bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated high-throughput small RNA and transcriptome sequencing unveil the shape-dependent toxicity of nano-alumina in rat astrocytes
Authors: Chen Yuanyuan , Dong Li , Deng Fuchang , Cao Yaqiang , Fu Yuanzheng , Zhu Mu , Qin Guangqiu , Schultz Dayna , Shekh Kamran , Tang Song
Published: August 2021

Background

The large-scale applications of alumina nanoparticles (Al2O3-NPs), one of the most important NPs in the global market, are causing severe damages to the environment and human health. Our previous research has revealed a critical role of nanoparticle morphology (e.g., flake and rod) in determining the toxic potencies of Al2O3-NPs, where nanorods demonstrated a significantly stronger toxic response than that of nanoflakes. However, their underlying mechanisms have not been completely elucidated yet. In the present study, we evaluated and compared the potential toxicological mechanisms of two shapes of γ-Al2O3-NPs (flake versus rod) by measuring miRNA and mRNA profiles of astrocytes in rat cerebral cortex, ex vivo.

Results

A total of 269 mRNAs and 122 miRNAs, 180 mRNAs and 116 miRNAs were differentially expressed after nanoflakes or nanorods exposure, respectively. Among them, 55 miRNAs (e.g., miR-760-5p, miR-326-3p, and miR-35) and 105 mRNAs (e.g., Kdm4d, Wdr62, and Rps6) showed the same trend between the two shapes. These miRNAs and mRNAs were mainly involved in apoptosis, inflammatory pathways (e.g., NF-kappa B), carcinogenic pathways (e.g., MAPK, p53, Notch, Rap1, and Ras), and cellular lipid metabolisms (e.g., glycerolipid metabolism, sphingolipid, and ether lipid metabolism). However, the remaining miRNAs and mRNAs either showed an opposite trend or only changed by a particular shape. Nanorods could specifically alter the changes of PI3K/Akt, AMPK and TNF pathways, cell cycle, and cellular senescence, while nanoflakes caused the changes of Toll and lmd signaling pathways.

Conclusions

Combined with previous research results, we further revealed the potential biomolecular mechanisms leading to the stronger toxicity of nanorods than that of nanoflakes, and multi-omics is a powerful approach to elucidate morphology-related mode of actions.
Genome-wide association study of individual sugar content in fruit of Japanese pear (Pyrus spp.)
Authors: Nishio Sogo , Hayashi Takeshi , Shirasawa Kenta , Saito Toshihiro , Terakami Shingo , Takada Norio , Takeuchi Yukie , Moriya Shigeki , Itai Akihiko
Published: August 2021

Background

Understanding mechanisms of sugar accumulation and composition is essential to determining fruit quality and maintaining a desirable balance of sugars in plant storage organs. The major sugars in mature Rosaceae fruits are sucrose, fructose, glucose, and sorbitol. Among these, sucrose and fructose have high sweetness, whereas glucose and sorbitol have low sweetness. Japanese pear has extensive variation in individual sugar contents in mature fruit. Increasing total sugar content and that of individual high-sweetness sugars is a major target of breeding programs. The objective of this study was to identify quantitative trait loci (QTLs) associated with fruit traits including individual sugar accumulation, to infer the candidate genes underlying the QTLs, and to assess the potential of genomic selection for breeding pear fruit traits.

Results

We evaluated 10 fruit traits and conducted genome-wide association studies (GWAS) for 106 cultivars and 17 breeding populations (1112 F1 individuals) using 3484 tag single-nucleotide polymorphisms (SNPs). By implementing a mixed linear model and a Bayesian multiple-QTL model in GWAS, 56 SNPs associated with fruit traits were identified. In particular, a SNP located close to acid invertase genePPAIV3on chromosome 7 and a newly identified SNP on chromosome 11 had quite large effects on accumulation of sucrose and glucose, respectively. We used ‘Golden Delicious’ doubled haploid 13 (GDDH13), an apple reference genome, to infer the candidate genes for the identified SNPs. In the region flanking the SNP on chromosome 11, there is a tandem repeat ofearly responsive to dehydration(ERD6)-like sugar transporter genes that might play a role in the phenotypes observed.

Conclusions

SNPs associated with individual sugar accumulation were newly identified at several loci, and candidate genes underlying QTLs were inferred using advanced apple genome information. The candidate genes for the QTLs are conserved across Pyrinae genomes, which will be useful for further fruit quality studies in Rosaceae. The accuracies of genomic selection for sucrose, fructose, and glucose with genomic best linear unbiased prediction (GBLUP) were relatively high (0.67–0.75), suggesting that it would be possible to select individuals having high-sweetness fruit with high sucrose and fructose contents and low glucose content.
Risk factors for mortality in patients over 70 years old with COVID-19 in Wuhan at the early break: retrospective case series
Authors: Zhu Xu , Yuan Wenzheng , Shao Junwei , Huang Kesheng , Wang Qingbo , Yao Shuang , Lu Wei , Liu Li , Fu Tao
Published: August 2021

Background

Elderly patients with COVID-19 were shown to have a high case-fatality rate. We aimed to explore the risk factors associated with death in patients over 70 years old (yr).

Methods

In this retrospective study, we enrolled consecutively hospitalized patients over 70 yr with COVID-19 between January 20 and February 15, 2020 in Renmin Hospital of Wuhan University. Epidemiological, demographic, and clinical data were collected. Clinical subtypes, including mild, moderate, severe, and critical types, were used to evaluate the severity of disease. Patients were classified into two groups: survivor and non-survivor groups. Clinical data were compared between the two groups. Univariable and multivariable Cox regression methods were used to explore the risk factors.

