Machine learning application for classification of Alzheimer's disease stages using 18F-flortaucipir positron emission tomography.

BACKGROUND: The progression of Alzheimer's dementia (AD) can be classified into three stages: cognitive unimpairment (CU), mild cognitive impairment (MCI), and AD. The purpose of this study was to implement a machine learning (ML) framework for AD stage classification using the standard uptake value ratio (SUVR) extracted from 18F-flortaucipir positron emission tomography (PET) images. We demonstrate the utility of tau SUVR for AD stage classification. We used clinical variables (age, sex, education, mini-mental state examination scores) and SUVR extracted from PET images scanned at baseline. Four types of ML frameworks, such as logistic regression, support vector machine (SVM), extreme gradient boosting, and multilayer perceptron (MLP), were used and explained by Shapley Additive Explanations (SHAP) to classify the AD stage. RESULTS: Of a total of 199 participants, 74, 69, and 56 patients were in the CU, MCI, and AD groups, respectively; their mean age was 71.5 years, and 106 (53.3%) were men. In the classification between CU and AD, the effect of clinical and tau SUVR was high in all classification tasks and all models had a mean area under the receiver operating characteristic curve (AUC) > 0.96. In the classification between MCI and AD, the independent effect of tau SUVR in SVM had an AUC of 0.88 (p < 0.05), which was the highest compared to other models. In the classification between MCI and CU, the AUC of each classification model was higher with tau SUVR variables than with clinical variables independently, which yielded an AUC of 0.75(p < 0.05) in MLP, which was the highest. As an explanation by SHAP for the classification between MCI and CU, and AD and CU, the amygdala and entorhinal cortex greatly affected the classification results. In the classification between MCI and AD, the para-hippocampal and temporal cortex affected model performance. Especially entorhinal cortex and amygdala showed a higher effect on model performance than all clinical variables in the classification between MCI and CU. CONCLUSIONS: The independent effect of tau deposition indicates that it is an effective biomarker in classifying CU and MCI into clinical stages using MLP. It is also very effective in classifying AD stages using SVM with clinical information that can be easily obtained at clinical screening.

The use of fluorinated gases and quantification of carbon emission for common vitreoretinal procedures.

PURPOSE: To report the contribution to carbon dioxide equivalent mass [CO2EM] of various types of VR surgery performed across three tertiary referral centres, according to their indication and fluorinated gas used. We secondarily reported on the difference in tamponade choice, and CO2EM between the different centres. MATERIALS: Retrospective, continuous, comparative multicentre study of all procedures using fluorinated gases between 01/01/17-31/12/20 at the Manchester Royal Eye Hospital and Birmingham and Midland Eye Centre, and between 01/01/19-31/12/2020 at the University Hospitals Coventry and Warwickshire. RESULTS: Across 4877 procedures, the use of fluorinated gases produced 284.2 tonnes (71.2 tonnes annually) CO2EM; an annual consumption of 30,330 l of gasoline. Rhegmatogenous-retinal-detachment (RRD) and macular hole repair had the highest CO2EM by indication, accounting for 191.4 tonnes CO2EM (67.3%) and 28.6 tonnes CO2EM (10.1%); a mean 60.0 kg and 32.0 kg of CO2EM produced per surgery respectively. The use of fluorinated gases and their respective CO2EM contributions were significantly different across all three centres (p < 0.001) for all indications. SF6, despite being used in 1883 procedures (38.6%), contributed to 195.5 tonnes CO2EM (68.8%). Relative to C2F6, procedures using C3F8 and SF6 produced 1.9 and 4.4 times more CO2EM. CONCLUSION: We demonstrated that SF6 causes significantly higher carbon emissions relative to C2F6 and C3F8 with RRD and macular hole repair having the greatest environmental impact. We also reported large variations between different large VR centres in fluorinated gas use, and therefore in carbon emission contributions depending on indications for surgery. Evidence-based protocols might help in making VR surgery "greener".

The Fruit Proteome Response to the Ripening Stages in Three Tomato Genotypes.

