Tag: nevin manimala

J Med Imaging (Bellingham). 2023 Sep;10(5):051806. doi: 10.1117/1.JMI.10.5.051806. Epub 2023 Apr 17.

ABSTRACT

PURPOSE: Lung transplantation is the standard treatment for end-stage lung diseases. A crucial factor affecting its success is size matching between the donor’s lungs and the recipient’s thorax. Computed tomography (CT) scans can accurately determine recipient’s lung size, but donor’s lung size is often unknown due to the absence of medical images. We aim to predict donor’s right/left/total lung volume, thoracic cavity, and heart volume from only subject demographics to improve the accuracy of size matching.

APPROACH: A cohort of 4610 subjects with chest CT scans and basic demographics (i.e., age, gender, race, smoking status, smoking history, weight, and height) was used in this study. The right and left lungs, thoracic cavity, and heart depicted on chest CT scans were automatically segmented using U-Net, and their volumes were computed. Eight machine learning models [i.e., random forest, multivariate linear regression, support vector machine, extreme gradient boosting (XGBoost), multilayer perceptron (MLP), decision tree, $k$ -nearest neighbors, and Bayesian regression) were developed and used to predict the volume measures from subject demographics. The 10-fold cross-validation method was used to evaluate the performances of the prediction models. $R$ -squared ( $R^2$ ), mean absolute error (MAE), and mean absolute percentage error (MAPE) were used as performance metrics.

RESULTS: The MLP model demonstrated the best performance for predicting the thoracic cavity volume ( $R^2$ : 0.628, MAE: 0.736 L, MAPE: 10.9%), right lung volume ( $R^2$ : 0.501, MAE: 0.383 L, MAPE: 13.9%), and left lung volume ( $R^2$ : 0.507, MAE: 0.365 L, MAPE: 15.2%), and the XGBoost model demonstrated the best performance for predicting the total lung volume ( $R^2$ : 0.514, MAE: 0.728 L, MAPE: 14.0%) and heart volume ( $R^2$ : 0.430, MAE: 0.075 L, MAPE: 13.9%).

CONCLUSIONS: Our results demonstrate the feasibility of predicting lung, heart, and thoracic cavity volumes from subject demographics with superior performance compared with available studies in predicting lung volumes.

PMID:37077858 | PMC:PMC10108239 | DOI:10.1117/1.JMI.10.5.051806

Pharmacol Res Perspect. 2023 Jun;11(3):e01075. doi: 10.1002/prp2.1075.

ABSTRACT

The opioid epidemic has impacted over 10 million Americans in 2019. Opioids, like morphine, bind non-selectively in both peripheral tissue, leading to effective pain relief, and central tissue, resulting in dangerous side effects and addiction. The inflamed conditions of injured tissues have a lower pH (pH = 6-6.5) environment than healthy tissue (pH = 7.4). We aim to design a morphine derivative that binds selectively within inflamed tissue using molecular extension and dissection techniques. Morphine binds to the μ-opioid receptor (MOR) when the biochemically active amine group is protonated. Fluorination of a β-carbon from the tertiary amine group led to a reduced pKa of the derivative through induction. Through a decrease in the pKa, protonation is still statistically favored in lower pH environments of inflamed tissue but primarily deprotonated in healthy tissue. The cyclohexenol and N-methyl-piperidine rings of morphine are removed to increase conformational flexibility when binding while still maintaining the interactions required for analgesia. Electronic structure calculations were performed with Gaussian16 using the Keck Computational Research Cluster at Chapman University to determine the pKa. The theoretical pKa values are determined at the M06-2X(SMD)/aug-cc-pVDZ level of theory to calculate the ΔG°aq values for the amine deprotonation reactions. Fluoromorphine β-C2 was designed computationally and modeled within the MOR using Maestro: Schrödinger. This derivative exhibits a pKa reduction and enhanced ligand-protein interactions within the MOR. β-fluorination decreased the overall pKa values of the morphine derivatives (pKa: 6.1-7.83) relative to morphine, reducing binding within healthy, central tissue.

PMID:37078224 | DOI:10.1002/prp2.1075

Stat Med. 2023 Apr 30;42(9):1323-1337. doi: 10.1002/sim.9672. Epub 2023 Jan 27.

