Nevin Manimala

NPJ Microgravity. 2022 Jul 20;8(1):27. doi: 10.1038/s41526-022-00208-5.

ABSTRACT

Otoliths are the primary gravity sensors of the vestibular system and are responsible for the ocular counter-roll (OCR). This compensatory eye torsion ensures gaze stabilization and is sensitive to a head roll with respect to gravity and the Gravito-Inertial Acceleration vector during, e.g., centrifugation. To measure the effect of prolonged spaceflight on the otoliths, we quantified the OCR induced by off-axis centrifugation in a group of 27 cosmonauts in an upright position before and after their 6-month space mission to the International Space Station. We observed a significant decrease in OCR early postflight, larger for first-time compared to experienced flyers. We also found a significantly larger torsion for the inner eye, the eye closest to the rotation axis. Our results suggest that experienced cosmonauts have acquired the ability to adapt faster after G-transitions. These data provide a scientific basis for sending experienced cosmonauts on challenging missions that include multiple g-level transitions.

PMID:35858981 | DOI:10.1038/s41526-022-00208-5

Sci Rep. 2022 Jul 20;12(1):12425. doi: 10.1038/s41598-022-16380-3.

ABSTRACT

The status of axillary lymph node metastases determines the treatment and overall survival of breast cancer (BC) patients. Three-dimensional (3D) assessment methods have advantages for spatial localization and are more responsive to morphological changes in lymph nodes than two-dimensional (2D) assessment methods, and we speculate that methods developed using 3D reconstruction systems have high diagnostic efficacy. This exploratory study included 43 patients with histologically confirmed BC diagnosed at Second Xiangya Hospital of Central South University between July 2017 and August 2020, all of whom underwent preoperative CT scans. Patients were divided into a training cohort to train the model and a validation cohort to validate the model. A 3D axillary lymph node atlas was constructed on a 3D reconstruction system to create various methods of assessing lymph node metastases for a comparison of diagnostic efficacy. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic values of these methods. A total of 43 patients (mean [SD] age, 47 [10] years) met the eligibility criteria and completed 3D reconstruction. An axillary lymph node atlas was established, and a correlation between lymph node sphericity and lymph node metastasis was revealed. By continuously fitting the size and characteristics of axillary lymph nodes on the 3D reconstruction system, formulas and models were established to determine the presence or absence of lymph node metastasis, and the 3D method had better sensitivity for axillary lymph node assessment than the 2D method, with a statistically significant difference in the correct classification rate. The combined diagnostic method was superior to a single diagnostic method, with a 92.3% correct classification rate for the 3D method combined with ultrasound. In addition, in patients who received neoadjuvant chemotherapy (NAC), the correct classification rate of the 3D method (72.7%) was significantly higher than that of ultrasound (45.5%) and CT (54.5%). By establishing an axillary lymph node atlas, the sphericity formula and model developed with the 3D reconstruction system achieve a high correct classification rate when combined with ultrasound or CT and can also be applied to patients receiving NAC.

PMID:35858979 | DOI:10.1038/s41598-022-16380-3

Sci Rep. 2022 Jul 20;12(1):12404. doi: 10.1038/s41598-022-16479-7.

ABSTRACT

Identifying medication errors is one method of improving patient safety. Peri operative anesthetic management of patient includes polypharmacy and the steps followed prior to drug administration. Our objective was to identify, extract and analyze the medication errors (MEs) reported in our critical incident reporting system (CIRS) database over the last 15 years (2004-2018) and to review measures taken for improvement based on the reported errors. CIRS reported from 2004 to 2018 were identified, extracted, and analyzed using descriptive statistics and presented as frequencies and percentages. MEs were identified and entered on a data extraction form which included reporting year, patients age, surgical specialty, American Society of Anesthesiologist (ASA) status, time of incident, phase and type of anesthesia and drug handling, type of error, class of medicine, level of harm, severity of adverse drug event (ADE) and steps taken for improvement. Total MEs reported were 311, medication errors were reported, 163 (52%) errors occurred in ASA II and 90 (29%) ASA III patient, and 133 (43%) during induction. During administration phase 60% MEs occurred and 65% were due to human error. ADEs were found in 86 (28%) reports, 58 of which were significant, 23 serious and five life-threatening errors. The majority of errors involved neuromuscular blockers (32%) and opioids (13%). Sharing of CI and a lesson to be learnt e-mail, colour coded labels, change in medication trolley lay out, decrease in floor stock and high alert labels were the low-cost steps taken to reduce incidents. Medication errors were more frequent during administration. ADEs were occurred in 28% MEs.

