Tag: pubmed

Genome Biol. 2022 Oct 17;23(1):222. doi: 10.1186/s13059-022-02774-z.

ABSTRACT

Single-cell high-throughput chromatin conformation capture methodologies (scHi-C) enable profiling of long-range genomic interactions. However, data from these technologies are prone to technical noise and biases that hinder downstream analysis. We develop a normalization approach, BandNorm, and a deep generative modeling framework, scVI-3D, to account for scHi-C specific biases. In benchmarking experiments, BandNorm yields leading performances in a time and memory efficient manner for cell-type separation, identification of interacting loci, and recovery of cell-type relationships, while scVI-3D exhibits advantages for rare cell types and under high sparsity scenarios. Application of BandNorm coupled with gene-associating domain analysis reveals scRNA-seq validated sub-cell type identification.

PMID:36253828 | DOI:10.1186/s13059-022-02774-z

BMC Med Genomics. 2022 Oct 17;15(1):217. doi: 10.1186/s12920-022-01372-z.

ABSTRACT

BACKGROUND: Bladder cancer (BC) is the 10^th most frequent tumor worldwide. Evidence shows an association between elevated risk of BC and various single nucleotide polymorphisms (SNP). BC incidence was the highest in Lebanon according to Globocan 2018 report, but little is known about the genetic susceptibility of Lebanese people to this disease. We aim to evaluate whether this prominent incidence of BC in Lebanon is attributable to known coding genetic variants.

METHODS: A case-control study was conducted at Hotel-Dieu de France Hospital, Beirut. A cohort of 51 Lebanese patients with BC were recruited between 2017 and 2020. Whole Exome Sequencing (WES) was performed on peripheral blood samples to detect coding genetic variants in the patients. An in-house database including WES data from 472 Lebanese individuals served as control. Literature review of the genetic predisposition to BC was conducted to establish a database of variants known to influence the risk of BC. In-common SNPs were identified between cases and the aforecited database, and their allelic frequencies was quantified in the former and in controls. Comparative analysis of the allelic frequencies of each in-common SNP was carried out between cases, controls, and the genome aggregation database (gnomAD). Analysis was performed by applying the binomial law and setting the p-value to 10^{– 10}.

RESULTS: 484 polymorphisms associated with BC were extracted from the literature review ;151 of which were in-common with the 206 939 variations detected by WES in our cases. Statistically significant differences (p-value < 10^{– 10}) in allelic frequencies was seen in 11 of the 151 in-common SNPs, but none of which corresponds with a higher BC risk. Moreover, rs4986782 variant in the NAT1 gene is not associated with BC in the Lebanese population. `.

CONCLUSION: This is the first next-generation sequencing (NGS)- based study investigating BC risk in a Lebanese cohort of 51 patients. The majority of known exonic variants in the literature were not associated with BC in our patients. Further studies with larger sample sizes are warranted to explore the association of BC in our population with known non-coding genetic variants, and the remainder of WES-generated private Lebanese variants.

PMID:36253817 | DOI:10.1186/s12920-022-01372-z

BMC Public Health. 2022 Oct 17;22(1):1927. doi: 10.1186/s12889-022-14305-3.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has been characterized by multiple waves with varying rates of transmission affecting countries at different times and magnitudes. Forced displacement settings were considered particularly at risk due to pre-existing vulnerabilities. Yet, the effects of COVID-19 in refugee settings are not well understood. In this study, we report on the epidemiology of COVID-19 cases in Uganda’s refugee settlement regions of West Nile, Center and South, and evaluate how health service utilization changed during the first year of the pandemic.

METHODS: We calculate descriptive statistics, testing rates, and incidence rates of COVID-19 cases in UNHCR’s line list and adjusted odds ratios for selected outcomes. We evaluate the changes in health services using monthly routine data from UNHCR’s health information system (January 2017 to March 2021) and apply interrupted time series analysis with a generalized additive model and negative binomial distribution, accounting for long-term trends and seasonality, reporting results as incidence rate ratios.

FINDINGS: The first COVID-19 case was registered in Uganda on March 20, 2020, and among refugees two months later on May 22, 2020 in Adjumani settlement. Incidence rates were higher at national level for the general population compared to refugees by region and overall. Testing capacity in the settlements was lower compared to the national level. Characteristics of COVID-19 cases among refugees in Uganda seem to align with the global epidemiology of COVID-19. Only hospitalization rate was higher than globally reported. The indirect effects of COVID-19 on routine health services and outcomes appear quite consistent across regions. Maternal and child routine and preventative health services seem to have been less affected by COVID-19 than consultations for acute conditions. All regions reported a decrease in consultations for respiratory tract infections.