The tomato is a horticultural crop that appears in various colors as it ripens. Differences in the proteome expression abundance of a tomato depend on its genotype and ripening stage. Thus, this study aimed to confirm the differences in changes in the proteome according to four ripening stages (green, breaker, turning, and mature) of three tomato genotypes, i.e., yellow, black, and red tomatoes, using a gel-based proteomic technique. The number of protein spots shown as two-dimensional electrophoresis (2-DE) gels differed according to tomato genotype and ripening stage. A total of 286 variant proteins were determined using matrix-assisted laser desorption-time of flight (MALDI-TOF) mass spectrometry (MS) analysis, confirming 233 identified protein functions. In three tomato genotypes in each ripening stage, grouping according to the Munich Information Center for Protein Sequences (MIPS) functional categories confirmed the variant proteins involved in the following: energy processes (21%); metabolism (20%); protein fate (15%); protein synthesis (10%); a protein with a binding function or cofactor requirement (8%); cell rescue, defense, and virulence (8%); cellular transport, transport facilitation, and transport routes (6%); the biogenesis of cellular components (5%); cell cycle and DNA processing (2%); others (5%). Among the identified protein spots in the function category, two proteins related to metabolism, four related to energy, four related to protein synthesis, and two related to interaction with the cellular environment showed significantly different changes according to the fruit color by the ripening stage. This study reveals the physiological changes in different types of tomatoes according to their ripening stage and provides information on the proteome for further improvement.

Retinal Detachment Repair With Vitrectomy: Air Tamponade Integration to a Vitreoretinal Service, Comparison With Gas Tamponade, and Literature Review.

BACKGROUND AND OBJECTIVE: Rhegmatogenous retinal detachment (RRD) repair by pars plana vitrectomy and gas tamponade (GT) has significant clinical and quality-of-life impacts compared with repair by short-acting air tamponade (AT). With AT, most authors minimize cryotherapy because of prolonged chorioretinal scar formation and use perfluorocarbon to maximize subretinal fluid drainage; this deviates from traditional technique, which discourages popularization of AT. PATIENTS AND METHODS: Prospective 12-month study from January to December 2019 of all primary macula-on RRD cases. Patients fulfilling the inclusion criteria for the Pneumatic Retinopexy Versus Vitrectomy for Retinal Detachment Trial received AT and otherwise were assigned to receive GT. RESULTS: Forty-six patients were enrolled: 22 (48%) receiving AT and 24 (52%) receiving GT. The primary success rate of AT was 21 (95%) and the primary success rate of GT was 23 (96%), with 100% final success. Cryopexy was used in 64% of AT cases and 58% of GT cases. Cataract surgery was required less when AT was used (1 [6%]) than when GT was used (3 [21%]). AT was used in 48% of primary macula-on RRD and 27% of all primary RRD cases. CONCLUSIONS: AT has visual and anatomical outcomes comparable to those of GT with conventional vitrectomy techniques, with faster postoperative rehabilitation enabling a swift return to normal daily activities. [Ophthalmic Surg Lasers Imaging Retina. 2022;53:87-95.].

Environmental effect of air versus gas tamponade in the management of rhegmatogenous retinal detachment VR surgery: A multicentre study of 3,239 patients.

