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Background Malnutrition is a factor associated with mortality, particularly for older residents in long-term care facilities. Aim This study aimed to evaluate the Minimum Data Set-based Screening for Nutritional Problem (MDS-SNP) and Mini Nutritional Assessment (MNA) in screening malnutrition among institutionalised older adults in Taiwan. Methods A cross-sectional research design was employed and data from 131 residents were collected in northern Taiwan. Demographic and clinical variables such as cognitive function, activities of daily living, depression status, MDS-SNP, MNA, and dietary habits were obtained from residents’ profiles. Findings The prevalence of malnutrition and risk of malnutrition defined by MNA were 32.8% (n = 43) and 30.5% (n = 40), respectively and 59.5% (n = 78) was at risk of malnutrition according to MDS-SNP. Multivariate logistic regression disclosed that some of the MDS-SNP items such as BMI and complaints of hunger, were significantly associated with MNA-defined risk and malnutrition but none of these were considered as trigger items in MDS-SNP. Discussion Our study suggested that the MDS-SNP may be considered as an appropriate malnutrition screening tool. Screening nutritional status of older people is important because of its significant association with chronic conditions and function as well as quality of life. Conclusion A modified MDS-based malnutrition screening tool in long-term care settings which considered BMI, complaints of hunger and nutritional approaches to deliver food as predictors is warranted.

Background/purpose The COVID-19 pandemic, caused by the spread of SARS-CoV-2 infection that is mainly through the airborne transmission, is a worldwide health concern. This review seeks to assess the potential effectiveness of mouthwash in reducing the oropharyngeal load of SARS-CoV-2 based on the available evidence. Methods Articles related to mouthwash and COVID-19 in PubMed were electronically searched in July, 2021. After manually excluding articles lacking sufficient scientific evidence or validation processes, those with inaccessible online full text, those that did not test the effectiveness of mouthwash against SARS-CoV-2, and those not written in English, 17 original and 13 review articles were chosen for this review. Results The eligible articles revealed that the main virucidal mechanism of mouthwash was via interactions with the viral envelope. Povidone-iodine (PVP-I), cetylpyridinium chloride (CPC), and essential oils with ethanol showed virucidal effects on SARS-CoV-2 in vitro, potentially by interfering with the viral envelope. A few clinical studies demonstrated that PVP-I, CPC, hydrogen peroxide, and chlorhexidine reduced the oropharyngeal load of SARS-CoV-2. Conclusion Although the available evidence is limited, mouthwash containing PVP-I or CPC shows potential for reducing the oropharyngeal load of SARS-CoV-2 and thus may present a risk-mitigation strategy for COVID-19 patients.

Background/purpose Covering the wounds from guided bone regeneration and sinus floor elevation with oral and sinus mucosa is a fundamental criterion for success. This study aimed to verify the regeneration capability of the mucosal connective tissue stromal cells by characterizing their stemness and osteogenic potentials. Methods Bone marrow stromal cells (BMSCs), alveolar mucosa cells (AMCs), keratinized gingival cells (KGCs), and sinus mucosal cells (SMCs), were isolated from four Sprague–Dawley rats. The morphology and viability of the cells were investigated under a confocal microscope and by Alamar Blue. Stem cell surface markers were evaluated by flow cytometry. Expressions of pluripotent factors after initial seeding and an early osteogenic gene following 24 h of osteoinduction were evaluated by realtime PCR. Trilineage differentiation capability in long-term inductive cell culture was assessed by Alizarin Red, Alcian Blue, and Oil Red O staining. Results BMSCs and AMCs were larger cells with smaller aspect ratios relative to KGCs and SMCs, and BMSCs revealed the greatest initial viability but the slowest proliferation. More than 94% of BMSCs, AMCs, and KGCs were double-positive for CD73 and CD90. Compared with BMSCs, AMCs expressed significantly higher Oct4 but reduced Cbfa1 after initial seeding, and AMCs and SMCs expressed significantly higher Cbfa1 following 24 h of osteoinduction. In long-term inductive cell culture, osteogenesis was observed in BMSCs, AMCs, and SMCs, chondrogenesis was observed in BMSCs, AMCs, and KGCs, and adipogenesis was evident in only BMSCs. Conclusion AMCs contain a high percentage of stem/progenitor cells and show differentiation capability toward osteogenic lineage.

Leishmaniasis is prevalent in Southern Europe, the Middle East, India, Africa, and Central and South America. Cutaneous leishmaniasis may spontaneously heal over time without treatment; however, risk of visceral dissemination and the impact of cosmetic defect are important concerns. We report a Case of cutaneous leishmaniasis in a patient who ever traveled to Mexico before the onset of a deteriorating wound around the swollen left eyebrow. A diagnosis of infection with Leishmania mexicana was made based on histopathological examination and molecular identification. Systemic treatment with liposomal amphotericin B and ketoconazole were administered with gradual healing of the lesion. Also, this traveler case implicates that the spread of endemic parasitic diseases may be a concealed risk on the public health for Taiwan underlying globalization.

Background/Purpose: Stereotactic ablative radiotherapy (SABR) is the treatment of choice for medically inoperable, early-stage non-small cell lung cancer (ES-NSCLC). The influence of oncogenic driver alterations and comorbidities are not well known. Here we present treatment outcomes based on clinicopathologic features and molecular profiles. Methods: We retrospectively analyzed patients treated with SABR for inoperable ES-NSCLC. Molecular features of oncogenic driver alterations included EGFR, ALK, and ROS1. Comorbidities were assessed using the age-adjusted Charlson Comorbidity Index (ACCI). Survival was calculated using the Kaplan–Meier method. The Cox regression model was performed for univariate and multivariate analyses of prognostic factors. Competing risk analysis was used to evaluate the cumulative incidence of disease progression. Results: From 2008 to 2020, 100 patients (median age: 82 years) were enrolled. The majority of patients were male (64%), ever-smokers (60%), and had adenocarcinoma (65%). With a median follow-up of 21.5 months, the median overall survival (OS) and real-world progression-free survival were 37.7 and 25.1 months, respectively. The competing-risk-adjusted 3-year cumulative incidences of local, regional, and disseminated failure were 8.2%, 14.5%, and 31.2%, respectively. An ACCI ≥7 was independently associated with inferior OS (hazard ratio [HR] 2.45, p = 0.03). Tumor size ≥4 cm (HR 4.16, p

Graph theory has been extensively used to investigate brain network topology and its changes in disease cohorts. However, many graph theoretic analysis-based brain network studies focused on the shortest paths or, more generally, cost-efficiency. In this work, we use two new concepts, connectedness and 2-connectedness, to measure different global properties compared to the previously widely adopted ones. We apply them to unravel interesting characteristics in the brain, such as redundancy design and further conduct a time-varying brain functional network analysis for characterizing the progression of Alzheimer's disease (AD). Specifically, we define different connectedness and 2-connectedness states and evaluate their dynamics in AD and its preclinical stage, mild cognitive impairment (MCI), compared to the normal controls (NC). Results indicate that, compared to MCI and NC, brain networks of AD tend to be more frequently connected at a sparse level. For MCI, we found that their brains are more likely to be 2-connected in the minimal connected state as well indicating increasing redundancy in brain connectivity. Such a redundant design could ensure maintained connectedness of the MCI's brain network in the case that pathological damages break down any link or silenced any node, making it possible to preserve cognitive abilities. Our study suggests that the redundancy in the brain functional chronnectome could be altered in the preclinical stage of AD. The findings can be successfully replicated in a retest study and with an independent MCI dataset. Characterizing redundancy design in the brain chronnectome using connectedness and 2-connectedness analysis provides a unique viewpoint for understanding disease affected brain networks.

