Detection of rare mutations, copy number alterations, and methylation in the same template DNA molecules.

The analysis of cell-free DNA (cfDNA) from plasma offers great promise for the earlier detection of cancer. At present, changes in DNA sequence, methylation, or copy number are the most sensitive ways to detect the presence of cancer. To further increase the sensitivity of such assays with limited amounts of sample, it would be useful to be able to evaluate the same template molecules for all these changes. Here, we report an approach, called MethylSaferSeqS, that achieves this goal, and can be applied to any standard library preparation method suitable for massively parallel sequencing. The innovative step was to copy both strands of each DNA-barcoded molecule with a primer that allows the subsequent separation of the original strands (retaining their 5-methylcytosine residues) from the copied strands (in which the 5-methylcytosine residues are replaced with unmodified cytosine residues). The epigenetic and genetic alterations present in the DNA molecules can then be obtained from the original and copied strands, respectively. We applied this approach to plasma from 265 individuals, including 198 with cancers of the pancreas, ovary, lung, and colon, and found the expected patterns of mutations, copy number alterations, and methylation. Furthermore, we could determine which original template DNA molecules were methylated and/or mutated. MethylSaferSeqS should be useful for addressing a variety of questions relating genetics and epigenetics.

Receptor binding and tortuosity explain morphogen local-to-global diffusion coefficient transition.

Morphogens are intercellular signaling molecules providing spatial information to cells in developing tissues to coordinate cell fate decisions. The spatial information is encoded within long-ranged concentration gradients of the morphogen. Direct measurement of morphogen dynamics in a range of systems suggests that local and global diffusion coefficients can differ by orders of magnitude. Further, local diffusivity can be large, which would potentially abolish any concentration gradient rapidly. Such observations have led to alternative transport models being proposed, including transcytosis and cytonemes. Here, we show that accounting for tissue architecture combined with receptor binding is sufficient to hinder the diffusive dynamics of morphogens, leading to an order of magnitude decrease in the effective diffusion coefficient from local to global scales. In particular, we built a realistic in silico architecture of the extracellular spaces of the zebrafish brain using light and electron microscopy data. Simulations on realistic architectures demonstrate that tortuosity and receptor binding within these spaces are sufficient to reproduce experimentally measured morphogen dynamics. Importantly, this work demonstrates that hindered diffusion is a viable mechanism for gradient formation, without requiring additional regulatory control.

What we have learned from in-vitro studies of the chimney endovascular technique for treatment of complex abdominal aortic aneurysms: A systematic review.

BACKGROUND: A considerable number of patients with abdominal aortic aneurysms (AAA) is not eligible for standard endovascular repair. These complex cases require alternative surgical approaches including the readily available chimney graft endovascular aneurysm repair (Ch-EVAR) or sealing (Ch-EVAS). The optimal configuration for Ch-EVAR or Ch-EVAS is important for success but not yet known. OBJECTIVE: The aim of the present study was to analyze current data of the outcomes of in-vitro chimney graft treatment in complex AAA. METHODS: A systematic review following PRISMA guidelines was conducted including studies reporting on gutter size, main graft compression, and chimney graft compression in in-vitro configurations. RESULTS: The search resulted in 285 articles. 11 studies considering 219 individual tests could be included. Gutter size was comparable between Ch-EVAR and Ch-EVAS configurations. In Ch-EVAR set-ups, the deployed BECG were Advanta V12, VIABAHN®, and BeGraft. One type of SECG was used: VIABAHN®. The four types of main grafts (MG) deployed were: Endurant™ I/II; EXCLUDER Conformable AAA Endoprosthesis and AAA Endoprosthesis, and AFX™ Endovascular AAA Delivery System. In the EVAS-configurations, the Nellix® EVAS system was deployed. In general, SECG presented smaller gutters with higher chimney graft compression. 30% main grafts oversizing seems to give the smallest gutters without high risk of infolding of MG. Oversizing, EndoAnchors, and secondary endobag filling (in Ch-EVAS) reduced gutter sizes. CG ballooning during the entire polymer injection in Ch-EVAS prevented CG compression. CONCLUSION: In-vitro investigations provide insight in optimal Ch-EVAR and Ch-EVAS configurations for simulated complex AAA repair. The findings above might aid physicians in their planning to potential CG set-ups and can be used in future research to refine the most optimal configuration for chimney graft technique in complex AAA.

