Nevin Manimala

Genome Med. 2021 Mar 9;13(1):39. doi: 10.1186/s13073-021-00848-4.

ABSTRACT

BACKGROUND: Macular telangiectasia type 2 (MacTel) is a rare, heritable and largely untreatable retinal disorder, often comorbid with diabetes. Genetic risk loci subtend retinal vascular calibre and glycine/serine/threonine metabolism genes. Serine deficiency may contribute to MacTel via neurotoxic deoxysphingolipid production; however, an independent vascular contribution is also suspected. Here, we use statistical genetics to dissect the causal mechanisms underpinning this complex disease.

METHODS: We integrated genetic markers for MacTel, vascular and metabolic traits, and applied Mendelian randomisation and conditional and interaction genome-wide association analyses to discover the causal contributors to both disease and spatial retinal imaging sub-phenotypes.

RESULTS: Genetically induced serine deficiency is the primary causal metabolic driver of disease occurrence and progression, with a lesser, but significant, causal contribution of type 2 diabetes genetic risk. Conversely, glycine, threonine and retinal vascular traits are unlikely to be causal for MacTel. Conditional regression analysis identified three novel disease loci independent of endogenous serine biosynthetic capacity. By aggregating spatial retinal phenotypes into endophenotypes, we demonstrate that SNPs constituting independent risk loci act via related endophenotypes.

CONCLUSIONS: Follow-up studies after GWAS integrating publicly available data with deep phenotyping are still rare. Here, we describe such analysis, where we integrated retinal imaging data with MacTel and other traits genomics data to identify biochemical mechanisms likely causing this disorder. Our findings will aid in early diagnosis and accurate prognosis of MacTel and improve prospects for effective therapeutic intervention. Our integrative genetics approach also serves as a useful template for post-GWAS analyses in other disorders.

PMID:33750426 | DOI:10.1186/s13073-021-00848-4

Plant Methods. 2021 Mar 9;17(1):27. doi: 10.1186/s13007-021-00727-4.

ABSTRACT

BACKGROUND: Stomata analysis using microscope imagery provides important insight into plant physiology, health and the surrounding environmental conditions. Plant scientists are now able to conduct automated high-throughput analysis of stomata in microscope data, however, existing detection methods are sensitive to the appearance of stomata in the training images, thereby limiting general applicability. In addition, existing methods only generate bounding-boxes around detected stomata, which require users to implement additional image processing steps to study stomata morphology. In this paper, we develop a fully automated, robust stomata detection algorithm which can also identify individual stomata boundaries regardless of the plant species, sample collection method, imaging technique and magnification level.

RESULTS: The proposed solution consists of three stages. First, the input image is pre-processed to remove any colour space biases occurring from different sample collection and imaging techniques. Then, a Mask R-CNN is applied to estimate individual stomata boundaries. The feature pyramid network embedded in the Mask R-CNN is utilised to identify stomata at different scales. Finally, a statistical filter is implemented at the Mask R-CNN output to reduce the number of false positive generated by the network. The algorithm was tested using 16 datasets from 12 sources, containing over 60,000 stomata. For the first time in this domain, the proposed solution was tested against 7 microscope datasets never seen by the algorithm to show the generalisability of the solution. Results indicated that the proposed approach can detect stomata with a precision, recall, and F-score of 95.10%, 83.34%, and 88.61%, respectively. A separate test conducted by comparing estimated stomata boundary values with manually measured data showed that the proposed method has an IoU score of 0.70; a 7% improvement over the bounding-box approach.

CONCLUSIONS: The proposed method shows robust performance across multiple microscope image datasets of different quality and scale. This generalised stomata detection algorithm allows plant scientists to conduct stomata analysis whilst eliminating the need to re-label and re-train for each new dataset. The open-source code shared with this project can be directly deployed in Google Colab or any other Tensorflow environment.

PMID:33750422 | DOI:10.1186/s13007-021-00727-4

BMC Sports Sci Med Rehabil. 2021 Mar 9;13(1):23. doi: 10.1186/s13102-021-00251-x.

ABSTRACT

BACKGROUND: We aimed to determine the effectiveness of 4 weeks of balance exercise compared with no intervention on objectively measured postural sway.

METHODS: This was a single-center parallel randomized controlled, open label, trial. A six-sided dice was used for allocation at a 1:1-ratio between exercise and control. The trial was performed at a university hospital clinic in Sweden and recruited community-dwelling older adults with documented postural instability. The intervention consisted of progressively challenging balance exercise three times per week, during 4 weeks, with follow-up at week five. Main outcome measures were objective postural sway length during eyes open and eyes closed conditions.

