bluuebunny/crossref_metadata_2025 huggingface dataset:
MutationalPatterns: the one stop shop for the analysis of mutational processes
Authors: Manders Freek , Brandsma Arianne M. , de Kanter Jurrian , Verheul Mark , Oka Rurika , van Roosmalen Markus J. , van der Roest Bastiaan , van Hoeck Arne , Cuppen Edwin , van Boxtel Ruben
Published: February 2022

Background

The collective of somatic mutations in a genome represents a record of mutational processes that have been operative in a cell. These processes can be investigated by extracting relevant mutational patterns from sequencing data.

Results

Here, we present the next version of MutationalPatterns, an R/Bioconductor package, which allows in-depth mutational analysis of catalogues of single and double base substitutions as well as small insertions and deletions. Major features of the package include the possibility to perform regional mutation spectra analyses and the possibility to detect strand asymmetry phenomena, such as lesion segregation. On top of this, the package also contains functions to determine how likely it is that a signature can cause damaging mutations (i.e., mutations that affect protein function). This updated package supports stricter signature refitting on known signatures in order to prevent overfitting. Using simulated mutation matrices containing varied signature contributions, we showed that reliable refitting can be achieved even when only 50 mutations are present per signature. Additionally, we incorporated bootstrapped signature refitting to assess the robustness of the signature analyses. Finally, we applied the package on genome mutation data of cell lines in which we deleted specific DNA repair processes and on large cancer datasets, to show how the package can be used to generate novel biological insights.

Conclusions

This novel version of MutationalPatterns allows for more comprehensive analyses and visualization of mutational patterns in order to study the underlying processes. Ultimately, in-depth mutational analyses may contribute to improved biological insights in mechanisms of mutation accumulation as well as aid cancer diagnostics. MutationalPatterns is freely available athttp://bioconductor.org/packages/MutationalPatterns.
Large-scale association study on daily weight gain in pigs reveals overlap of genetic factors for growth in humans
Authors: Cai Zexi , Christensen Ole Fredslund , Lund Mogens Sandø , Ostersen Tage , Sahana Goutam
Published: February 2022

Background

Imputation from genotyping array to whole-genome sequence variants using resequencing of representative reference populations enhances our ability to map genetic factors affecting complex phenotypes in livestock species. The accumulation of knowledge about gene function in human and laboratory animals can provide substantial advantage for genomic research in livestock species.

Results

In this study, 201,388 pigs from three commercial Danish breeds genotyped with low to medium (8.5k to 70k) SNP arrays were imputed to whole genome sequence variants using a two-step approach. Both imputation steps achieved high accuracies, and in total this yielded 26,447,434 markers on 18 autosomes. The average estimated imputation accuracy of markers with minor allele frequency ≥ 0.05 was 0.94. To overcome the memory consumption of running genome-wide association study (GWAS) for each breed, we performed within-breed subpopulation GWAS then within-breed meta-analysis for average daily weight gain (ADG), followed by a multi-breed meta-analysis of GWAS summary statistics. We identified 15 quantitative trait loci (QTL). Our post-GWAS analysis strategy to prioritize of candidate genes including information like gene ontology, mammalian phenotype database, differential expression gene analysis of high and low feed efficiency pig and human GWAS catalog for height, obesity, and body mass index, we proposedMRAP2,LEPROT, PMAIP1,ENSSSCG00000036234, BMP2, ELFN1, LIG4andFAM155Aas the candidate genes with biological support for ADG in pigs.

Conclusion

Our post-GWAS analysis strategy helped to identify candidate genes not just by distance to the lead SNP but also by multiple sources of biological evidence. Besides, the identified QTL overlap with genes which are known for their association with human growth-related traits. The GWAS with this large data set showed the power to map the genetic factors associated with ADG in pigs and have added to our understanding of the genetics of growth across mammalian species.
Performance evaluation of an automatic chemiluminescence immune platform for SARS-CoV-2 neutralizing antibody after vaccination in real world
Authors: Li Min , Jiang Ruiwei , Wang Enyun , Xiong Dan , Ou Tong , Zhang Xiuming , Dou Xiaowen
Published: February 2022

Objective

Reliable high-throughput serological assays for SARS-CoV-2 antibodies present an important role in the strength and duration of immunity after vaccination. The study investigated the analytical and clinical performances of neutralizing antibodies (NTAb) assay by chemiluminescent (CLIA), and SARS-CoV-2 neutralizing antibody after vaccination in real world.

Methods

The analytical performances of CLIA for SARS-CoV-2 NTAb were evaluated, followed by the sensitivity and specificity identified with a PRNT test from 50 volunteers. Then, a cohort of vaccine recipients (n = 37) were tracked with SARS-CoV-2 NTAb assay at prior to vaccination, one, three and six months post two doses. In real world, a total of 737 cases were recruited from physical examination center in Shenzhen Luohu People’s Hospital (from Jun to August 2021) to analyze vaccination status.