Results

A total of 147 patients were enrolled. The case-fatality rate was 28.6%. Multivariable Cox proportional hazard regression showed that clinical subtypes, including the severe type (HR = 2.983, 95% CI: 1.231–7.226, P = 0.016) and the critical type (HR = 3.267, 95%CI: 1.009–10.576, P = 0.048), were associated with increasing risk of death when compared with the general type. Blood urea nitrogen greater than 9.5 mmol/L (HR = 2.805, 95% CI: 1.141–6.892, P = 0.025) on admission was an independent risk factor for death among laboratory findings.

Conclusion

The patients over 70 yr with COVID-19 had a high case-fatality rate. The risk factors, including clinical subtypes and blood urea nitrogen greater than 9.5 mmol/L, could help physicians to identify elderly patients with poor clinical outcomes at an early stage.
Evaluation of China’s Hubei control strategy for COVID-19 epidemic: an observational study
Authors: Liu Yu , Zheng Fangfang , Du Zhicheng , Li Jinghua , Gu Jing , Jiang Mei , Yoneoka Daisuke , Gilmour Stuart , Hao Yuantao
Published: August 2021

Background

To fight against COVID-19, many policymakers are wavering on stricter public health interventions. Examining the different strategies both in and out of China’s Hubei province, which contained the epidemic in late February 2020, could yield valuable guidance for the management of future pandemics. This study assessed the response process and estimated the time-varying effects of the Hubei control strategy. Analysis of these strategies provides insights for the design and implementation of future policy interventions.

Methods

We retrospectively compared the spread and control of COVID-19 between China’s Hubei (excluding Wuhan) and non-Hubei areas using data that includes case reports, human mobility, and public health interventions from 1 January to 29 February 2020. Static and dynamic risk assessment models were developed to statistically investigate the effects of the Hubei control strategy on the virus case growth after adjusting importation risk and policy response timing with the non-Hubei strategy as a control.

Results

The analysis detected much higher but differential importation risk in Hubei. The response timing largely coincided with the importation risk in non-Hubei areas, but Hubei areas showed an opposite pattern. Rather than a specific intervention assessment, a comprehensive comparison showed that the Hubei control strategy implemented severe interventions characterized by unprecedentedly strict and ‘monitored’ self-quarantine at home, while the non-Hubei strategy included physical distancing measures to reduce contact among individuals within or between populations. In contrast with the non-Hubei control strategy, the Hubei strategy showed a much higher, non-linear and gradually diminishing protective effect with at least 3 times fewer cases.

Conclusions

A risk-based control strategy was crucial to the design of an effective response to the COVID-19 outbreak. Our study demonstrates that the stricter Hubei strategy achieves a stronger controlling effect compared to other strategies. These findings highlight the health benefits and policy impacts of precise and differentiated strategies informed by constant monitoring of outbreak risk.
Adoption of evidence-informed guidelines in prescribing protease inhibitors for HIV-Tuberculosis co-infected patients on rifampicin and effects on HIV treatment outcomes in Uganda
Authors: Mulindwa Frank , Castelnuovo Barbara , Kirenga Bruce , Kalibbala Dennis , Haguma Priscilla , Muddu Martin , Semitala Fred C.
Published: August 2021

Background

We aimed to determine how emerging evidence over the past decade informed how Ugandan HIV clinicians prescribed protease inhibitors (PIs) in HIV patients on rifampicin-based tuberculosis (TB) treatment and how this affected HIV treatment outcomes.

Methods

We reviewed clinical records of HIV patients aged 13 years and above, treated with rifampicin-based TB treatment while on PIs between1st—January -2013 and 30th—September—2018 from twelve public HIV clinics in Uganda. Appropriate PI prescription during rifampicin-based TB treatment was defined as; prescribing doubled dose lopinavir/ritonavir- (LPV/r 800/200 mg twice daily) and inappropriate PI prescription as prescribing standard dose LPV/r or atazanavir/ritonavir (ATV/r).

Results

Of the 602 patients who were on both PIs and rifampicin, 103 patients (17.1% (95% CI: 14.3–20.34)) received an appropriate PI prescription. There were no significant differences in the two-year mortality (4.8 vs. 5.7%,P = 0.318), loss to follow up (23.8 vs. 18.9%,P = 0.318) and one-year post TB treatment virologic failure rates (31.6 vs. 30.7%,P = 0.471) between patients that had an appropriate PI prescription and those that did not. However, more patients on double dose LPV/r had missed anti-retroviral therapy (ART) days (35.9 vs 21%,P = 0.001).

Conclusion

We conclude that despite availability of clinical evidence, double dosing LPV/r in patients receiving rifampicin-based TB treatment is low in Uganda’s public HIV clinics but this does not seem to affect patient survival and viral suppression.
Prevalence and influencing risk factors of eczema among preschool children in Urumqi city: a cross-sectional survey
Authors: Shi Haonan , Wan Guangsheng , Wang Tingting , Zhu Jia , Jiang Lan , Ma Shaowei , Yao Jian , Yin Zhe , Maimaiti Murizhati , Dong Huijuan
Published: August 2021

Background

Eczema is a chronic inflammatory disease associated with impaired quality of life. We identified indoor environmental risk factors, to provide strong evidence for the prevention and control of eczema in preschool children.

Methods

Using a cross-sectional study with stratified random cluster sampling, we conducted a self-administered questionnaire survey among 8153 parents of children aged 2–8 years in 60 kindergartens in six districts of Urumqi city during August 2019.

