RNA-sequencing technologies provide a powerful tool for expression analysis at gene and isoform level, but accurate estimation of isoform abundance is still a challenge. Standard assumption of ...uniform read intensity would yield biased estimates when the read intensity is in fact non-uniform. The problem is that, without strong assumptions, the read intensity pattern is not identifiable from data observed in a single sample.
We develop a joint statistical model that accounts for non-uniform isoform-specific read distribution and gene isoform expression estimation. The main challenge is in dealing with the large number of isoform-specific read distributions, which potentially are as many as the number of splice variants in the genome. A statistical regularization via a smoothing penalty is imposed to control the estimation. Also, for identifiability reasons, the method uses information across samples from the same region. We develop a fast and robust computational procedure based on the iterated-weighted least-squares algorithm, and apply it to simulated data and two real RNA-Seq datasets with reverse transcription-polymerase chain reaction validation. Empirical tests show that our model performs better than existing methods in terms of increasing precision in isoform-level estimation.
We have implemented our method in an R package called Sequgio as a pipeline for fast processing of RNA-Seq data.
During the first wave of COVID-19 pandemic, the most affected area in Italy was the southeast part of the Lombardy region. The University of Brescia is one of the largest in Northern Italy. The aim ...of this study is to investigate the psychological and somatic symptoms driven by lifestyle changes due to the lockdown among the students of the University of Brescia.15261 University students were enrolled through institutional email;14302 were Master's and Bachelor's Degreestudents,724 were Residents and 235 doctorates.3553 students (23.28% of total),aged on average 22 years, completed the survey. Physical health, dietary and sleep habits, physical activities, economic and social issues were investigated through an anonymous, online ad hoc form, available until July 2020 and approved by the local Ethic Committee. Five psychosomatic outcomes were assessed: digestive disorders, headache, panic-anxiety crises, depression-sadness, fear od COVID-19.Factor analysis was applied to reduce the number of variables while logistic and ordinal logistic regression models were used to test the association between the latent variables and each outcome. Female gender, medium-intensive use of telephone, worsening of sleep quality, mnemonic difficulties and performance reduction were associated with all the outcomes. Low physical activity, increased time spent watching television and the worsening of dietary habits represented a significant risk factor for at least three of the outcomes. Despite the relatively low compliance, the survey clearly identified few priorities of intervention to prevent psychological and somatic effects of pandemic in the next future: circadian rhythm, nutritional habits, physical activity, use of media, gender issues. The results of this study show the psychosomatic effects of social isolation and the pandemic on a population at risk of young adults and can promote interventions to minimize the occurrence of psychosomatic consequences on young adults.
Key messages
Analysis of the main risk and protection factors in a population of young adults in the development of psycho-physical symptoms during the period of isolation due to the covid-19 pandemic.
Support the need to implement public health services also to reduce health costs with possible methods of intervention, in harmony with the findings.
Prostate-specific antigen screening has led to enormous overtreatment of prostate cancer because of the inability to distinguish potentially lethal disease at diagnosis. We reasoned that by ...identifying an mRNA signature of Gleason grade, the best predictor of prognosis, we could improve prediction of lethal disease among men with moderate Gleason 7 tumors, the most common grade, and the most indeterminate in terms of prognosis.
Using the complementary DNA-mediated annealing, selection, extension, and ligation assay, we measured the mRNA expression of 6,100 genes in prostate tumor tissue in the Swedish Watchful Waiting cohort (n = 358) and Physicians' Health Study (PHS; n = 109). We developed an mRNA signature of Gleason grade comparing individuals with Gleason ≤ 6 to those with Gleason ≥ 8 tumors and applied the model among patients with Gleason 7 to discriminate lethal cases.
We built a 157-gene signature using the Swedish data that predicted Gleason with low misclassification (area under the curve AUC = 0.91); when this signature was tested in the PHS, the discriminatory ability remained high (AUC = 0.94). In men with Gleason 7 tumors, who were excluded from the model building, the signature significantly improved the prediction of lethal disease beyond knowing whether the Gleason score was 4 + 3 or 3 + 4 (P = .006).
Our expression signature and the genes identified may improve our understanding of the de-differentiation process of prostate tumors. Additionally, the signature may have clinical applications among men with Gleason 7, by further estimating their risk of lethal prostate cancer and thereby guiding therapy decisions to improve outcomes and reduce overtreatment.
•Somali men in Sweden debate between having a large family or adopting the Swedish practice of a smaller family.•The men have some knowledge of contraception but need more, possibly provided in ...collaboration with the mosque and Somali community.•The men favour joint decision-making and want to play an active role in family planning.
A growing body of research in Sweden has focused on migration and reproductive health, particularly on women’s perspectives, including family planning and contraception. However, knowledge is limited on how immigrant men perceive family planning. The topic is important because women’s use of family planning has been shown to be influenced by their partners and community. Therefore, this study aims to explore perceptions of family planning among Somali men living in Sweden.
