Nevin Manimala

Placenta. 2022 Mar 5;121:53-60. doi: 10.1016/j.placenta.2022.03.001. Online ahead of print.

ABSTRACT

INTRODUCTION: Obstructive sleep apnoea (OSA), a condition characterised by intermittent hypoxia and reoxygenation during sleep, is associated with an increased risk of adverse pregnancy outcomes including gestational diabetes and hypertensive disorders of pregnancy. The biological mechanisms of these associations are poorly understood. The impact of OSA on placental function has not been well characterised.

METHODS: We performed 3′ mRNA sequencing on placenta from women with obesity and OSA (n = 11) and women with obesity and no OSA (n = 9).

RESULTS: After correcting for multiple testing, there were no statistically significant differences in gene expression between OSA and no OSA groups (adjusted p < 0.05). In unadjusted analyses, 101 genes were differentially expressed in OSA compared to no OSA placentae (p < 0.01). In Reactome pathway and GO term analysis, this included downregulation of genes involved in O-linked glycosylation (B3GNT5 and B3GNT8) and Wnt signalling (TRABD2B and FRZB) pathways. In gene set enrichment analysis, genes within 24 pathways had a non-random distribution in OSA compared to no OSA placentae (adjusted p < 0.05). This included an increase in genes relating to the reversible hydration of carbon dioxide in OSA placentae, a potential novel mechanism contributing to the development of adverse pregnancy outcomes in women with OSA.

DISCUSSION: There is overall similarity in the placental transcriptome of women with obesity who do and do not have OSA during pregnancy. Alterations in the reversible hydration of carbon dioxide are a potential mechanism contributing to the development of adverse pregnancy outcomes in maternal OSA, however this finding requires validation in larger cohorts.

PMID:35278842 | DOI:10.1016/j.placenta.2022.03.001

J Biomech. 2022 Mar 2;135:111027. doi: 10.1016/j.jbiomech.2022.111027. Online ahead of print.

ABSTRACT

This study aimed to elucidate the overall spatial distribution of palmar aponeurosis (PA) thickness, d, and Young’s modulus, E, through two-dimensional ultrasound and shear wave elastography. Statistical analysis of the collected data of 14 subjects shows that the ICC_3,1 of thickness, d, and Young’s modulus, E, is 0.974 and 0.985 separately, which means thickness, d, and Young’s modulus, E, have acceptable retest reliability. According the results of this study, it is concluded that the thickness, d, and Young’s modulus, E, of the PA both exhibit specific spatial dependence. Along the direction from the capitate bone to the four fingers, the thickness, d, and Young’s modulus, E, of the four longitudinal bundles of the PA show a downward trend like Boltzmann’s function, with the maximum value at the capitate bone and the minimum values at palmar creases. The determination coefficients (R²) of the thickness, d, and Young’s modulus, E, fitting curves are all above 0.910 in all healthy subjects, whose palmar aponeurosis thickness, d, and Young’s modulus, E, distribution characteristics in space show satisfying consistency.

PMID:35278821 | DOI:10.1016/j.jbiomech.2022.111027

Comput Methods Programs Biomed. 2022 Feb 16;217:106694. doi: 10.1016/j.cmpb.2022.106694. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Nowadays the “low sample size, large dimension” scenario is often encountered in genetics and in the omic sciences, where the microarray data is typically formed by a large number of possibly dependent small samples. Standard methods to solve the k-sample problem in such a setting are of limited applicability due to lack of theoretical validation for large k, lengthy computational times, missing software solutions, or inability to deal with statistical dependence among the samples. This paper presents the R package Equalden.HD to overcome the referred limitations.

METHODS: The package implements several tests for the null hypothesis that a large number of samples follow a common density. These methods are particularly well suited to the “low sample size, large dimension” setting. The implemented procedures allow for dependent samples. For each method Equalden.HD reports, among other things, the standardized value of the test statistic and the corresponding p-value. The package also includes two high-dimensional genetic data sets, Hedenfalk and Rat, which are used in this paper for illustration purposes.

RESULTS: The usage of Equalden.HD has been illustrated through the analysis of Hedenfalk and Rat genetic data. Statistical dependence among the samples was found for both genetic data sets. The application of an appropriate k-sample test within Equalden.HD rejected the null hypothesis of inter-samples homogeneity. The methods were used to test for the within groups homogeneity in cluster analysis too, which is usually performed when the k samples are found to be significantly different. Equalden.HD helped to identify the individuals which are responsible for the lack of homogeneity of the samples. The limitations of the standard Kruskal-Wallis test for the identification of homogeneous clusters have been highlighted.

