Tag: nevin manimala

J Am Chem Soc. 2022 Nov 2. doi: 10.1021/jacs.2c08770. Online ahead of print.

ABSTRACT

RNA is challenging to target with bioactive small molecules, particularly those of low molecular weight that bind with sufficient affinity and specificity. In this report, we developed a platform to address this challenge, affording a novel bioactive interaction. An RNA-focused small-molecule fragment collection (n = 2500) was constructed by analyzing features in all publicly reported compounds that bind RNA, the largest collection of RNA-focused fragments to date. The RNA-binding landscape for each fragment was studied by using a library-versus-library selection with an RNA library displaying a discrete structural element, probing over 12.8 million interactions, the greatest number of interactions between fragments and biomolecules probed experimentally. Mining of this dataset across the human transcriptome defined a drug-like fragment that potently and specifically targeted the microRNA-372 hairpin precursor, inhibiting its processing into the mature, functional microRNA and alleviating invasive and proliferative oncogenic phenotypes in gastric cancer cells. Importantly, this fragment has favorable properties, including an affinity for the RNA target of 300 ± 130 nM, a molecular weight of 273 Da, and quantitative estimate of drug-likeness (QED) score of 0.8. (For comparison, the mean QED of oral medicines is 0.6 ± 0.2). Thus, these studies demonstrate that a low-molecular weight, fragment-like compound can specifically and potently modulate RNA targets.

PMID:36322830 | DOI:10.1021/jacs.2c08770

Geriatr Psychol Neuropsychiatr Vieil. 2022 Sep 1;20(3):293-302. doi: 10.1684/pnv.2022.1058.

ABSTRACT

INTRODUCTION: Giant cell arteritis (GCA) or Horton’s disease is a segmental and focal inflammation of large and medium-sized arteries mostly seen in patients of 50 years and older. There is also a peak frequency in individuals between the ages of 70 and 80. However, clinical data is scarce in this age group and especially in patients over 80.

METHODS: A retrospective study comprised of patients diagnosed with Horton’s arteritis between 2012 and 2017, according to the American Society of Rheumatology, was conducted at Reims University Hospital. Patients were assigned to two groups according to age (≤ 75 and < 75) in order to evaluate and compare the impact of age on diagnosis, treatment and prognosis.

RESULTS: A total of 67 patients were studied. The mean age upon diagnosis was 75,85 ±8.5 years; 36 patients (53.7%) 75 years or younger and 31 patients older than 75. There was a female predominance (43 patients), 22 patients aged 75 years or younger and 21 older than 75. The mean follow up duration was 43.02 months in patients aged 75 years or younger and 30.99 in patients older than 75. This represents a difference of more than one year in terms of follow up, but is not statistically significant (p = 0.620). Eleven patients (16.4%) died during follow up: 5 patients (13.9%) aged 75 years or younger and 6 patients (19.4%) older than 75 (p = 0.547). Aortitis was significantly less seen in patients older than 75 (p = 0.0410).

CONCLUSION: Our study showed no significant difference in either age group. However, aortitis was less seen in patients older than 75 years. Patients aged 75 or younger seemed more prone to relapses, but their follow up periods were shorter.

PMID:36322811 | DOI:10.1684/pnv.2022.1058

Proc Natl Acad Sci U S A. 2022 Nov 16;119(46):e2202538119. doi: 10.1073/pnas.2202538119. Epub 2022 Nov 2.

ABSTRACT

Understanding community-level selection using Lewontin’s criteria requires both community-level inheritance and community-level heritability, and in the discipline of community and ecosystem genetics, these are often conflated. While there are existing studies that show the possibility of both, these studies impose community-level inheritance as a product of the experimental design. For this reason, these experiments provide only weak support for the existence of community-level selection in nature. By contrast, treating communities as interactors (in line with Hull’s replicator-interactor framework or Dawkins’s idea of the “extended phenotype”) provides a more plausible and empirically supportable model for the role of ecological communities in the evolutionary process.

PMID:36322791 | DOI:10.1073/pnas.2202538119

Sci Adv. 2022 Nov 4;8(44):eabq4415. doi: 10.1126/sciadv.abq4415. Epub 2022 Nov 2.

ABSTRACT

Volcanic activity typically switches between high-activity states with many eruptions and low-activity states with few or no eruptions. We present a simple two-regime physics-informed statistical model that allows interpreting temporal modulations in eruptive activity. The model enhances comprehension and comparison of different volcanic systems and enables homogeneous integration into multivolcano hazard assessments that account for potential changes in volcanic regimes. The model satisfactorily fits the eruptive history of the three active volcanoes in the Neapolitan area, Italy (Mt. Vesuvius, Campi Flegrei, and Ischia) which encompass a wide range of volcanic behaviors. We find that these volcanoes have appreciably different processes for triggering and ending high-activity periods connected to different dominant volcanic processes controlling their eruptive activity, with different characteristic times and activity rates (expressed as number of eruptions per time interval). Presently, all three volcanoes are judged to be in a low-activity state, with decreasing probability of eruptions for Mt. Vesuvius, Ischia, and Campi Flegrei, respectively.