Results

Serological assays on the CLIA were found with excellent characteristics including imprecision, repeatability and linearity. Besides, it was robust to icterus, lipemia and hemolysis. The good sensitivity and specificity were obtained at 98% and 100%, respectively. NTAb results showed a high correlation with PRNT50 titers (r 0.61). Until July 2021, the BBIBP-CorV (76.3%) and Sinovac CoronaVac (20.5%) were the predominant vaccines injection in Shenzhen, China. Adolescent less than 18 years was the main unvaccinated group (52.1%). The seropositive rate of inactive SRAR-CoV-2 vaccines exceeded 97% after inoculation. The NTAb generated by Sinovac CoronaVac with the schedule of 0–56 days was found significantly lower than that by BBIBP-CorV (P < 0.001). The follow-up of NTAb changes in a cohort and the dynamic variation of NTAb in real world disclosed steep downward by almost three times for NTAb level occurred at three months post twice vaccinations. The seropositive ratio was at least 50% over 6 months.

Conclusions

SARS-CoV-2 neutralizing antibodies assay show excellent analytical and clinical performances, and a high correlation with neutralizing activity. Anti-epidemic measures and the urgent trial of SARS-CoV-2 vaccine was calling for adolescents.
Nectin-4 and DNA mismatch repair proteins expression in upper urinary tract urothelial carcinoma (UTUC) as a model for tumor targeting approaches: an ImGO pilot study
Authors: Calandrella Maria Letizia , Francesconi Simona , Caprera Cecilia , Mosillo Claudia , Caserta Claudia , Giannarelli Diana , Corsi Matteo , Macrini Serena , Guida Annalisa , Ascani Stefano , Bracarda Sergio
Published: February 2022

Background

Upper urinary tract urothelial carcinoma (UTUC) accounts for only about 5–10% of all urothelial cancers and is characterized by an aggressive and frequently rapidly fatal behavior. However, detailed knowledge of its molecular profile is still lacking.

Materials and methods

We identified, by chart analysis, patients who underwent radical nephroureterectomy or diagnostic biopsy for UTUC between January 2015 and August 2020 at the Santa Maria Hospital of Terni, in Italy. Eligible patients were required to have also adequate clinical informations and follow-up details. The primary objective of the study was to evaluate DNA mismatch repair (MMR) proteins and Nectin-4 immunohistochemical expression in UTUC, looking also for an eventual correlation between these molecular features. The secondary objective was to investigate genomic instability in the case of a MMR protein loss. Expression of proteins was assessed by using immunohistochemistry and microsatellite instability (MSI) performed by next generation sequencing. Nectin-4 expression was reported using an intensity scoring system (score, 0–3+), instead the expression of DNA MMR proteins was indicated as present (no loss) or not present (loss).

Results

Thirty four cases have been evaluated and 27 considered eligible for the study with their tumor samples analyzed. Nectin-4 was found to be expressed in 44% of cases and 18.5% of patients showed defective-MMR phenotype. We found a significant correlation between Nectin-4 expression and MSH2/MSH6 protein loss. Out of 7 patients with DNA MMR proteins loss or equivocal phenotype, 3 showed MSI.

Conclusions

Our pilot study suggest a possible relationship between Nectin-4 and DNA MMR protein expression in UTUC and a clinically significant correlation between defective MMR phenotype and genomic instability. Because of the possible implications of these data for innovative treatment approaches, the need for further studies in this area is warranted.
Lifestyle predictors for inconsistent participation to fecal based colorectal cancer screening
Authors: Knudsen Markus Dines , Kvaerner Ane Sørlie , Botteri Edoardo , Holme Øyvind , Hjartåker Anette , Song Mingyang , Thiis-Evensen Espen , Randel Kristin Ranheim , Hoff Geir , Berstad Paula
Published: February 2022

Background

Consistent participation in colorectal cancer (CRC) screening with repeated fecal immunochemical test (FIT) is important for the success of the screening program. We investigated whether lifestyle risk factors for CRC were related to inconsistent participation in up to four rounds of FIT-screening.

Method

We included data from 3,051 individuals who participated in up to four FIT-screening rounds and returned a lifestyle questionnaire. Using logistic regression analyses, we estimated associations between smoking habits, body mass index (BMI), physical activity, alcohol consumption, diet and a healthy lifestyle score (from least favorable 0 to most favorable 5), and inconsistent participation (i.e. not participating in all rounds of eligible FIT screening invitations).

Results

Altogether 721 (24%) individuals were categorized as inconsistent participants Current smoking and BMI ≥30 kg/m2 were associated with inconsistent participation; odds ratios (ORs) and 95% confidence intervals (CIs) were 1.54 (1.21-2.95) and 1.54 (1.20-1.97), respectively. A significant trend towards inconsistent participation by a lower healthy lifestyle score was observed (p < 0.05).

Conclusions

Lifestyle behaviors were associated with inconsistent participation in FIT-screening. Initiatives aimed at increasing participation rates among those with the unhealthiest lifestyle have a potential to improve the efficiency of screening.
The effect of orthokeratology treatment zone decentration on myopia progression
Authors: Sun Lu , Li Zheng-Xuan , Chen Yun , He Zhi-Qiang , Song Hong-Xin
Published: February 2022

Background

This study aimed to compare the changes in the axial length (AL) in myopic children that wear centered and decentered orthokeratology (Ortho-K).

Methods

This retrospective study included 217 subjects who were treated with an Ortho-K lens for >12 months. The subjects were divided into three groups based on the magnitude of the Ortho-K lens treatment zone decentration: mildly, moderately, and severely decentered groups. Distance and direction of treatment zone decentration were calculated using software that was developed in-house. The AL changes in different groups were compared.

