bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of Angiogenesis and Extracellular Matrix Remodeling: Synergistic Effect of Renin-Angiotensin System Inhibitors and Bevacizumab
Authors: Ren Tianshu , Jia Hui , Wu Qiong , Zhang Yan , Ma Qun , Yao Dong , Gao Xudong , Xie Danni , Xu Zihua , Zhao Qingchun , Zhang Yingshi
Published: July 2022

Bevacizumab (Bev) is a humanized vascular endothelial growth factor monoclonal antibody that is used with chemotherapeutic drugs for the treatment of metastatic colorectal cancer (mCRC). Bev-induced hypertension (HT) is the most common adverse reaction during clinical practice. However, at present, appropriate antihypertensive agents for Bev-induced HT are unavailable. In this study, retrospective analysis of clinical data from mCRC patients who received renin-angiotensin system inhibitors (RASIs) showed significant survival benefits of overall survival (OS) and progression-free survival (PFS) over patients who received calcium channel blockers (CCBs) and patients who received no antihypertensive drug (NO: Y2020046 retrospectively registered). An experiment of HCT116 colon cancer cell xenografts in mice confirmed that combined treatment of Bev and lisinopril (Lis), a RASI, synergistically inhibited subcutaneous tumor growth and enhanced the concentration of 5-fluorouracil (5-Fu) in tumor tissues. Our results showed that the addition of Lis did not interfere with the vascular normalization effect promoted by Bev, but also inhibited collagen and hyaluronic acid (HA) deposition and significantly downregulated the expression of TGF-β1 and downstream SMAD signaling components which were enhanced by Bev, ultimately remodeling primary extracellular matrix components. In conclusion, RASIs and Bev have synergistic effect in the treatment of colorectal cancer and RASIs might be an optimal choice for the treatment of Bev-induced HT.
Resistance Training Attenuates Activation of STAT3 and Muscle Atrophy in Tumor-Bearing Mice
Authors: Testa Mayra Tardelli de Jesus , Cella Paola Sanches , Marinello Poliana Camila , Frajacomo Fernando Tadeu Trevisan , Padilha Camila de Souza , Perandini Patricia Chimin , Moura Felipe Arruda , Duarte José Alberto , Cecchini Rubens , Guarnier Flavia Alessandra , Deminice Rafael
Published: July 2022

Purpose

Although the role of signal transducers and activators of transcription (STAT3) in cachexia due to the association of circulating IL-6 and muscle wasting has been extensively demonstrated, the effect of resistance training on STAT3 in mediating muscle atrophy in tumor-bearing mice is unknown. The aim of this study is to investigate the effects of resistance exercise training on inflammatory cytokines and oxidative-mediated STAT3 activation and muscle loss prevention in tumor-bearing mice.

Methods

Male Swiss mice were inoculated with Ehrlich tumor cells and exposed or not exposed to resistance exercise protocol of ladder climbing. Skeletal muscle STAT3 protein content was measured, compared between groups, and tested for possible association with plasma interleukins and local oxidative stress markers. Components of the ubiquitin-proteasome and autophagy pathways were assessed by real-time PCR or immunoblotting.

Results

Resistance training prevented STAT3 excessive activation in skeletal muscle mediated by the overabundance of plasma IL-6 and muscle oxidative stress. These mechanisms contributed to preventing the increased key genes and proteins of ubiquitin-proteasome and autophagy pathways in tumor-bearing mice, such as Atrogin-1, LC3B-II, and Beclin-1. Beyond preventing muscle atrophy, RT also prevented strength loss and impaired locomotor capacity, hallmarks of sarcopenia.

Conclusion

Our results suggest that STAT3 inhibition is central in resistance exercise protective effects against cancer-induced muscle atrophy and strength loss.
Mutant-Allele Tumor Heterogeneity, a Favorable Biomarker to Assess Intra-Tumor Heterogeneity, in Advanced Lung Adenocarcinoma
Authors: Wu Xiaoxuan , Song Peng , Guo Lei , Ying Jianming , Li Wenbin
Published: July 2022

Background

Intra-tumor heterogeneity (ITH) plays a vital role in drug resistance and recurrence of lung cancer. We used a mutant-allele tumor heterogeneity (MATH) algorithm to assess ITH and investigated its association with clinical and molecular features in advanced lung adenocarcinoma.

Methods

Tissues from 63 patients with advanced lung adenocarcinoma were analyzed by next-generation sequencing (NGS) using a panel targeting 520 cancer-relevant genes. We calculated the MATH values from NGS data and further investigated their correlation with clinical and molecular characteristics.

Results

Among the 63 patients with advanced lung adenocarcinoma, the median value of MATH was 33.06. Patients with EGFR mutation had higher level of MATH score than those with wild-type EGFR status (P = 0.008). Patients with stage IV disease showed a trend to have a higher MATH score than those with stage III (P = 0.052). MATH was higher in patients with disruptive TP53 mutations than in those with non-disruptive mutations (P = 0.036) or wild-type sequence (P = 0.023), but did not differ between tumors with non-disruptive mutations and wild-type TP53 (P = 0.867). High MATH is associated with mutations in mismatch repair (MMR) pathway (P = 0.026) and base excision repair (BER) pathway (P = 0.008). In addition, MATH was found to have a positive correlation with tumor mutational burden (TMB) (Spearman ρ = 0.354; P = 0.004). In 26 patients harboring EGFR mutation treated with first generation EGFR TKI as single-agent therapy, the objective response rate was higher in the Low-MATH group than in the High-MATH group (75% vs. 21%; P = 0.016) and Low-MATH group showed a significantly longer progression-free survival than High-MATH group (median PFS: 13.7 months vs. 10.1 months; P = 0.024).

