bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Influencers of COVID-19 Vaccine Acceptance Among Adults Living in the United States Who Have Accepted or Plan to Accept the Vaccine: An Online Survey
Authors: Duck Angela Allen , Hall Katie C. , Douglas Kimberly , Price Tara S.
Published: April 2022

Purpose

The purpose of this study was to 1) determine the demographic differences between adults who have accepted, or plan to accept, the COVID-19 vaccine and those who will not accept the COVID-19 vaccine and 2) describe the potential influencers in deciding to accept the COVID-19 vaccine among adults living in the United States who have accepted or plan to accept the vaccine.

Design

A cross-sectional design utilizing an online survey was deployed using social media and a crowdsourcing platform.

Setting

United States.

Subjects

One thousand three hundred ninety-five (1395) adults completed the survey. The majority were white, male, between the ages of 25 and 45, and with representation from 50 states and Puerto Rico.

Measures

A two-branched survey was used to assess demographic information, vaccination intention, and 19 potential influencers of COVID-19 vaccine acceptance.

Analysis

Analysis included descriptive statistics and Chi-square tests to determine differences between groups.

Results

A higher proportion of male ( P < .001), married ( P < .001), and college-educated ( P < .001) participants reported acceptance of the vaccine. The factors with the highest mean score of reported level of influence were duty to protect the vulnerable and contribution to move society back to a sense of normalcy.

Conclusion

Understanding the potential influencers of vaccine acceptance may provide insight into strategies that could increase vaccination uptake.
MALVIRUS: an integrated application for viral variant analysis
Authors: Ciccolella Simone , Denti Luca , Bonizzoni Paola , Della Vedova Gianluca , Pirola Yuri , Previtali Marco
Published: April 2022

Background

Being able to efficiently call variants from the increasing amount of sequencing data daily produced from multiple viral strains is of the utmost importance, as demonstrated during the COVID-19 pandemic, in order to track the spread of the viral strains across the globe.

Results

We present , an easy-to-install and easy-to-use application that assists users in multiple tasks required for the analysis of a viral population, such as the SARS-CoV-2. allows to: (1) construct a variant catalog consisting in a set of variations (SNPs/indels) from the population sequences, (2) efficiently genotype and annotate variants of the catalog supported by a read sample, and (3) when the considered viral species is the SARS-CoV-2, assign the input sample to the most likely Pango lineages using the genotyped variations.

Conclusions

Tests on Illumina and Nanopore samples proved the efficiency and the effectiveness of in analyzing SARS-CoV-2 strain samples with respect to publicly available data provided by NCBI and the more complete dataset provided by GISAID. A comparison with state-of-the-art tools showed that is always more precise and often have a better recall.
De novo identification of maximally deregulated subnetworks based on multi-omics data with DeRegNet
Authors: Winkler Sebastian , Winkler Ivana , Figaschewski Mirjam , Tiede Thorsten , Nordheim Alfred , Kohlbacher Oliver
Published: April 2022

Background

With a growing amount of (multi-)omics data being available, the extraction of knowledge from these datasets is still a difficult problem. Classical enrichment-style analyses require predefined pathways or gene sets that are tested for significant deregulation to assess whether the pathway is functionally involved in the biological process under study. De novo identification of these pathways can reduce the bias inherent in predefined pathways or gene sets. At the same time, the definition and efficient identification of these pathways de novo from large biological networks is a challenging problem.

Results

We present a novel algorithm, DeRegNet, for the identification of maximally deregulated subnetworks on directed graphs based on deregulation scores derived from (multi-)omics data. DeRegNet can be interpreted as maximum likelihood estimation given a certain probabilistic model for de-novo subgraph identification. We use fractional integer programming to solve the resulting combinatorial optimization problem. We can show that the approach outperforms related algorithms on simulated data with known ground truths. On a publicly available liver cancer dataset we can show that DeRegNet can identify biologically meaningful subgraphs suitable for patient stratification. DeRegNet can also be used to find explicitly multi-omics subgraphs which we demonstrate by presenting subgraphs with consistent methylation-transcription patterns. DeRegNet is freely available as open-source software.

Conclusion

The proposed algorithmic framework and its available implementation can serve as a valuable heuristic hypothesis generation tool contextualizing omics data within biomolecular networks.
Docosahexaenoic acid supplementation represses the early immune response against murine cytomegalovirus but enhances NK cell effector function
Authors: Wu Shuting , Wang Shanshan , Wang Lili , Peng Hongyan , Zhang Shuju , Yang Qinglan , Huang Minghui , Li Yana , Guan Shuzhen , Jiang Wenjuan , Zhang Zhaohui , Bi Qinghua , Li Liping , Gao Yuan , Xiong Peiwen , Zhong Zhaoyang , Xu Bo , Deng Yafei , Deng Youcai
Published: April 2022

Background

Docosahexaenoic acid (DHA) supplementation is beneficial for several chronic diseases; however, its effect on immune regulation is still debated. Given the prevalence of cytomegalovirus (CMV) infection and because natural killer (NK) cells are a component of innate immunity critical for controlling CMV infection, the current study explored the effect of a DHA-enriched diet on susceptibility to murine (M) CMV infection and the NK cell effector response to MCMV infection.

