Analysis of the chain mediation effect between intergenerational support and mental health of older adults in urban China: a structural equation model.

BACKGROUND: This study aimed investigate the impact of intergenerational support on the mental health of older adults in urban China. It also sought to evaluate the chain mediation effect of attitudes toward younger people and willingness to interact with younger people within a non-familial context between intergenerational support and mental health. METHODS: Data were derived from a community survey that adopted quota sampling in mainland China in 2022 (N = 780). Structural equation modeling was used to analyze the data, and the bootstrap technique was used to test the mediation effect. RESULTS: A significant positive association was found between intergenerational support and the mental health of older adults in urban China (B = 0.852, 95% confidence interval CI [0.157,1.617]). Intergenerational support had a specific indirect effect on mental health through older adults' attitudes toward younger people within a non-familial context (B = 0.665, 95% CI [0.443,1.046]). There was a chain mediation effect (B = 0.126, 95% CI [0.069,0.224]) in relation to attitudes toward younger people and the willingness to interact with younger people between intergenerational support and mental health. Mediation accounted for 44.44% of the total effects in the model. CONCLUSION: These findings help identify modifiable factors that can improve the mental health of older adults. In line with the proposed serial multiple mediation model, this study provides theoretical and practical insights concerning the synergistic effect of intergenerational support at the family level and intergenerational interaction at the community level. Policy and social service implications are also discussed.

Efficacy and Safety of Dose-Escalated Alectinib in Patients With Metastatic ALK-Positive NSCLC and Central Nervous System Relapse on Standard-Dose Alectinib.

Introduction: Central nervous system (CNS) metastases remain a common challenge in patients with ALK-positive NSCLC. We previously reported reinduction of CNS responses using dose-intensified alectinib in two patients with CNS progression on standard-dose alectinib. Nevertheless, this strategy has not been assessed in larger cohorts. Methods: Patients were eligible for this retrospective study if they had metastatic ALK-positive NSCLC with CNS relapse on alectinib 600 mg twice daily dosing and subsequently received escalated dosing (900 mg twice daily) of alectinib. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1. Results: Among 27 patients, median duration of dose-escalated alectinib was 7.7 months (95% confidence interval [CI]: 4.8-10.9), with median overall time-to-progression (TTP) of 7.1 months (95% CI: 4.4-9.6). Among 25 CNS response-assessable patients, CNS objective response rate was 12.0% (95% CI: 2.5-31.2) and CNS disease control rate was 92.0% (95% CI: 74.0-99.0), with median CNS duration of disease control of 5.3 months (95% CI: 3.4-8.3) and median CNS TTP of 7.1 months (95% CI: 4.4-9.6). Among four patients with measurable CNS disease at baseline, three experienced a best intracranial response of stable disease and one experienced intracranial partial response with CNS TTP ranging from 4.1 to 7.7 months. No patient required drug discontinuation due to treatment-related adverse event or experienced grade 3 or higher treatment-related adverse events. Conclusions: Dose-intensified alectinib was found to have tolerability and activity in patients with ALK-positive NSCLC who experienced CNS relapse on standard-dose alectinib and represents one clinically viable strategy for this population.

Hidden Flaws Behind Expert-Level Accuracy of Multimodal GPT-4 Vision in Medicine.

Recent studies indicate that Generative Pre-trained Transformer 4 with Vision (GPT-4V) outperforms human physicians in medical challenge tasks. However, these evaluations primarily focused on the accuracy of multi-choice questions alone. Our study extends the current scope by conducting a comprehensive analysis of GPT-4V's rationales of image comprehension, recall of medical knowledge, and step-by-step multimodal reasoning when solving New England Journal of Medicine (NEJM) Image Challenges - an imaging quiz designed to test the knowledge and diagnostic capabilities of medical professionals. Evaluation results confirmed that GPT-4V performs comparatively to human physicians regarding multi-choice accuracy (81.6% vs. 77.8%). GPT-4V also performs well in cases where physicians incorrectly answer, with over 78% accuracy. However, we discovered that GPT-4V frequently presents flawed rationales in cases where it makes the correct final choices (35.5%), most prominent in image comprehension (27.2%). Regardless of GPT-4V's high accuracy in multi-choice questions, our findings emphasize the necessity for further in-depth evaluations of its rationales before integrating such multimodal AI models into clinical workflows.

