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1.
Front Plant Sci ; 15: 1398762, 2024.
Article in English | MEDLINE | ID: mdl-39145192

ABSTRACT

Rice is a staple crop in Asia, with more than 400 million tons consumed annually worldwide. The protein content of rice is a major determinant of its unique structural, physical, and nutritional properties. Chemical analysis, a traditional method for measuring rice's protein content, demands considerable manpower, time, and costs, including preprocessing such as removing the rice husk. Therefore, of the technology is needed to rapidly and nondestructively measure the protein content of paddy rice during harvest and storage stages. In this study, the nondestructive technique for predicting the protein content of rice with husks (paddy rice) was developed using near-infrared spectroscopy and deep learning techniques. The protein content prediction model based on partial least square regression, support vector regression, and deep neural network (DNN) were developed using the near-infrared spectrum in the range of 950 to 2200 nm. 1800 spectra of the paddy rice and 1200 spectra from the brown rice were obtained, and these were used for model development and performance evaluation of the developed model. Various spectral preprocessing techniques was applied. The DNN model showed the best results among three types of rice protein content prediction models. The optimal DNN model for paddy rice was the model with first-order derivative preprocessing and the accuracy was a coefficient of determination for prediction, Rp 2 = 0.972 and root mean squared error for prediction, RMSEP = 0.048%. The optimal DNN model for brown rice was the model applied first-order derivative preprocessing with Rp 2 = 0.987 and RMSEP = 0.033%. These results demonstrate the commercial feasibility of using near-infrared spectroscopy for the non-destructive prediction of protein content in both husked rice seeds and paddy rice.

2.
Neuro Oncol ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38975694

ABSTRACT

BACKGROUND: The MEK inhibitor, selumetinib, reduces plexiform neurofibroma (PN) in pediatric patients with neurofibromatosis type 1 (NF1). Its safety and efficacy in adults with PN and effectiveness in other NF1manifestations (e.g., neurocognitive function, growth reduction, and café-au-lait spots) are unknown. METHODS: This open-label, phase 2 trial enrolled 90 pediatric or adult NF1 patients with inoperable, symptomatic, or potentially morbid, measurable PN (≥ 3 cm). Selumetinib was administered at doses of 20 or 25 mg/m2 or 50 mg q 12 hrs for 2 years. Pharmacokinetics, PN volume, growth parameters, neurocognitive function, café-au-lait spots, and quality of life (QoL) were evaluated. RESULTS: Fifty-nine children and 30 adults (median age, 16 years; range, 3-47) received an average of 22±5 (4-26) cycles of selumetinib. Eighty-eight (98.9%) out of 89 per-protocol patients showed volume reduction in the target PN (median, 40.8%; 4.2%-92.2%), and 81 (91%) patients showed partial response (≥ 20% volume reduction). The response lasted until cycle 26. Scores of neurocognitive functions (verbal comprehension, perceptual reasoning, processing speed, and full-scale IQ) significantly improved in both pediatric and adult patients (P <0.05). Prepubertal patients showed increases in height score and growth velocity (P <0.05). Café-au-lait spot intensity decreased significantly (P <0.05). Improvements in QoL and pain scores were observed in both children and adults. All adverse events were CTCAE grade 1 or 2 and were successfully managed without drug discontinuation. CONCLUSION: Selumetinib decrease PN volume in the majority of pediatric and adult NF1 patients while also showing efficacy in non-malignant diverse NF1 manifestations.

3.
Front Immunol ; 15: 1359209, 2024.
Article in English | MEDLINE | ID: mdl-39040104

ABSTRACT

Introduction: Although the safety and effectiveness of COVID-19 vaccination during pregnancy have been proven, there is still little data explaining neonatal outcomes of maternal pre-pregnancy vaccination. Methods: Here, we investigated the impact of vaccination and SARS-CoV-2 infection on maternal-neonate immune response in a cohort study involving 141 pregnant individuals, and defined the importance of maternal COVID-19 vaccination timing for its effectiveness. Results and discussion: Our data indicate that vertically transferred maternal hybrid immunity provides significantly better antiviral protection for a neonate than either maternal post-infection or post-vaccination immunity alone. Higher neutralization potency among mothers immunized before pregnancy and their newborns highlights the promising role of pre-pregnancy vaccination in neonatal protection. A comparison of neutralizing antibody titers calculated for each dyad suggests that infection and pre-/during-pregnancy vaccination all support transplacental transfer, providing the offspring with strong passive immunity against SARS-CoV-2. Analysis of neutralizing antibody levels in maternal sera collected during pregnancy and later during delivery shows that immunization may exert a positive effect on maternal protection.