Results

Male C57BL/6 mice fed a control or DHA-enriched diet for 3 weeks were infected with MCMV and sacrificed at the indicated time points postinfection. Compared with control mice, DHA-fed mice had higher liver and spleen viral loads at day 7 postinfection, but final MCMV clearance was not affected. The total numbers of NK cells and their terminal mature cell subset (KLRG1+and Ly49H+NK cells) were reduced compared with those in control mice at day 7 postinfection but not day 21. DHA feeding resulted in higher IFN-γ and granzyme B expression in splenic NK cells at day 7 postinfection. A mechanistic analysis showed that the splenic NK cells of DHA-fed mice had enhanced glucose uptake, increased CD71 and CD98 expression, and higher mitochondrial mass than control mice. In addition, DHA-fed mice showed reductions in the total numbers and activation levels of CD4+and CD8+T cells.

Conclusions

These results suggest that DHA supplementation represses the early response to CMV infection but preserves NK cell effector functions by improving mitochondrial activity, which may play critical roles in subsequent MCMV clearance.
Tea plant roots respond to aluminum-induced mineral nutrient imbalances by transcriptional regulation of multiple cation and anion transporters
Authors: Hao Jing , Peng Anqi , Li Yingying , Zuo Hao , Li Ping , Wang Jinsong , Yu Keke , Liu Chun , Zhao Shancen , Wan Xiaochun , Pittman Jon K. , Zhao Jian
Published: April 2022

Background

Tea is one of the most popular non-alcoholic beverages in the world for its flavors and numerous health benefits. The tea tree (Camellia sinensis L.) is a well-known aluminum (Al) hyperaccumulator. However, it is not fully understood how tea plants have adapted to tolerate high concentrations of Al, which causes an imbalance of mineral nutrition in the roots.

Results

Here, we combined ionomic and transcriptomic profiling alongside biochemical characterization, to probe the changes of metal nutrients and Al responsive genes in tea roots grown under increasing concentrations of Al. It was found that a low level of Al (~ 0.4 mM) maintains proper nutrient balance, whereas a higher Al concentration (2.5 mM) compromised tea plants by altering micro- and macro-nutrient accumulation into roots, including a decrease in calcium (Ca), manganese (Mn), and magnesium (Mg) and an increase in iron (Fe), which corresponded with oxidative stress, cellular damage, and retarded root growth. Transcriptome analysis revealed more than 1000 transporter genes that were significantly changed in expression upon Al exposure compared to control (no Al) treatments. These included transporters related to Ca and Fe uptake and translocation, while genes required for N, P, and S nutrition in roots did not significantly alter. Transporters related to organic acid secretion, together with other putative Al-tolerance genes also significantly changed in response to Al. Two of these transporters, CsALMT1 and CsALS8, were functionally tested by yeast heterologous expression and confirmed to provide Al tolerance.

Conclusion

This study shows that tea plant roots respond to high Al-induced mineral nutrient imbalances by transcriptional regulation of both cation and anion transporters, and therefore provides new insights into Al tolerance mechanism of tea plants. The altered transporter gene expression profiles partly explain the imbalanced metal ion accumulation that occurred in the Al-stressed roots, while increases to organic acid and Al tolerance gene expression partly explains the ability of tea plants to be able to grow in high Al containing soils. The improved transcriptomic understanding of Al exposure gained here has highlighted potential gene targets for breeding or genetic engineering approaches to develop safer tea products.
Activated TAZ induces liver cancer in collaboration with EGFR/HER2 signaling pathways
Authors: Moon Hyuk , Park Hyunjung , Chae Min Jee , Choi Hye Jin , Kim Do Young , Ro Simon Weonsang
Published: April 2022

Background

Liver cancer is a major global health concern due to the steady increases in its incidence and mortality. Transcription factors, yes-associated protein (YAP) and WW domain-containing transcription regulator protein 1 (WWTR1, also known as TAZ) have emerged as critical regulators in human hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC), the two major types of primary liver cancer. However, our study as well as other previous reports have shown that activation of YAP and TAZ (YAP/TAZ) in adult murine livers is insufficient for the development of liver cancer, suggesting a requirement for an additional oncogenic collaborator for liver carcinogenesis in adulthood. Therefore, we sought to identify the oncogenic partners of YAP/TAZ that promote hepatocarcinogenesis in adults.

Methods

Data analysis of the transcriptome of patients with liver cancer was performed using the national center for biotechnology information (NCBI) gene expression omnibus (GEO) database and the cancer genome atlas (TCGA). The cancer therapeutics response portal (CTRP) was used to investigate the correlation between sensitivity to chemicals and the copy number of TAZ in human cancer cell lines. Transposons encoding constitutively activated forms of TAZ (TAZS89A), BRAF (BRAFV600E), and PIK3CA (PI3KE545K) were used for hydrodynamic tail vein injection. Mice were monitored at least twice per week and sacrificed when moribund. Tumor-bearing livers were formalin fixed for hematoxylin–eosin staining and immunohistochemistry.

