Category: Nevin Manimala

Invest Ophthalmol Vis Sci. 2021 May 3;62(6):7. doi: 10.1167/iovs.62.6.7.

ABSTRACT

Analysis of time-to-event data, otherwise known as survival analysis, is a common investigative tool in ophthalmic research. For example, time-to-event data is useful when researchers are interested in investigating how long it takes for an ocular condition to worsen or whether treatment can delay the development of a potentially vision-threatening complication. Its implementation requires a different set of statistical tools compared to those required for analyses of other continuous and categorial outcomes. In this installment of the Focus on Data series, we present an overview of selected concepts relating to analysis of time-to-event data in eye research. We introduce censoring, model selection, consideration of model assumptions, and best practice for reporting. We also consider challenges that commonly arise when analyzing time-to-event data in ophthalmic research, including collection of data from two eyes per person and the presence of multiple outcomes of interest. The concepts are illustrated using data from the Laser Intervention in Early Stages of Age-Related Macular Degeneration study and statistical computing code for Stata is provided to demonstrate the application of the statistical methods to illustrative data.

PMID:33950248 | DOI:10.1167/iovs.62.6.7

Rheumatology (Oxford). 2021 May 5:keab401. doi: 10.1093/rheumatology/keab401. Online ahead of print.

ABSTRACT

BACKGROUND: Systemic lupus erythematosus (SLE) can affect any part of the gastrointestinal (GI) tract. GI symptoms are reported to occur in more than 50% of SLE patients.

AIMS: To describe the GI manifestations of SLE in the RELESSER (Registry of Systemic Lupus Erythematosus Patients of the Spanish Society of Rheumatology) cohort and to determine if these are associated with a more severe disease, damage accrual and a worse prognosis.

METHODS: We conducted a nationwide, retrospective, multicenter, cross-sectional cohort study of 3658 SLE patients who fulfill ≥ 4 ACR-97 criteria. Data on demographics, disease characteristics, activity (SLEDAI-2K or BILAG), damage (SLICC/ACR/DI) and therapies were collected. Demographic and clinical characteristics were compared between lupus patients with and without GI damage to establish whether GI damage is associated with a more severe disease.

RESULTS: From 3654 lupus patients, 3.7% developed GI damage. Patients in this group (group 1) were older, they had longer disease duration, and were more likely to have vasculitis, renal disease and serositis than patients without GI damage (group 2). Hospitalizations and mortality were significantly higher in group 1. Patients in group 1 had higher modified SDI. The presence of oral ulcers reduced risk of developing damage in 33% of patients.

CONCLUSIONS: Having GI damage is associated with a worse prognosis. Patients on high dose of glucocorticoids are at higher risk of developing GI damage which reinforces the strategy of minimizing glucocorticoids. Oral ulcers appear to decrease the risk of GI damage.

PMID:33950249 | DOI:10.1093/rheumatology/keab401

Brain. 2021 May 5:awab157. doi: 10.1093/brain/awab157. Online ahead of print.