Conclusions

For patients with advanced lung adenocarcinoma, MATH may serve as a clinically practical biomarker to assess intratumor heterogeneity.
Causes of Death Among Prostate Cancer Patients Aged 40 Years and Older in the United States
Authors: Ye Yuzhong , Zheng Yongqiang , Miao Qi , Ruan Hailong , Zhang Xiaoping
Published: July 2022

Purpose

Little is known about the detailed spectrum of the cause of death associated with prostate cancer (PCa). This study systematically characterized the cause of death among patients with PCa.

Methods

Patients aged 40 years and older with primary PCa were identified from the Surveillance, Epidemiology, and End Results program. Mortality rates were estimated. Standardized mortality ratios (SMRs) of non-cancer deaths were calculated to evaluate the risk of death and to compare with the cancer-free population.

Results

This study included 1,170,489 patients with PCa. There were 501,262 deaths, of which 27.4% were due to PCa and 57.0% were due to non-cancer causes. Non-cancer deaths increased over time from 1975 to 2016, and index cancer death decreased continually. The risk of non-cancer deaths was 1.45 times (SMR, 1.45; 95% confidence interval [CI], 1.45–1.46) that of the general population. Cardiovascular disease was the most common non-cancer cause of death, accounting for 30.2% of all deaths among PCa patients. Alzheimer’s disease (SMR, 3.92; 95% CI, 3.85–4.00) had the highest risk of death. The mortality rate and SMR of non-cancer deaths increased with increased follow-up after diagnosis.

Conclusion

Instead of the index cancer, non-cancer comorbidities were the leading cause of death among patients with PCa, and the risk of non-cancer deaths was much higher than among the general population. Clinicians and researchers should be aware of this trend to conduct timely and targeted interventions.
Identified Gefitinib Metabolism-Related lncRNAs can be Applied to Predict Prognosis, Tumor Microenvironment, and Drug Sensitivity in Non-Small Cell Lung Cancer
Authors: Ye Weilong , Wu Zhengguo , Gao Pengbo , Kang Jianhao , Xu Yue , Wei Chuzhong , Zhang Ming , Zhu Xiao
Published: July 2022

Gefitinib has shown promising efficacy in the treatment of patients with locally advanced or metastatic EGFR-mutated non-small cell lung cancer (NSCLC). Molecular biomarkers for gefitinib metabolism-related lncRNAs have not yet been elucidated. Here, we downloaded relevant genes and matched them to relevant lncRNAs. We then used univariate, LASSO, and multivariate regression to screen for significant genes to construct prognostic models. We investigated TME and drug sensitivity by risk score data. All lncRNAs with differential expression were selected for GO/KEGG analysis. Imvigor210 cohort was used to validate the value of the prognostic model. Finally, we performed a stemness indices difference analysis. lncRNA-constructed prognostic models were significant in the high-risk and low-risk subgroups. Immune pathways were identified in both groups at low risk. The higher the risk score the greater the value of exclusion, MDSC, and CAF. PRRophetic algorithm screened a total of 58 compounds. In conclusion, the prognostic model we constructed can accurately predict OS in NSCLC patients. Two groups of low-risk immune pathways are beneficial to patients. Gefitinib metabolism was again validated to be related to cytochrome P450 and lipid metabolism. Finally, drugs that might be used to treat NSCLC patients were screened.
Mechanistic Research for the Student or Educator (Part I of II)
Authors: Leak Rehana K. , Schreiber James B.
Published: July 2022

Many discoveries in the biological sciences have emerged from observational studies, but student researchers also need to learn how to design experiments that distinguish correlation from causation. For example, identifying the physiological mechanism of action of drugs with therapeutic potential requires the establishment of causal links. Only by specifically interfering with the purported mechanisms of action of a drug can the researcher determine how the drug causes its physiological effects. Typically, pharmacological or genetic approaches are employed to modify the expression and/or activity of the biological drug target or downstream pathways, to test if the salutary properties of the drug are thereby abolished. However, experimental techniques have caveats that tend to be underappreciated, particularly for newer methods. Furthermore, statistical effects are no guarantor of their biological importance or translatability across models and species. In this two-part series, the caveats and strengths of mechanistic preclinical research are briefly described, using the intuitive example of pharmaceutical drug testing in experimental models of human diseases. Part I focuses on technical practicalities and common pitfalls of cellular and animal models designed for drug testing, and Part II describes in simple terms how to leverage a full-factorial ANOVA, to test for causality in the link between drug-induced activation (or inhibition) of a biological target and therapeutic outcomes. Upon completion of this series, students will have forehand knowledge of technical and theoretical caveats in mechanistic research, and comprehend that “a model is just a model.” These insights can help the new student appreciate the strengths and limitations of scientific research.
Relation Between Gender and Concomitant Medications With Erythropoietin-Treatment on Wound Healing in Burn Patients. Post Hoc Subgroup-Analysis of the Randomized, Placebo-Controlled Clinical Trial “EPO in Burns”
Authors: Günter Christina Irene , Ilg Felicitas Paula , Hapfelmeier Alexander , Egert-Schwender Silvia , Jelkmann Wolfgang , Giri Shibashish , Bader Augustinus , Machens Hans-Günter ,   and EPO in Burns Study Group
Published: July 2022