PURPOSE: To report the potential reduction of carbon emissions by utilising air-tamponade (AT), where possible, instead of fluorinated gases in the management of rhegmatogenous retinal detachment (RRD). We compared the carbon CO2 emissions produced at two large tertiary referral vitreoretinal (VR) centres where RRD are exclusively repaired using fluorinated gases to a tertiary VR mass of each gas used according to the Intergovernmental Panel on Climate Change. MATERIALS AND METHODS: Retrospective, continuous, comparative multicentre study of all procedures using fluorinated gases between 01/01/17-31/12/20 at the Manchester Royal Eye Hospital (MREH) and Birmingham and Midland Eye Centre (BMEC), and between 01/01/19-31/12/2020 at the University Hospitals Coventry and Warwickshire (UHCW). RESULTS: We report on 3,239 (SF6:1,415 [43.7%], C2F6:1,235 [38.1%], C3F8:541 [16.7%], Air:48 [1.5%]) procedures. UHCW and BMEC utilise single use 30ml and 75ml cannisters, respectively and MREH use multi-use gas cylinders. UHCW used AT in 48 (70%) of RRD repairs. Mean equivalent mass CO2/patient was MREH:115.9kg, BMEC:7.9kg and UHCW:1.9kg. If assuming all centres used 30ml cannisters, the mean equivalent mass CO2/patient was MREH:3.5 kg, BMEC:3.1kg and UHCW:1.9kg. AT enabled UHCW to greatly reduce the need for the most environmentally damaging SF6 gas, leading to lower CO2 emissions by 47.0% and 41.1% compared to MREH and BMEC, respectively. CONCLUSION: We demonstrate how AT vs. the fluorinated gases can reduce in carbon footprint in the management of RRD. Further studies are required to determine the most 'environment-friendly' intraocular tamponade without compromising patient outcomes centre that also routinely employs AT in selected RRD cases.

Environmental Effect of Fluorinated Gases in Vitreoretinal Surgery: A Multicenter Study of 4,877 Patients.

PURPOSE: To investigate the direct contribution to carbon emissions of fluorinated gases used in all vitreoretinal (VR) procedures utilizing gas tamponade and assess the respective carbon footprint of the three different gas delivery systems. DESIGN: A multicenter, retrospective, environmental impact study. METHODS: All VR procedures using fluorinated gases between 2017 to 2020 at the Manchester Royal Eye Hospital (MREH) and Birmingham and Midland Eye Centre (BMEC) (the second and third largest VR centers in the UK), and between 2019 to 2020 at the University Hospitals Coventry and Warwickshire (UHCW) were included. CO2 equivalent mass (CO2EM) was calculated from the mass of each gas used, according to the Intergovernmental Panel on Climate Change. RESULTS: A total of 4877 (1883 SF6 [38.6%], 2096 C2F6 [43.0%], and 897 C3F8 [18.4%]) procedures were analyzed. UHCW and BMEC utilized single-use 30 mL and 75 mL cannisters, respectively. MREH used four cylinders of each gas over 4 years (2 kg SF6, 1 kg C2F6, 1 kg C3F8). Mean CO2EM per patient was: MREH 111.8 kg, BMEC 7.5 kg, and UHCW 2.7 kg. For MREH and BMEC, the CO2EM was 73.4 metric tons annually (if all cases were performed with i) 30 mL: 3.7 tons and ii) cylinders: 148.0 tons, x 40-fold difference), equating to 599,400 (30,500-1.2 million) km travelled by a passenger car. The current use of SF6 in VR surgery accounts for 0.11% of total SF6 use; if 30 mL cylinders were exclusively used in the UK, this could be lowered to 0.01%. CONCLUSIONS: This study highlights the significant waste associated with large gas cylinders and demonstrated that 30 mL cannisters can lead to a marked reduction in carbon emissions, even after accounting for the increased carbon footprint involved in their manufacture and disposal.

Effect of cataract surgery training on operating room productivity: How long trainees take.

