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PURPOSE: Surgical pathology reports play an integral role in postoperative management of head and neck cancer patients. Pathology reports of complex head and neck resections must convey critical information to all involved clinicians. Previously, we demonstrated the utility of 3D specimen and defect scanning for communicating margin status and documenting the location of supplemental margins. We introduce a newly designed permanent pathology report which improves documentation of intraoperative margin mapping and extent of corresponding supplemental margins harvested. METHODS: We test the hypothesis that gaps in understanding exist for head and neck resection pathology reports across providers. A cross-sectional exploratory study using human-centered design was implemented to evaluate the existing permanent pathology report with respect to understanding margin status. Pathologists, surgeons, radiation oncologists, and medical oncologists from United States-based medical institutions were surveyed. The results supported a redesign of our surgical pathology template, incorporating 3D specimen / defect scans and annotated radiographic images indicating the location of inadequate margins requiring supplemental margins, or indicating frankly positive margins discovered on permanent section. RESULTS: Forty-seven physicians completed our survey. Analyzing surgical pathology reports, 28/47 (60%) respondents reported confusion whether re-excised supplemental margins reflected clear margins, 20/47 (43%) reported uncertainty regarding final margin status, and 20/47 (43%) reported the need for clarity regarding the extent of supplemental margins harvested intraoperatively. From this feedback, we designed a new pathology report template; 61 permanent pathology reports were compiled with this new template over a 12-month period. CONCLUSION: Feedback from survey respondents led to a redesigned permanent pathology report that offers detailed visual anatomic information regarding intraoperative margin findings and exact location/size of harvested supplemental margins. This newly designed report reconciles frozen and permanent section results and includes annotated radiographic images such that clinicians can discern precise actions taken by surgeons to address inadequate margins, as well as to understand the location of areas of concern that may influence adjuvant radiation planning.
Subject(s)
Head and Neck Neoplasms , Margins of Excision , Pathology, Surgical , Humans , Head and Neck Neoplasms/surgery , Head and Neck Neoplasms/pathology , Cross-Sectional Studies , Pathology, Surgical/methods , Interdisciplinary Communication , Imaging, Three-DimensionalABSTRACT
Effective removal of phosphate from water is essential for preventing the eutrophication and worsening of water quality. This study aims to enhance phosphate removal by synthesizing starch-stabilized ferromanganese binary oxide (FMBO-S), discover the factors, and investigate adsorption mechanisms. FMBO and FMBO-S properties were studied using Scanning Electron Microscopy, BET analysis, Polydispersity Index (PDI), Fourier Transform Infrared Spectroscopy, and X-ray Photoelectron Spectroscopy (XPS). After starch loading, the average pore diameter increased from 14.89 Å to 25.16 Å, and significantly increased the pore volume in the mesopore region. FMBO-S showed a PDI value below 0.5 indicating homogeneous size dispersity and demonstrated faster and higher adsorption capacity: 61.24 mg g-1 > 28.57 mg g-1. Both FMBO and FMBO-S adsorption data fit well with the pseudo-second-order and Freundlich models, indicating a chemisorption and multilayered adsorption process. The phosphate adsorption by FMBO was pH-dependent, suggesting electrostatic attraction as the dominant mechanism. For the FMBO-S, phosphate adsorption was favored in a wide pH range, despite the weaker electrostatic attraction as evident from the point of zero charge and zeta potential values, indicating ligand exchange as a main mechanism. Moreover, the XPS analysis shows a significant change in the proportion of Fe species for FMBO-S than FMBO after phosphate adsorption, indicating significant involvement of Fe. Meanwhile, phosphate adsorption was almost unaffected by the presence of Cl-, NO3-, and SO42- anions, whereas CO32- significantly reduced the adsorption capacity. This study revealed that FMBO-S could be a promising, low-cost adsorbent for phosphate removal and recovery from water.
