Category: Statistics

Sci Rep. 2022 Jan 7;12(1):77. doi: 10.1038/s41598-021-03471-w.

ABSTRACT

Although the function of the BRCA1 gene has been extensively studied, the relationship between BRCA1 gene expression and tumor aggressiveness remains controversial in sporadic breast cancers. Because the BRCA1 protein is known to regulate estrogen signaling, we selected microarray data of ER⁺ breast cancers from the GEO public repository to resolve previous conflicting findings. The BRCA1 gene expression level in highly proliferative luminal B tumors was shown to be higher than that in luminal A tumors. Survival analysis using a cure model indicated that patients of early ER⁺ breast cancers with high BRCA1 expression developed rapid distant metastasis. In addition, the proliferation marker genes MKI67 and PCNA, which are characteristic of aggressive tumors, were also highly expressed in patients with high BRCA1 expression. The associations among high BRCA1 expression, high proliferation marker expression, and high risk of distant metastasis emerged in independent datasets, regardless of tamoxifen treatment. Tamoxifen therapy could improve the metastasis-free fraction of high BRCA1 expression patients. Our findings link BRCA1 expression with proliferation and possibly distant metastasis via the ER signaling pathway. We propose a testable hypothesis based on these consistent results and offer an interpretation for our reported associations.

PMID:34996912 | DOI:10.1038/s41598-021-03471-w

Proc Natl Acad Sci U S A. 2022 Jan 11;119(2):e2023340118. doi: 10.1073/pnas.2023340118.

ABSTRACT

Invariant stimulus recognition is a challenging pattern-recognition problem that must be dealt with by all sensory systems. Since neural responses evoked by a stimulus are perturbed in a multitude of ways, how can this computational capability be achieved? We examine this issue in the locust olfactory system. We find that locusts trained in an appetitive-conditioning assay robustly recognize the trained odorant independent of variations in stimulus durations, dynamics, or history, or changes in background and ambient conditions. However, individual- and population-level neural responses vary unpredictably with many of these variations. Our results indicate that linear statistical decoding schemes, which assign positive weights to ON neurons and negative weights to OFF neurons, resolve this apparent confound between neural variability and behavioral stability. Furthermore, simplification of the decoder using only ternary weights ({+1, 0, -1}) (i.e., an “ON-minus-OFF” approach) does not compromise performance, thereby striking a fine balance between simplicity and robustness.

PMID:34996867 | DOI:10.1073/pnas.2023340118

Sci Rep. 2022 Jan 7;12(1):118. doi: 10.1038/s41598-021-02808-9.

ABSTRACT

Integrating the spatiotemporal information acquired from the highly dynamic world around us is essential to navigate, reason, and decide properly. Although this is particularly important in a face-to-face conversation, very little research to date has specifically examined the neural correlates of temporal integration in dynamic face perception. Here we present statistically robust observations regarding the brain activations measured via electroencephalography (EEG) that are specific to the temporal integration. To that end, we generate videos of neutral faces of individuals and non-face objects, modulate the contrast of the even and odd frames at two specific frequencies ([Formula: see text] and [Formula: see text]) in an interlaced manner, and measure the steady-state visual evoked potential as participants view the videos. Then, we analyze the intermodulation components (IMs: ([Formula: see text]), a linear combination of the fundamentals with integer multipliers) that consequently reflect the nonlinear processing and indicate temporal integration by design. We show that electrodes around the medial temporal, inferior, and medial frontal areas respond strongly and selectively when viewing dynamic faces, which manifests the essential processes underlying our ability to perceive and understand our social world. The generation of IMs is only possible if even and odd frames are processed in succession and integrated temporally, therefore, the strong IMs in our frequency spectrum analysis show that the time between frames (1/60 s) is sufficient for temporal integration.

PMID:34996892 | DOI:10.1038/s41598-021-02808-9

J Int AIDS Soc. 2022 Jan;25(1):e25868. doi: 10.1002/jia2.25868.

ABSTRACT

INTRODUCTION: Little is known about the epidemiology of coronary artery disease (CAD) in sub-Saharan Africa, where the majority of people living with HIV (PLHIV) live. We assessed the association of HIV with CAD and explored relationships with monocyte activation in sex-stratified analyses of older PLHIV and people without HIV (PWOH) in Uganda.

