Tag: pubmed

PLoS One. 2022 May 26;17(5):e0268967. doi: 10.1371/journal.pone.0268967. eCollection 2022.

ABSTRACT

Integrated bioinformatics and statistical approaches are now playing the vital role in identifying potential molecular biomarkers more accurately in presence of huge number of alternatives for disease diagnosis, prognosis and therapies by reducing time and cost compared to the wet-lab based experimental procedures. Breast cancer (BC) is one of the leading causes of cancer related deaths for women worldwide. Several dry-lab and wet-lab based studies have identified different sets of molecular biomarkers for BC. But they did not compare their results to each other so much either computationally or experimentally. In this study, an attempt was made to propose a set of molecular biomarkers that might be more effective for BC diagnosis, prognosis and therapies, by using the integrated bioinformatics and statistical approaches. At first, we identified 190 differentially expressed genes (DEGs) between BC and control samples by using the statistical LIMMA approach. Then we identified 13 DEGs (AKR1C1, IRF9, OAS1, OAS3, SLCO2A1, NT5E, NQO1, ANGPT1, FN1, ATF6B, HPGD, BCL11A, and TP53INP1) as the key genes (KGs) by protein-protein interaction (PPI) network analysis. Then we investigated the pathogenetic processes of DEGs highlighting KGs by GO terms and KEGG pathway enrichment analysis. Moreover, we disclosed the transcriptional and post-transcriptional regulatory factors of KGs by their interaction network analysis with the transcription factors (TFs) and micro-RNAs. Both supervised and unsupervised learning’s including multivariate survival analysis results confirmed the strong prognostic power of the proposed KGs. Finally, we suggested KGs-guided computationally more effective seven candidate drugs (NVP-BHG712, Nilotinib, GSK2126458, YM201636, TG-02, CX-5461, AP-24534) compared to other published drugs by cross-validation with the state-of-the-art alternatives top-ranked independent receptor proteins. Thus, our findings might be played a vital role in breast cancer diagnosis, prognosis and therapies.

PMID:35617355 | DOI:10.1371/journal.pone.0268967

Glob Chang Biol. 2022 May 26. doi: 10.1111/gcb.16226. Online ahead of print.

ABSTRACT

The carbon use efficiency (CUE) of soil microorganisms is a critical parameter for the first step of organic carbon (C) transformation by and incorporation into microbial biomass and shapes C cycling in terrestrial ecosystems. As C and nitrogen (N) cycles interact closely and N availability affects microbial metabolism, N addition to soil may shift the microbial CUE. We conducted a meta-analysis (100 data pairs) to generalize information about the microbial CUE response to N addition in soil based on the two most common CUE estimation approaches: (i) ¹³ C-labelled substrate addition (¹³ C-substrate) and (ii) ¹⁸ O-labelled water addition (¹⁸ O-H₂ O). The mean microbial CUE in soils across all biomes and approaches was 0.37. The effects of N addition on CUE, however, were depended on the approach: CUE decreased by 12% if measured by the ¹³ C-substrate approach, while CUE increased by 11% if measured by the ¹⁸ O-H₂ O approach. These differences in the microbial CUE response depending on the estimation approach are explained by the divergent reactions of microbial growth to N addition: N addition decreases the ¹³ C incorporation into microbial biomass (this parameter is in the numerator by CUE calculation based on the ¹³ C-substrate approach). In contrast, N addition slightly increases (although statistically insignificant) the microbial growth rate (in the numerator of the CUE calculation when assessed by the ¹⁸ O-H₂ O approach), significantly raising the CUE. We explained these N addition effects based on CUE regulation mechanisms at the metabolic, cell, community, and ecosystem levels. Consequently, the differences in the microbial responses (microbial growth, respiration, C incorporation, community composition, and dormant or active states) between the ¹³ C-substrate and ¹⁸ O-H₂ O approaches need to be considered. Thus, these two CUE estimation approaches should be compared to understand microbially mediated C and nutrient dynamics under increasing anthropogenic N input and other global change effects.

PMID:35617026 | DOI:10.1111/gcb.16226

Environ Health Perspect. 2022 May;130(5):57702. doi: 10.1289/EHP11281. Epub 2022 May 26.

NO ABSTRACT

PMID:35617000 | DOI:10.1289/EHP11281

Wound Manag Prev. 2022 May;68(5):28-36.

ABSTRACT

BACKGROUND: Multiple factors affect the sleep quality of individuals with intestinal stomas.

PURPOSE: This study sought to determine sleep quality and factors affecting sleep in individuals with intestinal ostomies.