PURPOSE: To determine the effect of specialty training on cataract operation times and operating room efficiency. SETTING: Manchester Royal Eye Hospital, Manchester, United Kingdom. DESIGN: Retrospective consecutive case series. METHODS: Specialty training and consultant case times with preparation times were recorded between August 2014 and May 2015. Cases with posterior capsule rupture requiring anterior vitrectomy or iris hook insertion were analyzed. RESULTS: The study reviewed 1904 cases (906 consultant cases, 797 specialty training cases). Trainees' case time was significantly longer than consultants' (mean 24.25 minutes ± 12.36 [SD] versus 19.59 ± 10.05 minutes) (P < .0001). The difference between the 1- to 3-year trainees' mean surgical time and 4- to 7-year trainees' mean surgical time was statistically significant (P < .0001). Mean case time decreased from 27.63 ± 12.57 minutes (1- to 3-year trainees) to 22.55 ± 11.90 minutes (4- to 7-year trainees). The mean posterior capsule rupture rate was 2.76% for trainees and 1.77% for consultants. When posterior capsule rupture occurred, the mean surgical time increased to 49.81 ± 18.69 minutes for the consultant group and 67.00 ± 26.26 minutes for the trainee group (P = .024). When iris hooks were required, the mean case time was 26.41 ± 11.28 minutes and 34.11 ± 15.06 minutes, respectively (P = .026). CONCLUSIONS: Specialty training cases had a longer duration than consultant cases, although the mean surgical time decreased with increased trainee experience. After 3 years of training, trainees did not have a significant effect on operating room efficiency. FINANCIAL DISCLOSURE: None of the authors has a financial or proprietary interest in any material or method mentioned.

Radiation-Induced Esophagitis In Vivo and In Vitro Reveals That Epidermal Growth Factor Is a Potential Candidate for Therapeutic Intervention Strategy.

PURPOSE: To establish and characterize radiation-induced esophagitis (RIE) in vivo and in vitro. METHODS AND MATERIALS: Fractionated thoracic irradiation at 0, 8, 12, or 15 Gy was given daily for 5 days to Balb/c or C57Bl/6 mice. Changes in body weight gain and daily food intake were assessed. At the end of the study, we removed the esophagus and examined histology by hematoxylin and eosin staining, immune cell infiltration and apoptosis by fluorescence-activated cell sorting, and gene expression changes by quantitative real-time polymerase chain reaction. Het-1A human esophageal epithelial cells were irradiated at 6 Gy, treated with recombinant human growth factors, and examined for gene expression changes, apoptosis, proliferation, and signal transduction pathways. RESULTS: We observed that irradiation at 12 Gy or 15 Gy per fraction produced significant reduction in body weight and decreased food intake in Balb/c mice but not as much in C57Bl/6 mice. Further analyses of Balb/c mice irradiated at 12 Gy/fraction revealed attenuated epithelium, inflamed mucosa, and increased numbers of infiltrating CD4+ helper T cells and apoptotic cells. Moreover, we found that expression of tissue inhibitor for metalloproteinase-1, plasminogen activator inhibitor-1, granulocyte macrophage-colony stimulating factor, vascular endothelial growth factor, and stromal-derived factor-1 were increased, whereas epidermal growth factor (EGF) was decreased. Irradiated Het-1A cells similarly showed a significant decrease in expression of EGF and connective tissue growth factor (CTGF). Treatment of EGF but not CTGF partially protected Het-1A cells from radiation-induced apoptosis and revealed phosphorylation of EGFR, AKT, and ERK signaling pathways. CONCLUSIONS: We established a mouse model of RIE in Balb/c mice with 12 Gy × 5 fractions, which showed reduced body weight gain, food intake, and histopathologic features similar to those of human esophagitis. Decreased EGF expression in the irradiated esophagus suggests that EGF may be a potential therapeutic intervention strategy to treat RIE.

[Effects of an educational program of pregnancy and delivery on pregnancy related knowledge, newborn care knowledge, and postpartum care self-efficacy of marriage immigrant women].

PURPOSE: This study was designed to evaluate the effects of an educational program on pregnancy and delivery including pregnancy related knowledge, newborn care knowledge, and postpartum care self-efficacy for married immigrant women. METHODS: A nonequivalent control group quasi-experimental design was used. The educational program was developed by though an educational need assessment of married immigrant women and an expert opinion. The program was provided for 3 weeks, once a week for two hours. The data were analyzed with SPSS program using Kolmogorov-Smirnov, X(2)-test, Fisher's exact test, and t-test. RESULTS: The program significantly improved pregnancy related knowledge, newborn care knowledge, and postpartum care self-efficacy for the married immigrant women who participated in the program compared to the women who did not. CONCLUSION: The results indicate that the educational program has an affirmative effect on pregnancy related knowledge, knowledge of newborn care, and postpartum care self-efficacy in these women. It is suggested, therefore, that the educational program be used to every married immigrant woman at the public health centers or delivery clinics help them to adjust to the childbearing and childrearing experience and this will ultimately enhance the quality of family life of married immigrant women in Korea.

