bei , Zhang Hong , Wang Dan-Dan , Wang Xiao-Lu , Wen Jin-Kun , Qu Chang-Bao
Published: January 2021

Background

Both E2F transcription factor and cyclin-dependent kinases (CDKs), which increase or decrease E2F activity by phosphorylating E2F or its partner, are involved in the control of cell proliferation, and some circRNAs and miRNAs regulate the expression of E2F and CDKs. However, little is known about whether dysregulation among E2Fs, CDKs, circRNAs and miRNAs occurs in human PCa.

Methods

The expression levels of CDK13 in PCa tissues and different cell lines were determined by quantitative real-time PCR and Western blot analysis. In vitro and in vivo assays were preformed to explore the biological effects of CDK13 in PCa cells. Co-immunoprecipitation anlysis coupled with mass spectrometry was used to identify E2F5 interaction with CDK13. A CRISPR-Cas9 complex was used to activate endogenous CDK13 and circCDK13 expression. Furthermore, the mechanism of circCDK13 was investigated by using loss-of-function and gain-of-function assays in vitro and in vivo.

Results

Here we show that CDK13 is significantly upregulated in human PCa tissues. CDK13 depletion and overexpression in PCa cells decrease and increase, respectively, cell proliferation, and the pro-proliferation effect of CDK13 is strengthened by its interaction with E2F5. Mechanistically, transcriptional activation of endogenous CDK13, but not the forced expression of CDK13 by its expression vector, remarkably promotes E2F5 protein expression by facilitating circCDK13 formation. Further, the upregulation of E2F5 enhances CDK13 transcription and promotes circCDK13 biogenesis, which in turn sponges miR-212-5p/449a and thus relieves their repression of the E2F5 expression, subsequently leading to the upregulation of E2F5 expression and PCa cell proliferation.

Conclusions

These findings suggest that CDK13 upregulation-induced formation of the positive feedback loop among circCDK13, miR-212-5p/miR-449a and E2F5 is responsible for PCa development. Targeting this newly identified regulatory axis may provide therapeutic benefit against PCa progression and drug resistance.
Early clearance of serum HE4 and CA125 in predicting platinum sensitivity and prognosis in epithelial ovarian cancer
Authors: Rong Yan , Li Li
Published: January 2021

Objectives

To assess the clinical value of early clearance of HE4 and CA125 for platinum sensitivity and prognosis in patients with ovarian cancer.

Method

HE4 and CA125 value including clinical data of 89 patients with ovarian cancer were collected. The clearance of HE4 and CA125 were assessed base on the platinum sensitivity, two-year PFS, PFS and OS.

Results

Sixteen patients were classified as platinum resistant and 73 as platinum sensitive according to the response to platinum-base chemotherapy. When HE4 clearance after 3rd cycle chemotherapy or CA125 clearance after 1st cycle chemotherapy, it gave the highest AUC of 0.788, with 100% of sensitivity and 57.5% of specificity respectively between platinum resistant and platinum sensitive group. In addition, 59 patients were classified as two-year PFS group and 30 as not achieved two-year PFS group according to obtaining two-year PFS or not. It gave the highest AUC of 0.730, with 83.3% of sensitivity and 62.7% of specificity respectively when HE4 clearance after 3rd cycle chemotherapy or CA125 clearance after 1st cycle. The prolonged PFS and OS were significantly associated by the clearance of HE4 after 3rd cycle chemotherapy (p< 0.0001, p< 0.0001) as well as CA125 after 1st cycle chemotherapy (p< 0.0001, p< 0.0001).

Conclusions

Our data suggested that the early clearance of HE4 and CA125 could predict platinum response and prognosis in patients with ovarian cancer. Monitoring the HE4 and CA125 during first-line chemotherapy might be helpful in predicting platinum sensitivity and risk to progress and relapse.
Younger age and female gender are determinants of underestimated cardiovascular risk in rheumatoid arthritis patients: a prospective cohort study
Authors: Rohrich Daphne C. , van de Wetering Eline H. M. , Rennings Alexander J. , Arts Elke E. , Meek Inger L. , den Broeder Alfons A. , Fransen Jaap , Popa Calin D.
Published: January 2021

Background

Rheumatoid arthritis (RA) patients have an increased cardiovascular (CV) risk. Here, we aimed to investigate whether gender and age are contributing to the misclassification of CV risk in RA patients.

Methods

Prospectively collected data on cardiovascular risk factors and incident events from the Nijmegen inception cohort were analyzed, with up to 10 years follow-up. Original as well as the EULAR-modified (M)_SCORE algorithms were used to calculate CV risk. Patients were stratified in deciles according to predicted risk; the Hosmer-Lemeshow test was used to check concordance between observed and predicted risk, in subgroups of gender and age.

Results

There were 863 RA patients included with 128 incident CV events. When using SCORE in the whole group, there was evidence of a discrepancy between the predicted and observed CV risk (H-L test p < 0.003), mainly present in the female subgroup (H-L test p < 0.001). Interestingly, 36% of females who developed an event belonged to the low CV risk group, whereas this was just 10% in RA males. When analyzing the subgroups based on age, a discrepancy was present only in the youngest patients (H-L test p < 0.001 in patients < 55 years) consisting of an underestimation of CV risk (5.3% predicted vs. 8.0% observed). Similar results were obtained when the M_SCORE was applied.