Results

Based on the distance of the treatment zone decentration, 65 children (65 eyes) were included in the mildly decentered group, 114 children (114 eyes) in the moderately decentered group, and 38 children (38 eyes) in the severely decentered group. The mean decentration distance in the three groups was 0.35 ± 0.11 mm, 0.71 ± 0.13 mm, and 1.21 ± 0.22 mm, respectively. The mean AL increase in the three groups after 12 months of Ortho-K lens wear was 0.24 ± 0.21 mm, 0.23 ± 0.18 mm, and 0.19 ± 0.20 mm, respectively. There were no significant differences in AL changes among the three groups.

Conclusions

Ortho-K lens decentration is common in clinical practice. The AL change after Ortho-K lens wear was not significantly different in subjects with different magnitudes of Ortho-K lens decentration. Fitting the Ortho-K lens in the properly centered zone is recommended to ensure the safety of Ortho-K lens wear and to maintain visual quality.
Pediatric oral health: community-based participatory research
Authors: Ogenchuk Marcella , Graham Juanita , Uswak Gerry , Graham Holly , Weiler Robert , Ramsden Vivian R.
Published: February 2022

Background

The most common chronic disease affecting children in Canada is dental caries. The objective of this study was to explore, identify, and address the strengths and barriers related to oral health services with an independent Indigenous community in Saskatchewan.

Methods

Community-based participatory research used interviews with Elders, health care providers, teachers, and parents/guardians of elementary school-aged children. The research focused on the development of genuine partnerships with the community. During data collection, the findings/results were returned to the community to establish direction, build success, and establish next steps. Thematic analysis was undertaken with the community. Descriptive statistics were analyzed using SPSS.

Results

The most commonly identified themes included: community resilience; the need for resource development and process to improve oral health literacy and skills; and how access to care barriers dually affected and related to personal and community cost, time, and human resources.

Conclusions

The research process involved the co-creation of tools to identify strengths within the community and drive opportunities for change; subsequently generating solutions to the practical problems and potentially transform the health system accessed by the community.
An extended version of Necessary Condition Analysis (NCA) allows more specific conclusions: an example involving well-being and resilience
Authors: Sorjonen Kimmo , Melin Bo
Published: February 2022

Background

After conducting necessary condition analysis (NCA), researchers have concluded that a certain, not too low, level of well-being is necessary but not sufficient for a high level of resilience. However, as acknowledged by the developers of the test, NCA only evaluates if the association between two variables is characterized by some unspecified type of non-randomness and not conditions of necessity.

Method

Earlier reported data on the association between well-being and resilience among Filipino adults (N = 533) in COVID-19 quarantine were re-analyzed with an extended version of NCA.

Results

Analyses indicated a significant necessity effect of resilience on overall well-being, which is not logically compatible with well-being being necessary but not sufficient for resilience. Analyses with an extended version of NCA suggested that the association between overall well-being and resilience was characterized by equal degrees of necessity and sufficiency.

Conclusions

The original version of NCA is only capable of evaluating if the association between two variables is characterized by some unspecified type of non-randomness. The extended version of NCA allows researchers to draw more specific conclusions.
The effectiveness of raising Hong Kong parents’ awareness of antimicrobial resistance through an education program with peer support on social media: a randomized, controlled pilot study
Authors: Or Pui-Lai , Ching Tai-Yin
Published: February 2022

Background

The aim of this study was to address the misuse of antibiotics and test the feasibility of an education program with peer support on social media in improving parents’ knowledge on antimicrobial resistance at a regional level in Hong Kong. This pilot, if successful, will be developed into a main study.

Methods

A cluster randomized controlled trial with two-arms were implemented. The intervention program consisted of two weekly sessions and each session lasted for 90 min. Parents in the intervention group would join a Facebook Page of Antibiotic Use, this online platform would allow participants to build a social network. A total of 48 parents had participated in the program. Parental knowledge and attitude were measured before and after the program using the Parental Perception on Antibiotics (PAPA) scale and the General Self-Efficacy Scale (GSE) to assess differences between and within the intervention and control groups.

Results

All parents in the intervention group had an understanding that antibiotics could be effective at treating some infections only, as compared to 40% in the control group. All parents in the intervention group and 85% of the control group disagreed that they should reduce the dose of antibiotics when their children were recovering. The test was statistically significant (p = 0.039) at p < 0.05. There were a significant difference and a strong negative correlation between peer support on Facebook and the parents’ belief that antibiotics could be stopped when their children felt better, with Pearson coefficient of − 0.78 at p < 0.001. In general, there was no significant difference between the two groups with respect to the scale.

Conclusions

Based on the findings in this pilot study, a further study focused on the education program with enhancement and peer support should be implemented on a larger scale with considerations of how it might support reducing incidence of antimicrobial resistance and potentially influencing prescription expectations of patients when seeking healthcare.

Trial registration

Retrospectively registered Chinese Clinical Trial Registry ChiCTR2100044870.

Registered on 31 March 2021.
Screen time and developmental health: results from an early childhood study in Canada
Authors: Kerai Salima , Almas Alisa , Guhn Martin , Forer Barry , Oberle Eva
Published: February 2022

Background

Research has shown that longer hours of screen time are negatively associated with children’s healthy development. Whereas most research has focused on school-age children, less is known about this association in early childhood. To fill this gap, we examined the association between screen time and developmental health in preschool-aged children.