Subject(s)
Antibodies, Neutralizing , Antibodies, Viral , COVID-19 Vaccines , COVID-19 , Immunity, Maternally-Acquired , Pregnancy Complications, Infectious , SARS-CoV-2 , Vaccination , Humans , Female , Pregnancy , COVID-19/prevention & control , COVID-19/immunology , COVID-19 Vaccines/immunology , COVID-19 Vaccines/administration & dosage , Infant, Newborn , SARS-CoV-2/immunology , Antibodies, Neutralizing/blood , Antibodies, Neutralizing/immunology , Antibodies, Viral/blood , Antibodies, Viral/immunology , Vaccination/methods , Adult , Cohort Studies , Pregnancy Complications, Infectious/prevention & control , Pregnancy Complications, Infectious/immunology
4.
Transplant Proc ; 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-39025730

ABSTRACT

INTRODUCTION: Hepatic encephalopathy (HE) is a frequent complication of cirrhosis, leading to preventable hospitalizations and increased mortality. Despite the availability of validated neuro-psychometric tests to diagnose HE, only 10% of clinicians regularly screen for HE due to lack of time, equipment, and trained personnel. MATERIALS AND METHODS: We studied the association between patient-reported cognitive function and the National Institutes of Health Toolbox Cognition Battery (a validated measure of HE) in patients with cirrhosis. A single-center prospective study of adult patients undergoing liver transplantation evaluation was performed from 10/2020 to 12/2021. Cognition was assessed using the National Institutes of Health Toolbox Cognition Battery and a brief Patient-Reported Outcomes Measurement Information System (PROMIS) survey. RESULTS: Twenty-three liver transplantation candidates were enrolled; the mean age was 56.4 (±9.7) years, 39% were female and the most common etiologies of cirrhosis were primary biliary cirrhosis/primary sclerosing cholangitis/overlap syndrome (30%), hepatitis C (22%) and alcohol-associated liver disease (22%). The mean MELD-Na was 14.9 (±6.4). The mean PROMIS Cognitive Function T-score (PROMISCF) was 49.2 (±9.6). The mean T-scores for the List Sort Working Memory test, Flanker Inhibitory Control and Attention test, and Pattern Comparison Processing Speed test were 46.4 (±9.9), 37.8 (±6.2), and 50.22 (±16.4), respectively. PROMISCF correlated with the List Sort Working Memory test (r = 0.45, P = .03). The mean hospitalization rate was 1.6 days admitted per month. On adjusted multivariate analysis, PROMISCF predicted total hospitalization days (P < .001), hospital admissions (P = .01), and hospitalization rate (P < .001). CONCLUSIONS: A brief survey can screen for HE and predict hospitalizations in patients with cirrhosis.

5.
Int J Mol Sci ; 25(13)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-39000173

ABSTRACT

Tagetes erecta Linn. (TE) is traditionally used to treat cardiovascular, renal, and gastrointestinal diseases. In this study, we investigated the active compounds and targets of TE extract that may exert antiviral effects against influenza A. Active compounds and targets of TE extract were identified using the Traditional Chinese Medicine Systems Pharmacology database (TCSMP). The influenza A-related gene set was screened using GeneCards and the Kyoto Encyclopedia of Genes and Genomes (KEGG). A protein-protein interaction (PPI) network was built to establish the hub targets. Pathway and target studies were conducted using Gene Expression Omnibus (GEO). The interactions between active compounds and potential targets were assessed by molecular docking. An in vitro study was performed using antiviral and plaque reduction assays. From the compound and target search, we identified 6 active compounds and 95 potential targets. We retrieved 887 influenza-associated target genes and determined 14 intersecting core targets between TE and influenza. After constructing a compound-target network, we discovered lutein and beta-carotene to be the key compounds. Next, PPI network analysis identified the top three hub genes associated with influenza (IL-6, HIF1A, and IL-1ß). Similarly, GEO analysis revealed IL-6, TGFB1, and CXCL8 to be the top three target genes. In our docking study, we identified that lutein and IL-6 had the strongest bindings. Our in vitro experimental results revealed that the TE extract exhibited therapeutic rather than prophylactic effects on influenza disease. We identified lutein as a main active compound in TE extract, and IL-6 as an important target associated with influenza, by using data mining and bioinformatics. Our in vitro findings indicated that TE extract exerted protective properties against the influenza A virus. We speculated that lutein, as a key active component in TE extract, is largely responsible for its antiviral effects. Therefore, we suggest TE extract as an alternative in the treatment of influenza.