PMID:35858974 | DOI:10.1038/s41598-022-16479-7

Sci Rep. 2022 Jul 20;12(1):12373. doi: 10.1038/s41598-022-15767-6.

ABSTRACT

We develop here a novel modelling approach with the aim of closing the conceptual gap between tumour-level metabolic processes and the metabolic processes occurring in individual cancer cells. In particular, the metabolism in hepatocellular carcinoma derived cell lines (HEPG2 cells) has been well characterized but implementations of multiscale models integrating this known metabolism have not been previously reported. We therefore extend a previously published multiscale model of vascular tumour growth, and integrate it with an experimentally verified network of central metabolism in HEPG2 cells. This resultant combined model links spatially heterogeneous vascular tumour growth with known metabolic networks within tumour cells and accounts for blood flow, angiogenesis, vascular remodelling and nutrient/growth factor transport within a growing tumour, as well as the movement of, and interactions between normal and cancer cells. Model simulations report for the first time, predictions of spatially resolved time courses of core metabolites in HEPG2 cells. These simulations can be performed at a sufficient scale to incorporate clinically relevant features of different tumour systems using reasonable computational resources. Our results predict larger than expected temporal and spatial heterogeneity in the intracellular concentrations of glucose, oxygen, lactate pyruvate, f16bp and Acetyl-CoA. The integrated multiscale model developed here provides an ideal quantitative framework in which to study the relationship between dosage, timing, and scheduling of anti-neoplastic agents and the physiological effects of tumour metabolism at the cellular level. Such models, therefore, have the potential to inform treatment decisions when drug response is dependent on the metabolic state of individual cancer cells.

PMID:35858953 | DOI:10.1038/s41598-022-15767-6

Sci Rep. 2022 Jul 20;12(1):12375. doi: 10.1038/s41598-022-16142-1.

ABSTRACT

The limitations of BMI as a measure of adiposity and health risks have prompted the introduction of many alternative biomarkers. However, ranking diverse biomarkers from best to worse remains challenging. This study aimed to address this issue by introducing three new approaches: (1) a calculus-derived, normalized sensitivity score (NORSE) is used to compare the predictive power of diverse adiposity biomarkers; (2) multiple biomarkers are combined into multi-dimensional models, for increased sensitivity and risk discrimination; and (3) new visualizations are introduced that convey complex statistical trends in a compact and intuitive manner. Our approach was evaluated on 23 popular biomarkers and 6 common medical conditions using a large database (National Health and Nutrition Survey, NHANES, N ~ 100,000). Our analysis established novel findings: (1) regional composition biomarkers were more predictive of risk than global ones; (2) fat-derived biomarkers had stronger predictive power than weight-related ones; (3) waist and hip are always elements of the strongest risk predictors; (4) our new, multi-dimensional biomarker models yield higher sensitivity, personalization, and separation of the negative effects of fat from the positive effects of lean mass. Our approach provides a new way to evaluate adiposity biomarkers, brings forth new important clinical insights and sets a path for future biomarker research.

PMID:35858946 | DOI:10.1038/s41598-022-16142-1

Clin Genitourin Cancer. 2022 Jun 18:S1558-7673(22)00138-0. doi: 10.1016/j.clgc.2022.06.013. Online ahead of print.

ABSTRACT

BACKGROUND: Upper tract urothelial carcinomas (UTUCs) arise in the renal pelvis or the ureter, accounting for approximately 5% of all urothelial carcinomas. Recent years have witnessed the publication of several studies aimed at assessing the molecular, biologic, and clinical features of UTUC, reporting that FGFR3 mutations are the most observed genetic aberrations; however, several knowledge gaps persist in the understanding of the genomic landscape of this genitourinary malignancy with few treatment options.