Conclusion

CV risk is especially underestimated in female and younger RA patients. This suggests that modifying the weight for the female gender and/or younger age in currently used CV risk algorithms might improve their predictive value in RA, contributing to better CV risk management.
Region-specific amyloid-β accumulation in the olfactory system influences olfactory sensory neuronal dysfunction in 5xFAD mice
Authors: Son Gowoon , Yoo Seung-Jun , Kang Shinwoo , Rasheed Ameer , Jung Da Hae , Park Hyunjun , Cho Bongki , Steinbusch Harry W. M. , Chang Keun-A , Suh Yoo-Hun , Moon Cheil
Published: January 2021

Background

Hyposmia in Alzheimer’s disease (AD) is a typical early symptom according to numerous previous clinical studies. Although amyloid-β (Aβ), which is one of the toxic factors upregulated early in AD, has been identified in many studies, even in the peripheral areas of the olfactory system, the pathology involving olfactory sensory neurons (OSNs) remains poorly understood.

Methods

Here, we focused on peripheral olfactory sensory neurons (OSNs) and delved deeper into the direct relationship between pathophysiological and behavioral results using odorants. We also confirmed histologically the pathological changes in 3-month-old 5xFAD mouse models, which recapitulates AD pathology. We introduced a numeric scale histologically to compare physiological phenomenon and local tissue lesions regardless of the anatomical plane.

Results

We observed the odorant group that the 5xFAD mice showed reduced responses to odorants. These also did not physiologically activate OSNs that propagate their axons to the ventral olfactory bulb. Interestingly, the amount of accumulated amyloid-β (Aβ) was high in the OSNs located in the olfactory epithelial ectoturbinate and the ventral olfactory bulb glomeruli. We also observed irreversible damage to the ectoturbinate of the olfactory epithelium by measuring the impaired neuronal turnover ratio from the basal cells to the matured OSNs.

Conclusions

Our results showed that partial and asymmetrical accumulation of Aβ coincided with physiologically and structurally damaged areas in the peripheral olfactory system, which evoked hyporeactivity to some odorants. Taken together, partial olfactory dysfunction closely associated with peripheral OSN’s loss could be a leading cause of AD-related hyposmia, a characteristic of early AD.
Differences between memory encoding and retrieval failure in mild cognitive impairment: results from quantitative electroencephalography and magnetic resonance volumetry
Authors: Han Su-Hyun , Pyun Jung-Min , Yeo Soeun , Kang Dong Won , Jeong Ho Tae , Kang Seung Wan , Kim SangYun , Youn Young Chul
Published: January 2021

Background

The memory impairments in mild cognitive impairment (MCI) can be classified into encoding (EF) and retrieval (RF) failure, which can be affected by underlying pathomechanism. We explored the differences structurally and functionally.

Methods

We compared quantitative electroencephalography (qEEG) power spectra and connectivity between 87 MCI patients with EF and 78 MCI with RF using iSyncBrain® (iMediSync Inc., Republic of Korea) (https://isyncbrain.com/). Voxel-based morphometric analysis of the gray matter (GM) in the MCI groups and 71 cognitive normal controls was also done using the Computational Anatomy Toolbox 12 (http://www.neuro.uni-jena.de/cat/).

Results

qEEG showed higher frontal theta and lower beta2 band power, and higher theta connectivity in the EF. There was no statistically significant difference in GM volume between the EF and RF. However, when compared to normal control, GM volume reductions due to EF in the left thalamus and bilateral hippocampi and reductions due to RF in the left thalamus, right superior frontal lobe, right superior temporal lobe, and right middle cingulum were observed (p < 0.05, family-wise error correction).

Conclusions

MCI differs functionally and structurally according to their specific memory impairments. The EF findings are structurally and functionally more consistent with the prodromal Alzheimer’s disease stage than the RF findings. Since this study is a cross-sectional study, prospective follow-up studies are needed to investigate whether different types of memory impairments can predict the underlying pathology of amnestic MCI. Additionally, insufficient sample size may lead to ambiguous statistical findings in direct comparisons, and a larger patient cohort could more robustly identify differences in GM volume reductions between the EF and the RF group.
The association of APOE ε4 with cognitive function over the adult life course and incidence of dementia: 20 years follow-up of the Whitehall II study
Authors: Gharbi-Meliani Amin , Dugravot Aline , Sabia Séverine , Regy Melina , Fayosse Aurore , Schnitzler Alexis , Kivimäki Mika , Singh-Manoux Archana , Dumurgier Julien
Published: January 2021

Background

Approximately 25% of the general population carries at least one ε4 allele of the Apolipoprotein E (APOEε4), the strongest genetic risk factor for late onset Alzheimer’s disease. Beyond its association with late-onset dementia, the association betweenAPOEε4 and change in cognition over the adult life course remains uncertain. This study aims to examine whether the association between Apolipoprotein E (APOE) ε4 zygosity and cognition function is modified between midlife and old age.

Methods

A cohort study of 5561 participants (mean age 55.5 (SD = 5.9) years, 27.1% women) withAPOEgenotyping and repeated cognitive tests for reasoning, memory, and semantic and phonemic fluency, during a mean (SD) follow-up of 20.2 (2.8) years (the Whitehall II study). We used joint models to examine the association ofAPOEgenotype with cognitive function trajectories between 45 and 85 years taking drop-out, dementia, and death into account and Fine and Gray models to examine associations with dementia.