Comparison of control and transmission of COVID-19 across epidemic waves in Hong Kong: an observational study.

Background: Hong Kong contained COVID-19 for two years but experienced a large epidemic of Omicron BA.2 in early 2022 and endemic transmission of Omicron subvariants thereafter. We reflected on pandemic preparedness and responses by assessing COVID-19 transmission and associated disease burden in the context of implementation of various public health and social measures (PHSMs). Methods: We examined the use and impact of pandemic controls in Hong Kong by analysing data on more than 1.7 million confirmed COVID-19 cases and characterizing the temporal changes non-pharmaceutical and pharmaceutical interventions implemented from January 2020 through to 30 December 2022. We estimated the daily effective reproductive number (Rt) to track changes in transmissibility and effectiveness of community-based measures against infection over time. We examined the temporal changes of pharmaceutical interventions, mortality rate and case-fatality risks (CFRs), particularly among older adults. Findings: Hong Kong experienced four local epidemic waves predominated by the ancestral strain in 2020 and early 2021 and prevented multiple SARS-CoV-2 variants from spreading in the community before 2022. Strict travel-related, case-based, and community-based measures were increasingly tightened in Hong Kong over the first two years of the pandemic. However, even very stringent measures were unable to contain the spread of Omicron BA.2 in Hong Kong. Despite high overall vaccination uptake (>70% with at least two doses), high mortality was observed during the Omicron BA.2 wave due to lower vaccine coverage (42%) among adults ≥65 years of age. Increases in antiviral usage and vaccination uptake over time through 2022 was associated with decreased case fatality risks. Interpretation: Integrated strict measures were able to reduce importation risks and interrupt local transmission to contain COVID-19 transmission and disease burden while awaiting vaccine development and rollout. Increasing coverage of pharmaceutical interventions among high-risk groups reduced infection-related mortality and mitigated the adverse health impact of the pandemic. Funding: Health and Medical Research Fund.

Effectiveness of social distancing measures and lockdowns for reducing transmission of COVID-19 in non-healthcare, community-based settings.

Social distancing measures (SDMs) are community-level interventions that aim to reduce person-to-person contacts in the community. SDMs were a major part of the responses first to contain, then to mitigate, the spread of SARS-CoV-2 in the community. Common SDMs included limiting the size of gatherings, closing schools and/or workplaces, implementing work-from-home arrangements, or more stringent restrictions such as lockdowns. This systematic review summarized the evidence for the effectiveness of nine SDMs. Almost all of the studies included were observational in nature, which meant that there were intrinsic risks of bias that could have been avoided were conditions randomly assigned to study participants. There were no instances where only one form of SDM had been in place in a particular setting during the study period, making it challenging to estimate the separate effect of each intervention. The more stringent SDMs such as stay-at-home orders, restrictions on mass gatherings and closures were estimated to be most effective at reducing SARS-CoV-2 transmission. Most studies included in this review suggested that combinations of SDMs successfully slowed or even stopped SARS-CoV-2 transmission in the community. However, individual effects and optimal combinations of interventions, as well as the optimal timing for particular measures, require further investigation. This article is part of the theme issue 'The effectiveness of non-pharmaceutical interventions on the COVID-19 pandemic: the evidence'.

Intrinsic and Effective Severity of Coronavirus Disease 2019 Cases Infected With the Ancestral Strain and Omicron BA.2 Variant in Hong Kong.