A qualitative phenomenographic approach was used. Four focus group discussions were conducted with 41 men aged 28–59 years. Data were analysed using phenomenographic analysis.
Findings.
The following four categories were identified in the analysis: 1) a happier and more sustainable family; 2) ideal family size versus cultural commitment; 3) fears of using modern family planning methods; and 4) a need to be included in family planning. The findings illuminated the complexities of perceptions of family planning. Although Somali men understood the benefits of family planning, they seemed to prefer a large family. However, due to their new social context in Sweden, they had also changed their views on having as large a family as in their home country.
Our findings suggest that Somali men living in Sweden want to be involved in family planning counselling, which may increase women’s use of contraception. However, healthcare providers must ensure that the woman desires her partner’s involvement and be culturally sensitive about couples’ needs.
Human papillomaviruses (HPVs), particularly HPV-16/18, are linked to cervical cancer development. Full-length, recombinant HPV-16/18 E7 oncoproteins were used in a new streptavidin-biotin capture ...ELISA method to investigate anti-HPV E7 antibody prevalence in serum. Sera from 99 healthy women, 70 cervical cancer patients, and 30 patients with cervical pre-invasive neoplasia were analyzed. Anti-HPV-16/18 E7 positivity was found in 53% of cervical cancer patients, in 40% with cervical pre-invasive neoplasia, and in 8% of healthy women. Serum samples from 12 cervical cancer patients were obtained at different time intervals during the treatment. Eleven out of 12 showed a correspondence between HPV-E7 antibody levels (decreasing versus increasing) and the type of response (clinically complete or partial response versus progression or stable disease) at each serological evaluation. Five patients with recurrent HPV-16/18-positive cervical carcinoma were analyzed before and after vaccination with HPV-16/18 E7-pulsed autologous dendritic cells; anti-HPV-16/18 E7 positivity was found in 3 out of 5 women. In conclusion, this assay could potentially be used as an adjunctive tool to monitor the type of response to treatment and possibly to detect antibody induction in cervical cancer patients after vaccination, as a potential marker to evaluate its efficacy.
CCRL2 is a nonsignaling seven-transmembrane domain receptor. CCRL2 binds chemerin, a protein that promotes chemotaxis of leukocytes, including macrophages and natural killer (NK) cells. In addition, ...CCRL2 controls the inflammatory response in different pathologic settings, such as hypersensitivity, inflammatory arthritis, and experimental autoimmune encephalitis. Here, we investigated the role of CCRL2 in the regulation of lung cancer-related inflammation. The genetic deletion of
promoted tumor progression in urethane-induced and in
/
lung tumor mouse models. Similarly, a
-mutant lung tumor displayed enhanced growth in
-deficient mice. This phenotype was associated with a reduced inflammatory infiltrate characterized by the impaired recruitment of several leukocyte populations including NK cells. Bone marrow chimeras showed that CCRL2 expression by the nonhematopoietic cell compartment was responsible for the increased tumor formation observed in
-mutant
-deficient mice. In human and mouse lungs, CCRL2 was expressed by a fraction of CD31
endothelial cells, where it could control NK infiltration. Elevated CCRL2 expression in biopsies from human lung adenocarcinoma positively correlated with clinical outcome. These results provide evidence for a crucial role of CCRL2 in shaping an anti-lung tumor immune response.
Introduction
Longitudinal studies of maternal hemodynamics in twin pregnancy are scarce and preload reserve in twin pregnancies has not been studied. Thus, we aimed to investigate serial changes in ...maternal systemic hemodynamics from the first to third trimester, and cardiovascular response to passive leg raising to evaluate preload reserve using impedance cardiography in a cohort of uncomplicated twin pregnancies.
Material and methods
This was a prospective longitudinal study of 50 twin pregnancies. Maternal hemodynamics was assessed at baseline and 120 seconds after passive leg raising using impedance cardiography, at five time points during gestation. Women were excluded from the analysis if there were pregnancy complications or fewer than three of five planned assessments were available.
Results
Data from 37 uncomplicated twin pregnancies were available for analysis. Mean arterial pressure slightly decreased until 17 weeks’ gestation, then increased. Systemic vascular resistance was constant in the first half of pregnancy before rising steadily thereafter, whereas the cardiac output increased from the first trimester, peaked by the end of the second trimester and then decreased in the third trimester. The change in stroke volume and cardiac output following passive leg raising during pregnancy ranged from −2.2% to 1.6% and from −3.7% to 3.2%, respectively. Although passive leg raising caused no significant changes in systemic vascular resistance, cardiac output or heart rate, mean arterial pressure decreased in the first and second trimesters.
Conclusions
In uncomplicated twin pregnancies, maternal cardiovascular adaptation is evident from the first trimester. Twin pregnancies show a reduced preload reserve in the second half of gestation.
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