Results

Compared to non-carriers, heterozygote (prevalence 25%) and homozygote (prevalence 2%)APOEε4 carriers had increased risk of dementia, sub-distribution hazard ratios 2.19 (95% CI 1.73, 2.77) and 5.97 (95% CI 3.85, 9.28) respectively. Using data spanning 45–85 years with non-ε4 carriers as the reference, ε4 homozygotes had poorer global cognitive score starting from 65 years; ε4 heterozygotes had better scores between 45 and 55 years, then no difference until poorer cognitive scores from 75 years onwards. In analysis of individual cognitive tests, better cognitive performance in the younger ε4 heterozygotes was primarily attributable to executive function.

Conclusions

Both heterozygous and homozygous ε4 carriers had poorer cognition and greater risk of dementia at older ages. Our findings show some support for a complex antagonist pleiotropic effect ofAPOEε4 heterozygosity over the adult life course, characterized by cognitive advantage in midlife.
The molecular tweezer CLR01 improves behavioral deficits and reduces tau pathology in P301S-tau transgenic mice
Authors: Di Jing , Siddique Ibrar , Li Zizheng , Malki Ghattas , Hornung Simon , Dutta Suman , Hurst Ian , Ishaaya Ella , Wang Austin , Tu Sally , Boghos Ani , Ericsson Ida , Klärner Frank-Gerrit , Schrader Thomas , Bitan Gal
Published: January 2021

Background

Molecular tweezers (MTs) are broad-spectrum inhibitors of abnormal protein aggregation. A lead MT, called CLR01, has been demonstrated to inhibit the aggregation and toxicity of multiple amyloidogenic proteins in vitro and in vivo. Previously, we evaluated the effect of CLR01 in the 3 × Tg mouse model of Alzheimer’s disease, which overexpresses mutant human presenilin 1, amyloid β-protein precursor, and tau and found that subcutaneous administration of the compound for 1 month led to a robust reduction of amyloid plaques, neurofibrillary tangles, and microgliosis. CLR01 also has been demonstrated to inhibit tau aggregation in vitro and tau seeding in cell culture, yet because in Alzheimer’s disease (AD) and in the 3 × Tg model, tau hyperphosphorylation and aggregation are thought to be downstream of Aβ insults, the study in this model left open the question whether CLR01 affected tau in vivo directly or indirectly.

Methods

To determine if CLR01 could ameliorate tau pathology directly in vivo, we tested the compound similarly using the P301S-tau (line PS19) mouse model. Mice were administered 0.3 or 1.0 mg/kg per day CLR01 and tested for muscle strength and behavioral deficits, including anxiety- and disinhibition-like behavior. Their brains then were analyzed by immunohistochemical and biochemical assays for pathological forms of tau, neurodegeneration, and glial pathology.

Results

CLR01 treatment ameliorated muscle-strength deterioration, anxiety-, and disinhibition-like behavior. Improved phenotype was associated with decreased levels of pathologic tau forms, suggesting that CLR01 exerts a direct effect on tau in vivo. Limitations of the study included a relatively short treatment period of the mice at an age in which full pathology is not yet developed. In addition, high variability in this model lowered the statistical significance of the findings of some outcome measures.

Conclusions

The findings suggest that CLR01 is a particularly attractive candidate for the treatment of AD because it targets simultaneously the two major pathogenic proteins instigating and propagating the disease, amyloid β-protein (Aβ), and tau, respectively. In addition, our study suggests that CLR01 can be used for the treatment of other tauopathies in the absence of amyloid pathology.
Trichostatin A ameliorates Alzheimer’s disease-related pathology and cognitive deficits by increasing albumin expression and Aβ clearance in APP/PS1 mice
Authors: Su Qiang , Li Tian , He Pei-Feng , Lu Xue-Chun , Yu Qi , Gao Qi-Chao , Wang Zhao-Jun , Wu Mei-Na , Yang Dan , Qi Jin-Shun
Published: January 2021

Background

Alzheimer’s disease (AD) is an intractable neurodegenerative disorder in the elderly population, currently lacking a cure. Trichostatin A (TSA), a histone deacetylase inhibitor, showed some neuroprotective roles, but its pathology-improvement effects in AD are still uncertain, and the underlying mechanisms remain to be elucidated. The present study aims to examine the anti-AD effects of TSA, particularly investigating its underlying cellular and molecular mechanisms.

Methods

Novel object recognition and Morris water maze tests were used to evaluate the memory-ameliorating effects of TSA in APP/PS1 transgenic mice. Immunofluorescence, Western blotting, Simoa assay, and transmission electron microscopy were utilized to examine the pathology-improvement effects of TSA. Microglial activity was assessed by Western blotting and transwell migration assay. Protein-protein interactions were analyzed by co-immunoprecipitation and LC-MS/MS.

Results

TSA treatment not only reduced amyloid β (Aβ) plaques and soluble Aβ oligomers in the brain, but also effectively improved learning and memory behaviors of APP/PS1 mice. In vitro study suggested that the improvement of Aβ pathology by TSA was attributed to the enhancement of Aβ clearance, mainly by the phagocytosis of microglia, and the endocytosis and transport of microvascular endothelial cells. Notably, a meaningful discovery in the study was that TSA dramatically upregulated the expression level of albumin in cell culture, by which TSA inhibited Aβ aggregation and promoted the phagocytosis of Aβ oligomers.