Methods

This study draws from a data linkage on children (N = 2983; Mean age = 5.2, SD = 0.3 years, 51% male) in British Columbia (BC), Canada, who entered Kindergarten in public elementary schools in 2019. Parent reports on children’s screen time, health behaviors, demographics, and family income collected upon kindergarten entry (09/2019), were linked to teacher reports on children’s developmental health, collected halfway through the school year (02/2020). Screen time was assessed with the Childhood Experiences Questionnaire. Developmental vulnerability versus developmental health in five domains (physical, social, emotional, language and cognition, and communication skills) was measured with the Early Development Instrument.

Results

Logistic regression analyses using generalized estimating equation showed that children with more than one hour of daily screen time were more likely to be vulnerable in all five developmental health domains: physical health and wellbeing (odds ratio [OR] =1.41; 95% confidence interval [CI], 0.99 - 2.0; p=0.058), social competence (OR=1.60; 95% CI, 1.16 – 2.2; p=0.004), emotional maturity (OR=1.29; 95% CI, 0.96 - 1.73; p=0.097), language and cognitive development (OR=1.81; 95% CI, 1.19 - 2.74; p=0.006) and communication skills (OR=1.60; 95% CI, 1.1 – 2.34; p=0.015) compared to children reporting up to one hour of screen time/day. An interaction effect between income and screen time on developmental health outcomes was non-significant. Results were adjusted for child demographics, family income, and other health behaviors.

Conclusions

Daily screen time that exceeds the recommended one-hour limit for young children, as suggested by the Canadian 24-h Movement Guidelines for Children and Youth (Tremblay et al. BMC Public Health. 17:874, 2017; Tremblay J Physical Activity Health. 17:92–5, 2020) is negatively associated with developmental health outcomes in early childhood. Screen-based activities should thus be limited for young children. Future research needs to examine the underlying mechanisms through which screen time is linked to developmental vulnerabilities.
Therapeutic effect of platelet-rich plasma on glucocorticoid-induced rat bone marrow mesenchymal stem cells in vitro
Authors: Wang Yanxue , Luan Shuo , Yuan Ze , Lin Caina , Fan Shengnuo , Wang Shaoling , Ma Chao , Wu Shaoling
Published: February 2022

Background

Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a progressive and disabling disease caused by long-term or high-dose glucocorticoid use. Decreased osteogenesis and proliferation of bone marrow mesenchymal stem cells (BMSCs) are the main pathogenesis of GIONFH. Platelet-rich plasma (PRP) has been shown to play a promising role in bone regeneration. However, the effects of PRP on glucocorticoid-induced BMSCs inhibition remains elusive. The objective of this study was to explore whether PRP could improve thein vitrobiological activities of BMSCs inhibited by high-dose glucocorticoidin vitro.

Methods

In this study, a dexamethasone (Dex)-induced in vitro cell model was established. The effects of PRP on proliferation, migration, cell cycle and apoptosis of rat BMSCs induced with high-dose Dex compared to BMSCCTRL, using CCK-8 assay, transwell, flow cytometry and TUNEL assay, respectively. We further performed the alkaline phosphatase (ALP) and alizarin red (ALR) staining to explore the influence of PRP on osteogenic differentiation. Western Blot was used to detect the expression of Bcl-2, Caspase-3, RUNX2 apoptosis, and osteogenic-related proteins.

Results

We observed increased apoptosis rate and Caspase-3 expression, and the decreased migration and osteogenic differentiation, and down-regulation of RUNX-2 and Bcl-2 expression in Dex-induced BMSCs. PRP could reverse these inhibitory effects of Dex, and enhance the BMSCs proliferation, migration, and osteogenic abilityin vitro.

Conclusion

Ourvitrostudy showed that PRP significantly protected BMSCs from Dex-induced apoptosis, and further promoted BMSCs proliferation, migration, and osteogenic differentiation. This study provides a scientific basis for the prevention and treatment of GIONFH with PRP. Meanwhile, it also lays the foundation for the application of PRP in other musculoskeletal diseases.
A retrospective cohort study on the association between poor sleep quality in junior high school students and high hemoglobin A1c level in early adults with higher body mass index values
Authors: Kasahara Tomoko , Tsujiguchi Hiromasa , Takeshita Yumie , Hara Akinori , Suzuki Keita , Narukawa Nobuhiko , Hayashi Koichiro , Miyagi Masateru , Asai Atsushi , Yamada Yohei , Nakamura Haruki , Suzuki Fumihiko , Pham Kim-Oanh , Hamagishi Toshio , Nakamura Masaharu , Shibata Aki , Shimizu Yukari , Nguyen Thao Thi Thu , Miyagi Sakae , Kambayashi Yasuhiro , Kannon Takayuki , Tajima Atsushi , Tsuboi Hirohito , Konoshita Tadashi , Takamura Toshinari , Nakamura Hiroyuki
Published: February 2022

Background

Few epidemiological studies have been performed to clarify the association between glucose metabolism disorders in early adults (20 years old) and physiological and environmental factors, including body mass index (BMI) in junior high school days. Therefore, we examined the association between hemoglobin A1c (HbA1c) level and body size (BMI) in early adulthood and lifestyles, including sleep habits and BMI in junior high school days in Shika town, a small town in Japan, by conducting a retrospective cohort study.

Methods

We examined the HbA1c levels and body size (BMI) of 99 early adults who turned 20 years old between 2016 and 2020 and were residing in Shika town, Ishikawa Prefecture. We obtained the information on lifestyles and living environment factors, including BMI, from a questionnaire survey conducted among the subjects during their junior high school days (13–15 years old) from 2009 to 2013.