Subject(s)
Oxides , Phosphates , Starch , Water Pollutants, Chemical , Water Purification , Adsorption , Starch/chemistry , Phosphates/chemistry , Water Pollutants, Chemical/chemistry , Oxides/chemistry , Water Purification/methods , Photoelectron Spectroscopy , Hydrogen-Ion Concentration , Kinetics , Spectroscopy, Fourier Transform InfraredABSTRACT
To investigate the efficacy of chiropractic rehabilitation therapy in Crowe IV developmental dysplasia of the hip (DDH) patients after total hip arthroplasty. Seventy-two patients with Crowe IV type DDH hospitalized in the Department of Orthopedics I of Ya'an Hospital of Traditional Chinese Medicine from January 2021 to June 2023 were selected for the study, and they were divided into 36 cases in the chiropractic rehabilitation therapy group (the treatment group) and 36 cases in the traditional rehabilitation therapy group (the control group) according to the method of randomized grouping. All patients were evaluated at preoperative, 1, 3, and 6 months postoperatively for follow-up, and the muscle strength of the affected limb, the patient's walking gait, the shortened length of the affected limb, the visual analog scale score (VAS score), the Oswestry Dysfunction Index Score (ODI score), the Harris Hip Score, and the degree of pelvic tilt were recorded to evaluate the results of the study. A total of 4 subjects withdrew from the study, 2 in the treatment group, and 2 in the control group. The muscle strength of the affected limb, walking gait, shortened length of the affected limb, VAS score, ODI score, Harris score, and pelvic tilt in the treatment and control groups improved significantly compared with the preoperative period. Comparisons between the 2 groups revealed that at the final follow-up visit, the limp gait of the patients in the treatment group was significantly reduced, the shortened length of the affected limb was significantly reduced, the VAS score was significantly reduced, and the ODI score was significantly reduced, in the treatment group relative to that of the control group, Harris Hip Score was significantly improved, and the degree of pelvic tilt was significantly reduced, but the improvement in muscle strength of the affected limb was not statistically significant. In future clinical practice, we recommend that chiropractic rehabilitation be used as a routine adjunctive treatment after TKA in patients with Crowe IV DDH to optimize outcomes and improve patients' quality of life.
Subject(s)
Arthroplasty, Replacement, Hip , Humans , Female , Male , Arthroplasty, Replacement, Hip/rehabilitation , Middle Aged , Manipulation, Chiropractic/methods , Muscle Strength , Treatment Outcome , Aged , Developmental Dysplasia of the Hip/surgery , Developmental Dysplasia of the Hip/rehabilitation , Adult , Gait/physiologyABSTRACT
OBJECTIVES: To investigate the added value of extracellular volume fraction (ECV) and arterial enhancement fraction (AEF) derived from enhanced CT to conventional image and clinical features for differentiating between pleomorphic adenoma (PA) and atypical parotid adenocarcinoma (PCA) pre-operation. METHODS: From January 2010 to October 2023, a total of 187 cases of parotid tumors were recruited, and divided into training cohort (102 PAs and 51 PCAs) and testing cohort (24 PAs and 10 atypical PCAs). Clinical and CT image features of tumor were assessed. Both enhanced CT-derived ECV and AEF were calculated. Univariate analysis identified variables with statistically significant differences between the two subgroups in the training cohort. Multivariate logistic regression analysis with the forward variable selection method was used to build four models (clinical model, clinical model+ECV, clinical model+AEF, and combined model). Diagnostic performances were evaluated using receiver operating characteristic (ROC) curve analyses. Delong's test compared model differences, and calibration curve and decision curve analysis (DCA) assessed calibration and clinical application. RESULTS: Age and boundary were chosen to build clinical model, and to construct its ROC curve. Amalgamating the clinical model, ECV, and AEF to establish a combined model demonstrated superior diagnostic effectiveness compared to the clinical model in both the training and test cohorts (AUC = 0.888, 0.867). There was a significant statistical difference between the combined model and the clinical model in the training cohort (p = 0.0145). CONCLUSIONS: ECV and AEF are helpful in differentiating PA and atypical PCA, and integrating clinical and CT image features can further improve the diagnostic performance.
