Tag: nevin manimala

Mol Biol Evol. 2023 Jul 11:msad157. doi: 10.1093/molbev/msad157. Online ahead of print.

ABSTRACT

Natural selection leaves a spatial pattern along the genome, with a haplotype distribution distortion near the selected locus that fades with distance. Evaluating the spatial signal of a population-genetic summary statistic across the genome allows for patterns of natural selection to be distinguished from neutrality. Considering the genomic spatial distribution of multiple summary statistics is expected to aid in uncovering subtle signatures of selection. In recent years, numerous methods have been devised that consider genomic spatial distributions across summary statistics, utilizing both classical machine learning and deep learning architectures. However, better predictions may be attainable by improving the way in which features are extracted from these summary statistics. We apply wavelet transform, multitaper spectral analysis, and S-transform to summary statistic arrays to achieve this goal. Each analysis method converts one-dimensional summary statistic arrays to two-dimensional images of spectral analysis, allowing simultaneous temporal and spectral assessment. We feed these images into convolutional neural networks and consider combining models using ensemble stacking. Our modeling framework achieves high accuracy and power across a diverse set of evolutionary settings, including population size changes and test sets of varying sweep strength, softness, and timing. A scan of central European whole-genome sequences recapitulated well-established sweep candidates and predicted novel cancer-associated genes as sweeps with high support. Given that this modeling framework is also robust to missing genomic segments, we believe that it will represent a welcome addition to the population-genomic toolkit for learning about adaptive processes from genomic data.

PMID:37433019 | DOI:10.1093/molbev/msad157

Proc Natl Acad Sci U S A. 2023 Jul 18;120(29):e2303222120. doi: 10.1073/pnas.2303222120. Epub 2023 Jul 11.

ABSTRACT

Many systems in physics, chemistry, and biology exhibit oscillations with a pronounced random component. Such stochastic oscillations can emerge via different mechanisms, for example, linear dynamics of a stable focus with fluctuations, limit-cycle systems perturbed by noise, or excitable systems in which random inputs lead to a train of pulses. Despite their diverse origins, the phenomenology of random oscillations can be strikingly similar. Here, we introduce a nonlinear transformation of stochastic oscillators to a complex-valued function [Formula: see text](x) that greatly simplifies and unifies the mathematical description of the oscillator’s spontaneous activity, its response to an external time-dependent perturbation, and the correlation statistics of different oscillators that are weakly coupled. The function [Formula: see text] (x) is the eigenfunction of the Kolmogorov backward operator with the least negative (but nonvanishing) eigenvalue λ₁ = μ₁ + iω₁. The resulting power spectrum of the complex-valued function is exactly given by a Lorentz spectrum with peak frequency ω₁ and half-width μ₁; its susceptibility with respect to a weak external forcing is given by a simple one-pole filter, centered around ω₁; and the cross-spectrum between two coupled oscillators can be easily expressed by a combination of the spontaneous power spectra of the uncoupled systems and their susceptibilities. Our approach makes qualitatively different stochastic oscillators comparable, provides simple characteristics for the coherence of the random oscillation, and gives a framework for the description of weakly coupled oscillators.

PMID:37432992 | DOI:10.1073/pnas.2303222120

J Am Acad Orthop Surg. 2023 Jul 10. doi: 10.5435/JAAOS-D-23-00062. Online ahead of print.

ABSTRACT

INTRODUCTION: Patients with adolescent idiopathic scoliosis (AIS) are susceptible to high doses of radiation from radiographs. The purpose of this study was to examine the future cost of radiation-induced breast cancer in patients with AIS and its potential financial and mortality impact.

METHODS: A literature review identified articles relating radiation exposure in patients with AIS to increased risk for cancer. Based on population statistics and breast cancer treatment costs in the year 2020, the financial impact of radiation-induced breast cancer and the estimated number of additional deaths per year due to breast cancer for patients with AIS were calculated.