Subject(s)
Antiviral Agents , Computational Biology , Molecular Docking Simulation , Plant Extracts , Protein Interaction Maps , Tagetes , Antiviral Agents/pharmacology , Antiviral Agents/chemistry , Plant Extracts/pharmacology , Plant Extracts/chemistry , Computational Biology/methods , Protein Interaction Maps/drug effects , Humans , Tagetes/chemistry , Influenza A virus/drug effects , Influenza A virus/genetics , Influenza, Human/drug therapy , Influenza, Human/virology , Animals , Madin Darby Canine Kidney Cells , Dogs , Medicine, Chinese Traditional/methods
7.
Article in English | MEDLINE | ID: mdl-38860754

ABSTRACT

OBJECTIVE: Patient-reported outcome measures, while valuable, may not correlate with diagnostic test results. To better understand this potential discrepancy, our objective was to determine whether psychological health is an effect modifier of the association between patient-reported allergy outcome scores and allergy test results. STUDY DESIGN: Prospective outcomes study. SETTING: Tertiary care hospital and community-based clinic. METHODS: This study included 600 patients at least 18 years of age who presented for symptoms related to allergic rhinitis and completed the related sinonasal outcome test (SNOT), which includes validated nasal, allergy, and psychological domains. Stratified analyses of odds ratios and Spearman correlation coefficients were utilized to assess for effect modification by psychological status. RESULTS: Worse patient-reported allergic rhinitis symptoms were significantly associated with positive allergy test results (odds ratio [OR] 1.69, 95% confidence interval [CI] 1.22-2.34, P = .002) in patients with better psychological health. In contrast, there was no association in patients with worse psychological health (OR 1.06, 95% CI 0.36-3.10, P = .92). These findings were corroborated by assessments of correlation: allergy domain scores were positively correlated with allergy testing scores (Spearman rho 0.18, 95% CI 0.10-0.25, P < .001) in patients with better psychological health, while there was no correlation in patients with worse psychological health (-0.02, 95% CI -0.16-0.12, P = .77). CONCLUSIONS: Psychological status was an effect modifier of the association between allergy domain and allergy testing data. When assessing the relationship between subjective measures, such as sinonasal validated instruments, and objective measures, such as allergy test results, accounting for effect modifiers such as psychological state can provide clinical and research-related insights.

8.
Epilepsia ; 65(8): e148-e155, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38837761

ABSTRACT

In response to the evolving treatment landscape for new-onset refractory status epilepticus (NORSE) and the publication of consensus recommendations in 2022, we conducted a comparative analysis of NORSE management over time. Seventy-seven patients were enrolled by 32 centers, from July 2016 to August 2023, in the NORSE/FIRES biorepository at Yale. Immunotherapy was administered to 88% of patients after a median of 3 days, with 52% receiving second-line immunotherapy after a median of 12 days (anakinra 29%, rituximab 25%, and tocilizumab 19%). There was an increase in the use of second-line immunotherapies (odds ratio [OR] = 1.4, 95% CI = 1.1-1.8) and ketogenic diet (OR = 1.8, 95% CI = 1.3-2.6) over time. Specifically, patients from 2022 to 2023 more frequently received second-line immunotherapy (69% vs 40%; OR = 3.3; 95% CI = 1.3-8.9)-particularly anakinra (50% vs 13%; OR = 6.5; 95% CI = 2.3-21.0), and the ketogenic diet (OR = 6.8; 95% CI = 2.5-20.1)-than those before 2022. Among the 27 patients who received anakinra and/or tocilizumab, earlier administration after status epilepticus onset correlated with a shorter duration of status epilepticus (ρ = .519, p = .005). Our findings indicate an evolution in NORSE management, emphasizing the increasing use of second-line immunotherapies and the ketogenic diet. Future research will clarify the impact of these treatments and their timing on patient outcomes.


