Explore the vast range of titles available.

Background: The spike D614G substitution became globally dominant early in the COVID-19 pandemic, and reversion to ancestral D614 is expected to be rare once D614G is fixed. SARS-CoV-2 sequences lacking D614G detected later raise questions about the origin of these reversions. Methods: We analyzed spike protein amino-acid sequences from 22 SARS-CoV-2 Variants of Concern (VOCs) deposited in the NCBI GenBank database, screening for sequences carrying ancestral D614 and comparing their distributions across VOCs. Results: D614 reversions (reverse mutations of D614G) were not evenly distributed across VOCs but were strongly enriched in Delta (B.1.617.2) and Omicron BA.2, reaching levels statistically inconsistent with other VOCs. In both lineages, D614-containing sequences showed limited mutational diversity and pronounced geographic clustering within specific U.S. regions. Conclusions: These non-random patterns are difficult to reconcile with spontaneous reverse mutation arising and spreading through typical community transmission and are more consistent with localized reintroduction of an older genetic background. Further investigation is warranted to assess whether laboratory-associated events could be involved.

[This corrects the article DOI: 10.1371/journal.pone.0289368.].

This paper introduces an innovative approach to integral volumetric imaging employing time and polarization multiplexing techniques to present volumetric three-dimensional images. Traditional integral volumetric imaging systems with a coarse lens array often face moiré pattern issues stemming from layered panel structures. In response, our proposed system utilizes a combination of time and polarization multiplexing to achieve two focal planes using a single display panel.

The odours encountered on a daily basis are dependent on an individual’s society and culture. Therefore, when conducting olfactory tests, the odour stimuli utilized must be appropriate for the individual’s environment. In this study, we gathered and classified the odours experienced by Japanese individuals in their daily lives through a large dataset of product reviews encompassing food and household items. Specifically, we performed morphological analysis on product review sentences in Japanese that contained odour descriptions, and we compiled the nouns used to describe odours. A total of 617,208 sentences that reviewed odour experiences and their corresponding nouns were collected. The top 100 frequently used odour nouns were classified into 15 clusters according to the context in which they were used. The methodology employed in collecting and classifying odour nouns as presented in this study can be utilized in other situations. It can assist in selecting appropriate odour stimuli for the olfactory test based on the society, culture, and time period.

While post-chemotherapy retroperitoneal lymph node dissection (PC-RPLND) benefits patients with teratoma or viable germ cell tumors (GCT), it becomes overtreatment if necrosis is detected in PC-RPLND specimens. Serum microRNA-371a-3p correctly predicts residual viable GCT with 100% sensitivity; however, prediction of residual teratoma in PC-RPLND specimens using current modalities remains difficult. Therefore, we developed a machine learning model using CT imaging and clinical variables to predict the presence of residual teratoma in PC-RPLND specimens. This study included 58 patients who underwent PC-RPLND between 2005 and 2019 at the University of Tsukuba Hospital. On CT imaging, 155 lymph nodes were identified as regions of interest (ROIs). The ResNet50 algorithm and/or Support Vector Machine (SVM) classification were applied and a nested, 3-fold cross-validation protocol was used to determine classifier accuracy. PC-RPLND specimen analysis revealed 35 patients with necrosis and 23 patients with residual teratoma, while histology of 155 total ROIs showed necrosis in 84 ROIs and teratoma in 71 ROIs. The ResNet50 algorithm, using CT imaging, achieved a diagnostic accuracy of 80.0%, corresponding to a sensitivity of 67.3%, a specificity of 90.5%, and an AUC of 0.84, whereas SVM classification using clinical variables achieved a diagnostic accuracy of 74.8%, corresponding to a sensitivity of 59.0%, a specificity of 88.1%, and an AUC of 0.84. Our machine learning models reliably distinguish between necrosis and residual teratoma in clinical PC-RPLND specimens.