RESULTS: Sixty-five participants aged 70 years (balance exercise n = 32; no intervention n = 33) were randomized. 14 participants were excluded from analysis because of early dropout before follow-up at week five, leaving 51 (n = 22; n = 29) participants for analysis. No significant differences were detected between the groups in any of the postural sway outcomes. Within-group analyses showed significant improvements in hand grip strength for the intervention group, while Timed Up & Go improvements were comparable between groups but only statistically significant in the control group.

CONCLUSIONS: Performing balance exercise over a four-week intervention period did not acutely improve postural sway in balance-deficient older adults. The lower limit in duration and frequency to achieve positive effects remains unclear.

TRIAL REGISTRATION: Clinical trials NCT03227666 , July 24, 2017, retrospectively registered.

PMID:33750421 | DOI:10.1186/s13102-021-00251-x

Plant Methods. 2021 Mar 9;17(1):26. doi: 10.1186/s13007-021-00726-5.

ABSTRACT

BACKGROUND: Wheat spike architecture is a key determinant of multiple grain yield components and detailed examination of spike morphometric traits is beneficial to explain wheat grain yield and the effects of differing agronomy and genetics. However, quantification of spike morphometric traits has been very limited because it relies on time-consuming manual measurements.

RESULTS: In this study, using X-ray Computed Tomography imaging, we proposed a method to efficiently detect the 3D architecture of wheat spikes and component spikelets by clustering grains based on their Euclidean distance and relative positions. Morphometric characteristics of wheat spikelets and grains, e.g., number, size and spatial distribution along the spike can be determined. Two commercial wheat cultivars, one old, Maris Widgeon, and one modern, Siskin, were studied as examples. The average grain volume of Maris Widgeon and Siskin did not differ, but Siskin had more grains per spike and therefore greater total grain volume per spike. The spike length and spikelet number were not statistically different between the two cultivars. However, Siskin had a higher spikelet density (number of spikelets per unit spike length), with more grains and greater grain volume per spikelet than Maris Widgeon. Spatial distribution analysis revealed the number of grains, the average grain volume and the total grain volume of individual spikelets varied along the spike. Siskin had more grains and greater grain volumes per spikelet from spikelet 6, but not spikelet 1-5, compared with Maris Widgeon. The distribution of average grain volume along the spike was similar for the two wheat cultivars.

CONCLUSION: The proposed method can efficiently extract spike, spikelet and grain morphometric traits of different wheat cultivars, which can contribute to a more detailed understanding of the sink of wheat grain yield.

PMID:33750418 | DOI:10.1186/s13007-021-00726-5

Theor Biol Med Model. 2021 Mar 9;18(1):10. doi: 10.1186/s12976-021-00140-3.

ABSTRACT

BACKGROUND: The COVID-19 pandemic poses a serious threat to global health, and pathogenic mutations are a major challenge to disease control. We developed a statistical framework to explore the association between molecular-level mutation activity of SARS-CoV-2 and population-level disease transmissibility of COVID-19.

METHODS: We estimated the instantaneous transmissibility of COVID-19 by using the time-varying reproduction number (R_t). The mutation activity in SARS-CoV-2 is quantified empirically depending on (i) the prevalence of emerged amino acid substitutions and (ii) the frequency of these substitutions in the whole sequence. Using the likelihood-based approach, a statistical framework is developed to examine the association between mutation activity and R_t. We adopted the COVID-19 surveillance data in California as an example for demonstration.

RESULTS: We found a significant positive association between population-level COVID-19 transmissibility and the D614G substitution on the SARS-CoV-2 spike protein. We estimate that a per 0.01 increase in the prevalence of glycine (G) on codon 614 is positively associated with a 0.49% (95% CI: 0.39 to 0.59) increase in R_t, which explains 61% of the R_t variation after accounting for the control measures. We remark that the modeling framework can be extended to study other infectious pathogens.

CONCLUSIONS: Our findings show a link between the molecular-level mutation activity of SARS-CoV-2 and population-level transmission of COVID-19 to provide further evidence for a positive association between the D614G substitution and R_t. Future studies exploring the mechanism between SARS-CoV-2 mutations and COVID-19 infectivity are warranted.

PMID:33750399 | DOI:10.1186/s12976-021-00140-3

BMC Endocr Disord. 2021 Mar 9;21(1):44. doi: 10.1186/s12902-021-00706-9.