Results

Among 8153 preschool children, 12.0% of the children have been diagnosed with eczema. Multivariate logistic regression analysis showed that caesarean section (odds ratio [OR] = 1.18, 95% confidence interval [CI]: 1.03–1.36), being an only child (OR = 1.36, 95% CI: 1.18–1.57), presence of mould or moisture in the mother’s home before pregnancy (OR = 1.53, 95% CI: 1.17–2.00), presence of flies or mosquitoes in the dwelling currently (OR = 1.31, 95% CI: 1.10–1.55), pets kept in the child’s home currently (OR = 1.23, 95% CI: 1.01–1.51), presence of pets during child’s first year (OR = 1.45, 95% CI: 1.14–1.85), and family history of eczema (OR = 3.53, 95% CI: 2.98–4.19) are the risk factors for the development of eczema, whereas ethnicity other than the Han Chinese (OR = 0.77, 95% CI: 0.61–0.96) is a protective factor for eczema.

Conclusion

Preschool children in Urumqi are at a high risk of eczema, particularly those of the Han Chinese ethnicity. Parents should be attentive to the indoor living environment of children and take actions to reduce indoor humidity, pest control and elimination, and avoid raising pets to reduce the risk of development of eczema in children.
Smoking is associated with worse outcomes of COVID-19 particularly among younger adults: a systematic review and meta-analysis
Authors: Patanavanich Roengrudee , Glantz Stanton A.
Published: August 2021

Background

Smoking impairs lung immune function and damages upper airways, increasing risks of contracting and severity of infectious diseases. This paper quantifies the association between smoking and COVID-19 disease progression.

Methods

We searched PubMed and Embase for studies published from January 1–May 25, 2020. We included studies reporting smoking behavior of COVID-19 patients and progression of disease, including death. We used random effects meta-analysis, meta-regression and locally weighted regression and smoothing to examine relationships in the data.

Results

We identified 46 peer-reviewed papers with a total of 22,939 COVID-19 patients, 5421 (23.6%) experienced disease progression and 2914 (12.7%) with a history of smoking (current and former smokers). Among those with a history of smoking, 33.5% experienced disease progression, compared with 21.9% of non-smokers. The meta-analysis confirmed an association between ever smoking and COVID-19 progression (OR 1.59, 95% CI 1.33–1.89,p = 0.001). Ever smoking was associated with increased risk of death from COVID-19 (OR 1.19, 95% CI 1.02–1.39,p = 0.003). We found no significant difference (p = 0.864) between the effects of ever smoking on COVID-19 disease progression between adjusted and unadjusted analyses, suggesting that smoking is an independent risk factor for COVID-19 disease progression. We also found the risk of having COVID-19 progression higher among younger adults (p = 0.001), with the effect most pronounced among younger adults under about 45 years old.

Conclusions

Smoking is an independent risk for having progression of COVID-19, including mortality. The effects seem to be higher among young people. Smoking prevention and cessation should remain a priority for the public, physicians, and public health professionals during the COVID-19 pandemic.
Screening of miRNAs in plasma as a diagnostic biomarker for cardiac disease based on optimization of extraction and qRT-PCR condition assay through amplification efficiency
Authors: Ban Eunmi , Kwon Haejin , Seo Hong Seog , Yoo Young Sook , Song Eun Joo
Published: August 2021

Background

Although quantitative real-time PCR (qRT-PCR) is a common and sensitive method for miRNAs analysis, it is necessary to optimize conditions and minimize qRT-PCR inhibitors to achieve reliable results. The aim of this study was to minimize interference by contaminants in qRT-PCR, maximize product yields for miRNA analyses, and optimize PCR conditions for the reliable screening of miRNAs in plasma.

Methods

The annealing temperature was first optimized by assessing amplification efficiencies. The effects of extraction conditions on levels of inhibitors that interfere with PCR were evaluated. The tested extraction conditions were the volume of the upper layer taken, number of chloroform extractions, and the inclusion of ethanol washing, a process that reduces PCR interference during RNA extraction using TRIzol.

Results

An acceptable amplification efficiency of RT-qPCR was achieved by the optimization of the annealing temperature of the tested miRNAs and by the collection a supernatant volume corresponding to about 50% of the volume of TRIzol with triple chloroform extraction. These optimal extraction and PCR conditions were successfully applied to plasma miRNA screening to detect biomarker candidates for the diagnosis of acute myocardial infarction.

Conclusion

This is the first study to optimize extraction and qRT-PCR conditions, while improving miRNA yields and minimizing the loss of extracted miRNA by evaluations of the amplification efficiency.
Assessment of root morphology and canal configuration of maxillary premolars in a Saudi subpopulation: a cone-beam computed tomographic study
Authors: Al‑Zubaidi Saad M. , Almansour Moazzy I. , Al Mansour Nada N. , Alshammari Ahad S. , Alshammari Ahad F. , Altamimi Yazeed S. , Madfa Ahmed A.
Published: August 2021

Background

The objective of this study was to use CBCT to look into the root canal morphology of maxillary premolars in a Saudi Arabian subpopulation and associate the results to existing canal morphology classifications.

Methods

The sample size for this analysis was 500 right and left untreated maxillary first and second premolars with fully formed roots from 250 Saudi residents (125 male and 125 female). The following observations were made using CBCT on the teeth related: (1) The number and morphology of roots; (2) The canal morphology for each root according to Vertucci's classification. The frequency and similarities between the right and left sides, as well as between females and males, were studied. The Chi-square test was used to assess the results.

Results

Of the 500 maxillary first premolars studied, 199 teeth had one root (39.8%), whilst 293 (58.6%) were two-rooted. Three-rooted maxillary first premolars were found in 8 (1.6%). For maxillary second premolars, 416 premolars had one root (83.2%), whilst 79 (15.8%) had two roots and the rest 5 (1.0%) were three roots. There were significant differences of number of root were found between groups (p > 0.05). For maxillary first premolar, Type IV was the most frequent, accounting for 57.8% of the sample (n = 289), followed by type II (32.8%, n = 164). For maxillary second premolar, Type I was mainly occurrence 302 (60.4%), followed by Type II (16.4%, n = 82).