ABSTRACT

Cerebellar ataxias represent a heterogeneous group of disabling disorders characterized by motor and cognitive disturbances, for which no effective treatment is currently available. In this randomized, double-blind, sham-controlled trial, followed by an open-label phase, we investigated whether treatment with cerebello-spinal transcranial direct current stimulation (tDCS) could improve both motor and cognitive symptoms in patients with neurodegenerative ataxia at short and long-term. Sixty-one patients were randomized in two groups for the first controlled phase. At baseline (T0), Group 1 received placebo stimulation (sham tDCS) while Group 2 received anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5 days/week for two weeks (T1), with a 12-week (T2) follow-up (randomized, double-blind, sham controlled phase). At the 12-week follow-up (T2), all patients (Group 1 and Group 2) received a second treatment of anodal cerebellar tDCS and cathodal spinal tDCS (real tDCS) for 5 days/week for two weeks, with a 14-week (T3), 24-week (T4), 36-week (T5) and 52-week follow-up (T6) (open-label phase). At each time point, a clinical, neuropsychological and neurophysiological evaluation was performed. Cerebellar-motor cortex connectivity was evaluated using transcranial magnetic stimulation (TMS). We observed a significant improvement in all motor scores (scale for the assessment and rating of ataxia, international cooperative ataxia rating scale), in cognition (evaluated with the cerebellar cognitive affective syndrome scale), in quality-of-life scores, in motor cortex excitability and in cerebellar inhibition after real tDCS compared to sham stimulation and compared to baseline (T0), both at short and long-term. We observed an addon-effect after two repeated treatments with real tDCS compared to a single treatment with real tDCS. The improvement at motor and cognitive scores correlated with the restoration of cerebellar inhibition evaluated with TMS. Cerebello-spinal tDCS represents a promising therapeutic approach for both motor and cognitive symptoms in patients with neurodegenerative ataxia, a still orphan disorder of any pharmacological intervention.

PMID:33950222 | DOI:10.1093/brain/awab157

Bioinformatics. 2021 May 5:btab240. doi: 10.1093/bioinformatics/btab240. Online ahead of print.

ABSTRACT

MOTIVATION: Genetic or epigenetic events can rewire molecular networks to induce extraordinary phenotypical divergences. Among the many network rewiring approaches, no model-free statistical methods can differentiate gene-gene pattern changes not attributed to marginal changes. This may obscure fundamental rewiring from superficial changes.

RESULTS: Here we introduce a model-free Sharma-Song test to determine if patterns differ in the second order, meaning that the deviation of the joint distribution from the product of marginal distributions is unequal across conditions. We prove an asymptotic chi-squared null distribution for the test statistic. Simulation studies demonstrate its advantage over alternative methods in detecting second-order differential patterns. Applying the test on three independent mammalian developmental transcriptome datasets, we report a lower frequency of co-expression network rewiring between human and mouse for the same tissue group than the frequency of rewiring between tissue groups within the same species. We also find secondorder differential patterns between microRNA promoters and genes contrasting cerebellum and liver development in mice. These patterns are enriched in the spliceosome pathway regulating tissue specificity. Complementary to previous mammalian comparative studies mostly driven by first-order effects, our findings contribute an understanding of system-wide second-order gene network rewiring within and across mammalian systems. Second-order differential patterns constitute evidence for fundamentally rewired biological circuitry due to evolution, environment, or disease.

AVAILABILITY: The generic Sharma-Song test is available from the R package ‘DiffXTables’ at https://cran.rproject.org/package=DiffXTables. Other code and data are described in Methods.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:33950233 | DOI:10.1093/bioinformatics/btab240

JAMA Surg. 2021 May 5. doi: 10.1001/jamasurg.2021.1546. Online ahead of print.

ABSTRACT

IMPORTANCE: Diversity in academic surgery is lacking, particularly among positions of leadership.

OBJECTIVE: To evaluate trends among racial/ethnical minority groups stratified by gender along the surgical pipeline, as well as in surgical leadership.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional and longitudinal analysis assessed US surgical faculty census data obtained from the Association of American Medical Colleges faculty roster in the Faculty Administrative Management Online User System database. Surgical faculty members captured in census data from December 31, 2013, to December 31, 2019, were included in the analysis. Faculty were identified from the surgery category of the faculty roster, which includes general surgeons and subspecialists, neurosurgeons, and urologists.

MAIN OUTCOMES AND MEASURES: Gender and race/ethnicity were obtained for surgical faculty stratified by rank. Descriptive statistics with annual percentage of change in representation are reported based on faculty rank.