INTERPRETATION: COVID-19 transmission seemed lower in settlement regions than the national average, but so was testing capacity. Disruptions to health services were limited, and mainly affected consultations for acute conditions. This study, focusing on the first year of the pandemic, warrants follow-up research to investigate how susceptibility evolved over time, and how and whether health services could be maintained.

PMID:36253816 | DOI:10.1186/s12889-022-14305-3

BMC Med Educ. 2022 Oct 17;22(1):726. doi: 10.1186/s12909-022-03776-y.

ABSTRACT

BACKGROUNDS: On March 11, 2020, the World Health Organization (WHO) declared the novel coronavirus (COVID-19) outbreak a global pandemic, which changed the residents’ teaching and learning process. The purpose of this study was to determine residents’ satisfaction and impressions on their training during the pandemic in a tertiary pediatric hospital.

METHODS: This was a descriptive cross-sectional study. An online survey was designed to determine residents’ demographic and personal characteristics, as well as their perception about the theoretical and practical training, as well as about their emotional situation. The analysis separated medical students from surgical students in order to identify any differences existing between these groups, for which χ2 was calculated.

RESULTS: Overall, 148 of 171 residents (86.5%) responded to the questionnaire; 75% belonged to the medical specialty and 25% to the surgical specialty. Statistically significant differences were found in terms of those training aspects they were concerned about during the pandemic (p < 0.001) and about the difficulties associated with online learning (p = 0.001). Differences were also found regarding their satisfaction toward the time needed to complete their thesis (p = 0.059) and activities outside the hospital (p = 0.029). Regarding their degree of satisfaction in general, most medical specialty students felt slightly satisfied (43.2%) and surgical specialty students felt mostly neutral (37.8%). Regarding their feelings about their mental health, statistically significant differences were found between both groups (p = 0.038) although both groups reported the same percentage of overall dissatisfaction (2.7%) in this area.

CONCLUSION: The COVID-19 pandemic has brought significant challenges to medical education systems. Lack of practice in decision-making and maneuver execution are concerns for residents and may affect their future professional performance.

PMID:36253812 | DOI:10.1186/s12909-022-03776-y

BMC Nutr. 2022 Oct 17;8(1):113. doi: 10.1186/s40795-022-00598-5.

ABSTRACT

INTRODUCTION: Malnutrition is a major public health problem that is experienced by many developing countries, like Ethiopia. Though some studies were conducted to identify the magnitude and determinants of acute malnutrition among under-five children, there is a lack of evidence that is representative of all children in Ethiopia. Hence, this national-level data could be representative of all targets and provide us with updated information on the nation-wide magnitude of nutritional status among children under the age of five in Ethiopia.

METHODS: This study used data from the 2019 Mini-Ethiopia Demographic and Health Survey (EDHS). Children aged 0-59 months with anthropometry data were included. Data processing and analysis were performed using STATA 15 software. Cross-tabulations and summary statistics were done to describe the study population. Generalized Linear Mixed Models (GLMMs) were used to estimate the association between nutritional status and explanatory variables and were expressed as an odds ratio with a 95% confidence interval (CI). Model comparison was done based on Akaike and Bayesian information criteria (AIC and BIC).

RESULTS: The magnitude of stunting was 37.71% [95%CI: 36.35-39.08], while the magnitude of wasting was 7.14% [95%CI: 6.52-7.91]. Living in Tigray [AOR = 2.90, 95%CI: 2.05-4.11], Amhara [AOR = 1.98, 95%CI: 1.41-2.79], having a child aged 24-35 [AOR = 3.79, 95%CI: 3.07-4.68], and being a rural resident were all significantly associated with stunting. Being born in Tigray [AOR = 1.75, 95% CI: 1.02-3.01], being born into the richest family [AOR = 0.74, 95% CI: 0.27-0.80], and being born from mothers aged 25-29 [AOR = 0.73, 95% CI: 0.55-0.96] were all significantly associated with wasting.

CONCLUSION: The magnitude of stunting and wasting is relatively high in Ethiopia. Region, place of residence, and age of the child were significantly associated with stunting, and region, wealth index, and age of the child were significantly associated with wasting. This result provides a clue to give due consideration to under-five children to mitigate the risks of malnutrition through various techniques.

PMID:36253811 | DOI:10.1186/s40795-022-00598-5

Acta Vet Scand. 2022 Oct 17;64(1):27. doi: 10.1186/s13028-022-00647-w.