CONCLUSIONS: The methods implemented by Equalden.HD are the unique omnibus nonparametric k-sample tests that have been validated as k grows. Furthermore, the package provides suitable corrections for possibly dependent samples, which is another distinctive feature. Thus, the package opens new doors for the statistical analysis of omic data. Limitations of standard methods (e.g. Anderson-Darling and Kruskal-Wallis) and existing software solutions in the setting with a large k have been emphasized.

PMID:35278813 | DOI:10.1016/j.cmpb.2022.106694

J Stomatol Oral Maxillofac Surg. 2022 Mar 9:S2468-7855(22)00058-1. doi: 10.1016/j.jormas.2022.03.011. Online ahead of print.

ABSTRACT

BACKGROUND: YouTube has been increasingly used as a source of information by patients in the field of health, but many studies revealed poor information quality. This study evaluated the content and quality of YouTube videos on Temporomandibular Joint Arthrocentesis (TMJA) as an information resource for patients.

MATERIAL AND METHODS: YouTube search with the two keywords “temporomandibular joint arthrocentesis” and ”temporomandibular joint lavage” was performed. The first 160 videos were listed for each term according to relevancy. Results were assessed for inclusion and categorized for source, purpose, target, arthrocentesis method described, and the narrator of the videos. An evaluation was performed independently by two oral and maxillofacial surgeons. The quality of videos was analyzed for the content and defined as poor, moderate, and excellent. DISCERN was also performed by scoring between 0 and 5.

RESULTS: A total of 43 videos were evaluated. The most upload source was individual users (46.5%) and the most video upload purpose was information for professionals (37.2%). The method with the most information about was the two-needle technic, which had a rate of 44.2 percent. The average usefulness score of the videos was 3.00 and 57.1% of the videos resulted in poor quality. A statistically significant positive high correlation was found between DISCERN and usefulness scoring (r=0.793; p<0.001).

CONCLUSION: The majority of YouTube videos are of poor quality and this situation affects the patients’ decisions about treatment. Health professionals should be aware of the content on YouTube and produce high-quality, accurate, and up-to-date information for patient education.

PMID:35278759 | DOI:10.1016/j.jormas.2022.03.011

Ophthalmol Retina. 2022 Mar 9:S2468-6530(22)00089-6. doi: 10.1016/j.oret.2022.03.002. Online ahead of print.

ABSTRACT

PURPOSE: To compare nonmydriatic and mydriatic handheld retinal imaging with standard ETDRS 7-field color fundus photography (ETDRS photos) for the assessment of diabetic retinopathy (DR) and diabetic macular edema (DME).

DESIGN: Prospective, comparative, instrument validation study SUBJECTS: 225 eyes from 116 patients with diabetes mellitus METHODS: Following a standardized protocol, nonmydriatic and mydriatic images were acquired using handheld retinal cameras [Nonmydriatic (NM): Aurora (AUNM), Smartscope (SSNM), RetinaVue-700 (RVNM); Mydriatic (MD): Aurora (AUMD), Smartscope (SSMD), RetinaVue-700 (RVMD), iNview (NVMD)] and dilated ETDRS photos. Grading was performed at a centralized reading center using the International Clinical Classification for DR and DME. Kappa statistics [simple (K), weighted (Kw)] assessed the level of agreement for DR and DME. Sensitivity and specificity were calculated for any DR, referable DR (refDR) and vision-threatening DR (vtDR).

MAIN OUTCOME MEASURES: Agreement for DR and DME, sensitivity and specificity for any DR, refDR and vtDR, ungradable rates RESULTS: Severity by ETDRS photos: no DR 33.3%, mild NPDR 20.4%, moderate 14.2%, severe in 11.6%, proliferative DR 20.4%; no DME 68.0%, DME 9.3%, ciDME 17.3%, ungradable 5.3%. For nonmydriatic handheld retinal imaging, Kw was 0.70 to 0.73 for DR and 0.76 to 0.83 for DME. For mydriatic handheld retinal imaging, Kw was 0.68 to 0.75 for DR and 0.77 to 0.91 for DME. Thresholds for sensitivity (0.80) and specificity (0.95) were met by SSNM, AUMD and RVMD for anyDR, and by AUMD and RVMD for refDR. Thresholds for sensitivity and specificity were met by AUMD and RVMD for DME. Nonmydriatic and Mydriatic ungradable rate for DR was 15.1% to 38.3% and 0% to 33.8%, respectively.

CONCLUSIONS: Following standardized protocols, nonmydriatic and mydriatic handheld retinal imaging devices have substantial agreement levels for DR and DME. With mydriasis, not all handheld retinal imaging devices meet standards for sensitivity and specificity in identifying any DR and refDR. None of the handheld devices met the established 95% specificity for vtDR, suggesting that lower referral thresholds should be used if handheld devices must be utilized. When using handheld devices, the ungradable rate is significantly reduced with mydriasis and DME sensitivity thresholds are only achieved following dilation.