RESULTS: A total of 15 653 US surgical faculty, including 3876 women (24.8%), were included in the data set for 2019. Female faculty from racial/ethnic minority groups experienced an increase in representation at instructor and assistant and associate professorship appointments, with a more favorable trajectory than male faculty from racial/ethnic minority groups across nearly all ranks. White faculty maintain most leadership positions as full professors (3105 of 3997 [77.7%]) and chairs (294 of 380 [77.4%]). The greatest magnitude of underrepresentation along the surgical pipeline has been among Black (106 of 3997 [2.7%]) and Hispanic/Latinx (176 of 3997 [4.4%]) full professors. Among full professors, although Black and Hispanic/Latinx male representation increased modestly (annual change, 0.07% and 0.10%, respectively), Black female representation remained constant (annual change, 0.00004%) and Hispanic/Latinx female representation decreased (annual change, -0.16%). Overall Hispanic/Latinx (20 of 380 [5.3%]) and Black (13 of 380 [3.4%]) representation as chairs has not changed, with only 1 Black and 1 Hispanic/Latinx woman ascending to chair from 2013 to 2019.

CONCLUSIONS AND RELEVANCE: A disproportionately small number of faculty from minority groups obtain leadership positions in academic surgery. Intersectionality may leave female members of racial/ethnic minority groups more disadvantaged than their male colleagues in achieving leadership positions. These findings highlight the urgency to diversify surgical leadership.

PMID:33950242 | DOI:10.1001/jamasurg.2021.1546

Eur J Orthod. 2021 May 5:cjab017. doi: 10.1093/ejo/cjab017. Online ahead of print.

ABSTRACT

OBJECTIVES: To compare the long-term skeletal stability following maxillary advancement using Rigid External Distraction (RED) in growing and non-growing patients with Cleft Lip and Palate (CLP).

METHODS: Data sources: A systematic literature search was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines from database inception till August 2020 in MEDLINE-PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Science Direct, Google Scholar and a manual search in the institutional library. Study eligibility criteria, participants and intervention: All available literature published in English, with a minimum of six human subjects with well-defined age range either 7-14.9 years or 15-30 years, follow up period of a minimum of 12 months assessing the skeletal stability as horizontal change at Point A (Subspinale) following maxillary advancement using a RED device, without the use of rigid internal fixation or bone grafts were included in the study. Study appraisal and synthesis method: The quality assessment of selected articles was done using the Newcastle-Ottawa scale. The meta-analysis was carried out with Q statistic method, I-squared statistics, fixed-effect model to estimate pooled mean and Begg-Mazumdar bias indicator.

RESULTS: Selected nine articles that were qualitatively assessed for relapse rate following maxillary advancement using a RED device, showed consistent and stable results. The meta-analysis found no significant difference in long-term skeletal stability of maxillary advancement by RED device in growing and non-growing patients with CLP [(growing group: Pooled proportion = 0.2927; 95% CI = 0.1534 to 0.4319) (non-growing group: Pooled proportion = 0.23077; 95% CI = 0.09854 to 0.36300)].

LIMITATIONS: No study, as revealed by the search, was available that compared the two groups as defined by the inclusion criteria. Data for the two groups were retrieved from different studies and meta-analysed.

CONCLUSION: RED is an effective modality for correction of maxillary hypoplasia secondary to CLP, requiring large maxillary advancement. The technique can be used in young and adult patients with similar long-term results.

PROSPERO REGISTRATION NUMBER: CRD42020205513.

PMID:33950171 | DOI:10.1093/ejo/cjab017

JAMA Surg. 2021 May 5. doi: 10.1001/jamasurg.2021.1438. Online ahead of print.

ABSTRACT

IMPORTANCE: Cohort studies show better survival after breast-conserving surgery (BCS) with postoperative radiotherapy (RT) than after mastectomy (Mx) without RT. It remains unclear whether this is an independent effect or a consequence of selection bias.

OBJECTIVE: To determine whether the reported survival benefit of breast conservation is eliminated by adjustment for 2 pivotal confounders, comorbidity and socioeconomic status.