Burns are leading causes of mortality and morbidity, including prolonged hospitalization, disfigurement, and disability. Erythropoietin (EPO) is a well-known hormone causing erythropoiesis. However, EPO may play a role in healing acute and chronic wounds due to its anti-inflammatory and pro-regenerative effects. Therefore, the large, prospective, placebo-controlled, randomized, double-blind, multi-center clinical trial “EPO in Burns” was initiated to investigate the effects of EPO versus placebo treatment in severely burned patients. The primary endpoint of “EPO in Burns” was defined as the time elapsed until complete re-epithelialization of a defined split skin graft donor site. Additional analyses of post hoc defined subgroups were performed in view of the primary endpoint. The verum (n 45) and control (n 39) groups were compared with regard to the time it took for study wounds (a predefined split skin graft donor site) to reach the three stages of wound healing (re-epithelialization levels). In addition, the effects of gender (females n 18) and concomitant medications insulin (n 36), non-steroidal anti-inflammatory drugs (NSAIDs) (n 41), and vasopressor agents (n 43) were tested. Life tables were used to compare study groups (EPO vs. placebo) within subgroups. The Cox regression model was applied to evaluate interactions between the study drug (EPO) and concomitant medications for each re-epithelialization level. Using our post hoc defined subgroups, we observed a lower chance of wound healing for women compared to men (in terms of hazard ratio: hr100%: 5.984 [95%-CI: (0.805–44.490), p = 0.080]) in our study population, regardless of the study medication. In addition, results indicated an earlier onset of re-epithelialization in the first days of EPO treatment (EPO: 10% vs. Placebo: 3%). Moreover, the interpretation of the hazard ratio suggested EPO might have a positive, synergistic effect on early stages of re-epithelialization when combined with insulin [hr50%: 1.307 (p = 0.568); hr75%: 1,199 (p = 0.715)], as well as a stabilizing effect on critically ill patients [reduced need for vasopressors in the EPO group (EPO: 44% vs. Placebo 59%)]. However, additional high-quality data from clinical trials designed to address these endpoints are required to gain further insight into these effects.
Studies on Jackfruit–Okra Mucilage-Based Curcumin Mucoadhesive Tablet for Colon Targeted Delivery
Authors: Kurra Pallavi , Narra Kishore , Orfali Raha , Puttugunta Srinivasa Babu , Khan Shah Alam , Meenakshi Dhanalekshmi Unnikrishnan , Francis Arul Prakash , Asdaq Syed Mohammed Basheeruddin , Imran Mohd.
Published: July 2022

The present work investigates a blend of jack fruit mucilage (JFM) and okra mucilage (OKM) as promising mucoadhesive carriers for colon-specific delivery of a curcumin (CMN)-loaded mucoadhesive tablet (CMT) formulation. Formulation optimization was performed using central composite design (CCD) to further decipher the effect of varying proportions of the mucoadhesive carriers JFM and OKG on response factors such as drug release (% DR) and mucoadhesive strength (MA). The optimized formulation CMT (F14) demonstrated a favorable 54.35% in vitro release of CMN in 12 h with release kinetics resulting from a zero-order anomalous diffusion mechanism and MA of 34.1733 ± 1.26 g. Accelerated stability testing of CMT (F14) confirmed a shelf life of about 4.7 years. In vivo drug targeting studies performed using rabbit models in order to observe transit behavior (colon-specific delivery) of the dosage form were assessed by fluoroscopic images of the GI tract. Taking the results together, the results confirm that the combination of JFM and OKM could be exploited as an ideal mucoadhesive carrier for effective delivery of macromolecules to the colon.
Non-Antimicrobial Adjuvant Therapy Using Ticagrelor Reduced Biofilm-Related Staphylococcus aureus Prosthetic Joint Infection
Authors: Pant Narayan , Miranda-Hernandez Socorro , Rush Catherine , Warner Jeffrey , Eisen Damon P.
Published: July 2022

Background: Prosthetic joint infection (PJI), frequently caused by Staphylococcus aureus, leads to a significant arthroplasty failure rate. Biofilm is a crucial virulence factor of S. aureus that is intrinsic to the pathogenesis of PJI. Biofilm-related infections are recalcitrant to antibiotic treatment. Surgical and antibiotic therapy could be combined with non-antibacterial adjuvants to improve overall treatment success. Ticagrelor, a P2Y12 receptor inhibitor antiplatelet drug, is known to have anti-staphylococcal antibacterial and antibiofilm activity. However, the molecular mechanism for ticagrelor’s antibiofilm activity and its efficacy in the treatment of S. aureus PJI are unknown.

Methods: To study the in vitro antibacterial and antibiofilm activity of ticagrelor, broth microdilution and crystal violet staining method were used. Ticagrelor’s effect on the expression of S. aureus biofilm genes (icaA, icaD, ebps, fib, eno, and agr) was studied using the relative quantification method. To test ticagrelor’s in vivo efficacy to treat S. aureus PJI, mice were randomized into five groups (n = 8/group): infected femoral implants treated with ticagrelor alone; infected implants treated with cefazolin alone; infected implants treated with ticagrelor and cefazolin; infected implants treated with phosphate buffer solution (PBS)-positive controls, and sterile implants-negative controls. Ticagrelor was administered orally from day 4 to day 7 post-surgery, while cefazolin was injected intravenously on day 7.