PATIENTS AND METHODS: In the current study, we aimed to comprehensively analyze clinicopathological features of FGFR3-mutated UTUCs patients in public datasets to increase the current knowledge of the molecular and biologic profile of UTUC. Data regarding clinical outcomes, mutational profiles, and copy number alterations in patients affected by UTUC were downloaded from the cBioPortal for Cancer Genomics Database. UTUC data were available from 4 studies, for a total number of 358 patients; among these, 150 UTUC patients presented FGFR3 mutations.

RESULTS: The current database analysis of the mutational profile of 150 FGFR3-mutated UTUCs suggested that FGFR3 mutations may represent a prognostic factor in this disease, with a statistically longer overall survival compared to wild-type patients treated with radical surgery. In addition, FGFR3 mutations were more frequent in low-grade UTUCs with early-stage disease (pT1, pT2, and pT3).

CONCLUSION: Genomic characterization of UTUC is destined to become increasingly important, and more efforts aimed at implementing UTUC genomics analysis are warranted.

PMID:35858936 | DOI:10.1016/j.clgc.2022.06.013

Sci Rep. 2022 Jul 20;12(1):12426. doi: 10.1038/s41598-022-15606-8.

ABSTRACT

Direct interspecies electron transfer (DIET) has been identified as an efficient metabolism between symbiotically interacting organisms. One method of DIET uses conductive materials (e.g., granular activated carbon (GAC)) as a medium to shuttle electrons from electron donating organisms (eg., Geobacter metallireducens) to electron accepting organisms (e.g., Geobacter sulfurreducens and Methanosarcina barkeri). Conductive materials such as GAC, become negatively charged in DIET processes due to reduction by electron donating organisms. This high excess electron density in GAC leads to quantum tunnelling of electrons being a significant electron transfer mechanism for DIET. Thus, a theoretical model obeying the Wentzel-Kramers-Brillouin (WKB) approximation and Fermi-Dirac statistics was developed and simulated. In the model, the electron tunnelling transfer barrier was described by an effective rectangular barrier. The result of our 1D tunnelling simulations indicates that within 29.4 nm of the GAC, tunnelling can sufficiently supply electrons from GAC to G. sulfurreducens and M. barkeri. The phenomenon of tunnelling may also have significance as a stimulant of chemotaxis for G. sulfurreducens and other electron accepting microbes when attempting to adsorb onto GAC. This study sheds light on quantum tunnelling’s significant potential in both bacterium and archaeon DIET-centric processes.

PMID:35858919 | DOI:10.1038/s41598-022-15606-8

Clin Lymphoma Myeloma Leuk. 2022 Jun 30:S2152-2650(22)00217-8. doi: 10.1016/j.clml.2022.06.013. Online ahead of print.

ABSTRACT

BACKGROUND: Managing double-expressor lymphomas (DEL) is controversial given the dearth of data and lack of standardized guidelines on this high-risk subset of lymphomas. No prospective and few retrospective studies limited by either their sample size or short follow-up address the question of initial treatment of choice for DEL. We performed the largest analysis to date exploring R-CHOP vs DA-EPOCH-R in DEL.

METHODS: Adults with DEL diagnosed from 6/2012-2/2021 at 4 unique sites were retrospectively analyzed. Progression-free survival (PFS) was the primary endpoint. Key secondary endpoints include overall survival (OS), overall and complete response rates (ORR and CRR), cumulative incidence of relapse, and autologous hematopoietic cell transplantation (autoHCT) utilization.

RESULTS: 155 patients were included, 61 treated with R-CHOP and 94 with DA-EPOCH-R. 3-year PFS and OS were similar between R-CHOP and DA-EPOCH-R, 33.2% vs 57.2%,(P = .063), and 72.2% vs 71.6% (P = .43) after median follow-up times of 2.43 and 2.89 years, respectively. Patients <65 had improved PFS with DA-EPOCH-R, hazard ratio 0.41 (P = .01). CRR and ORR rates were also similar. Relapse rates were not statistically different, 51.9% vs 28.6% (P = .069). AutoHCT utilization was higher with R-CHOP vs DA-EPOCH-R, 23.0% vs 8.5% (P = .017).

CONCLUSIONS: Our findings do not support the use of DA-EPOCH-R over R-CHOP for DEL. Patients <65 years may experience longer PFS with DA-EPOCH-R, but limitations to the analysis make this interpretation difficult.