METHODS: The Ugandan Study of HIV effects on the Myocardium and Atherosclerosis (mUTIMA) follows 100 PLHIV on antiretroviral therapy (ART) and 100 age- and sex-matched PWOH controls in Kampala, Uganda; all >45 years of age with >1 cardiovascular disease risk factor. At the year 2 exam (2017-2019), 189 participants had available coronary calcium score and 165 had coronary CT angiography (CCTA) for this analysis. A subset of participants (n = 107) had both CCTA and fresh whole blood flow cytometry for monocyte phenotyping.

RESULTS: Median age was 57.8 years and 63% were females. Overall, 88% had hypertension, 37% had diabetes and 4% were smokers. Atherosclerotic cardiovascular disease (ASCVD) risk was modestly higher for PWOH, but not statistically significant (median 10-year ASCVD risk 7.2% for PLHIV vs. 8.6% for PWOH, p = 0.09). Median duration of ART was 12.7 years and 86% had suppressed viral load. Despite a high prevalence of risk factors, only 34/165 (21%, 95% CI 15-28%) had any coronary plaque. After adjustment for ASCVD risk score, HIV status was not associated with CAD (OR 0.55, 95% CI 0.23-1.30) but was associated with more severe CAD (segment severity score>3) among those with disease (OR 10.9, 95% CI 1.67-70.45). Females had a trend towards higher odds of CAD among PLHIV (OR 4.1, 95% CI 0.4-44.9), but a trend towards lower odds of CAD among PWOH (OR 0.30; 95% CI 0.07-1.3; HIV*sex interaction p = 0.019). CAD was positively correlated with classical monocytes (r = 0.3, p = 0.012) and negatively correlated with CX3CR1 expression (r = -0.31, p = 0.011) in PLHIV and negatively correlated with patrolling monocytes (r = -0.36, p = 0.031) and tissue factor expression (r = -0.39, p = 0.017) in PWOH.

CONCLUSIONS: Our results suggest that HIV may be associated more with severity rather than the presence of CAD in Uganda. Sex differences in the HIV effect suggest that tailored CAD prevention strategies may be required in this setting.

PMID:34995413 | DOI:10.1002/jia2.25868

Int J Gynaecol Obstet. 2022 Jan 7. doi: 10.1002/ijgo.14089. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the functional outcomes of nerve-sparing surgery for deep infiltrating endometriosis (DIE) with or without postero-lateral parametrectomy.

METHODS: A multicenter, observational, retrospective, cohort study was performed including all symptomatic women who underwent nerve-sparing laparoscopic excision of DIE and preoperative and postoperative assessment of functional outcomes through validated questionnaires between April 2019 and March 2020. Women with postero-lateral parametrial DIE (P-group) and women with no parametrial involvement (NP-group) were compared in term of preoperative and postoperative: functional outcomes related to pelvic organs assessed through validated questionnaires (KESS and GIQLI for bowel function, BFLUTS for urinary function, and FSFI for sexual function); pain symptoms at 3-month follow-up assessed through a 11-points Visual Analogue Scales (VAS) for dyschezia, dysmenorrhea, dyspareunia and chronic pelvic pain; surgical outcomes; rate of urinary voiding dysfunction at 3-month follow-up.

RESULTS: One-hundred patients were included: 69 in the P-group and 31 in the NP-group. Preoperative and postoperative values of questionnaires, pain symptoms and postoperative complications rates were comparable between the two groups, except for postoperative dyspareunia and sexual dysfunction, which were statistically higher in the P-group. Only patients in the P-group experienced urinary voiding dysfunction, but no statistical significance was reached (p=.173).

CONCLUSION: Postero-lateral parametrectomy for DIE appears associated to a higher risk of post-operative dyspareunia and sexual dysfunction.

PMID:34995374 | DOI:10.1002/ijgo.14089

Int J Gynaecol Obstet. 2022 Jan 7. doi: 10.1002/ijgo.14091. Online ahead of print.

ABSTRACT

OBJECTIVE: To apply a new classification based on 7 clinically relevant subgroups to accurately describe episiotomy practices and evaluate the association between episiotomy and obstetrical anal sphincter injuries (OASIS) rates according to the classification’s subgroups.

