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The emergence of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) with decreased susceptibility to neutralization has generated interest in assessments of booster doses and variant-specific vaccines. Clinical trial participants who received a two-dose primary series of the COVID-19 vaccine mRNA-1273 approximately 6 months earlier entered an open-label phase 2a study ( NCT04405076 ) to evaluate the primary objectives of safety and immunogenicity of a single booster dose of mRNA-1273 or variant-modified mRNAs, including multivalent mRNA-1273.211. As the trial is currently ongoing, this exploratory interim analysis includes preliminary descriptive results only of four booster groups ( n  = 20 per group). Immediately before the booster dose, neutralizing antibodies against wild-type D614G virus had waned ( P  < 0.0001) relative to peak titers against wild-type D614G measured 1 month after the primary series, and neutralization titers against B.1.351 (Beta), P.1 (Gamma) and B.1.617.2 (Delta) VOCs were either low or undetectable. Both the mRNA-1273 booster and variant-modified boosters were safe and well-tolerated. All boosters, including mRNA-1273, numerically increased neutralization titers against the wild-type D614G virus compared to peak titers against wild-type D614G measured 1 month after the primary series; significant increases were observed for mRNA-1273 and mRNA-1273.211 ( P  < 0.0001). In addition, all boosters increased neutralization titers against key VOCs and VOIs, including B.1.351, P.1. and B.1.617.2, that were statistically equivalent to peak titers measured after the primary vaccine series against wild-type D614G virus, with superior titers against some VOIs. This trial is ongoing. Preliminary and exploratory analyses show that a third dose of the COVID-19 vaccine mRNA-1273 or variant-modified boosters can boost levels of neutralizing antibodies against SARS-CoV-2 variants.

Non-small-cell lung cancer (NSCLC) patients often demonstrate varying clinical courses and outcomes, even within the same tumor stage. This study explores deep learning applications in medical imaging allowing for the automated quantification of radiographic characteristics and potentially improving patient stratification. We performed an integrative analysis on 7 independent datasets across 5 institutions totaling 1,194 NSCLC patients (age median = 68.3 years [range 32.5-93.3], survival median = 1.7 years [range 0.0-11.7]). Using external validation in computed tomography (CT) data, we identified prognostic signatures using a 3D convolutional neural network (CNN) for patients treated with radiotherapy (n = 771, age median = 68.0 years [range 32.5-93.3], survival median = 1.3 years [range 0.0-11.7]). We then employed a transfer learning approach to achieve the same for surgery patients (n = 391, age median = 69.1 years [range 37.2-88.0], survival median = 3.1 years [range 0.0-8.8]). We found that the CNN predictions were significantly associated with 2-year overall survival from the start of respective treatment for radiotherapy (area under the receiver operating characteristic curve [AUC] = 0.70 [95% CI 0.63-0.78], p < 0.001) and surgery (AUC = 0.71 [95% CI 0.60-0.82], p < 0.001) patients. The CNN was also able to significantly stratify patients into low and high mortality risk groups in both the radiotherapy (p < 0.001) and surgery (p = 0.03) datasets. Additionally, the CNN was found to significantly outperform random forest models built on clinical parameters-including age, sex, and tumor node metastasis stage-as well as demonstrate high robustness against test-retest (intraclass correlation coefficient = 0.91) and inter-reader (Spearman's rank-order correlation = 0.88) variations. To gain a better understanding of the characteristics captured by the CNN, we identified regions with the most contribution towards predictions and highlighted the importance of tumor-surrounding tissue in patient stratification. We also present preliminary findings on the biological basis of the captured phenotypes as being linked to cell cycle and transcriptional processes. Limitations include the retrospective nature of this study as well as the opaque black box nature of deep learning networks. Our results provide evidence that deep learning networks may be used for mortality risk stratification based on standard-of-care CT images from NSCLC patients. This evidence motivates future research into better deciphering the clinical and biological basis of deep learning networks as well as validation in prospective data.

There has been broad variation among states in policy approaches to unwinding of continuous Medicaid coverage. But there is still time for policymakers and others to minimize the risk of coverage loss.

Screening methods available for colorectal cancer (CRC) to date are burdened by poor reliability and low patient adherence and compliance. An altered pattern of volatile organic compounds (VOCs) in exhaled breath has been proposed as a non-invasive potential diagnostic tool for distinguishing CRC patients from healthy controls (HC). The aim of this study was to evaluate the reliability of an innovative portable device containing a micro-gas chromatograph in enabling rapid, on-site CRC diagnosis through analysis of patients’ exhaled breath. In this prospective trial, breath samples were collected in a tertiary referral center of colorectal surgery, and analysis of the chromatograms was performed by the Biomedical Engineering Department. The breath of patients with CRC and HC was collected into Tedlar bags through a Nafion filter and mouthpiece with a one-way valve. The breath samples were analyzed by an automated portable gas chromatography device. Relevant volatile biomarkers and discriminant chromatographic peaks were identified through machine learning, linear discriminant analysis and principal component analysis. A total of 68 subjects, 36 patients affected by histologically proven CRC with no evidence of metastases and 32 HC with negative colonoscopies, were enrolled. After testing a training set (18 CRC and 18 HC) and a testing set (18 CRC and 14 HC), an overall specificity of 87.5%, sensitivity of 94.4% and accuracy of 91.2% in identifying CRC patients was found based on three VOCs. Breath biopsy may represent a promising non-invasive method of discriminating CRC patients from HC.