Conclusions

The majority of maxillary first premolars had two roots and two root canals, while one root and one root canal was the most common anatomical configuration for maxillary second premolars. Additional canal forms do occur on occasion, and clinicians should pay close attention to them.
Pseudoaneurysm of the uterine artery post loop electrosurgical excision procedure
Authors: Ong Judith , Lee Kelvin , Choo Soe-Na , Loh Stanley , Lim Li Min , Chen Yee Yong , Singh Kuldip
Published: August 2021

Background

The formation of a uterine artery pseudoaneurysm is rare and isolated cases have been reported in the existing literature following caesarean sections, curettages and cone biopsies. There has been no report of pseudoaneurysm formation following a loop electrosurgical excision procedure. Vaginal bleeding could potentially be life threatening if this diagnosis is not considered following cervical instrumentation or surgery. Management options range from haemostatic sutures, image-guided embolisation to surgical repair. We report the diagnosis and management of a case of uterine artery pseudoaneurysm after a loop electrosurgical excision procedure.

Case presentation

A 37-year-old woman was diagnosed with cervical intraepithelial neoplasia grade 3 (CIN3) and underwent a therapeutic loop electrosurgical excision procedure. One month after the procedure, the patient presented to the emergency department with repeated episodes of sudden-onset heavy vaginal bleeding associated with hypotension and syncope. A computed tomography angiogram was performed, which demonstrated a pseudoaneurysm of the right uterine artery. Following the diagnosis, image-guided embolisation was performed successfully. Post-embolisation angiograms showed successful embolisation of the pseudoaneurysm and the patient had no further episodes of bleeding.

Conclusions

Loop electrosurgical excision procedures are generally safe but rarely, can be complicated by the formation of uterine artery pseudoaneurysms. The depth of the loop electrosurgical excision procedure and vascular anatomy should be considered to prevent such complications. A computed tomography angiogram appears to be ideal for diagnosis. Image-guided embolisation is safe and effective as a therapeutic measure, with minimal morbidity.
A qualitative exploration of medical students’ placement experiences with telehealth during COVID-19 and recommendations to prepare our future medical workforce
Authors: Pit Sabrina W. , Velovski Sue , Cockrell Krista , Bailey Jannine
Published: August 2021

Background

Clinical practice is increasingly being digitalised. Little is known about how medical students learn and were exposed to telehealth during COVID-19. This is particularly important if we wish to further improve healthcare access and equity in rural areas and vulnerable populations. This formative study sought to explore the exposure and attitudes of medical students on telehealth and COVID-19 during their rural clinical placement in 2020 and provide recommendations.

Methods

Focus groups were held in August 2020 after completion of a 12-month rural placement. Questions centred around students’ exposure and experiences with telehealth during COVID-19. Data was analysed using thematic analysis.

Results

There has been a clear shift in students now acknowledging the importance of telehealth and, more importantly, expressing a clear wish for telehealth to be embedded in the curriculum starting in their first year. In tandem with this, students expressed the need for their clinical supervisors or hospital teams to have the capability to practice telehealth efficiently as this will improve the telehealth experience and lead to better engagement for both staff and students. Furthermore, it was felt that rural clinicians should play a lead role in telehealth implementation given it is integral to rural practice.

Conclusions

Medical students are more exposed to and more interested to learn about telehealth since COVID-19 and wish to see telehealth training built into their curriculum from the outset of medical school. Themes that emerged from this formative study can potentially assist in planning for telehealth education during and post COVID-19 and inform further telehealth research. Embedding telehealth skills training and guidelines into the medical program, and particularly rural medicine training programs, is essential to prepare the future medical workforce to ensure access and quality patient care during pandemics and also to improve access for rural Australians.
Genetic polymorphism of the extracellular region in surface associated interspersed 1.1 gene of Plasmodium falciparum field isolates from Thailand
Authors: Chaianantakul Natpasit , Sungkapong Tippawan , Changpad Jirapinya , Thongma Keawalin , Sim-ut Sasiwimon , Kaewthamasorn Morakot
Published: August 2021

Background

A novel variable surface antigens (VSAs), Surface-associated interspersed proteins (SUFRINs), is a protein that is modified on the surface of infected red blood cell (iRBC). Modified proteins on the iRBC surface cause severe malaria, which can lead to death throughout the life cycle of a malaria parasite. Previous study suggested that SURFIN1.1 is an immunogenic membrane-associated protein which was encoded by using the surf1.1 gene expressed during the trophozoite and schizont stages. This study aimed to identify the regions of SURFIN1.1 and investigate the genetic diversity of the extracellular region of the surf1.1 gene.

Methods

A total of 32 blood samples from falciparum malaria cases that were diagnosed in Si Sa Ket Province, Thailand were collected. Plasmodium genomic DNA was extracted, and the extracellular region of surf1.1 gene was amplified using the polymerase chain reaction (PCR). A sequence analysis was then performed to obtain the number of haplotypes (H), the haplotype diversity (Hd), and the segregating sites (S), while the average number of nucleotide differences between two sequences (Pi); in addition, neutrality testing, Tajima’s D test, Fu and Li’s D* and F* statistics was also performed.