Results

Through database analyses, we identified EGFR/HER2 signaling to be essential in human cancers with high TAZ activity. Furthermore, immunohistochemical analyses showed that human HCC and CC tissues with high YAP/TAZ activities exhibited concomitant activation of EGFR/HER2 signaling pathways. To demonstrate that EGFR/HER2 signaling promotes YAP/TAZ-mediated hepatocarcinogenesis, TAZS89A was simultaneously expressed in murine adult livers with BRAFV600E or PI3KE545K, activated forms of effector molecules downstream of EGFR/HER2 signaling pathways. Expression of TAZS89A plus BRAFV600E induced HCC, whereas TAZS89A and PI3KE545K led to the development of CC-like cancer.

Conclusions

Our study demonstrates that TAZ collaborates with EGFR/HER2 signaling pathways to induce both HCC and CC.
CT-707 overcomes hypoxia-mediated sorafenib resistance in Hepatocellular carcinoma by inhibiting YAP signaling
Authors: Chen Zibo , Yuan Tao , Yan Fangjie , Ye Song , Xie Qin , Zhang Bo , Lin Nengmin , He Qiaojun , Yang Bo , Zhu Hong
Published: April 2022

Background

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. Sorafenib is the first-line treatment for advanced HCC, but the anti-cancer effects remain to be improved as indicated by its low response rates and failure to prolong the progression-free survival (PFS). Thus, it is urgent to explore approaches to improve the clinical outcome.

Materials and methods

The effect of Sorafenib in HCC was analyzed by SRB (sulforhodamine B) assay in normoxia and hypoxia, respectively. The different dose combination effect of CT707 and sorafenib was analyzed by SRB assay in hypoxia. Flow cytometry assay was used to detect the cell apoptosis rate with CT707 and sorafenib treatment in hypoxia. Western blotting was used to detect the expression levels of apoptosis -related proteins and the mechanism of CT707 overcome the resistance of sorafenib in hypoxia.

Results

Our study showed that the characteristic intratumor hypoxia of advanced HCC is one of the major factors which mediated the drug resistance towards sorafenib in HCC. And CT-707, a novel multi-kinase inhibitor, could sensitize the hypoxic HCC cells towards sorafenib. Further studies showed that CT-707 abolished the nuclear translocation of Yes Associate-Protein (YAP), which has been demonstrated as one of mechanism of hypoxia-mediated sorafenib-resistance in HCC.

Conclusions

Overall, this study not only favors the development of this novel multi-kinase inhibitor CT-707 as a therapeutic agent against HCC, but also provides a potential strategy to overcome the hypoxia-mediated resistance to sorafenib in HCC patients.
Individual and residency program factors related to depression, anxiety and burnout in physician residents – a Brazilian survey
Authors: de Mélo Silva Júnior Mário Luciano , Valença Marcelo Moraes , Rocha-Filho Pedro Augusto Sampaio
Published: April 2022

Background

Psychological distress is common among medical trainees. This study aimed to assess the frequency of depression, anxiety and burnout among physician residents and their association with both individual and residency program-related factors.

Methods

This was a cross-sectional study applying an online survey in a national-wide sample of medical residents from Brazil. Depression, anxiety, burnout and diurnal somnolence were assessed with validated tools (Patient Health Questionnaire-4, 2 items version of Maslach Burnout Inventory, and Epworth Sleepiness Scale). Socio-demographic and residency program-related factors were measured with internally validated instruments. We performed multivariate binary logistic regression analysis for each of the main outcomes.

Results

Screening for depression, anxiety and burnout was positive respectively in 46.9%, 56.6% and 37.0% of our sample (n = 1,419). Depression was independently related to female sex, longer duty hours, absence of day off, poor learning perception, poor feeling about the residency program, overall occurrence of psychological abuse, anxiety, diurnal somnolence and burnout (AUROC = .859 [95%CI = .840-.878], p < .001). Anxiety was independently associated with female sex, higher age and duty hours, work-personal life conflicts, few classroom activities, providing assistance without supervision, depression and diurnal somnolence (837 [.816-.857], p < .001). Burnout was related to lower age and leisure time, male sex, longer duty hours, absence of day off, provision of care without supervision, choice of the wrong specialty, poor learning, psychological abuse, depression and diurnal somnolence (.780 [.753-.806], p < .001).

Conclusion

Frequency of psychological distress in residency training is high and related to both individuals and environmental factors, namely high workloads, occurrence of psychological abuse, poor faculty supervision, poor learning experience and work-personal life conflicts.
Administrative data deficiencies plague understanding of the magnitude of rape-related crimes in Indian women and girls
Authors: Dandona Rakhi , Gupta Aradhita , George Sibin , Kishan Somy , Kumar G. Anil
Published: April 2022

Background

This paper investigates trends in rape-related crimes against women and girls reported in the Indian administrative data from 2001 to 2018 to assess the burden of crime, describe sub-national variations, and highlight data gaps to address sexual violence effectively in India.

Methods

Data on five rape-related crimes were extracted from the annual reports of National Crimes Record Bureau (NCRB), and included assault with the intent to outrage modesty of woman, rape, insult to the modesty of women, attempt to commit rape, and murder with rape/gang-rape. Rates for all categories combined, and for each crime were estimated for women and girls for India and its states. Trends for type of offender for rape, mean number of people arrested, and legal status of the cases was also assessed.