PMID:35278726 | DOI:10.1016/j.oret.2022.03.002

Pract Radiat Oncol. 2022 Mar 9:S1879-8500(22)00078-9. doi: 10.1016/j.prro.2022.02.013. Online ahead of print.

ABSTRACT

PURPOSE: Radiotherapy is a standard part of limb conserving therapy for extremity soft tissue sarcoma (STS) at high risk of recurrence. Toxicities increase with radiation dose and volume of normal tissue irradiated. This study sought to compare dosimetry of volumetric modulated arc radiotherapy (VMAT), with intensity modulated radiotherapy (IMRT) and to investigate the optimal planning technique.

METHODS AND MATERIALS: Twenty patients with extremity STS who underwent preoperative radiotherapy (50 Gy in 25 fractions) between 2016 and 2020 at a sarcoma specialist centre were included. The original treatment techniques were sliding window IMRT or 3D conformal. VMAT plans were retrospectively generated according to the original tumour and organ at risk constraints. Quality assurance was performed as per departmental protocol. Wilcoxon signed-rank test was used to compare dosimetric parameters (for planning target volume, in-field bone, and soft tissue structures), monitor units (MU) and treatment time.

RESULTS: Median patient age was 65 years and majority were male (n=14, 70%). Commonest subtype was undifferentiated pleomorphic sarcoma (n=14, 70%) and most tumours were located on the thigh (n=12, 60%). Median PTV volume was 1110 cm³ and median volume of in-field bone 236 cm³. VMAT plans had significantly lower average MU (480 vs 862 MU, p<0.001) and overall treatment time (300 vs 153 seconds, p<0.001). PTV coverage favoured VMAT, with marginally higher mean, minimum, and maximum doses, and higher Conformity Index. However, differences were not statistically significant. Dose to infield bone and soft tissue structures were similar or slightly lower with VMAT.

CONCLUSIONS: In extremity soft tissue sarcoma, VMAT plans demonstrated a favourable trend toward tumour coverage and dose conformity compared to IMRT along with significantly lower monitor units and half the overall treatment time.

PMID:35278718 | DOI:10.1016/j.prro.2022.02.013

Neuroimage. 2022 Mar 9:119083. doi: 10.1016/j.neuroimage.2022.119083. Online ahead of print.

ABSTRACT

Machine learning methods exploiting multi-parametric biomarkers, especially based on neuroimaging, have huge potential to improve early diagnosis of dementia and to predict which individuals are at-risk of developing dementia. To benchmark algorithms in the field of machine learning and neuroimaging in dementia and assess their potential for use in clinical practice and clinical trials, seven grand challenges have been organized in the last decade: MIRIAD (2012), Alzheimer’s Disease Big Data DREAM (2014), CADDementia (2014), Machine Learning Challenge (2014), MCI Neuroimaging (2017), TADPOLE (2017), and the Predictive Analytics Competition (2019). Based on two challenge evaluation frameworks, we analyzed how these grand challenges are complementing each other regarding research questions, datasets, validation approaches, results and impact. The seven grand challenges addressed questions related to screening, clinical status estimation, prediction and monitoring in (pre-clinical) dementia. There was little overlap in clinical questions, tasks and performance metrics. Whereas this aids providing insight on a broad range of questions, it also limits the validation of results across challenges. The validation process itself was mostly comparable between challenges, using similar methods for ensuring objective comparison, uncertainty estimation and statistical testing. In general, winning algorithms performed rigorous data pre-processing and combined a wide range of input features. Despite high state-of-the-art performances, most of the methods evaluated by the challenges are not clinically used. To increase impact, future challenges could pay more attention to statistical analysis of which factors (i.e., features, models) relate to higher performance, to clinical questions beyond Alzheimer’s disease, and to using testing data beyond the Alzheimer’s Disease Neuroimaging Initiative. Grand challenges would be an ideal venue for assessing the generalizability of algorithm performance to unseen data of other cohorts. Key for increasing impact in this way are larger testing data sizes, which could be reached by sharing algorithms rather than data to exploit data that cannot be shared. Given the potential and lessons learned in the past ten years, we are excited by the prospects of grand challenges in machine learning and neuroimaging for the next ten years and beyond.

PMID:35278709 | DOI:10.1016/j.neuroimage.2022.119083

J Shoulder Elbow Surg. 2022 Mar 9:S1058-2746(22)00269-5. doi: 10.1016/j.jse.2022.01.151. Online ahead of print.

ABSTRACT

BACKGROUND: The development of radioulnar synostosis secondary to posttraumatic injuries to the elbow or forearm can lead to debilitating outcomes. Several treatment options are available to hinder the progression and prevent reoccurrence. The authors used a combination of these treatments on a series of patients and observed the outcomes.

