Category: Nevin Manimala

Nat Commun. 2023 Sep 23;14(1):5935. doi: 10.1038/s41467-023-41649-0.

ABSTRACT

Single-molecule Real-time Isoform Sequencing (Iso-seq) of transcriptomes by PacBio can generate very long and accurate reads, thus providing an ideal platform for full-length transcriptome analysis. We present an integrated computational toolkit named TAGET for Iso-seq full-length transcript data analyses, including transcript alignment, annotation, gene fusion detection, and quantification analyses such as differential expression gene analysis and differential isoform usage analysis. We evaluate the performance of TAGET using a public Iso-seq dataset and newly sequenced Iso-seq datasets from tumor patients. TAGET gives significantly more precise novel splice site prediction and enables more accurate novel isoform and gene fusion discoveries, as validated by experimental validations and comparisons with RNA-seq data. We identify and experimentally validate a differential isoform usage gene ECM1, and further show that its isoform ECM1b may be a tumor-suppressor in laryngocarcinoma. Our results demonstrate that TAGET provides a valuable computational toolkit and can be applied to many full-length transcriptome studies.

PMID:37741817 | DOI:10.1038/s41467-023-41649-0

Insights Imaging. 2023 Sep 23;14(1):155. doi: 10.1186/s13244-023-01515-5.

ABSTRACT

BACKGROUND: Colon cancer is a particularly prevalent malignancy that produces postoperative complications (POCs). However, limited imaging modality exists on the accurate diagnosis of POCs. The purpose of this study was therefore to construct a model combining tumor spectral CT parameters and clinical features to predict POCs before surgery in colon cancer.

METHODS: This retrospective study included 85 patients who had preoperative abdominal spectral CT scans and underwent radical colon cancer resection at our institution. The patients were divided into two groups based on the absence (no complication/grade I) or presence (grades II-V) of POCs according to the Clavien-Dindo grading system. The visceral fat areas (VFA) of patients were semi-automatically outlined and calculated on L3-level CT images using ImageJ software. Clinical features and tumor spectral CT parameters were statistically compared between the two groups. A combined model of spectral CT parameters and clinical features was established by stepwise regression to predict POCs in colon cancer. The diagnostic performance of the model was evaluated using the receiver operating characteristic (ROC) curve, including area under the curve (AUC), sensitivity, and specificity.

RESULTS: Twenty-seven patients with POCs and 58 patients without POCs were included in this study. MonoE_40keV-VP and VFA were independent predictors of POCs. The combined model based on predictors yielded an AUC of 0.84 (95% CI: 0.74-0.91), with a sensitivity of 77.8% and specificity of 87.9%.

CONCLUSIONS: The model combining MonoE_40keV-VP and VFA can predict POCs before surgery in colon cancer and provide a basis for individualized management plans.

CRITICAL RELEVANCE STATEMENT: The model combining MonoE40keV-VP and visceral fat area can predict postoperative complications before surgery in colon cancer and provide a basis for individualized management plans.

KEY POINTS: • Visceral fat area and MonoE40keV-VP were independent predictors of postoperative complications in colon cancer. • The combined model yielded a high AUC, sensitivity, and specificity in predicting postoperative complications. • The combined model was superior to the single visceral fat area or MonoE40keV-VP in predicting postoperative complications.

PMID:37741813 | DOI:10.1186/s13244-023-01515-5

Cancer Med. 2023 Sep 23. doi: 10.1002/cam4.6590. Online ahead of print.

ABSTRACT

BACKGROUND: Pancreatic cancer is often diagnosed at a late stage with a poor prognosis due to insidious symptoms and lack of evidence-based screening in general population. Palliative care’s acceptance in Asian cultures is hindered by misconceptions and ineffective communication about management that improve quality of life other than cancer directed treatment. Our study aimed to determine the effect of the Shared decision-making with Oncologists and Palliative care specialists (SOP) model developed from the traditional shared decision-making (SDM) model on the palliative care acceptance rate and medical resource utilization.

METHODS: This is a prospective cohort study implementing the SOP model at the National Taiwan University Hospital from January 2018 to December 2019 for patients with advanced pancreatic cancer. Medical resource utilization was defined and recorded as the rate of hospitalization, emergency room (ER), and intensive care unit admissions. We compared the results between two groups: patients who received the SOP model in 2019 and patients who did not receive it in 2018.