Subject(s)
Diet, Ketogenic , Immunotherapy , Status Epilepticus , Humans , Status Epilepticus/therapy , Status Epilepticus/drug therapy , Male , Female , Diet, Ketogenic/methods , Immunotherapy/methods , Immunotherapy/trends , Adolescent , Adult , Drug Resistant Epilepsy/therapy , Drug Resistant Epilepsy/diet therapy , Child , Antibodies, Monoclonal, Humanized/therapeutic use , Middle Aged , Child, Preschool , Anticonvulsants/therapeutic use , Young Adult , Rituximab/therapeutic use , Disease Management
9.
J Clin Monit Comput ; 2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38896344

ABSTRACT

Hand hygiene among anesthesia personnel is important to prevent hospital-acquired infections in operating rooms; however, an efficient monitoring system remains elusive. In this study, we leverage a deep learning approach based on operating room videos to detect alcohol-based hand hygiene actions of anesthesia providers. Videos were collected over a period of four months from November, 2018 to February, 2019, at a single operating room. Additional data was simulated and added to it. The proposed algorithm utilized a two-dimensional (2D) and three-dimensional (3D) convolutional neural networks (CNNs), sequentially. First, multi-person of the anesthesia personnel appearing in the target OR video were detected per image frame using the pre-trained 2D CNNs. Following this, each image frame detection of multi-person was linked and transmitted to a 3D CNNs to classify hand hygiene action. Optical flow was calculated and utilized as an additional input modality. Accuracy, sensitivity and specificity were evaluated hand hygiene detection. Evaluations of the binary classification of hand-hygiene actions revealed an accuracy of 0.88, a sensitivity of 0.78, a specificity of 0.93, and an area under the operating curve (AUC) of 0.91. A 3D CNN-based algorithm was developed for the detection of hand hygiene action. The deep learning approach has the potential to be applied in practical clinical scenarios providing continuous surveillance in a cost-effective way.

10.
Pediatr Neurol ; 156: 17-25, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38692086

ABSTRACT

BACKGROUND: The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to be more infectious and less severe than the other variants. Despite the increasing number of symptomatic patients, severe neurological complications in children with the Omicron variant have been reported rarely, unlike with wild-type or Delta variants. This study aimed to investigate severe neurological complications in children with Omicron variant infection. METHODS: We conducted a retrospective study of 17 pediatric patients with severe neurological manifestations associated with coronavirus disease 2019 in Korea during the Omicron variant prevalence, from January 1 to April 30, 2022. RESULTS: Among the 17 patients, 11 had pre-existing neurological disabilities and nine met the criteria for multisystem inflammatory syndrome in children (MIS-C). Four of the five vaccine-eligible patients (12 years and older) were unvaccinated. Severe neurological manifestations included acute necrotizing encephalopathy, acute fulminant cerebral edema, acute disseminated encephalomyelitis, basal ganglia encephalitis, unclassified severe encephalopathy/encephalitis, and refractory status dystonicus. Patients with MIS-C and underlying neurological disabilities had longer median hospital and intensive care unit stays compared with those without these conditions. Five patients survived with new neurological deficits at the one-year follow-up, and three died, all of whom had underlying neurological disabilities. CONCLUSIONS: This study shows that severe neurological complications in pediatric patients with the Omicron variant of SARS-CoV-2 occur infrequently but may lead to significant morbidity and mortality, especially among those with pre-existing neurological disabilities and unvaccinated individuals. Continued efforts are necessary to prevent and manage such complications in these vulnerable populations.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , COVID-19/complications , Male , Female , Child , Retrospective Studies , Child, Preschool , Adolescent , Republic of Korea , Infant , Nervous System Diseases/etiology , Systemic Inflammatory Response Syndrome
11.
JAMA Otolaryngol Head Neck Surg ; 150(7): 537-544, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38722618

ABSTRACT

Importance: Although patient-reported outcomes provide valuable insights, these subjective data may not align with objective test results. Hearing loss is a pervasive problem, such that concordance between subjective perceptions of hearing ability and objective audiogram assessments would be beneficial. Objectives: To determine (1) whether psychological status is an effect modifier of the association between subjective patient reports of hearing ability and objective audiometry results, and (2) whether any effect modification observed in standard static questionnaires would be either mitigated or exacerbated by adaptive testing based on Item Response Theory analyses. Design, Setting, and Participants: This diagnostic study at a tertiary care center and community-based practice included consecutive adults who presented with queries related to hearing loss. Participants were recruited and enrolled and data analyses occurred from 2022 to 2024. Exposures: Participants prospectively reported their hearing-specific abilities through either a standard static or adaptive version of the Inner Effectiveness of Auditory Rehabilitation (EAR) scale, alongside validated measures of their mental health and audiometry. Word recognition scores (WRS) and pure tone averages (PTA) were used to analyze audiometric testing. Main Outcomes and Measures: The association between subjective Inner EAR results and audiometry was evaluated. Stratified analyses were used to assess for effect modification by psychological status. The results of standard static and adaptive testing were compared. Results: In this study of 395 patients (mean [range] age, 55.9 [18-89] years; 210 [53.2%] female), standard static Inner EAR mean scores were appropriately higher in patients with higher (better) WRS (50.7, 95% CI, 46.4-54.9), compared with patients with lower (worse) WRS (34.7, 95% CI, 24.3-45.1). However, among patients with worse mental health, there was no association between standard static Inner EAR scores and WRS. In contrast, adaptive Inner EAR mean scores were significantly higher for those with better WRS, regardless of mental health status. Thus, effect modification was observed in standard static assessments, whereas adaptive testing remained durably associated with audiometry, regardless of mental health. Conclusions and Relevance: Psychological status was an effect modifier of the association between standard Inner EAR scale scores and audiometry, with a positive association observed only in those with better mental health. Adaptive testing scores, however, remained significantly associated with audiometry, even when mental status was worse. Adaptive testing may stabilize the association between subjective and objective hearing outcomes.