Conclusions

These findings provide a new insight into the pathogenesis of AD and suggest TSA as a novel promising candidate for the AD treatment.
Gender differences in the efficacy of pioglitazone treatment in nonalcoholic fatty liver disease patients with abnormal glucose metabolism
Authors: Yan Hongmei , Wu Weiyun , Chang Xinxia , Xia Mingfeng , Ma Sicheng , Wang Liu , Gao Jian
Published: January 2021

Background

Pioglitazone is a promising therapeutic method for nonalcoholic fatty liver disease (NAFLD) patients with or without type 2 diabetes. However, there is remarkable variability in treatment response. We analyzed our previous randomized controlled trial to examine the effects of gender and other factors on the efficacy of pioglitazone in treating Chinese nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism.

Methods

This is a post hoc analysis of a previous randomized, parallel controlled, open-label clinical trial (RCT) with an original purpose of evaluating the efficacy of berberine and pioglitazone on NAFLD. The total population (n = 185) was randomly divided into three groups: lifestyle intervention (LSI), LSI + pioglitazone (PGZ) 15 mg qd, and LSI + berberine (BBR) 0.5 g tid, respectively, for 16 weeks. The study used proton magnetic resonance spectroscopy (1H-MRS) to assess liver fat content.

Results

As compared with LSI, PGZ + LSI treatment further decreased liver fat content in women (− 15.24% ± 14.54% vs. − 8.76% ± 13.49%, p = 0.025), but less decreased liver fat content in men (− 9.95% ± 15.18% vs. − 12.64% ± 17.78%, p = 0.046). There was a significant interaction between gender and efficacy of pioglitazone before and after adjustment for age, smoking, drinking, baseline BMI, BMI change, treatment adherence, baseline liver fat content, and glucose metabolism.

Conclusion

The study recommends pioglitazone plus lifestyle intervention for Chinese NAFLD female patients with abnormal glucose metabolism.

Trial registration

Role of Pioglitazone and Berberine in Treatment of Non-Alcoholic Fatty Liver Disease, NCT00633282. Registered on 3 March 2008, https://register.clinicaltrials.gov.
The associations of hostility and defensiveness with telomere length are influenced by sex and health status
Authors: Starnino Louisia , Dupuis Gilles , Busque Lambert , Bourgoin Vincent , Dubé Marie-Pierre , Busseuil David , D’Antono Bianca
Published: January 2021

Background

Shorter telomere length (TL) may indicate premature cellular aging and increased risk for disease. While there is substantial evidence for shorter TL in individuals suffering from psychiatric disorders, data is scarce on maladaptive personality traits related to coronary artery disease (CAD). The purpose of this study was to evaluate the association of TL with hostility and defensiveness in individuals with CAD or other non-cardiovascular illnesses and whether associations were moderated by CAD status and sex.

Methods

One thousand thirty-six individuals (Mage = 65.40 ± 6.73 years) with and without CAD completed the Marlowe-Crowne Social Desirability Scale and the Cook–Medley Hostility Scale. Relative TL was measured via quantitative polymerase chain reaction of total genomic DNA samples. Analyses involved hierarchical regressions on TL, performed separately for hostility and defensiveness, controlling for pertinent sociodemographic, behavioural, and medical risk factors. Separate analyses were performed on 25 healthy participants.

Results

A hostility by sex interaction emerged (β = − .08, p = .006) in the patient groups, where greater hostility was associated with shorter TL in women only (p < .01). A Defensiveness by CAD status interaction (β = − .06, p = .049) revealed longer TL in more defensive CAD patients only (p = .06). In healthy men, shorter TL was observed in those with greater defensiveness (β = .52, p = .006) but lower hostility (β = − .43, p = .049).

Conclusion

Hostility and defensiveness are differentially associated with TL as a function of sex and health status. The implication of these results for health remains to be determined, but propose an additional pathway through which the effect of maladaptive personality traits may contribute to CV and other disease.
Do consumers’ values and attitudes affect food retailer choice? Evidence from a national survey on farmers’ market in Germany
Authors: Cicia Gianni , Furno Marilena , Del Giudice Teresa
Published: January 2021

New trends in food consumption are shaping consumers’ preferences and buying behavior. Non-traditional food retailing and short supply chains (SSCs) are offering bundles of attributes that fit the needs of larger consumers’ segments. Several studies have analyzed factors affecting the choice of traditional and non-traditional food retailing. Very few, however, are those studies that analyze the predictive role of human values and attitudes on the choice of traditional and non-traditional food retailing and supply chains. Usually, due to the low percentage of consumers involved in SSC, analyses of consumer behavior have been conducted using convenience samples. This study, based on online questionnaires submitted to a representative sample composed by 1009 German consumers, tests the hypothesis that the frequency of purchases at farmers’ markets is related to human values: attitude toward the industrialized food market and attitude toward the environment. The econometric approach here implemented computes the model on average and in the tails of the dependent variable, frequency of purchases at farmers’ market, thus investigating the model in a representative sample even where the percentage of non-traditional food retailing consumers is low, as occurs in the tails for low/high frequency of purchases. The questionnaire included the Schwartz value survey, attitudes toward environment and attitude toward industrialized food market, and self-reported estimates of the frequency of buying at farmers’ market. Results suggest that the frequency of buying at farmers’ market is hierarchically related to attitudes and values. The frequency of purchases at farmers’ market is negatively related to industrialized food attitude and positively related to pro-environment attitude. Attitudes are in turn affected by values: self-transcendence has a positive impact on pro-environment attitude and the reverse is true for conservation. Furthermore, these relationships are not constant in the sample: they change according to the selected frequency of purchases.
Case report of combination therapy with Azacytidine, Enasidenib and Venetoclax in primary refractory AML
Authors: Jasra Sakshi , Kazemi Mohammed , Shah Nishi , Chen Jiahao , Fehn Karen , Wang Yanhua , Mantzaris Ioannis , Kornblum Noah , Sica Alejandro , Bachier LizaMarie , Goldfinger Mendel , Gritsman Kira , Braunschweig Ira , Steidl Ulrich , Shastri Aditi , Verma Amit
Published: January 2021