Objectives/hypothesis To examine the pathogenic bacterial spectra and prognosis of deep neck infection (DNI) in end-stage renal disease (ESRD) patients. Study design Retrospective study. Methods Patients diagnosed with DNI between 2004 and 2015 in Chang Gung Memorial Hospital were enrolled and divided into three groups, namely ESRD-DNI, chronic kidney disease (CKD)-DNI, and non-CKD-DNI. Differences in pathogenic bacteria, treatment, and prognosis were compared across the three groups. Results The bacterial spectra differed among the three groups. The main three facultative anaerobic or aerobic bacteria causing ESRD-DNIs were methicillin-resistant Staphylococcus aureus (MRSA; 25.4%), methicillin-susceptible S. aureus (MSSA; 14.1%), and Klebsiella pneumoniae (KP; 12.7%). For CKD-DNIs, they were KP (23.5%), Viridans streptococci (VS; 23.5%), and MSSA (14.7%). For non-CKD-DNIs, they were VS (31.7%), KP (17.2%), and coagulase-negative staphylococci (8.0%). Compared with the other groups, the ESRD-DNI group had higher white blood cell and C-reactive protein levels, longer hospital stays, more frequent admissions to the intensive care unit, more mediastinal complications, and a significantly higher mortality rate. Conclusions The ESRD-DNI group exhibited more severe disease activity and higher mortality compared with those of the CKD-DNI and non-CKD-DNI groups. MRSA was the leading pathogen for patients with ESRD-DNI. Physicians must implement strategies for the early detection of MRSA to accurately prescribe antibiotics and prevent nosocomial transmission. Level of evidence 4 Laryngoscope, 2021.

ObjectivesMAP4K3 (GLK) overexpression in T cells induces interleukin (IL)-17A production and autoimmune responses. GLK overexpressing T-cell population is correlated with severity of human systemic lupus erythematosus (SLE); however, it is unclear how GLK is upregulated in patients with SLE.MethodsWe enrolled 181 patients with SLE and 250 individuals without SLE (93 healthy controls and 157 family members of patients with SLE) in two independent cohorts from different hospitals/cities. Genomic DNAs of peripheral blood mononuclear cells were subjected to next-generation sequencing to identify GLK gene variants. The functional consequences of the identified GLK germline or somatic variants were investigated using site-directed mutagenesis and cell transfection, followed by reporter assays, mass spectrometry, immunoblotting, coimmunoprecipitation, and in situ proximity ligation assays.ResultsWe identified 58 patients with SLE from Cohort #1 and #2 with higher frequencies of a somatic variant (chr2:39 477 124 A>G) in GLK 3′-untranslated region (UTR); these patients with SLE showed increased serum anti-double-stranded DNA levels and decreased serum C3/C4 levels. This somatic variant in 3′-UTR enhanced GLK mRNA levels in T cells. In addition, we identified five patients with SLE with GLK (A410T) germline variant in Cohort #1 and #2, as well as two other patients with SLE with GLK (K650R) germline variant in Cohort #1. Another GLK germline variant, A579T, was also detected in one patient with SLE from Cohort #2. Both GLK (A410T) and GLK (K650R) mutants inhibited GLK ubiquitination induced by the novel E3 ligase makorin ring-finger protein 4 (MKRN4), leading to GLK protein stabilisation.ConclusionsMultiple GLK germline and somatic variants cause GLK induction by increasing mRNA or protein stability in patients with SLE.

Purpose This large-scale nationwide population-based study aimed to determine the recurrence rate and risk factors for recurrence after video-assisted thoracoscopic surgery (VATS) for primary spontaneous pneumothorax (PSP). Methods This retrospective study used data from the Taiwan National Health Insurance Database to identify individuals who underwent VATS for PSP from 2007 to 2014. All patients were followed up until December 31, 2017. Study variables included demographic characteristics, intensive care unit admission, lung resection status, use of non-steroidal anti-inflammatory drugs (NSAIDs), and hospital level. The primary outcome was 1-year recurrence, and the secondary outcomes were the 1-year rate of reintervention for recurrence and overall recurrence rate. Results During the study period, 6654 patients underwent VATS for PSP (average age: 23.2 years, 89.1% male), including 910 patients (13.7%) who experienced recurrence within 1 year and 531 patients (8.0%) who required reintervention within 1 year. The overall recurrence rate was 24.8%, with an average follow-up time of 6.7 years. Age ≤18 years and the use of NSAIDs, especially ketorolac, were significant risk factors for 1-year recurrence and overall recurrence. Younger age was a risk factor for 1-year reintervention. In subgroup analysis, NSAID use was a significant risk factor for 1-year recurrence, 1-year reintervention, and overall recurrence in pediatric patients but not in adult patients. Conclusions In Taiwan, the 1-year recurrence rate was 13.7% after VATS for PSP. Younger age and the use of NSAIDs, especially ketorolac, were significant risk factors for short- and long-term recurrence after VATS for PSP.

Juncus effusus L. (J. effusus) is a Traditional Chinese Medicine (TCM) that has long been used for dealing with gynaecological disorders, such as relieving insomnia, preventing tinnitus, reducing edema with diuretic effect. In our course of evidence-based medical research focused on this herb, one new phenanthrene, Junfusol B (2), together with seventeen known compounds were isolated and identified. All the structures of these compounds were elucidated by spectroscopic methods. The absolute stereochemistry of compounds 1 and 2 was further determined by comparing their calculated and experimental Electronic Circular Dichroism (ECD) spectra and optical rotation (OR) values. The isolates were evaluated for their estrogenic and anti-inflammatory activities which were considered as relevant etiological factors of insomnia, tinnitus and edema in the ancient TCM theory. The results revealed that most of the obtained phenanthrenes in this work were found exerting agonistic effects on estrogen receptor. This is the first report to declare the exact estrogen-regulating potential among this type of compounds from J. effusus. Moreover, phenanthrenes 3 - 7 exhibited significant inhibitions on superoxide anion generation and elastase release in fMLP/CB-induced human neutrophilic inflammation model. J. effusus may be developed as a complementary agent utilized in menopausal multiple syndromes.