Results

From a total of 32 patient-isolated samples, 31 DNA sequences were obtained and analysed for surf1.1 gene extracellular region polymorphism. Researchers observed six distinct haplotypes in the current research area. Haplotype frequencies were 61.3%, 16.2%, and 12.9% for H1, H2, and H3, respectively. The remaining haplotype (H4-H6) frequency was 3.2% for each haplotype. Hd was 0.598 ± 0.089 with the Pi of 0.00381, and S was 15. The most common amino acid polymorphic site was E251Q; other sites included N48D, I49V, E228D, E235S, L265F, K267T, E276Q, and S288F. Fu and Li’s D* test value was − 1.24255, Fu and Li’s F* test value was − 1.10175, indicating a tendency toward negative balancing selection acting on the surf1.1 N-terminal region. The most polymorphic region was variable 2 (Var2) while cysteine-rich domain (CRD) was conserved in both the amino acid and nucleotide extracellular region of surf1.1 gene.

Conclusions

The Thai surf1.1 N-terminal region was well-conserved with only a few polymorphic sites remaining. In this study, the data regarding current bearing on the polymorphism of extracellular region of surf1.1 gene were reported, which might impact the biological roles of P. falciparum. In addition, may possibly serve as a suitable candidate for future development of SURFIN-based vaccines regarding malaria control.

Graphic abstract
Association of serum 25-OH-vitamin D level with FTO and IRX3 genes expression in obese and overweight boys with different FTO rs9930506 genotypes
Authors: Gholamalizadeh Maryam , Doaei Saeid , Mokhtari Zohreh , Jalili Vahideh , Bourbour Fatemeh , Omidi Saeed , Ebrahimi Kamal , Kalantari Naser , Abdi Sheyda , Azizi Tabesh Ghasem , Naimi Joubani Mohammad , Roohbakhsh Esmaeil , Mosavi Jarrahi Seyed Alireza
Published: August 2021

Background

The roles of FTO gene and the level of serum 25-OH-vitamin D in obesity are frequently reported. This study aimed to investigate the interactions of serum 25-OH-vitamin D level, FTO and IRX3 genes expression, and FTO genotype in obese and overweight boys.

Methods

This study was carried out on the 120 male adolescents with overweight in Tehran, Iran. Blood samples were collected from the participants in order to evaluate the serum level of 25-OH-vitamin D, the expression level of FTO and IRX3 genes, and FTO genotype for rs9930506 at baseline and after 18 weeks of the study.

Results

In general, no significant association was found between serum 25-OH-vitamin D level and IRX3 and FTO genes expression. The results of linear regression on the relationship between 25-OH-vitamin D serum level and FTO and IRX3 genes expression based on FTO genotypes for rs9930506 indicated that in AA/AG genotype carriers, serum 25-OH-vitamin D level was positively associated with FTO gene expression (B = 0.07, p = 0.02) and inversely associated with IRX3 gene expression (B = − 0.07, p = 0.03). In GG carriers, serum 25-OH-vitamin D level was not associated with expression of IRX3 and FTO genes.

Conclusion

There are significant interactions between 25-OH-vitamin D and the expression of FTO and IRX3 genes in the subset of obese patients with specific genotypes for FTO rs9930506. There was no association between serum 25-OH-vitamin D levels and the expression of FTO and IRX genes in individuals with a homozygous genotype for the risk allele of the FTO gene polymorphism.
Prioritization and selection of high fuelwood producing plant species at Boset District, Central Ethiopia: an ethnobotanical approach
Authors: Bahru Tinsae , Kidane Berhane , Tolessa Amsalu
Published: August 2021

Background

In Ethiopia, about 92.3% of all the fuelwood (firewood and/or charcoal) is consumed for cooking, heating and lighting purposes by domestic households and the demand is growing from 10 to 14%. However, there are little/no practical experiences or documented indigenous knowledge on how traditional people identify and select high fuelwood producing plant species with short rotation periods at Boset District. Therefore, the present study was aimed at: (1) selecting and documenting high fuelwood producing plant species at Boset District; (2) identifying major predictor variables that influence the prioritization and selection of species; and (3) develop a Generalized Linear Model (GLM) to predict the selection of species.

Methods

A total of 96 informants comprising 59 men and 37 women between the ages of 18 and 81 were sampled. Data were collected using structured interviews, guided field walk, discussions and field observations.

Results

Collected data indicated that 88.5% of the informants involved in firewood collection, while 90% practiced charcoal making. A total of 1533.60 Birr per household on average was earned annually from this activity. A total of 25 fuelwood producing plant species were identified and documented at Boset District. Of these,Acacia senegal, Acacia tortilisandAcacia robustawere the three best prioritized and selected indigenous high fuelwood producing species.Prosopis juliflora,Parthenium hysterophorus,Azadirachta indica,Calotropis procera, Cryptostegia grandiflora, Lantana camaraandSenna occidentalisfurther grouped under introduced fuelwood species. Prediction of GLM assured sampledKebelesand source of income generated from fuelwood species positively and significantly (p < 0.001) related to selection of species. Higher efficiency to provide energy and heat; little or no smoke or soot; easier to cut and split the wood and easier availability were some of the main selection criteria.

Conclusions

This study provides valuable information in selecting and documenting of high fuelwood producing plant species for proper management and sustainable use at Boset District. The three most selected species (A. senegal, A. tortilisandA. robusta) should be further evaluated at laboratory to determine their calorific value and combustion characteristics.
Does the protocol-required uniform margin around the CTV adequately account for setup inaccuracies in whole breast irradiation?
Authors: Luo Jurui , Yin Zhihai , Zhang Zhen , Guo Xiaomao , Yu Xiaoli , Wang Juanqi
Published: August 2021

Purpose

To use cone-beam computed tomography (CBCT) imaging to determine the impacts of patient characteristics on the magnitude of geometric setup errors and obtain patient-specific planning target volume (PTV) margins from the correlated patient characteristics in whole breast irradiation (WBI).