Optimal treatment of acute myeloid leukemia (AML) arising in elderly patients remains a challenge. FDA approval of Ivosidenib and Enasidenib, small molecule inhibitors of isocitrate dehydrogenase enzymes (IDH1 and 2) have opened new avenues of treatment. We present a 60-year-old woman with refractory AML, achieving complete response to the combination therapy of hypomethylating agent, Azacytidine with the IDH2 inhibitor, Enasidenib, and BCL2 inhibitor, Venetoclax. To our knowledge, this is the first case report of a patient with IDH2 mutated refractory AML achieving complete response to combination therapy with azacytidine, enasidenib and venetoclax.
Neglected tropical diseases activities in Africa in the COVID-19 era: the need for a “hybrid” approach in COVID-endemic times
Authors: Molyneux David , Bush Simon , Bannerman Ron , Downs Philip , Shu’aibu Joy , Boko-Collins Pelagie , Radvan Ioasia , Wohlgemuth Leah , Boyton Chris
Published: January 2021

With the coronavirus disease 2019 (COVID-19) pandemic showing no signs of abating, resuming neglected tropical disease (NTD) activities, particularly mass drug administration (MDA), is vital. Failure to resume activities will not only enhance the risk of NTD transmission, but will fail to leverage behaviour change messaging on the importance of hand and face washing and improved sanitation—a common strategy for several NTDs that also reduces the risk of COVID-19 spread. This so-called “hybrid approach” will demonstrate best practices for mitigating the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by incorporating physical distancing, use of masks, and frequent hand-washing in the delivery of medicines to endemic communities and support action against the transmission of the virus through water, sanitation and hygiene interventions promoted by NTD programmes. Unless MDA and morbidity management activities resume, achievement of NTD targets as projected in the WHO/NTD Roadmap (2021–2030) will be deferred, the aspirational goal of NTD programmes to enhance universal health coverage jeopardised and the call to ‘leave no one behind’ a hollow one. We outline what implementing this hybrid approach, which aims to strengthen health systems, and facilitate integration and cross-sector collaboration, can achieve based on work undertaken in several African countries.
All-soft multiaxial force sensor based on liquid metal for electronic skin
Authors: Kim Kyuyoung , Ahn Junseong , Jeong Yongrok , Choi Jungrak , Gul Osman , Park Inkyu
Published: January 2021

Electronic skin (E-skin) capable of detecting various physical stimuli is required for monitoring external environments accurately. Here, we report an all-soft multiaxial force sensor based on liquid metal microchannel array for electronic skin applications. The proposed sensor is composed of stretchable elastomer and Galinstan, a eutectic gallium-indium alloy, providing a high mechanical flexibility and electro-mechanical durability. Liquid metal microchannel arrays are fabricated in multilayer and positioned along a dome structure to detect multi-directional forces, supported by numerical simulation results. By adjusting the height of the dome, we could control the response of the multiaxial sensor with respect to the deflection. As a demonstration of multiaxial force sensing, we were able to monitor the direction of multidirectional forces using a finger by the response of liquid metal microchannel arrays. This research could be applied to various fields including soft robotics, wearable devices, and smart prosthetics for artificial intelligent skin applications.
A sensitive HPLC-FLD method for the quantification of 6-O-demethylmenisporphine isolated from Menispermi Rhizoma in rat plasma
Authors: Wei Jinxia , Shao Jia , Li Yanan , Li Yubo
Published: January 2021

Background

To investigate the pharmacokinetics of 6-O-demethylmenisporphine, an oxoisoaporphine alkaloid with significant anti-tumor activities and isolated from Menispermi Rhizoma, a novel and sensitive HPLC assay was established for 6-O-demethylmenisporphine quantification in rat plasma.

Methods

Peak responses were detected by a highly selective and sensitive fluorescence detector with 426-nm excitation and 514-nm emission wavelengths. Curcumin was employed as the internal standard (IS). A Capcell Pak C18 column (150 mm × 4.6 mm i.d., 5 μm) and an isocratic elution procedure with a flow rate of 1.0 mL/min were used to exclude the endogenous interfering substance. Acetonitrile-water (68:32, v/v) containing 1% formic acid was employed as mobile phase. A 7-point calibration curve that covered the concentration range of 10–2500 ng/mL was constructed.

Results

A good linearity was observed with a correlation coefficient (r) of 0.9993. The lower limit of quantification for 6-O-demethylmenisporphine was 10 ng/mL. The mean recoveries of analyte in rat plasma exceeded 80.5%. The precision at four concentration levels was within 11.3% and the accuracy ranged from − 7.6 to 6.7%.