Support of deep learning to classify vocal fold images in flexible laryngoscopy.

PURPOSE: To collect a dataset with adequate laryngoscopy images and identify the appearance of vocal folds and their lesions in flexible laryngoscopy images by objective deep learning models. METHODS: We adopted a number of novel deep learning models to train and classify 4549 flexible laryngoscopy images as no vocal fold, normal vocal folds, and abnormal vocal folds. This could help these models recognize vocal folds and their lesions within these images. Ultimately, we made a comparison between the results of the state-of-the-art deep learning models, and another comparison of the results between the computer-aided classification system and ENT doctors. RESULTS: This study exhibited the performance of the deep learning models by evaluating laryngoscopy images collected from 876 patients. The efficiency of the Xception model was higher and steadier than almost the rest of the models. The accuracy of no vocal fold, normal vocal folds, and vocal fold abnormalities on this model were 98.90 %, 97.36 %, and 96.26 %, respectively. Compared to our ENT doctors, the Xception model produced better results than a junior doctor and was near an expert. CONCLUSION: Our results show that current deep learning models can classify vocal fold images well and effectively assist physicians in vocal fold identification and classification of normal or abnormal vocal folds.

Using GARDEN-NET and ChAseR to explore human haematopoietic 3D chromatin interaction networks.

We introduce an R package and a web-based visualization tool for the representation, analysis and integration of epigenomic data in the context of 3D chromatin interaction networks. GARDEN-NET allows for the projection of user-submitted genomic features on pre-loaded chromatin interaction networks, exploiting the functionalities of the ChAseR package to explore the features in combination with chromatin network topology properties. We demonstrate the approach using published epigenomic and chromatin structure datasets in haematopoietic cells, including a collection of gene expression, DNA methylation and histone modifications data in primary healthy myeloid cells from hundreds of individuals. These datasets allow us to test the robustness of chromatin assortativity, which highlights which epigenomic features, alone or in combination, are more strongly associated with 3D genome architecture. We find evidence for genomic regions with specific histone modifications, DNA methylation, and gene expression levels to be forming preferential contacts in 3D nuclear space, to a different extent depending on the cell type and lineage. Finally, we examine replication timing data and find it to be the genomic feature most strongly associated with overall 3D chromatin organization at multiple scales, consistent with previous results from the literature.

Vertical distributions and risk assessment of phosphorus in core sediments from the Can Gio coastal district in southern Vietnam.

In this study, total phosphorus (P) and P released forms were measured in core sediments from the areas affected by human settlement and shrimp farming activities and the core zone of the Can Gio Biosphere Reserve, a coastal district in south Vietnam. Furthermore, ecological risk assessment and parameters controlling P release from sediments were investigated, including pH, major elements (Al-Ca-Mg-Fe), and fine fraction. The average total amount of P in the sediments varied from 287 to 669 mg/kg, with significantly lower values being observed in the mangrove biosphere reserve area. According to the results of the correlation analysis, organic matter was the primary source of P in the sediments, but the majority of the P released was inorganic. Positive correlations were found between Fe and non-apatite inorganic P (NAIP) and apatite P (AP), as well as intercorrelations between P fractions (r = 0.40-0.79, p < 0.05), suggesting that Fe might be the controlling factor of P release in the investigated sediments. The rank orders of concentrations of P forms were significantly different between the areas. The range of P forms was AP (35-248 mg/kg) > NAIP (63-201 mg/kg) > LP (labile P) (4-25 mg/kg) in the human settlement and aquaculture areas and NAIP (84-99 mg/kg) > AP (20-38 mg/kg) > LP (7-12 mg/kg) in the mangrove biosphere reserve area. Risk assessment based on the total concentration of P and the availability of P from a single extraction suggested a relatively low risk of P from sediment as an internal load in the studied areas.

Trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City, Vietnam (1996-2015): a population-based study.