Subject(s)
Adenoma, Pleomorphic , Contrast Media , Parotid Neoplasms , Tomography, X-Ray Computed , Humans , Male , Female , Adenoma, Pleomorphic/diagnostic imaging , Adenoma, Pleomorphic/pathology , Middle Aged , Parotid Neoplasms/diagnostic imaging , Parotid Neoplasms/pathology , Tomography, X-Ray Computed/methods , Diagnosis, Differential , Aged , Adult , ROC Curve , Retrospective Studies , Adenocarcinoma/diagnostic imaging , Adenocarcinoma/pathologyABSTRACT
Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virus-infected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105 PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.
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PURPOSE: This study compared treatment and outcomes for patients with HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) based on their travel distance to treatment facility. MATERIALS AND METHODS: Patients with cT1-4, N0-3, M0 HPV-positive OPSCC in the National Cancer Database from 2010 to 2019 were identified and split into four quartiles based on distance to facility, with quartile 4 representing patients with furthest travel distances. Multivariable-adjusted logistic regression and Cox proportional hazards modeling were used to analyze the primary outcome of treatment received, and secondary outcomes of clinical stage, overall survival, surgical approach (i.e., TORS versus other), and 30-day surgical readmissions. RESULTS: 17,207 patients with HPV-positive OPSCC were evenly distributed into four quartiles. Compared to patients in quartile 1, patients in quartile 4 were 40 % less likely to receive radiation versus surgery (OR = 0.60; 95 % CI = 0.54-0.66). Among the patients who received surgery, quartile 4 had a higher odds of receiving TORS treatment compared to quartile 1 (4v1: OR = 2.38; 95 % CI = 2.05-2.77), quartile 2 (4v2: OR = 2.31, 95 % CI = 2.00-2.66), and quartile 3 (4v3: OR = 1.75; 95 % CI = 1.54-1.99). Quartile 4 had a decreased odds of mortality compared to Quartile 1 (4v1: OR = 0.87; 95 % CI = 0.79-0.97). There were no differences among the quartiles in presenting stage and 30-day readmissions. CONCLUSIONS: This study found that patients with furthest travel distance to facility were more often treated surgically over non-surgical management, with TORS over open surgery, and had better overall survival. These findings highlight potential disparities in access to care for patients with HPV-positive OPSCC.
Subject(s)
Oropharyngeal Neoplasms , Papillomavirus Infections , Humans , Male , Female , Oropharyngeal Neoplasms/mortality , Oropharyngeal Neoplasms/therapy , Oropharyngeal Neoplasms/virology , Middle Aged , Aged , Papillomavirus Infections/therapy , Papillomavirus Infections/complications , Papillomavirus Infections/mortality , Papillomavirus Infections/virology , Treatment Outcome , Health Services Accessibility , Neoplasm Staging , Survival Rate , Carcinoma, Squamous Cell/therapy , Carcinoma, Squamous Cell/mortality , Carcinoma, Squamous Cell/virology , Travel , Time FactorsABSTRACT
The thermophysical properties and elemental abundances of the noble gases in terrestrial materials can provide unique insights into the Earth's evolution and mantle dynamics. Here, we perform extensive ab initio molecular dynamics simulations to determine the melting temperature and sound velocity of neon up to 370 GPa and 7500 K to constrain its physical state and storage capacity, together with to reveal its implications for the deep interior of the Earth. It is found that solid neon can exist stably under the lower mantle and inner core conditions, and the abnormal melting of neon is not observed under the entire temperature (T) and pressure (P) region inside the Earth owing to its peculiar electronic structure, which is substantially distinct from other heavier noble gases. An inspection of the reduction for sound velocity along the Earth's geotherm evidences that neon can be used as a light element to account for the low-velocity anomaly and density deficit in the deep Earth. A comparison of the pair distribution functions and mean square displacements of MgSiO3-Ne and Fe-Ne alloys further reveals that MgSiO3 has a larger neon storage capacity than the liquid iron under the deep Earth condition, indicating that the lower mantle may be a natural deep noble gas storage reservoir. Our results provide valuable information for studying the fundamental behavior and phase transition of neon in a higher T-P regime, and further enhance our understanding for the interior structure and evolution processes inside the Earth.