ABSTRACT

BACKGROUND: The human ovary is the target of autoimmune attack in cases of autoimmune disorders, which can cause ovarian dysfunction. Due to the higher prevalence of Hashimoto’s Thyroiditis (HT) in Polycystic Ovary Syndrome (PCOS) patients, we aimed to evaluate ovarian reserve and the effect of autoimmune exposure time on ovarian reserve in PCOS patients with HT by Anti-Müllerian hormone (AMH) levels.

METHODS: Forty-six PCOS patients and 46 PCOS with HT diagnosed patients who are between 18 and 35 years old were recruited for this study. Detailed medical histories were obtained from all participants. Polycystic ovary image was evaluated and antral follicles were counted by transvaginal ultrasound. Modified Ferriman Gallwey score, body mass index, waist/hip ratio of the patients were examined. Hormonal, biochemical profiles and AMH levels of the patients were evaluated during the early follicular phase. The data of both groups were statistically analyzed with SPSS 18.0.

RESULTS: 20 (43.5%) patients in the PCOS group were fertile, 8 (17.4%) patients in the PCOS + HT group were fertile, fertility rate was significantly lower in PCOS + HT group. The mean AMH value was 8.8 ± 8.8 in the PCOS + HT group and 12.4 ± 8.1 in the PCOS group and it was significantly lower in the PCOS + HT group (p = 0.043). AMH values were significantly negatively correlated with anti-thyroid peroxidase antibody (anti-TPO) level and the duration of HT. There was a significant positive correlation between the anti-TPO level and the duration of HT. CONCLUSıON: We pointed out that the coexistence of PCOS and HT, two prevalent diseases of reproductive age, further diminished ovarian reserve. More exposure of the ovaries to autoantibodies can cause ovarian destruction, similar to the thyroid gland like HT. Because of all these close relations with PCOS and thyroid dysfunctions, we recommend evaluating both thyroid autoantibodies and hormone levels in PCOS patients at the first visit. Patients with PCOS + HT should be monitored more closely to determine the fertility treatment options and control premature ovarian failure (POF) table.

PMID:33750377 | DOI:10.1186/s12902-021-00706-9

BMC Womens Health. 2021 Mar 9;21(1):101. doi: 10.1186/s12905-021-01249-w.

ABSTRACT

BACKGROUND: Post-fistula-repair incontinence (PFRI) is a common complication of vesicovaginal fistula (VVF) surgeries. It entails continuous leakage of urine after successful VVF closure. Pelvic Floor Muscle Training (PFMT) plays a vital role in the management of PFRI, however, an evolving exercise approach is the Paula Exercise Method (PEM) which has shown a promising effect in stopping urinary incontinence, but there is no data on its effect on PFRI. This study therefore, proposes to primarily investigate the effect of PEM on urine leakage and secondarily, pelvic floor strength (PFS), quality of life (QoL), sexual function (SF), and mental health (MH) in women with PFRI.

METHODS: This is a study protocol for a randomized controlled trial. A total of 182 participants are expected to participate in the study after satisfying the inclusion criteria. The participants will be randomized into either PEM or PFMT study groups. The demographic data of all the participants will be recorded. Each participant will be assessed for urine leakage, PFS, QoL, SF, and MH at baseline and subsequently, at four, eight and 12 weeks of intervention. Demographic parameters will be summarized using descriptive statistics. Continuous data will be computed for differences using inferential statistic of Analysis of variance, t-test and Man Whitney U as appropriate. All analyses will be performed using SPSS version 22.0 with probability set at 0.05 alpha level.

DISCUSSION: It is hoped that the outcome of this study will determine the effect of the Paula exercise method on urine leakage, pelvic floor strength, quality of life, sexual function, and mental health among women with post-fistula-repair incontinence and also provide evidence for the use of the Paula method in urinary incontinence.

TRIAL REGISTRATION: Pan African Clinical Trials Registry ( www.pactr.org ), identifier PACTR201906515532827.

PMID:33750376 | DOI:10.1186/s12905-021-01249-w

BMC Infect Dis. 2021 Mar 9;21(1):249. doi: 10.1186/s12879-021-05849-7.

ABSTRACT

BACKGROUND: Presymptomatic COVID-19 patients have been identified as a major stumbling block in efforts to break the chain of transmission. Studies on temporal dynamics of its shedding suggests it peaks 1-2 days prior to any symptom onset. Therefore, a large proportion of patients are actively spreading the disease unknowingly whilst undetected. However, lengthy lockdowns and isolation leads to a host of socioeconomic issues and are impractical. Conversely, there exists no study describing this group and their clinical significance despite their key role in disease transmission.