Methods

Between January 2019 and December 2019, a total of 97 patients who underwent breast-conserving surgery, followed by intensity-modulated radiation therapy in WBI, were scanned with pre-treatment CBCT for the first three treatment fractions and weekly for the subsequent fractions. Setup errors in the left–right (LR), superior–inferior (SI) and anterior–posterior (AP) directions were recorded and analyzed with patient characteristics—including age, tumor location, body mass index (BMI), chest circumference (CC) and breast volume (BV)—to examine the predictors for setup errors and obtain specific PTV margins.

Results

A total of 679 CBCT images from 97 patients were acquired for analysis. The mean setup errors for the whole group were 2.32 ± 1.21 mm, 3.71 ± 2.21 mm and 2.75 ± 1.56 mm in the LR, SI and AP directions, respectively. Patients’ BMI, CC and BV were moderately associated with setup errors, especially in the SI directions (R = 0.40, 0.43 and 0.22, respectively). Setup errors in the SI directions for patients with BMI > 23.8 kg/m2, CC > 89 cm and BV > 657 cm3 were 4.56 ± 2.59 mm, 4.77 ± 2.42 mm and 4.30 ± 2.43 mm, respectively, which were significantly greater than those of patients with BMI ≤ 23.8 kg/m2, CC ≤ 89 cm and BV ≤ 657 cm3 (P < 0.05). Correspondingly, the calculated PTV margins in patients with BMI > 23.8 kg/m2, CC > 89 cm and BV > 657 cm3 were 4.25/7.95/4.93 mm, 4.37/7.66/5.24 mm and 4.22/7.54/5.29 mm in the LR/SI/AP directions, respectively, compared with 3.64/4.64/5.09 mm, 3.31/4.50/4.82 mm and 3.29/5.74/4.73 mm for BMI ≤ 23.8 kg/m2, CC ≤ 89 cm and BV ≤ 657 cm3, respectively.

Conclusions

The magnitude of geometric setup errors was moderately correlated with BMI, CC and BV. It was recommended to set patient-specific PTV margins according to patient characteristics in the absence of daily image-guided treatment setup.
HPV16 E6 enhances the radiosensitivity in HPV-positive human head and neck squamous cell carcinoma by regulating the miR-27a-3p/SMG1 axis
Authors: Long Dan , Xu Li , Deng Zeyi , Guo Dandan , Zhang Yangchun , Liu Zhaohui , Zhang Chunlin
Published: August 2021

Background

Head and neck squamous cell carcinoma (HNSCC) is the 6th most common malignant cancer type worldwide. Radiosensitivity has been shown to be significantly increased in patients with human papillomavirus (HPV)-positive HNSCC compared with HPV-negative patients. However, the clinical significance of HPV and its regulatory mechanisms in HNSCC are largely unknown. The aim of our study was to explore the regulatory mechanism of miR-27a-3p in the radiosensitivity of HPV-positive HNSCC cells.

Methods

E6-overexpressing and E6-knockdown HNSCC cell lines were generated and the transfection efficiencies were evaluated by quantitative real-time PCR (RT-qPCR) and western blotting. The expression of miR-27a-3p and DiGeorge syndrome critical region 8 (DGCR8) was examined by RT-qPCR after transfection with E6 overexpressing plasmid or E6 siRNA. The effects of miR-27a-3p on the radiosensitivity of HNSCC cells were explored by a colony formation and TUNEL staining assays. Bioinformatic tools and luciferase reporter assays were used to identify that SMG1 is the direct target of miR-27a-3p. Furthermore, the effect of E6 overexpression on the regulation of the miR-27a-3p/SMG1 axis was investigated.

Results

In our study, we found overexpression of HPV E6 upregulated the expression of DGCR8 and miR-27a-3p in HNSCC cells. We next confirmed that DGCR8 positively regulated the expression of miR-27a-3p in HNSCC cells. The luciferase reporter gene results verified that miR-27a-3p targeted the 3’UTR of SMG1 mRNA. MiR-27a-3p mimics transfection resulted in a decrease in SMG1 expression and miR-27a-3p inhibitor transfection increased SMG1 expression. Apoptotic activity of HNSCC cells was significantly increased in miR-27a-3p mimics HNSCC cells compared with control HNSCC cells. After treatment with 4 Gy irradiation, UM-SCC47 cells transfected with miR-27a-3p inhibitor or SMG1 overexpressing plasmid formed more colonies than the corresponding control cells. Furthermore, the rescue experiments demonstrated that HPV16 E6 improved the radiosensitivity of HNSCC cells by targeting miR-27a-3p/SMG1.

Conclusion

Our study demonstrated that HPV16 E6 activated the DGCR8/miR-27a-3p/SMG1 axis to enhance the radiosensitivity. Our findings might provide a novel therapeutic target to improve the response of HNSCC to radiotherapy.
Chromatin interaction neural network (ChINN): a machine learning-based method for predicting chromatin interactions from DNA sequences
Authors: Cao Fan , Zhang Yu , Cai Yichao , Animesh Sambhavi , Zhang Ying , Akincilar Semih Can , Loh Yan Ping , Li Xinya , Chng Wee Joo , Tergaonkar Vinay , Kwoh Chee Keong , Fullwood Melissa J.
Published: August 2021

Chromatin interactions play important roles in regulating gene expression. However, the availability of genome-wide chromatin interaction data is limited. We develop a computational method, chromatin interaction neural network (ChINN), to predict chromatin interactions between open chromatin regions using only DNA sequences. ChINN predicts CTCF- and RNA polymerase II-associated and Hi-C chromatin interactions. ChINN shows good across-sample performances and captures various sequence features for chromatin interaction prediction. We apply ChINN to 6 chronic lymphocytic leukemia (CLL) patient samples and a published cohort of 84 CLL open chromatin samples. Our results demonstrate extensive heterogeneity in chromatin interactions among CLL patient samples.
CardioTox net: a robust predictor for hERG channel blockade based on deep learning meta-feature ensembles
Authors: Karim Abdul , Lee Matthew , Balle Thomas , Sattar Abdul
Published: August 2021

