Category: Statistics

FASEB J. 2022 Feb;36(2):e22124. doi: 10.1096/fj.202101332R.

ABSTRACT

Nerve growth factor-induced gene B (Nur77) has been shown to ameliorate several biological processes in chronic diseases, including inflammatory response, cellular proliferation, and metabolism. Chronic kidney disease (CKD) is characterized by tubulointerstitial fibrosis for which no targeted therapies are available as yet. In this study, we performed in vivo and in vitro experiments to demonstrate that Nur77 targets fibrosis signals and attenuates renal tubulointerstitial fibrosis during the aging process. We observed that the TGF-β/Smads signal pathway was significantly suppressed by Nur77, suggesting that Nur77 controlled the activation of key steps in TGF-β/Smads signaling. We further showed that Nur77 interacted with Smad7, the main repressor of nuclear translocation of Smad2/3, and stabilized Smad7 protein homeostasis. Nur77 deficiency resulted in Smad7 degradation, aggravating Smad2/3 phosphorylation, and promoting transcription of its downstream target genes, ACTA2 and collagen I. Our findings demonstrate that Nur77 is a potential therapeutic target for age-related kidney diseases including CKD. Maintenance of Nur77 may be an effective strategy for blocking renal tubulointerstitial fibrosis and improving renal function in the elderly.

PMID:34972249 | DOI:10.1096/fj.202101332R

Chem Senses. 2022 Jan 1;47:bjab052. doi: 10.1093/chemse/bjab052.

ABSTRACT

CD36 and GNAT3 mediate taste responses, with CD36 acting as a lipid detector and GNAT3 acting as the α subunit of gustducin, a G protein governing sweet, savory, and bitter transduction. Strikingly, the genes encoding CD36 and GNAT3 are genomically superimposed, with CD36 completely encompassing GNAT3. To characterize genetic variation across the CD36-GNAT3 region, its implications for phenotypic diversity, and its recent evolution, we analyzed from ~2,500 worldwide subjects sequenced by the 1000 Genomes Project (1000GP). CD36-GNAT3 harbored extensive diversity including 8,688 single-nucleotide polymorphisms (SNPs), 414 indels, and other complex variants. Sliding window analyses revealed that nucleotide diversity and population differentiation across CD36-GNAT3 were consistent with genome-wide trends in the 1000GP (π = 0.10%, P = 0.64; FST = 9.0%, P = 0.57). In addition, functional predictions using SIFT and PolyPhen-2 identified 60 variants likely to alter protein function, and they were in weak linkage disequilibrium (r2 < 0.17), suggesting their effects are largely independent. However, the frequencies of predicted functional variants were low (P¯ = 0.0013), indicating their contributions to phenotypic variance on population scales are limited. Tests using Tajima’s D statistic revealed that pressures from natural selection have been relaxed across most of CD36-GNAT3 during its recent history (0.39 < P < 0.67). However, CD36 exons showed signs of local adaptation consistent with prior reports (P < 0.035). Thus, CD36 and GNAT3 harbor numerous variants predicted to affect taste sensitivity, but most are rare and phenotypic variance on a population level is likely mediated by a small number of sites.

PMID:34972209 | DOI:10.1093/chemse/bjab052

Thorac Cardiovasc Surg. 2021 Dec 31. doi: 10.1055/s-0041-1740539. Online ahead of print.

ABSTRACT

BACKGROUND: Decellularized pulmonary homografts are being increasingly adopted for right ventricular outflow tract reconstruction in adult patients undergoing the Ross procedure. Few reports presented Matrix PplusN xenograft (Matrix) in a negative light. The objective of this study was to compare our midterm outcomes of Matrix xenograft versus standard cryopreserved pulmonary homograft (CPHG).

METHODS: Eighteen patients received Matrix xenograft between January 2012 and June 2016, whereas 66 patients received CPHG. Using nonparametric statistical tests and survival analysis, we compared midterm echocardiographic and clinical outcomes between the groups.

RESULTS: Except for significant age difference (the Matrix group was significantly older with 57 ± 8 years than the CPHG group, 48 ± 9 years, p = 0.02), the groups were similar in all other baseline characteristics. There were no significant differences in cardiopulmonary bypass times (208.3 ± 32.1 vs. 202.8 ± 34.8) or in cross-clamp times (174 ± 33.9 vs. 184.4 ± 31.1) for Matrix and CPHG, respectively. The Matrix group had significantly inferior freedom from reintervention than the CPHG group with 77.8 versus 98.5% (p = 0.02). Freedom from pulmonary valve regurgitation ≥ 2 was not significantly different between the groups with 82.4 versus 90.5% for Matrix versus CPHG, respectively. After median follow-up of 4.9 years, Matrix xenograft developed significantly higher peak pressure gradients compared with CPHG (20.4 ± 15.5 vs. 12.2 ± 9.0 mm Hg; p = 0.04).