BACKGROUND: Understanding severity of infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants is crucial to inform public health measures. Here we used coronavirus disease 2019 (COVID-19) patient data from Hong Kong to characterize the severity profile of COVID-19. METHODS: Time-varying and age-specific effective severity measured by case hospitalization risk and hospitalization fatality risk was estimated with all individual COVID-19 case data collected in Hong Kong from 23 January 2020 through 26 October 2022 over 6 epidemic waves. The intrinsic severity of Omicron BA.2 was compared with the estimate for the ancestral strain with the data from unvaccinated patients without previous infections. RESULTS: With 32 222 COVID-19 hospitalizations and 9669 deaths confirmed over 6 epidemic waves, the time-varying hospitalization fatality risk dramatically increased from <10% before the largest fifth wave of Omicron BA.2 to 41% during the peak of the fifth wave when hospital resources were severely constrained. The age-specific fatality risk in unvaccinated hospitalized Omicron cases was comparable to the estimates for unvaccinated cases with the ancestral strain. During epidemics predominated by Omicron BA.2, fatality risk was highest among older unvaccinated patients. CONCLUSIONS: Omicron has comparable intrinsic severity to the ancestral Wuhan strain, although the effective severity is substantially lower in Omicron cases due to vaccination.

Hospitalizations and mortality during the first year of the COVID-19 pandemic in Hong Kong, China: An observational study.

Background: Hong Kong followed a strict COVID-19 elimination strategy in 2020. We estimated the impact of the COVID-19 pandemic responses on all-cause and cause-specific hospitalizations and deaths in 2020. Methods: Interrupted time-series analysis using negative binomial regression accounting for seasonality and long-term trend was used on weekly 2010-2020 data to estimate the change in hospitalization risk and excess mortality occurring both within and out of hospitals. Findings: In 2020, as compared to a 2010-2019 baseline, we observed an overall reduction in all-cause hospitalizations, and a concurrent increase in deaths. The overall hospitalization reduction (per 100,000 population) was 4809 (95% CI: 4692, 4926) in 2020, with respiratory diseases (632, 95% CI: 607, 658) and cardiovascular diseases (275, 95% CI: 264, 286) contributing most. The overall excess mortality (per 100,000 population) was 25 (95% CI: 23, 27) in 2020, mostly among individuals with pre-existing cardiovascular diseases (12, 95% CI: 11, 13). A reduction in excess in-hospital mortality (-10 per 100,000, 95% CI: -12, -8) was accompanied by an increase in excess out-of-hospital mortality (32, 95% CI: 29, 34). Interpretation: The COVID-19 pandemic might have caused indirect impact on population morbidity and mortality likely through changed healthcare seeking particularly in youngest and oldest individuals and those with cardiovascular diseases. Better healthcare planning is needed during public health emergencies with disruptions in healthcare services. Funding: Health and Medical Research Fund, Collaborative Research Fund, AIR@InnoHK and RGC Senior Research Fellow Scheme, Hong Kong.

More than a duologue: In-depth insights into epitranscriptomics and ferroptosis.

Beyond transcription, RNA molecules are enzymatically modified to influence the biological functions of living organisms. The term "epitranscriptomics" describes the changes in RNA strands aside from altering the innate sequences. Modifications on adenosine (A) are the most widely characterized epitranscriptomic modification, including N6-methyladenosine (m6A), N1-methyladenosine (m1A), polyadenylation, and adenosine-to-inosine (A-to-I) RNA editing, and modifications on other nucleotides seem to be fewer, such as N7-methylguanosine (m7G), 5-methylcytosine (m5C), and pseudouridine (Ψ). These changes on the RNA strand surface, exclusively by their RNA-modifying proteins (RMPs), are reported in various biological phenomena, including programmed cell death (PCD). One necro-biological phenomenon that has been observed for long but has started to gain heed in recent years is "ferroptosis." The phospholipid peroxidation by polyunsaturated-fatty-acid-containing-phospholipid hydroperoxyl (PLOOH) radicals destroys membrane integrity due to a series of mechanisms. The Fenton reaction, constituting the final Haber-Weiss reaction that is less recognized, collaboratively leading to the conversion of polyunsaturated fatty acid (PUFA) to PLOOH, is the etymological origin of ferroptosis. However, it is with increasing evidence that ferroptotic signaling is also intervened by epitranscriptomic modifications, although the truth is still ambiguous. We attempted to delineate some up-to-date discoveries on both epitranscriptomics and ferroptosis, bringing up the fundamentals to address any potential connection between the two. Next, we discussed whether a duologal relationship, or more, exists between the two, taking the ROS level and iron status into consideration. Lastly, we surveyed future perspectives that would favor the understanding of these topics.