Motivation

Ether-a-go-go-related gene (hERG) channel blockade by small molecules is a big concern during drug development in the pharmaceutical industry. Blockade of hERG channels may cause prolonged QT intervals that potentially could lead to cardiotoxicity. Various in-silico techniques including deep learning models are widely used to screen out small molecules with potential hERG related toxicity. Most of the published deep learning methods utilize a single type of features which might restrict their performance. Methods based on more than one type of features such as DeepHIT struggle with the aggregation of extracted information. DeepHIT shows better performance when evaluated against one or two accuracy metrics such as negative predictive value (NPV) and sensitivity (SEN) but struggle when evaluated against others such as Matthew correlation coefficient (MCC), accuracy (ACC), positive predictive value (PPV) and specificity (SPE). Therefore, there is a need for a method that can efficiently aggregate information gathered from models based on different chemical representations and boost hERG toxicity prediction over a range of performance metrics.

Results

In this paper, we propose a deep learning framework based on step-wise training to predict hERG channel blocking activity of small molecules. Our approach utilizes five individual deep learning base models with their respective base features and a separate neural network to combine the outputs of the five base models. By using three external independent test sets with potency activity of IC50at a threshold of 10$$\upmu$$μm, our method achieves better performance for a combination of classification metrics. We also investigate the effective aggregation of chemical information extracted for robust hERG activity prediction. In summary, CardioTox net can serve as a robust tool for screening small molecules for hERG channel blockade in drug discovery pipelines and performs better than previously reported methods on a range of classification metrics.
Multiple functions of autophagy in vascular calcification
Authors: Zhou Xin , Xu Sui-Ning , Yuan Shu-Tong , Lei Xinjuan , Sun Xiaoying , Xing Lu , Li Hui-Jin , He Chun-Xia , Qin Wei , Zhao Dong , Li Peng-Quan , Moharomd Edward , Xu Xuehong , Cao Hui-Ling
Published: August 2021

Background

Vascular calcification is a closely linked to cardiovascular diseases, such as atherosclerosis, chronic kidney disease, diabetes, hypertension and aging. The extent of vascular calcification is closely correlate with adverse clinical events and cardiovascular all-cause mortality. The role of autophagy in vascular calcification is complex with many mechanistic unknowns.

Methods

In this review, we analyze the current known mechanisms of autophagy in vascular calcification and discuss the theoretical advantages of targeting autophagy as an intervention against vascular calcification.

Results

Here we summarize the functional link between vascular calcification and autophagy in both animal models of and human cardiovascular disease. Firstly, autophagy can reduce calcification by inhibiting the osteogenic differentiation of VSMCs related to ANCR, ERα, β-catenin, HIF-1a/PDK4, p62, miR-30b, BECN1, mTOR, SOX9, GHSR/ERK, and AMPK signaling. Conversely, autophagy can induce osteoblast differentiation and calcification as mediated by CREB, degradation of elastin, and lncRNA H19 and DUSP5 mediated ERK signaling. Secondly, autophagy also links apoptosis and vascular calcification through AMPK/mTOR/ULK1, Wnt/β-catenin and GAS6/AXL synthesis, as apoptotic cells become the nidus for calcium-phosphate crystal deposition. The failure of mitophagy can activate Drp1, BNIP3, and NR4A1/DNA‑PKcs/p53 mediated intrinsic apoptotic pathways, which have been closely linked to the formation of vascular calcification. Additionally, autophagy also plays a role in osteogenesis by regulating vascular calcification, which in turn regulates expression of proteins related to bone development, such as osteocalcin, osteonectin, etc. and regulated by mTOR, EphrinB2 and RhoA. Furthermore, autophagy also promotes vitamin K2-induced MC3T3 E1 osteoblast differentiation and FGFR4/FGF18- and JNK/complex VPS34–beclin-1-related bone mineralization via vascular calcification.

Conclusion

The interaction between autophagy and vascular calcification are complicated, with their interaction affected by the disease process, anatomical location, and the surrounding microenvironment. Autophagy activation in existent cellular damage is considered protective, while defective autophagy in normal cells result in apoptotic activation. Identifying and maintaining cells at the delicate line between these two states may hold the key to reducing vascular calcification, in which autophagy associated clinical strategy could be developed.
Solutions of nonlinear difference equations in the domain of $(\zeta _{n})$-Cesàro matrix in $\ell _{t(\cdot)}$ of nonabsolute type, and its pre-quasi ideal
Authors: Bakery Awad A. , Mohammed Mustafa M.
Published: August 2021

We have constructed the sequence space$(\Xi (\zeta ,t) )_{\upsilon }$(Ξ(ζ,t))υ, where$\zeta =(\zeta _{l})$ζ=(ζl)is a strictly increasing sequence of positive reals tending to infinity and$t=(t_{l})$t=(tl)is a sequence of positive reals with$1\leq t_{l}<\infty $1≤tl<∞, by the domain of$(\zeta _{l})$(ζl)-Cesàro matrix in the Nakano sequence space$\ell _{(t_{l})}$ℓ(tl)equipped with the function$\upsilon (f)=\sum^{\infty }_{l=0} ( \frac{ \vert \sum^{l}_{z=0}f_{z}\Delta \zeta _{z} \vert }{\zeta _{l}} )^{t_{l}}$υ(f)=∑l=0∞(|∑z=0lfzΔζz|ζl)tlfor all$f=(f_{z})\in \Xi (\zeta ,t)$f=(fz)∈Ξ(ζ,t). Some geometric and topological properties of this sequence space, the multiplication mappings defined on it, and the eigenvalues distribution of operator ideal withs-numbers belonging to this sequence space have been investigated. The existence of a fixed point of a Kannan pre-quasi norm contraction mapping on this sequence space and on its pre-quasi operator ideal formed by$(\Xi (\zeta ,t) )_{\upsilon }$(Ξ(ζ,t))υands-numbers is presented. Finally, we explain our results by some illustrative examples and applications to the existence of solutions of nonlinear difference equations.
Long-term antimicrobial effectiveness of a silver-impregnated foil on high-touch hospital surfaces in patient rooms
Authors: Widmer Andreas F. , Kuster Sonja , Dangel Marc , Jäger Sammy , Frei Reno
Published: August 2021