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Nonclinical studies involve in vitro, in silico, and in vivo experiments to assess the toxicokinetics, toxicology, and safety pharmacology of drugs according to regulatory requirements by a national or international authority. In this review, we summarize the potential effects of various underlying diseases governing the absorption, distribution, metabolism, and excretion (ADME) of drugs to consider the use of animal models of diseases in nonclinical trials. Obesity models showed alterations in hepatic metabolizing enzymes, transporters, and renal pathophysiology, which increase the risk of drug-induced toxicity. Diabetes models displayed changes in hepatic metabolizing enzymes, transporters, and glomerular filtration rates (GFR), leading to variability in drug responses and susceptibility to toxicity. Animal models of advanced age exhibited impairment of drug metabolism and kidney function, thereby reducing the drug-metabolizing capacity and clearance. Along with changes in hepatic metabolic enzymes, animal models of metabolic syndrome-related hypertension showed renal dysfunction, resulting in a reduced GFR and urinary excretion of drugs. Taken together, underlying diseases can induce dysfunction of organs involved in the ADME of drugs, ultimately affecting toxicity. Therefore, the use of animal models of representative underlying diseases in nonclinical toxicity studies can be considered to improve the predictability of drug side effects before clinical trials.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Animals , Humans , Pharmaceutical Preparations/metabolism , Drug-Related Side Effects and Adverse Reactions/etiology , Liver/metabolism , Liver/drug effects , Kidney/metabolism , Kidney/drug effects , Drug Evaluation, Preclinical , Glomerular Filtration RateABSTRACT
BACKGROUND AND AIMS: Accurate preoperative prediction of microvascular invasion (MVI) and recurrence-free survival (RFS) is vital for personalised hepatocellular carcinoma (HCC) management. We developed a multitask deep learning model to predict MVI and RFS using preoperative MRI scans. METHODS: Utilising a retrospective dataset of 725 HCC patients from seven institutions, we developed and validated a multitask deep learning model focused on predicting MVI and RFS. The model employs a transformer architecture to extract critical features from preoperative MRI scans. It was trained on a set of 234 patients and internally validated on a set of 58 patients. External validation was performed using three independent sets (n = 212, 111, 110). RESULTS: The multitask deep learning model yielded high MVI prediction accuracy, with AUC values of 0.918 for the training set and 0.800 for the internal test set. In external test sets, AUC values were 0.837, 0.815 and 0.800. Radiologists' sensitivity and inter-rater agreement for MVI prediction improved significantly when integrated with the model. For RFS, the model achieved C-index values of 0.763 in the training set and ranged between 0.628 and 0.728 in external test sets. Notably, PA-TACE improved RFS only in patients predicted to have high MVI risk and low survival scores (p < .001). CONCLUSIONS: Our deep learning model allows accurate MVI and survival prediction in HCC patients. Prospective studies are warranted to assess the clinical utility of this model in guiding personalised treatment in conjunction with clinical criteria.
