Tag: pubmed

Cell. 2022 Jan 5:S0092-8674(21)01481-1. doi: 10.1016/j.cell.2021.12.018. Online ahead of print.

ABSTRACT

The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of the healthy and obese human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multi-omic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells, including a population of lipid-associated macrophages (LAMs) at the bile ducts. We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and LAMs. We also uncover the respective spatially resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that LAMs are induced by local lipid exposure, leading to their induction in steatotic regions of the murine and human liver, while Kupffer cell development crucially depends on their cross-talk with hepatic stellate cells via the evolutionarily conserved ALK1-BMP9/10 axis.

PMID:35021063 | DOI:10.1016/j.cell.2021.12.018

Acta Med Port. 2022 Jan 12. doi: 10.20344/amp.15446. Online ahead of print.

ABSTRACT

INTRODUCTION: Pre-exposure prophylaxis (PrEP) has gained relevance as a method of prevention for HIV in certain people and settings. Following the publication of the guideline on PrEP prescribing in Portugal, we aimed to assess the knowledge of Portuguese Medical Students about PrEP.

MATERIAL AND METHODS: An online survey was sent to Medical students of Portuguese Medical Schools. We conducted a descriptive analysis of the results and an analytic cross-sectional study to identify factors associated with “knowing about PrEP”, “having had one class about PrEP” and “identifying eligible groups correctly”.

RESULTS: Of the 796 students that responded to the survey, 64.6% were aware of what PrEP is. Of these, 34.44% acquired this knowledge during their training. Out of the total amount of respondents, 4.77% could identify correctly and completely the eligible groups for PrEP. As the training years went by, the probability of being aware of PrEP, having had one class about PrEP, and identifying the eligible groups correctly, increased. Of the sixth-year students, 43.48% had had one class about PrEP and among the students that were aware of PrEP, 28% identified what the eligible groups were. After adjusting for the school year, we found differences between Medical Schools regarding the outcomes. The association between the different ways of learning about PrEP and the ability to correctly identify eligible groups for PrEP was not statistically significant.

CONCLUSION: The differences between Medical Schools could be harmonized through changes in the medical curricula that would allow this topic to be addressed more often.

PMID:35021038 | DOI:10.20344/amp.15446

Skin Res Technol. 2022 Jan 12. doi: 10.1111/srt.13133. Online ahead of print.

ABSTRACT

BACKGROUND: The elasticity of the dermal layer decreases with aging, leading to ulcer formation and wrinkling, but the mechanism of this change is not fully understood, because it is difficult to access the complex three-dimensional (3D) internal structure of the dermis.

OBJECTIVE: To clarify age-dependent changes in the overall 3D structure of the dermal layer by means of 3D analysis technology.

METHODS: We observed sun-protected human skin by means of X-ray micro CT, identified the layers of the skin, and reconstructed the 3D structure on computer. Age-dependent structural changes of the dermal layer were evaluated by statistical comparison of young and aged skin.

RESULTS: Histological observations suggested the presence of two types of ectopic fat deposits, namely infiltrated subcutaneous fat and isolated fat, in the lower region of the reticular dermal layer in aged skin. To elucidate their nature, we observed skin specimens by X-ray microCT. The epidermis, dermal layer, and subcutaneous adipose layer were well differentiated on CT images, and 3D skin was digitally reconstructed on computer. This method clearly showed that the isolated fat observed histologically was in fact connected to the subcutaneous fat, namely all ectopic fat is connected to the subcutaneous adipose layer. Statistical analysis showed that the severity of fat infiltration into dermal layer is significantly increased in aged skin compared with young skin.

CONCLUSION: Our findings indicate that subcutaneous fat infiltrates into the dermal layer of aged skin. Our 3D analysis approach is advantageous to understand changes of complex internal skin structures with aging.

PMID:35020969 | DOI:10.1111/srt.13133

Pain Med. 2022 Jan 10:pnac006. doi: 10.1093/pm/pnac006. Online ahead of print.

ABSTRACT

OBJECTIVE: Multidimensional aspects of pain have raised awareness about cognitive appraisals, such as perceived injustice (PI) and pain catastrophizing (PC). It has been demonstrated that they play an important role in patients’ pain experience. However, the mediating effect of these appraisals has not been investigated in breast cancer survivors (BCS), nor have they been related to fatigue and sleep.