Results

No correlations were observed between the HbA1c levels and the BMI values of the early adults. A two-way analysis of covariance (with the HbA1c levels and BMI values of the early adults as main factors) of the body size and lifestyle habits of the junior high school students revealed that “sleep quality in junior high school” was significantly poorer in the high HbA1c group than in the low HbA1c group in the early adults with high BMI values only. This result was also supported by the logistic regression analysis result.

Conclusions

The present results indicate that poor sleep quality in junior high school was associated with the high HbA1c levels of the early adults with higher BMI values, which suggests that good sleep quality in junior high school prevents the development of hyperglycemia. However, the present study did not find any relationship between early-adult BMI and HbA1c level.
Learning dynamic treatment strategies for coronary heart diseases by artificial intelligence: real-world data-driven study
Authors: Guo Haihong , Li Jiao , Liu Hongyan , He Jun
Published: February 2022

Background

Coronary heart disease (CHD) has become the leading cause of death and one of the most serious epidemic diseases worldwide. CHD is characterized by urgency, danger and severity, and dynamic treatment strategies for CHD patients are needed. We aimed to build and validate an AI model for dynamic treatment recommendations for CHD patients with the goal of improving patient outcomes and learning best practices from clinicians to help clinical decision support for treating CHD patients.

Methods

We formed the treatment strategy as a sequential decision problem, and applied an AI supervised reinforcement learning-long short-term memory (SRL-LSTM) framework that combined supervised learning (SL) and reinforcement learning (RL) with an LSTM network to track patients’ states to learn a recommendation model that took a patient’s diagnosis and evolving health status as input and provided a treatment recommendation in the form of whether to take specific drugs. The experiments were conducted by leveraging a real-world intensive care unit (ICU) database with 13,762 admitted patients diagnosed with CHD. We compared the performance of the applied SRL-LSTM model and several state-of-the-art SL and RL models in reducing the estimated in-hospital mortality and the Jaccard similarity with clinicians’ decisions. We used a random forest algorithm to calculate the feature importance of both the clinician policy and the AI policy to illustrate the interpretability of the AI model.

Results

Our experimental study demonstrated that the AI model could help reduce the estimated in-hospital mortality through its RL function and learn the best practice from clinicians through its SL function. The similarity between the clinician policy and the AI policy regarding the surviving patients was high, while for the expired patients, it was much lower. The dynamic treatment strategies made by the AI model were clinically interpretable and relied on sensible clinical features extracted according to monitoring indexes and risk factors for CHD patients.

Conclusions

We proposed a pipeline for constructing an AI model to learn dynamic treatment strategies for CHD patients that could improve patient outcomes and mimic the best practices of clinicians. And a lot of further studies and efforts are needed to make it practical.
Hyaluronidase-1-mediated glycocalyx impairment underlies endothelial abnormalities in polypoidal choroidal vasculopathy
Authors: Wu Kan Xing , Yeo Natalie Jia Ying , Ng Chun Yi , Chioh Florence Wen Jing , Fan Qiao , Tian Xianfeng , Yang Binxia , Narayanan Gunaseelan , Tay Hui Min , Hou Han Wei , Dunn N. Ray , Su Xinyi , Cheung Chui Ming Gemmy , Cheung Christine
Published: February 2022

Background

Polypoidal choroidal vasculopathy (PCV), a subtype of age-related macular degeneration (AMD), is a global leading cause of vision loss in older populations. Distinct from typical AMD, PCV is characterized by polyp-like dilatation of blood vessels and turbulent blood flow in the choroid of the eye. Gold standard anti-vascular endothelial growth factor (anti-VEGF) therapy often fails to regress polypoidal lesions in patients. Current animal models have also been hampered by their inability to recapitulate such vascular lesions. These underscore the need to identify VEGF-independent pathways in PCV pathogenesis.

Results

We cultivated blood outgrowth endothelial cells (BOECs) from PCV patients and normal controls to serve as our experimental disease models. When BOECs were exposed to heterogeneous flow, single-cell transcriptomic analysis revealed that PCV BOECs preferentially adopted migratory-angiogenic cell state, while normal BOECs undertook proinflammatory cell state. PCV BOECs also had a repressed protective response to flow stress by demonstrating lower mitochondrial functions. We uncovered that elevated hyaluronidase-1 in PCV BOECs led to increased degradation of hyaluronan, a major component of glycocalyx that interfaces between flow stress and vascular endothelium. Notably, knockdown of hyaluronidase-1 in PCV BOEC improved mechanosensitivity, as demonstrated by a significant 1.5-fold upregulation of Krüppel-like factor 2 (KLF2) expression, a flow-responsive transcription factor. Activation of KLF2 might in turn modulate PCV BOEC migration. Barrier permeability due to glycocalyx impairment in PCV BOECs was also reversed by hyaluronidase-1 knockdown. Correspondingly, hyaluronidase-1 was detected in PCV patient vitreous humor and plasma samples.