Procalcitonin versus C-reactive protein and immature-to-total neutrophil ratio as markers of infection after cardiopulmonary bypass in children.

OBJECTIVE: To document concentrations of procalcitonin (PCT), C-reactive protein (CRP), and immature-to-total neutrophil ratio (ITR), postcardiopulmonary bypass (CPB), and to test the hypothesis that PCT is a more reliable marker of infection than CRP or ITR in the post-CPB child. DESIGN: Prospective cohort study. SETTING: Pediatric intensive care units at Royal Children's Hospital, Melbourne, Australia and Birmingham Children's Hospital, UK. PATIENTS: First stage: 283 post-CPB children; second stage: 65 post-CPB children with suspected infection. INTERVENTIONS: In the first stage, PCT, ITR, and CRP were measured serially on the first, second, third, and fifth postoperative day (POD). In the second stage, PCT, ITR, and CRP were measured in the specimens taken in the period before and after the clinical diagnosis of infection. MEASUREMENTS AND MAIN RESULTS: In children without infection, the median peak PCT concentration more than 5 PODs was 1.0 ng/mL, in children with local infection 1.0 ng/mL, and in children with definite sepsis 14.8 ng/mL. CRP increased in all subgroups of children studied, reaching a peak on POD 3 (median 51 mg/L). In definite sepsis, CRP was increased more than the other subgroups. ITR remained high with a median of 0.08 from POD 1 and gradually decreased, except in definite sepsis, where it remained high. In a receiver operating characteristic curve analysis, PCT was the most reliable variable for the diagnosis of probable/definite sepsis with area under the curve 0.84 (95% confidence interval, 0.75-0.92) compared with 0.73 (0.62-0.84) for ITR and 0.62 (0.52-0.73) for CRP. CONCLUSIONS: CRP was a poor marker of sepsis in this study. Children with a PCT <2.2 ng/mL or ITR <0.08 were unlikely to have definite or probable sepsis. However, only a third of children with high values of PCT and ITR had definite or probable sepsis.

Genotype-phenotype relationship between DNA repair gene genetic polymorphisms and DNA repair capacity.

Genotype-phenotype relationships between genetic polymorphisms of DNA repair genes and DNA repair capacity were evaluated in a case-control study of breast cancer. Selected DNA repair genes included were those involved in double-strand break repair (ATM, XRCC2, XRCC4, XRCC6, LIG4, RAD51, RAD52), base excision repair (LIG1), nucleotide excision repair (ERCC1), and mismatch repair (hMLH1). The subjects consisted of histologically confirmed breast cancer cases (n=132) and controls (n=75) with no present or previous history of cancer. Seventeen single nucleotide polymorphisms of 10 genes (ATM -5144A>T, IVS21+1049T>C, IVS33-55T>C, IVS34+60G>A, and 3393T>G, XRCC2 31479G/A, XRCC4 921G/T, XRCC6 1796G/T, LIG4 1977T/C, RAD51 135G/C, 172G/T, RAD52 2259C/T, LIG1 583A/C, ERCC1 8092A/C, 354C/T, hMLH1 5' region -93G/A, 655A/G) were determined by TaqMan assay (ATM) or MALDI-TOF (all other genes). DNA repair capacity was measured by a host cell reactivation assay of repair of ultraviolet damage. The DNA repair capacity (%) did not differ between cases (median 37.2, interquartile range: 23.6-59.6) and controls (median 32.7, interquartile range: 26.7-53.2). However, DNA repair capacity significantly differed by the genotypes of ATM and RAD51 genes among cancer-free controls. Our findings suggest that DNA repair capacity might be influenced by genetic polymorphisms of DNA damage response genes and DNA repair genes.