Results

The rate of all rape-related crime increased from 11.6 in 2001 to 19.8 in 2018 per 100,000 women and girls. Most of the 70.7% increase in rate between 2001 and 2018 was post 2012 following a gang-rape and murder case in India’s capital. The largest proportion of crimes was recorded as assault with the intent to outrage modesty of the woman, followed by rape. The cited offender in rape cases was for the majority a close known person (44·3%) or other known person (43·1%). By the end of 2018, only 9·6% of the cases had completed trials, with acquittals in 73% cases.

Conclusions

The wide variations in the yearly crime rates at state-level highlighted significant issues in data quality including under-reporting, non-comparability, possible bias in data reporting in NCRB, definition of rape-related crime in India, and access in reporting of crimes. Addressing barriers to reporting, improving quality and scope of administrative data recorded on sexual violence is urgently needed for India to meet SDG targets of eliminating all forms of violence against women and girls.
Maximal inspiratory and expiratory flow at moderate altitude: a study of a Latin American population
Authors: Gochicoa-Rangel Laura , Rodríguez-Peralta Keylin Yaoska , Gutiérrez-Bautista Ana Karen , Guzmán-Valderrábano Carlos , Fernández-Plata Rosario , Torre-Bouscoulet Luis , Martínez-Briseño David
Published: April 2022

Background

Peak inspiratory and expiratory flows (PIF, PEF) are parameters used to evaluate the mechanics of the respiratory system. These parameters can vary based on whether they are measured using mechanical devices vs. spirometry and based on the barometric pressure at which the measurements are obtained. Our objectives were (1) to report the normal values and variability of PEF and PIF of a Latin American population living at a moderate altitude (2240 m above sea level), (2) to analyze the adjustment of reference values obtained at sea level with those obtained in healthy subjects living at a moderate altitude, and (3) to assess the correlation between PEF obtained by spirometry (PEFs) and PEF obtained by mechanical devices (PEFm).

Methods

In this prospective and transversal study, men and women with good respiratory health aged between 2.8 and 68 years old were invited to participate. Randomly, they underwent spirometry (to measure PEFs and PIFs) and mechanical flowmetry (to measure PEFm).

Results

A total of 314 subjects participated, with an average age of 24.3 ± 16.4 years; 59% were Women. The main determinants for the reference equations were age, weight, height and sex at birth. The agreement of the PEFm, PEFs and PIFs values was inconsistent with that reported by other authors, even at the same barometric pressure. The association between PEFm and PEFs was r = 0.91 (p < 0.001), and the correlation coefficient of concordance was 0.84.

Conclusions

The PEFm, PEFs, and PIFs measurements in individuals living at moderate altitudes are different from those found by other authors in cities with different barometric pressures and ethnicities.
Gender differences in response to medical red packets (Hongbao, monetary gifts): a questionnaire study on young doctors in China
Authors: Yuan Mengci , Xu Hanhui
Published: April 2022

Background

The acceptance of informal payments by doctors is usually viewed as unethical behavior. However, in China, such behavior is a common practice. In this study, we focus on the gender differences in accepting red packets (informal payments) by young doctors in China.

Methods

A total of 413 young doctors were selected for the study, all of whom were grouped by gender. The questionnaire was designed to include general demographic characteristics, whether they had ever been offered red packets, whether they had ever accepted red packets, the reasons for accepting red packets and so on. Wilcoxon rank-sum test, Pearson’s chi-squared test, univariable and multi-variable logistic regressions were used for all analyses by Stata 17.0 SE and p-value < 0.05 was considered statistically significant.

Results

Compared to women, men were more likely to be offered red packets (69.5% [180/259] vs.53.9% [83/154]), and the odds ratio (OR) was statistically significant after adjusting for age, education, position and geographical areas (adjusted OR 1.81, p = 0.012). In terms of the question of whether or not they had accepted red packets, more male doctors answered “yes” compared to female doctors (33.3% [60/180] vs.15.7% [13/83], adjusted OR 2.80, p = 0.004). However, among those who had accepted red packets, we found that only 42.0% [25/60] of male doctors considered that it was normal to accept such red packets, compared to 85.0% [11/13] of women (adjusted OR 12.01, p = 0.023).

Conclusion

The study revealed that Chinese patients and their families were more likely to offer red packets to male doctors. Secondly, among doctors who had been offered red packets, male doctors were more likely to accept red packets than female doctors. In addition, among doctors who had accepted red packets, female doctors were more likely to believe that it was not morally wrong to accept such red packets.
An assessment of implementation and effectiveness of mass drug administration for prevention and control of schistosomiasis and soil-transmitted helminths in selected southern Malawi districts
Authors: Makaula Peter , Kayuni Sekeleghe Amos , Mamba Kondwani Chidzammbuyo , Bongololo Grace , Funsanani Mathias , Musaya Janelisa , Juziwelo Lazarus Tito , Furu Peter
Published: April 2022

Background

Mass drug administration (MDA) is one of the key interventions recommended by WHO for prevention and control of neglected tropical diseases (NTD). In Malawi, MDA is widely carried out annually since 2009 for prevention and control of schistosomiasis and soil-transmitted helminths (STH). No study has been carried out to assess effectiveness of the MDA approach and to document perceptions of health providers and beneficiaries regarding use of MDA. This study was done to understand how well MDA is being implemented and to identify opportunities for improvement in MDA delivery in Malawi.