DESIGN, SETTING, AND PARTICIPANTS: Cohort study using prospectively collected national data. Swedish public health care; nationwide clinical data from the National Breast Cancer Quality Register, comorbidity data from Patient Registers at the National Board of Health and Welfare, and individual-level education and income data from Statistics Sweden. The cohort included all women diagnosed as having primary invasive T1-2 N0-2 breast cancer and undergoing breast surgery in Sweden from 2008 to 2017. Data were analyzed between August 19, 2020, and November 12, 2020.

EXPOSURES: Locoregional treatment comparing 3 groups: breast-conserving surgery with radiotherapy (BCS+RT), mastectomy without radiotherapy (Mx-RT), and mastectomy with radiotherapy (Mx+RT).

MAIN OUTCOMES AND MEASURES: Overall survival (OS) and breast cancer-specific survival (BCSS). Main outcomes were determined before initiation of data retrieval.

RESULTS: Among 48 986 women, 29 367 (59.9%) had BCS+RT, 12413 (25.3%) had Mx-RT, and 7206 (14.7%) had Mx+RT. Median follow-up was 6.28 years (range, 0.01-11.70). All-cause death occurred in 6573 cases, with death caused by breast cancer in 2313 cases; 5-year OS was 91.1% (95% CI, 90.8-91.3) and BCSS was 96.3% (95% CI, 96.1-96.4). Apart from expected differences in clinical parameters, women receiving Mx-RT were older, had a lower level of education, and lower income. Both Mx groups had a higher comorbidity burden irrespective of RT. After stepwise adjustment for all covariates, OS and BCSS were significantly worse after Mx-RT (hazard ratio [HR], 1.79; 95% CI, 1.66-1.92 and HR, 1.66; 95% CI, 1.45-1.90, respectively) and Mx+RT (HR, 1.24; 95% CI, 1.13-1.37 and HR, 1.26; 95% CI, 1.08-1.46, respectively) than after BCS+RT.

CONCLUSIONS AND RELEVANCE: Despite adjustment for previously unmeasured confounders, BCS+RT yielded better survival than Mx irrespective of RT. If both interventions are valid options, mastectomy should not be regarded as equal to breast conservation.

PMID:33950173 | DOI:10.1001/jamasurg.2021.1438

Nucleic Acids Res. 2021 May 5:gkab349. doi: 10.1093/nar/gkab349. Online ahead of print.

ABSTRACT

Deep learning has demonstrated its predictive power in modeling complex biological phenomena such as gene expression. The value of these models hinges not only on their accuracy, but also on the ability to extract biologically relevant information from the trained models. While there has been much recent work on developing feature attribution methods that discover the most important features for a given sequence, inferring cooperativity between regulatory elements, which is the hallmark of phenomena such as gene expression, remains an open problem. We present SATORI, a Self-ATtentiOn based model to detect Regulatory element Interactions. Our approach combines convolutional layers with a self-attention mechanism that helps us capture a global view of the landscape of interactions between regulatory elements in a sequence. A comprehensive evaluation demonstrates the ability of SATORI to identify numerous statistically significant TF-TF interactions, many of which have been previously reported. Our method is able to detect higher numbers of experimentally verified TF-TF interactions than existing methods, and has the advantage of not requiring a computationally expensive post-processing step. Finally, SATORI can be used for detection of any type of feature interaction in models that use a similar attention mechanism, and is not limited to the detection of TF-TF interactions.

PMID:33950192 | DOI:10.1093/nar/gkab349

Codas. 2021 May 3;33(1):e20190026. doi: 10.1590/2317-1782/20202019026. eCollection 2021.

ABSTRACT

PURPOSE: evaluate the influence of frenotomy on the breastfeeding of newborns diagnosed with ankyloglossia.

METHODS: this is an intervention study performed with 50 newborns diagnosed with ankyloglossia. It was conducted in three stages: diagnosis, intervention and reassessment. In the diagnostic phase, the Protocol for the Assessment of Speech Language with Scores for Babies was applied to diagnose ankyloglossia and a questionnaire assessing the symptoms and coordination of sucking, swallowing and breathing during breastfeeding. In the intervention, frenotomy was performed, and at reassessment, the diagnostic protocol and questionnaire in order to compare the post-surgical effects.