Results: Ticagrelor, alone and with selected antibiotics, showed in vitro antibacterial and antibiofilm activity against S. aureus. Strain-specific downregulation of biofilm-related genes, fib, icaD, ebps, and eno, was shown. In an animal model of biofilm-related S. aureus PJI, ticagrelor alone and combined with cefazolin significantly reduced bacterial concentrations on the implants compared with the positive control group. Ticagrelor significantly reduced bacterial dissemination to periprosthetic tissue compared with the positive controls.

Conclusion: Ticagrelor adjuvant therapy reduced S. aureus PJI in an animal model. However, this study is very preliminary to make a conclusion on the clinical implication of the findings. Based on the current results, more studies are recommended to better understand its implication.
Research on Unmanned Driving Interface Based on Lidar Imaging Technology
Authors: Wang Yuli , Zhu Yanfei , Liu Hui
Published: July 2022

As an autonomous mobile robot, the unmanned intelligent vehicle is often installed with sensors to collect the road environment information, and then process the information and control the speed and steering. In this study, vehicle-mounted camera, laser scanning radar and other sensors were equipped to collect real-time environmental information to efficiently process and accurately detect the specific location and shape of the obstacle. This study then investigated the impact of two In-Vehicle Information Systems (IVISS) on both usability and driving safety. Besides, the laser perception sensing technology was applied to transmit the information of the surrounding around the real-time driving area to the vehicle system. Simulating vehicle checkerboard and hierarchical IVIS interface layouts, we also examined their usability based on task completion time, error rate, NASA-TLX, and System Usability Scale (SUS). It was suggested that the results offer a supporting evidence for further design of IVIS interface.
Expression and Functional Study of BcWRKY1 in Baphicacanthus cusia (Nees) Bremek
Authors: Zeng Meijuan , Zhong Yongjia , Guo Zhiying , Yang Huiyong , Zhu Haisheng , Zheng Liling , Diao Yong
Published: July 2022

Baphicacanthus cusia (Nees) Bremek (B. cusia) is an important medicinal plant. Its effective substances including indigo and indirubin are metabolites in indoleacetate metabolic pathway. Based on a previous transcriptome sequencing analysis, a WRKY transcription factor, BcWRKY1, in B. cusia was identified, showing significant correlation with effective substances from B. cusia. In this study, BcWRKY1 was cloned by reverse transcription-polymerase chain reaction (RT-PCR). Further analysis showed that the BcWRKY1 gene was 916 bp in length, containing three exons and two introns. The open reading frame (ORF) of BcWRKY1 was 534 bp in length and encoded a WRKY domain-containing protein with 177 amino acids residues. Subcellular localization showed that BcWRKY1 protein was mainly localized in the nucleus. It could bind to the W-box motif and its role in transcriptional activation was confirmed in yeast. The function of BcWRKY1 was investigated by overexpressing BcWRKY1 in Arabidopsis thaliana. Metabolic profiles in wild type and BcWRKY1-OX1 transgenic Arabidopsis thaliana were analyzed with LC-MS. Results showed that the metabolic profile was significantly changed in BcWRKY1-OX1 transgenic Arabidopsis thaliana compared with wild type. Furthermore, indole-related metabolites were significantly increased in BcWRKY1-OX1 transgenic Arabidopsis thaliana, and the metabolic pathway analysis showed that flavonoid biosynthesis was significantly enriched. Overexpression of BcWRKY1 significantly changed flavonoid and indole metabolism and indole-related metabolites were significantly upregulated. We postulated that the BcWRKY1 transcription factor might be involved in the regulation of effective substances metabolism in B. cusia.
The Achievement Motive in the Brain: BOLD Responses to Pictures of Challenging Activities Predicted by Implicit Versus Explicit Achievement Motives
Authors: Quirin Markus , Loktyushin Alexander , Küstermann Ekkehard , Kuhl Julius
Published: July 2022

The achievement motive refers to a preference for mastering challenges and competing with some standard of excellence. Along with affiliation and power motives, the achievement motive is typically considered to occur on the level of implicit versus explicit representations. Specifically, whereas implicit motives involve pictorial, emotional goal representations and facilitate corresponding action effortlessly, explicit motives involve propositional (“verbalized”) goal representations but need some effort to translate into action (McClelland et al., 1989). We used functional magnetic resonance imaging (fMRI) to investigate whether and to which degree the implicit and explicit achievement motives differentially predict blood-oxygen-level-dependent (BOLD) responses to pictures of individuals engaging in challenging activities. Whereas the implicit AM predicted activity in areas associated with emotion (orbitofrontal cortex) and visual processing (right dorsolateral prefrontal cortex, premotor and occipital cortices), the explicit AM predicted activity in areas associated with cognitive self-control or verbal goal processing (dorsal anterior cingulate cortex, left dorsolateral prefrontal cortex). The findings support the commonly assumed distinction between implicit and explicit motives with neuronal data. They also suggest that explicit motives require cognitive self-control to overcome potential lacks of motivation.
The Influence of Design Aesthetics on Consumers’ Purchase Intention Toward Cultural and Creative Products: Evidence From the Palace Museum in China
Authors: Li Yang , Li Jie
Published: July 2022