Conclusion

Using this new HPLC-FLD method, the investigation of plasma samples from rats following oral dosing of neat compound and Menispermi Rhizoma extract was successfully conducted. The results will provide a reference for the evaluation of preclinical safety of 6-O-demethylmenisporphine.
General practitioner practice-based pharmacist input to medicines optimisation in the UK: pragmatic, multicenter, randomised, controlled trial
Authors: Syafhan Nadia Farhanah , Al Azzam Sayer , Williams Steven D. , Wilson Wendy , Brady Jayne , Lawrence Peter , McCrudden Mark , Ahmed Mustafa , Scott Michael G. , Fleming Glenda , Hogg Anita , Scullin Claire , Horne Robert , Ahir Harblas , McElnay James C.
Published: January 2021

Background

Changing demographics across the UK has led to general practitioners (GPs) managing increasing numbers of older patients with multi-morbidity and resultant polypharmacy. Through government led initiatives within the National Health Service, an increasing number of GP practices employ pharmacist support. The purpose of this study is to evaluate the impact of a medicines optimisation intervention, delivered by GP practice-based pharmacists, to patients at risk of medication-related problems (MRPs), on patient outcomes and healthcare costs.

Methods

A multi-centre, randomised (normal care or pharmacist supplemented care) study in four regions of the UK, involving patients (n = 356) from eight GP practices, with a 6-month follow-up period. Participants were adult patients who were at risk of MRPs.

Results

Median number of MRPs per intervention patient were reduced at the third assessment, i.e. 3 to 0.5 (p < 0.001) in patients who received the full intervention schedule. Medication Appropriateness Index (MAI) scores were reduced (medications more appropriate) for the intervention group, but not for control group patients (8 [4–13] to 5 [0–11] vs 8 [3–13] to 7 [3–12], respectively;p = 0.001). Using the intention-to-treat (ITT) approach, the number of telephone consultations in intervention group patients was reduced and different from the control group (1 [0–3] to 1 [0–2] vs 1 [0–2] to 1 [0–3],p = 0.020). No significant differences between groups were, however, found in unplanned hospital admissions, length of hospital stay, number of A&E attendances or outpatient visits. The mean overall healthcare cost per intervention patient fell from £1041.7 ± 1446.7 to £859.1 ± 1235.2 (p = 0.032). Cost utility analysis showed an incremental cost per patient of − £229.0 (95% CI − 594.6, 128.2) and a mean QALY gained of 0.024 (95% CI − 0.021 to 0.065), i.e. indicative of a health status gain at a reduced cost (2016/2017).

Conclusion

The pharmacist service was effective in reducing MRPs, inappropriateness of medications and telephone consultations in general practice in a cost-effective manner.

Trial registration:ClinicalTrials.Gov, NCT03241498. Registered 7 August 2017—Retrospectively registered,https://clinicaltrials.gov/ct2/show/NCT03241498
Exploring healthcare professionals’ knowledge, attitude, and practices towards pharmacovigilance: a cross-sectional survey
Authors: Hussain Rabia , Hassali Mohamed Azmi , Hashmi Furqan , Akram Tayyaba
Published: January 2021

Background

Spontaneous reporting of adverse drug reactions (ADRs) is a method of monitoring the safety of drugs and is the basic strategy for the post-marketing surveillance of the suspected drugs. Despite its importance, there is very little reporting of ADRs by healthcare professionals. The present study has evaluated the knowledge, attitude and practices of health care professionals (HCPs) regarding pharmacovigilance activities in Lahore, Pakistan.

Methods

A cross-sectional questionnaire-based survey was employed, and a convenience sampling was opted to collect the data among physicians, pharmacists and nurses working in tertiary care public hospitals of Lahore, Pakistan from September 2018 to January 2019.

Results

Of the 384 questionnaires distributed, 346 health care professionals responded to the questionnaire (90.10% response rate). Most participants had good knowledge about ADR reporting, but pharmacist had comparatively better knowledge than other HCPs regarding ADR (89.18%) pharmacovigilance system (81.08%), its centres (72.97%) and function (91.89%). Most of the participants exhibited positive attitude regarding ADR reporting, such as 49.1% of physicians (P < 0.05), 70.2% pharmacists and 76.1% nurses showed a positive attitude that they are the most important HCPs to report an ADR. About 64.3% of physicians (P < 0.05) emphasized that consulting other colleagues is important before reporting an ADR. Of all, 77.7% physicians, 75.7% pharmacists and 68% of nurses had positive attitude that ADR reporting is a professional obligation and 67.6% of the pharmacists stated that they have reported ADRs in their workplace and 77.2% nurses have verbally reported ADRs to the concerned personnel or department.

Conclusion

Among all HCPs, pharmacists had better knowledge about ADR reporting and pharmacovigilance. All HCPs had positive attitude and inclination towards ADR reporting. The discrepancies were observed in the practices related to ADR reporting, whereas most of the participants including physicians and nurses did not report any ADR. Based on the above, strategies are needed to educate, train, and empower the HCPs in the domain of pharmacovigilance.
Adhesively bonded joints of jute, glass and hybrid jute/glass fibre-reinforced polymer composites for automotive industry
Authors: de Queiroz H. F. M. , Banea M. D. , Cavalcanti D. K. K.
Published: January 2021

