Nevin Manimala

J Neurosurg. 2021 Jul 23:1-12. doi: 10.3171/2020.12.JNS203652. Online ahead of print.

ABSTRACT

OBJECTIVE: Gliomas frequently involve the insula both primarily and secondarily by invasion. Despite the high connectivity of the human insula, gliomas do not spread randomly to or from the insula but follow stereotypical anatomical involvement patterns. In the majority of cases, these patterns correspond to the intrinsic connectivity of the limbic system, except for tumors with aggressive biology. On the basis of these observations, the authors hypothesized that these different involvement patterns may be correlated with distinct outcomes and analyzed these correlations in an institutional cohort.

METHODS: Fifty-nine patients who had undergone surgery for insular diffuse gliomas and had complete demographic, pre- and postoperative imaging, pathology, molecular genetics, and clinical follow-up data were included in the analysis (median age 37 years, range 21-71 years, M/F ratio 1.68). Patients with gliomatosis and those with only minor involvement of the insula were excluded. The presence of T2-hyperintense tumor infiltration was evaluated in 12 anatomical structures. Hierarchical biclustering was used to identify co-involved structures, and the findings were correlated with established functional anatomy knowledge. Overall survival was evaluated using Kaplan-Meier and Cox proportional hazards regression analysis (17 parameters).

RESULTS: The tumors involved the anterior insula (98.3%), posterior insula (67.8%), temporal operculum (47.5%), amygdala (42.4%), frontal operculum (40.7%), temporal pole (39%), parolfactory area (35.6%), hypothalamus (23.7%), hippocampus (16.9%), thalamus (6.8%), striatum (5.1%), and cingulate gyrus (3.4%). A mean 4.2 ± 2.6 structures were involved. On the basis of hierarchical biclustering, 7 involvement patterns were identified and correlated with cortical functional anatomy (pure insular [11.9%], olfactocentric [15.3%], olfactoopercular [33.9%], operculoinsular [15.3%], striatoinsular [3.4%], translimbic [11.9%], and multifocal [8.5%] patterns). Cox regression identified hippocampal involvement (p = 0.006) and postoperative tumor volume (p = 0.027) as significant negative independent prognosticators of overall survival and extent of resection (p = 0.015) as a significant positive independent prognosticator.

CONCLUSIONS: The study findings indicate that insular gliomas primarily involve the olfactocentric limbic girdle and that involvement in the hippocampocentric limbic girdle is associated with a worse prognosis.

PMID:34298512 | DOI:10.3171/2020.12.JNS203652

J Neurosurg Spine. 2021 Jul 23:1-12. doi: 10.3171/2020.12.SPINE201527. Online ahead of print.

ABSTRACT

OBJECTIVE: Rod fracture (RF) after adult spinal deformity (ASD) surgery is reported in approximately 6.8%-33% of patients and is associated with loss of deformity correction and higher reoperation rates. The authors’ objective was to determine the effect of accessory supplemental rod (ASR) placement on postoperative occurrence of primary RF after ASD surgery.

METHODS: This retrospective analysis examined patients who underwent ASD surgery between 2014 and 2017 by the senior authors. Inclusion criteria were age > 18 years, ≥ 5 instrumented levels including sacropelvic fixation, and diagnosis of ASD, which was defined as the presence of pelvic tilt ≥ 25°, sagittal vertical axis ≥ 5 cm, thoracic kyphosis ≥ 60°, coronal Cobb angle ≥ 20°, or pelvic incidence to lumbar lordosis mismatch ≥ 10°. The primary focus was patients with a minimum 2-year follow-up.