As a symbol of Chinese culture, the Palace Museum undertakes the mission of spreading Chinese culture. In recent years, through the innovative integration of traditional culture, the Palace Museum has provided a series of cultural and creative products to meet consumers’ personalized expectations, which has attracted wide attention from both academia and practice. Cultural and creative products, as one of the means of cultural dissemination by museums, affect the revenue and sustainable development of museums. Thus, it is of great significance to study how consumers arrive at the decision to purchase these products. This article explores the influence mechanism of design aesthetics on consumers’ purchase intention (N = 201). The results show that design aesthetics has a positive influence on consumers’ purchase intention through perceived value and that Chinese traditionality moderates the indirect influence of perceived value. The contributions and implications are discussed.
Moderating Role of Resilience Between Depression and Stress Response of Vocational Middle School Students During the COVID-19 Pandemic
Authors: Jin Mingqi , Ding Lingling , Fan Jiali , Sheng Xin , Luo Bingqing , Hang Ronghua , Feng Linpu , Huang Long
Published: July 2022

Object

In this study, we aimed to explore the influences of stress responses and psychological resilience on depression of vocational middle school students during the initial COVID-19 outbreak in China.

Methods

An online questionnaire survey on the students of a medical school in Jiangxi Province, China, and obtained 3,532 valid questionnaires. A self-compiled general situation questionnaire, Stress Response of COVID-19 Questionnaire, the Resilience Scale for Chinese Adolescents and Center for Epidemiological Studies Depression Scale (CES-D) were used. Hierarchical regression analysis was used to explore the regulatory role of psychological resilience between stress response and depression.

Results

(1) There were significant differences in gender between vocational middle school students' evaluation (t = 3.07, P = 0.002) and defense (t = 3.28, P = 0.001) of the pandemic. Males had higher cognitive evaluation of the pandemic than females, and females had more defense against the pandemic than males. (2) There is a significant difference between vocational middle school students from different grades in depression level (F = 3.62, P = 0.03), pneumonia defense (F = 13.65, P < 0.001) and pneumonia panic (F = 3.10, P = 0.045). (3) Depression level (F = 7.17, P < 0.001), pneumonia evaluation (F = 2.78, P = 0.04) and pneumonia panic (F = 3.32, P = 0.02) of the students concerning the spatial distance of the pandemic. (4) The severity of urban pandemic affects the evaluation of pneumonia among vocational middle school students. (5) Depression was negatively correlated with psychological resilience and pneumonia evaluation, and positively correlated with pneumonia panic. Psychological resilience was positively correlated with pneumonia evaluation and pneumonia defense, and negatively correlated with pneumonia panic. (6) Psychological resilience could reduce the level of depression caused by pneumonia evaluation and pneumonia panic.

Conclusion

There were significant differences in depression level and stress responses in grades, gender and spatial distance of pandemic. Resilience has a significant negative moderator effect on the relationship between pandemic panic and depression. Resilience has a significant positive moderator effect on the relationship between pandemic evaluation and depression.
Understanding COVID-19 Vaccine Hesitancy in Ethnic Minorities Groups in the UK
Authors: Naqvi Maryam , Li Lan , Woodrow Michael , Yadav Punam , Kostkova Patty
Published: July 2022

COVID-19 vaccines have been developed and administered at record pace in order to curtail the impact of the COVID-19 pandemic. Vaccine hesitancy has impacted uptake unequally across different groups. This study explores the drivers for vaccine hesitancy in ethnic minority groups in the UK, the impact of social media on vaccine hesitancy and how vaccine hesitancy may be overcome. Twelve semi-structured interviews were conducted, coded and thematically analyzed with participants from ethnic minority groups in the UK who identified as vaccine hesitant. Social media played a significant role in vaccine hesitancy. For those who considered themselves healthy, seeing misinformation of extreme side effects relating to COVID-19 vaccinations on social media resulted in the opinion that the risk of vaccination is greater than risk from COVID-19 infection. For women, misinformation on social media regarding fertility was a reason for delaying or not getting vaccinated. Participants who had sources of information they trusted in outside of social media were more likely to choose to get vaccinated. This study identified the broad spectrum of views on vaccine hesitancy in ethnic minority groups in the UK. Enabling factors such as a desire to travel, and positive public health messaging can increase vaccine uptake, whereas a lack of trusted sources of information may cause vaccine hesitancy. Further research is required to combat misinformation and conspiracy theories. Effective methods include actively responding and disproving the misinformation. For an inclusive vaccination programme that reduces health inequality, policy makers should build trust amongst marginalized communities and address their concerns through tailored public health messaging.
Impact of the National Reimbursement Drug List Negotiation Policy on Accessibility of Anticancer Drugs in China: An Interrupted Time Series Study
Authors: Zhu Hong , Zhu Jingmin , Zhou Yingyu , Shan Linghan , Li Cui , Cui Yu , Kang Zheng , Jiao Mingli , Liu Huan , Gao Lijun , Wu Qunhong , Hao Yanhua
Published: July 2022

Objective

Since 2016, the Chinese government has been regularly implementing the National Reimbursement Drug List Negotiation (NRDLN) to improve the accessibility of drugs. In the second round of NRDLN in July 2017, 18 anticancer drugs were included. This study analyzed the impact of the NRDLN on the accessibility of these 18 anticancer drugs in China.