Natural fibre-reinforced composites have attracted a great deal of attention by the automotive industry mainly due to their sustainable characteristics and low cost. The use of sustainable composites is expected to continuously increase in this area as the cost and weight of vehicles could be partially reduced by replacing glass fibre composites and aluminium with natural fibre composites. Adhesive bonding is the preferred joining method for composites and is increasingly used in the automotive industry. However, the literature on natural fibre reinforced polymer composite adhesive joints is scarce and needs further investigation. The main objective of this study was to investigate experimentally adhesively bonded joints made of natural, synthetic and interlaminar hybrid fibre-reinforced polymer composites. The effect of the number of the interlaminar synthetic layers required in order to match the bonded joint efficiency of a fully synthetic GFRP bonded joint was studied. It was found that the failure load of the hybrid jute/glass adherend joints increased by increasing the number of external synthetic layers (i.e. the failure load of hybrid 3-layer joint increased by 28.6% compared to hybrid 2-layer joint) and reached the pure synthetic adherends joints efficiency due to the optimum compromise between the adherend material property (i.e. stiffness and strength) and a diminished bondline peel stress state.
The influence of epoxy adhesive toughness on the strength of hybrid laminate adhesive joints
Authors: Carbas R. J. C. , Marques E. A. S. , da Silva L. F. M.
Published: January 2021

The use of composite materials in structural applications has significantly expanded in recent years. The transport industry accounts for an increasingly larger share of the final structural weight of vehicles, as manufacturers pursue improvements in fuel economy, lighter more efficient designs, and reduction of emissions. However, the delamination of adhesively bonded composite joints causes premature failure of the bond, inhibiting the use of its full potential and leading to inefficient and over-designed components. A hybrid composite metallic material technology is studied in this work, a method inspired in the fibre metal laminate concept, and which combines the best properties of FRPs and metal alloys. The hybrid composite-metallic adherends aims to increase the joint strength in the through thickness direction, minimise peel stresses and limit delamination. The objective of this work was to evaluate the performance of hybrid joints, bonded with different adhesives by comparing them against a reference joint using a conventional Carbon fibre reinforced polymer (CFRP) adherend. The joints were experimentally tested using a universal testing machine for a crosshead speed of 1 mm/min. Numerical models were developed, using the ABAQUS software, to study the behaviour of all joints studied. The numerical predictions of failure loads and modes were compared to the experimentally obtained results.
Lateral variations of electrical conductivity in the lower mantle constrained by Swarm and CryoSat-2 missions
Authors: Velímský Jakub , Knopp Ondřej
Published: January 2021

The electrical conductivity is an important geophysical parameter connected to the thermal, chemical, and mineralogical state of the Earth’s mantle. In this paper, we apply the previously developed methodology of forward and inverse EM induction modeling to the latest version of satellite-derived spherical harmonic coefficients of external and internal magnetic field, and obtain the first 3-D mantle conductivity models with contributions from Swarm and CryoSat-2 satellite data. We recover degree 3 conductivity structures which partially overlap with the shape of the large low-shear velocity provinces in the lower mantle.
Relationship between Na layer and CNA variations observed at Syowa, Antarctic
Authors: Tsuda T. T. , Tanaka Y. -M. , Tozu R. , Takizawa K. , Ejiri M. K. , Nishiyama T. , Kawahara T. D. , Nakamura T.
Published: January 2021

We have performed a statistical data analysis on relationship between simultaneous Na density data and cosmic noise absorption (CNA) data, which is an indicator for energetic particle precipitation, obtained at Syowa, Antarctic in 2000–2002. It is found that the Na densities around the topside of Na layers (above $$\sim 95 \,\hbox {km}$$

∼
95

km

height) tended to be smaller when the CNA was larger. The amounts of Na density responses, i.e., Na density decrease or Na loss, were increasing with magnetic local time (MLT) from dusk hours to dawn hours, and those of CNA responses, i.e., CNA increase, were also increasing with MLT. Thus, there were clear negative correlations between the Na density and CNA variations. These results indicate that the Na loss around the topside of Na layer would be induced by the energetic particle precipitation, and its effect would be more severe in dawn hours.
X-ray fluorescence core scanning, magnetic signatures, and organic geochemistry analyses of Ryukyu Trench sediments: turbidites and hemipelagites
Authors: Hsiung Kan-Hsi , Kanamatsu Toshiya , Ikehara Ken , Usami Kazuko , Horng Chorng-Shern , Ohkouchi Naohiko , Ogawa Nanako O. , Saito Saneatsu , Murayama Masafumi
Published: January 2021

The southwestern Ryukyu Trench represents the ultimate sink of sediments shed from Taiwan into the Philippine Sea, which are mainly transported to the trench by turbidity currents via submarine canyons. Here, we present trench turbidites intercalated with hemipelagites in a gravity pilot core and a piston core acquired on the Ryukyu Trench floor at 6147 m water depth. We performed X-ray fluorescence core scans (ITRAX profiles), magnetic measurements, and organic geochemistry analyses to discriminate turbidites from hemipelagites. We identified 36 turbidites (0.9–4.2 cm thick) based on visual core descriptions and Ca/Fe ratios in the ITRAX profiles. Three of these turbidites show magnetic signatures indicating the presence of pyrrhotite and peaks in the magnetic susceptibility profile, suggesting that Taiwan-sourced sediments are transported to the Ryukyu Trench by long-runout turbidity currents. Pyrrhotite is also present in hemipelagites of the upper part of the retrieved cores, indicating a dominant sediment source in Taiwan over the last several thousand years. Ca/Fe and Zr/Rb ratios in the ITRAX profiles mark distal turbidites (about 1–3 cm thick), and Zr/Rb peaks mainly reflect grain size changes. Detailed analyses of a representative turbidite show good correlation between Ca/Fe and Zr/Rb peaks with upward-coarsening and upward-fining trends that delimit the turbidite. Sedimentary organic matter in hemipelagites is characterized by higher total organic carbon and total nitrogen contents and higher δ13C values than that in turbidites. Our multi-proxy approach employing high-resolution XRF core scans to differentiate turbidites from hemipelagites contributes to establishing a comprehensive view of modern trench sedimentation from Taiwan to the southwestern Ryukyu Trench.
Back to the past: gains and losses in Brazilian society
Authors: Scalon Celi , Caetano André Junqueira , Chaves Hugo , Costa Luana
Published: January 2021