RESULTS: 137 patients with advanced pancreatic cancer were included in our study. The result showed that the acceptance rate of palliative care significantly increased from 50% to 78.69% after the SOP model (p = 0.01). The hospitalization rate did not show a significant difference between 2018 (93.42%, 95% CI: 0.88-0.99) and 2019 (93.44%, 95% CI: 0.87-1.00). 83.61% (95% CI: 0.74-0.93) of our patients in 2019 had at least one ER visit; the rate was 81.5% (95% CI: 0.73-0.91) in 2018 (p = 0.28). The percentage of patients admitted to the ICU increased from 3.95% in 2018 to 8.2% (95% CI: -0.05-0.08) in 2019 (95% CI: 0.11-0.15) (p = 0.00). The hospitalization and ER visit showed no statistically difference between 2 years.

CONCLUSIONS: The modified SOP model markedly augmented palliative care’s acceptance of patients with advanced pancreatic cancer. Adoption of the SOP model would provide these patients a more proactive and systematic approach to deliver needed healthcare.

PMID:37740620 | DOI:10.1002/cam4.6590

J Viral Hepat. 2023 Sep 23. doi: 10.1111/jvh.13878. Online ahead of print.

ABSTRACT

To investigate the effects of hepatitis B virus (HBV) infection on the outcomes of Chinese couples undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) and the clinical data of their neonates. A total of 21,999 first embryo transfer cycles were included. They were categorized into four groups based on the couple’s hepatitis B surface antigen (HBsAg) result (Group A = female HBsAg^– and male HBsAg^– ; Group B = female HBsAg⁺ and male HBsAg^– ; Group C = female HBsAg^– and male HBsAg⁺ ; Group D = female HBsAg⁺ and male HBsAg⁺ ). The fertilization rate (FR), cleavage rate (CR), implantation rate (IPR), clinical pregnancy rate (CPR), live birth rate (LBR) and miscarriage rate (MCR) were analysed. Multilevel logistic regression was applied to evaluate the association. The total prevalence of HBV infection was 5.74% (2526/43998). There were no statistically significant differences in CRs (98.69%, 98.76%, 98.66%, 98.72%, p > .05), IPRs (45.86%, 47.33%, 45.19%, 39.61%, p > .05), CPRs (62.84%, 65.05%, 61.80%, 56.81%, p > .05), MCRs (12.70%, 11.99%, 12.58%, 4%, p > .05) and LBRs (53.43%, 55.38%, 52.70%, 54.54%, p > .05) among the four groups. However, there were significant differences in FRs (66.25%, 66.55%, 66.32%, 61.92%, p < .05). Group D had the lowest FR. After adjusting for confounders, the multilevel logistic regression showed that HBsAg⁺ had no impact on the LBR, CPR or MCR. We also analysed the data of 14,465 newborns, including 8593 singletons and 2936 twins. Among the four groups, no variables reached statistical significance, including neonatal birth weight (NBW), twin ratio, gestational age, premature birth, delivery type, fetal macrosomia or low birth weight (p > .05). Our study demonstrates that, although biparental HBV infection may affect the FR, neither single-parent infection nor biparental HBV infection affects IVF/ICSI outcomes or neonatal outcomes.

PMID:37740608 | DOI:10.1111/jvh.13878

Clin Pharmacol Drug Dev. 2023 Sep 23. doi: 10.1002/cpdd.1330. Online ahead of print.

ABSTRACT

The effects of food on the pharmacokinetics (PKs) and safety of 10-mg rivaroxaban tablets in healthy Chinese subjects were investigated from 1 bioequivalence trial. The bioequivalence trial was designed as randomized, open-label, 2-sequence, 4-period crossover under both fasted and fed conditions. A total of 56 healthy subjects were enrolled, 62.5% were male. These subjects received a single oral 10-mg dose of rivaroxaban with a 7-day washout between 4 periods. Serial PK samples were collected and plasma concentrations were analyzed using validated high-performance liquid chromatography-mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental methods. The BE module of WinNonLin was used for statistical analysis of the maximum concentration (C_max ), the area under the concentration-time curve from zero to the final measurable concentration (AUC_0-t ), and the area under the concentration-time curve from time zero to infinity (AUC_0-∞ ) of rivaroxaban in plasma. Compared with the fasted state, the C_max , AUC_0-t , and AUC_0-∞ of rivaroxaban significantly increased by 47%, 28%, and 26%, respectively, with oral administration of rivaroxaban 10 mg in the fed state. The incidence of adverse events (AEs) was similar between the fasted and fed states, and no serious AEs were observed. Food significantly increased the exposure to rivaroxaban 10 mg in Chinese subjects.