ABSTRACT

BACKGROUND: In the Danish Veterinary Statistics Program, VetStat, sales data on medicinal products prescribed for veterinary consumption is collected. The Danish Food and Veterinary Administration (DVFA) manages the database and each purchase contains detailed product-specific information linked with a species-specific ID. National surveillance systems are also implemented or being developed in the other European Union Member States. By 2029, all Member States are required to report data on antimicrobial usage for companion animals to the European Medicines Agency. This study aimed to assess the challenges encountered when using the VetStat database to quantify antimicrobial use in Danish companion animals. Raw VetStat data were propagated by the DVFA and originated from veterinary practitioners and Danish pharmacies.

RESULTS: Comprehensive estimates of antimicrobial use in Danish companion animals were not readily available due to database construct. Antimicrobials sold for use in companion animals (linked to a companion animal ID) comprised a large number of products licensed solely for horses or livestock, while data assigned a replacement code encompassed both topical and peroral antimicrobials licensed for companion animals. Additionally, antimicrobials sold from pharmacies to veterinary practitioners presented the biggest challenge in data retrieval and validation. Treatment data are only transferred to VetStat through the billing systems when Danish veterinarians are treating livestock, but not companion animals. Information on products sold for in-house use in companion animals is only available from pharmacy records without a species-specific ID. As a result, parenteral antimicrobials with multi-species authorization utilized by small animal veterinary practitioners are not accounted for in the overall estimate for companion animals.

CONCLUSIONS: Owing to the database structure and requirements for data entry, antimicrobial use in companion animals is an approximation. The actual consumption may be significantly higher than what is currently calculated from the database, as the majority of parenteral products are not included. Consumption data can be measured more accurately provided treatment data from veterinary practitioners in small or mixed practices are transferred to the database through the billing system. This would equal the legal requirements for Danish veterinary practitioners treating livestock.

PMID:36253805 | DOI:10.1186/s13028-022-00647-w

Exp Hematol Oncol. 2022 Oct 17;11(1):73. doi: 10.1186/s40164-022-00328-4.

ABSTRACT

There are considerable new data on mutation topography in persons with myelodysplastic syndromes (MDS). These data have been used to update conventional risk models such as the Revised International Prognostic Scoring System (IPSS-R). Whether the molecular IPSS (IPSS-M) which includes these data improves survival prediction accuracy is untested. To answer this question, we compared survival prediction accuracies of the IPSS-R and IPSS-M in 852 consecutive subjects with de novo MDS. Concordance statistics (C-statistics) of the IPSS-R and IPSS-M in the entire cohort were similar, 0.67 (95% Confidence Interval [CI] 0.64, 0.71) and 0.68 (0.64, 0.71). Average numbers of mutations and of IPSS-M related mutations were greater in persons ≥ 60 years (2.0 [Interquartile Range [IQR], 1, 3] vs. 1.6 [0, 2], P = 0.003; 1.6 [0, 2] vs. 1.3 [0, 2], P = 0.006). Subjects ≥ 60 years had a higher incidence of mutations in RUNX1, TP53, TET2, SRSF2, DNMT3A, STAG2, EZH2 and DDX41. In contrast, mutations in U2AF1 were more common in persons < 60 years. Next we tested survival prediction accuracy based on age < or ≥ 60 years. C-statistics of the IPSS-R and IPSS-M in subjects ≥ 60 years were 0.66 (0.61, 0.71) and 0.69 (0.64, 0.73) whereas in subjects < 60 years they were 0.67 (0.61, 0.72) and 0.65 (0.59, 0.71). These data indicate an advantage for the IPSS-M over the IPSS-R in subjects ≥ 60 years but not in those < 60 years probably because of a great frequency of mutations correlated with survival in those ≥ 60 years.

PMID:36253799 | DOI:10.1186/s40164-022-00328-4

Genome Biol. 2022 Oct 17;23(1):218. doi: 10.1186/s13059-022-02783-y.

ABSTRACT

BACKGROUND: Cell-cell interactions are important for information exchange between different cells, which are the fundamental basis of many biological processes. Recent advances in single-cell RNA sequencing (scRNA-seq) enable the characterization of cell-cell interactions using computational methods. However, it is hard to evaluate these methods since no ground truth is provided. Spatial transcriptomics (ST) data profiles the relative position of different cells. We propose that the spatial distance suggests the interaction tendency of different cell types, thus could be used for evaluating cell-cell interaction tools.

RESULTS: We benchmark 16 cell-cell interaction methods by integrating scRNA-seq with ST data. We characterize cell-cell interactions into short-range and long-range interactions using spatial distance distributions between ligands and receptors. Based on this classification, we define the distance enrichment score and apply an evaluation workflow to 16 cell-cell interaction tools using 15 simulated and 5 real scRNA-seq and ST datasets. We also compare the consistency of the results from single tools with the commonly identified interactions. Our results suggest that the interactions predicted by different tools are highly dynamic, and the statistical-based methods show overall better performance than network-based methods and ST-based methods.