During the first 15 years of the twenty-first century, Brazil’s economic growth and public policies were in the center of the debate on the growing “new middle class.” This new middle class is defined by people’s household income between the upper 10th percentile and the median (Neri, A Nova Classe Média, 2008). Although there has been a consensus about the increase in consumption and the improvement of living conditions for a significant proportion of the population, there is less agreement about the decline in inequality and the change in class distribution. Previous work was directed at challenging the very idea that Brazil had become a middle-class country during the first decade of this century, basically weighting class distribution against income distribution. In this article, we aim to step into the income distribution debate using six income groups as proportions of the median household per-capita income. Our data source is the National Household Sample Survey (PNAD-IBGE/Brazil) in 2001, 2008, and 2015. We analyze groups’ income distribution and characteristics using multinomial logistic models to take into account the effects of socioeconomic variables. We argue that there is significant stability in groups’ income structure during the period, revealing their resistance to inequalities (similar to the findings in the works of Piketty and Souza). We also indicate that the odds of being included in the upper-income categories are quite unequal, considering socioeconomic variables. Finally, we point out that the gains observed from 2001 to 2008 had faded by 2015 when the odds of being included in the upper-income categories were remarkably similar to those of 2001.
The nationalist-indigenous and colonial modernity: an assessment of two sociologists in India
Authors: Patel Sujata
Published: January 2021

This paper analyzes the work of two Indian sociologists who defined the contours of sociology in India in the immediate post-independence decades, M. N. Srinivas and A. R. Desai. It argues that their scholarship can be linked to sociology’s legacy as anthropology in India and its embeddedness in the episteme of colonial modernity. It contends that Srinivas’s methodology, the field view, attempted to make a break with earlier methods, such as book view. However, his three concepts, that of dominant caste, Sanskritization and Westernization were perceived as civilizational attributes and which had organized social change in India. A. R. Desai, a Marxist historical sociologist, made an incisive critique of capitalist exploitation and elaborated the material conditions that led to peasant and working-class revolts. However, his sociology could not unravel the caste-class linkages that organized the Indian ‘social’ which was embedded in Indian nationalism. This paper suggests that a definitive understanding of modernity emerges in Indian sociology in the late 70s when the feminist, dalit and tribal movements interrogated the material basis of contemporary India’s developmentalism and its capitalist and exploitative character.
A 10-year trend in piglet pre-weaning mortality in breeding herds associated with sow herd size and number of piglets born alive
Authors: Koketsu Yuzo , Iida Ryosuke , Piñeiro Carlos
Published: January 2021

Background

Piglet pre-weaning mortality (PWM) is one of the biggest problems regarding sow performance and piglet welfare. Recently, PWM has increased in some countries, but it is not known if there are similar increases in other countries, nor whether increased PWM is related to either increased numbers of piglets born alive (PBA) or to sow herd size. So, the objectives of the present study were 1) to explore the trend in PWM in Spanish sow herds over a recent 10-year period, along with related measurements such as PBA, stillborn piglets, herd productivity and herd size; and 2) to examine the relationships between PWM and the related measurements.

Methods

Herd-level annual data from 2007 to 2016 for 91 herds in Spain were abstracted from a sow database compiled by a veterinary consultancy firm that asked client producers to mail data files on a regular basis. The database software automatically calculated herd-level PWM (%) as follows: the total number of piglets born alive to a sow completely weaned during a year (TPBA) minus the total number of piglets weaned by the completely weaned sow during the year divided by TPBA × 100. All the statistical analyses were performed by using SAS University Edition. A growth curve model was applied to incorporate correlations for all of the observations arising from the same farm.

Results

Over the 10 years, herd means of PWM (standard deviation) increased from 11.9 (4.1) % to 14.4 (3.2) %, and mean PBA increased by 1.9 pigs. Mean age of piglet death during lactation increased by 3.8 days, and later years were significantly associated with herd size and the number of piglets weaned per sow per year (PSY; P <  0.05). Higher PWM was associated with more PBA, more stillborn piglets and small-to-mid herds (lower than the median size: < 570 sows; P <  0.05). Also, there was a significant interaction between the herd size groups and PBA for PWM (P <  0.05): as PBA increased from 9 to 14 pigs, PWM increased by 9.6% in small-to-mid herds, compared with an increase of only 6.6% in large herds (> 570 sows). Furthermore, as PWM decreased from 18 to 8%, herd productivity measured as PSY increased by 2.2 pigs in large herds, compared with only 0.6 pigs in small-to-mid herds.

Conclusion

Large herds were better than small-to-mid herds at alleviating the association between increased PBA and increased PWM. Also, the relationship between decreased PWM and increased herd productivity was improved more in large herds than in small-to-mid herds.