RESULTS: Of 148 patients who otherwise met the inclusion criteria, 114 (77.0%) achieved minimum 2-year follow-up and were included (68.4% were women, mean age 67.9 years, average body mass index 30.4 kg/m2). Sixty-two (54.4%) patients were treated with traditional dual-rod construct (DRC), and 52 (45.6%) were treated with ASR. Overall, the mean number of levels fused was 11.7, 79.8% of patients underwent Smith-Petersen osteotomy (SPO), 19.3% underwent pedicle subtraction osteotomy (PSO), and 66.7% underwent transforaminal lumbar interbody fusion (TLIF). Significantly more patients in the DRC cohort underwent SPO (88.7% of the DRC cohort vs 69.2% of the ASR cohort, p = 0.010) and TLIF (77.4% of the DRC cohort vs 53.8% of the ASR cohort, p = 0.0001). Patients treated with ASR had greater baseline sagittal malalignment (12.0 vs 8.6 cm, p = 0.014) than patients treated with DRC, and more patients in the ASR cohort underwent PSO (40.3% vs 1.6%, p < 0.0001). Among the 114 patients who completed follow-up, postoperative occurrence of RF was reported in 16 (14.0%) patients, with mean ± SD time to RF of 27.5 ± 11.8 months. There was significantly greater occurrence of RF among patients who underwent DRC compared with those who underwent ASR (21.0% vs 5.8%, p = 0.012) at comparable mean follow-up (38.4 vs 34.9 months, p = 0.072). Multivariate analysis demonstrated that ASR had a significant protective effect against RF (OR 0.231, 95% CI 0.051-0.770, p = 0.029).

CONCLUSIONS: This study demonstrated a statistically significant decrease in the occurrence of RF among ASD patients treated with ASR, despite greater baseline deformity and higher rate of PSO. These findings suggest that ASR placement may provide benefit to patients who undergo ASD surgery.

PMID:34298503 | DOI:10.3171/2020.12.SPINE201527

Biosens Bioelectron. 2021 Jul 13;192:113502. doi: 10.1016/j.bios.2021.113502. Online ahead of print.

ABSTRACT

Extracellular vesicles (EVs) are essential intercellular communicators that are of increasing interest as diagnostic biomarkers. Exploring their biological functions and clinical values, however, remains challenging due to their small sizes and high heterogeneity. Herein, we report an ultrasensitive method that employs target-initiated construction of DNA nanostructure to detect single EVs with an input as low as 100 vesicles/μL. Taking advantage of both DNA nanostructure labeling and EV membrane staining, the method can also permit calibration-free analysis of the protein profiles among different EV samples, leading to clear EV differentiation by their cell of origin. Moreover, this method allows co-localization of dual protein markers on the same EV, and the increased number of EVs carrying dual tumor proteins present in human serum could differentiate cancer patients at the early developmental stage from healthy controls. Our results demonstrate the great potential of this single-EV visualization method in non-invasive detection of the EV-based protein biomarkers for cancer diagnosis and treatment monitoring.

PMID:34298496 | DOI:10.1016/j.bios.2021.113502

Comput Methods Programs Biomed. 2021 Jul 13;208:106269. doi: 10.1016/j.cmpb.2021.106269. Online ahead of print.

ABSTRACT

Background and Objective Electrocardiogram (ECG) quality assessment is significant for automatic diagnosis of cardiovascular disease and reducing the massive workload of reviewing continuous ECGs. Hence, how to design an appropriate algorithm for objectively evaluating the multi-lead ECG recordings is particularly important. Despite the deep learning methods performing well in many fields, as a data-driven method, it may not be entirely suitable for ECG analysis due to the difficulty in obtaining sufficient data and the low signal-to-noise ratio of ECG recordings. In this study, with the aim of providing an accurate and automatic ECG quality assessment scheme, we propose an innovative ECG quality assessment algorithm based on hand-crafted statistical features and deep-learned spectral features. Methods In this paper, a novel approach, combining the deep-learned Stockwell transform (S-Transform) spectrogram features and hand-crafted statistical features, is proposed for ECG quality assessment. Firstly, a double-input convolutional neural network (CNN) is established. Then, the S-Transform with a novel online augmentation scheme is performed on the multi-lead raw ECG signal received from one input layer to obtain proper time-frequency representation. After that, the CNN with three convolutional layers is employed to extract robust deep-learned features automatically. Simultaneously, the hand-crafted statistical features, including lead-fall, baseline drift, and R peak features, are calculated and fed into another input layer for feature fusion training. Finally, the deep-learned and hand-crafted features are concatenated and further fused by a fully connected layer for quality classification. Furthermore, a log-odds analysis scheme combining with a gradient-based method can localize the abnormal zone in time, frequency, and spatial domains. Results and Conclusion Our proposed method is evaluated on a publicly available database with 10-fold cross-validation. The experimental results demonstrate that the proposed assessment algorithm reached a mean accuracy of 93.09%, a mean F1-score of 0.8472, and a sensitivity of 0.9767. Moreover, comprehensive experiments indicate that the fusion of CNN features and statistical features has complementary advantages and ideal interpretability, achieving end-to-end multi-lead ECG assessment with satisfying performance.