Methods

Designed as a cross-sectional and multi-methods research, the study was carried out in three southern Malawi districts of Chiradzulu, Mangochi and Zomba. In each district, four health centres and 16 villages were randomly selected to participate. A mixed-methods approach to data collection focusing on quantitative data for coverage and knowledge, attitudes and practices assessments; and qualitative data for assessing perceptions of health providers and beneficiaries regarding MDA was used. Quantitative data were processed and analyzed using IBM SPSS software version 26 while qualitative data were analysed using NVivo 12 for Windows.

Results

Knowledge levels about schistosomiasis and STH in the districts varied according to disease aspects asked about. Majority are more knowledgeable about what schistosomiasis is (78%) and whether STH are treatable with drugs (97%); with least knowledgeable about the organism that transmits schistosomiasis (18%), types of schistosomiasis (11%) and what causes STH (20%). In 2018 and 2019 the districts registered high coverage rates for praziquantel and albendazole using community-based MDA (73–100%) and using school-based MDA (75–91%). Both the health authorities and community members perceived the MDA approach as good because it brings treatment closer to people.

Conclusion

With the high MDA coverage obtained in communities and schools, the effectiveness of MDA in the target districts is satisfactory. There are, however, several challenges including disproportionate knowledge levels, which are hampering progress towards attainment of the 2030 global NTD goals. There is a need for promotion of community participation and partnerships as well as implementation of other recommended interventions for sustainable prevention and control of schistosomiasis and STH.
United, can we be stronger? Did French general practitioners in multi-professional groups provide more chronic care follow-up during lockdown?
Authors: Zaytseva Anna , Verger Pierre , Ventelou Bruno
Published: April 2022

Background

Given the importance of the continuous follow-up of chronic patients, we evaluated the performance of French private practice general practitioners (GPs) practicing in multi-professional group practices (MGP) regarding chronic care management during the first Covid-19 lockdown in Spring 2020 compared to GPs not in MGP. We consider two outcomes: continuity of care provision for chronic patients and proactivity in contacting these patients.

Methods

The cross-sectional web questionnaire of 1191 GPs took place in April 2020. We exploit self-reported data on: 1) the frequency of consultations for chronic patients during lockdown compared to their “typical” week before the pandemic, along with 2) GPs’ proactive behaviour when contacting their chronic patients. We use probit and bivariate probit models (adjusted for endogeneity of choice of engagement in MGP) to test whether GPs in MGP had significantly different responses to the Covid-19 crisis compared to those practicing outside MGP.

Results

Out of 1191 participants (response rate: 43.1%), around 40% of GPs were female and 34% were younger than 50 years old. Regression results indicate that GPs in MGP were less likely to experience a drop in consultations related to complications of chronic diseases (− 45.3%). They were also more proactive (+ 13.4%) in contacting their chronic patients compared to their peers practicing outside MGP.

Conclusion

We demonstrate that the MGP organisational formula was beneficial to the follow-up of patients with chronic conditions during the lockdown; therefore, it appears beneficial to expand integrated practices, since they perform better when facing a major shock. Further research is needed to confirm the efficiency of these integrated practices outside the particular pandemic setup.
Angiographic complete revascularization versus incomplete revascularization in patients with diabetes mellitus
Authors: Hwang Doyeon , Park Jiesuck , Yang Han-Mo , Yang Seokhun , Kang Jeehoon , Han Jung-Kyu , Park Kyung Woo , Kang Hyun-Jae , Koo Bon-Kwon , Kim Hyo-Soo
Published: April 2022

Background

Considering the nature of diabetes mellitus (DM) in coronary artery disease, it is unclear whether complete revascularization is beneficial or not in patients with DM. We investigated the clinical impact of angiographic complete revascularization in patients with DM.

Methods

A total of 5516 consecutive patients (2003 patients with DM) who underwent coronary stenting with 2nd generation drug-eluting stent were analyzed. Angiographic complete revascularization was defined as a residual SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) score of 0. The patient-oriented composite outcome (POCO, including all-cause death, any myocardial infarction, and any revascularization) and target lesion failure (TLF) at three years were analyzed.

Results

Complete revascularization was associated with a reduced risk of POCO in DM population [adjusted hazard ratio (HR) 0.70, 95% confidence interval (CI) 0.52–0.93, p = 0.016], but not in non-DM population (adjusted HR 0.90, 95% CI 0.69–1.17, p = 0.423). The risk of TLF was comparable between the complete and incomplete revascularization groups in both DM (adjusted HR 0.75, 95% CI 0.49–1.16, p = 0.195) and non-DM populations (adjusted HR 1.11, 95% CI 0.75–1.63, p = 0.611). The independent predictors of POCO were incomplete revascularization, multivessel disease, left main disease and low ejection fraction in the DM population, and old age, peripheral vessel disease, and low ejection fraction in the non-DM population.

Conclusions

The clinical benefit of angiographic complete revascularization is more prominent in patients with DM than those without DM after three years of follow-up. Relieving residual disease might be more critical in the DM population than the non-DM population.