The incidence of ocular candidiasis (OC) in patients with candidemia varies across different reports, and the issue of whether routine ophthalmoscopy improves outcomes has been raised. This study investigated the incidence of OC and evaluate whether the extent of OC impacts the clinical outcomes. This retrospective study included non-neutropenic patients with candidemia who underwent treatment at one of 15 medical centers between 2010 and 2016. Chorioretinitis without other possible causes for the ocular lesions and endophthalmitis was classified as a probable OC. If signs of chorioretinitis were observed in patients with a systemic disease that causes similar ocular lesions, they were classified as a possible OC. In total, 781 of 1089 patients with candidemia underwent an ophthalmic examination. The prevalence of OC was 19.5%. The time from the collection of a positive blood culture to the initial ophthalmic examination was 5.0 ± 3.9 days in patients with OC. The leading isolate was Candida albicans (77.9%). Possible OC was associated with unsuccessful treatments (resolution of ocular findings) (odds ratio: 0.354, 95% confidence interval: 0.141-0.887), indicating an overdiagnosis in patients with a possible OC. If these patients were excluded, the incidence fell to 12.8%. Endophthalmitis and/or macular involvement, both of which require aggressive therapy, were detected in 43.1% of patients; a significantly higher incidence of visual symptoms was observed in these patients. Even when early routine ophthalmic examinations were performed, a high incidence of advanced ocular lesions was observed. These results suggest that routine ophthalmic examinations are still warranted in patients with candidemia.

Objectives The aim of this trial is to evaluate the antiviral efficacy, clinical efficacy, and safety of nelfinavir in patients with asymptomatic and mild COVID-19. Trial design The study is designed as a multicenter, open-label, blinded outcome assessment, parallel group, investigator-initiated, exploratory, randomized (1:1 ratio) controlled clinical trial. Participants Asymptomatic and mild COVID-19 patients will be enrolled in 10 university and teaching hospitals in Japan. The inclusion and exclusion criteria are as follows: Inclusion criteria: Japanese male or female patients aged ≥ 20 years SARS-CoV-2 detected from a respiratory tract specimen (e.g., nasopharyngeal swab or saliva) using PCR, LAMP, or an antigen test within 3 days before obtaining the informed consent Provide informed consent Exclusion criteria: Symptoms developed ≥ 8 days prior to enrolment SpO 2 < 96 % (room air) Any of the following screening criteria: ALT or AST ≥ 5 × upper limit of the reference range Child-Pugh class B or C Serum creatinine ≥ 2 × upper limit of the reference range and creatinine clearance < 30 mL/min Poorly controlled diabetes (random blood glucose ≥ 200 mg/dL or HbA1c ≥ 7.0%, despite treatment) Unsuitable serious complications based on the assessment of either the principal investigator or the sub-investigator Hemophiliac or patients with a marked hemorrhagic tendency Severe diarrhea Hypersensitivity to the investigational drug Breastfeeding or pregnancy With childbearing potential and rejecting contraceptive methods during the study period from the initial administration of the investigational drug Receiving rifampicin within the previous 2 weeks Participated in other clinical trials and received drugs within the previous 12 weeks Undergoing treatment for HIV infection History of SARS-CoV-2 vaccination or wishes to be vaccinated against SARS-CoV-2 Deemed inappropriate (for miscellaneous reasons) based on the assessment of either the principal investigator or the sub-investigator Intervention and comparator Patients who meet the inclusion criteria and do not meet any of the exclusion criteria will be randomized to either the nelfinavir group or the symptomatic treatment group. The nelfinavir group will be administered 750 mg of nelfinavir orally, three times daily for 14 days (treatment period). However, if a participant tests negative on two consecutive PCR tests of saliva samples, administration of the investigational drug for that participant can be discontinued at the discretion of the investigators. The symptomatic treatment group will not be administered the investigational drug, but all other study procedures and conditions will be the same for both groups for the duration of the treatment period. After the treatment period of 14 days, each group will be followed up for 14 days (observational period). Main outcomes The primary endpoint is the time to negative conversion of SARS-CoV-2. During the study period from Day 1 to Day 28, two consecutive negative PCR results of saliva samples will be considered as the negative conversion of the virus. The secondary efficacy endpoints are as follows: For patients with both asymptomatic and mild disease: area under the curve of viral load, half decay period of viral load, body temperature at each time point, all-cause mortality, incidence rate of pneumonia, percentage of patients with newly developed pneumonia, rate of oxygen administration, and the percentage of patients who require oxygen administration. For asymptomatic patients: incidence of symptomatic COVID-19, incidence of fever (≥ 37.0 °C for two consecutive days), incidence of cough For patients with mild disease: incidence of defervescence (< 37.0 °C), incidence of recovery from clinical symptoms, incidence of improvement of each symptom The secondary safety endpoints are adverse events and clinical examinations. Randomization Patients will be randomized to either the nelfinavir group or the symptomatic treatment group using the electric data capture system (1:1 ratio, dynamic allocation based on severity [asymptomatic], and age [< 60 years]). Blinding (masking) Only the assessors of the primary outcome will be blinded (blinded outcome assessment). Numbers to be randomized (sample size) The sample size was determined based on our power analysis to reject the null hypothesis, S (t | z =1) = S (t | z = 0) where S is a survival function, t is time to negative conversion, and z denotes randomization group, by the log-rank test with a two-sided p value of 0.05. We estimated viral dynamic parameters by fitting a nonlinear mixed-effects model to reported viral load data, and simulated our primary endpoint from viral-load time-courses that were realized from sets of viral dynamics parameters sampled from the estimated probability distribution of the parameters (sample size: 2000; 1000 each for randomization group). From this estimation of the hazard ratio between the randomization groups for the event of negative conversion using this simulation dataset, the required number of events for rejecting our null hypothesis with a power of 0.80 felled 97.345 by plugging the estimated hazard ratio, 1.79, in Freedman’s equation. Therefore, we decided the required number of randomizations to be 120 after consideration of the frequency of censoring and the anticipated rate of withdrawal caused by factors such as withdrawal of consent. Trial Status Protocol version 6.0 of February 12, 2021. Recruitment started on July 22, 2020 and is anticipated to be completed by March 31, 2022. Trial registration This trial was registered in Japan Registry of Clinical Trials (jRCT) ( jRCT2071200023 ) on 21 July 21, 2020. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1 ). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2 ).