METHODS: A descriptive cross-sectional design was used. This study followed 68 individuals with intestinal stomas at the stoma therapy unit of a university hospital. A form was used to gather information about patient demographic and stoma-related data (age, sex, work status, stoma duration, cause and type of stoma, stoma care provider, sleep status during the day, daily coffee consumption, and stoma-related factors affecting sleep), and the Pittsburgh Sleep Quality Index was used to score patient sleep patterns. Descriptive statistics, t-test, chi-square test, Fisher’s exact test, and logistic regression analysis were used for statistical analysis.

RESULTS: The patients’ mean age was 53.7 ± 13.8 years; 51.5% were male, and 66.2% were married. Of the 68 patients, 41.2% had a diagnosis of rectal cancer, and 55.9% had ileostomies. Mean stoma duration was 24.1 ± 5.8 months, and 57.4% of participants performed their own stoma care. On a scale of 0 to 21, the participants’ mean sleep score was 9.08 ± 5.03, and 66.2% of patients were found to have poor sleep quality. High sleep quality was significantly positively associated with colostomy (odds ratio, 1.78; 95% confidence interval [CI], 1.18-2.69; P = .006) and self-performed stoma care (odds ratio, 1.54; 95% confidence interval, 1.03-2.30; P = .036).

CONCLUSION: The results of the current study can provide reference data for future studies and highlight the importance of assessing sleep quality in persons with intestinal stomas.

PMID:35617011

JAMA Oncol. 2022 May 26. doi: 10.1001/jamaoncol.2022.1479. Online ahead of print.

ABSTRACT

IMPORTANCE: Women with large breast size treated with adjuvant breast radiotherapy (RT) have a high rate of acute toxic effects of the skin. Breast RT in the prone position is one strategy that may decrease these toxic effects.

OBJECTIVE: To determine if breast RT in the prone position reduces acute toxic effects of the skin when compared with treatment in the supine position.

DESIGN, SETTING, AND PARTICIPANTS: This phase 3, multicenter, single-blind randomized clinical trial accrued patients from 5 centers across Canada from April 2013 to March 2018 to compare acute toxic effects of breast RT for women with large breast size (bra band ≥40 in and/or ≥D cup) in the prone vs supine positions. A total of 378 patients were referred for adjuvant RT and underwent randomization. Seven patients randomized to supine position were excluded (5 declined treatment and 2 withdrew consent), and 14 patients randomized to prone position were excluded (4 declined treatment, 3 had unacceptable cardiac dose, and 7 were unable to tolerate being prone). Data were analyzed from April 2019 through September 2020.

INTERVENTIONS: Patients were randomized to RT in the supine or prone position. From April 2013 until June 2016, all patients (n = 167) received 50 Gy in 25 fractions (extended fractionation) with or without boost (range, 10-16 Gy). After trial amendment in June 2016, the majority of patients (177 of 190 [93.2%]) received the hypofractionation regimen of 42.5 Gy in 16 fractions.

MAIN OUTCOMES AND MEASURES: Main outcome was moist desquamation (desquamation).

RESULTS: Of the 357 women (mean [SD] age, 61 [9.9] years) included in the analysis, 182 (51.0%) were treated in the supine position and 175 (49.0%) in prone. There was statistically significantly more desquamation in patients treated in the supine position compared with prone (72 of 182 [39.6%] patients vs 47 of 175 [26.9%] patients; OR, 1.78; 95% CI, 1.24-2.56; P = .002), which was confirmed on multivariable analysis (OR, 1.99; 95% CI, 1.48-2.66; P < .001), along with other independent factors: use of boost (OR, 2.71; 95% CI, 1.95-3.77; P < .001), extended fractionation (OR, 2.85; 95% CI, 1.41-5.79; P = .004), and bra size (OR, 2.56; 95% CI, 1.50-4.37; P < .001).

CONCLUSIONS AND RELEVANCE: This randomized clinical trial confirms that treatment in the prone position decreases desquamation in women with large breast size receiving adjuvant RT. It also shows increased toxic effects using an RT boost and conventional fractionation.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01815476.

PMID:35616948 | DOI:10.1001/jamaoncol.2022.1479

JAMA Netw Open. 2022 May 2;5(5):e2213945. doi: 10.1001/jamanetworkopen.2022.13945.

ABSTRACT

IMPORTANCE: New-onset atrial fibrillation (AF) is commonly reported in patients with severe infections. However, the absolute risk of thromboembolic events without anticoagulation remains unknown.

OBJECTIVE: To investigate the thromboembolic risks associated with AF in patients with pneumonia, assess the risk of recurrent AF, and examine the association of initiation of anticoagulation therapy with new-onset AF.

DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study used linked Danish nationwide registries. Participants included patients hospitalized with incident community-acquired pneumonia in Denmark from 1998 to 2018. Statistical analysis was performed from August 15, 2021, to March 12, 2022.

EXPOSURES: New-onset AF.