RESULTS: The US female population in 1970 was 205.1 million. Based on a prevalence of 3.0%, an estimated 3.1 million patients had AIS in 1970. With an incidence of breast cancer in the general population of 128.3/100,000 and a standardized incidence ratio of 1.82-2.4 for breast cancer in patients with scoliosis, there will be a 3,282 to 5,603 patient increase in radiation-induced breast cancer in patients with scoliosis over the general population. With a projected base cost of $34,979 per patient for the first year of breast cancer diagnosis in 2020, the cost of radiation-induced breast cancer will be 114.8 to 196.0 million dollars per year. Using a standardized mortality ratio of 1.68 for scoliosis radiation-induced breast cancer, there will be an expected increase in deaths of 420 patients due to breast cancer presumably secondary to radiation exposure in the evaluation and treatment of AIS.

CONCLUSION: The estimated radiation-induced breast cancer financial impact in 2020 will be between 114.8 and 196.0 million dollars per year, with an increase in deaths of 420 patients per year. Low-dose imaging systems reduce radiation exposure by up to 45 times while maintaining sufficient image quality. New low-dose radiography should be used whenever possible with patients with AIS.

LEVEL OF EVIDENCE: Level 5.

PMID:37432975 | DOI:10.5435/JAAOS-D-23-00062

PLoS One. 2023 Jul 11;18(7):e0287409. doi: 10.1371/journal.pone.0287409. eCollection 2023.

ABSTRACT

A blood-based integrated classifier (IC) has been clinically validated to improve accuracy in assessing probability of cancer risk (pCA) for pulmonary nodules (PN). This study evaluated the clinical utility of this biomarker for its ability to reduce invasive procedures in patients with pre-test pCA ≤ 50%. This was a propensity score matching (PSM) cohort study comparing patients in the ORACLE prospective, multicenter, observational registry to control patients treated with usual care. This study enrolled patients meeting the intended use criteria for IC testing: pCA ≤ 50%, age ≥40 years, nodule diameter 8-30 mm, and no history of lung cancer and/or active cancer (except for non-melanomatous skin cancer) within 5 years. The primary aim of this study was to evaluate invasive procedure use on benign PNs of registry patients as compared to control patients. A total of 280 IC tested, and 278 control patients met eligibility and analysis criteria and 197 were in each group after PSM (IC and control groups). Patients in the IC group were 74% less likely to undergo an invasive procedure as compared to the control group (absolute difference 14%, p <0.001) indicating that for every 7 patients tested, one unnecessary invasive procedure was avoided. Invasive procedure reduction corresponded to a reduction in risk classification, with 71 patients (36%) in the IC group classified as low risk (pCA < 5%). The proportion of IC group patients with malignant PNs sent to surveillance were not statistically different than the control group, 7.5% vs 3.5% for the IC vs. control groups, respectively (absolute difference 3.91%, p 0.075). The IC for patients with a newly discovered PN has demonstrated valuable clinical utility in a real-world setting. Use of this biomarker can change physicians’ practice and reduce invasive procedures in patients with benign pulmonary nodules. Trial registration: Clinical trial registration: ClinicalTrials.gov NCT03766958.

PMID:37432960 | DOI:10.1371/journal.pone.0287409

PLoS One. 2023 Jul 11;18(7):e0288265. doi: 10.1371/journal.pone.0288265. eCollection 2023.

ABSTRACT

This study examines whether income distribution in Thailand has a property of scale invariance or self-similarity across years. By using the data on income shares by quintile and by decile of Thailand from 1988 to 2021, the results from 306-pairwise Kolmogorov-Smirnov tests indicate that income distribution in Thailand is statistically scale-invariant or self-similar across years with p-values ranging between 0.988 and 1.000. Based on these empirical findings, this study would like to propose that, in order to change income distribution in Thailand whose pattern had been persisted for over three decades, the change itself cannot be gradual but has to be like a phase transition of substance in physics.

PMID:37432918 | DOI:10.1371/journal.pone.0288265

PLoS One. 2023 Jul 11;18(7):e0287440. doi: 10.1371/journal.pone.0287440. eCollection 2023.

ABSTRACT

BACKGROUND: Women who use hormonal contraception face delayed return of fertility upon discontinuation. There was limited evidence of fertility return after hormonal contraceptive discontinuation in the study area. Hence this study assessed fertility return after hormonal contraceptive discontinuation and associated factors among pregnant women attending Family Guidance Association Ethiopia (FGAE) Dessie model clinic, Northeast Ethiopia, 2019.