An exopolysaccharide (EPS) synthesizing potentially probiotic Gram-positive bacterial strain was isolated from fish (Tor putitora) gut, and its EPS was structurally characterized. The isolate, designated as FW2, was identified as Lactobacillus reuteri through 16S rRNA gene sequencing and phylogenetic analysis. This isolate produces fructan-type EPS using sucrose as a substrate. Based on 13C-NMR spectroscopy, methylation analysis and monosaccharide composition, the EPS was identified as a linear levan polymer with fructose as main constituent linked via β(2 → 6) linkages. Based on molecular weight (MW) distribution, two groups of levan were found to be produced by the isolate FW2: one with high MW (4.6 × 106 Da) and the other having much lower MW (1.2 × 104 Da). The isolate yielded about 14 g/L levan under optimized culturing parameters including aeration conditions, pH, temperature and substrate concentration. The obtained bimodal molecular weight linear levan is the first of its type to be synthesized by a L. reuteri isolate from fish gut. Bimodal molecular weight prebiotic levan together with the probiotic potential of the producing strain would provide a new promising synbiotic combination for use in aqua culture.

A goal of computational psychiatry is to ground symptoms in basic mechanisms. Theory suggests that avoidance in anxiety disorders may reflect dysregulated mental simulation, a process for evaluating candidate actions. If so, these covert processes should have observable consequences: choices reflecting increased and biased deliberation. In two online general population samples, we examined how self-report symptoms of social anxiety disorder predict choices in a socially framed reinforcement learning task, the patent race, in which the pattern of choices reflects the content of deliberation. Using a computational model to assess learning strategy, we found that self-report social anxiety was indeed associated with increased deliberative evaluation. This effect was stronger for a particular subset of feedback ('upward counterfactual') in one of the experiments, broadly matching the biased content of rumination in social anxiety disorder, and robust to controlling for other psychiatric symptoms. These results suggest a grounding of symptoms of social anxiety disorder in more basic neuro-computational mechanisms.

Consumer research has explored several dimensions of maladaptive decision-making, including compulsive consumption and behavioral addiction. Here we propose extending this work by integrati...

5-iododeoxyuridine (IUdR), a radiosensitizer able to be incorporated into nascent DNA during synthesis, makes the DNA easy to break upon irradiation. IUdR has been used together with low energy radiation in cancer treatments mechanistically by Auger electron induction to damage DNA. In this study, a small-sized transmission X-ray tube equipped with a Lanthalum target (La-tX ray) generating 33–40 keV-enriched photons was used in combination with IUdR for Auger cancer therapy, and the performance was evaluated by multiple assays in vitro and in vivo. Cytotoxicity, thymidine replacement and nuclear incorporation of IUdR were evaluated in NG4TL4 fibrosarcoma cells and SAS head and neck cancer cells. After treatment of IUdR + La-tX ray irradiation or IUdR + Co-60 irradiation, cell survival and DNA damages were evaluated by colony forming assay and comet assay/γH2AX staining, respectively. Growth of tumor xenografts receiving an intratumoral IUdR injection (45 μg) and/or La-tX ray irradiation were measured. For NG4TL4 and SAS cells, the IC50 of IUdR were ~ 7 and ~ 10 μg/ml, respectively. As compared to IUdR + Co-60 irradiation, IUdR + La-tX ray resulted in higher DNA breaks in cancer cells. Also, IUdR + La-tX ray resulted in higher cell toxicity than IUdR + Co-60. In the in vivo study, tumor xenografts showed inhibited growth in the IUdR + La-tX ray treatment, compared to those in the IUdR or La-tX ray treatment alone. This study demonstrated the potential of cancer Auger electron therapy using a small-sized transmission X ray tube that generated enriched specific energy X rays for Auger electron induction.

Biliary atresia (BA) is a challenging liver disease in infancy. Early diagnosis of BA is important for timely hepatoportoenterostomy. We evaluated the age‐specific diagnostic performance of transient elastography (TE) with a liver stiffness measurement (LSM) greater than 7.7 kPa in BA among infants with cholestasis. A total of 61 infants with cholestasis (5‐121 days of age) were enrolled in this prospective follow‐up study; 15 infants were BA. Four age groups were defined (≤30, 31‐60, 61‐90, and 91‐180 days). Picrosirius red staining was performed to quantify the percentage of collagen fibers in liver specimens. The utility of an LSM greater than 7.7 kPa for diagnosis of BA among infants with cholestasis was compared among age groups. In all four groups, TE showed high diagnostic power for BA using the criterion of an LSM greater than 7.7 kPa. Positive predictive values were 100%, 100%, and 100% in the groups aged 30 days or younger, 31 to 60 days, and 61 to 90 days, respectively. Respective negative predictive values were 90.9%, 94.7%, and 100%, and respective diagnostic accuracies were 92.9%, 95.2%, and 100%. The positive predictive value, negative predictive value, and diagnostic accuracy were 100%, 100%, and 100%, respectively, for LSM greater than 8.8 kPa in the group aged 91 to 180 days. The LSM was positively correlated with the percentage of collagen fibers stained by picrosirius red (P = 0.03). Conclusion: In this prospective follow‐up study, TE had good diagnostic accuracy for differentiation of BA from non‐BA cholestasis in infants with cholestasis who were 90 days of age or younger. The LSM was significantly positive correlated with the liver fibrosis status stained by picrosirius red in infants with cholestasis.

OBJECTIVE To investigate whether prognostic nutritional index (PNI) predicts patient survival outcomes in oral cavity squamous cell carcinoma (OSCC). MATERIALS AND METHODS The data of a total of 360 patients subjected to primary surgery for OSCC were retrospectively analysed. Patients were categorised into high-PNI (≥51.75) and low-PNI (

Colonoscopy screening and colonoscopic polypectomy can decrease the incidence and mortality rate of colorectal cancer (CRC). The adenoma detection rate and accuracy of diagnosis of colorectal polyp which vary in different experienced endoscopists have impact on the colonoscopy protection effect of CRC. The work proposed a colorectal polyp image detection and classification system through grayscale images and deep learning. The system collected the data of CVC-Clinic and 1000 colorectal polyp images of Linkou Chang Gung Medical Hospital. The red-green-blue (RGB) images were transformed to 0 to 255 grayscale images. Polyp detection and classification were performed by convolutional neural network (CNN) model. Data for polyp detection was divided into five groups and tested by 5-fold validation. The accuracy of polyp detection was 95.1% for grayscale images which is higher than 94.1% for RGB and narrow-band images. The diagnostic accuracy, precision and recall rates were 82.8%, 82.5% and 95.2% for narrow-band images, respectively. The experimental results show that grayscale images achieve an equivalent or even higher accuracy of polyp detection than RGB images for lightweight computation. It is also found that the accuracy of polyp detection and classification is dramatically decrease when the size of polyp images small than 1600 pixels. It is recommended that clinicians could adjust the distance between the lens and polyps appropriately to enhance the system performance when conducting computer-assisted colorectal polyp analysis.