CONCLUSION: After 5 years of clinical and echocardiographic follow-up, the decellularized Matrix xenograft had inferior freedom from reintervention compared with the standard CPHG. Closer follow-up is necessary to avoid progression of valve failure into right ventricular deterioration.

PMID:34972237 | DOI:10.1055/s-0041-1740539

PLoS One. 2021 Dec 31;16(12):e0262145. doi: 10.1371/journal.pone.0262145. eCollection 2021.

ABSTRACT

User-friendly interfaces have been increasingly used to facilitate the learning of advanced statistical methodology, especially for students with only minimal statistical training. In this paper, we illustrate the use of MBGapp for teaching geostatistical analysis to population health scientists. Using a case-study on Loa loa infections, we show how MBGapp can be used to teach the different stages of a geostatistical analysis in a more interactive fashion. For wider accessibility and usability, MBGapp is available as an R package and as a Shiny web-application that can be freely accessed on any web browser. In addition to MBGapp, we also present an auxiliary Shiny app, called VariagramApp, that can be used to aid the teaching of Gaussian processes in one and two dimensions using simulations.

PMID:34972193 | DOI:10.1371/journal.pone.0262145

PLoS One. 2021 Dec 31;16(12):e0262171. doi: 10.1371/journal.pone.0262171. eCollection 2021.

ABSTRACT

OBJECTIVE: The Childhood Diabetes Registry of Saxony has been existing since 1999. The aim of this study was to investigate the incidence rates, cohort and point prevalence, and the trends of type 1 diabetes among children and adolescents based on the registry data over the past 21 years.

METHODS: A completeness check of the Childhood Diabetes Registry of Saxony for the observation period 2012-2019 was performed using the capture-recapture method. The age-standardized incidence rates per 100,000 person years (PY) were estimated for the observation period 1999-2019. Prevalence was estimated per 100,000 children and adolescents as the point prevalence of five consecutive years, and as a cohort prevalence for the birth cohorts, which result from the difference of age and year at diagnosis. Trend analyses were executed using join point regression.

RESULTS: A completeness of 98% (95% CI 89-100) was determined for the period from 2012 to 2019. The standardized incidence rate of type 1 diabetes among children and adolescents increased from 17.1 per 100,000 PY in 1999 to 24.7 per 100,000 PY in 2019. If this trend continues, the incidence rate will increase to 34.8 (95% CI 24.4-49.6) per 100,000 PY in 2030. The point prevalence of 5 consecutive years did not show a continuous trend over time. According to this method, the prevalence reached a plateau in the last segment (2013-2019). The calculation of cohort prevalence indicated a continuous increase from 2013 to 2019 with no significant statistical difference in terms of sex.

CONCLUSION: The point prevalence and the last incidence rates indicate that type 1 diabetes of children and adolescents is slowing down or has reached a plateau in Saxony. Nevertheless, the cohort prevalence predicts a steady increase. Future studies should continue investigating these trends in a longer observation period and consider including possible correlating environmental factors.

PMID:34972197 | DOI:10.1371/journal.pone.0262171

PLoS One. 2021 Dec 31;16(12):e0261974. doi: 10.1371/journal.pone.0261974. eCollection 2021.

ABSTRACT

INTRODUCTION: Obstetric intensive care unit admission (ICU) suggests severe morbidity. However, there is no available data on the subject in Ghana. This retrospective review was conducted to determine the indications for obstetric ICU admission, their outcomes and factors influencing these outcomes to aid continuous quality improvement in obstetric care.

METHODS: This was a retrospective review conducted in a tertiary hospital in Ghana. Data on participant characteristics including age and whether participant was intubated were collected from patient records for all obstetric ICU admissions from 1st January 2010 to 31st December 2019. Descriptive statistics were presented as frequencies, proportions and charts. Hazard ratios were generated for relations between obstetric ICU admission outcome and participant characteristics. A p-value <0.05 was deemed statistically significant.

RESULTS: There were 443 obstetric ICU admissions over the review period making up 25.7% of all ICU admissions. The commonest indications for obstetric ICU admissions were hypertensive disorders of pregnancy (70.4%, n = 312/443), hemorrhage (14.4%, n = 64/443) and sepsis (9.3%, n = 41/443). The case fatality rates for hypertension, hemorrhage, and sepsis were 17.6%, 37.5%, and 63.4% respectively. The obstetric ICU mortality rate was 26% (115/443) over the review period. Age ≥25 years and a need for mechanical ventilation carried increased mortality risks following ICU admission while surgery in the index pregnancy was associated with a reduced risk of death.