Conclusions

Hyaluronidase-1 inhibition could be a potential therapeutic modality in preserving glycocalyx integrity and endothelial stability in ocular diseases with vascular origin.
Obesity, metabolic risk and adherence to healthy lifestyle behaviours: prospective cohort study in the UK Biobank
Authors: Heath Laura , Jebb Susan A. , Aveyard Paul , Piernas Carmen
Published: February 2022

Background

Contested evidence suggests that obesity confers no risk to health in people who have a healthy lifestyle, particularly if there are no metabolic complications of obesity. The aim was to examine the association between adherence to lifestyle recommendations and the absence of metabolic complications on the incident or fatal cardiovascular disease and all-cause mortality across different categories of body mass index (BMI).

Methods

This contemporary prospective cohort study included 339,902 adults without cardiovascular disease at baseline, recruited between 2006 and 2010 from the UK Biobank and followed until 2018–2020. The main exposures were four healthy lifestyle behaviours: never smoker, alcohol intake ≤ 112g/ week, 150 min moderate physical activity or 75 min vigorous activity/week, ≥ 5 servings of fruit or vegetables/day, and we assessed these overall and across the BMI groups. Metabolic complications of excess adiposity were hypertension, diabetes and hyperlipidaemia, and we examined whether obesity was associated with increased risk in the absence of these complications. The outcomes were all-cause mortality, death from, and incident cardiovascular disease (CVD).

Results

Individuals who met four lifestyle recommendations but had excess weight had higher all-cause mortality; for BMI 30–34.9 kg/m2, the hazard ratio (HR) was 1.42 (95% confidence interval 1.20 to 1.68), and for BMI ≥ 35 kg/m2, HR was 2.17 (95% CI 1.71 to 2.76). The risk was lower, but still increased for people with no metabolic complications; for all-cause mortality, BMI 30–34.9 kg/m2 had an HR of 1.09 (95% CI 0.99 to 1.21), and BMI ≥ 35 kg/m2 had an HR of 1.44 (95% CI 1.19 to 1.74) for all-cause mortality. Similar patterns were found for incident and fatal CVD.

Conclusions

Meeting healthy lifestyle recommendations, or the absence of metabolic complications of obesity offsets some, but not all, of the risk of subsequent CVD, and premature mortality in people with overweight or obesity. Offering support to achieve and maintain a healthy weight and to adopt healthy behaviours are likely to be important components in effective preventative healthcare.
Characterization of DNA methylation as well as mico-RNA expression and screening of epigenetic markers in adipogenesis
Authors: Zhang Yong , Chen Fancheng , Zhang Fangxue , Huang Xiaowei
Published: February 2022

This study aimed to use bioinformatics methods to characterize epigenetic changes in terms of micro-RNA(miRNA) expression and DNA methylation during adipogenesis. The mRNA and miRNA expression microarray and DNA methylation dataset were obtained from the GEO database. Differentially expressed genes (DEGs), differentially expressed miRNAs (DEMs) and differentially methylated probes (DMPs) were filtered using the limma package. The R language cluster profile package was used for functional and enrichment analysis. A protein–protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape. The Connection map (CMap) website tool was used to screen potential therapeutic drugs for adipogenesis. When comparing the early and late stages of adipogenesis, 111 low miRNA targeted upregulated genes and 64 high miRNA targeted downregulated genes were obtained, as well as 663 low-methylated high-expressed genes and 237 high-methylated low-expressed genes. In addition, 41 genes (24 upregulated and 17 downregulated) were simultaneously regulated by abnormal miRNA changes and DNA methylation. Ten chemicals were identified as putative therapeutics for adipogenesis. In addition, among the dual-regulated genes identified, CANX, HNRNPA1, MCL1, and PPIF may play key roles in the epigenetic regulation of adipogenesis and may serve as aberrant methylation or miRNA targeting biomarkers.
The prevalence and pattern of cannabis use among patients attending a methadone treatment clinic in Nairobi, Kenya
Authors: Ngarachu Elizabeth Wambui , Kiburi Sarah Kanana , Owiti Frederick R. , Kangethe Rachel
Published: February 2022

Background

Cannabis use during methadone treatment may negatively impact treatment outcomes. The aim of this study was to determine the prevalence and pattern of cannabis use among patients attending a methadone treatment clinic in Nairobi, Kenya.

Methods

This was a retrospective study of 874 patients on methadone therapy at a methadone maintenance treatment clinic in Nairobi, Kenya from December 2014 to November 2018. Data on sociodemographic characteristics and drug use patterns based on urine drug screens was collected from patient files. Data was analyzed using Statistical Package for the Social Sciences (SPSS) for windows version 23.0.

Results

Point prevalence of cannabis use was 85.8% (95% CI, 83.3 – 88.0) at baseline and 62.7% (95% CI, 59.5 – 65.8) during follow-up. A pattern of polysubstance use was observed where opioids, cannabis and benzodiazepines were the most commonly used drugs. The mean age of the patients was 35.3 (SD 9.0) years with the majority being male, unemployed (76%), (51.4%) had reached primary level of education, and (48.5%) were divorced or separated. University education was associated with reduced risk for cannabis use OR = 0.1 (95% CI, 0.02-0.8, p = 0.031).

Conclusion

Cannabis use is prevalent among patients attending a methadone treatment clinic in Kenya, suggesting need for targeted interventions to address the problem of cannabis use during methadone treatment.
Efficiently sparse listing of classes of optimal cophylogeny reconciliations
Authors: Wang Yishu , Mary Arnaud , Sagot Marie-France , Sinaimeri Blerina
Published: February 2022

Background

Cophylogeny reconciliation is a powerful method for analyzing host-parasite (or host-symbiont) co-evolution. It models co-evolution as an optimization problem where the set of all optimal solutions may represent different biological scenarios which thus need to be analyzed separately. Despite the significant research done in the area, few approaches have addressed the problem of helping the biologist deal with the often huge space of optimal solutions.