Background

The hospital environment has got more attention as evidence as source for bacterial transmission and subsequent hospital-acquired infection increased. Regular cleaning and disinfection have been proposed to lower the risk of infection, in particular for gram-positive bacteria. Auto-disinfecting surfaces would allow to decrease survival of pathogens, while limiting resource to achieve a safe environment in patient rooms.

Methods

A controlled trial to evaluate the antimicrobial effectiveness of a polyvinyl chloride foil containing an integrated silver-based agent (containing silver ions 2%) on high-touch surfaces in patient rooms.

Results

The overall log reduction of the mean values was 1.8 log10 CFU, the median 0.5 log10 CFU comparing bioburden of control vs antimicrobial foil (p < 0.01). Important pathogens were significantly less likely recovered from the foil, in particular enterococci. These effects were present even after 6 months of in-use.

Conclusions

A foil containing an integrated silver-based agent applied to high-touch surfaces effectively results in lower recovery of important pathogens from such surfaces over a 6-month study period.
Determination of phytocomponents and validation of squalene in ethanolic extract of Clerodendrum serratum Linn roots—using gas chromatography-mass spectroscopy and GC-FID technique
Authors: Reddy Kalyani , Gurupadayya B M  , Choezom Lodoe , Vikram P R Hemanth
Published: August 2021

Background

Clerodendrum serratum Linn commonly known as Bharangi in India has wide applications in the Ayurveda and Siddha system of medicine which has been attributed to the treatment of various diseases like asthma, cough, fever, rheumatism, and cephalalgia ophthalmia. Squalene has nutritional, medicinal, and pharmaceutical health benefits, hence possess antioxidant and cytoprotective effects.

Method

The study presents the GC-MS analysis of phytoconstituents present in the Clerodendrum serratum roots and further estimation of one of the constituents, i.e., squalene which is ought to be present in the roots as per mass spectral data obtained. Squalene was determined from the ethanolic extract of C. serratum roots using GC-FID without derivatization.

Results

Four major constituents, i.e., squalene, methyl palmitate, hexadecenoic acid, and stigmasterol were detected by GC-MS. Squalene from the extract was eluted at 17.5min which was confirmed with the standard squalene peak eluted at the same retention time. The linearity range chosen was 5–30ug/mL, and the method was found to be pretty linear (R=0.995), accurate with satisfactory repeatability. Hence, the phytochemical compounds were detected by GC-MS and the squalene was determined and validated according to the ICH guidelines.

Conclusion

Thus, the green gas chromatographic method can be used for quantification and qualification of active constituents in the roots of ethanolic extract of C. serratum. In addition, the presence of metabolite squalene by the GC-FID method was developed for the extract which is simple, fast, and environmentally friendly.
Multiple sclerosis is not associated with an increased risk for severe COVID-19: a nationwide retrospective cross-sectional study from Germany
Authors: Richter Daniel , Faissner Simon , Bartig Dirk , Tönges Lars , Hellwig Kerstin , Ayzenberg Ilya , Krogias Christos , Gold Ralf
Published: August 2021

Background

Since the coronavirus disease 2019 (COVID-19) has risen, several risk factors have been identified, predicting a worse outcome. It has been speculated that patients with Multiple sclerosis (MS) have an increased risk for a severe course of COVID-19 due to a suspected higher vulnerability. Therefore, we aimed to analyze the impact of comorbid MS on the outcome of patients with COVID-19 in Germany.

Methods

We conducted a retrospective cross-sectional study using the administrative database of all hospitalized patients diagnosed with PCR-confirmed COVID-19 (n = 157,524) in Germany during 2020. The cohort was stratified according to the presence (n = 551) or absence (n = 156,973) of comorbid MS, including discrimination of MS subtypes. Primary outcome measures were admission to the intensive care unit (ICU), use of invasive or non-invasive ventilation, and in-hospital mortality. Differences were investigated using rates and odds ratios as estimates. Pooled overall estimates, sex-stratified estimates, age-group stratified estimates, and MS subtype stratified estimates were calculated for all outcomes under the random-effects model.

Results

Among 157,524 patients hospitalized with COVID-19, 551 had a concurrent MS diagnosis (0.3%). Overall, univariate analysis showed lower rates of ICU admission (17.1% versus 22.7%, p < 0.001), lower use of ventilation (9.8% versus 14.5%, p < 0.001) and lower in-hospital mortality (11.1% versus 19.3%, p < 0.001) among COVID-19 patients with comorbid MS. This finding was stable across the subgroup analysis of sex and MS subtype but was attenuated by age-stratification, confirming equal odds of in-hospital mortality between COVID-19 patients with and without MS (log OR: 0.09 [95% CI: − 0.40, 0.59]).

Conclusions

Although there might be differences in risk within the MS patients’ population, this large-scale nationwide analysis found no evidence for a worse outcome of COVID-19 in patients with comorbid MS compared to non-MS individuals.