PMID:34298474 | DOI:10.1016/j.cmpb.2021.106269

Epilepsy Res. 2021 Jul 15;176:106726. doi: 10.1016/j.eplepsyres.2021.106726. Online ahead of print.

ABSTRACT

BACKGROUND: Magnetic resonance-guided laser interstitial thermal therapy (MRgLiTT) is becoming a first-line surgical therapy for mesial temporal lobe epilepsy (mTLE) due to good seizure control and low complication risk. However, seizure outcomes after MRgLiTT remain highly variable and there is a need to improve patient selection and post-operative prognostication. In this retrospective study, we investigated whether the pre-operative MRI-derived apparent diffusion coefficient (ADC), used as a marker of tissue pathology in the mesial temporal structures could help predict seizure outcome.

METHODS: Thirty-five patients who underwent MRgLiTT at our institution between 2014 and 2019 were included in the study. Demographic and clinical data were retrospectively collected. Seizure outcome was defined as good (ILAE Class I-II) and poor (ILAE Class III-VI). Volumetrics were performed on pre-ablation hippocampus and amygdala. Ablation volumes, and the proportion of ablated hippocampus and amygdala calculated via their respective mean voxel-wise ADC intensities were quantified from pre-operative and intra-operative post-ablation MRIs and statistically compared between the two outcome cohorts. Univarate and multivariate regression analysis was performed to identify demographic, clinical, and radiographic predictors of seizure outcome.

RESULTS: Mean age at LiTT was 36 years and 14 (40 %) were female. Mean follow-up duration was 1.90 ± 0.17 years. Twenty-seven (77 %) patients had mesial temporal sclerosis. There was no significant difference in the ablation volumes and proportion of ablated volume of hippocampus and amygdala between the two outcome groups. Patients with good seizure outcome had significantly higher normalized ADC intensities in the ablated mesial temporal structures compared to those with poor outcome (0.01 ± 0.08 vs.-0.29 ± 0.06; p = 0.015).

CONCLUSIONS: mTLE patients with higher ADC intensities in the ablated regions of the hippocampus and the amygdala are more likely to have good seizure outcome following MRgLiTT. Our results suggest that pre-operative ADC analysis may improve both patient selection and epileptogenic zone targeting during MRgLiTT. Further investigation with large, prospective cohorts is needed to validate the clinical utility of ADC in improving seizure outcome following MRgLiTT.

PMID:34298428 | DOI:10.1016/j.eplepsyres.2021.106726

Reprod Biol. 2021 Jul 20;21(3):100536. doi: 10.1016/j.repbio.2021.100536. Online ahead of print.