PMID:36322667 | DOI:10.1126/sciadv.abq4415

Logoped Phoniatr Vocol. 2022 Nov 2:1-13. doi: 10.1080/14015439.2022.2140455. Online ahead of print.

ABSTRACT

Background and Aim: To date, little research is available that objectively quantifies female adolescent singing-voice characteristics in light of the physiological and functional developments that occur from puberty to adulthood. This exploratory study sought to augment the pool of data available that offers objective voice analysis of female singers in late adolescence.Methods: Using long-term average spectra (LTAS) and inverse filtering techniques, dynamic range and voice-source characteristics were determined in a cohort of vocally healthy cis-gender female adolescent singers (17 to 19 years) from high-school choirs in Aotearoa New Zealand. Non-parametric statistics were used to determine associations and significant differences.Results: Wide intersubject variation was seen between dynamic range, spectral measures of harmonic organisation (formant cluster prominence, FCP), noise components in the spectrum (high-frequency energy ratio, HFER), and the normalised amplitude quotient (NAQ) suggesting great variability in ability to control phonatory mechanisms such as subglottal pressure (P_sub), glottal configuration and adduction, and vocal tract shaping. A strong association between the HFER and NAQ suggest that these non-invasive measures may offer complimentary insights into vocal function, specifically with regard to glottal adduction and turbulent noise in the voice signal.Conclusion: Knowledge of the range of variation within healthy adolescent singers is necessary for the development of effective and inclusive pedagogical practices, and for vocal-health professionals working with singers of this age. LTAS and inverse filtering are useful non-invasive tools for determining such characteristics.

PMID:36322641 | DOI:10.1080/14015439.2022.2140455

J Can Dent Assoc. 2022 Aug;88:m7.

ABSTRACT

OBJECTIVE: Various teething remedies have been widely marketed to caregivers. Unsafe remedies, including teething necklaces and topical anesthetics, have been implicated in adverse events, such as suffocation injuries and death. However, little is known about the extent of their use. Our primary objective was to assess the prevalence of teething remedy use among caregivers. A secondary objective was to determine whether the use of unsafe teething remedies is related to socioeconomic status (SES) or maternal education.

METHODS: Children aged 12-18 months visiting primary care providers for routine checkups were included. Children outside that age group and those with chronic medical conditions were excluded. Caregivers completed a questionnaire about their children’s teething symptoms and remedies used to relieve them. Unsafe remedies were defined on the basis of American Academy of Pediatrics and Canadian Paediatric Society recommendations and included topical anesthetics, teething necklaces and liquid-filled teething rings.

RESULTS: Of the 130 questionnaires, 123 were complete and included in statistical analysis: 98% of families used teething remedies and 67% were unsafe. Of these families, 27% used amber teething necklaces; 28% used more than 1 unsafe remedy. Apart from topical anesthetic use, no significant correlations were found between overall unsafe remedy use and SES or maternal education.

CONCLUSION: Unsafe teething remedies are commonly used despite recommendations against them. Use of unsafe teething remedies transcends SES and education level.

PMID:36322634

J Can Dent Assoc. 2022 Jul;88:m5.

ABSTRACT

OBJECTIVES: To understand the risk factors that may be associated with the development of oral lichen planus (OLP) and its progression.

STUDY DESIGN: We conducted retrospective chart reviews of adult patients with OLP who presented to oral medicine and oral pathology clinics in 2 provinces between September 2016 and January 2020. Data regarding age, sex, disease duration, sites of involvement, comorbidities, medications, allergies, smoking, alcohol use, treatment and follow up were collected. Descriptive statistics were assessed.

RESULTS: Among the 94 patients with OLP, mean age was 62 years and most were female (73%). Mean disease duration was 3.1 years. Hypertension, thyroid disorders and diabetes were present in 32%, 28% and 17% of patients, respectively. A significant proportion of patients reported a major surgical procedure (47%) as a preceding event and an additional 7% reported a preceding stressful life event. Three OLP patients (3%) developed squamous cell carcinoma or dysplasia. The mean disease duration for these patients was 4.06 years and the frequency of biopsy in our study was approximately 14%.

CONCLUSIONS: Female sex, endocrine and immunological comorbidities, such as thyroid disease and diabetes, and psychological stress may play a role in the development of OLP in the Canadian population. A small percentage of patients may develop malignant transformation and, thus, require long-term monitoring.

PMID:36322633

Fam Community Health. 2022 Oct 31. doi: 10.1097/FCH.0000000000000350. Online ahead of print.