METHODS: Cross-sectional data from 128 BCS were analysed by structural path analysis with the aim to examine the mediating effect of PI and PC in the relationship of pain on fatigue and sleep.

RESULTS: The indirect mediating effects of PI on fatigue (CSI*PI = 0.21; P < 0.01 and VAS*PI = 1.19; P < 0.01) and sleep (CSI*PI = 0.31; P < 0.01 and VAS*PI = 1.74; P < 0.01) were found significant for both pain measures (Central Sensitization Inventory (CSI) and Visual Analogue Scale (VAS)). PC, on the other hand, only mediated the relationship between pain measured by VAS and fatigue (VAS*PC = 0.80; P = 0.03). Positive associations were found, indicating that higher pain levels are positively correlated with PI and PC, which go hand in hand with higher levels of fatigue and sleep problems.

CONCLUSION: PI is an important mediator in the relationship of pain on fatigue and sleep, while PC is a mediator on fatigue after cancer treatment. These findings highlight that both appraisals are understudied and open new perspectives regarding treatment strategies in BCS.

PMID:35020939 | DOI:10.1093/pm/pnac006

Occup Med (Lond). 2022 Jan 10:kqab185. doi: 10.1093/occmed/kqab185. Online ahead of print.

ABSTRACT

BACKGROUND: Medical incapacity at the wheel is a small but significant factor in accident causation. To mitigate against this, in July 2017 a UK-based bus operator changed its medical assessment policy, requiring all future medicals to include a request to the General Practitioner (GP) for information about any conditions in the medical record which could affect fitness to drive.

AIMS: To evaluate the impact of the change in policy on accident rates.

METHODS: Accident data were obtained over a 5-year period, with information on age and length of service of drivers, from three bus depots. Monthly accident rates, before and after the change in policy were compared with the Wilcoxon matched pairs test, and a line of best fit/R2 obtained via a scatter graph.

RESULTS: Although a general downward trend in accident rates was seen, there was no statistically significant difference between the overall accident rates in the 12 months before and after the policy change in July 2017 (P-value = 0.519, significance level P < 0.05).

CONCLUSIONS: The downward trend in accident rates observed over the study period could not be attributed to the change of policy. However, this intervention warrants further scrutiny due to the potential consequences of passenger service vehicle accidents. Evidence suggests that professional awareness of the UK Driver and Vehicle Licensing Agency fitness to drive standards can be limited, so requesting GP input into driver medicals may raise awareness of these standards from an occupational health perspective.

PMID:35020941 | DOI:10.1093/occmed/kqab185

Int J Epidemiol. 2021 Nov 22:dyab238. doi: 10.1093/ije/dyab238. Online ahead of print.

ABSTRACT

BACKGROUND: Thinness at <5 years of age, also known as wasting, is used to assess the nutritional status of populations for programmatic purposes. Thinness may be defined when either weight-for-height or body-mass-index-for-age (BMI-for-age) are below -2 SD of the respective World Health Organization standards. These definitions were compared for quantifying the burden of thinness.

METHODS: Theoretical consequences of ignoring age were evaluated by comparing, at varying height-for-age z-scores, the age- and sex-specific cut-offs of BMI that would define thinness with these two metrics. Thinness prevalence was then compared in simulated populations (short, intermediate and tall) and real-life data sets from research and the National Family Health Survey-4 (NFHS-4) in India.

RESULTS: In short (-2 SD) children, the BMI cut-offs with weight-for-height criteria were higher in comparison to BMI-for-age after 1 year of age but lower at earlier ages. In Indian research and NFHS-4 data sets (short populations), thinness prevalence with weight-for-height was lower from 0.5 to 1 years but higher at subsequent ages. The absolute difference (weight-for-height – BMI-for-age) for 0.5-5 years was 4.6% (15.9-11.3%) and 2.2% (19.2-17.0%), respectively; this attenuated in the 0-5 years age group. The discrepancy was higher in boys and maximal for stunted children, reducing with increasing stature. In simulated data sets from intermediate and tall populations, there were no meaningful differences.