BACKGROUND: The burden and trend of thyroid cancer in Vietnam have not been well documented. This study aimed to investigate the trends in incidence and histological pattern of thyroid cancer in Ho Chi Minh City from 1996 to 2015. METHODS: A population-based study retrieved data from the Ho Chi Minh City Cancer Registry during 1996-2015. Trends in the incidence of thyroid cancer were investigated based on age, gender, and histology for each 5-year period. Annual percentage change (APC) in incidence rates was estimated using Joinpoint regression analysis. RESULTS: In the study period, there were 5953 thyroid cancer cases (men-to-women ratio 1:4.5) newly diagnosed in Ho Chi Minh City with the mean age of 42.9 years (±14.9 years). The age-standardized incidence rate of thyroid cancer increased from 2.4 per 100,000 during 1996-2000 (95% confidence interval [95% CI]: 2.2-2.6) to 7.5 per 100,000 during 2011-2015 (95% CI: 7.3-7.9), corresponded to an overall APC of 8.7 (95% CI 7.6-9.9). The APC in men and women was 6.2 (95% CI: 4.2-8.2) and 9.2 (95% CI: 8.0-10.4), respectively. The incidence rate in the < 45 years age group was the highest diagnosed overall and increased significantly in both men (APC 11.0) and women (APC 10.1). Both genders shared similar distribution of subtype incidences, with papillary thyroid cancer constituted the most diagnosed (73.3% in men and 85.2% in women). The papillary thyroid cancer observed a markedly increase overall (APC of 10.7 (95% CI 9.3-12.0)). CONCLUSIONS: There were appreciable increases in the age-standardized incidence rate of thyroid cancer in both genders, mainly contributed by the papillary subtype. The age of patients at diagnosis decreased gradually. The widespread utilization of advanced diagnostic techniques and healthcare accessibility improvement might play a potential role in these trends. Further investigations are needed to comprehend the risk factors and trends fully.

Field- and clinically derived estimates of Wolbachia-mediated blocking of dengue virus transmission potential in Aedes aegypti mosquitoes.

The wMel strain of Wolbachia can reduce the permissiveness of Aedes aegypti mosquitoes to disseminated arboviral infections. Here, we report that wMel-infected Ae. aegypti (Ho Chi Minh City background), when directly blood-fed on 141 viremic dengue patients, have lower dengue virus (DENV) transmission potential and have a longer extrinsic incubation period than their wild-type counterparts. The wMel-infected mosquitoes that are field-reared have even greater relative resistance to DENV infection when fed on patient-derived viremic blood meals. This is explained by an increased susceptibility of field-reared wild-type mosquitoes to infection than laboratory-reared counterparts. Collectively, these field- and clinically relevant findings support the continued careful field-testing of wMel introgression for the biocontrol of Ae. aegypti-born arboviruses.

Fungal-specific Cyp51 inhibitor VT-1598 demonstrates in vitro activity against Candida and Cryptococcus species, endemic fungi, including Coccidioides species, Aspergillus species and Rhizopus arrhizus.

Background: Invasive fungal infections, including those caused by yeasts, moulds and endemic organisms, can be significant causes of morbidity and mortality in immunocompromised hosts, those with multiple comorbidities and occasionally immunocompetent hosts. Current antifungal agents are often limited by drug toxicities, drug interactions or the development of resistance. VT-1598 is a novel tetrazole that has greater specificity for fungal Cyp51 than currently available triazoles and thus the potential for clinically significant drug interactions is reduced. We measured the in vitro activity of VT-1598 against clinical isolates of Candida and Cryptococcus species, endemic fungi, including Coccidioides, Blastomyces and Histoplasma, Aspergillus species and Rhizopus arrhizus. Methods: Antifungal susceptibility testing was performed by broth microdilution or macrodilution methods per CLSI standards. Clinical isolates of each species were used and clinically available antifungal agents were tested against each isolate. Results: VT-1598 demonstrated in vitro activity against yeasts and moulds that was similar to or greater than that of clinically available antifungal agents, including amphotericin B, fluconazole, caspofungin, voriconazole and posaconazole. The in vitro activity of VT-1598 was also maintained against resistant isolates, including fluconazole-resistant Candida isolates. In vitro activity was also observed against endemic fungi, including Blastomyces, Histoplasma and both Coccidioides immitis and Coccidioides posadasii. Conclusions: VT-1598 demonstrated in vitro activity against yeasts, moulds and endemic fungi, which was maintained against isolates that had reduced susceptibility to other antifungals. Further studies are warranted to evaluate the in vivo efficacy of VT-1598 against various fungal pathogens.