Epidemiology of Infections with SARS-CoV-2 Omicron BA.2 Variant, Hong Kong, January-March 2022.

Our analysis of data collected from multiple epidemics in Hong Kong indicated a shorter serial interval and generation time of infections with the SARS-CoV-2 Omicron variant. The age-specific case-fatality risk for Omicron BA.2.2 case-patients without complete primary vaccination was comparable to that of persons infected with ancestral strains in earlier waves.

Extended gene set analysis of human neuro-psychiatric traits shows enrichment in brain-expressed human accelerated regions across development.

Human neuropsychiatric disorders are associated with genetic and environmental factors affecting the brain, which has been subjected to strong evolutionary pressures resulting in an enlarged cerebral cortex and improved cognitive performance. Thus, genes involved in human brain evolution may also play a role in neuropsychiatric disorders. We test whether genes associated with 7 neuropsychiatric phenotypes are enriched in genomic regions that have experienced rapid changes in human evolution (HARs) and importantly, whether HAR status interacts with developmental brain expression to predict associated genes. We used the most recent publicly available GWAS and gene expression data to test for enrichment of HARs, brain expression, and their interaction. These revealed significant interactions between HAR status and whole-brain expression across developmental stages, indicating that the relationship between brain expression and association with schizophrenia and intelligence is stronger among HAR than non-HAR genes. Follow-up regional analyses indicated that predicted HAR-expression interaction effects may vary substantially across regions and developmental stages. Although depression indicated significant enrichment of HAR genes, little support was found for HAR enrichment among bipolar, autism, ADHD, or Alzheimer's associated genes. Our results indicate that intelligence, schizophrenia, and depression-associated genes are enriched for those involved in the evolution of the human brain. These findings highlight promising candidates for follow-up study and considerations for novel drug development, but also caution careful assessment of the translational ability of animal models for studying neuropsychiatric traits in the context of HARs, and the importance of using humanized animal models or human-derived tissues when researching these traits.

Vaccine effectiveness of one, two, and three doses of BNT162b2 and CoronaVac against COVID-19 in Hong Kong: a population-based observational study.

BACKGROUND: Hong Kong maintained low circulation of SARS-CoV-2 until a major community epidemic of the omicron (B.1.1.529) sublineage BA.2 began in January, 2022. Both mRNA (BNT162b2 [Fosun Pharma-BioNTech]) and inactivated CoronaVac (Sinovac, Beijing, China) vaccines are widely available; however, vaccination coverage has been low, particularly in older adults aged 70 years or older. We aimed to assess vaccine effectiveness in this predominantly infection-naive population. METHODS: In this observational study, we used individual-level case data on mild or moderate, severe or fatal, and fatal disease in patients hospitalised with COVID-19 along with census information and coverage data of BNT162b2 and CoronaVac. We used a negative binomial model, adjusting for age, sex, and calendar day to estimate vaccine effectiveness of one, two, and three doses of both BNT162b2 and CoronaVac vaccines, and relative effectiveness by number of doses and vaccine type. FINDINGS: Between Dec 31, 2020, and March 16, 2022, 13·2 million vaccine doses were administered in Hong Kong's 7·4-million population. We analysed data from confirmed cases with mild or moderate (n=5566), severe or fatal (n=8875), and fatal (n=6866) COVID-19. Two doses of either vaccine protected against severe disease and death within 28 days of a positive test, with higher effectiveness among adults aged 60 years or older with BNT162b2 (vaccine effectiveness 89·3% [95% CI 86·6-91·6]) compared with CoronaVac (69·9% [64·4-74·6]). Three doses of either vaccine offered very high levels of protection against severe or fatal outcomes (97·9% [97·3-98·4]). INTERPRETATION: Third doses of either BNT162b2 or CoronaVac provide substantial additional protection against severe COVID-19 and should be prioritised, particularly in older adults older than 60 years and others in high-risk populations who received CoronaVac primary schedules. Longer follow-up is needed to assess duration of protection across different vaccine platforms and schedules. FUNDING: COVID-19 Vaccines Evaluation Program, Chinese Center for Disease Control and Prevention.