Subject(s)
Hearing Loss , Humans , Female , Male , Middle Aged , Hearing Loss/psychology , Aged , Audiometry, Pure-Tone , Adult , Patient Reported Outcome Measures , Prospective Studies , Surveys and Questionnaires , Audiometry , Mental Health
12.
Dig Dis ; 42(4): 309-318, 2024.
Article in English | MEDLINE | ID: mdl-38648736

ABSTRACT

INTRODUCTION: Endoscopic submucosal dissection (ESD) has been popular worldwide to treat laterally spreading tumors and large polyps. Post-ESD coagulation syndrome (PECS) is more common than the two major ESD-related complications, perforation, and bleeding. The aim of this study was to assess the prevalence of PECS, identify the risk factors for PECS, and create a risk prediction model for PECS. METHODS: Retrospective cross-sectional study analyzed a total of 986 patients who underwent colorectal ESD. Logistic regression models were used to assess risk factors with PECS. Each risk factor was scored, and the 3-step risk stratification index of prediction model was assessed. RESULTS: The prevalence of PECS was 21.4% (95% confidence interval [CI] = 18.9-24.1%). The risk factors of PECS in the multivariate logistic regression were tumor size (+1 cm: odds ratio [OR], 1.29; 95% CI, 1.16-7.09), cecal lesion (OR, 1.96; 95% CI, 1.09-1.53), procedure time (+30 min: OR, 1.19; 95% CI, 1.02-1.39), and ESD with snaring (OR, 0.64; 95% CI, 0.43-0.95). Applying a simplified weighted scoring system based on adjusted OR increments of 1, the risk of PECS was 12.3% (95% CI, 0.3-16.0%) for the low-risk group (score ≤4) and was 36.0% (95% CI = 29.4-43.2%) for the high-risk group (score ≥8). Overall discrimination (C-statistic = 0.629; 95% CI = 0.585-0.672) and calibration (p = 0.993) of the model were moderate to good. CONCLUSION: PECS occurs frequently, and the prediction model can be helpful for effective treatment and prevention of PECS.


Subject(s)
Endoscopic Mucosal Resection , Postoperative Complications , Humans , Male , Female , Endoscopic Mucosal Resection/adverse effects , Retrospective Studies , Middle Aged , Aged , Cross-Sectional Studies , Risk Factors , Postoperative Complications/etiology , Postoperative Complications/epidemiology , Syndrome , Colorectal Neoplasms/surgery , Colorectal Neoplasms/pathology , Risk Assessment , Logistic Models , Prevalence
13.
Epilepsia ; 65(6): e87-e96, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38625055

ABSTRACT

Febrile infection-related epilepsy syndrome (FIRES) is a subset of new onset refractory status epilepticus (NORSE) that involves a febrile infection prior to the onset of the refractory status epilepticus. It is unclear whether FIRES and non-FIRES NORSE are distinct conditions. Here, we compare 34 patients with FIRES to 30 patients with non-FIRES NORSE for demographics, clinical features, neuroimaging, and outcomes. Because patients with FIRES were younger than patients with non-FIRES NORSE (median = 28 vs. 48 years old, p = .048) and more likely cryptogenic (odds ratio = 6.89), we next ran a regression analysis using age or etiology as a covariate. Respiratory and gastrointestinal prodromes occurred more frequently in FIRES patients, but no difference was found for non-infection-related prodromes. Status epilepticus subtype, cerebrospinal fluid (CSF) and magnetic resonance imaging findings, and outcomes were similar. However, FIRES cases were more frequently cryptogenic; had higher CSF interleukin 6, CSF macrophage inflammatory protein-1 alpha (MIP-1a), and serum chemokine ligand 2 (CCL2) levels; and received more antiseizure medications and immunotherapy. After controlling for age or etiology, no differences were observed in presenting symptoms and signs or inflammatory biomarkers, suggesting that FIRES and non-FIRES NORSE are very similar conditions.