Subject(s)
Carcinoma, Hepatocellular , Deep Learning , Liver Neoplasms , Magnetic Resonance Imaging , Neoplasm Invasiveness , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/mortality , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Liver Neoplasms/mortality , Magnetic Resonance Imaging/methods , Retrospective Studies , Female , Male , Middle Aged , Aged , Microvessels/diagnostic imaging , Microvessels/pathology , Disease-Free Survival , Neoplasm Recurrence, LocalABSTRACT
Percutaneous thermotherapy, a minimally invasive operational procedure, is employed in the ablation of deep tumor lesions by means of target-delivering heat. Conventional thermal ablation methods, such as radiofrequency or microwave ablation, to a certain extent, are subjected to extended ablation time as well as biosafety risks of unwanted overheating. Given its effectiveness and safety, percutaneous thermotherapy gains a fresh perspective, thanks to magnetic hyperthermia. In this respect, an injectable- and magnetic-hydrogel-construct-based thermal ablation agent is likely to be a candidate for the aforementioned clinical translation. Adopting a simple and environment-friendly strategy, a magnetic colloidal hydrogel injection is introduced by a binary system comprising super-paramagnetic Fe3O4 nanoparticles and gelatin nanoparticles. The colloidal hydrogel constructs, unlike conventional bulk hydrogel, can be easily extruded through a percutaneous needle and then self-heal in a reversible manner owing to the unique electrostatic cross-linking. The introduction of magnetic building blocks is exhibited with a rapid magnetothermal response to an alternating magnetic field. Such hydrogel injection is capable of generating heat without limitation of deep penetration. The materials achieve outstanding therapeutic results in mouse and rabbit models. These findings constitute a new class of locoregional interventional thermal therapies with minimal collateral damages.
Subject(s)
Carcinoma, Hepatocellular , Colloids , Hydrogels , Liver Neoplasms , Animals , Rabbits , Mice , Hydrogels/chemistry , Liver Neoplasms/therapy , Liver Neoplasms/pathology , Carcinoma, Hepatocellular/therapy , Carcinoma, Hepatocellular/pathology , Colloids/chemistry , Gelatin/chemistry , Humans , Magnetite Nanoparticles/chemistry , Magnetite Nanoparticles/therapeutic use , Hyperthermia, Induced/methods , Cell Line, Tumor , Injections , Magnetic Iron Oxide Nanoparticles/chemistryABSTRACT
INTRODUCTION: The multiple treatment options available to patients with thyroid nodules can generate uncertainty and confusion. Radiofrequency ablation (RFA) and ethanol ablation (EA) are two alternative modalities to manage thyroid nodules. As patients more frequently utilize online resources to guide their decision-making, the quality of such resources must be evaluated. The goal of this study was to assess the quality of online patient materials relating to RFA and EA compared to standard thyroidectomy. METHODS: The terms "thyroidectomy," "thyroid radiofrequency ablation," and "thyroid ethanol ablation" were searched on Google. Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FKGL), Simple Measure of Gobbledygook (SMOG), and Patient Education Materials Assessment Tool (PEMAT) understandability and actionability were calculated for each website. Statistical analysis was conducted on SPSS Statistics. Google trends were used to determine search interest for each term (May 2016 - May 2021). RESULTS: Of the 77 websites that met our inclusion criteria (30 thyroidectomy sites, 30 RFA sites, and 17 EA sites), the average FRE, FKGL, and SMOG scores of the RFA websites were significantly worse than those of the thyroidectomy websites (p < 0.05). The FKGL and SMOG scores of the EA websites were significantly worse than those of the thyroidectomy websites (p < 0.05). The average understandability and actionability scores for thyroidectomy websites were significantly higher than those of RFA and EA websites (p < 0.05). CONCLUSION: Ablation websites have lower search interest, readability, validity, understandability, and actionability scores in comparison to traditional thyroidectomy websites. Our findings emphasize the need to consider readability and PEMAT scores when developing online educational resources for ablative alternatives to thyroidectomy to allow for greater patient accessibility.