METHODS: A cross-sectional study was conducted on 423 samples selected by using systematic random sampling. Data were collected by face-to-face interview using a pretested and structured questionnaire and reviewing client records. Data were entered using Epi Data version 3.1 and analyzed using SPSS version 23. Both bi-variable and multivariable binary logistic regressions were used to identify predictors of delayed fertility return. Adjusted odds ratio (AOR) along with a 95% Confidence Interval (CI) was used to measure the strength and the direction of the association and statistical significance was declared at a P-value less than 0.05.

RESULT: The proportion of fertility return among currently pregnant women after discontinuation of any hormonal contraceptive methods was 88.6% (95% CI; (85.6%-92%)). The proportion of fertility return among Depo-Provera, implant, Intrauterine Contraceptive Device (IUCD), and Oral Contraceptive Pill (OCP) users was 75%, 99.1%, 100%, and 97.8% respectively. Age, (AOR = 5.37, (95% CI; (1.48, 13.6)) and using Depo-Provera (AOR = 4.82, 95% CI; (1.89, 14.2)) had a significant association with delayed fertility return.

CONCLUSIONS: The proportion of fertility return among women after discontinuation of any hormonal contraceptive methods was high. Age and using Depo-Provera had a positive association with delayed fertility return. This study recommends a contraceptive counseling approach that addresses concerns about delay in the return of fertility after hormonal contraceptive discontinuation to avoid confusion among family planning users.

PMID:37432916 | DOI:10.1371/journal.pone.0287440

PLoS One. 2023 Jul 11;18(7):e0288018. doi: 10.1371/journal.pone.0288018. eCollection 2023.

ABSTRACT

Men who have sex with men (MSM) experience a high degree of discrimination and marginalization in Senegal. Homophobia is pervasive in Senegalese society at the cultural, religious, and political levels. Its effects are reflected in the disproportionately high levels of depression, anxiety, and substance abuse among men who have sex with men when compared to the general population. Given the widespread stigma and the lack of structural support, healthcare providers play a critical role in reconciling the physical and psychological needs of men who have sex with men. This led to the design of a training program that aimed to improve the capacity of healthcare providers to deliver MSM-competent psychosocial care. The training was delivered virtually to 37 Senegal-based nurses and physicians. The program was quantitatively and qualitatively evaluated using pre- and post-testing. The findings demonstrate a general post-training increase in knowledge acquisition (9. 23%, p-value = 0.0021) and a 6.39% reduction in homophobia, which was statistically significant (p = 0.0376); with male providers outperforming female providers, and physicians outperforming nurses. This demonstrates the effectiveness and applicability of the program to support the psychosocial needs of men who have sex with men, and its capacity for future and broader implementation among healthcare providers.

PMID:37432914 | DOI:10.1371/journal.pone.0288018

J Hypertens. 2023 Jul 6. doi: 10.1097/HJH.0000000000003497. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare adherence to antihypertensive treatment between patients prescribed a three-drug single-pill combination (SPC) of perindopril/amlodipine/indapamide (P/A/I) vs. the combination of an angiotensin-converting enzyme inhibitor (ACEI), a calcium-channel blocker (CCB), and a diuretic (D) as a two-drug SPC plus a third drug given separately.

METHODS: Using the healthcare utilization database of the Lombardy Region (Italy), the 28 210 patients, aged at least 40 years, who were prescribed P/A/I SPC during 2015-2018 were identified and the date of the first prescription was defined as the index date. For each patient prescribed the SPC, a comparator who started ACEI/CCB/D treatment as a two-pill combination was considered. Adherence to the triple combination was assessed over the year after the index date as the proportion of the follow-up days covered by prescription (PDC). Patients who had a PDC >75% were defined as highly adherent to drug therapy. Log-binomial regression models were fitted to estimate the risk ratio of treatment adherence in relation to the drug treatment strategy.

RESULTS: About 59 and 25% of SPC and two-pill combination users showed high adherence, respectively. Compared with patients under a three-drug two-pill combination, those who were treated with the three-drug SPC had a higher propensity to be highly adherent to the triple combination (2.38, 95% confidence interval: 2.32-2.44). This was the case regardless of the sex, age, comorbidities, and number of co-treatments.