ABSTRACT

Covariate balance is one of the fundamental issues in designing experiments for treatment comparisons, especially in randomized clinical trials. In this article, we introduce a new class of covariate-adaptive procedures based on the Simulated Annealing algorithm aimed at balancing the allocations of two competing treatments across a set of pre-specified covariates. Due to the nature of the simulated annealing, these designs are intrinsically randomized, thus completely unpredictable, and very flexible: they can manage both quantitative and qualitative factors and be implemented in a static version as well as sequentially. The properties of the suggested proposal are described, showing a significant improvement in terms of covariate balance and inferential accuracy with respect to all the other procedures proposed in the literature. An illustrative example based on real data is also discussed.

PMID:37078360 | DOI:10.1002/sim.9672

Zhonghua Zhong Liu Za Zhi. 2023 Apr 23;45(4):330-334. doi: 10.3760/cma.j.cn112152-20220125-00059.

ABSTRACT

Objective: To investigate the relationship between miR-199b and clinicopathologic features and prognosis of patients with colorectal cancer. Methods: Cancer tissues and adjacent normal tissues of 202 patients with colorectal cancer treated in Cancer Hospital of Chinese Academy of Medical Sciences from March to December 2011 were collected. Reverse transcription-quantitative real-time polymerase chain reaction was used to detect the expression level of miR-199b in colorectal cancer tissues and corresponding adjacent normal tissues. Kaplan-Meier method and Log rank test were used for survival analysis, and receiver operating characteristic (ROC) curve was used to evaluate the prognostic value of miR-199b in colorectal cancer patients. Results: The relative expression level of miR-199b in colorectal cancer tissues (-7.88±0.11) was lower than that in adjacent normal tissues (-6.49±0.12, P<0.001). The expression level of miR-199b in colorectal cancer tissues with lymph node metastasis (-7.51±0.14) was higher than that in colorectal cancer tissues without lymph node metastasis (-8.23±0.17, P<0.001). The relative expression levels of miR-199b in stage Ⅰ/Ⅱ, Ⅲ and Ⅳ colorectal cancer tissues were gradually increased, which were -8.26±0.17, -7.70±0.16 and -6.57±0.27, respectively, and the difference was statistically significant (P<0.001). The 5-year survival rates of patients with high and low expressions of miR-199b were 75.6% and 84.6%(P=0.045) respectively. ROC curve showed that when miR-199b was -7.965, the area under the curve was 0.578 (95% CI: 0.468, 0.688). Conclusion: The high expression of miR-199b in colorectal cancer tissues is associated with late TNM stage, lymph node metastasis and poor prognosis in colorectal cancer patients, and miR-199b may be used as a potential marker for postoperative progress and prognosis in colorectal cancer patients.

PMID:37078214 | DOI:10.3760/cma.j.cn112152-20220125-00059

Zhonghua Zhong Liu Za Zhi. 2023 Apr 23;45(4):322-329. doi: 10.3760/cma.j.cn112152-20211008-00745.

ABSTRACT

Objective: To produce chimeric antigen receptor T cells (CAR-T) targeting human hepatocyte growth factor/c-Met (HGF/c-Met) protein and detect its cytotoxicity against non-small cell lung cancer (NSCLC) cells H1975 in vitro. Methods: The whole gene sequence of c-Met CAR containing c-Met single-chain fragment variable was synthesized and linked to lentiviral vector plasmid, plasmid electrophoresis was used to detect the correctness of target gene. HEK293 cells were transfected with plasmid and the concentrated solution of the virus particles was collected. c-Met CAR lentivirus was transfected into T cells to obtain second-generation c-Met CAR-T and the expression of CAR sequences was verified by reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) and western blot, and the positive rate and cell subtypes of c-Met CAR-T cells were detected by flow cytometry. The positive expression of c-Met protein in NSCLC cell line H1975 was verified by flow cytometry, and the negative expression of c-Met protein in ovarian cancer cell line A2780 was selected as the control. The cytotoxicity of c-Met CAR-T to H1975 was detected by lactate dehydrogenase (LDH) cytotoxicity assay at 1∶1, 5∶1, 10∶1 and 20∶1 of effector: target cell ratio (E∶T). Enzyme-linked immunosorbent assay (ELISA) was used to detect the release of cytokines such as TNF-α, IL-2 and IFN-γ from c-Met CAR-T co-cultured with H1975. Results: The size of band was consistent with that of designed c-Met CAR, suggesting that the c-Met CAR plasmid was successfully constructed. The results of gene sequencing were consistent with the original design sequence and lentivirus was successfully constructed. CAR molecules expression in T cells infected with lentivirus was detected by western blot and RT-qPCR, which showed c-Met CAR-T were successfully constructed. Flow cytometry results showed that the infection efficiency of c-Met CAR in T cells was over 38.4%, and the proportion of CD8(+) T cells was increased after lentivirus infection. The NSCLC cell line H1975 highly expressed c-Met while ovarian cancer cell line A2780 negatively expressed c-Met. LDH cytotoxicity assay indicated that the killing efficiency was positively correlated with the E∶T, and higher than that of control group, and the killing rate reached 51.12% when the E∶T was 20∶1. ELISA results showed that c-Met CAR-T cells released more IL-2, TNF-α and IFN-γ in target cell stimulation, but there was no statistical difference between c-Met CAR-T and T cells in the non-target group. Conclusions: Human NSCLC cell H1975 expresses high level of c-Met which can be used as a target for immunotherapy. CAR-T cells targeting c-Met have been successfully produced and have high killing effect on c-Met positive NSCLC cells in vitro.