Subject(s)
Ethanol , Internet , Radiofrequency Ablation , Thyroid Nodule , Thyroidectomy , Humans , Radiofrequency Ablation/methods , Ethanol/therapeutic use , Thyroidectomy/methods , Thyroid Nodule/surgery , Patient Education as Topic/methodsABSTRACT
OBJECTIVE: The primary objective of this study was to evaluate oncologic outcomes of all published cases of supracricoid partial laryngectomy (SCPL) performed in the United States. The secondary objective was to assess the functional outcomes associated with this procedure. REVIEW METHODS: A systematic review of PubMed, SCOPUS, and Embase for all English-language studies pertaining to SCPL performed in the United States was conducted until August 2021. Primary outcomes included disease-specific survival (DSS), overall survival, and local recurrence rate. Secondary outcomes included larynx preservation rate, gastrostromy tube dependency, days to gastrostomy tube removal, decannulation rate, and days to decannulation. RESULTS: A total of six studies were included in the analysis. A total of 113 patients (58.5%) underwent SCPL surgery as a primary treatment method whereas 80 patients (41.5%) underwent SCPL as salvage surgery. The 5-year DSS rates were 87.8% and 100% for primary and salvage procedures, respectively. Approximately 10.3% of patients undergoing a salvage SCPL procedure experienced a local recurrence whereas only 1.85% of primary SCPL procedures resulted in local recurrence. The rates of decannulation following primary and salvage SCPL were 92.7% and 88.1%, respectively. With regard to swallowing, primary and salvage SCPL procedures demonstrated comparably low postoperative gastrostomy tube dependency rates of 3.66% and 4.76%, respectively. CONCLUSIONS: SCPL performed in the United States is an effective surgical technique that produces excellent outcomes in qualifying patients, thus validating its viability as an organ-preserving surgical alternative. Laryngoscope, 134:3003-3011, 2024.
Subject(s)
Cricoid Cartilage , Laryngeal Neoplasms , Laryngectomy , Humans , Laryngectomy/methods , Laryngeal Neoplasms/surgery , Laryngeal Neoplasms/mortality , United States/epidemiology , Cricoid Cartilage/surgery , Treatment Outcome , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/surgery , Salvage Therapy/methods , Salvage Therapy/statistics & numerical dataABSTRACT
OBJECTIVE(S): Despite advancements in imaging techniques and cytological analysis, plunging ranula remains a challenging surgical, radiologic, and pathologic phenomenon. Of the 18 patients we evaluated at our institution, we highlight three cases that illustrate the high rate of misleading imaging and cytological results when assessing plunging ranula. METHODS: Imaging results, biopsy findings, operative techniques, and pathological reports were reviewed from patients who had either a preoperative or postoperative diagnosis of ranula and underwent surgery by a single head and neck surgeon at a tertiary care center. RESULTS: Of the 18 identified patients, computed tomography was correct on preoperative imaging 73% of the time and magnetic resonance imaging was correct on preoperative imaging 71% of the time. Two patients underwent preoperative ultrasound and their ultrasound reports did not accurately diagnose the presence of a ranula. Two patients underwent preoperative fine needle aspiration biopsy due to inconclusive preoperative imaging, in which results suggested either a ranula or epidermal cyst. Both ultimately did not match the final pathology. Three of eighteen patients (17%) underwent an inappropriate initial surgery due to incorrect imaging diagnoses and/or biopsy findings. CONCLUSION: Despite use of preoperative modalities to distinguish plunging ranula from other cystic floor of mouth lesions, surgeons must be aware that no workup modality is fully precise. The potential for revision surgery must be included in all preoperative discussions for presumed plunging ranula. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:2689-2696, 2024.