Estimating excess septicaemia mortality and hospitalisation burden associated with influenza in Hong Kong, 1998 to 2019.

Influenza virus infections can lead to a number of secondary complications, including sepsis. We applied linear regression models to mortality and hospital admission data coded for septicaemia from 1998 to 2019 in Hong Kong, and estimated that septicaemia was associated with an annual average excess mortality rate of 0.23 (95% CI 0.04-0.40) per 100 000 persons per year and an excess septicaemia hospitalisation rate of 1.73 (95% CI 0.94-2.50) per 100 000 persons per year. The highest excess morbidity and mortality was found in older adults and young children, and during influenza A(H3N2) epidemics.

Temporal changes in factors associated with COVID-19 vaccine hesitancy and uptake among adults in Hong Kong: Serial cross-sectional surveys.

Background: COVID-19 vaccine hesitancy can lead to reduced vaccine uptake and hinder the safe relaxation of other public health measures. This study aims to explore the factors associated with vaccine hesitancy and uptake among adults before and after the implementation of the COVID-19 vaccination program in Hong Kong. Methods: Cross-sectional telephone surveys were conducted every four weeks over a nine-month period from November 2020 through July 2021. Target respondents were Hong Kong resident aged 18 or above and recruited by random-digit dialling. In each survey, responses on COVID-19 vaccine hesitancy and COVID-19 vaccine uptake were collected as primary and secondary outcomes, respectively. Data of potentially associated factors, including socio-demographics, chronic medical conditions, perceived risk of COVID-19, perceived personal efficacy in self-protection, confidence in the government's ability to control the pandemic, compliance with social distancing measures, and confidence in COVID-19 vaccines, were also collected. Multivariable logistic regression models were used to examine the factors associated with COVID-19 vaccine hesitancy at different time points. Findings: Ten cross-sectional surveys were conducted, including 7411 respondents. The levels of vaccine hesitancy fluctuated over time. From December 2020 to May 2021, the age group with the highest vaccine hesitancy was young adults 18-34y, while the vaccine hesitancy was highest among adults ≥ 65y in June-July 2021 (Fig. 2C). Our regression analyses (Fig. 3) showed that before and at the beginning of the rollout of the mass vaccination program, there was no statistically significant association between chronic medical conditions and vaccine hesitancy. However, two-five months after the program implementation respondents with chronic medical conditions were more likely to be hesitant. From January to June 2021, higher confidence in the government was associated with lower vaccine hesitancy (Fig. 3). Confidence in COVID-19 vaccines was consistently associated with lower vaccine hesitancy at different stages of the program. Interpretation: The factors associated with COVID-19 vaccine hesitancy changed over time. This study highlighted the importance to monitor temporal changes in COVID-19 vaccine hesitancy and associated factors, and adjust promotion strategies correspondingly to boost vaccination uptake. Funding: Health and Medical Research Fund, Hong Kong.

Incorporating temporal distribution of population-level viral load enables real-time estimation of COVID-19 transmission.

Many locations around the world have used real-time estimates of the time-varying effective reproductive number ([Formula: see text]) of COVID-19 to provide evidence of transmission intensity to inform control strategies. Estimates of [Formula: see text] are typically based on statistical models applied to case counts and typically suffer lags of more than a week because of the latent period and reporting delays. Noting that viral loads tend to decline over time since illness onset, analysis of the distribution of viral loads among confirmed cases can provide insights into epidemic trajectory. Here, we analyzed viral load data on confirmed cases during two local epidemics in Hong Kong, identifying a strong correlation between temporal changes in the distribution of viral loads (measured by RT-qPCR cycle threshold values) and estimates of [Formula: see text] based on case counts. We demonstrate that cycle threshold values could be used to improve real-time [Formula: see text] estimation, enabling more timely tracking of epidemic dynamics.