The peritonsillar abscess (PTA)–rheumatoid arthritis (RA) association remains unclear. Here, the effects of RA on PTA incidence and prognosis are elucidated. We compared PTA incidence and prognosis of 30,706 RFCIP-registered patients with RA (RA cohort) with matched individuals without RA from another database of 1 million randomly selected people representing Taiwan’s population (non-RA cohort). The RA cohort had significantly higher PTA incidence [incidence rate ratio (IRR) (95% CI) 1.73 (1.10–2.71), P = 0.017) and cumulative incidence (P = 0.016, Kaplan–Meier curves). Cox regression analyses demonstrated RA cohort to have an estimated 1.72-fold increased PTA risk (95% CI 1.09–2.69, P = 0.019). PTA was more likely within the first 5 years of RA diagnosis (for

Background/purpose Anastomotic stricture (AS) is a major morbidity of patients with esophageal atresia (EA) after surgical reconstruction. Our study determined the risk factors of AS after EA reconstruction. The therapeutic efficacy and complications of esophageal dilatation for children with AS were also evaluated. Methods Forty children treated for EA between January 2008 and December 2018 were included in this retrospective analysis. Esophageal dilatation was performed when AS was diagnosed. The therapeutic effect of esophageal dilatation was determined based on nutritional status, as assessed by the weight-for-age z-score. Results Sixteen EA patients developed AS. A gap >1.5 cm between the esophageal pouches (P = 0.02) in patients with EA and type A EA was a risk factor for developing AS. A mean of 7.7 sessions of esophageal dilatation were performed per patient, and no complications occurred. The nutritional status of EA children with AS after dilatation was not inferior to that of the children without AS at the 6-month follow-up. Conclusions A gap >1.5 cm between the esophageal pouches and type A EA are risk factors for AS after esophageal reconstruction. Esophageal dilatation is both safe and effective for managing strictures and improves nutritional status in EA children with AS.

Purpose Nerve injury-induced pain is difficult to treat. In this study, we developed an alginate scaffold with human umbilical cord mesenchymal stem cell exosomes (EX-SC) to treat nerve injury-induced pain. Materials and Methods The scaffold was prepared and characterized for its physical traits and biocompatibility. In vitro studies of PC12 and HEK293 cells were used to evaluate the neuroprotective and neurotrophic effects of exosomes. Right L5/6 spinal nerve ligation (SNL) was performed in Sprague-Dawley rats to induce mechanical allodynia and thermal hyperalgesia, evaluated by von Frey hair and radiant heat tests. The EX-SC was wrapped around ligated L5/6 spinal nerves for treatment. Western blotting and immunofluorescence staining were used to evaluate neuron/glial activation, cytokines and neurotrophic factor of affected dorsal root ganglion (DRG). Results In cell culture assay, the exosomes induce neurite outgrowth of PC12 cells and protect PC12 and HEK293 cells against formaldehyde acid treatment. On post-ligation day 21, rats receiving EX-SC had significantly higher median (interquartile range) withdrawal threshold and latency [14.1 (13.7–15.5) g, 14.2 (13.7–15.3) s] than saline-SC-treated rats [2.1 (1.7–3.0) g, 2.0 (1.8–2.4) s, P=0.02 and 0.002]. The EX-SC also attenuated SNL-induced up-regulation of c-Fos, GFAP, Iba1, TNF-α and IL-1β, while enhancing the level of IL-10 and GDNF, in the ipsilateral L5/6 DRG. After implantation for 21 days, the EX-SC enhanced the expression of myelin basic protein and IL-10 in injured L5/6 axons. Conclusion We demonstrate the EX-SC possesses antinociceptive, anti-inflammation and pro-neurotrophic effects in the SNL pain model. It could be a promising therapeutic alternative for nerve injury-induced pain.

Highlights • Down-regulation of CISH in OSCC tissues and cell lines. • CISH mediates cellular functions through STAT3 inhibition. • MiR-944 regulates cellular functions through direct binding of CISH. • Cigarette smoking-mediated miR-944/CISH/STAT3 axis plays a role in oral carcinogenesis., The cytokine-inducible Src homology 2-containing protein (CISH) is an endogenous suppressors of signal transduction and activator of transcription (STAT) and acts as a key negative regulator of inflammatory cytokine responses. Downregulation of CISH has been reported to associate with increased activation of STAT and enhanced inflammatory pathways. However, whether microRNAs (miRNAs) play a crucial role in CISH/STAT regulation in oral squamous cell carcinoma (OSCC) remains unknown. The expression of CISH on OSCC patients was determine by quantitative real-time PCR (qRT-PCR) and immunohistochemistry. Specific targeting by miRNAs was determined by software prediction, luciferase reporter assay, and correlation with target protein expression. The functions of miR-944 and CISH were accessed by transwell migration and invasion analyses using gain- and loss-of-function approaches. Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were used to evaluate the pro-inflammation cytokines expression under the miR-944, CISH, NNK or combinations treatment. We found that the CISH protein, which modulates STAT3 activity, as a direct target of miR-944. CISH protein was significantly down-regulated in OSCC patients and cell lines and its level was inversely correlated with miR-944 expression. The miR-944-induced STAT3 phosphorylation, pro-inflammation cytokines secretion, migration and invasion were abolished by CISH restoration, suggesting that the oncogenic activity of miR-944 is CISH dependent. Furthermore, tobacco extract (NNK) may contribute to miR-944 induction and STAT3 activation. Antagomir-mediated inactivation of miR-944 prevented the NNK-induced STAT3 phosphorylation and pro-inflammation cytokines secretion. Altogether, these data demonstrate that NNK-induced miR944 expression plays an important role in CISH/STAT3-mediated inflammatory response and activation of tumor malignancy.

Biliary atresia is a progressive obliterative cholangiopathy affecting both extrahepatic and intrahepatic biliary trees, resulting in fibrous obliteration of the biliary tract and subsequent development of cirrhosis. The aim of this study was to find noninvasive indices to predict the status of hepatic fibrosis in children with biliary atresia. We retrospectively measured the volume of the hepatic lobes and spleen from MR images, obtained biochemical data and analyzed the relationship between the imaging and biochemical indices, and the pathological status of hepatic fibrosis in 35 children with biliary atresia. A combined index was obtained by logistic regression: logit (likelihood of cirrhosis) = 0.00043 x age at MR examination + 1.67 x aspartate aminotransferase and platelet ratio index (APRI) + 0.0029 x body-surface-area-adjusted left liver lobe volume (BSA adLLV) – 6.57 (log-likelihood chi-square P

Sertraline is one of the most commonly prescribed antidepressants. Major depressive disorder (MDD) is characterized by spontaneous thoughts that are laden with negative affect—a “malignant sadness”. Prior neuroimaging studies have identified abnormal resting-state functional connectivity (rsFC) in the spontaneous brain networks of MDD patients. But how antidepressant medication acts to relieve the experience of depression as well as adjust its associated spontaneous networks and mood-regulation circuits remains an open question. In this study, we recruited 22 drug-naive MDD patients along with 35 normal controls and investigated whether the functional integrity of cortical networks associated with spontaneous thoughts is modulated by sertraline treatment. We attempted to predict post-treatment effects based upon what we observed in the pre-treatment rsFC of drug-naive MDD patients. In the result, we demonstrated that (1) after the sertraline treatment, the medial temporal lobe of default network (DNMTL) and mood regulation pathway—the fronto-parietal control network (FPCN), the thalamus, and the salience network (SN)—were restored to normal connectivity, relative to the pre-treatment condition; however, the altered connections of FPCN-core DN (DNCORE), FPCN-SN, and intra-FPCN among MDD patients remained impaired; (2) thalamo-prefrontal connectivity provides moderate predictive power (r2 = 0.63) for the effectiveness of sertraline treatment. In summary, our findings contribute to a body of evidence that suggests salubrious effects of sertraline treatment primarily involve the FPCN-thalamus-SN pathway. The pre-treatment rsFC in this pathway could serve as a predictor of sertraline treatment outcome.