ABSTRACT

Cervical cancer markedly threatens women’s health worldwide and currently ranks fourth leading cause of cancer mortality in women according to recent global cancer statistics. Recent advances have proven that not only tumor suppressor and oncogenes but also non-coding RNAs including micro RNAs (miRNAs) have significant impact in the development and progression of cervical cancers. Previous studies have identified many cancer-specific miRNAs for the early detection of cervical cancers. However, the diagnostic and prognostic use of autophagy-associated miRNAs for the cervical squamous cell cancer (SCC) cases and high-grade squamous intraepithelial lesion (HSIL) have not been uncovered. In the present study, we revealed that miRNAs are differentially expressed in both cervical SCC and HSIL. A total of 35 HSIL, 35 cervical SCC and 30 healthy controls were enrolled for the present study. Total RNA including miRNAs were isolated from the FFPE tissue samples and miRNA expression levels were quantified by quantitative PCR. Predicted miRNA targets of autophagy related genes were determined using miRNA-target prediction algorithms. MiR-143, miR-372, miR-375 and miR-30c were markedly downregulated in HSIL and cervical SCC. MiR-130a was significantly upregulated in the cervical SCC group compared to HSIL and control groups. MiR-30a, miR-520e, miR-548c and miR-372 were significantly associated with the overall survival of cervical SCC patients and these miRNAs were determined to be significant diagnostic markers as revealed by ROC analysis. Together, these results indicate that autophagy-associated miRNAs are potentially valuable for the differential diagnosis and targeted therapy to cervical cancer.

PMID:34298410 | DOI:10.1016/j.repbio.2021.100536

Eur J Cancer. 2021 Jul 20;154:277-287. doi: 10.1016/j.ejca.2021.05.039. Online ahead of print.

ABSTRACT

PURPOSE: The analysis of circulating tumor DNA (ctDNA), a fraction of total cell-free DNA (cfDNA), might be of special interest in retinoblastoma patients. Because the accessibility to tumor tissue is very limited in these patients, either for histopathological diagnosis of suspicious intraocular masses (biopsies are proscribed) or for somatic RB1 studies and genetic counseling (due to current successful conservative approaches), we aim to validate the detection of ctDNA in plasma of non-hereditary retinoblastoma patients by molecular analysis of RB1 gene.

EXPERIMENTAL DESIGN: In a cohort of 19 intraocular unilateral non-hereditary retinoblastoma patients for whom a plasma sample was available at diagnosis, we performed high-deep next-generation sequencing (NGS) of RB1 in cfDNA. Two different bioinformatics/statistics approaches were applied depending on whether the somatic RB1 status was available or not.

RESULTS: Median plasma sample volume was 600 μL [100-1000]; median cfDNA plasma concentration was 119 [38-1980] and 27 [11-653] ng/mL at diagnosis and after complete remission, respectively. In the subgroup of patients with known somatic RB1 alterations (n = 11), seven of nine somatic mutations were detected (median allele fraction: 6.7%). In patients without identified somatic RB1 alterations (n = 8), six candidate variants were identified for seven patients.

CONCLUSIONS: Despite small tumor size, blood-ocular barrier, poor ctDNA blood release and limited plasma sample volumes, we confirm that it is possible to detect ctDNA with high-deep NGS in plasma from patients with intraocular non-hereditary retinoblastoma. This may aid in diagnosis of suspicious cases, family genetic counseling or follow-up of residual intraocular disease.

PMID:34298378 | DOI:10.1016/j.ejca.2021.05.039

Eur J Cancer. 2021 Jun 30;154:246-252. doi: 10.1016/j.ejca.2021.06.029. Online ahead of print.

ABSTRACT

BACKGROUND: Specific data regarding coronavirus disease 2019 (COVID-19) in patients with neuroendocrine neoplasms (NENs) are lacking. The aim of this study is to describe the characteristics of patients with NENs who tested severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive.

MATERIAL AND METHODS: This is a worldwide study collecting cases of patients with NENs along with a positive nasopharyngeal swab reverse transcriptase-polymerase chain reaction (RT-PCR) test for SARS-CoV-2 between June 1, 2020, and March 31, 2021. Centres treating patients with NENs were directly contacted by the principal investigator. Patients with NENs of any primary site, grade and stage were included, excluding small-cell lung carcinoma and mixed adenoneuroendocrine carcinoma.