Subject(s)
Ranula , Tomography, X-Ray Computed , Humans , Ranula/diagnosis , Ranula/surgery , Ranula/pathology , Ranula/diagnostic imaging , Male , Female , Adult , Magnetic Resonance Imaging , Middle Aged , Diagnosis, Differential , Biopsy, Fine-Needle , Ultrasonography , Retrospective Studies , Adolescent , Young Adult , Diagnostic ErrorsABSTRACT
Unintended genetic modifications that occur during the differentiation and proliferation of human induced pluripotent stem cells (hiPSCs) can lead to tumorigenicity. This is a crucial concern in the development of stem cell-based therapies to ensure the safety and efficacy of the final product. Moreover, conventional genetic stability testing methods are limited by low sensitivity, which is an issue that remains unsolved. In this study, we assessed the genetic stability of hiPSCs and hiPSC-derived cardiomyocytes using various testing methods, including karyotyping, CytoScanHD chip analysis, whole-exome sequencing, and targeted sequencing. Two specific genetic mutations in KMT2C and BCOR were selected from the 17 gene variants identified by whole-exome and targeted sequencing methods, which were validated using droplet digital PCR. The applicability of this approach to stem cell-based therapeutic products was further demonstrated with associated validation according to the International Council for Harmonisation (ICH) guidelines, including specificity, precision, robustness, and limit of detection. Our droplet digital PCR results showed high sensitivity and accuracy for quantitatively detecting gene mutations, whereas conventional qPCR could not avoid false positives. In conclusion, droplet digital PCR is a highly sensitive and precise method for assessing the expression of mutations with tumorigenic potential for the development of stem cell-based therapeutics.
Subject(s)
Induced Pluripotent Stem Cells , Humans , Myocytes, Cardiac , Carcinogenesis , Cell Differentiation/genetics , Polymerase Chain ReactionABSTRACT
BACKGROUND: Childhood is a crucial neurodevelopmental period. We investigated whether childhood reading for pleasure (RfP) was related to young adolescent assessments of cognition, mental health, and brain structure. METHODS: We conducted a cross-sectional and longitudinal study in a large-scale US national cohort (10 000 + young adolescents), using the well-established linear mixed model and structural equation methods for twin study, longitudinal and mediation analyses. A 2-sample Mendelian randomization (MR) analysis for potential causal inference was also performed. Important factors including socio-economic status were controlled. RESULTS: Early-initiated long-standing childhood RfP (early RfP) was highly positively correlated with performance on cognitive tests and significantly negatively correlated with mental health problem scores of young adolescents. These participants with higher early RfP scores exhibited moderately larger total brain cortical areas and volumes, with increased regions including the temporal, frontal, insula, supramarginal; left angular, para-hippocampal; right middle-occipital, anterior-cingulate, orbital areas; and subcortical ventral-diencephalon and thalamus. These brain structures were significantly related to their cognitive and mental health scores, and displayed significant mediation effects. Early RfP was longitudinally associated with higher crystallized cognition and lower attention symptoms at follow-up. Approximately 12 h/week of youth regular RfP was cognitively optimal. We further observed a moderately significant heritability of early RfP, with considerable contribution from environments. MR analysis revealed beneficial causal associations of early RfP with adult cognitive performance and left superior temporal structure. CONCLUSIONS: These findings, for the first time, revealed the important relationships of early RfP with subsequent brain and cognitive development and mental well-being.
Subject(s)
Mental Health , Pleasure , Adult , Adolescent , Humans , Child , Longitudinal Studies , Cross-Sectional Studies , Reading , Magnetic Resonance Imaging , Brain/diagnostic imaging , CognitionABSTRACT
OBJECTIVE: Opportunities exist to improve intraoperative communication and documentation of resection margin details. We instituted a "frozen section timeout" that centers around visualization of the paired resection specimen and surgical defect-facilitating effective, bidirectional exchange of information. METHODS: We designed an interactive form for use during the "frozen section timeout" including annotated 3D virtual models of the resected specimen and surgical defect, plus a "line-item" table for primary and supplemental margin results. The "timeout" was conducted over a Zoom call between the operating room and frozen section laboratory. The form was simultaneously projected and discussed while all members of the surgical care team stopped activities. Nurses, co-surgeons, and all other members of the surgical team were encouraged to take part in this process. RESULTS: Twenty-six frozen section timeouts were conducted during head and neck surgeries in the Department of Otolaryngology at Mount Sinai West Hospital. These timeouts were facilitated by the lead surgeon, and all other activities were halted to ensure that critical information was shared, documented, and agreed upon. During the timeout, the annotated specimen and defect scans were displayed, clearly demonstrating the at-risk margins and the corresponding location and breadth of supplemental margins harvested. CONCLUSION: Incorporating a frozen section timeout can improve intraoperative communication, increase transparency, and potentially eliminate uncertainty regarding margin status and tumor clearance. Visualization of at-risk margins and the corresponding location and breadth of supplemental margins promises an unprecedented level of documentation and understanding. This novel technique can establish a new and improved standard of care. LEVEL OF EVIDENCE: NA Laryngoscope, 134:725-731, 2024.