PMID:37740607 | DOI:10.1002/cpdd.1330

NMR Biomed. 2023 Sep 23:e5040. doi: 10.1002/nbm.5040. Online ahead of print.

ABSTRACT

The purpose of this study is to investigate the use of ultrashort echo time (UTE) magnetic resonance imaging (MRI) techniques (T1 and magnetization transfer [MT] modeling) for imaging of the Achilles tendons and entheses in patients with psoriatic arthritis (PsA) compared with asymptomatic volunteers. The heels of twenty-six PsA patients (age 59 ± 15 years, 41% female) and twenty-seven asymptomatic volunteers (age 33 ± 11 years, 47% female) were scanned in the sagittal plane with UTE-T1 and UTE-MT modeling sequences on a 3-T clinical scanner. UTE-T1 and macromolecular proton fraction (MMF; the main outcome of MT modeling) were calculated in the tensile portions of the Achilles tendon and at the enthesis (close to the calcaneus bone). Mann-Whitney-U tests were used to examine statistically significant differences between the two cohorts. UTE-T1 in the entheses was significantly higher for the PsA group compared with the asymptomatic group (967 ± 145 vs. 872 ± 133 ms, p < 0.01). UTE-T1 in the tendons was also significantly higher for the PsA group (950 ± 145 vs. 850 ± 138 ms, p < 0.01). MMF in the entheses was significantly lower in the PsA group compared with the asymptomatic group (15% ± 3% vs. 18% ± 3%, p < 0.01). MMF in the tendons was also significantly lower in the PsA group compared with the asymptomatic group (17% ± 4% vs. 20% ± 5%, p < 0.01). Percentage differences in MMF between the asymptomatic and PsA groups (-16.6% and -15.0% for the enthesis and tendon, respectively) were higher than the T1 differences (10.8% and 11.7% for the enthesis and tendon, respectively). The results suggest higher T1 and lower MMF in the Achilles tendons and entheses in PsA patients compared with the asymptomatic group. This study highlights the potential of UTE-T1 and UTE-MT modeling for quantitative evaluation of entheses and tendons in PsA patients.

PMID:37740595 | DOI:10.1002/nbm.5040

J Radiat Res. 2023 Sep 22:rrad069. doi: 10.1093/jrr/rrad069. Online ahead of print.

ABSTRACT

To investigate radiation-induced cytopenia and establish predictive nomograms for hematological toxicity, we reviewed 3786 patients aged 18 or older who received radiation monotherapy between 2010 and 2021 for non-hematologic malignancies. We collected data on patient background, treatment content and hematologic toxicities for 12 weeks after the start of radiotherapy. The patients were randomly divided into training and test groups in 7:3 ratio. In the training group, we conducted ordered logistic regression analysis to identify predictive factors for neutropenia, lymphocytopenia, anemia and thrombocytopenia. Nomograms to predict Grade 2-4 cytopenia were generated and validated in the test group. Grade 3 or higher hematologic toxicities were observed in 9.7, 44.6, 8.3 and 3.1% of patients with neutropenia, lymphocytopenia, anemia and thrombocytopenia, respectively. We identified six factors for neutropenia grade, nine for lymphocytopenia grade and six for anemia grade with statistical significance. In the analysis of thrombocytopenia, the statistical model did not converge because of a small number of events. Nomograms were generated using factors with high predictive power. In evaluating the nomograms, we found high area under the receiver operating characteristic curve values (neutropenia; 0.75-0.85, lymphopenia; 0.89-0.91 and anemia; 0.85-0.86) in predicting Grade 2-4 cytopenia in the test group. We established predictive nomograms for neutropenia, leukocytopenia and anemia and demonstrated high reproducibility when validated in an independent cohort of patients.

PMID:37740569 | DOI:10.1093/jrr/rrad069

Orthop Surg. 2023 Sep 22. doi: 10.1111/os.13863. Online ahead of print.

ABSTRACT

BACKGROUND: Iliosacral screw insertion by computer-assisted navigation gradually became the main technique in some hospitals, but the expensive price limited the extensive application. But other techniques such as 3D printed template was used to place iliosacral screw as novel method. This study was to compare the efficiency of percutaneous iliosacral screw placement by using patient-specific template and computer-assisted navigation.

METHODS: Total of 58 patients from September 2017 to September 2021 with sacral injury were treated operatively with percutaneous screw technique, which was selected for this retrospective analysis and divided into two groups (template and computer-assisted navigation). There were 31 patients in template group and 27 patients in computer-assisted navigation group. The surgical details (operation time, blood loss, number of screw placements, and number of fluoroscopies), complications, radiographic and clinical results were recorded. The quality of reduction was assessed by the Matta scoring system. T-test and rank-sum test was used in this study.