ABSTRACT

Congestive heart failure (CHF) readmissions are frequent and costly but preventable. The purpose of this study was to analyze socioeconomic and health-related factors of CHF readmissions by examining the relationship between 30-day readmissions of individuals with CHF and their payer status, race, ethnicity, primary language spoken, living arrangement, and comorbidities. This retrospective case-control study used secondary data from 450 CHF patients admitted to a not-for-profit Northern Virginia hospital from July 2014 to December 2017. Data were analyzed using χ2 and logistic regression. Living arrangements and comorbid chronic renal failure (CRF) were statistically significant predictors of CHF readmissions; all other factors were nonsignificant. Patients who lived with family and those in assisted living facilities were less likely to be readmitted than those who lived alone (odds ratio [OR] = 0.2 and 0.5, respectively). Patients without CRF were less likely to be readmitted than those who had CRF (OR = 0.6). This study contributes data to inform community-based health programs tailored toward frequently readmitted individuals due to CHF exacerbation.

PMID:36322616 | DOI:10.1097/FCH.0000000000000350

Pediatr Blood Cancer. 2022 Nov 2:e30046. doi: 10.1002/pbc.30046. Online ahead of print.

ABSTRACT

INTRODUCTION: There is limited understanding of pain, patient-reported outcomes (PROs) of health-related quality of life (HRQoL), psychological factors, and experimental pain sensitivity before and following hematopoietic cell transplant (HCT) in children with sickle cell disease (SCD).

METHODS: Individuals aged 8 years and older, English speaking, and scheduled for a HCT were invited to participate in an observational study where they completed assessments of pain, PROs, psychological factors, and qualitative interviews before and around 3 months, 6 months, 1 year, and 2 years post-HCT. An optional substudy of experimental pain sensitivity before and around 6 month, 1 year, and 2 years post-HCT was also offered.

RESULTS: Data from eight participants (median age 13.5 years, 25% female) with sickle cell anemia (SCA) or similarly severe genotype, and successful donor-derived erythropoiesis post-HCT are reported. We found that collection of pain, PROs, psychological factors, and qualitative data were feasible in the context of HCT. We found moderate to large differences in pain and some PROs between baseline to 1 year and baseline to 2 year post-HCT based on effect sizes, but only some differences were statistically significant. We found moderate to large differences in pressure pain threshold and moderate differences in cold pain threshold between baseline to 1 year and baseline to 2 year post-HCT based on effect sizes, but these differences were not statistically significant. Qualitative data indicated an improvement in pain and HRQoL post-HCT.

CONCLUSION: This study provides a framework for the conduct of multimodal pain assessments before and after HCT, which is feasible but faced with unique barriers.

PMID:36322607 | DOI:10.1002/pbc.30046

PLoS One. 2022 Nov 2;17(11):e0276860. doi: 10.1371/journal.pone.0276860. eCollection 2022.

ABSTRACT

Providing access to non-confidential government data to the public is one of the initiatives adopted by many governments today to embrace government transparency practices. The initiative of publishing non-confidential government data for the public to use and re-use without restrictions is known as Open Government Data (OGD). Nevertheless, after several years after its inception, the direction of OGD implementation remains uncertain. The extant literature on OGD adoption concentrates primarily on identifying factors influencing adoption decisions. Yet, studies on the underlying factors influencing OGD after the adoption phase are scarce. Based on these issues, this study investigated the post-adoption of OGD in the public sector, particularly the data provider agencies. The OGD post-adoption framework is crafted by anchoring the Technology-Organization-Environment (TOE) framework and the innovation adoption process theory. The data was collected from 266 government agencies in the Malaysian public sector. This study employed the partial least square-structural equation modeling as the statistical technique for factor analysis. The results indicate that two factors from the organizational context (top management support, organizational culture) and two from the technological context (complexity, relative advantage) have a significant contribution to the post-adoption of OGD in the public sector. The contribution of this study is threefold: theoretical, conceptual, and practical. This study contributed theoretically by introducing the post-adoption framework of OGD that comprises the acceptance, routinization, and infusion stages. As the majority of OGD adoption studies conclude their analysis at the adoption (decisions) phase, this study gives novel insight to extend the analysis into unexplored territory, specifically the post-adoption phase. Conceptually, this study presents two new factors in the environmental context to be explored in the OGD adoption study, namely, the data demand and incentives. The fact that data providers are not influenced by data requests from the agency’s external environment and incentive offerings is something that needs further investigation. In practicality, the findings of this study are anticipated to assist policymakers in strategizing for long-term OGD implementation from the data provider’s perspective. This effort is crucial to ensure that the OGD initiatives will be incorporated into the public sector’s service thrust and become one of the digital government services provided to the citizen.

PMID:36322601 | DOI:10.1371/journal.pone.0276860