Subject(s)
Carcinoma, Squamous Cell , Frozen Sections , Humans , Pilot Projects , Carcinoma, Squamous Cell/pathology , Intraoperative Care/methods , Margins of Excision , Retrospective StudiesABSTRACT
Every person should engage in exercise or physical activity for health benefits. Primary healthcare physicians should assess the physical activity levels of patients and encourage them to exercise.Current Concepts: World Health Organization physical activity guidelines for adults include 150 to 300 minutes of moderate-intensity aerobic physical activity per week and muscle-strengthening activities for at least two days per week. People over 65 years of age should engage in adult physical activities and exercises to improve balance and prevent falls at least three times per week. Children and adolescents should engage in physical activity for at least 60 minutes daily and high-intensity aerobic physical activity for at least three days per week. Muscle and bone strengthening activities should be performed at least three days per week. Pregnant and postpartum women should regularly engage in physical activity, including moderate-intensity aerobic activity, muscle-strengthening activities, and light stretching exercises.Discussion and Conclusion: Only 16.9% of adults in Korea met the physical activity guidelines in 2020. The percentage was even lower for adolescents, older adults, and women. Therefore, primary healthcare physicians should monitor and encourage physical activity among their patients, although ensuring that they engage in sufficient physical activity is difficult. During clinical practice, counseling methods to improve compliance should be appropriately utilized. Physical activity is part of a healthy lifestyle that should be implemented along with smoking cessation, a reduction in alcohol consumption, and dietary control. Primary healthcare physicians should encourage improvement in patients’ physical activity levels through counseling.
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Objective@#Emergency department (ED) overcrowding is a global issue that negatively impacts the clinical outcome. Through the coronavirus disease 2019 (COVID-19) pandemic era, overcrowding of ED isolated territory (isolation bed) was aggravated. This study analyzed overcrowding indices of ED isolation beds during the COVID-19 pandemic. @*Methods@#This study was a single-center, retrospective, observational study. The study analyzed 34,925 patients who visited the ED during the COVID-19 pandemic from April 2021 to August 2022. Patients who were treated in isolation beds and regular beds were compared. Among the patients using isolation beds, patients who stayed longer than 720 minutes were also classified and analyzed. @*Results@#During the analysis period, 4,479 and 34,943 patients were treated in the ED isolation bed and ED regular bed, respectively. The overcrowding indices (general ward admission rate, intensive care unit admission rate, ED-length of stay, transfer rate, mortality rate, prolonged ED stay patient ratio) of the isolation beds were significantly higher than those of the ED regular bed (P<0.05). The prolonged ED stay-patient ratio of isolation beds and regular beds was affected by the number of COVID-19 patients (regular bed, r=0.617 and P=0.01; isolation bed, r=0.525 and P=0.03). The average ED-length of stay of isolation beds was longer than that of the ED regular beds. One hundred and forty-five patients were classified as prolonged ED stay patients. Their time from the decision point to the discharge point comprised a higher rate with an average of 76.52%. @*Conclusion@#ED isolation beds are more vulnerable to infectious disease outbreaks. A proper medical policy and arrangement management system that can flexibly deal with disaster emergencies are required