CONCLUSIONS: The two definitions produce cut-offs, and hence estimates of thinness, that differ with the age, sex and height of children. The relative invariance, with age and stature, of the BMI-for-age thinness definition favours its use as the preferred index for programmatic purposes.

PMID:35020895 | DOI:10.1093/ije/dyab238

Hum Reprod. 2022 Jan 11:deab285. doi: 10.1093/humrep/deab285. Online ahead of print.

ABSTRACT

STUDY QUESTION: Do fertility drugs increase the risk of thyroid cancer among infertile women?

SUMMARY ANSWER: The use of most types of fertility drugs was not associated with an increased risk of thyroid cancer.

WHAT IS KNOWN ALREADY: The incidence of thyroid cancer is higher for women than men, especially during reproductive years, indicating that reproductive hormones may be involved in the development of thyroid cancer. Only a few previous studies have examined the association between the use of fertility drugs and incidence of thyroid cancer and the results are inconclusive.

STUDY DESIGN, SIZE, DURATION: A retrospective, population-based cohort study including all 146 024 infertile women aged 20-45 years and living in Denmark in the period 1995-2017. The women were followed from the date of entry in the cohort (i.e. date of first infertility diagnosis) until the occurrence of thyroid cancer or any other cancer (except non-melanoma skin cancer), death, emigration, total thyroidectomy or the end of follow-up (31 December 2018), whichever occurred first. The median length of follow-up was 11.3 years.

PARTICIPANTS/MATERIALS, SETTING, METHODS: In total, 167 women were diagnosed with thyroid cancer during the follow-up period. Information on the use of specific fertility drugs (clomiphene citrate, gonadotropins, hCGs, GnRH receptor modulators and progesterone), thyroid cancer, covariates and vital status was obtained from the Danish Infertility Cohort and various Danish national registers. Cox proportional hazard regression models were used to calculate hazard ratios (HRs) and 95% CIs for thyroid cancer overall and for papillary thyroid cancer.

MAIN RESULTS AND THE ROLE OF CHANCE: After adjustment for the calendar year of infertility diagnosis, the highest obtained level of education, parity status, obesity or thyroid disease and mutual adjustment for other registered fertility drugs, no marked associations were observed between the use of clomiphene citrate, hCG, gonadotropins or GnRH receptor modulators and risk of overall or papillary thyroid cancer. However, ever use of progesterone was associated with an increased rate of both overall (HR 1.63; 95% CI 1.07-2.48) and papillary (HR 1.66, 95% CI 1.04-2.65) thyroid cancer after mutual adjustment for other specific fertility drugs. For most specific fertility drugs, we observed a tendency toward higher associations with thyroid cancer within the first 5 years after the start of drug use than after 5 years from the start of use. No marked associations were detected according to the cumulative dose for any of the specific fertility drugs.

LIMITATIONS, REASONS FOR CAUTION: Despite a large study population, the statistical precision in some subgroup analyses may be affected due to the low number of thyroid cancer cases. Although we were able to adjust for a number of potential confounders, residual and unmeasured confounding may potentially have affected the observed associations, as we could not adjust for some factors that may influence the association between fertility drugs and thyroid cancer, including age at menarche and BMI.

WIDER IMPLICATIONS OF THE FINDINGS: Although this study, which is the largest to date, provides reassuring evidence that there is no strong link between the use of fertility drugs and thyroid cancer incidence, we observed a modest increased thyroid cancer incidence after the use of progesterone. However, we cannot rule out that this is a chance finding and the potential association between the use of progesterone and thyroid cancer should therefore be investigated further in large epidemiological studies. The results of the present study provide valuable knowledge for clinicians and other health care personnel involved in the diagnosis and treatment of infertility.

STUDY FUNDING/COMPETING INTEREST(S): The study was supported by research grants from the Jascha Foundation and the Aase and Ejner Danielsens Foundation. B.N. received honoraria and/or non-financial support by Gedeon Richter Nordics AB, IBSA Nordic APS and Merck KGAA. The remaining authors have no competing interests.

TRIAL REGISTRATION NUMBER: N/A.

PMID:35020884 | DOI:10.1093/humrep/deab285

J Am Med Inform Assoc. 2022 Jan 10:ocab290. doi: 10.1093/jamia/ocab290. Online ahead of print.