RESULTS: Operation time in template group was less (33.97 ± 16.61 < 60.31 ± 11.46 min, p < 0.01), but the preoperative preparation time was more (6.35 ± 1.60 > 5.41 ± 1.58, p < 0.05). The quality of reduction in both groups was no difference (p = 0.352). A patient was complicated with gluteal vessel injury in operation in navigation group, which was treated with ligation, but the same injury was not observed in template group. The related surgical data of patient with gluteal injury was ignored in statistical analysis.

CONCLUSION: Both of the two techniques could improve surgical efficiency, the operation time in template was less than computer-assisted navigation group, but the preoperative preparation time was more.

PMID:37740552 | DOI:10.1111/os.13863

Dev Med Child Neurol. 2023 Sep 22. doi: 10.1111/dmcn.15757. Online ahead of print.

ABSTRACT

AIM: To investigate the prevalence of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) in a population-based birth cohort and correlate the findings with prenatal and perinatal factors. We hypothesized that children born preterm, having experienced preeclampsia or maternal overweight, would have an increased risk of ADHD or ASD.

METHOD: A Swedish cohort of 2666 children (1350 males, 1316 females) has been followed from birth with parental and perinatal data. The National Board of Health and Welfare’s registries were used to collect data regarding perinatal status and assigned diagnoses at the age of 12 years.

RESULTS: The prevalence of ADHD and ASD was 7.6% and 1.1% respectively. Maternal obesity early in pregnancy resulted in a three-fold increased risk of ADHD in the child. Similarly, paternal obesity resulted in a two-fold increased risk. The association was significant also when adjusted for sex, preterm birth, smoking, and lower educational level. The prevalence of ASD was too low for statistically relevant risk factor analyses.

INTERPRETATION: Our results corroborate earlier findings regarding prevalence and sex ratio for both ADHD and ASD. Maternal body mass index and preterm birth were correlated with an ADHD diagnosis at the age of 12 years.

PMID:37740541 | DOI:10.1111/dmcn.15757

Am J Sports Med. 2023 Sep 22:3635465231198051. doi: 10.1177/03635465231198051. Online ahead of print.

ABSTRACT

BACKGROUND: During the early evolution of femoroacetabular impingement (FAI) treatment, undercorrection of femoral deformity was a leading cause of hip arthroscopy failures. As the pendulum has swung, overresection of femoral deformity has increased in prevalence as a cause of persistent hip pain after arthroscopy. Computed tomography (CT) scans are increasingly being used in hip arthroscopy for preoperative planning purposes and may allow for improved 3-dimensional (3D) assessment of complex femoral deformities after previous femoroplasty.

PURPOSE: To assess whether CT scans provide additional utility over standard radiographs in understanding proximal femoral morphology in patients being evaluated for revision hip arthroscopy after previous femoroplasty in the setting of FAI.

STUDY DESIGN: Cohort study (Diagnosis); Level of evidence, 3.

METHODS: Preoperative CT scans and standard radiographs were obtained in 80 patients who underwent revision hip arthroscopy for FAI. The anteroposterior and Dunn radiographic views were used to assess patients for residual proximal femoral deformity and were compared with the CT scan views using a commercially available software program. Determinations of underresection were made using alpha angle, while overresection was determined according to a previously described technique. Chi-square tests were performed to determine statistical significance between radiographic and CT classifications of overresection, underresection, and concomitant over- and underresection. A kappa value was calculated to determine the agreement between measurements on the radiographs and CT scans.

RESULTS: There were 30 patients (37.5%) for whom the CT scans revealed information about femoral morphology that was not detected on the radiographs. The kappa value of agreement was 0.28 between CT and radiographic measurements. Underresected cams were detected in 30 patients (37.5%) on CT scans versus 17 patients (21.3%) on radiographs (P = .024). Overresected cams were detected in 31 patients (38.8%) on CT scans versus 14 patients (17.5%) on radiographs (P = .0049). Concomitant areas of under- and overresection were detected in 12 patients (15.0%) on CT scans versus 3 patients (3.8%) on radiographs (P = .027).

CONCLUSION: CT scans with 3D planning software may be more sensitive than traditional radiographic views at detecting aberrant proximal femoral anatomy in the setting of failed FAI surgery. The use of 3D planning software may be considered as an adjunctive tool to better understand complex deformity in the proximal femur for the planning of revision hip arthroscopy.

PMID:37740538 | DOI:10.1177/03635465231198051