Results

In this paper, we propose a new approach to tackle this problem. We introduce three different criteria under which two solutions may be considered biologically equivalent, and then we propose polynomial-delay algorithms that enumerate only one representative per equivalence class (without listing all the solutions).

Conclusions

Our results are of both theoretical and practical importance. Indeed, as shown by the experiments, we are able to significantly reduce the space of optimal solutions while still maintaining important biological information about the whole space.
In vitro effect of triamcinolone and platelet-rich plasma on cytokine levels of elbow lateral epicondylitis-derived cells
Authors: de Melo Viveiros Márcio Eduardo , Viveiros Magda Massae Hata , da Silva Márcia Guimarães , Rainho Cláudia Aparecida , Schellini Silvana Artioli
Published: February 2022

Background

The pathogenesis and treatment of lateral elbow epicondylitis (LEE) are still controversial. The purpose of the current study was to evaluate the production of inflammatory cytokines by LEE-derived cells and to compare the anti-inflammatory effect of triamcinolone acetonide with platelet-rich plasma (PRP) on cytokines production in primary culture of these cells.

Methods

Third passage cells from primary cultures of LEE were assessed for the production of the cytokines IL-1β, IL-6, IL-8, IL-10 and TNF-α by immune-enzymatic assay (ELISA), after the treatment with 1, 10 and 100 μM triamcinolone compared to no treated controls at the time points 6, 12, 18, 24, 48, 72 and 96 h, and to PRP at 48, 72 and 96 h.

Results

The cytokines IL-6 and IL-8 were produced in high concentrations by LEE cells. One, 10 and 100 μM triamcinolone induced significant decrease in the production of IL-6 and IL-8 at 48, 72 and 96 h, adding the time point 12 h for IL-8. Compared to controls, PRP caused a significant increase in the production of IL-6 and IL-8 and there was a significant increase in IL-10 production with the use of 100 μM triamcinolone at 48 h. The production of IL1-β and TNF-α was very low and did not change when the cultures were treated with triamcinolone or PRP.

Conclusion

LEE-derived cells produce IL-6 and IL-8, confirming the inflammatory nature of this condition. While triamcinolone inhibited the production of IL-6 and IL-8 by LEE cells, PRP induced an increase in these cytokines compared with controls.
Global prevalence of Duchenne and Becker muscular dystrophy: a systematic review and meta-analysis
Authors: Salari Nader , Fatahi Behnaz , Valipour Elahe , Kazeminia Mohsen , Fatahian Reza , Kiaei Aliakbar , Shohaimi Shamarina , Mohammadi Masoud
Published: February 2022

Background

A variety of mutations in the largest human gene, dystrophin, cause a spectrum from mild to severe dystrophin-associated muscular dystrophies. Duchenne (DMD) and Becker (BMD) muscular dystrophies are located at the severe end of the spectrum that primarily affects skeletal muscle. Progressive muscle weakness in these purely genetic disorders encourages families with a positive history for genetic counseling to prevent a recurrence, which requires an accurate prevalence of the disorder. Here, we provide a systematic review and meta-analysis to determine the prevalence of DMD and BMD worldwide.

Method

The current systematic review and meta-analysis was carried out using Cochrane seven-step procedure. After determining the research question and inclusion and exclusion criteria, the MagIran, SID, ScienceDirect, WoS, ProQuest, Medline (PubMed), Embase, Cochrane, Scopus, and Google Scholar databases were searched to find relevant studies using defined keywords and all possible keyword combinations using the AND and OR, with no time limit until 2021. The heterogeneity of studies was calculated using the I2 test, and the publication bias was investigated using the Begg and Mazumdar rank correlation test. Statistical analysis of data was performed using Comprehensive Meta-Analysis software (version 2).

Results

A total of 25 articles involving 901,598,055 people were included. The global prevalence of muscular dystrophy was estimated at 3.6 per 100,000 people (95 CI 2.8–4.5 per 100,000 people), the largest prevalence in the Americans at 5.1 per 100,000 people (95 CI 3.4–7.8 per 100,000 people). According to the subgroup analysis, the prevalence of DMD and BMD was estimated at 4.8 per 100,000 people (95 CI 3.6–6.3 per 100,000 people) and 1.6 per 100,000 people (95 CI 1.1–2.4 per 100,000 people), respectively.

Conclusion

Knowing the precise prevalence of a genetic disorder helps to more accurately predict the likelihood of preventing its occurrence in families. The global prevalence of DMD and BMD was very high, indicating the urgent need for more attention to prenatal screening and genetic counseling for families with a positive history.
α-Tocopherol phosphate as a photosensitizer in the reaction of nucleosides with UV light: formation of 5,6-dihydrothymidine
Authors: Suzuki Toshinori , Ono Chiaki
Published: February 2022

Introduction

α-Tocopherol phosphate, a natural water-soluble α-tocopherol analog, exists in biological tissues and fluids. Synthesized α-tocopherol phosphate is used as an ingredient of cosmetics.