Neuroblastoma, a common childhood tumor, remains one of the most elusive diseases to treat. To date, high-risk neuroblastoma is associated with low survival rates. To address this, novel and more effective therapeutic strategies must continue to be explored. We employed a bioinformatics approach corroborated with in vitro and in vivo data. Samples from neuroblastoma patients were retrieved and immuno-stained for Bruton’s tyrosine kinase (BTK). To evaluate its effect on cellular functions, BTK expression in SK-N-BE(2) and SH-SY5Y neuroblastoma cells was downregulated using gene silencing or inhibition with ibrutinib or acalabrutinib. Xenograft mouse models were used to investigate the in vivo role of BTK in neuroblastoma tumorigenesis. We found that BTK was highly expressed in primary neuroblastoma samples, preferentially in MYCN-amplified neuroblastoma cases, and was associated with a poor prognosis. Immunohistochemical staining of tissues from our neuroblastoma cohort revealed a strong BTK immunoreactivity. We also found that neuroblastoma SK-N-BE(2) and SH-SY5Y cells were sensitive to treatment with ibrutinib and acalabrutinib. Pharmacologic or molecular inhibition of BTK elicited a reduction in the migratory and invasive abilities of neuroblastoma cells, and ibrutinib considerably attenuated the neurosphere-forming ability of neuroblastoma cells. Both inhibitors showed synergism with cisplatin. In vivo assays showed that acalabrutinib effectively inhibited neuroblastoma tumorigenesis. From our data we conclude that BTK is a therapeutically targetable driver of neuroblastoma.

Esophageal atresia with/without tracheoesophageal fistula (EA/TEF) is a congenital digestive tract anomaly that represents a major therapeutic challenge. Postoperative digestive morbidities such as gastroesophageal reflux disease (GERD) and esophageal stricture are common. The aim of this study was to identify the incidence of and potential risk factors for digestive morbidities after EA/TEF repair. We retrospectively reviewed all EA/TEF patients who underwent repair at a single institution between January 1999 and December 2018, excluding patients who died prior to discharge. Patient demographics, perioperative management, and postoperative GERD and esophageal stricture rates were collected. We performed univariate and multivariate analyses to examine risk factors associated with postoperative GERD and esophageal stricture. The study enrolled 58 infants (58.6% male, 17.2% with type A EA/TEF, 62.1% with associated anomalies). Postoperative GERD occurred in 67.2% of patients and was the most common digestive morbidity. Esophageal stricture occurred in 37.9% of patients after EA/TEF repair. Multivariate analysis showed that long-gap EA/TEF and postoperative GERD were independent risk factors for esophageal stricture after repair surgery.Conclusion: The incidence of postoperative GERD and esophageal stricture was 67.2% and 37.9%, respectively. The risk factors for postoperative esophageal stricture were long-gap EA/TEF and postoperative GERD. What is Known: • EA/TEF is a congenital digestive tract anomaly with a high postoperative survival rate but can be complicated by many long-term morbidities. What is New: • Long-gap EA/TEF and postoperative GERD are risk factors of anastomotic stricture after repair. • Surgeons and pediatricians should be highly experienced in managing anastomotic tension and the GERD.

Previous experimental work demonstrates the power of classical theories of economic dynamics to accurately characterize equilibration in multiple market systems. Building on the literature, this study examines the behavior of experimental continuous double auction markets in convergence-challenging environments identified by Scarf (Int Econ Rev 1:157–171, 1960) and Hirota (Int Econ Rev 22:461–467, 1981). The experiments provide insight into two important economic questions: (a) Do markets necessarily converge to a unique interior equilibrium? and (b) which model, among a set of classical specifications, most accurately characterizes observed price dynamics? We observe excess demand-driven prices spiraling outwardly away from the interior equilibrium prices as predicted by the theory of disequilibrium price dynamics. We estimate a structural model establishing that partial equilibrium dynamics characterize price changes even in an unstable general equilibrium environment. We observe linkages between excess demand in one market and price changes in another market, but the sign of expected price change in a market does not depend on the magnitude of excess demand in other markets unless disequilibrium is severe.

High-risk neuroblastoma is associated with low long-term survival rates due to recurrence or metastasis. Retinoids, including 13-cis-retinoic acid (13cRA), are commonly used for the treatment of high-risk neuroblastoma after myeloablative therapy; however, there are significant side effects and resistance rates. In this study, we demonstrated that 13cRA has a better antiproliferative effect in MYCN-amplified neuroblastoma cells than in MYCN-nonamplified neuroblastoma cells. In MYCN-amplified SK-N-DZ cells, 13cRA induced significant upregulation of toll-like receptor 3 (TLR3) and mitochondrial antiviral-signaling protein (MAVS) expression in a time-dependent manner. Furthermore, poly (I:C), a synthetic agonist of TLR3, effectively synergized with 13cRA to enhance antiproliferative effects through upregulation of the innate immune signaling and the mitochondrial stress response, leading to augmentation of the apoptotic response in 13cRA-responsive cancer cells. In addition, the 13cRA/poly (I:C) combination induced neural differentiation through activation of retinoic acid receptors beta (RAR-β), restoring expression of α-thalassemia/mental retardation syndrome X-linked (ATRX) protein, and inhibiting vessel formation, leading to retarded tumor growth in a mouse xenograft model. These results suggest that the combination of poly (I:C) and RA may provide synergistic therapeutic benefits for treatment of patients with high-risk neuroblastoma.

The aim of this study was to investigate the prognostic role of MYCN RNA expression by quantitative RNA in situ hybridization and its association with MYCN amplification in neuroblastoma. MYCN RNA expression in 69 neuroblastoma tumors was evaluated by an ultrasensitive quantitative RNA in situ hybridization technique, RNAscope. The correlations between MYCN RNA expression, MYCN amplification, and other clinicopathologic variables of neuroblastoma were analyzed. High expression levels of MYCN RNA were detected 30 of 69 (43%) of neuroblastomas, mainly in those with undifferentiated or poorly differentiated histology. High expression of MYCN RNA was significantly associated with MYCN amplification (P 0.001) and other adversely prognostic factors, including older age at diagnosis (18 months, P = 0.017), advanced clinical stage (International Neuroblastoma Staging System stage 3, 4, P = 0.002), unfavorable International Neuroblastoma Pathology Classification tumor histology (P 0.001), and high-risk Children's Oncology Group risk group (P = 0.001). In Kaplan-Meier analysis, MYCN RNA levels determined by quantitative in situ hybridization were better than MYCN gene dosages determined by chromogenic in situ hybridization in discriminating good and poor prognostic groups of neuroblastoma patients. In multivariate analysis, we further confirmed that high expression of MYCN RNA was an independent adverse prognostic factor for event-free and overall survival. Furthermore, high expression of MYCN RNA predicted unfavorable survival outcomes for neuroblastoma patients with MYCN non-amplification or high-risk Children's Oncology Group risk group. In conclusion, our study is the first report to show the application of MYCN RNA in situ hybridization in neuroblastoma and established that high expression of MYCN RNA could be a better biomarker than MYCN amplification for predicting poor prognosis of neuroblastoma patients.