METHODS: A retrospective study was conducted on 10 patients with posttraumatic radioulnar synostosis (9 males and 1 female) that required surgical intervention in a tertiary orthopedic center. All of these patients were subjected to the same treatment combination (preoperative radiotherapy, tissue interposition post heterotopic ossification resection and adjuvant indomethacin Postoperatively). Improvement in range of motion (flexion, extension, and rotation) and Mayo score was performed and compared pre- and postoperatively via statistical analysis.

RESULTS: In comparison to their preoperative state that ranged from fair to poor, all 10 patients reported excellent Mayo score results post intervention with triple therapy combination with a mean of 36 ± 10.2 points. Flexion, extension, and rotation scores improved with means of 55.2° ± 38.7, 50.2° ± 34.0, and 47.9° ± 40.0, respectively. We had one complication that has subsided on follow-up.

CONCLUSION: The triple therapy combination has been noted to provide good functional and prophylactic results preventing recurrence.

PMID:35278681 | DOI:10.1016/j.jse.2022.01.151

Mol Ther. 2022 Mar 9:S1525-0016(22)00158-7. doi: 10.1016/j.ymthe.2022.03.002. Online ahead of print.

ABSTRACT

As mediators of intercellular communication, extracellular vesicles containing molecular cargo such as microRNAs, are secreted by cells and taken up by recipient cells to influence their cellular phenotype and function. Here, we report that cardiac stress-induced differential microRNA content, with miR-200c-3p being one of the most enriched, in cardiomyocyte-derived extracellular vesicles mediates functional crosstalk with endothelial cells. Silencing of miR-200c-3p in mice subjected to chronic increased cardiac pressure overload resulted in attenuated hypertrophy, smaller fibrotic areas, higher capillary density and preserved cardiac ejection fraction. Interestingly, we were able to maximal rescue microvascular and cardiac function with very low doses of antagomir, which specifically silences miR-200c-3p expression in the non-myocyte cells. Our results reveal vesicle transfer of miR-200c-3p from cardiomyocytes to cardiac endothelial cells, underlining the importance of cardiac intercellular communication in the pathophysiology of heart failure.

PMID:35278675 | DOI:10.1016/j.ymthe.2022.03.002

J Vasc Surg. 2022 Mar 9:S0741-5214(22)00421-9. doi: 10.1016/j.jvs.2022.02.053. Online ahead of print.

ABSTRACT

OBJECTIVE: The Gore Excluder iliac branch endoprosthesis (IBE; W.L. Gore & Associates, Flagstaff, AZ) is the only iliac branch device approved in the United States to preserve blood flow to the external and internal iliac arteries (IIAs). Some surgeons have used the Gore Viabahn VBX balloon expandable endoprosthesis (VBX; W.L. Gore & Associates) in the IIA rather than the self-expanding endograft designed for the IBE, the internal iliac component (IIC). The objective of the present study was to examine outcomes in patients treated for aortoiliac artery aneurysms with the IBE using either the IIC or VBX stent.

METHODS: We performed a retrospective, single-center review of patients treated for aortoiliac artery aneurysms using the Gore IBE device, with either the IIC or VBX stent into the internal iliac artery from February 2016 to March 2021. Patient demographics, procedure details, 30-day morbidity and mortality, and 6-month and 1-year outcomes and mortality were analyzed. The categorical factors were summarized using frequencies and percentages. Continuous measures were summarized using mean ± standard deviation. A significance level of P = .05 was assumed for all test results. The analyses were performed using SAS software, version 9.4 (SAS Institute, Cary, NC).

RESULTS: Sixty-four patients underwent elective aortoiliac artery aneurysm repair with IBE. IIC was used exclusively in 35 patients (55%) and VBX in 29 (45%). Patients receiving VBX had higher American Society of Anesthesiologists class (P = .006). Upper extremity access was used for VBX delivery in 24.1% of the procedures. No return to the operating room was required in either group. No differences were found in technical success (97.1% IIC vs 93.1% VBX; P = .59), presence of endoleak upon completion (20.0% vs 6.9%; P = .17), readmission (97.1% vs 93.1%; P = .59), or mortality (1.6% vs 0%; P = .45) at 30 days. No differences were found in the requirement for any IBE reintervention after 30 days. No type Ia, Ib, or III endoleaks occurred in either group at any follow-up point. There was no significant difference in internal iliac limb primary patency (IIC 100% vs VBX 96.3%) between groups. A non-statistically significant trend was found toward fewer trunk-ipsilateral leg type II endoleaks in the VBX group during post-procedure follow-up.

CONCLUSIONS: These data suggest that VBX is a reasonable substitute for IIC and has a comparable safety and efficacy profile. Given its inherent conformability, greater range of diameters, and longer working length, VBX offers expanded internal iliac artery branch options with IBE.

PMID:35278651 | DOI:10.1016/j.jvs.2022.02.053