Subject(s)
Fever , Status Epilepticus , Humans , Status Epilepticus/etiology , Male , Female , Adult , Middle Aged , Fever/etiology , Fever/complications , Young Adult , Adolescent , Drug Resistant Epilepsy/etiology , Child , Seizures, Febrile/etiology , Electroencephalography , Aged , Magnetic Resonance Imaging , Epileptic Syndromes , Child, Preschool
14.
Vaccines (Basel) ; 12(3)2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38543967

ABSTRACT

Varicella-zoster virus (VZV) poses lifelong risks, causing varicella and herpes zoster (HZ, shingles). Currently, varicella and HZ vaccines are predominantly live attenuated vaccines or adjuvanted subunit vaccines utilizing VZV glycoprotein E (gE). Here, we propose our vaccine candidates involving a comparative analysis between recombinant baculoviral vector vaccines (AcHERV) and a live attenuated vaccine strain, vOka. AcHERV vaccine candidates were categorized into groups encoding gE only, VZV glycoprotein B (gB) only, or both gE and gB (gE-gB) as AcHERV-gE, AcHERV-gB, and AcHERV-gE-gB, respectively. Humoral immune responses were evaluated by analyzing total IgG, IgG1, IgG2a, and neutralizing antibodies. Cell-mediated immunity (CMI) responses were evaluated by enzyme-linked immunospot (ELISPOT) assay and Th1/Th2/Th17 cytokine profiling. In the mouse model, AcHERV-gE-gB elicited similar or higher total IgG, IgG2a, and neutralizing antibody levels than vOka and showed robust VZV-specific CMI responses. From the perspective of antigens encoded in vaccines and their relationship with CMI response, both AcHERV-gB and AcHERV-gE-gB demonstrated results equal to or superior to AcHERV-gE, encoding only gE. Taken together, these results suggest that AcHERV-gE-gB can be a novel candidate for alleviating risks of live attenuated vaccine-induced latency and effectively preventing varicella during early stages of life while providing strong CMI for effective resistance against HZ and therapeutic potential in later stages of life.

15.
Sci Rep ; 14(1): 7436, 2024 03 28.
Article in English | MEDLINE | ID: mdl-38548901

ABSTRACT

CRISPR/Cas9 technology has effectively targeted cancer-specific oncogenic hotspot mutations or insertion-deletions. However, their limited prevalence in tumors restricts their application. We propose a novel approach targeting passenger single nucleotide variants (SNVs) in haploinsufficient or essential genes to broaden therapeutic options. By disrupting haploinsufficient or essential genes through the cleavage of DNA in the SNV region using CRISPR/Cas9, we achieved the selective elimination of cancer cells without affecting normal cells. We found that, on average, 44.8% of solid cancer patients are eligible for our approach, a substantial increase compared to the 14.4% of patients with CRISPR/Cas9-applicable oncogenic hotspot mutations. Through in vitro and in vivo experiments, we validated our strategy by targeting a passenger mutation in the essential ribosomal gene RRP9 and haploinsufficient gene SMG6. This demonstrates the potential of our strategy to selectively eliminate cancer cells and expand therapeutic opportunities.


Subject(s)
CRISPR-Cas Systems , Neoplasms , Humans , Genes, Essential , Mutation , Nucleotides , Gene Editing , Neoplasms/genetics , Neoplasms/therapy
16.
Adv Nutr ; 15(4): 100199, 2024 04.
Article in English | MEDLINE | ID: mdl-38432592

ABSTRACT

Within 20 y, the number of adults in the United States over the age of 65 y is expected to more than double and the number over age 85 y is expected to more than triple. The risk for most chronic diseases and disabilities increases with age, so this demographic shift carries significant implications for the individual, health care providers, and population health. Strategies that delay or prevent the onset of age-related diseases are becoming increasingly important. Although considerable progress has been made in understanding the contribution of nutrition to healthy aging, it has become increasingly apparent that much remains to be learned, especially because the aging process is highly variable. Most federal nutrition programs and nutrition research studies define all adults over age 65 y as "older" and do not account for physiological and metabolic changes that occur throughout older adulthood that influence nutritional needs. Moreover, the older adult population is becoming more racially and ethnically diverse, so cultural preferences and other social determinants of health need to be considered. The Research Centers Collaborative Network sponsored a 1.5-d multidisciplinary workshop that included sessions on dietary patterns in health and disease, timing and targeting interventions, and health disparities and the social context of diet and food choice. The agenda and presentations can be found at https://www.rccn-aging.org/nutrition-2023-rccn-workshop. Here we summarize the workshop's themes and discussions and highlight research gaps that if filled will considerably advance our understanding of the role of nutrition in healthy aging.