Systemic lupus erythematosus (SLE) might increase deep neck infection (DNI) risk, but evidence supporting this hypothesis is limited. In this retrospective follow-up study, the SLE–DNI association was investigated using data from the Registry for Catastrophic Illness Patients, which is a subset of the Taiwan National Health Insurance Research Database. All patients newly diagnosed as having SLE in 1997–2011 were identified, and every SLE patient was individually matched to four patients without SLE according to sex, age, and socioeconomic status. The study outcome was DNI occurrence. DNI treatment modalities and prognoses in SLE and non-SLE patients, along with the association of steroid dose with DNI risk, were also studied. In total, 17,426 SLE and 69,704 non-SLE patients were enrolled. Cumulative DNI incidence was significantly higher in the SLE cohort than in the non-SLE cohort (p p p = 0.033). The between-group differences in tracheostomy use and hospitalisation duration were nonsignificant. In SLE patients, high steroid doses significantly increased DNI incidence (≥3 vs. p

The default mode network (DMN) of the brain is involved in cognition, emotion regulation, impulsivity, and balancing between internally and externally focused states. DMN dysregulation has been implicated in several neurological and neuropsychiatric disorders. In this study, we used functional magnetic resonance imaging (fMRI), positron emission tomography (PET), and spectral fiber-photometry to investigate the selective neuromodulatory effect of norepinephrine (NE)-releasing noradrenergic neurons in the locus coeruleus (LC) on the DMN in mice. Chemogenetic-induced tonic LC-NE activity decreased cerebral blood volume (CBV) and glucose uptake, and increased synchronous low frequency fMRI activity within the frontal cortices of the DMN. Fiber-photometry results corroborated these findings, showing that LC-NE activation induced NE release, enhanced calcium-weighted neuronal spiking, and reduced CBV in the anterior cingulate cortex. These data suggest that LC-NE alters conventional stimulus-evoked coupling between neuronal activity and CBV in the frontal DMN. We also demonstrated that chemogenetic activation of LC-NE neurons strengthened functional connectivity within the frontal DMN, and this effect was causally mediated by reduced modulatory inputs from retrosplenial and hippocampal regions to the association cortices of the DMN.

DNA replication is initiated with the recognition of the starting point of multiple replication forks by the origin recognition complex and activation of the minichromosome maintenance complex 10 (MCM10). Subsequently, DNA helicase, consisting of the MCM protein subunits MCM2-7, unwinds double-stranded DNA and DNA synthesis begins. In previous studies, replication factors have been used as clinical targets in cancer therapy. The results showed that MCM2 could be a proliferation marker for numerous types of malignant cancer. We analyzed samples obtained from patients with neuroblastoma, revealing that higher levels of MCM2 and MCM10 mRNA were associated with poor survival rate. Furthermore, we combined the results of the perturbation-induced reversal effects on the expression levels of MCM2 and MCM10 and the sensitivity correlation between perturbations and MCM2 and MCM10 from the Cancer Therapeutics Response Portal database. Small molecule BI-2536, a polo-like kinase 1 (PLK-1) inhibitor, is a candidate for the inhibition of MCM2 and MCM10 expression. To test this hypothesis, we treated neuroblastoma cells with BI-2536. The results showed that the drug decreased cell viability and reduced the expression levels of MCM2 and MCM10. Functional analysis further revealed enrichments of gene sets involved in mitochondria, cell cycle, and DNA replication for BI-2536-perturbed transcriptome. We used cellular assays to demonstrate that BI-2536 promoted mitochondria fusion, G2/M arrest, and apoptosis. In summary, our findings provide a new strategy for neuroblastoma therapy with BI-2536.

Simple Summary Although uncommonly encountered, ocular melanoma may threaten the vision and even the life of a patient. The clinical feature and long-term results of ocular melanoma have rarely been described in the Asian population, as it has a low incidence for non-Caucasians. Therefore, we investigated the epidemiology, clinical manifestation, treatment strategy, and long-term outcome of ocular melanoma in a tertiary referral center in Taiwan. Abstract Malignant melanoma can arise from melanocytes in various structures of the eye, orbit, and ocular adnexa. We reviewed the clinical features and long-term results of all subjects with histologically proved melanoma originating from any of the ocular and periocular structures in a tertiary referral center. Overall, 88 patients including 47 men were recruited. The tumor was primarily located in the uvea, followed by the conjunctiva, orbit, eyelid, and lacrimal sac. Patients with uveal melanoma were diagnosed at a relatively younger age (47.0 years), while those with orbital and eyelid melanomas were older at presentation (79.5 years and 78.5 years, respectively). The overall local recurrence rate was 9% at a median follow-up of 41.0 months, among which orbital and eyelid melanomas recurred most commonly. The overall mortality rate was 41% in a median duration of 27.2 months (IQR, 13–58 months) from diagnosis, with the highest for lacrimal sac melanoma, followed by melanoma of the orbit, uveal, conjunctiva, and eyelid. Despite prompt local control, the risk for metastasis and mortality was high. Therefore, efficient modalities for early diagnosis and treatment of ocular melanoma are necessary.

Since the start of the outbreak of coronavirus disease 2019 in Wuhan, China, there have been more than 150 million confirmed cases of the disease reported to the World Health Organization. The beta variant (B.1.351 lineage), the mutation lineages of SARS-CoV-2, had increase transmissibility and resistance to neutralizing antibodies due to multiple mutations in the spike protein. N501Y, K417N and E484K, in the receptor binding domain (RBD) region may induce a conformational change of the spike protein and subsequently increase the infectivity of the beta variant. The L452R mutation in the epsilon variant (the B.1.427/B.1.429 variants) also reduced neutralizing activity of monoclonal antibodies. In this study, we discovered that 300 μg/mL GB-2, from Tian Shang Sheng Mu of Chiayi Puzi Peitian Temple, can inhibit the binding between ACE2 and wild-type (Wuhan type) RBD spike protein. GB-2 can inhibit the binding between ACE2 and RBD with K417N-E484K-N501Y mutation in a dose-dependent manner. GB-2 inhibited the binding between ACE2 and the RBD with a single mutation (K417N or N501Y or L452R) except the E484K mutation. In the compositions of GB-2, glycyrrhiza uralensis Fisch. ex DC., theaflavin and (+)-catechin cannot inhibit the binding between ACE2 and wild-type RBD spike protein. Theaflavin 3-gallate can inhibit the binding between ACE2 and wild-type RBD spike protein. Our results suggest that GB-2 could be a potential candidate for the prophylaxis of some SARS-CoV-2 variants infection in the further clinical study because of its inhibition of binding between ACE2 and RBD with K417N-E484K-N501Y mutations or L452R mutation., Graphical Abstract ga1