CONCLUSION: Hypertension, haemorrhage and sepsis are the leading indications for obstetric ICU admissions. Thus, preeclampsia screening and prevention, as well as intensifying antenatal education on the danger signs of pregnancy can minimize obstetric complications. The establishment of an obstetric HDU in CCTH and the strengthening of communication between specialists and the healthcare providers in the lower facilities, are also essential for improved pregnancy outcomes. Further studies are needed to better appreciate the wider issues underlying obstetric ICU admission outcomes.

PLAIN LANGUAGE SUMMARY: This was a review of the reasons for admitting severely-ill pregnant women and women who had delivered within the past 42 days to the intensive care unit (ICU), the admission outcomes and risk factors associated with ICU mortality in a tertiary hospital in a low-resource country. High blood pressure and its complications, bleeding and severe infections were observed as the three most significant reasons for ICU admissions in decreasing order of significance. Pre-existing medical conditions and those arising as a result of, or aggravated by pregnancy; obstructed labour and post-operative monitoring were the other reasons for ICU admission over the study period. Overall, 26% of the admitted patients died at the ICU and maternal age of at least 25 years and the need for intubation were identified as risk factors for ICU deaths. Attention must be paid to high blood pressure during pregnancy.

PMID:34972184 | DOI:10.1371/journal.pone.0261974

PLoS One. 2021 Dec 31;16(12):e0261951. doi: 10.1371/journal.pone.0261951. eCollection 2021.

ABSTRACT

PURPOSE: Maternal surgical site infection after cesarean delivery is a clinical problem which contributes to significant morbidity and mortality. In Ethiopia admissions following cesarean section due to surgical site infection have been routine activities of health care institutions but there is limited scientific evidence on both the magnitude of the problem and factors associated with it making prevention mechanisms less effective. Therefore, this study aimed to assess magnitude and risk factors of post-cesarean section surgical site infection at primary hospitals of East Gojjam Zone, Northwest Ethiopia.

METHODS: Institution-based cross sectional study with retrospective chart review was conducted from September 10-30 /2020 at 3 randomly selected primary hospitals of east Gojjam zone. The data were entered in Epi data version 3.1 and exported to Statistical Package for Social Science Software version 26. Post-cesarean section surgical site infection was measured based on disease classification and definition of the term by Center for Disease Control and Prevention. After checking for presence of multicollinarity, presence and degree of association of factors with outcome variable were computed through logistic regression analysis. Factors with P value ≤ 0.2 in bi-variable logistic regression analysis were included in the multivariable logistic regression analysis and those variables with P-value of <0.05 in multivariable analysis were considered statistically significant.

RESULT: From 622 medical records of women who underwent cesarean section, 77 (12.4%) of them developed surgical site infection. Rural residence [(AOR = 2.30, 95%CI: (1.29, 4.09)], duration of labor greater than 24hrs [(AOR = 3.48, 95%CI: (1.49, 8.09)], rupture of membrane>12hrs[(AOR = 4.61,95%CI:(2.34,9.09)], hypertension[(AOR = 3.14,95%CI:(1.29,7.59)] and preoperative Hematocrit ≤30%[(AOR = 3.22,95%CI:(1.25,8.31)] were factors significantly associated with post-cesarean section surgical site infections.

CONCLUSION: Magnitude of post-cesarean section surgical site infection was a significant problem in primary hospitals. Minimizing prolonged labor; minimize early rupture of membrane, properly managing patients with comorbidities like hypertension, strengthen prophylaxis and treatment for anemia during antenatal care and raising awareness for rural residents can reduce the problem. Zonal police makers should give emphasis to reduce its burden.

PMID:34972176 | DOI:10.1371/journal.pone.0261951

PLoS One. 2021 Dec 31;16(12):e0261954. doi: 10.1371/journal.pone.0261954. eCollection 2021.