MAIN OUTCOMES AND MEASURES: Thromboembolic events, recurrent AF, and all-cause death. Estimated risks were calculated for thromboembolism without anticoagulation therapy, new hospital or outpatient clinic contact with AF, initiation of anticoagulation therapy, and all-cause death at 1 and 3 years of follow-up. Death was treated as a competing risk, and inverse probability of censoring weights was used to account for patient censoring if they initiated anticoagulation therapy conditioned on AF.

RESULTS: Among 274 196 patients hospitalized for community-acquired pneumonia, 6553 patients (mean age [SD], 79.1 [11.0] years; 3405 women [52.0%]) developed new-onset AF. The 1-year risk of thromboembolism was 0.8% (95% CI, 0.8%-0.8%) in patients without AF vs 2.1% (95% CI, 1.8%-2.5%) in patients with new-onset AF without anticoagulation; this risk was 1.4% (95% CI, 1.0%-2.0%) among patients with AF with intermediate stroke risk and 2.8% (95% CI, 2.3%-3.4%) in patients with AF with high stroke risk. Three-year risks were 3.5% (95% CI, 2.8%-4.3%) among patients with intermediate stroke risk and 5.3% (95% CI, 4.4%-6.5%) among patients with high stroke risk. Among patients with new-onset AF, 32.9% (95% CI, 31.8%-34.1%) had a new hospital contact with AF, and 14.0% (95% CI, 13.2%-14.9%) initiated anticoagulation therapy during the 3 years after incident AF diagnosis. At 3 years, the all-cause mortality rate was 25.7% (95% CI, 25.6%-25.9%) in patients with pneumonia without AF vs 49.8% (95% CI, 48.6%-51.1%) in patients with new-onset AF.

CONCLUSIONS AND RELEVANCE: This cohort study found that new-onset AF after community-acquired pneumonia was associated with an increased risk of thromboembolism, which may warrant anticoagulation therapy. Approximately one-third of patients had a new hospital or outpatient clinic contact for AF during the 3-year follow-up, suggesting that AF triggered by acute infections is not a transient, self-terminating condition that reverses with resolution of the infection.

PMID:35616941 | DOI:10.1001/jamanetworkopen.2022.13945

JAMA Netw Open. 2022 May 2;5(5):e2214171. doi: 10.1001/jamanetworkopen.2022.14171.

ABSTRACT

IMPORTANCE: In emergency epidemic and pandemic settings, public health agencies need to be able to measure the population-level attack rate, defined as the total percentage of the population infected thus far. During vaccination campaigns in such settings, public health agencies need to be able to assess how much the vaccination campaign is contributing to population immunity; specifically, the proportion of vaccines being administered to individuals who are already seropositive must be estimated.

OBJECTIVE: To estimate population-level immunity to SARS-CoV-2 through May 31, 2021, in Rhode Island, Massachusetts, and Connecticut.

DESIGN, SETTING, AND PARTICIPANTS: This observational case series assessed cases, hospitalizations, intensive care unit occupancy, ventilator occupancy, and deaths from March 1, 2020, to May 31, 2021, in Rhode Island, Massachusetts, and Connecticut. Data were analyzed from July 2021 to November 2021.

EXPOSURES: COVID-19-positive test result reported to state department of health.

MAIN OUTCOMES AND MEASURES: The main outcomes were statistical estimates, from a bayesian inference framework, of the percentage of individuals as of May 31, 2021, who were (1) previously infected and vaccinated, (2) previously uninfected and vaccinated, and (3) previously infected but not vaccinated.

RESULTS: At the state level, there were a total of 1 160 435 confirmed COVID-19 cases in Rhode Island, Massachusetts, and Connecticut. The median age among individuals with confirmed COVID-19 was 38 years. In autumn 2020, SARS-CoV-2 population immunity (equal to the attack rate at that point) in these states was less than 15%, setting the stage for a large epidemic wave during winter 2020 to 2021. Population immunity estimates for May 31, 2021, were 73.4% (95% credible interval [CrI], 72.9%-74.1%) for Rhode Island, 64.1% (95% CrI, 64.0%-64.4%) for Connecticut, and 66.3% (95% CrI, 65.9%-66.9%) for Massachusetts, indicating that more than 33% of residents in these states were fully susceptible to infection when the Delta variant began spreading in July 2021. Despite high vaccine coverage in these states, population immunity in summer 2021 was lower than planned owing to an estimated 34.1% (95% CrI, 32.9%-35.2%) of vaccines in Rhode Island, 24.6% (95% CrI, 24.3%-25.1%) of vaccines in Connecticut, and 27.6% (95% CrI, 26.8%-28.6%) of vaccines in Massachusetts being distributed to individuals who were already seropositive.

