Cancer-Associated Fibroblasts in Esophageal Cancer.

Cancer-associated fibroblasts (CAFs), a heterogenous population, can promote cancer cell proliferation, migration, invasion, immunosuppression, and therapeutic resistance in solid tumors. These effects are mediated through secretion of cytokines and growth factors, remodeling of the extracellular matrix, and providing metabolic support for cancer cells. The presence of CAFs in esophageal carcinoma are associated with reduced overall survival and increased resistance to chemotherapy and radiotherapy; thus, identifying therapeutic vulnerabilities of CAFs is a necessity. In esophageal cancer, the mechanisms for CAF recruitment, CAF-mediated promotion of tumorigenesis, metastatic dissemination, and therapeutic resistance have yet to be fully evaluated. Here, we provide an overview of the current understanding of CAFs in esophageal cancer, namely in esophageal squamous cell carcinoma and esophageal adenocarcinoma, as well as in the preneoplastic conditions that predispose to these cancers. Interestingly, there is a discrepancy in our knowledge of CAF biology between esophageal cancer subtypes, with very few studies in esophageal adenocarcinoma, and its precursor lesion Barrett's esophagus, compared with esophageal squamous cell carcinoma. We propose that although great strides have been made, certain questions remain to which answers hopefully will emerge to have an impact on biomarker diagnostics and translational therapeutics.

Survival at older ages: are greater influenza antibody titers protective?

Antibodies are a core element of the immune system's defense against infectious diseases. We hypothesize that antibody titres might therefore be an important predictor of survival in older individuals. This is important because biomarkers that robustly measure survival have proved elusive, despite their potential utility in health care settings. We present evidence supporting the hypothesis that influenza antibody titres are associated with overall survival of older individuals, and indicate a role for biological sex in modulating this association. Since antibody titres can be modulated by vaccination, these results have important implications for public health policy on influenza control in aging populations.

Anatomical tilt lateral wrist X-ray - Not always 22°.

INTRODUCTION: Open Reduction and Internal Fixation (ORIF) with volar locking plates are commonly used to manage distal radial fractures. The anatomical tilt lateral (ATL) wrist X-ray is often required for evaluation of intra-articular screw penetration due to the screw position. This study aims to evaluate the correlation between the tube angulation given by performing radiographers for the ATL projection and the post-examination measurement of radial inclination (RI) on the Posterior Anterior (PA) wrist image. METHODS: A retrospective review was performed for 36 patients. A standardised method developed by Kreder et al. (1996) was used to measure the RI on the PA wrist image. All ATL images sent into Picture Archiving and Communications System (PACS) have the tube angulation applied annotated on the image. Pearson's correlation was used to analyse the co-relationship between the RI and the tube angle applied for ATL projection. RESULTS: The average angle of RI measured by the four observers was 19. Normality of 0.385 was established. A positive correlation (p = 0.792) between the RI and the tube angle applied for ATL was found. CONCLUSION: Our study found a strong positive correlation between the tube angulation applied by performing radiographers for the ATL projection and the post-examination RI measured on the PA wrist image by the independent reviewers. This suggests that radiographers can use the measured RI to apply the tube angulation when performing the ATL wrist X-ray, instead of estimating the tube angulation to be applied. IMPLICATIONS FOR PRACTICE: Using the measured RI to apply the tube angulation when performing the ATL wrist X-ray will ensure a more reliable and reproducible way that could reduce the number of repeated images and, thus, unnecessary radiation dose to patients.

Evaluation of a group-based sensorimotor intervention programme to improve Chinese handwriting of primary school students.

Objective: Sensorimotor performance is influential in Chinese handwriting, but few studies have examined the efficacy of sensorimotor-based interventions on Chinese handwriting among primary school students with poor handwriting performance. The study aims to evaluate a sensorimotor-based intervention to improve handwriting in the mainstream primary schools. Methods: This study adopted a two-group pretest-posttest design. An 8-session group-based sensorimotor intervention was delivered to school-aged children (mean age = 8.1, 68% male). Group A had 2 sessions every week, while Group B had 4 sessions every week. Analysis of variance with repeated measures was used to test the effects. Results: The intervention had a significant time effect (p < .05) in terms of improving handwriting process (d = 0.33-1.10), manual dexterity (d = 0.57), visual memory (d = 0.70), visual-spatial perception (d = 0.37), and motor and postural skills (d = 0.73). The effect sizes ranged from medium to large. For the handwriting process, time per character had a significant group × time interaction, with post hoc analysis showing that Group A had a significantly large effect (d = 1.89, p < .001) while Group B did not. Conclusions: The group-based sensorimotor intervention programme appeared to show improvements in students with fair skills in writing Chinese characters. It appears that the effect is better if the training sessions are spaced out in one month rather than intensively conducted within two weeks. It might be related to more involvement from parents, and students need more time for practice after the training sessions.

Antibiotic use for respiratory tract infections among older adults living in long-term care facilities: a systematic review and meta-analysis.