PMID:35858904 | DOI:10.1016/j.clml.2022.06.013

World J Surg Oncol. 2022 Jul 20;20(1):238. doi: 10.1186/s12957-022-02699-8.

ABSTRACT

BACKGROUND: Signet-ring cell carcinoma of the stomach (SRCC) is a particular gastric cancer entity. Its incidence is increasing. Its diagnosis is pathological; it corresponds to adenocarcinoma with a majority of signet-ring cells component (> 50%). These histological features give it its aggressiveness characteristics. This has repercussions on the prognostic level and implications for the alternatives of therapy, especially since some authors suggest a potential chemoresistance. This survey aimed to identify the epidemiological, pathological, therapeutic, and prognostic characteristics of SRCC as a separate disease entity.

METHODS: This was a retrospective study of 123 patients admitted for gastric adenocarcinoma to Habib Thameur Hospital in Tunis over 11 years from January 2006 to December 2016. A comparative study was performed between 2 groups: the SRCC group with 62 patients and the non-SRCC (non-signet-ring cell carcinoma of the stomach) with 61 patients.

RESULTS: The prevalence of SRCC in our series was 50%. SRCC affected significantly younger patients (55 vs 62 years; p = 0.004). The infiltrative character was more common in SRCC tumors (30.6 vs 14.8%; p = 0.060), whereas the budding character was more often noted in non-SRCC tumors (78.7 vs 58.1%; p = 0.039). There was no significant difference in tumor localization between both groups. Linitis plastica was noted in 14 patients with SRCC against a single patient with non-SRCC (p = 0.001). The tumor size was more important in the non-SRCC group (6.84 vs 6.39 cm; p = 0.551). Peritoneal carcinomatosis was noted in 4.3% of cases in the SRCC group versus 2.2% of cases in the NSRCC group (p = 0.570). Total gastrectomy was more often performed in the SRCC group (87 vs 56%; p = 0.001). Resection was more often curative in the non-SRCC group (84.4 vs 78.3%; p = 0.063). Postoperative chemotherapy was more commonly indicated in the SRCC group (67.4 vs 53.3%; p = 0.339). Tumor recurrence was more common in the non-SRCC group (35.7 vs 32%; p = 0.776). The most common type of recurrence was peritoneal carcinomatosis in the SRCC group (62.5%) and hepatic metastasis in the non-SRCC group (60%; p = 0.096). The overall 5-year survival in the SRCC group was lower than in the non-SRCC group, with no statistically significant difference (47.1 vs 51.5%; p = 0.715). The overall survival was more important for SRCC in early cancer (100 vs 80%; p = 0.408), whereas it was higher for non-SRCC in advanced cancer (48.1 vs 41.9%; p = 0.635).

CONCLUSION: Apart from its epidemiological and pathological features, SRCC seems to have a worse prognosis. Indeed, it is diagnosed at a more advanced stage and has a worse prognosis in advanced cancer than non-SRCC. It is therefore to be considered as a particular entity of gastric adenocarcinoma requiring a specific therapeutic protocol where the place of chemotherapy remains to be more investigated.

PMID:35858903 | DOI:10.1186/s12957-022-02699-8

Sci Rep. 2022 Jul 20;12(1):12380. doi: 10.1038/s41598-022-15983-0.

ABSTRACT

This research aims to contribute in developing a mathematical model for the composite probabilistic energy emissions dispatch (CPEED) with renewable energy systems, and it proposes a novel framework, based on an existing astute black widow optimization (ABWO) algorithm. Renewable energy power generation technology has contributed to pollution reduction and sustainable development. Therefore, this research aims to explore the CPEED problem in the context of renewable energy generation systems to enhance the energy and climate benefits of the power systems. Five benchmark test systems, combined with conventional thermal power plants and renewable energy sources such as wind and solar, are considered herein to obtain the optimum solution for cost and pollutant emission by using the ABWO approach. The ascendancy is not limited to environmental impacts, but it also provides the diversification of energy supply and reduction of reliance on imported fuels. As a result, the research findings contribute in lowering the cost of fuel and pollutant emissions, correlated with electricity generation systems, while increasing the renewable energy usage and penetration. Finally, the performance and efficacy of the designed scheme have been fully validated by comprehensive experimental results and statistical analyses.

PMID:35858895 | DOI:10.1038/s41598-022-15983-0