Findings

When a neutral mixed solution of 2′-deoxycytidine, 2′-deoxyguanosine, thymidine, and 2′-deoxyadenosine was irradiated with UV light at wavelengths longer than 300 nm in the presence of α-tocopherol phosphate, thymidine was markedly consumed in an α-tocopherol phosphate dose-dependent manner, whereas other nucleosides only slightly decreased. Two major product peaks were detected in an HPLC chromatogram. The products were identified as diastereomers of 5,6-dihydrothymidine. The addition of radical scavengers had almost no effects on the generation of 5,6-dihydrothymidine, whereas the reactions of nucleosides other than thymidine were suppressed. Trolox, another water-soluble α-tocopherol analog, did not generate 5,6-dihydrothymidine, although all nucleosides were slightly consumed. When UV irradiation of thymidine with α-tocopherol phosphate was conducted in D2O, two deuterium atoms were added to 5 and 6 positions of thymidine with both syn and anti configurations. The ratio of syn and anti configurations alternated depending on pD of the solution.

Conclusions

The results indicate that α-tocopherol phosphate is a photosensitizer of nucleosides, especially thymidine, and that it introduces two hydrogen atoms to thymidine from H2O, generating 5,6-dihydrothymidine.
Effect of cationic monomer structure on the aggregation behavior of amphoteric acrylic polymer around isoelectric point
Authors: Li Qijun , Yi Yudan , Wang Ya-nan , Li Jing , Shi Bi
Published: February 2022

Amphoteric polymer can be used as retanning agent in leather manufacture. It is particularly useful in chrome-free tanning systems since it can regulate the charge properties of chrome-free leather and enhance the fixation of anionic post-tanning chemicals in leather. However, the aggregation and precipitation of amphoteric polymer retanning agents around the isoelectric point (pI) hinder their wide application. Herein, we synthesized five amphoteric acrylic polymers (AAPs) by free radical copolymerization with acrylic acid and five different cationic acrylic monomers. The effect of cationic monomer structure on the aggregation behavior of AAPs was investigated. The aggregation of AAPs in aqueous solution showed pH and concentration dependence. Light scattering analysis showed that Poly (AA-co-MAPTAC) and Poly (AA-co-DMAPMA) were in the shape of coiled linear flexible chains with small particle size (Rg 7.6 nm and 14.8 nm, respectively) near the pI. However, Poly (AA-co-DAC), Poly (AA-co-DMC) and Poly (AA-co-DMAEMA) were in the shape of hollow spheres and exhibited serious aggregation. Quantum chemical calculations suggested that the amide groups in the cationic monomers MAPTAC and DMAPMA enhanced the nucleophilicity of AAPs. Thus the corresponding AAPs could carry a large number of cationic charges to slow their aggregation when the pH just climbed over the pI. The results are expected to provide theoretical reference for the synthesis and widespread application of AAPs.
Bletilla striata polysaccharide modified collagen fiber composite sponge with rapid hemostasis function
Authors: Yan Xingyu , Chen Yining , Dan Weihua , Dan Nianhua , Li Zhengjun
Published: February 2022

Emergencies often result in uncontrollable bleeding, which is thought to be the leading cause of death at the scene of the injured. Among various hemostasis scenarios, collagen fiber (CF) is gradually replacing traditional hemostatic materials due to its superior properties and ease of sourcing from animals. Herein, we use CF and the natural herbaceous Bletilla striata as raw materials to prepare a collagen fiber-oxidized Bletilla striata composite hemostatic sponge (CFOB). During the cross-linking process, the triple helix structure of collagen stays intact, and its porous three-dimensional network structure brings excellent bulkiness and water absorption properties. Experiments show that the optimal amount of sponge CFOB-10, namely oxidized Bletilla striata polysaccharide 0.5 mg/mL and CF 5 mg/mL, only needed 25 ± 4.06 s for hemostasis time in the rat liver hemorrhage model. In addition, CFOB meets the safety performance requirements of cytotoxicity classification standard 0. Therefore, the optimal amount of CFOB is an excellent new hemostatic material with application potential.

Graphical Abstract
Emerging complications of COVID-19 in a subset of Indian population: a pathological review with clinico-radiological case scenarios
Authors: Agarwal Aniket , Prachi  , Haider Andaleeb , Lalit Ekansh , Agarwal Ajay Kumar , Agarwal Seema
Published: February 2022

Background

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was declared a pandemic by the World Health Organization on 11 March 2020 has been reported in most countries around the world since its origins in Wuhan, China. As of September 2021, there have been over 229 million cases of COVID-19 reported worldwide, with over 4.7 million COVID-19–associated deaths.

Body

The devastating second wave of the COVID-19 pandemic in India has seen a rise in various extrapulmonary manifestations. One of key components in the pathogenesis of COVID-19 is downregulation of ACE-2, which is expressed on many organs and counterbalances the pro-inflammatory effects of ACE/angiotensin-II axis. This leads to influx of inflammatory cells into alveoli, increased vascular permeability and activation of prothrombotic mediators. Imaging findings such as ground glass opacities, interlobular septal thickening, vascular dilatation and pulmonary thrombosis correlate well with the pathogenesis.

Conclusion

We hypothesize that the systemic complications of COVID-19 are caused by either direct viral invasion or effect of cytokine storm leading to inflammation and thrombosis or a combination of both. Gaining insights into pathobiology of SARS-CoV-2 will help understanding the various multisystemic manifestations of COVID-19. To date, only a few articles have been published that comprehensively describe the pathophysiology of COVID-19 along with its various multisystemic imaging manifestations.