Overcoming the data drought: exploring general practice in Australia by network analysis of big data.

OBJECTIVES: To investigate the organisation and characteristics of general practice in Australia by applying novel network analysis methods to national Medicare claims data. DESIGN: We analysed Medicare claims for general practitioner consultations during 1994-2014 for a random 10% sample of Australian residents, and applied hierarchical block modelling to identify provider practice communities (PPCs). PARTICIPANTS: About 1.7 million patients per year. MAIN OUTCOME MEASURES: Numbers and characteristics of PPCs (including numbers of providers, patients and claims), proportion of bulk-billed claims, continuity of care, patient loyalty, patient sharing. RESULTS: The number of PPCs fluctuated during the 21-year period; there were 7747 PPCs in 2014. The proportion of larger PPCs (six or more providers) increased from 32% in 1994 to 43% in 2014, while that of sole provider PPCs declined from 50% to 39%. The median annual number of claims per PPC increased from 5000 (IQR, 40-19 940) in 1994 to 9980 (190-23 800) in 2014; the proportion of PPCs that bulk-billed all patients was lowest in 2004 (21%) and highest in 2014 (29%). Continuity of care and patient loyalty were stable; in 2014, 50% of patients saw the same provider and 78% saw a provider in the same PPC for at least 75% of consultations. Density of patient sharing in a PPC was correlated with patient loyalty to that PPC. CONCLUSIONS: During 1994-2014, Australian GP practice communities have generally increased in size, but continuity of care and patient loyalty have remained stable. Our novel approach to the analysis of routinely collected data allows continuous monitoring of the characteristics of Australian general practices and their influence on patient care.

Predicting Weight Gain in Patients Treated With Clozapine: The Role of Sex, Body Mass Index, and Smoking.

OBJECTIVES: Weight gain on clozapine is highly variable and poorly predictable. Its mechanisms are not well understood. This study explores the factors that predict weight gain between 3 and 12 months of clozapine therapy in community-dwelling patients. METHODS: We conducted a retrospective audit of patients attending an outpatient clozapine clinic. Weight change from 3 to 12 months of therapy was recorded, expressed as a percentage of the 3-month weight. Univariate analyses compared percent weight change according to sex, smoking status, country of birth, and baseline body mass index. Correlations between weight gain, age, and clozapine dose were explored. A general linear model identified independent predictors of weight gain. RESULTS: The mean weight change from 3 to 12 months in 117 patients was +3.1% (range, -17% to +30%). Females gained more weight than males (+5.5% vs +1.3%, P = 0.01), smokers gained more than nonsmokers (+5.1% vs +1.2%, P = 0.02), and obese patients gained less than normal or overweight individuals (0.15% vs 4.6% and 5.2%, respectively, P = 0.01). Age and clozapine dose had no relation to weight change. On multivariate analysis, baseline BMI and smoking status remained independent predictors of percent weight change in females. These 2 predictors explained 25% of weight change in females in the first 3 to 12 months of therapy. These associations were not observed in males. CONCLUSIONS: We hypothesize that smoking affects weight change by promoting clozapine metabolism to norclozapine via cytochrome P450 enzymes. Verifying this hypothesis and exploring the mechanisms underpinning the sex dichotomy are areas for further research.

Effect of vitamin D supplementation on selected inflammatory biomarkers in older adults: a secondary analysis of data from a randomised, placebo-controlled trial.

Observational studies have suggested that 25-hydroxyvitamin D (25(OH)D) levels are associated with inflammatory markers. Most trials reporting significant associations between vitamin D intake and inflammatory markers used specific patient groups. Thus, we aimed to determine the effect of supplementary vitamin D using secondary data from a population-based, randomised, placebo-controlled, double-blind trial (Pilot D-Health trial 2010/0423). Participants were 60- to 84-year-old residents of one of the four eastern states of Australia. They were randomly selected from the electoral roll and were randomised to one of three trial arms: placebo (n 214), 750 µg (n 215) or 1500 µg (n 215) vitamin D3, each taken once per month for 12 months. Post-intervention blood samples for the analysis of C-reactive protein (CRP), IL-6, IL-10, leptin and adiponectin levels were available for 613 participants. Associations between intervention group and biomarker levels were evaluated using quantile regression. There were no statistically significant differences in distributions of CRP, leptin, adiponectin, leptin:adiponectin ratio or IL-10 levels between the placebo group and either supplemented group. The 75th percentile IL-6 level was 2·8 pg/ml higher (95 % CI 0·4, 5·8 pg/ml) in the 1500 µg group than in the placebo group (75th percentiles:11·0 v. 8·2 pg/ml), with a somewhat smaller, non-significant difference in 75th percentiles between the 750 µg and placebo groups. Despite large differences in serum 25(OH)D levels between the three groups after 12 months of supplementation, we found little evidence of an effect of vitamin D supplementation on cytokine or adipokine levels, with the possible exception of IL-6.