PMID:37078213 | DOI:10.3760/cma.j.cn112152-20211008-00745

Zhonghua Zhong Liu Za Zhi. 2023 Apr 23;45(4):313-321. doi: 10.3760/cma.j.cn112152-20220604-00386.

ABSTRACT

Objective: To analyze the trends of incidence and age change for global female breast cancer in different regions of the world according to the database from Cancer Incidence in Five Continents Time Trends (CI5plus) published by the International Association of Cancer Registries (IACR). Methods: The recorded annual female breast cancer (ICD-10: C50) incidence data and corresponding population at-risk data (1998-2012) were extracted from CI5plus published by IACR. The annual change percentage and average annual change percentage (AAPC) were calculated to examine the trends of incidence. The age-standardized mean age at diagnosis and proportion of incidence cases by age were calculated to analyze the relationship between incidence and age. Results: For crude incidence, except in Northern America, all other regions showed an upward trend, with Asia showing the most obvious upward trend (AAPC: 4.1%, 95% CI: 3.9%, 4.3%). For age-standardized incidence, in Asia, Latin America and Europe, the rising trends had slowed down, in Oceania and Africa, the trends began to be stable, and in Northern America, the trend showed a downward trend (APPC: -0.6%; 95% CI: -1.0%, -0.1%). The mean age at diagnosis were increased from 1998 to 2012 in Asia, Latin America, Oceania and Europe, with an annual increase of 0.12 years, 0.09 years, 0.04 years and 0.03 years, respectively. But after age-standardized, only Europe still kept increasing year by year, with an annual increase of 0.02 years, while Northern America showed a decreasing trend, with an annual decrease of about 0.03 years. Conclusions: From 1998 to 2012, the trends of incidence and age change for global female breast cancer vary in different regions of the world, and the global population aging is widespread, which affects the trend of the actual age change. Prevention and control strategies should be targeted at different age groups in different regions.

PMID:37078212 | DOI:10.3760/cma.j.cn112152-20220604-00386

Clin Chem Lab Med. 2023 Apr 21. doi: 10.1515/cclm-2023-0162. Online ahead of print.

ABSTRACT

OBJECTIVES: The objective of our study is to evaluate the effect of storage temperature and time to analysis on arterial blood gas parameters in order to extend the CLSI recommendations.

METHODS: Stability of 12 parameters (pH, pCO₂, pO₂, Na⁺, K⁺, Ca²⁺, glucose, lactate, hemoglobin, oxyhemoglobin, carboxyhemoglobin, methemoglobin) measured by GEM PREMIER™ 5000 blood gas analyzer was studied at room temperature and at +4 °C (52 patients). The storage times were 30, 45, 60, 90 and 120 min. Stability was evaluated on the difference from baseline, the difference from the analyte-specific measurement uncertainty applied to the baseline value, and the impact of the variation on the clinical interpretation.