RESULTS: of the 50 babies participating in the study, 35 (70%) were boys and 15 (30%) girls. A total of 68% of ankyloglossia cases were reported in the family, a majority (38%) involving cousins. There was a statistically significant reduction in the average protocol score in the reassessment stage, from 8.38 (7-12 points) to 0.86 (0-5 points), as well as a statistically significant improvement in all variables related to the symptoms of breastfeeding.

CONCLUSION: surgical intervention, known as frenotomy, made it possible to improve the negative symptoms of breastfeeding in newborns diagnosed with ankyloglossia.

PMID:33950144 | DOI:10.1590/2317-1782/20202019026

JAMA Psychiatry. 2021 May 5. doi: 10.1001/jamapsychiatry.2021.0480. Online ahead of print.

ABSTRACT

IMPORTANCE: Racial/ethnic and sex disparities in suicide ideation and attempts are well established, with higher risk of suicide ideation and attempt among US racial/ethnic minority school-aged youths (than their White peers) and girls and women (than boys and men). The suicide-related risk of racial/ethnic minority young adults, especially young women, may be strongly influenced by adverse childhood experiences, known early determinants of suicide ideation and attempts.

OBJECTIVES: To assess lifetime and past-year prevalence estimates of suicide ideation and suicide attempt and to examine sex differences in the role of adverse childhood experiences as a prospective risk factor for Puerto Rican young adults from 2 sociocultural contexts.

DESIGN, SETTING, AND PARTICIPANTS: Data in this longitudinal cohort study are from 4 waves of the Boricua Youth Study, a population-based cohort study of Puerto Rican children from San Juan and Caguas, Puerto Rico, and the South Bronx, New York, 5 to 17 years of age (N = 2491; waves 1-3: 2000-2004) and 15 to 29 years of age (wave 4: 2013-2017). Data analysis was performed from February 26, 2019, to October 16, 2020.

EXPOSURES: Adverse childhood experiences were assessed by interview in childhood and early adolescence (waves 1-3) and included child maltreatment (physical, sexual, and emotional abuse and neglect), exposure to violence, parental loss (separation, divorce, and death), and parental maladjustment (mental health problems, substance or alcohol abuse, intimate partner violence, and incarceration).

MAIN OUTCOMES AND MEASURES: Lifetime and past-year suicide ideation and attempt were assessed in young adulthood (wave 4) using the World Health Organization Composite International Diagnostic Interview.

RESULTS: Among 2004 Puerto Rican young adults (80.4% of the original cohort; mean [SD] age, 22.9 [2.8] years; 1019 [50.8%] male), young women compared with young men had a higher prevalence of lifetime suicide attempt (9.5% vs 3.6%) and lifetime suicide ideation (16.4% vs 11.5%), whereas past-year suicide ideation (4.4% vs 2.4%) was not statistically different. Logistic regression models, adjusting for demographics and lifetime psychiatric disorders, found that young women but not young men with more adverse childhood experiences had higher odds of suicide ideation (lifetime; odds ratio [OR], 2.44; 95% CI, 1.54-3.87; past year: OR, 2.56; 95% CI, 1.18-5.55). More adverse childhood experiences were also prospectively associated with lifetime suicide attempt (OR, 1.16; 95% CI, 1.04-1.29), irrespective of sex.

CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that, among Puerto Rican young adults from 2 different sociocultural contexts, adverse childhood experiences were relevant to understanding suicide attempt and suicide ideation, the latter specifically among young women. The prevention of cumulative adverse childhood experiences could reduce later risk of suicide attempts and, among young women, for suicide ideation.

PMID:33950163 | DOI:10.1001/jamapsychiatry.2021.0480