Association between fat-mass-and-obesity-associated (FTO) gene and hip fracture susceptibility.

OBJECTIVE: Common variants in the fat-mass-and-obesity-associated (FTO) gene are related to body mass index (BMI), which is a predictor of hip fracture risk. This study sought to examine the association between variants in the FTO gene and hip fracture risk. DESIGN AND PARTICIPANTS: This is a prospective study including 934 postmenopausal women aged 60 years and above living in Dubbo, Australia (Dubbo Osteoporosis Epidemiology Study), followed up between 1989 and 2007. MEASUREMENTS: Six single nucleotide polymorphisms (SNPs) (rs1421085, rs1558902, rs1121980, rs17817449, rs9939609 and rs9930506) of the FTO gene were genotyped using Taqman assay. Bone mineral density at the lumbar spine and femoral neck was measured by DXA (GE-Lunar) at baseline. Incidence of hip fractures during the follow-up was ascertained by reviewing X-ray reports. We used Cox's models to estimate the association between the genetic variants and hip fracture risk. We also utilized Bayes factor to evaluate the association. RESULTS: One hundred and two women (11%) had sustained a hip fracture. The incidence of hip fracture was greater in women homozygous for the minor allele of all SNPs. Women homozygous for the minor allele (AA) of rs1121980 had significantly higher risk of hip fracture (hazard ratio, 2.06; 95% CI 1.17-3.62) than women homozygous for the major allele (TT). The observed data favoured the hypothesis of FTO gene and fracture association over the hypothesis of nonassociation by a factor of nine. CONCLUSION: Common variations in the FTO gene are associated with hip fracture risk in women and that FTO gene may help improve the predictive value of hip fracture risk.

IL-10 acts as a developmental switch guiding monocyte differentiation to macrophages during a murine peritoneal infection.

The peritoneal wash of BALB/c or C57BL/6 mice contains two populations of macrophages that differ in their level of expression of MHC class II (MHC II). Although both populations efficiently phagocytose bacteria in vivo, only the MHC II(lo) population is effective at phagocytosing apoptotic cells in vivo and only the MHC II(hi) population is effective at presenting Ag to T cells in vitro. Soon after induction of a peritoneal infection both of these macrophage populations are lost from the peritoneal wash fraction. Blood monocytes then enter the inflamed peritoneum and develop into new peritoneal macrophages. Whether these monocytes develop into MHC II(lo) or into MHC II(hi) macrophages is crucially dependent on the cytokine IL-10, which is transiently elevated in the peritoneal wash during the early phase of infection. Monocytes from CD45.1 animals transferred early in infection when the IL-10 concentration is high into congenic CD45.2 recipients develop into the MHC II(lo) macrophage population. Monocytes transferred later, when the IL-10 concentration has fallen, develop into the MHC II(hi) population. In infected IL-10-deficient animals monocytes fail to develop into the MHC II(lo) population but can be induced to do so by exogenous application of IL-10. Finally, high numbers of wild-type monocytes injected into IL-10R1-deficient animals develop into MHC II(lo) macrophages and were able by a bystander effect to induce the differentiation of the endogenous monocytes to the same fate.

Care practices and traditional beliefs related to neonatal jaundice in northern Vietnam: a population-based, cross-sectional descriptive study.