CONCLUSIONS AND RELEVANCE: These findings suggest that future emergency-setting vaccination planning may have to prioritize high vaccine coverage over optimized vaccine distribution to ensure that sufficient levels of population immunity are reached during the course of an ongoing epidemic or pandemic.

PMID:35616938 | DOI:10.1001/jamanetworkopen.2022.14171

Dermatol Ther (Heidelb). 2022 May 26. doi: 10.1007/s13555-022-00745-7. Online ahead of print.

ABSTRACT

INTRODUCTION: The tuberculosis (TB) positive conversion rate among psoriasis patients who received biologics has been reported worldwide, particularly in regions with low TB risk. Nonetheless, the TB-related safety of biologics such as adalimumab and secukinumab remains elusive in areas with high TB risk. According to the World Tuberculosis Report 2021, China is the country with the second highest TB burden, but data on TB conversion are also limited. Thus, we performed a retrospective, single-center study to profile the TB infection status conversion ratio among psoriasis patients treated with adalimumab and secukinumab in China.

METHODS: Patients were enrolled between April 2019 and February 2021 from West China Hospital, Sichuan University. Baseline and relevant clinical information were summarized, and proper statistical analysis was used under different conditions.

RESULTS: Five (5.43%) patients suffered TB conversion in the adalimumab group, two of whom developed active TB within the first 6 months. In the secukinumab group, four (5.26%) patients had TB positive conversion with no reports of active TB.

CONCLUSION: Our data show a relatively high rate of TB conversion among these psoriasis patients after mean treatment duration of 17.13 months. We recommend that, in patients who receive adalimumab, TB be reevaluated after the first 3 months and then monitored semiannually for the next 2 years. For patients treated with secukinumab, annual examination is sufficient.

PMID:35616884 | DOI:10.1007/s13555-022-00745-7

Ann Med. 2022 Dec;54(1):1538-1547. doi: 10.1080/07853890.2022.2076900.

ABSTRACT

BACKGROUND: Throughout the years significant progress has been observed in all medical fields. It was possible to achieve thanks to a wide range of scientists, including physician-scientists. However, in recent years their number is significantly declining. Thus we have aimed to explore the attitudes of medical students towards research.

METHODS: The cross-sectional study was conducted among medical students of Medical University of Warsaw between the 1st and 23rd of December 2019. Survey examining scientific interests and activities, opinions on selected research issues, and perception of potential barriers to research activities has been distributed to 838 students and collected from 695 (391 students of the 2nd year and 304 of the 5th year) with a response rate of 82.9%. Descriptive statistics, the Chi-squared test, U-Mann-Whitney, and Kruskal-Wallis tests were used for between-group comparisons. The differences were considered statistically significant if the p values were <.05.

RESULTS: 55.2% of responders rated their scientific interests in high school as high, with no significant differences between 2nd and 5th-year students. 33.8% (n = 233) of all students plan to pursue research activity after graduation, and 52.8% (n = 360) plan to obtain PhD title. Students who presented higher scientific interests in high school more often were involved in research projects at the university (24.7% vs 17.5%, p = .044), and showed higher interest in pursuing a research career (37.9% vs 28.9%, p = .02). Lack of time and knowledge on starting a research project were perceived as the main barriers to scientific work.

CONCLUSIONS: Many medical students express research interests, are involved in scientific projects, and plan to pursue their careers in this direction. There is a majority of students with lower attitudes towards research. Medical universities should consider adapting their curricula accordingly to accommodate the needs of both groups and respond to the shortage of physicians working in clinics and research.KEY MESSAGESOne-third of medical students plan to pursue career in medical research after graduation.Students who presented higher scientific interests in the high school are more often involved in research projects at the university and show higher interest in pursuing a research career.According to medical students, lack of time, resources and funding and insufficient knowledge how to start a research project are the most important barriers to research activity.

PMID:35616902 | DOI:10.1080/07853890.2022.2076900

Methods Mol Biol. 2022;2480:295-310. doi: 10.1007/978-1-0716-2241-4_16.

ABSTRACT

The efficient extraction and purification of recombinant proteins from leaf and seed tissues is often a challenging task, involving multiple steps that must be optimized by identifying and accommodating complex parameter interactions. Conventional one-factor-at-a-time approaches fail to reveal these complex interactions and often result in sub-optimal processes with unnecessary costs. Here, we describe generic considerations to identify global optima for the extraction and purification of recombinant proteins from complex plant matrices. The corresponding experiments can help to streamline downstream processing by reducing the time, costs, and number of unit operations. The procedure involves the knowledge-based selection of factors for screening, the systematic design and analysis of experiments, and the iterative refinement of suitable conditions. The resulting descriptive models can be used to guide process scale-up and offer scientific justifications for process development decisions in negotiations with regulatory authorities.

PMID:35616869 | DOI:10.1007/978-1-0716-2241-4_16