Community psychological and behavioural responses to coronavirus disease 2019 over one year of the pandemic in 2020 in Hong Kong.

Monitoring community psychological and behavioural responses to coronavirus disease 2019 (COVID-19) is important for informing policy making and risk communication to sustain public compliance with challenging precautionary behaviours and mitigating the psychological impacts. Monthly telephone-based cross-sectional surveys in January-April 2020 and then weekly surveys from May through December 2020 were conducted to monitor changes in public risk perception of COVID-19, personal efficacy in self-protection, confidence in government's ability to control the pandemic, precautionary behaviours, perceived impact of precautionary behaviours, psychological fatigue and distress in Hong Kong, and examine their inter-relationships. While worry about contracting COVID-19 increased, personal efficacy and confidence in government declined as the community incidence of COVID-19 increased. The public maintained high compliance with most precautionary behaviours throughout but relaxed behaviours that were more challenging when disease incidence declined. Public confidence in government was persistently low throughout, of which, a lower level was associated with more psychological fatigue, lower compliance with precautionary behaviours and greater psychological distress. Perceived greater negative impact of precautionary behaviours was also associated with more psychological fatigue which in turn was associated with relaxation of precautionary behaviours. Female, younger and unemployed individuals reported greater psychological distress throughout different stages of the pandemic. Risk communication should focus on promoting confidence in self-protection and pandemic control to avoid helplessness to act when the pandemic resurges. Policy making should prioritize building public trust, enhancing support for sustaining precautionary behaviours, and helping vulnerable groups to adapt to the stress during the pandemic.

Kidney-Targeted Redox Scavenger Therapy Prevents Cisplatin-Induced Acute Kidney Injury.

Cisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. We investigated a drug delivery strategy to improve the pharmacokinetics of an approved therapy that does not normally demonstrate appreciable efficacy in CI-AKI, as a preventive intervention. In prior work, we developed a kidney-selective mesoscale nanoparticle (MNP) that targets the renal proximal tubular epithelium. Here, we found that the nanoparticles target the kidneys in a mouse model of CI-AKI with significant damage. We evaluated MNPs loaded with the reactive oxygen species scavenger edaravone, currently used to treat stroke and ALS. We found a marked and significant therapeutic benefit with edaravone-loaded MNPs, including improved renal function, which we demonstrated was likely due to a decrease in tubular epithelial cell damage and death imparted by the specific delivery of edaravone. The results suggest that renal-selective edaravone delivery holds potential for the prevention of acute kidney injury among patients undergoing cisplatin-based chemotherapy.

Nanoreporter of an Enzymatic Suicide Inactivation Pathway.

Enzymatic suicide inactivation, a route of permanent enzyme inhibition, is the mechanism of action for a wide array of pharmaceuticals. Here, we developed the first nanosensor that selectively reports the suicide inactivation pathway of an enzyme. The sensor is based on modulation of the near-infrared fluorescence of an enzyme-bound carbon nanotube. The nanosensor responded selectively to substrate-mediated suicide inactivation of the tyrosinase enzyme via bathochromic shifting of the nanotube emission wavelength. Mechanistic investigations revealed that singlet oxygen generated by the suicide inactivation pathway induced the response. We used the nanosensor to quantify the degree of enzymatic inactivation by measuring response rates to small molecule tyrosinase modulators. This work resulted in a new capability of interrogating a specific route of enzymatic death. Potential applications include drug screening and hit-validation for compounds that elicit or inhibit enzymatic inactivation and single-molecule measurements to assess population heterogeneity in enzyme activity.

Automatic Vertebral Body Segmentation Based on Deep Learning of Dixon Images for Bone Marrow Fat Fraction Quantification.