Trial registration The Grand Drug-Eluting Stent registry NCT03507205.
The relationships between FLAIS, a novel insulin sensitivity index, and cardiovascular risk factors in a population-based study
Authors: Karczewska-Kupczewska Monika , Nikołajuk Agnieszka , Kondraciuk Marcin , Stachurska Zofia , Dubatówka Marlena , Szpakowicz Anna , Strączkowski Marek , Kowalska Irina , Kamiński Karol
Published: April 2022

Background

Insulin resistance is a risk factor for cardiovascular disease. Recently, we have developed a novel index, FLAIS (Fasting Laboratory Assessment of Insulin Sensitivity), which accurately reflects insulin sensitivity, measured with hyperinsulinemic-euglycemic clamp, in different groups of subjects. The aim of the present study was to assess the relationship of FLAIS with cardiovascular risk factors in a population-based study.

Methods

The study group comprised 339 individuals from the ongoing Białystok Plus study, without previously known diabetes. Clinical examination, oral glucose tolerance test and the measurement of blood laboratory parameters were performed.

Results

Prediabetes (impaired fasting glucose and/or impaired glucose tolerance) was diagnosed in 165 individuals whereas type 2 diabetes was diagnosed in 19 subjects. FLAIS was lower in individuals with prediabetes and diabetes in comparison with individuals with normal glucose tolerance. FLAIS was significantly related to waist circumference, systolic and diastolic blood pressure, triglycerides, HDL-cholesterol and LDL-cholesterol in the entire study group and in the subgroups with normal glucose tolerance and with prediabetes/diabetes. HOMA-IR, QUICKI and Matsuda index were not related to blood pressure and LDL-cholesterol in individuals with normal glucose tolerance. Majority of the adjusted models with FLAIS were characterized by better fit with the data in comparison with other indices for all cardiovascular risk factors except waist circumference.

Conclusions

FLAIS represents useful index to assess the cluster of insulin resistance-associated cardiovascular risk factors in general population.
Efficient D-allulose synthesis under acidic conditions by auto-inducing expression of the tandem D-allulose 3-epimerase genes in Bacillus subtilis
Authors: Hu Mengkai , Wei Yuxia , Zhang Rongzhen , Shao Minglong , Yang Taowei , Xu Meijuan , Zhang Xian , Rao Zhiming
Published: April 2022

Background

D-allulose, a hexulose monosaccharide with low calorie content and high sweetness, is commonly used as a functional sugar in food and nutrition. However, enzyme preparation of D-allulose from D-frutose was severely hindered by the non-enzymatic browning under alkaline and high-temperature, and the unnecessary by-products further increased the difficulties in separation and extraction for industrial applications. Here, to address the above issue during the production process, a tandem D-allulose 3-epimerase (DPEases) isomerase synergistic expression strategy and an auto-inducible promoter engineering were levered in Bacillus subtilis 168 (Bs168) for efficient synthesis of D-allulose under the acidic conditions without browning.

Results

First, based on the dicistron expression system, two DPEases with complementary functional characteristics from Dorea sp. CAG:317 (DSdpe) and Clostridium cellulolyticum H10 (RCdpe) were expressed in tandem under the promoter HpaII in one cell. A better potential strain Bs168/pMA5-DSdpe-RCdpe increases enzyme activity to 18.9 U/mL at acidic conditions (pH 6.5), much higher than 17.2 and 16.7 U/mL of Bs168/pMA5-DSdpe and Bs168/pMA5-RCdpe, respectively. Subsequently, six recombinant strains based on four constitutive promoters were constructed in variable expression cassettes for improving the expression level of protein. Among those engineered strains, Bs168/pMA5-PspoVG-DSdpe-PsrfA-RCdpe exhibited the highest enzyme activity with 480.1 U/mL on fed-batch fermentation process in a 5 L fermenter at pH 6.5, about 2.1-times higher than the 228.5 U/mL of flask fermentation. Finally, the maximum yield of D-allulose reached as high as 163.5 g/L at the fructose concentration (50% w/v) by whole-cell biocatalyst.

Conclusion

In this work, the engineered recombinant strain Bs168/pMA5-PspoVG-DSdpe-PsrfA-RCdpe was demonstrated as an effective microbial cell factory for the high-efficient synthesis of D-allulose without browning under acidic conditions. Based on the perspectives from this research, this strategy presented here also made it possible to meet the requirements of the industrial hyper-production of other rare sugars under more acidic conditions in theory.
A novel risk score model based on five angiogenesis-related long non-coding RNAs for bladder urothelial carcinoma
Authors: Li Xinyuan , Zhang Chunlin , Peng Xiang , Li Yang , Chen Guo , Gou Xin , Zhou Xiang , Ma Chao
Published: April 2022

Background

Tumour angiogenesis is an independent risk factor for bladder urothelial carcinoma (BUC) progression, but viable and promising antiangiogenic targets are understudied. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play prominent role in the tumour microenvironment and tumour angiogenesis.

Methods

The clinical data of BUC patients were obtained from TCGA database and clinical specimens of 138 BUC patients. Univariate and multivariate COX regression analyses were used to identify survival-related ARLNRs (sARLNRs) from The Molecular Signatures Database v4.0. Fisher’s exact probability method was used to detect the correlations between sARLNRs levels and clinicopathological characteristics. A chain of experiments including FACS, qPCR, immunohistochemistry, tube formation, migration and invasion assays, combining with co-culture models, were utilized to validate the clinical significance and angiogenetic correlation of sARLNRs.