ObjectivesFor patients with oral cavity squamous cell carcinoma (OSCC), particularly for those with advanced disease, quality of life (QoL) is a key outcome measure. Therefore, we estimated survival-weighted psychometric scores (SWPS), life expectancy (LE), and quality-adjusted LE (QALE) in patients with advanced OSCC.Methods and MaterialsFor estimation of survival function, we enrolled 2313 patients with advanced OSCC diagnosed between January 1, 2007, and December 31, 2013. The patients were followed until death or December 31, 2014. To acquire the QoL data, data from 194 patients were collected by employing the Taiwan Chinese versions of the Quality of Life Questionnaire Core 30 and Quality of Life Questionnaire Head and Neck 35 developed by the European Organisation for Research and Treatment of Cancer and the EQ-5D-3L between October 1, 2013, and December 31, 2017. The LE of the patients with OSCC were estimated through linear extrapolation of a logit-transformed curve. SWPS and QALE were determined by integrating the LE and corresponding QoL outcomes.ResultsFor the patients with advanced OSCC, the estimated LE and QALE were 8.7 years and 7.7 quality-adjusted life years (QALYs), respectively. The loss of LE and QALE was 19.0 years and 20.0 QALYs, respectively. The estimated lifetime impairments of swallowing, speech, cognitive functioning, physical functioning, social functioning, and emotional functioning were 8.3, 6.5, 6.5, 6.1, 5.7, and 5.4 years, respectively. The estimated lifetime problems regarding mouth opening, teeth, social eating, and social contact were 6.6, 6.1, 7.5, and 6.1 years, respectively. The duration of feeding tube dependency was estimated to be 1.6 years.ConclusionsPatients with advanced OSCC had an estimated LE of 8.7 years and QALE of 7.7 QALYs. SWPS provided useful information regarding how advanced OSCC affects the subjective assessment of QoL. Our study results may serve as a reference for the allocation of cancer treatment resources.

AimThe aim of our study was to investigate the prognostic value of preoperative advanced lung cancer inflammation index (ALI) and to establish prognostic nomograms for the prediction of survival outcomes in patients with oral cavity squamous cell carcinoma (OSCC).Materials and MethodsA total of 372 patients who received primary curative surgery for OSCC during 2008–2017 at a tertiary referral center were enrolled. We used the receiver operating characteristic curve to determine the optimal cutoff point of ALI. Through a Cox proportional hazards model and Kaplan–Meier analysis, we elucidated the ALI–overall survival (OS) and ALI–disease-free survival (DFS) associations. Prognostic nomograms based on ALI and the results of multivariate analysis were created to predict the OS and DFS. We used the concordance indices (C-indices) and calibration plots to assess the discriminatory and predictive ability.ResultsThe results revealed that the ALI cutoff was 33.6, and 105 and 267 patients had ALI values of p < 0.001) and DFS (33.6% vs. 62.8%; p < 0.001). In multivariate analysis, ALI < 33.6 was independently associated with poor OS and DFS (both p < 0.001). The C-indices of established nomograms were 0.773 and 0.674 for OS and DFS, respectively; moreover, the calibration plots revealed good consistency between nomogram-predicted and actual observed OS and DFS.ConclusionALI is a promising prognostic biomarker in patients undergoing primary surgery for OSCC; moreover, ALI-based nomograms may be a useful prognostic tool for individualized OS and DFS estimations.

Arthropods may become lodged inside the ear and cause considerable emotional and physical trauma. Cases of centipedes being lodged in the external auditory canal have rarely been reported. In this article, we present the case of woman who had a centipede lodged inside her right external auditory canal. Removal using a topical local anesthetic can lead to vigorous activity of the centipede, which can cause harm to the patient and clinicians. Therefore, we developed and successfully applied a practicable method that involved using a modified plastic bottle for safe centipede removal. In conclusion, centipedes can express distinct and threatening behavior, and clinicians should pay attention to the activity of the lodged centipede and possibly use the proposed method to safely remove it.

Recently Helm (2020) provides an excellent review and preliminary assessment of the environmental impacts of the Coronavirus. He concludes that “The evidence from the pandemic is that it is not the case that decoupling has occurred at the global level, or even at the European level. Emissions and GDP have both fallen sharply” (p. 3). Using the case of Taiwan, this study provides a local evidence to support Helm (2020)’s proposition. GDP and emissions in Taiwan have been highly correlated in the coronavirus pandemic. However, we found that there exists a significant asymmetry of the correlation (or coupling) between GDP and CO2 emission under each period of prosperity and depression from 2005 to 2020. In this respect, the analysis of the causal link between CO2 emission and GDP under the depression period like that in the coronavirus pandemic cannot be considered as a trivial duplicate of the analysis under the prosperous period.

Background Cleaning workers experience severe musculoskeletal symptoms. Objective The objective of this paper was to examine musculoskeletal symptoms in cleaners of different heights to evaluate the effects of height on working postures in the work environment (schools). Methods We used a three-stage method including using the Nordic Musculoskeletal Questionnaire (NMQ) to evaluate musculoskeletal symptoms, a task analysis to confirm typical cleaning tasks, and the OVAKO Working Posture Assessment System (OWAS) for posture analysis. Multinomial logistic regression was performed to evaluate the adjusted effects of individual characteristics on painful body regions, using individuals without any pain as the reference category. Results This study found that the prevalence of musculoskeletal symptoms is very high for cleaners, especially in the shoulders, elbows, and lower back. Odds ratios for the accumulation of two or more risk factors were higher among men and were inversely associated with national economic indicators. The relatively high prevalence of musculoskeletal symptoms may stem from the multiple operations involved in cleaning tasks, such as trash collecting, floor mopping, toilet cleaning, and mirror polishing. Workers of different heights had differential work loadings for different tasks. Conclusions This paper proposes recommendations for job adaptations and occupational safety training. Cleaners of different heights execute the typical tasks via different postures, and awkward postures often result in musculoskeletal symptoms. Cleaners should be provided with specific tools and training regarding working postures on the basis of height. These findings can be used as a reference for related operation designs and task improvements to ensure correct tool usage and safer working postures during cleaning.

Neuroblastoma is the most common malignant disease of infancy, and amplification of the MYCN oncogene is closely associated with poor prognosis. Recently, expression of MYCN was shown to be inversely correlated with aryl hydrocarbon receptor (AHR) expression in neuroblastoma, and overexpression of AHR downregulated MYCN expression, promoting cell differentiation. Therefore, we further investigated the potential of AHR to serve as a prognostic indicator or a therapeutic target in neuroblastoma. First, the clinical significance of AHR in neuroblastoma was examined. Positive AHR immunostaining strongly correlated with differentiated histology of neuroblastoma and predicted better survival for patients. The mouse xenograft model showed that overexpression of AHR significantly suppressed neuroblastoma tumor growth. In addition, activation of AHR by the endogenous ligand kynurenine inhibited cell proliferation and promoted cell differentiation in vitro and in vivo. kynurenine treatment also upregulated the expression of KISS1, a tumor metastasis suppressor, and attenuated metastasis in the xenograft model. Finally, analysis of KISS1 levels in neuroblastoma patient tumors using the R2: Genomics Analysis and Visualization Platform revealed that KISS1 expression positively correlated with AHR, and high KISS1 expression predicted better survival for patients. In conclusion, our results indicate that AHR is a novel prognostic biomarker for neuroblastoma, and that overexpression or activation of AHR offers a new therapeutic possibility for patients with neuroblastoma. Significance: These findings show that AHR may function as a tumor suppressor in childhood neuroblastoma, potentially influencing the aetiologic and therapeutic targeting of the disease.