Understanding the relationship between exogenous melatonin and water deficit stress is crucial for achieving high yields and alleviating the effects of water deficit stress on soybean (Glycine max (L.) Merrill) plants in agriculture. This study investigated the effects of exogenous melatonin on soybean photosynthetic capacity under water deficit stress induced by polyethylene glycol (PEG) 6000. We conducted a potting experiment in 2018 using the soybean (Glycine max L. Merrill) cultivar Suinong 26. We identified the impacts of a concentration of PEG 6000 simulating drought (15%, w/v) and an appropriate melatonin concentration (100 μmol/L) on the growth of soybean seedlings and flowering stages in a preliminary test. We applied exogenous melatonin by foliar spraying and root application to determine the effects on leaf photosynthesis during water deficit stress. Our results indicated that 15% PEG 6000 had an obvious inhibitory effect on the growth of soybean seedlings and flowering stages, causing oxidative stress and damage due to reactive oxygen species (ROS) (H2O2 and O2·-) accumulation and potentially reducing air exchange parameters and photosystem II (PSII) efficiency. The application of exogenous melatonin significantly relieved the inhibitory effects of PEG 6000 stress on seedlings and flowering growth, and gas exchange parameters, potentially improved PSII efficiency, improved the leaf area index (LAI) and the accumulation of dry matter, slowed down oxidative stress and damage to leaves by increasing the activity of antioxidant enzymes (SOD, POD, and CAT), reduced the content of malondialdehyde (MDA), and ultimately improved soybean yield. Overall, the results of this study demonstrated that application of exogenous melatonin at the seedlings and flowering stages of soybean is effective in alleviating plant damage caused by water deficit stress and improving the drought resistance of soybean plants. In addition, the results showed that application of exogenous melatonin by root is superior to foliar spraying.

The composition of the gut microbiota can be influenced by dietary composition. In pregnancy, the maternal gut microbiome has associations with maternal and infant metabolic status. There is little known regarding the impact of a vegetarian diet in pregnancy on maternal gut microbiota. This study explored the gut microbiota profile in women who were vegetarian or omnivorous in early gestation. Women were selected from participants in the Study of PRobiotics IN Gestational diabetes (SPRING) randomised controlled trial. Nine women identified as vegetarians were matched to omnivorous women in a 1:2 ratio. Microbiota analyses were performed using 16S rRNA gene amplicon sequencing and analysed using the Quantitative Insights Into Microbial Ecology (QIIME) and Calypso software tools. There was no difference in alpha diversity, but beta diversity was slightly reduced in vegetarians. There were differences seen in the relative abundance of several genera in those on a vegetarian diet, specifically a reduction in Collinsella, Holdemania, and increases in the relative abundances of Roseburia and Lachnospiraceae. In this sub-analysis of gut microbiota from women in early pregnancy, a vegetarian as compared to omnivorous diet, was associated with a different gut microbiome, with features suggesting alterations in fermentation end products from a mixed acid fermentation towards more acetate/butyrate.

A growing body of evidence indicates that dietary polyphenols show protective effects against various cancers. However, little is known yet about their activity in brain tumors. Here we investigated the interaction of dietary flavonoid quercetin (QCT) with the human glioblastoma A172 and LBC3 cell lines. We demonstrated that QCT evoked cytotoxic effect in both tested cell lines. Microscopic observations, Annexin V-FITC/PI staining, and elevated expression and activity of caspase 3/7 showed that QCT caused predominantly apoptotic death of A172 cells. Further analyses confirmed enhanced ROS generation, deregulated expression of SOD1 and SOD2, depletion of ATP levels, and an overexpression of CHOP, suggesting the activation of oxidative stress and ER stress upon QCT exposure. Finally, elevated expression and activity of caspase 9, indicative of a mitochondrial pathway of apoptosis, was detected. Conversely, in LBC3 cells the pro-apoptotic effect was observed only after 24 h incubation with QCT, and a shift towards necrotic cell death was observed after 48 h of treatment. Altogether, our data indicate that exposure to QCT evoked cell death via activation of intrinsic pathway of apoptosis in A172 cells. These findings suggest that QCT is worth further investigation as a potential pharmacological agent in therapy of brain tumors.