RESULTS: At room temperature, all parameters except the lactate remained stable for at least 60 min. A statistically significant difference was observed for pH at T45 and T60 and for pCO₂ at T60 without modification of clinical interpretation. For lactate, clinical interpretation was modified from T45 and values were outside the range of acceptability defined by the measurement uncertainty. All parameters except pO₂ remained stable for at least 120 min at +4 °C.

CONCLUSIONS: A one-hour transport at room temperature is compatible with the performance of all the analyses studied except lactate. If the delay exceeds 30 min, the sample should be placed at +4 °C for lactate measurement. If the samples are stored in ice, it is important to note that the pO₂ cannot be interpreted.

PMID:37078234 | DOI:10.1515/cclm-2023-0162

Clin Chem Lab Med. 2023 Apr 21. doi: 10.1515/cclm-2023-0195. Online ahead of print.

ABSTRACT

OBJECTIVES: Acute cholecystitis is a gallbladder inflammation, and the Tokyo Guidelines 2018 (TG18) can be used to predict its presence and severity with high sensitivity and specificity. However, TG18 grading require the collection of excessive parameters. Monocyte distribution width (MDW) is a parameter used to detect sepsis early. Therefore, we investigated the correlation between MDW and cholecystitis severity.

METHODS: We conducted a retrospective study of patients with cholecystitis admitted to our hospital from November 1, 2020, to August 31, 2021. The primary outcome was severe cholecystitis analyzed as a composite of intensive care unit (ICU) admission and mortality. The secondary outcomes were length of hospital stay, ICU stay, and TG18 grade.

RESULTS: A total of 331 patients with cholecystitis were enrolled in this study. The average MDWs for TG18 grades 1, 2, and 3 were 20.21 ± 3.99, 20.34 ± 3.68, and 25.77 ± 6.61, respectively. For patients with severe cholecystitis, the average MDW was 25.42 ± 6.83. Using the Youden J statistic, we set a cutoff MDW of 21.6. Multivariate logistic regression revealed that patients with an MDW≥21.6 had a higher risk of severe cholecystitis (odds ratio=4.94; 95 % CI, 1.71-14.21; p=0.003). The Cox model revealed that patients with an MDW≥21.6 were more likely to have a prolonged hospital stay.

CONCLUSIONS: MDW is a reliable indicator of severe cholecystitis and prolonged length of stay. Additional MDW testing and a complete blood count may provide simple information for predicting severe cholecystitis early.

PMID:37078229 | DOI:10.1515/cclm-2023-0195

Psychol Med. 2023 Apr 20:1. doi: 10.1017/S0033291723001022. Online ahead of print.

NO ABSTRACT

PMID:37078398 | DOI:10.1017/S0033291723001022

United European Gastroenterol J. 2023 Apr 20. doi: 10.1002/ueg2.12385. Online ahead of print.

ABSTRACT

BACKGROUND: Patients with inflammatory bowel disease (IBD) consider that their diet is important for controlling symptoms and frequently ask their physician for additional guidance on this matter. The objectives of the present study of patients with IBD were to characterize the prevalence of exclusion diets and fasting and to identify associated risk factors.

METHODS: Using an anonymous questionnaire, we screened patients attending our IBD nutrition clinic between November 2021 and April 2022 for exclusion diets. The avoidance of a food category completely was defined as total exclusion and avoidance most of the time was defined as partial exclusion. We also asked patients whether they fasted totally, intermittently, or partially.

RESULT: A total of 434 patients with IBD were included. On inclusion, 159 patients (36.6%) totally excluded at least one food category and 271 (62.4%) partially excluded at least one food. Intermittent, total, or partial fasting was reported by 30.8% of the patients. Disease activity (odds ratio (OR) [95% confidence interval] = 1.7 [1.1-2.7], p = 0.0130) and treatment with a small-molecule or an investigational drug (OR = 4.0 [1.5-10.6], p = 0.0059) were independently associated with an exclusion diet. A history of stenosis (OR = 2.0 [1.2-3.2], p = 0.0063) and active disease (OR = 1.9 [1.2-3.1], p = 0.0059) were associated with fasting.

CONCLUSION: In this real-world study, approximately two-thirds of our patients with IBD reported the partial or total exclusion of at least one food category and one third reported fasting. A systematic nutritional evaluation might improve clinical management and quality of care for patients with IBD both Crohn’s disease and ulcerative colitis.

PMID:37078395 | DOI:10.1002/ueg2.12385