Methods

National hospital procurement data were collected from 2015 to 2019. As measurements of drug accessibility, monthly average of drug availability or defined daily dose cost (DDDc) was calculated. Interrupted time series (ITS) analysis was employed to evaluate the impact of NRDLN on drug accessibility. Multilevel growth curve models were estimated for different drug categories, regions or levels of hospitals.

Results

The overall availability of 18 anticancer drugs increased from about 10.5% in 2015 to slightly over 30% in 2019. The average DDDc dropped from 527.93 CNY in 2015 to 401.87 CNY in 2019, with a reduction of 23.88%. The implementation of NRDLN was associated with higher availability and lower costs for all 18 anticancer drugs. We found an increasing level in monthly drug availability (β2 = 2.1126), which ascended more sharply after the implementation of NRDLN (β3 = 0.3656). There was a decreasing level in DDDc before July 2017 (β2 = −108.7213), together with a significant decline in the slope associated with the implementation of NRDLN (β3 = −4.8332). Compared to Traditional Chinese Medicines, the availability of Western Medicines was higher and increased at a higher rate (β3 = 0.4165 vs. 0.1108). Drug availability experienced a larger instant and slope increase in western China compared to other regions, and in secondary hospitals than tertiary hospitals. Nevertheless, regional and hospital-level difference in the effect of NRDLN on DDDc were less evident.

Conclusion

The implementation of NRDLN improves the availability and reduces the cost of some anticancer drugs in China. It contributes to promoting accessibility of anticancer drugs, as well as relieving regional or hospital-level disparities. However, there are still challenges to benefit more patients sufficiently and equally. It requires more policy efforts and collaborative policy combination.
Vibrotactile Perception for Sensorimotor Augmentation: Perceptual Discrimination of Vibrotactile Stimuli Induced by Low-Cost Eccentric Rotating Mass Motors at Different Body Locations in Young, Middle-Aged, and Older Adults
Authors: Pomplun Ella , Thomas Ashiya , Corrigan Erin , Shah Valay A. , Mrotek Leigh A. , Scheidt Robert A.
Published: July 2022

Sensory augmentation technologies are being developed to convey useful supplemental sensory cues to people in comfortable, unobtrusive ways for the purpose of improving the ongoing control of volitional movement. Low-cost vibration motors are strong contenders for providing supplemental cues intended to enhance or augment closed-loop feedback control of limb movements in patients with proprioceptive deficits, but who still retain the ability to generate movement. However, it remains unclear what form such cues should take and where on the body they may be applied to enhance the perception-cognition-action cycle implicit in closed-loop feedback control. As a step toward addressing this knowledge gap, we used low-cost, wearable technology to examine the perceptual acuity of vibrotactile stimulus intensity discrimination at several candidate sites on the body in a sample of participants spanning a wide age range. We also sought to determine the extent to which the acuity of vibrotactile discrimination can improve over several days of discrimination training. Healthy adults performed a series of 2-alternative forced choice experiments that quantified capability to perceive small differences in the intensity of stimuli provided by low-cost eccentric rotating mass vibration motors fixed at various body locations. In one set of experiments, we found that the acuity of intensity discrimination was poorer in older participants than in middle-aged and younger participants, and that stimuli applied to the torso were systematically harder to discriminate than stimuli applied to the forearm, knee, or shoulders, which all had similar acuities. In another set of experiments, we found that older adults could improve intensity discrimination over the course of 3 days of practice on that task such that their final performance did not differ significantly from that of younger adults. These findings may be useful for future development of wearable technologies intended to improve the control of movements through the application of supplemental vibrotactile cues.
Carbon Isotope Discrimination as an Indicator of Vine Water Status is Comparable in Grape Must, Wine, and Distilled Wine Spirits
Authors: Gowdy Mark , Julliard Sébastien , Frouin Marina , Poitou Xavier , Destrac Irvine Agnès , van Leeuwen Cornelis
Published: July 2022

Measurement of carbon isotope discrimination (δ13C) in berry juice sugars provides an integrative indicator of grapevine water status during berry ripening. Characterizing vine water status during this critical period is useful because it has an important effect on the quality of grapes and the resulting wine. The δ13C of the sugar in grapes is also strongly correlated to the δ13C of the ethanol that results when they are fermented into wine. This then provides a means of estimating from a sample of wine the vine water status that existed during the corresponding berry ripening period, and can be used to establish relations between vine water status and specific sensory attributes of wine quality. The same would be possible for evaluating the sensory attributes of wine spirit (eau de vie) if it was understood how the δ13C signal was affected by the distillation process. In this study, the δ13C in eau de vie, produced by a double distillation process similar to that used in the Cognac region of France, was measured and compared to its source wine and parent grape must. A strong relationship was found between the δ13C of grape must and subsequent wine and eau de vie, suggesting the latter can indeed be used to estimate the vine water status that existed during the corresponding berry ripening period. In this way, future studies of sensory attributes of eau de vie can be linked to vine water status during berry ripening, such as has been done previously for wine.
Can the Concentration of a Transcription Factor Affect Gene Expression?
Authors: Koşar Zafer , Erbaş Aykut
Published: July 2022