Subject(s)
Healthy Aging , Humans , United States , Aged , Aged, 80 and over , Nutritional Status , Diet
17.
Sensors (Basel) ; 24(5)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38475048

ABSTRACT

Citrus fruits were sorted based on external qualities, such as size, weight, and color, and internal qualities, such as soluble solid content (SSC), acidity, and firmness. Visible and near-infrared (VNIR) hyperspectral imaging techniques were used as rapid and nondestructive techniques for determining the internal quality of fruits. The applicability of the VNIR hyperspectral imaging technique for predicting the SSC in citrus fruits was evaluated in this study. A VNIR hyperspectral imaging system with a wavelength range of 400-1000 nm and 100 W light source was used to acquire hyperspectral images from citrus fruits in two orientations (i.e., stem and calyx ends). The SSC prediction model was developed using partial least-squares regression (PLSR). Spectrum preprocessing, effective wavelength selection through competitive adaptive reweighted sampling (CARS), and outlier detection were used to improve the model performance. The performance of each model was evaluated using the coefficient of determination (R2) and root mean square error (RMSE). In the present study, the PLSR model was developed using only a citrus cultivar. The SSC prediction CARS-PLSR model with outliers removed exhibited R2 and RMSE values of approximatively 0.75 and 0.56 °Brix, respectively. The results of this study are expected to be useful in similar fields such as agricultural and food post-harvest management, as well as in the development of an online system for determining the SSC of citrus fruits.


Subject(s)
Citrus , Spectroscopy, Near-Infrared , Spectroscopy, Near-Infrared/methods , Hyperspectral Imaging , Fruit , Algorithms , Least-Squares Analysis
18.
Sci Rep ; 14(1): 4344, 2024 02 22.
Article in English | MEDLINE | ID: mdl-38383725

ABSTRACT

The purpose of this study was to demonstrate the performance of a fully automated, deep learning-based brain segmentation (DLS) method in healthy controls and in patients with neurodevelopmental disorders, SCN1A mutation, under eleven. The whole, cortical, and subcortical volumes of previously enrolled 21 participants, under 11 years of age, with a SCN1A mutation, and 42 healthy controls, were obtained using a DLS method, and compared to volumes measured by Freesurfer with manual correction. Additionally, the volumes which were calculated with the DLS method between the patients and the control group. The volumes of total brain gray and white matter using DLS method were consistent with that volume which were measured by Freesurfer with manual correction in healthy controls. Among 68 cortical parcellated volume analysis, the volumes of only 7 areas measured by DLS methods were significantly different from that measured by Freesurfer with manual correction, and the differences decreased with increasing age in the subgroup analysis. The subcortical volume measured by the DLS method was relatively smaller than that of the Freesurfer volume analysis. Further, the DLS method could perfectly detect the reduced volume identified by the Freesurfer software and manual correction in patients with SCN1A mutations, compared with healthy controls. In a pediatric population, this new, fully automated DLS method is compatible with the classic, volumetric analysis with Freesurfer software and manual correction, and it can also well detect brain morphological changes in children with a neurodevelopmental disorder.


Subject(s)
Deep Learning , Humans , Child , Magnetic Resonance Imaging/methods , Hippocampus/anatomy & histology , Brain/diagnostic imaging , Software , Image Processing, Computer-Assisted/methods
19.
N Engl J Med ; 390(8): 701-711, 2024 Feb 22.
Article in English | MEDLINE | ID: mdl-38329148