CONCLUSIONS: Our study presents a comprehensive evaluation of cell-cell interaction tools for scRNA-seq. CellChat, CellPhoneDB, NicheNet, and ICELLNET show overall better performance than other tools in terms of consistency with spatial tendency and software scalability. We recommend using results from at least two methods to ensure the accuracy of identified interactions. We have packaged the benchmark workflow with detailed documentation at GitHub ( https://github.com/wanglabtongji/CCI ).

PMID:36253792 | DOI:10.1186/s13059-022-02783-y

BMC Cancer. 2022 Oct 18;22(1):1072. doi: 10.1186/s12885-022-10179-1.

ABSTRACT

BACKGROUND: Although there is broad consensus that only a subset of CIN3 will progress to cancer, there is currently no surefire way to predict which CIN3 will regress. Understanding the natural history of CIN3 is important, and finding markers for progression or regression could improve treatment strategies. According to the guidelines of the American Society for Colposcopy and Cervical Pathology of 2006, positive CIN3 p16 in women should be managed with excisional treatment (LEEP). For ethical reasons we cannot fail to treat women with CIN3 in order to study their regression capacity so we conducted a retrospective study to evaluate the regression rate of CIN3 diagnosed with a biopsy by studying the histological result of the cone removed by LEEP. We also investigated age, HPV genotypes and biopsy-cone interval distance as possible regression factors.

METHODS: We selected 171 women with a histological diagnosis of positive CIN3 p16 as an entry criterion. All patients underwent LEEP / biopsy. A histological diagnosis of the cone of CIN3 or higher was considered as persistence or progression, the diagnosis of CIN1 or lower was considered as regression of the lesion. We used out a logistic model to study the probability of spontaneous regression of CIN3 as a function of the patient’s age, the time elapsed between the biopsy and the cone (in weeks) and the HPV genotype.

RESULTS: We found that the spontaneous regression rate of CIN3 was 15,8%, which was strongly associated with the biopsy-cone interval > 11 weeks. Genotype 16, the most represented, was present both in cases of regression (77.8%) and in persistence (83.3%). Regarding age, the estimated odds ratio of the probability of observing a regression in women over 25 years of age was 0.0045 times that of women under 25 years of age (CI: 0.00020, 0.036). Neither age nor viral genotype are significant as predictors of regression.

CONCLUSION: To wait at least 11 weeks from the biopsy before subjecting the woman to LEEP could prevent unnecessary LEEP procedures, considering also that from CIN3 to carcinoma it takes years before the neoplastic transformation takes place.

PMID:36253767 | DOI:10.1186/s12885-022-10179-1

Nutr J. 2022 Oct 17;21(1):64. doi: 10.1186/s12937-022-00817-6.

ABSTRACT

BACKGROUND: Auraptene (AUR) and naringenin (NAR) are citrus-derived phytochemicals that influence several biological mechanisms associated with cognitive decline, including neuronal damage, oxidative stress and inflammation. Clinical evidence of the efficacy of a nutraceutical with the potential to enhance cognitive function in cohorts at risk of cognitive decline would be of great value from a preventive perspective. The primary aim of this study is to determine the cognitive effects of a 36-week treatment with citrus peel extract standardized in levels of AUR and NAR in older adults experiencing subjective cognitive decline (SCD). The secondary aim is to determine the effects of these phytochemicals on blood-based biomarkers indicative of neuronal damage, oxidative stress, and inflammation.

METHODS: Eighty older persons with SCD will be recruited and randomly assigned to receive the active treatment (400 mg of citrus peel extract containing 0.1 mg of AUR and 3 mg of NAR) or the placebo at a 1:1 ratio for 36 weeks. The primary endpoint is a change in the Repeatable Battery for the Assessment of Neuropsychological Status score from baseline to weeks 18 and 36. Other cognitive outcomes will include changes in verbal and nonverbal memory, attention, executive and visuospatial functions. Blood samples will be collected from a consecutive subsample of 60 participants. The secondary endpoint is a change in interleukin-8 levels over the 36-week period. Other biological outcomes include changes in markers of neuronal damage, oxidative stress, and pro- and anti-inflammatory cytokines.

CONCLUSION: This study will evaluate whether an intervention with citrus peel extract standardized in levels of AUR and NAR has cognitive and biological effects in older adults with SCD, facilitating the establishment of nutrition intervention in people at risk of cognitive decline.

TRIAL REGISTRATION: The trial is registered with the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT04744922 on February 9^th, 2021 ( https://www.

CLINICALTRIALS: gov/ct2/show/NCT04744922 ).

PMID:36253765 | DOI:10.1186/s12937-022-00817-6