DNA is the ultimate molecule that encodes life through genes. Genes positioned along the meter-long DNA molecule have to be expressed at the right time and in the right amount via strict regulatory processes. Regulation of a gene starts with the binding of a DNA-binding protein known as a transcription factor (TF) to a target regulatory element along the double-stranded DNA molecule. Often, TFs attach to DNA in a sequence-specific manner and can target DNA motifs of various lengths, yet some TFs can also interact with DNA nonspecifically. The resulting DNA-TF complexes can control gene expression directly via controlling the recruitment of RNA polymerase on the target DNA sequence. Recent single-molecule experiments have added a new dimension to such control mode; the lifetime of a DNA-TF complex (i.e., the residence time of the protein on its DNA site) can function as a regulatory component. This breakthrough inevitably suggests that any physiochemical constituent that can alter the residence time of a DNA-binding protein can also be involved in gene regulation. In this perspective, we argue that a TF protein’s cellular concentration can contribute to the cell-scale transcription activity by modulating the DNA-residence time of the protein. Cells can achieve this either by enabling a concentration-dependent dissociation mechanism or by promoting the formation of multiprotein-DNA complexes. While our discussion here will consider examples from prokaryotic cells, we will also briefly argue that similar mechanisms could also be functional in eukaryotic cells.
The Potential of Immersive Virtual Reality for the Study of Event Perception
Authors: Misersky Julia , Peeters David , Flecken Monique
Published: July 2022

In everyday life, we actively engage in different activities from a first-person perspective. However, experimental psychological research in the field of event perception is often limited to relatively passive, third-person computer-based paradigms. In the present study, we tested the feasibility of using immersive virtual reality in combination with eye tracking with participants in active motion. Behavioral research has shown that speakers of aspectual and non-aspectual languages attend to goals (endpoints) in motion events differently, with speakers of non-aspectual languages showing relatively more attention to goals (endpoint bias). In the current study, native speakers of German (non-aspectual) and English (aspectual) walked on a treadmill across 3-D terrains in VR, while their eye gaze was continuously tracked. Participants encountered landmark objects on the side of the road, and potential endpoint objects at the end of it. Using growth curve analysis to analyze fixation patterns over time, we found no differences in eye gaze behavior between German and English speakers. This absence of cross-linguistic differences was also observed in behavioral tasks with the same participants. Methodologically, based on the quality of the data, we conclude that our dynamic eye-tracking setup can be reliably used to study what people look at while moving through rich and dynamic environments that resemble the real world.
Perspectives on Water Quality Monitoring Approaches for Behavioral Change Research
Authors: Jordan Phil , Cassidy Rachel
Published: July 2022

This review considers enhanced approaches to river water quality monitoring in north-western Europe following a series of study visits (11 sites in 7 countries). Based on the evidence gathered, options were identified and evaluated for their suitability to deliver specific water quality monitoring objectives and with a focus on effecting behavioral change. Monitoring programs were diverse, ranging from enhanced grab sampling and laboratory analysis to sub-hourly sampling of multiple parameters and nutrients in autonomous high-specification, bank-side or mobile laboratories. Only one program out of all the cases evaluated could readily identify influences that had produced behavioral change among stakeholders. This was principally because the other programs were focused on top-down policy change or surveillance rather than specifically focused on influencing behavior. Nevertheless, program researchers were clear that stakeholder engagement potential was very high and that the sites acted as important focus points for discussion on water quality issues, and so part of a suite of tools that might ultimately change behavior. This identifies a space where water quality monitoring solutions could be adapted for behavioral change research.
Management of Long COVID—The CoviMouv' Pilot Study: Importance of Adapted Physical Activity for Prolonged Symptoms Following SARS-CoV2 Infection
Authors: Colas Claire , Bayle Manon , Labeix Pierre , Botelho-Nevers Elisabeth , Gagneux-Brunon Amandine , Cazorla Céline , Schein Flora , Breugnon Emma , Garcin Arnauld , Feasson Léonard , Roche Frédéric , Hupin David
Published: July 2022

Context

After a COVID-19 infection, some patients have persistent symptoms, the most common is fatigue. To prevent it from becoming chronic (post-COVID-19 syndrome), early management before 3 months could be useful. Exercise and education are recommended.

Objective

To assess fatigue in patients with prolonged symptoms after COVID-19 infection and who received a mixed program of remote adapted physical activity and therapeutic education. The secondary objective was to evaluate the efficacy and safety of this training method thanks to aerobic and anaerobic parameters.

Methods

“CoviMouv': From Coaching in Visual to Mouv in real” is a nonrandomized controlled pilot study. Patients in telerehabilitation followed 12 remote exercise sessions and 3 therapeutic education workshops. Patients on traditional rehabilitation followed their program with a community-based physiotherapist.

Results

Fatigue was reduced after the one-month intervention in both groups (p = 0.010). The majority of aerobic parameters were significantly improved, e.g., maximal oxygen uptake (p = 0.005), walking distance (p = 0.019) or hyperventilation values (p = 0.035). The anaerobic parameter was not improved (p = 0.400). No adverse event was declared.