Abstract Background A bedside scoring system to assess the severity of disease is lacking for candidaemia. The Pitt candidaemia score (PCS) was evaluated for its association with mortality. Methods The PCS consists of five components, namely dialysis, hypotension, mechanical ventilation, cardiac arrest and mental status. Patients were classified into four categories according to their PCS. The correlation between PCS category at blood culture collection and 30 day mortality was studied individually for five Candida species. Results Leading rates of mortality were observed in Candida tropicalis and Candida krusei. The interval from inoculation to positive culture was 19.4 ± 9.7 h for C. tropicalis and 21.3 ± 5.6 h for C. krusei; these intervals were significantly shorter than those for other Candida species. In a Kaplan–Meier survival curve, a significant risk stratification by PCS category was demonstrated in all Candida species. A high PCS was an independent risk factor for mortality, and source control decreased the risk for C. tropicalis and Candida glabrata infections. Regarding antifungal therapy, the median PCS was 8 for liposomal amphotericin B, 2 for echinocandins and 0 for azoles, and this trend was consistent among four Candida species. Conclusions The mortality rate was well stratified by the PCS, and the PCS affected the selection of antifungals. A future prospective study is required for the PCS in guiding therapy for candidaemia.

Background We previously developed management bundles for candidemia and beneficial effects on clinical outcomes were shown in compliant patients (JAC 2015). However, there is a risk for bias because some elements cannot be achieved in patients who have an early death. Methods Patients with candidemia who were treated at six medical centers between 2015 and 2017 were prospectively evaluated. Bundle elements consisted of removal of central venous catheters within 24 hours, initial appropriate selection and dosing of antifungals, an ophthalmological examination, follow-up blood cultures, consideration of alternative antifungals on the 3rd to 5th days, and at least 2 weeks of therapy. To exclude bias by early death, we investigated the clinical results in patients who survived ≥2 weeks. Results Among 221 patients with candidemia, 190 patients were analyzed (31 patients were excluded because of early death). Clinical success and the 28-day mortality rate were 77.4% (171/221) and 22.2% (49/221) in all patients with candidemia and 88.9% (167/190) and 9.5% (18/190) in eligible patients, respectively. Compliance in achieving all bundle elements was accomplished in 67.9% of eligible patients. In multivariate analysis, compliance with the bundles was an independent factor for 28-day mortality (4.7% vs. 19.7%, odds ratio 0.19, 95% confidence interval 0.05–0.63). However, compliance did not affect clinical success (92.2% vs. 82.0%, odds ratio 2.13, 95% CI 0.77–5.86). Non-Candida albicans, disseminated candidiasis, and total parenteral nutrition were independent factors for poor clinical success. Severe severity and total parenteral nutrition were independent factors for 28-day mortality. Conclusion With prospective use of bundles as a checklist in patients with candidemia, compliance of bundles has a beneficial effect on clinical outcomes. This research was supported by AMED (JP18fk0108045). Disclosures All authors: No reported disclosures.