BackgroundA new hybrid technique for single-axillary-incision endoscopic-assisted nipple-sparing mastectomy (E-NSM) was introduced. Preliminary results are reported.MethodsPatients who received single-axillary-incision E-NSM from August 2013 to August 2017 were searched from a single institution. Data were analyzed to determine the effectiveness and oncologic safety of single-axillary-incision E-NSM. Patient-oriented cosmetic outcome report was also obtained.ResultsDuring the study period, a total of 50 E-NSM with single-incision procedures were performed in 41 female patients with breast cancer, including 11 (26.8%) patients with bilateral disease. Their mean age was 45.3 ± 8.4 years. The mean size of tumors encountered during the 50 single-incision E-NSM procedures was 2.3 ± 1.8 (0.1–7.3) cm for invasive tumors and 2.6 ± 1.7 (0.2–5.7) cm for carcinoma in situ lesions. Six (12%) of those tumors were multifocal/multicentric. Lymph node metastasis was found during 12% of the procedures. Forty-five (90%) received immediate breast reconstruction with gel implant. Mean operating time was 244.3 ± 82.8 min. The overall complication rate was 6%, and no total nipple necrosis or implant loss was observed. No locoregional recurrence or distant metastasis was found during mean follow-up of 21.6 months. About 94.4% of patients were satisfied with the postoperative scar location and wound length. All patients who responded would choose the same operation again.ConclusionsThe proposed single-axillary-incision endoscopic hybrid technique for nipple-sparing mastectomy was a safe procedure with low morbidity and associated with high patient satisfaction.

BackgroundOne Anastomosis Gastric Bypass–Mini Gastric Bypass (OAGB-MGB) is rapidly gaining popularity and is currently being performed by an increasing number of bariatric surgeons worldwide. However, excessive postoperative weight loss and malnutrition still remain a major concern regarding this procedure. The aim of this observational retrospective study was to investigate whether a tailored biliopancreatic limb (BPL) length relative to small bowel length (SBL) is superior to a fixed BPL length of 200 cm in terms of weight loss results and nutritional deficiencies in morbidly obese patients 1 year following OAGB-MGB.Materials and MethodsSixty-four patients who underwent OAGB-MGB were divided into two consecutive groups depending on the BPL length used: fixed 200-cm BPL and tailored BPL groups. Anthropometric measurements (%EWL, TWL, %TWL) and nutritional parameters (vitamin A, vitamin D3, vitamin B12, serum iron, serum albumin, total protein) were compared between the two groups at 1-year follow-up.ResultsNo statistically significant differences were observed between the patients in two groups in terms of %EWL, TWL, %TWL. The number of patients with deficiencies of vitamin A (p = 0.030), vitamin D3 (p = 0.020), and albumin (p = 0.030) was significantly higher in fixed 200-cm BPL group as compared with tailored BPL group, 1 year following OAGB-MGB. No statistically significant differences were seen between the patients in two groups in terms of vitamin B12, iron, and total protein deficiencies.ConclusionTailoring BPL length by bypassing about 40% of the SBL seems to be safe and effective. According to preliminary results of this study, a tailored BPL length relative to SBL is even likely to be superior to the fixed 200-cm BPL as it is associated with less nutritional deficiencies while providing similar weight loss results. Further randomized studies with larger sample sizes and longer follow-up periods are necessary to confirm the primary results of this study.

PurposeWe present the preliminary results of the STRA-MI-VT Study (NCT04066517), a spontaneous, phase Ib/II study, designed to prospectively test the safety and efficacy of stereotactic body radiotherapy (SBRT) in patientswith advanced cardiac disease and intractable ventricular tachycardia (VT).MethodsCardiac computed tomography (CT) integrated by electroanatomical mapping was used for substrate identification and merged with dedicated CT scans for treatment plan preparation. A single 25-Gy radioablation dose was delivered by a LINAC-based volumetric modulated arc therapy technique in a non-invasive matter. The primary safety endpoint was treatment-related adverse effects during acute and long-term follow-up (FU), obtained by regular in-hospital controls and implantable cardioverter defibrillator (ICD) remote monitoring. The primary efficacy endpoint was the reduction at 3 and 6 months of VT episodes and ICD shocks.ResultsSeven out of eight patients (men; age, 70 ± 7 years; ejection fraction, 27 ± 11%; 3 ischemic, 4 non-ischemic cardiomyopathies) underwent SBRT. At a median 8-month FU, no treatment-related serious adverse event occurred. Three patients died from non-SBRT-related causes. Four patients completed the 6-month FU: the number of VT decreased from 29 ± 33 to 11 ± 9 (p = .05) and 2 ± 2 (p = .08), at 3 and 6 months, respectively; shocks decreased from 11 to 0 and 2, respectively. At 6 months, all patients. showed a significant reduction of VT episodes and no electrical storm recurrence, with the complete regression of iterative VTs in 2/2 patients.ConclusionThe STRA-MI-VT Study suggests that SBRT can be considered an alternative option for the treatment of VT in patients with structural heart disease and highlights the need for further clinical investigation addressing safety and efficacy.