Discussion

Telerehabilitation is a good alternative when a face-to-face program is not possible. This care at an early stage of the disease could help prevent the chronicity of post-COVID-19 symptoms and the installation of vicious circles of physical deconditioning. A larger study would be necessary.
Vancomycin Containing PDLLA and PLGA/β-TCP Inhibit Biofilm Formation but Do Not Stimulate Osteogenic Transformation of Human Mesenchymal Stem Cells
Authors: Kankilic Berna , Bayramli Erdal , Korkusuz Petek , Eroglu Hakan , Sener Burcin , Mutlu Pelin , Korkusuz Feza
Published: July 2022

Aims

Chronic osteomyelitis, including implant-related prosthetic joint infection, is extremely difficult to cure. We develop vancomycin containing release systems from poly(d,l-lactide) (PDLLA) and poly(d,l-lactide-co-glycolide) (PLGA) composites with beta-tricalcium phosphate (β-TCP) to treat methicillin-resistant Staphylococcus aureus osteomyelitis. We ask whether vancomycin containing PDLLA/β-TCP and PLGA/β-TCP composites will prevent early biofilm formation, allow cell proliferation and osteogenic differentiation, and stimulate osteogenic signaling molecules in the absence of an osteogenic medium.

Methods

Composites were produced and characterized with scanning electron microscopy. In vitro vancomycin release was assessed for 6 weeks. Biofilm prevention was calculated by crystal violet staining. Human bone marrow-derived mesenchymal stem cells (hBM-MSCs) and osteosarcoma cell (SaOS-2) proliferation and differentiation were assessed with water soluble tetrazolium salt and alkaline phosphatase (ALP) staining. Real-time quantitative polymerase chain reaction defined osteogenic signaling molecules for hBM-MSCs.

Results

Totally, 3.1 ± 0.2 mg and 3.4 ± 0.4 mg vancomycin released from PDLLA/β-TCP and the PLGA/β-TCP composites, respectively, and inhibited early biofilm formation. hBM-MSCs and SaOS-2 cells proliferated on the composites and stimulated ALP activity of cells. Runt-related transcription factor 2 (RUNX2) and SRY-Box transcription Factor 9 (SOX9) expressions were, however, lower with composites when compared with control.

Conclusion

Vancomycin containing PDLLA/β-TCP and PLGA/β-TCP composites inhibited early biofilm formation and proliferated and differentiated hBM-MSCs and SaOS-2 cells, but osteogenesis-related RUNX2 and SOX9 transcription factors were not strongly expressed in the absence of an osteogenic medium for 14 days.
Oncocytic Carcinoma of the Cranio-Orbital Area: A Case Report
Authors: Yang Peng , Jiang Libin , Liu Honggang , Zhang Jialiang , Kang Jun
Published: July 2022

Oncocytic carcinoma is a malignant tumor characterized by a proliferation of epithelial cells with abundant eosinophilic granular cytoplasm. In this article, we report on the first case of a 61-year-old male patient presenting with oncocytic carcinoma involving the cranio-orbital area. An oncocytic carcinoma in the patient, who reported a sudden decrease in vision in his right eye, was removed through a frontal orbital approach craniotomy. The patient's postoperative development was rapid, and he was admitted to the neurosurgery department for a combined operation after ophthalmological screening. Pathological analysis revealed the tumour cells were large, round or polygonal, and the cytoplasm was finely granular and appeared to be more pleomorphic than the eosinophilic adenoma. Oncocytic carcinoma in the cranio-orbital area is extremely rare. The most effective treatment is early resection to be performed jointly by ophthalmology and neurosurgery, and long-term follow-up and adjuvant chemoradiotherapy are beneficial.
Toxicological Impact and in Vivo Tracing of Rhodamine Functionalised ZIF-8 Nanoparticles
Authors: Goyal Prateek , Soppina Pushpanjali , Misra Superb K. , Valsami-Jones Eugenia , Soppina Virupakshi , Chakraborty Swaroop
Published: July 2022

Metal Organic Frameworks (MOFs) are extensively used for a wide range of applications due to their exceptionally high surface area. MOF particles are conventionally in micron size, but the nanosized MOFs show good transportation/mobility due to their small size, and when combined with the high surface area of MOFs, it makes MOF nanoparticles an ideal candidate to study for environmental remediation. Therefore, it is important to study the ecotoxicological impact of these MOFs. In this study, we developed rhodamine labelled nanoparticles of zinc imidazolate metal organic framework (ZIF-8 MOFs) as a means of in vivo tracing the MOF translocation in C. elegans. Rhodamine B isothiocyanate functionalized ZIF-8 MOFs nanoparticles (RBITC@ZIF-8 MOF nanoparticles; size 44 ± 7 nm) were fed to the worms naturally within a concentration range of 0.16–16.4 μg mg−1. Fluorescence was detected in the pharyngeal and gut lumen regions of the worms after 4 h of treatment, for exposure concentrations >0.163 μg mg−1. A higher intensity of fluorescence was observed at the end of 24 h for all exposure concentrations. Worms treated with RBITC@ZIF-8 MOF concentrations of ≥1.63 μg mg−1 for 24 h showed a bright stable fluorescence signal at the tail region. The uptake of RBITC@ZIF-8 MOF for an exposure concentration of 0.163, 1.63, and 8.2 μg mg−1 was found to be 52.1, 11.4 and 28.6%, respectively. Through this study, we showed that RBITC@ZIF-8 MOFs can be exposed to C. elegans and imaged at low concentrations of ∼0.16 μg mg−1.