BACKGROUND: The National Hospital of Pediatrics in Vietnam performed >200 exchange transfusions annually (2006-08), often on infants presenting encephalopathic from lower-level hospitals. As factors delaying care-seeking are not known, we sought to study care practices and traditional beliefs relating to neonatal jaundice in northern Vietnam. METHODS: We conducted a prospective, cross-sectional, population-based, descriptive study from November 2008 through February 2010. We prospectively identified mothers of newborns through an on-going regional cohort study. Trained research assistants administered a 78-item questionnaire to mothers during home visits 14-28 days after birth except those we could not contact or whose babies remained hospitalized at 28 days. RESULTS: We enrolled 979 mothers; 99% delivered at a health facility. Infants were discharged at a median age of 1.35 days. Only 11% received jaundice education; only 27% thought jaundice could be harmful. During the first week, 77% of newborns were kept in dark rooms. Only 2.5% had routine follow-up before 14 days. Among 118 mothers who were worried by their infant's jaundice but did not seek care, 40% held non-medical beliefs about its cause or used traditional therapies instead of seeking care. Phototherapy was uncommon: 6 (0.6%) were treated before discharge and 3 (0.3%) on readmission. However, there were no exchange transfusions, kernicterus cases, or deaths. CONCLUSIONS: Early discharge without follow-up, low maternal knowledge, cultural practices, and use of traditional treatments may limit or delay detection or care-seeking for jaundice. However, in spite of the high prevalence of these practices and the low frequency of treatment, no bad outcomes were seen in this study of nearly 1,000 newborns.

Home-use icterometry in neonatal hyperbilirubinaemia: Cluster-randomised controlled trial in Vietnam.

AIM: To determine whether home-use icterometry improves parental recognition of neonatal jaundice, early care seeking and treatment to minimize risks of bilirubin encephalopathy. METHODS: Cluster-randomised controlled trial of community-level icterometry used at home by mothers in Chi Linh, Vietnam. Rural health-care workers identified and enrolled term newborns. Post-partum mothers received jaundice education and icterometry instructions and were cluster-randomised by commune. Cases received icterometers (icterometer group (IG)) and controls did not (control group (CG)). Subjects received mobile telephone calls from post-natal days 2-7 to determine maternal recognition by visual inspection and icterometer detection of jaundice (≥ 3.0 on five-point scale). Mothers without telephones, premature newborns (<35 weeks) or newborns hospitalised >5 days were excluded. RESULTS: Three hundred fifty-two subjects were enrolled (183 IG and 169 CG), of whom 11 (3.4%) were lost to telephone follow-up. Jaundice was recognised and/or detected in 94 (27%) of all newborns. Icterometry helped 11 mothers (6%) detect neonatal jaundice that was not visually recognised by IG mothers. Detection by IG mothers was not statistically greater than CG mothers (P = 0.09). Follow-up care seeking was 8% in both groups (P = 0.2), and 11% of jaundiced newborns received treatment (9% IG vs. 16% CG, P = 0.3). Newborns who received care had bilirubin measurements that averaged 257 µmol/L IG vs. 322 µmol/L CG (P = 0.3). There were no deaths. CONCLUSIONS: In this pilot study, home-use icterometry may help improve parental detection of jaundice in rural Vietnam. However, larger studies are necessary to determine the changes in recognition, care seeking and treatment.

The association between patient-reported experiences with hospital food services and recovery outcomes - A population survey of patients from 75 public hospitals.

BACKGROUND: The quality of food service is vital to patients' experiences in care and recovery in hospitals. This study aimed to identify opportunities for improving hospital food services to enhance overall patient experiences and outcomes. METHODS: This retrospective cross-sectional study uses the Adult Admitted Patient Survey in 2019. Adult patients discharged from acute or rehabilitation care across 75 public hospitals were surveyed about their in-hospital experiences, including ratings of hospital food services, overall ratings of hospital care, complications acquired, and delayed discharge due to feeling unwell. Population weighting was applied in descriptive and multivariable logistic regression analyses. We used adjusted odds ratios (AORs) and 95% confidence intervals (CIs) to estimate the association between hospital food service and the overall rating of hospital care and two recovery outcomes. RESULTS: Eight in ten participants (weighted, 16,919/21,900) consumed food in a hospital [mean age: 60.6 years (SE:0.5; SD: 18.3), 53% female]. Compared to a fair rating, adults who rated "poor/very poor" of hospital food service were 2.7 times more likely to report dissatisfaction with overall care in the hospital [Adjusted Odds Ratio (AOR) (95% CI): 2.73 (1.49, 4.99)], 1.4 times more likely to report complications [AOR:1.43 (1.11, 1.83)] and 1.9 times more likely to report delayed discharge [AOR 1.85 (1.30, 2.62)]. More moderate ratings were associated with attenuation of risk for these outcomes. Furthermore, the magnitude of the effect for these associations was more substantial among patients from non-English-speaking backgrounds (n = 1,759) after controlling for patient characteristics. Food service attributes, including received food as ordered, food delivered within reach, the taste of the meals, and meal interruption, were significant factors for the outcomes assessed. CONCLUSION: These findings underscore the importance of patients' positive experiences of hospital food service in recovery outcomes and identify several food service indicators that can be used to monitor and improve patient experiences and recovery outcomes in hospitals.