BACKGROUND: Antibiotics are commonly prescribed for respiratory tract infections (RTIs) among older adults in long-term care facilities (LTCFs), and this contributes to the emergence of antimicrobial resistance. The objective of this study was to determine the antibiotic prescribing rate for RTIs among LTCF residents, and to analyse the antibiotic consumption patterns with the AwaRe monitoring tool, developed by the World Health Organization. METHODS: MEDLINE, EMBASE and CINAHL were searched from inception to March 2022. Original articles reporting antibiotic use for RTIs in LTCFs were included in this review. Study quality was assessed using the Joanna Briggs Institute's Critical Appraisal Checklist for Prevalence Data. A random-effects meta-analysis was employed to calculate the pooled estimates. Subgroup analysis was conducted by type of RTI, country, and study start year. RESULTS: In total, 47 articles consisting of 50 studies were included. The antibiotic prescribing rate ranged from 21.5% to 100% (pooled estimate 69.8%, 95% confidence interval 55.2-82.6%). The antibiotic prescribing rate for lower respiratory tract infections (LRTIs) was higher than the rates for viral and general RTIs. Compared with Italy, France and the USA, the Netherlands had lower antibiotic use for LRTIs. A proportion of viral RTIs were treated with antibiotics, and all the antibiotics were from the Watch group. Use of antibiotics in the Access group was higher in the Netherlands, Norway, Switzerland and Slovenia compared with the USA and Australia. CONCLUSION: The antibiotic prescribing rate for RTIs in LTCFs was high, and AWaRe antibiotic use patterns varied by type of RTI and country. Improving antibiotic use may require coordination efforts.

Bimodal-Structured 0.9KNbO3-0.1BaTiO3 Solid Solutions with Highly Enhanced Electrocaloric Effect at Room Temperature.

0.9KNbO3-0.1BaTiO3 ceramics, with a bimodal grain size distribution and typical tetragonal perovskite structure at room temperature, were prepared by using an induced abnormal grain growth (IAGG) method at a relatively low sintering temperature. In this bimodal grain size distribution structure, the extra-large grains (~10-50 µm) were evolved from the micron-sized filler powders, and the fine grains (~0.05-0.35 µm) were derived from the sol precursor matrix. The 0.9KNbO3-0.1BaTiO3 ceramics exhibit relaxor-like behavior with a diffused phase transition near room temperature, as confirmed by the presence of the polar nanodomain regions revealed through high resolution transmission electron microscope analyses. A large room-temperature electrocaloric effect (ECE) was observed, with an adiabatic temperature drop (ΔT) of 1.5 K, an isothermal entropy change (ΔS) of 2.48 J·kg-1·K-1, and high ECE strengths of |ΔT/ΔE| = 1.50 × 10-6 K·m·V-1 and ΔS/ΔE = 2.48 × 10-6 J·m·kg-1·K-1·V-1 (directly measured at E = 1.0 MV·m-1). These greatly enhanced ECEs demonstrate that our simple IAGG method is highly appreciated for synthesizing high-performance electrocaloric materials for efficient cooling devices.

MUC1-C integrates type II interferon and chromatin remodeling pathways in immunosuppression of prostate cancer.

The oncogenic MUC1-C protein drives dedifferentiation of castrate resistant prostate cancer (CRPC) cells in association with chromatin remodeling. The present work demonstrates that MUC1-C is necessary for expression of IFNGR1 and activation of the type II interferon-gamma (IFN-γ) pathway. We show that MUC1-C→ARID1A/BAF signaling induces IFNGR1 transcription and that MUC1-C-induced activation of the NuRD complex suppresses FBXW7 in stabilizing the IFNGR1 protein. MUC1-C and NuRD were also necessary for expression of the downstream STAT1 and IRF1 transcription factors. We further demonstrate that MUC1-C and PBRM1/PBAF are necessary for IRF1-induced expression of (i) IDO1, WARS and PTGES, which metabolically suppress the immune tumor microenvironment (TME), and (ii) the ISG15 and SERPINB9 inhibitors of T cell function. Of translational relevance, we show that MUC1 associates with expression of IFNGR1, STAT1 and IRF1, as well as the downstream IDO1, WARS, PTGES, ISG15 and SERPINB9 immunosuppressive effectors in CRPC tumors. Analyses of scRNA-seq data further demonstrate that MUC1 correlates with cancer stem cell (CSC) and IFN gene signatures across CRPC cells. Consistent with these results, MUC1 associates with immune cell-depleted "cold" CRPC TMEs. These findings demonstrate that MUC1-C integrates chronic activation of the type II IFN-γ pathway and induction of chromatin remodeling complexes in linking the CSC state with immune evasion.

Spatial deviations of the temporomandibular joint after oncological mandibular reconstruction.