CONCLUSIONS: In a real-life setting, patients under three-drug SPC exhibited more frequently a high adherence to antihypertensive treatment than those prescribed a three-drug two-pill combination.

PMID:37432906 | DOI:10.1097/HJH.0000000000003497

J Hypertens. 2023 Jul 6. doi: 10.1097/HJH.0000000000003486. Online ahead of print.

ABSTRACT

INTRODUCTION: Hypertensive disorders of pregnancy are associated with adverse feto-maternal outcomes. Existing evidence is mostly limited to observational studies, which are liable to confounding and bias. This study investigated the causal relevance of component hypertensive indices on multiple adverse pregnancy outcomes using Mendelian randomization.

METHODS: Uncorrelated (r2 < 0.001) genome-wide significant (P < 5 × 10-8) single-nucleotide polymorphisms associated with SBP, DBP and pulse pressure (PP) were selected as instrumental variables. Genetic association estimates for outcomes of preeclampsia or eclampsia, preterm birth, placental abruption and hemorrhage in early pregnancy were extracted from summary statistics of genome-wide association studies in the FinnGen cohort. Two-sample, inverse-variance weighted Mendelian randomization formed the primary analysis method. Odds ratios (OR) are presented per-10 mmHg higher genetically predicted hypertensive index.

RESULTS: Higher genetically predicted SBP were associated with higher odds of preeclampsia or eclampsia [OR 1.81, 95% confidence interval (CI) 1.68-1.96, P = 5.45 × 10-49], preterm birth (OR 1.09, 95% CI 1.03-1.16, P = 0.005) and placental abruption (OR 1.33, 95% CI 1.05-1.68, P = 0.016). Higher genetically-predicted DBP was associated with preeclampsia or eclampsia (OR 2.54, 95% CI 2.21-2.92, P = 5.35 × 10-40). Higher genetically predicted PP was associated with preeclampsia or eclampsia (OR 1.68, 95% CI 1.47-1.92, P = 1.9 × 10-14) and preterm birth (OR 1.18, 95% CI 1.06-1.30, P = 0.002).

CONCLUSION: This study provides genetic evidence to support causal associations of SBP, DBP and PP on multiple adverse outcomes of pregnancy. SBP and PP were associated with the broadest range of adverse outcomes, suggesting that optimized management of blood pressure, particularly SBP, is a key priority to improve feto-maternal health.

PMID:37432894 | DOI:10.1097/HJH.0000000000003486

J Hypertens. 2023 Jul 6. doi: 10.1097/HJH.0000000000003504. Online ahead of print.

ABSTRACT

OBJECTIVE: Saline infusion test (SIT) requires 2 l of isotonic saline for intravenous infusion over 4 h to suppress plasma aldosterone concentration (PAC). To shorten the procedure time and minimize the volume load, we study the performance of SIT at 1, 2 and 4 h for diagnosing primary aldosteronism.

METHODS: This is a cross-sectional study. PAC was measured before and 1, 2 and 4 h after saline infusion at a rate of 500 ml/h in patients suspected to have primary aldosteronism. Primary aldosteronism was diagnosed based on 4 h PAC, adrenal imaging and/or adrenal venous sampling (AVS).

RESULTS: Of the 93 patients, 32 had primary aldosteronism. The area under the receiver operating characteristic (ROC) curve of the 1, 2 and 4 h PAC were not statistically different. All of the nonprimary aldosteronism group had a 1 h PAC lower than 15 ng/dl and all of the primary aldosteronism group had a 1 h PAC higher than 5 ng/dl. Nearly 30% of the nonprimary aldosteronism and primary aldosteronism groups had a 1 h PAC between 5 and 15 ng/dl (equivocal range) and could be discriminated by using percentage suppression of 1 h PAC from baseline. Using 1 h PAC of more than 15 ng/dl together with percentage suppression of 1 h PAC from baseline of less than 60 when 1 h PAC was 5-15 ng/dl, primary aldosteronism could be detected with a sensitivity of 93.7% and specificity of 96.7%.

CONCLUSION: The 1 h SIT has a similar diagnostic performance to the standard SIT. Using 1 h PAC together with percentage suppression from baseline when 1 h PAC is equivocal, primary aldosteronism can be diagnosed with good accuracy.

PMID:37432888 | DOI:10.1097/HJH.0000000000003504