Results

Five sARLNRs were employed to establish an angiogenesis-related risk score model, by which patients in the low-risk group obtained better overall survival than those in the high-risk group. The expression of AC005625.1 and AC008760.1 was significantly related to ECs percentage, tumour size and muscle invasion status. Besides, AC005625.1 and AC008760.1 expressed lower in BUC cell lines and tumour tissues than that in normal urothelial cells and adjacent normal tissues, with much lower levels in more advanced T stages. A prominently higher proportion of ECs was detected in tumour tissues with lower expression of AC005625.1 and AC008760.1. In the co-culture models, we found that knockdown of AC005625.1 and AC008760.1 in BUC cells increased the tube formation, migration and invasion abilities of HUVEC. The expression levels of CD31, VEGF-A, VIMENTIN and N-CADHERIN were also enhanced in HUVEC cells co-cultured with siR-AC005625.1 and siR-AC008760.1-treated T24 cells.

Conclusion

In the study, we identify five sARLNRs and validate their clinical significance, angiogenesis correlation and prognosis-predictive values in BUC. These findings may provide a new perspective and some promising antiangiogenic targets for clinical diagnosis and treatment strategies of BUC.
Technique integration of single-cell RNA sequencing with spatially resolved transcriptomics in the tumor microenvironment
Authors: Yan Hailan , Shi Jinghua , Dai Yi , Li Xiaoyan , Wu Yushi , Zhang Jing , Gu Zhiyue , Zhang Chenyu , Leng Jinhua
Published: April 2022

Background

The tumor microenvironment contributes to tumor initiation, growth, invasion, and metastasis. The tumor microenvironment is heterogeneous in cellular and acellular components, particularly structural features and their gene expression at the inter-and intra-tumor levels.

Main text

Single-cell RNA sequencing profiles single-cell transcriptomes to reveal cell proportions and trajectories while spatial information is lacking. Spatially resolved transcriptomics redeems this lack with limited coverage or depth of transcripts. Hence, the integration of single-cell RNA sequencing and spatial data makes the best use of their strengths, having insights into exploring diverse tissue architectures and interactions in a complicated network. We review applications of integrating the two methods, especially in cellular components in the tumor microenvironment, showing each role in cancer initiation and progression, which provides clinical relevance in prognosis, optimal treatment, and potential therapeutic targets.

Conclusion

The integration of two approaches may break the bottlenecks in the spatial resolution of neighboring cell subpopulations in cancer, and help to describe the signaling circuitry about the intercommunication and its exact mechanisms in producing different types and malignant stages of tumors.
Prenatal and childhood exposure to chlordecone and adiposity of seven-year-old children in the Timoun mother–child cohort study in Guadeloupe (French West Indies)
Authors: Costet Nathalie , Lafontaine Antoine , Rouget Florence , Michineau Léah , Monfort Christine , Thomé Jean-Pierre , Kadhel Philippe , Multigner Luc , Cordier Sylvaine
Published: April 2022

Background

Exposure to persistent environmental organic pollutants may contribute to the development of obesity among children. Chlordecone is a persistent organochlorine insecticide with estrogenic properties that was used in the French West Indies (1973–1993) and is still present in the soil and the water and food consumed by the local population. We studied the association between prenatal and childhood exposure to chlordecone and the adiposity of prepubertal children.

Methods

Within the Timoun Mother–Child Cohort Study in Guadeloupe (French West Indies), 575 children had a medical examination at seven years of age, including adiposity measurements. A Structural Equation Modeling approach was used to create a global adiposity score from four adiposity indicators: the BMI z-score, percentage of fat mass, sum of the tricipital and subscapular skinfold thickness, and waist-to-height ratio. Chlordecone concentrations were measured in cord blood at birth and in the children’s blood at seven years of age. Models were adjusted for prenatal and postnatal covariates. Sensitivity analyses accounted for co-exposure to PCB-153 and pp’-DDE. Mediation analyses, including intermediate birth outcomes, were conducted.

Results

Prenatal chlordecone exposure tended to be associated with increased adiposity at seven years of age, particularly in boys. However, statistical significance was only reached in the third quartile of exposure and neither linear nor non-linear trends could be formally identified. Consideration of preterm birth or birth weight in mediation analyses did not modify the results, as adjustment for PCB-153 and pp’-DDE co-exposures.

Conclusion

Globally, we found little evidence of an association between chlordecone exposure during the critical in utero or childhood periods of development and altered body-weight homeostasis in childhood. Nevertheless, some associations we observed at seven years of age, although non-significant, were consistent with those observed at earlier ages and would be worth investing during further follow-ups of children of the Timoun Mother–Child Cohort Study when they reach puberty.
Extended two-stage designs for environmental research
Authors: Sera Francesco , Gasparrini Antonio
Published: April 2022

Background

The two-stage design has become a standard tool in environmental epidemiology to model multi-location data. However, its standard form is rather inflexible and poses important limitations for modelling complex risks associated with environmental factors. In this contribution, we illustrate multiple design extensions of the classical two-stage method, all implemented within a unified analytic framework.

Methods

We extended standard two-stage meta-analytic models along the lines of linear mixed-effects models, by allowing location-specific estimates to be pooled through flexible fixed and random-effects structures. This permits the analysis of associations characterised by combinations of multivariate outcomes, hierarchical geographical structures, repeated measures, and/or longitudinal settings. The analytic framework and inferential procedures are implemented in the R package mixmeta.