METHODS: As a result, we devised a retrospective study to look at the prevalence of presymptomatic patients with COVID-19 from data sourced via our medical records office. Subsequently, we identify early indicators of infection through demographic information, biochemical and radiological abnormalities which would allow early diagnosis and isolation. In addition, we will look into the clinical significance of this group and their outcome; if it differs from asymptomatic or symptomatic patients. Descriptive statistics were used in addition to tabulating the variables and corresponding values for reference. Variables are compared between the presymptomatic group and others via Chi-square testing and Fisher’s exact test, accepting a p value of < 0.05 as significant.

RESULTS: Our analysis shows a higher proportion of presymptomatic patients with atypical symptoms like chest pain while symptomatic patients commonly present with respiratory symptoms like cough and shortness of breath. Besides that, there were more females presenting as presymptomatic patients compared to males (p = 0.019) and these group of patients were likely to receive treatment (p < 0.001). Otherwise, we were not able to identify other statistically significant markers suggesting a patient is presymptomatic.

CONCLUSION: As we have little means of identifying these silent spreaders, it highlights further the importance of general measures implemented to stop COVID-19 transmission like social distancing, face mask, and widespread testing.

PMID:33750347 | DOI:10.1186/s12879-021-05849-7

BMC Ophthalmol. 2021 Mar 9;21(1):131. doi: 10.1186/s12886-021-01889-4.

ABSTRACT

BACKGROUND: Conjunctival autograft transplantation from superior conjunctiva is often chosen to lower the postoperative recurrence rate for pterygium treatment. However, inferior conjunctival autograft (ICA) might be taken as an alternative surgery method, especially under certain conditions. Consequently, we designed this research to estimate and contrast the result of inferior conjunctival autograft and superior conjunctival autograft (SCA) on the postoperative recurrence rate.

METHODS: We searched through network database (PubMed, Embase and Cochrane Central Register of Controlled Trials) to choose suitable randomized controlled trials (RCTs). Based on Cochrane review methods, we evaluated eligibility and risk of bias of included studies. The primary measures included postoperative recurrence rate. Pooled risk ratios (RRs) and 95% confidence intervals (CIs) were assessed. RevMan 5.3 software was utilized to conduct statistical analysis.

RESULTS: Four RCTs composed of a total of 438 eyes were included in this meta-analysis, with 234 eyes in the inferior conjunctival autograft group and 204 eyes in the superior conjunctival autograft group. Statistical meta-analysis revealed that the postoperative recurrence rate was similar between the two groups (RR = 0.77, 95% CI: 0.36 to 1.62, P = 0.49). Only two RCTs applied the postoperative pain scale and one of them did not provided adequate numbers.

CONCLUSIONS: Our meta-analysis indicated that inferior autograft transplantation and superior autograft transplantation had a similar effect on postoperative recurrence rate. The inferior autograft group might have a less postoperative pain. Subsequent RCTs which have more patients participated and more outcomes are needed to confirm our conclusions in years to come.

PMID:33750344 | DOI:10.1186/s12886-021-01889-4

BMC Med Imaging. 2021 Mar 9;21(1):45. doi: 10.1186/s12880-021-00578-4.

ABSTRACT

OBJECTIVE: To investigate left atrial shape differences on CT scans of atrial fibrillation (AF) patients with (AF+) versus without (AF-) post-ablation recurrence and whether these shape differences predict AF recurrence.

METHODS: This retrospective study included 68 AF patients who had pre-catheter ablation cardiac CT scans with contrast. AF recurrence was defined at 1 year, excluding a 3-month post-ablation blanking period. After creating atlases of atrial models from segmented AF+ and AF- CT images, an atlas-based implicit shape differentiation method was used to identify surface of interest (SOI). After registering the SOI to each patient model, statistics of the deformation on the SOI were used to create shape descriptors. The performance in predicting AF recurrence using shape features at and outside the SOI and eight clinical factors (age, sex, left atrial volume, left ventricular ejection fraction, body mass index, sinus rhythm, and AF type [persistent vs paroxysmal], catheter-ablation type [Cryoablation vs Irrigated RF]) were compared using 100 runs of fivefold cross validation.

RESULTS: Differences in atrial shape were found surrounding the pulmonary vein ostia and the base of the left atrial appendage. In the prediction of AF recurrence, the area under the receiver-operating characteristics curve (AUC) was 0.67 for shape features from the SOI, 0.58 for shape features outside the SOI, 0.71 for the clinical parameters, and 0.78 combining shape and clinical features.

CONCLUSION: Differences in left atrial shape were identified between AF recurrent and non-recurrent patients using pre-procedure CT scans. New radiomic features corresponding to the differences in shape were found to predict post-ablation AF recurrence.

PMID:33750343 | DOI:10.1186/s12880-021-00578-4