METHODS: Observational retrospective cohort study based on a population comprising 39487 women from 01/01/2004 to 31/12/2020 in a level III university maternity unit. The primary outcome was the overall episiotomy rate in the institution, its trend over the time as well as in each subgroup of obstetric population classification. Secondary outcome was the rate of OASIS third and fourth degree, its association with episiotomy practice.

RESULTS: The episiotomy rate decreased significantly from 43,2% to 20% in the total population. The overall OASIS rate was 0,34%, it remained significantly the same during the study period, although the association between OASIS and episiotomy was significant only in group 2 (Nulliparous with instrumental delivery) with a decrease of OASIS rate if using episiotomy (OR 0.5; 95% CI[0,3-0,8]).

CONCLUSION: The episiotomy rate can be decreased without exposing women to an increased risk of OASIS. It encourages restrictive practice of episiotomy, but episiotomy should be considered in case of nulliparous women with instrumental delivery.

PMID:34995361 | DOI:10.1002/ijgo.14091

Int J Gynaecol Obstet. 2022 Jan 7. doi: 10.1002/ijgo.14087. Online ahead of print.

ABSTRACT

BACKGROUND: During pregnancy, urinary infections are an important cause of maternofetal morbimortality and may lead to several complications.

OBJECTIVES: Verify whether the use of antibiotic therapy in a single dose when compared to multiple doses in lower tract urinary infections during pregnancy is effective to obtain microbiological cure.

SEARCH STRATEGY: Online databases were searched. Keywords used were “single-drug dose”, “antibiotic”, “fosfomycin”, “amoxicillin”, “trimethoprim”, “pregnancy” and “urinary tract infection”.

SELECTION CRITERIA: Studies were included if: were randomized controlled trials, population was pregnant woman, microbiological cure was attained and one of the treatment groups received single-dose antibiotic therapy.

DATA COLLECTION AND ANALYSIS: Preselected studies have been independently read by pairs, and data were extracted according to a predetermined sheet. The Cochrane tool was used for the risk of bias.

MAIN RESULTS: 1063 women from 9 studies were included. The primary outcome was the microbiological cure attested by urine culture. When compared to the multiple-day use of antibiotics, the single-dose treatment has shown statistically similar results in reaching culture cure (OR 1.02, 95% IC 0.73-1.44).

CONCLUSION: The current study has shown that the use of single dose treatment for lower tract urinary infections during pregnancy can be recommended, specially using fosfomycin.

PMID:34995367 | DOI:10.1002/ijgo.14087

Blood. 2022 Jan 7:blood.2021014804. doi: 10.1182/blood.2021014804. Online ahead of print.

ABSTRACT

In acute myeloid leukemia (AML), measurable residual disease (MRD) before or after allogeneic hematopoietic cell transplantation (HCT) is an established, independent indicator of poor outcome. To address how peri-HCT MRD dynamics could refine risk assessment across different conditioning intensities, we analyzed 810 adults transplanted in remission after myeloablative conditioning (MAC; n=515) or non-MAC (n=295) who underwent multiparameter flow cytometry-based MRD testing before and 20-40 days after allografting. Patients without pre- and post-HCT MRD (MRDneg/MRDneg) had the lowest risks of relapse and highest relapse-free survival (RFS) and overall survival (OS). Relative to those patients, outcomes for MRDpos/MRDpos and MRDneg/MRDpos patients were poor regardless of conditioning intensity. Outcomes for MRDpos/MRDneg patients were intermediate. Among 161 patients with MRD before HCT, MRD was cleared more commonly with a MAC (85/104 [81.7%]) than non-MAC (33/57 [57.9%]) regimen (P=0.002). Although non-MAC regimens were less likely to clear MRD, if they did the impact on outcome was greater. Thus, there was a significant interaction between conditioning intensity and “MRD conversion” for relapse (P=0.020), RFS (P=0.002), and OS (P=0.001). Similar findings were obtained in the subset of 590 patients receiving HLA-matched allografts. C-statistic values were higher (indicating higher predictive accuracy) for peri-HCT MRD dynamics compared to the isolated use of pre-HCT MRD status and post-HCT MRD status for prediction of relapse, RFS, and OS. Across conditioning intensities, peri-HCT MRD dynamics improve risk assessment over isolated pre- or post-HCT MRD assessments.

