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Τετάρτη 18 Μαΐου 2022

Sparstolonin B inhibits pancreatic adenocarcinoma through the NF-κB signaling pathway

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Publication date: Available online 18 May 2022

Source: Experimental Cell Research

Author(s): Yang Lyu, Bowen Duan, Ziming Liu, Fan Yang, Chen Chen, Xuejiao Jiang, Xiang Liu
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Efficacy and safety of Lenzumestrocel (Neuronata-R® inj.) in patients with amyotrophic lateral sclerosis (ALSUMMIT study): study protocol for a multicentre, randomized, double-blind, parallel-group, sham procedure-controlled, phase III trial

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A single cycle (two repeated treatments) with intrathecal autologous bone marrow-derived mesenchymal stem cells (BM-MSCs, 26-day interval) showed safety and provided therapeutic benefit lasting 6 months in pat...
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High flow nasal cannula in the management of obstructive sleep Apnoea postoperatively. Is flow a new alternative to positive pressure?

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Publication date: Available online 17 May 2022

Source: American Journal of Otolaryngology

Author(s): Abhijit S. Nair, Antonio M. Esquinas
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Magnetic resonance imaging assessment of juvenile idiopathic arthritis using OMERACT and EuroTMjoint classifications

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This retrospective case –control study compared inflammatory and structural damage in the temporomandibular joint of patients with juvenile idiopathic arthritis (JIA) and its subtypes and healthy patients using the Outcome Measures in Rheumatology Clinical Trials (OMERACT) and EuroTMjoint classifications. Correlations be tween the scores of the two classifications and time of diagnosis were evaluated. Twenty-nine JIA patients and 48 age-matched healthy participants were examined. TMJ images on each side were considered individually. (Source: International Journal of Oral and Maxillofacial Surgery)
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Machine Learning Based Forecast of Dengue Fever in Brazilian Cities using Epidemiological and Meteorological Variables

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Abstract
Dengue is a serious public health concern in Brazil and globally. In the absence of a universal vaccine or specific treatments, prevention relies on vector control and disease surveillance. Accurate and early forecasts can help reduce the spread of the disease. In this study, we develop a model to predict monthly dengue cases in Brazilian cities one month ahead from 2007-2019. We compare different machine learning algorithms and feature selection methods using epidemiological and meteorological variables. We find that different models work best in different cities, and a random forests model trained on monthly dengue cases performs best overall. It produces lower errors than a seasonal naïve baseline model, gradient boosting regression, feed-forward neural network, and support vector regression. For each city, we compute the mean absolute error between predictions and true monthly dengue cases on the test set. For the median city, the error is 1 2.2 cases. This error is reduced to 11.9 when selecting the optimal combination of algorithm and input features for each city individually. Machine learning and especially decision tree ensemble models may contribute to dengue surveillance in Brazil, as they produce low out-of-sample prediction errors for a geographically diverse set of cities.
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Τρίτη 17 Μαΐου 2022

Oral swabs tested with Xpert MTB/RIF Ultra for diagnosis of pulmonary tuberculosis in children: a diagnostic accuracy study

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Abstract
Background
Microbiological diagnosis of childhood tuberculosis may be difficult. Oral swabs are a potential non-invasive alternative to sputum for diagnosis.
Methods
A prospective diagnostic accuracy study of oral swabs (buccal and tongue) for pulmonary tuberculosis (PTB) diagnosis in children (aged ≤15 years) in two South African hospital sites. Children with cough of any duration and either: a positive tuberculin skin test, TB contact, loss of weight or chest X-ray suggestive of PTB were enrolled. Two induced sputum specimens were tested with Xpert MTB/RIF (or Ultra) and liquid culture. Oral swabs were taken preceding sputum, frozen and later tested with Xpert MTB/RIF Ultra. Children were classified as microbiologically confirmed TB, Unconfirmed TB (received TB treatment) or unlikely TB according to NIH consensus definitions based on sputum microbiological results.
Results
Among 291 participants (median age 32 [IQR 14-73] months), 57 (20%) were living with HIV and 87 (30%) were malnourished. 90 (31%) had confirmed PTB (six (7%) with rifampicin-resistant TB), 157 (54%) unconfirmed PTB and 44 (15%) unlikely TB. One oral swab was obtained from 126 (43%) participants (96 tongue, 30 buccal) and two swabs from 165 (57%) (110 tongue, 55 buccal). Sensitivity was low; 22% (95% CI 15-32) for all swabs combined (confirmed PTB as reference), but specificity was high (100%, 95% CI 91-100). The highest sensitivity was 33% (15-58) among participants living with HIV. Overall yield was 6.9% with one oral swab, and 7.2% with two.
Conclusions
Ultra on oral swabs provides poor yield for microbiologic PTB confirmation in children.
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Similar long-term swallowing outcomes for accelerated, mildly-hypofractionated radiotherapy compared to conventional fractionation in oropharynx cancer: a multi-centre study