Vision-Based Assistance for Vocal Fold Identification in Laryngoscopy with Knowledge Distillation.

Laryngoscopy images play a vital role in merging computer vision and otorhinolaryngology research. However, limited studies offer laryngeal datasets for comparative evaluation. Hence, this study introduces a novel dataset focusing on vocal fold images. Additionally, we propose a lightweight network utilizing knowledge distillation, with our student model achieving around 98.4% accuracy-comparable to the original EfficientNetB1 while reducing model weights by up to 88%. We also present an AI-assisted smartphone solution, enabling a portable and intelligent laryngoscopy system that aids laryngoscopists in efficiently targeting vocal fold areas for observation and diagnosis. To sum up, our contribution includes a laryngeal image dataset and a compressed version of the efficient model, suitable for handheld laryngoscopy devices.

Improving Laryngoscopy Image Analysis Through Integration of Global Information and Local Features in VoFoCD Dataset.

The diagnosis and treatment of vocal fold disorders heavily rely on the use of laryngoscopy. A comprehensive vocal fold diagnosis requires accurate identification of crucial anatomical structures and potential lesions during laryngoscopy observation. However, existing approaches have yet to explore the joint optimization of the decision-making process, including object detection and image classification tasks simultaneously. In this study, we provide a new dataset, VoFoCD, with 1724 laryngology images designed explicitly for object detection and image classification in laryngoscopy images. Images in the VoFoCD dataset are categorized into four classes and comprise six glottic object types. Moreover, we propose a novel Multitask Efficient trAnsformer network for Laryngoscopy (MEAL) to classify vocal fold images and detect glottic landmarks and lesions. To further facilitate interpretability for clinicians, MEAL provides attention maps to visualize important learned regions for explainable artificial intelligence results toward supporting clinical decision-making. We also analyze our model's effectiveness in simulated clinical scenarios where shaking of the laryngoscopy process occurs. The proposed model demonstrates outstanding performance on our VoFoCD dataset. The accuracy for image classification and mean average precision at an intersection over a union threshold of 0.5 (mAP50) for object detection are 0.951 and 0.874, respectively. Our MEAL method integrates global knowledge, encompassing general laryngoscopy image classification, into local features, which refer to distinct anatomical regions of the vocal fold, particularly abnormal regions, including benign and malignant lesions. Our contribution can effectively aid laryngologists in identifying benign or malignant lesions of vocal folds and classifying images in the laryngeal endoscopy process visually.

A Collagen10a1 mutation disrupts cell polarity in a medaka model for metaphyseal chondrodysplasia type Schmid.

Heterozygous mutations in COL10A1 lead to metaphyseal chondrodysplasia type Schmid (MCDS), a skeletal disorder characterized by epiphyseal abnormalities. Prior analysis revealed impaired trimerization and intracellular retention of mutant collagen type X alpha 1 chains as cause for elevated endoplasmic reticulum (ER) stress. However, how ER stress translates into structural defects remained unclear. We generated a medaka (Oryzias latipes) MCDS model harboring a 5 base pair deletion in col10a1, which led to a frameshift and disruption of 11 amino acids in the conserved trimerization domain. col10a1Δ633a heterozygotes recapitulated key features of MCDS and revealed early cell polarity defects as cause for dysregulated matrix secretion and deformed skeletal structures. Carbamazepine, an ER stress-reducing drug, rescued this polarity impairment and alleviated skeletal defects in col10a1Δ633a heterozygotes. Our data imply cell polarity dysregulation as a potential contributor to MCDS and suggest the col10a1Δ633a medaka mutant as an attractive MCDS animal model for drug screening.