Background: Bone marrow fat (BMF) fraction quantification in vertebral bodies is used as a novel imaging biomarker to assess and characterize chronic lower back pain. However, manual segmentation of vertebral bodies is time consuming and laborious. Purpose: (1) Develop a deep learning pipeline for segmentation of vertebral bodies using quantitative water-fat MRI. (2) Compare BMF measurements between manual and automatic segmentation methods to assess performance. Materials and Methods: In this retrospective study, MR images using a 3D spoiled gradient-recalled echo (SPGR) sequence with Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) reconstruction algorithm were obtained in 57 subjects (28 women, 29 men, mean age, 47.2 ± 12.6 years). An artificial network was trained for 100 epochs on a total of 165 lumbar vertebrae manually segmented from 31 subjects. Performance was assessed by analyzing the receiver operating characteristic curve, precision-recall, F1 scores, specificity, sensitivity, and similarity metrics. Bland-Altman analysis was used to assess performance of BMF fraction quantification using the predicted segmentations. Results: The deep learning segmentation method achieved an AUC of 0.92 (CI 95%: 0.9186, 0.9195) on a testing dataset (n = 24 subjects) on classification of pixels as vertebrae. A sensitivity of 0.99 and specificity of 0.80 were achieved for a testing dataset, and a mean Dice similarity coefficient of 0.849 ± 0.091. Comparing manual and automatic segmentations on fat fraction maps of lumbar vertebrae (n = 124 vertebral bodies) using Bland-Altman analysis resulted in a bias of only -0.605% (CI 95% = -0.847 to -0.363%) and agreement limits of -3.275% and +2.065%. Automatic segmentation was also feasible in 16 ± 1 s. Conclusion: Our results have demonstrated the feasibility of automated segmentation of vertebral bodies using deep learning models on water-fat MR (Dixon) images to define vertebral regions of interest with high specificity. These regions of interest can then be used to quantify BMF with comparable results as manual segmentation, providing a framework for completely automated investigation of vertebral changes in CLBP.

Peptide-TLR-7/8a conjugate vaccines chemically programmed for nanoparticle self-assembly enhance CD8 T-cell immunity to tumor antigens.

Personalized cancer vaccines targeting patient-specific neoantigens are a promising cancer treatment modality; however, neoantigen physicochemical variability can present challenges to manufacturing personalized cancer vaccines in an optimal format for inducing anticancer T cells. Here, we developed a vaccine platform (SNP-7/8a) based on charge-modified peptide-TLR-7/8a conjugates that are chemically programmed to self-assemble into nanoparticles of uniform size (~20 nm) irrespective of the peptide antigen composition. This approach provided precise loading of diverse peptide neoantigens linked to TLR-7/8a (adjuvant) in nanoparticles, which increased uptake by and activation of antigen-presenting cells that promote T-cell immunity. Vaccination of mice with SNP-7/8a using predicted neoantigens (n = 179) from three tumor models induced CD8 T cells against ~50% of neoantigens with high predicted MHC-I binding affinity and led to enhanced tumor clearance. SNP-7/8a delivering in silico-designed mock neoantigens also induced CD8 T cells in nonhuman primates. Altogether, SNP-7/8a is a generalizable approach for codelivering peptide antigens and adjuvants in nanoparticles for inducing anticancer T-cell immunity.

Congenital Granular Cell Epulis: Classic Presentation and Its Differential Diagnosis.

Congenital granular cell epulis (CGCE) is an uncommon lesion of unclear pathogenesis. It occurs predominantly in female newborns with a predilection site of the maxillary alveolar ridge. The mass enlarges prenatally but the growth arrests after birth. Histologically, CGCE is characterized by a proliferation of polygonal cells with eosinophilic, granular cytoplasm and eccentric, bland-appearing nuclei. It closely resembles adult granular cell tumor (GCT) microscopically and S-100 immunostain is often helpful in distinguishing the two (S-100-positive in GCT and S-100-negative in CGCE). Clinically, the lesion should also be distinguished from entities such as infantile myofibroma, rhabdomyoma, melanotic neuroectodermal tumor of infancy, peripheral odontogenic fibroma, and neurofibroma. CGCE demonstrates an excellent prognosis and has not been associated with any syndromes/genetic defects or malignant transformation. Clinicians and pathologists should be familiar with this rare entity and its differential diagnosis for accurate diagnosis and management.