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Publication date: Available online 17 May 2022

Source: Radiotherapy and Oncology

Author(s): J.M. Price, C.M. West, L.M. Dixon, Z. Iyizoba-Ebozue, K. Garcez, L. Lee, A. McPartlin, F. Slevin, A. Sykes, R.J.D. Prestwich, D.J. Thomson
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The Conventional Technique Versus the No-touch Isolation Technique for Primary Tumor Resection in Patients With Colon Cancer (JCOG1006): A Multicenter, Open-label, Randomized, Phase III Trial

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imageObjective: This phase III trial evaluated whether the no touch was superior to the conventional in patients with cT3/T4 colon cancer. Background: No touch involves ligating blood vessels that feed the primary tumor to limit cancer cell spreading. However, previous studies did not confirm the efficacy of the no touch. Methods: This open-label, randomized, phase III trial was conducted at 30 Japanese centers. The eligibility criteria were histologically proven colon cancer; clinical classification of T3–4, N0–2, andM0; and patients aged 20 to 80years. Patients were randomized (1:1) to undergo open surgery with conventional or the no touch. Patients with pathological stage III disease received adjuvant capecitabine chemotherapy. The primary endpoint was disease-free survival (DFS) according to the intention-to-treat principle. Results: Between January 2011 and November 2015, 853 patients were randomized to the conventional group (427 patients) or the no touch group (426 patients). The 3-year DFS were 77.3% [95% confidence interval (CI) 73.1%–81.0%] and 76.2% (95% CI 71.9%–80.0%) in the conventional and no touch groups, respectively. The superiority of no touch was not confirmed: hazard ratio for DFS = 1.029 (95% CI 0.800– 1.324; 1-sided P = 0.59). Operative morbidity was observed in 31 of 427 conventional patients (7%) and 26 of 426 no touch patients (6%). All grade adverse events were similar between the conventional and no touch groups. No in-hospital mortality occurred in either group. Conclusion: The present study failed to confirm the superiority of the no touch.
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Δευτέρα 16 Μαΐου 2022

ORF8 protein of SARS‐CoV‐2 reduces male fertility in mice

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Abstract

As one of the most rapidly evolving proteins of the genus Betacoronavirus, ORF8's function and potential pathological consequence in vivo are still obscure. In this study, we show that the secretion of ORF8 is dependent on its N-terminal signal peptide sequence and can be inhibited by ROS scavenger and ER-Golgi transportation inhibitor in cultured cells. To trace the effect of its possible in vivo secretion，we examined the plasma samples of COVID-19 convalescent patients and found that the patients aged 40 to 60 had higher antibody titers than those under 40. To explore ORF8's in vivo function, we administered the mice with ORF8 via tail-vein injection to simulate the circulating ORF8 in the patient. Although no apparent difference in body weight, food intake, and vitality was detected between vehicle- and ORF8-treated mice, the latter displayed morphological abnormalities of testes and epididymides, as indicated by the loss of the central ductal lumen accompanied by a decreased fertility in five-week-old male mice. Furthermore, the analysis of gene expression in the testes between vehicle- and ORF8-treated mice identified a decreased expression of Col1a1, the loss of which is known to be associated with mice's infertility. Although whether our observation in mice could be translated to humans remains unclear, our study provides a potential mouse model that can be used to investigate the impact of SARS-CoV-2 infection on the human reproductive system.

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In silico analysis of mutations near S1/S2 cleavage site in SARS‐CoV‐2 spike protein reveals increased propensity of glycosylation in Omicron strain

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Abstract

Cleavage of the Severe Respiratory Syndrome Coronavirus–2 (SARS-CoV-2) spike protein has been demonstrated to contribute to viral-cell fusion and syncytia formation. Studies have shown that variants of concern (VOC) and variants of interest (VOI) show differing membrane fusion capacity. Mutations near cleavage motifs, such as the S1/S2 and S2' sites, may alter interactions with host proteases and, thus, the potential for fusion. The biochemical basis for the differences in interactions with host proteases for the VOC/VOI spike proteins has not yet been explored. Using sequence and structure-based bioinformatics, mutations near the VOC/VOI spike protein cleavage sites were inspected for their structural effects. All mutations found at the S1/S2 sites were predicted to increase affinity to the furin protease but not TMPRSS2. Mutations at the spike residue P681 in several strains, such P681R in the Delta strain, resulted in the disruption of a proline-directe d kinase phosphorylation motif at the S1/S2 site, which may lessen the impact of phosphorylation for these variants. However, the unique N679K mutation in the Omicron strain was found to increase the propensity for O-linked glycosylation at the S1/S2 cleavage site, which may prevent recognition by proteases. Such glycosylation in the Omicron strain may hinder entry at the cell surface and, thus, decrease syncytia formation and induce cell entry through the endocytic pathway as has been shown in previous studies. Further experimental work is needed to confirm the effect of mutations and post-translational modifications on SARS-CoV-2 spike protein cleavage sites.

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