ABSTRACT

BACKGROUND: Thrombolytic agents, including tenecteplase, are generally used within 4.5 hours after the onset of stroke symptoms. Information on whether tenecteplase confers benefit beyond 4.5 hours is limited. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial involving patients with ischemic stroke to compare tenecteplase (0.25 mg per kilogram of body weight, up to 25 mg) with placebo administered 4.5 to 24 hours after the time that the patient was last known to be well. Patients had to have evidence of occlusion of the middle cerebral artery or internal carotid artery and salvageable tissue as determined on perfusion imaging. The primary outcome was the ordinal score on the modified Rankin scale (range, 0 to 6, with higher scores indicating greater disability and a score of 6 indicating death) at day 90. Safety outcomes included death and symptomatic intracranial hemorrhage. RESULTS: The trial enrolled 458 patients, 77.3% of whom subsequently underwent thrombectomy; 228 patients were assigned to receive tenecteplase, and 230 to receive placebo. The median time between the time the patient was last known to be well and randomization was approximately 12 hours in the tenecteplase group and approximately 13 hours in the placebo group. The median score on the modified Rankin scale at 90 days was 3 in each group. The adjusted common odds ratio for the distribution of scores on the modified Rankin scale at 90 days for tenecteplase as compared with placebo was 1.13 (95% confidence interval, 0.82 to 1.57; P = 0.45). In the safety population, mortality at 90 days was 19.7% in the tenecteplase group and 18.2% in the placebo group, and the incidence of symptomatic intracranial hemorrhage was 3.2% and 2.3%, respectively. CONCLUSIONS: Tenecteplase therapy that was initiated 4.5 to 24 hours after stroke onset in patients with occlusions of the middle cerebral artery or internal carotid artery, most of whom had undergone endovascular thrombectomy, did not result in better clinical outcomes than those with placebo. The incidence of symptomatic intracerebral hemorrhage was similar in the two groups. (Funded by Genentech; TIMELESS ClinicalTrials.gov number, NCT03785678.).


Subject(s)
Brain Ischemia , Ischemic Stroke , Perfusion Imaging , Tenecteplase , Thrombectomy , Tissue Plasminogen Activator , Humans , Brain Ischemia/diagnostic imaging , Brain Ischemia/drug therapy , Brain Ischemia/mortality , Brain Ischemia/surgery , Fibrinolytic Agents/administration & dosage , Fibrinolytic Agents/adverse effects , Fibrinolytic Agents/therapeutic use , Intracranial Hemorrhages/chemically induced , Intracranial Hemorrhages/diagnostic imaging , Perfusion , Perfusion Imaging/methods , Stroke/diagnostic imaging , Stroke/drug therapy , Stroke/mortality , Stroke/surgery , Tenecteplase/administration & dosage , Tenecteplase/adverse effects , Tenecteplase/therapeutic use , Thrombectomy/adverse effects , Thrombectomy/methods , Tissue Plasminogen Activator/administration & dosage , Tissue Plasminogen Activator/adverse effects , Tissue Plasminogen Activator/therapeutic use , Treatment Outcome , Double-Blind Method , Ischemic Stroke/diagnostic imaging , Ischemic Stroke/drug therapy , Ischemic Stroke/mortality , Ischemic Stroke/surgery , Infarction, Middle Cerebral Artery/diagnostic imaging , Infarction, Middle Cerebral Artery/drug therapy , Infarction, Middle Cerebral Artery/surgery , Carotid Artery Diseases/diagnostic imaging , Carotid Artery Diseases/drug therapy , Carotid Artery Diseases/surgery , Brain/blood supply , Brain/diagnostic imaging , Time-to-Treatment
20.
Sensors (Basel) ; 24(2)2024 Jan 05.
Article in English | MEDLINE | ID: mdl-38257409

ABSTRACT

Apples are widely cultivated in the Republic of Korea and are preferred by consumers for their sweetness. Soluble solid content (SSC) is measured non-destructively using near-infrared (NIR) spectroscopy; however, the SSC measurement error increases with the change in apple size since the distance between the light source and the near-infrared sensor is fixed. In this study, spectral characteristics caused by the differences in apple size were investigated. An optimal SSC prediction model applying partial least squares regression (PLSR) to three measurement conditions based on apple size was developed. The three optimal measurement conditions under which the Vis/NIR spectrum is less affected by six apple size levels (Levels I-VI) were selected. The distance from the apple center to the light source and that to the sensor were 125 and 75 mm (Distance 1), 123 and 75 mm (Distance 2), and 135 and 80 mm (Distance 3). The PLSR model applying multiplicative scatter correction pretreatment under Distance 3 measurement conditions showed the best performance for Level IV-sized apples (Rpre2 = 0.91, RMSEP = 0.508 °Brix). This study shows the possibility of improving the SSC prediction performance of apples by adjusting the distance between the light source and the NIR sensor according to fruit size.

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