PMID:34995355 | DOI:10.1182/blood.2021014804

Rheumatology (Oxford). 2022 Jan 6:keab937. doi: 10.1093/rheumatology/keab937. Online ahead of print.

ABSTRACT

OBJECTIVE: To better understand rheumatology patient and clinician pandemic-related experiences, medical relationships and behaviours in order to help identify the persisting impacts of the Covid-19 pandemic, and inform efforts to ameliorate the negative impacts and build-upon the positive ones.

METHODS: Rheumatology patients and clinicians completed surveys (Patients N = 1,543, Clinicians N = 111) and interviews (Patients N = 41, Clinicians N = 32) between April 2021 and August 2021. A cohort (N = 139) of systemic autoimmune rheumatic disease patients was also followed-up from March 2020 to April 2021. Analyses used sequential mixed methods. Pre-specified outcome measures included the Warwick-Edinburgh Mental wellbeing score (WEMWBS), satisfaction with care, and healthcare-behaviours.

RESULTS: We identified multiple ongoing pandemic-induced/increased barriers to receiving care. The percentage of patients agreeing they were medically supported reduced from 74.4% pre-pandemic to 39.7% during-pandemic. Ratings for medical support, medical-security and trust were significantly (p< 0.001) positively correlated with patient WEMWBS and healthcare-behaviours, and decreased during the pandemic. Healthcare-seeking was reduced, potentially long-term, including from patients feeling ‘abandoned’ by clinicians, and a ‘burden’ from Government messaging to protect the NHS. Blame and distrust were frequent, particularly between primary and secondary care, and towards the UK Government, whom <10% of clinicians felt had supported clinicians during the pandemic. Clinicians’ efforts were reported to be impeded by inefficient administration systems, and chronic understaffing, suggestive of the pandemic having exposed and exacerbated existing healthcare-system weaknesses.

CONCLUSION: Without concerted action-such as rebuilding trust, improved administrative systems, and more support for clinicians-barriers to care and negative impacts of the pandemic on trust, medical relationships, medical-security and patient help-seeking may persist longer-term.

TRIAL REGISTRATION: This study is part of a pre-registered longitudinal multi-stage trial, the LISTEN study (ISRCTN-14966097), with later Covid-related additions registered in March 2021, including a pre-registered statistical analysis plan.

PMID:34995345 | DOI:10.1093/rheumatology/keab937

PLoS One. 2022 Jan 7;17(1):e0262340. doi: 10.1371/journal.pone.0262340. eCollection 2022.

ABSTRACT

BACKGROUND: Readmission to hospital is frequent among older patients and reported as a post-discharge adverse outcome. The effect of treatment in a geriatric ward for acutely admitted older patients on mortality and function is well established, but less is known about the possible influence of such treatment on the risk of readmission, particularly in the oldest and most vulnerable patients. Our aim was to assess the risk for early readmission for multimorbid patients > 75 years treated in a geriatric ward compared to medical wards and to identify risk factors for 30-day readmissions.

METHODS: Prospective cohort study of patients acutely admitted to a medical department at a Norwegian regional hospital. Eligible patients were community-dwelling, multimorbid, receiving home care services, and aged 75+. Patients were consecutively included in the period from 1 April to 31 October 2012. Clinical data were retrieved from the referral letter and medical records.

RESULTS: We included 227 patients with a mean (SD) age of 86.0 (5.7) years, 134 (59%) were female and 59 (26%) were readmitted within 30 days after discharge. We found no statistically significant difference in readmission rate between patients treated in a geriatric ward versus other medical wards. In adjusted Cox proportional hazards regression analyses, lower age (hazard ratio (95% confidence interval) 0.95 (0.91-0.99) per year), female gender (2.17 (1.15-4.00)) and higher MMSE score (1.03 (1.00-1.06) per point) were significant risk factors for readmission.

CONCLUSIONS: Lower age, female gender and higher cognitive function were the main risk factors for 30-day readmission to hospital among old patients with multimorbidity. We found no impact of geriatric care on the readmission rate.

PMID:34995327 | DOI:10.1371/journal.pone.0262340