Spatial deviations of the temporomandibular joint (TMJ) after oncological mandibular reconstruction are important to the aesthetic and functional rehabilitation. The aim of this study was to clarify whether and how three dimensionally (3D) printed patient-specific surgical plates, and the preservation of the condyle or ramus, affect spatial deviations of the TMJ. A total of 33 patients who underwent mandibular reconstruction via computer-assisted surgery were included. Regarding absolute deviations, patients in the 3D-printed plate group showed smaller TMJ deviations compared to those in the conventional plate group. There was no difference in absolute deviations of the TMJ regardless of whether the condyle or ramus was preserved. Regarding physiological deviations, the impact on the contralateral TMJ was smaller in the 3D-printed plate group. Patients with both the condyle and ramus removed had significantly higher deviations of the condyle and joint space. In summary, 3D-printed patient-specific surgical plates improved the spatial accuracy of the TMJ. Under physiological conditions, TMJ deviations on the operated side were mainly affected by the preservation of the condyle. Removal of both the condyle and ramus caused more severe spatial interference to the TMJ; this should be further confirmed.

Mutant p53 regulates Survivin to foster lung metastasis.

Esophageal squamous cell carcinoma (ESCC) is one of the most lethal cancers worldwide and evolves often to lung metastasis. P53R175H (homologous to Trp53R172H in mice) is a common hot spot mutation. How metastasis is regulated by p53R175H in ESCC remains to be investigated. To investigate p53R175H-mediated molecular mechanisms, we used a carcinogen-induced approach in Trp53R172H/- mice to model ESCC. In the primary Trp53R172H/- tumor cell lines, we depleted Trp53R172H (shTrp53) and observed a marked reduction in cell invasion in vitro and lung metastasis burden in a tail-vein injection model in comparing isogenic cells (shCtrl). Furthermore, we performed bulk RNA-seq to compare gene expression profiles of metastatic and primary shCtrl and shTrp53 cells. We identified the YAP-BIRC5 axis as a potential mediator of Trp53R172H -mediated metastasis. We demonstrate that expression of Survivin, an antiapoptotic protein encoded by BIRC5, increases in the presence of Trp53R172H Furthermore, depletion of Survivin specifically decreases Trp53R172H-driven lung metastasis. Mechanistically, Trp53R172H but not wild-type Trp53, binds with YAP in ESCC cells, suggesting their cooperation to induce Survivin expression. Furthermore, Survivin high expression level is associated with increased metastasis in several GI cancers. Taken together, this study unravels new insights into how mutant p53 mediates metastasis.

Automated Cerebral Hemorrhage Detection Using RAPID.

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) is an important event that is diagnosed on head NCCT. Increased NCCT utilization in busy hospitals may limit timely identification of ICH. RAPID ICH is an automated hybrid 2D-3D convolutional neural network application designed to detect ICH that may allow for expedited ICH diagnosis. We determined the accuracy of RAPID ICH for ICH detection and ICH volumetric quantification on NCCT. MATERIALS AND METHODS: NCCT scans were evaluated for ICH by RAPID ICH. Consensus detection of ICH by 3 neuroradiology experts was used as the criterion standard for RAPID ICH comparison. ICH volume was also automatically determined by RAPID ICH in patients with intraparenchymal or intraventricular hemorrhage and compared with manually segmented ICH volumes by a single neuroradiology expert. ICH detection accuracy, sensitivity, specificity, positive predictive value, negative predictive value, and positive and negative likelihood ratios by RAPID ICH were determined. RESULTS: We included 308 studies. RAPID ICH correctly identified 151/158 ICH cases and 143/150 ICH-negative cases, which resulted in high sensitivity (0.956, CI: 0.911-0.978), specificity (0.953, CI: 0.907-0.977), positive predictive value (0.956, CI: 0.911-0.978), and negative predictive value (0.953, CI: 0.907-0.977) for ICH detection. The positive likelihood ratio (20.479, CI 9.928-42.245) and negative likelihood ratio (0.046, CI 0.023-0.096) for ICH detection were similarly favorable. RAPID ICH volumetric quantification for intraparenchymal and intraventricular hemorrhages strongly correlated with expert manual segmentation (correlation coefficient r = 0.983); the median absolute error was 3 mL. CONCLUSIONS: RAPID ICH is highly accurate in the detection of ICH and in the volumetric quantification of intraparenchymal and intraventricular hemorrhages.

Inferring super-spreading from transmission clusters of COVID-19 in Hong Kong, Japan, and Singapore.

Super-spreading events in an outbreak can change the nature of an epidemic. Therefore, it is useful for public health teams to determine whether an ongoing outbreak has any contribution from such events, which may be amenable to interventions. We estimated the basic reproductive number (R0) and the dispersion factor (k) from empirical data on clusters of epidemiologically linked coronavirus disease 2019 (COVID-19) cases in Hong Kong, Japan and Singapore. This allowed us to infer the presence or absence of super-spreading events during the early phase of these outbreaks. The relatively large values of k implied that large cluster sizes, compatible with super-spreading, were unlikely.

Author Correction: MUC1-C regulates lineage plasticity driving progression to neuroendocrine prostate cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.