RESULTS: Among 81 centres directly contacted, 88.8% responded and 48.6% of them declined due to lack of cases or interest. On March 31^st, 2021, eight recruiting centres enrolled 89 patients. The median age was 64 years at the time of COVID-19 diagnosis. Most patients had metastatic, non-functioning, low-/intermediate-grade gastroenteropancreatic NENs on treatment with somatostatin analogues and radioligand therapy. Most of them had comorbidities. Only 8% of patients had high-grade NENs and 12% were receiving chemotherapy. Most patients had symptoms or signs of COVID-19, mainly fever and cough. Only 3 patients underwent sub-intensive treatment, whereas most of them received medical therapies, mostly antibiotics. In two third of cases, no changes occurred for the anti-NEN therapy. More than 80% of patients completely recovered without sequelae, whereas 7.8% patients died due to COVID-19.

CONCLUSIONS: Patients included in this study reflect the typical NEN population regardless of SARS-CoV-2. In most cases, they overcome COVID-19 without need of intensive care, short-term sequelae and discontinuation of systemic oncological therapy.

PMID:34298375 | DOI:10.1016/j.ejca.2021.06.029

Psychiatry Res. 2021 Jul 17;303:114113. doi: 10.1016/j.psychres.2021.114113. Online ahead of print.

ABSTRACT

The COVID-19 pandemic shined a light on mental health care and led to a deepening of the study of people’s consumption habits. Individuals to dampen negative emotions experienced in crisis and to try to feel in control of their lives engaged in excessive buying. When we analyzed the predictive power of anxiety, depression, and stress over excessive buying as a coping strategy in a sample of Brazilian participants that a questionnaire throughout May 2020, we concluded depression and stress were statistically significant predictors of excessive buying as a coping strategy. Excessive buying functions as a coping strategy at an endangered time, as a way for individuals to protect themselves, decrease fear, and relieve negative feelings. It is imperative to focus on mental health literacy so that individuals appropriately identify signs of mental distress and seek professional help, and to educate society to conscientious consumption habits.

PMID:34298372 | DOI:10.1016/j.psychres.2021.114113

J Environ Manage. 2021 Jul 20;297:113258. doi: 10.1016/j.jenvman.2021.113258. Online ahead of print.

ABSTRACT

An analysis of the influence of water regime on the metal accumulation processes of wetland plants can improve the efficiency of phytoremediation. However, few studies have clearly explored the mechanism of influence of water regime on the process of accumulation of metals by the dominant vegetation in Poyang Lake wetland, the largest freshwater lake in China. The aim of this study was to investigate the influence of water regime (Flooding condition [FC], Dry condition [DC] and alternate dry and flooding condition [DFC]) on the accumulation of cadmium (Cd) by Artemisia selengensis Turcz. ex Bess., a dominant plant in the Poyang Lake wetland. The results indicated that FC treatment significantly enhanced the accumulation of Cd by Artemisia roots compared with DFC and DC treatments. In addition, the DFC treatment significantly increased the translocation of Cd from roots to shoots compared with the FC treatment. A multivariate statistical analysis indicated that the rhizosphere Cd fraction, iron plaque on the root surface and rhizosphere pH directly or indirectly significantly influence the process of accumulation of Cd. The conversion of exchangeable fraction to Fe/Mn oxide bound and organic fraction under the DFC and FC treatments decreased the accumulation of Cd in Artemisia. The formation of increased amounts of iron plaque under the FC treatment may enhance the accumulation of Cd in roots, while it may reduce the translocation of Cd to aboveground tissues. In addition, a higher rhizosphere pH under the FC treatment may promote accumulation of Cd in the root by inducing formation of iron plaque. Similarly, compared with the FC treatment, a lower rhizosphere pH and iron plaque can induce the processes of Cd translocation under the DFC treatment. Based on the bioaccumulation factor, translocation factor and the ratio of root/aerial Cd content, treatment with DC benefited the phytoextraction of Cd, while treatment with DFC and FC enhanced the phytostabilization of Cd by Artemisia. This study provides valuable information for deeply understanding the resilience of wetland ecosystems and for enhancing the phytoremediation with wetland plants using water management.

PMID:34298349 | DOI:10.1016/j.jenvman.2021.113258