ABSTRACT

OBJECTIVE: Evidence synthesis teams, physicians, policy makers, and patients and their families all have an interest in following the outcomes of clinical trials and would benefit from being able to evaluate both the results posted in trial registries and in the publications that arise from them. Manual searching for publications arising from a given trial is a laborious and uncertain process. We sought to create a statistical model to automatically identify PubMed articles likely to report clinical outcome results from each registered trial in ClinicalTrials.gov.

MATERIALS AND METHODS: A machine learning-based model was trained on pairs (publications known to be linked to specific registered trials). Multiple features were constructed based on the degree of matching between the PubMed article metadata and specific fields of the trial registry, as well as matching with the set of publications already known to be linked to that trial.

RESULTS: Evaluation of the model using known linked articles as gold standard showed that they tend to be top ranked (median best rank = 1.0), and 91% of them are ranked in the top 10.

DISCUSSION: Based on this model, we have created a free, public web-based tool that, given any registered trial in ClinicalTrials.gov, presents a ranked list of the PubMed articles in order of estimated probability that they report clinical outcome data from that trial. The tool should greatly facilitate studies of trial outcome results and their relation to the original trial designs.

PMID:35020887 | DOI:10.1093/jamia/ocab290

Clin Exp Immunol. 2021 Nov 18:uxab015. doi: 10.1093/cei/uxab015. Online ahead of print.

ABSTRACT

Although there is an ever-increasing number of disease-modifying treatments for relapsing multiple sclerosis (MS), few appear to influence COVID-19 severity. There is concern about the use of anti-CD20-depleting monoclonal antibodies, due to the apparent increased risk of severe disease following SARS-CoV-2 infection and inhibition of protective anti-COVID-19 vaccine responses. These antibodies are given as maintenance infusions/injections and cause persistent depletion of CD20+ B cells, notably memory B cell populations that may be instrumental in the control of relapsing MS. However, they also continuously deplete immature and mature/naïve B cells that form the precursors for infection-protective antibody responses, thus blunting vaccine responses. Seroconversion and maintained SARS-CoV-2 neutralizing antibody levels provide protection from COVID-19. However, it is evident that poor-seroconversion occurs in the majority of individuals following initial and booster COVID-19 vaccinations, based on standard 6-monthly dosing intervals. Seroconversion may be optimized in the anti-CD20-treated population by vaccinating prior to treatment-onset or using extended/delayed interval dosing (3-6 month extension to dosing interval) in those established on therapy, with B cell monitoring until (1-3%) B cell repopulation occurs prior to vaccination. Some people will take more than a year to replete and therefore protection may depend on either the vaccine-induced T cell responses that typically occur or may require prophylactic, or rapid post-infection therapeutic, antibody or small molecule anti-viral treatment to optimise protection against COVID-19. Further studies are warranted to demonstrate the safety and efficacy of such approaches and whether or not immunity wanes prematurely as has been observed in the other populations.

PMID:35020857 | DOI:10.1093/cei/uxab015

Bioinformatics. 2022 Jan 10:btac024. doi: 10.1093/bioinformatics/btac024. Online ahead of print.

ABSTRACT

MOTIVATION: Polygenic risk score (PRS) has been widely exploited for genetic risk prediction due to its accuracy and conceptual simplicity. We introduce a unified Bayesian regression framework, NeuPred, for PRS construction, which accommodates varying genetic architectures and improves overall prediction accuracy for complex diseases by allowing for a wide class of prior choices. To take full advantage of the framework, we propose a summary-statistics-based cross-validation strategy to automatically select suitable chromosome-level priors, which demonstrates a striking variability of the prior preference of each chromosome, for the same complex disease, and further significantly improves the prediction accuracy.

RESULTS: Simulation studies and real data applications with seven disease datasets from the Wellcome Trust Case Control Consortium cohort and eight groups of large-scale genome-wide association studies demonstrate that NeuPred achieves substantial and consistent improvements in terms of predictive r2 over existing methods. In addition, NeuPred has similar or advantageous computational efficiency compared with the state-of-the-art Bayesian methods.

AVAILABILITY: The R package implementing NeuPred is available at https://github.com/shuangsong0110/NeuPred.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:35020805 | DOI:10.1093/bioinformatics/btac024