Results

The design extensions are illustrated in examples using multi-city time series data collected as part of the National Morbidity, Mortality and Air Pollution Study (NMMAPS). Specifically, four case studies demonstrate applications for modelling complex associations with air pollution and temperature, including non-linear exposure–response relationships, effects clustered at multiple geographical levels, differential risks by age, and effect modification by air conditioning in a longitudinal analysis.

Conclusions

The definition of several design extensions of the classical two-stage design within a unified framework, along with its implementation in freely-available software, will provide researchers with a flexible tool to address novel research questions in two-stage analyses of environmental health risks.
Guidelines development protocol and findings: part of the 2021 Australian evidence‐based guidelines for diabetes‐related foot disease
Authors: Lazzarini Peter A. , Raspovic Anita , Prentice Jenny , Commons Robert J. , Fitridge Robert A. , Charles James , Cheney Jane , Purcell Nytasha , Twigg Stephen M. ,   Australian Diabetes‐related Foot Disease Guidelines & Pathways Project
Published: April 2022

Background

Diabetes‐related foot disease (DFD) is a leading cause of the Australian disease burden. The 2011 Australian DFD guidelines were outdated. We aimed to develop methodology for systematically adapting suitable international guidelines to the Australian context to become the new Australian evidence‐based guidelines for DFD.

Methods

We followed the Australian National Health Medical Research Council (NHMRC) guidelines for adapting guidelines. We systematically searched for all international DFD guideline records. All identified records were independently screened and assessed for eligibility. Those deemed eligible were further assessed and included if scoring at least moderate quality, suitability and currency using AGREE II and NHMRC instruments. The included international guidelines had all recommendations extracted into six sub‐fields: prevention, wound classification, peripheral artery disease, infection, offloading and wound healing. Six national panels, each comprising 6–8 multidisciplinary national experts, screened all recommendations within their sub‐field for acceptability and applicability in Australia using an ADAPTE form. Where panels were unsure of any acceptability and applicability items, full assessments were undertaken using a GRADE Evidence to Decision tool. Recommendations were adopted, adapted, or excluded, based on the agreement between the panel's and international guideline's judgements. Each panel drafted a guideline that included all their recommendations, rationale, justifications, and implementation considerations. All underwent public consultation, final revision, and approval by national peak bodies.

Results

We screened 182 identified records, assessed 24 full text records, and after further quality, suitability, and currency assessment, one record was deemed a suitable international guideline, the International Working Group Diabetic Foot Guidelines (IWGDF guidelines). The six panels collectively assessed 100 IWGDF recommendations, with 71 being adopted, 27 adapted, and two excluded for the Australian context. We received 47 public consultation responses with > 80% (strongly) agreeing that the guidelines should be approved, and ten national peak bodies endorsed the final six guidelines. The six guidelines and this protocol can be found at: https://www.diabetesfeetaustralia.org/new‐guidelines/

Conclusion

New Australian evidence‐based guidelines for DFD have been developed for the first time in a decade by adapting suitable international guidelines. The methodology developed for adaptation may be useful for other foot‐related conditions. These new guidelines will now serve as the national multidisciplinary best practice standards of DFD care in Australia.
Experimental demonstration and pan-structurome prediction of climate-associated riboSNitches in Arabidopsis
Authors: Ferrero-Serrano Ángel , Sylvia Megan M. , Forstmeier Peter C. , Olson Andrew J. , Ware Doreen , Bevilacqua Philip C. , Assmann Sarah M.
Published: April 2022

Background

Genome-wide association studies (GWAS) aim to correlate phenotypic changes with genotypic variation. Upon transcription, single nucleotide variants (SNVs) may alter mRNA structure, with potential impacts on transcript stability, macromolecular interactions, and translation. However, plant genomes have not been assessed for the presence of these structure-altering polymorphisms or “riboSNitches.”

Results

We experimentally demonstrate the presence of riboSNitches in transcripts of twoArabidopsisgenes,ZINC RIBBON 3(ZR3) andCOTTON GOLGI-RELATED 3(CGR3), which are associated with continentality and temperature variation in the natural environment. These riboSNitches are also associated with differences in the abundance of their respective transcripts, implying a role in regulating the gene's expression in adaptation to local climate conditions. We then computationally predict riboSNitches transcriptome-wide in mRNAs of 879 naturally inbredArabidopsisaccessions. We characterize correlations between SNPs/riboSNitches in these accessions and 434 climate descriptors of their local environments, suggesting a role of these variants in local adaptation. We integrate this information in CLIMtools V2.0 and provide a new web resource, T-CLIM, that reveals associations between transcript abundance variation and local environmental variation.

Conclusion

We functionally validate two plant riboSNitches and, for the first time, demonstrate riboSNitch conditionality dependent on temperature, coining the term “conditional riboSNitch.” We provide the first pan-genome-wide prediction of riboSNitches in plants. We expand our previous CLIMtools web resource with riboSNitch information and with 1868 additionalArabidopsisgenomes and 269 additional climate conditions, which will greatly facilitate in silico studies of natural genetic variation, its phenotypic consequences, and its role in local adaptation.