ABSTRACT

Cybersecurity affects us all in our daily lives. New knowledge on best practices, new vulnerabilities, and timely fixes for cybersecurity issues is growing super-linearly, and is spread across numerous, heterogeneous sources. Because of that, community contribution-based, question and answer sites have become clearinghouses for cybersecurity-related inquiries, as they have for many other topics. Historically, Stack Overflow has been the most popular platform for different kinds of technical questions, including for cybersecurity. That has been changing, however, with the advent of Security Stack Exchange, a site specifically designed for cybersecurity-related questions and answers. More recently, some cybersecurity-related subreddits of Reddit, have become hubs for cybersecurity-related questions and discussions. The availability of multiple overlapping communities has created a complex terrain to navigate for someone looking for an answer to a cybersecurity question. In this paper, we investigate how and why people choose among three prominent, overlapping, question and answer communities, for their cybersecurity knowledge needs. We aggregated data of several consecutive years of cybersecurity-related questions from Stack Overflow, Security Stack Exchange, and Reddit, and performed statistical, linguistic, and longitudinal analysis. To triangulate the results, we also conducted user surveys. We found that the user behavior across those three communities is different, in most cases. Likewise, cybersecurity-related questions asked on the three sites are different, more technical on Security Stack Exchange and Stack Overflow, and more subjective and personal on Reddit. Moreover, there appears to have been a differentiation of the communities along the same lines, accompanied by overall popularity trends suggestive of Stack Overflow’s decline and Security Stack Exchange’s rise within the cybersecurity community. Reddit is addressing the more subjective, discussion type needs of the lay community, and is growing rapidly.

PMID:34972166 | DOI:10.1371/journal.pone.0261954

PLoS One. 2021 Dec 31;16(12):e0261433. doi: 10.1371/journal.pone.0261433. eCollection 2021.

ABSTRACT

Diagnostic tests for hearing impairment not only determines the presence (or absence) of hearing loss, but also evaluates its degree and type, and provides physicians with essential data for future treatment and rehabilitation. Therefore, accurately measuring hearing loss conditions is very important for proper patient understanding and treatment. In current-day practice, to quantify the level of hearing loss, physicians exploit specialized test scores such as the pure-tone audiometry (PTA) thresholds and speech discrimination scores (SDS) as quantitative metrics in examining a patient’s auditory function. However, given that these metrics can be easily affected by various human factors, which includes intentional (or accidental) patient intervention, there are needs to cross validate the accuracy of each metric. By understanding a “normal” relationship between the SDS and PTA, physicians can reveal the need for re-testing, additional testing in different dimensions, and also potential malingering cases. For this purpose, in this work, we propose a prediction model for estimating the SDS of a patient by using PTA thresholds via a Random Forest-based machine learning approach to overcome the limitations of the conventional statistical (or even manual) methods. For designing and evaluating the Random Forest-based prediction model, we collected a large-scale dataset from 12,697 subjects, and report a SDS level prediction accuracy of 95.05% and 96.64% for the left and right ears, respectively. We also present comparisons with other widely-used machine learning algorithms (e.g., Support Vector Machine, Multi-layer Perceptron) to show the effectiveness of our proposed Random Forest-based approach. Results obtained from this study provides implications and potential feasibility in providing a practically-applicable screening tool for identifying patient-intended malingering in hearing loss-related tests.

PMID:34972151 | DOI:10.1371/journal.pone.0261433

PLoS One. 2021 Dec 31;16(12):e0261850. doi: 10.1371/journal.pone.0261850. eCollection 2021.

ABSTRACT

OBJECTIVE: Identify risk factors for poor pain outcomes six months after primary knee replacement surgery.

METHODS: Observational cohort study on patients receiving primary knee replacement from the UK Clinical Practice Research Datalink, Hospital Episode Statistics and Patient Reported Outcomes. A wide range of variables routinely collected in primary and secondary care were identified as potential predictors of worsening or only minor improvement in pain, based on the Oxford Knee Score pain subscale. Results are presented as relative risk ratios and adjusted risk differences (ARD) by fitting a generalized linear model with a binomial error structure and log link function.

RESULTS: Information was available for 4,750 patients from 2009 to 2016, with a mean age of 69, of whom 56.1% were female. 10.4% of patients had poor pain outcomes. The strongest effects were seen for pre-operative factors: mild knee pain symptoms at the time of surgery (ARD 18.2% (95% Confidence Interval 13.6, 22.8), smoking 12.0% (95% CI:7.3, 16.6), living in the most deprived areas 5.6% (95% CI:2.3, 9.0) and obesity class II 6.3% (95% CI:3.0, 9.7). Important risk factors with more moderate effects included a history of previous knee arthroscopy surgery 4.6% (95% CI:2.5, 6.6), and use of opioids 3.4% (95% CI:1.4, 5.3) within three months after surgery. Those patients with worsening pain state change had more complications by 3 months (11.8% among those in a worse pain state vs. 2.7% with the same pain state).

CONCLUSIONS: We quantified the relative importance of individual risk factors including mild pre-operative pain, smoking, deprivation, obesity and opioid use in terms of the absolute proportions of patients achieving poor pain outcomes. These findings will support development of interventions to reduce the numbers of patients who have poor pain outcomes.

PMID:34972159 | DOI:10.1371/journal.pone.0261850