Although induction chemotherapy improves the resectability of thymic neoplasms, it is unclear whether surgery after induction chemotherapy can improve outcomes. We compared long-term outcomes of surgery with and without induction chemotherapy in patients with thymic neoplasms.We retrospectively investigated the clinical information of patients with thymic neoplasms at the National Taiwan University Hospital between 2005 and 2013.Of 204 patients, 119 underwent direct surgery (group 1), 45 underwent surgery after induction chemotherapy (group 2), and 40 underwent no surgery (group 3). The 5-year overall survival rates of groups 1, 2, and 3 were as follows: for 204 patients, 96.3%, 76.4%, and 35.5% (P .001); for 119 thymoma patients, 96.6%, 88.9%, and 100.0% (P = .835); for 85 thymic carcinoma patients, 94.7%, 69.7%, and 17.7% (P .001); for 36 American Joint Committee on Cancer (AJCC) stage III-IVA thymoma patients, 92.9%, 83.3%, and 100% (P = .833); and for 28 stage III-IVA thymic carcinoma patients, 75.0%, 76.2%, and 62.5%, (P = .160). Univariate analysis showed that for group 2 (P = .0208) and group 3 (P .0001), thymic carcinoma pathology type (P = .0010) and stage IVB disease (P .0001) were poor prognostic factors. Multivariate analysis found thymic carcinoma (P = .0026) and stage IVB disease (P = .0449) to be poor prognostic factors.Up-front surgery leads to best overall survival, and induction chemotherapy followed by surgery may improve resectability and outcomes. Only thymic carcinoma and stage IVB disease were poor prognostic factors in multivariate analysis.

This study aimed to investigate dosimeter characteristics by using a photon beam with and without the flattening filter of intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT) by using a 3D N-isopropylacrylamide (NIPAM) polymer gel. A self-developed optical computed tomography scheme was used to measure the dose distribution. Gamma evaluation was performed between the dose distribution calculated by a treatment planning system and the measured dose distribution by using the criteria of 3% dose difference and 3 mm distance to agreement. Under these criteria, the passing rates showed no significant difference between IMRT and VMAT irradiation with and without the flattening filter. All these results revealed that the NIPAM gel dosimeter was for high-dose-rate radiation and clinical-pretreatment verifications.

Background Postoperative urology patients may require the insertion of a ureteral stent. However, the delayed removal or change of the ureteral stent may lead to serious consequences for some patients. This study primarily aimed to examine the risk factors and complications associated with forgotten double-J stents (DJSs). Methods In this retrospective study, postoperative patients who underwent DJS insertion were recruited. Based on the brand of DJS, the maximal stent life (MSL) was classified into 3-month, 6-month, and 12-month groups, and a forgotten DJS was defined as the one that had yet to be removed 2 weeks past its MSL. A total of 479 patients were analyzed. The reasons for the use of DJSs use and the time and method of their insertion were recorded, and the risk factors and possible complications associated with forgotten DJSs were analyzed. Results The primary reason for DJS insertion was urolithiasis (69.7%), and insertions performed using ureterorenoscopy were the most common (413/479, 86.2%). Eighteen patients (3.8%) had forgotten DJSs, with an average overdue period of 63.17 days (18-189 days). Multivariate analysis revealed that patients older than 60 years (odds ratio [OR] = 3.626, 95% confidence interval [CI] = 1.070-12.289; p = 0.039) and DJSs exchanged using fibrocystoscopy (OR = 5.437, 95% CI = 1.060-28.256; p = 0.042) were significantly associated with forgotten DJSs. Out of the 18 patients with forgotten DJS, three (16.67%) experienced symptomatic complications, with one developing acute pyelonephritis, and the remaining two experiencing stone encrustation. Conclusion Patients older than 60 years were 3.6 times more likely to have forgotten DJSs than patients aged 60 and below, and DJSs exchanged using fibrocystoscopy were 5.4 times more likely to be forgotten than those inserted using ureterorenoscopy. Greater attention with regards to tracking and recalling DJSs should be paid in high-risk patients to prevent forgotten DJSs and associated complications.

AimsTo investigate the relations between anaplastic lymphoma kinase (ALK) and v-myc myelocytomatosis viral related oncogene neuroblastoma derived homolog (MYCN) protein expression and their prognostic roles in neuroblastoma tumours.MethodsSixty-one neuroblastoma tumours obtained at diagnosis were stained with anti-MYCN and anti-ALK antibodies by immunohistochemical staining. The correlations between protein expression of MYCN, ALK and clinicopathological and biological variables of neuroblastoma tumours were analysed.ResultsHigh expression of ALK protein could be detected in 25 (41%) and high expression of MYCN protein could be detected in 24 (39.3%) of the 61 neuroblastoma tumours, respectively. The majority of neuroblastoma tumours with evident of ALK or MYCN protein high expression exhibited undifferentiated or poorly differentiated histology (30/35, 85.7%). ALK or MYCN protein high expression in neuroblastoma tumours was associated with adverse clinical prognostic factors and ALK protein high expression was significantly associated with MYCN protein high expression. In addition, either ALK or MYCN protein high expression in neuroblastoma tumours was the independent adverse prognostic factor and also predicted worse survival outcomes for neuroblastoma patients with MYCN non-amplified status or non-high-risk Children’s Oncology Group grouping.ConclusionsOur study showed a novel coordinately prognostic role of ALK and MYCN protein expression in neuroblastoma and is the first report to demonstrate the correlation between ALK and MYCN protein expression in primary neuroblastoma tumours.

OBJECTIVE To investigate the association between rheumatoid arthritis (RA) and deep neck infection (DNI). STUDY DESIGN Retrospective cohort study. METHODS Patients newly diagnosed with RA between 2000 and 2011 were identified from the National Health Insurance Research Database in Taiwan. Moreover, patients without RA were randomly selected and matched at a 1:4 ratio by age, sex, urbanization level, income, and diabetes mellitus. The patients were followed up until death or the end of the study period (December 31, 2013). The primary outcome was the occurrence of DNI. RESULTS In total, 30,207 patients with RA and 120,828 matched patients without RA were enrolled. Patients with RA had a significantly higher cumulative incidence of DNI than those without RA (P

Aryl hydrocarbon receptor (AHR) signaling has been suggested to play roles in various physiological functions independent of its xenobiotic activity, including cell cycle regulation, immune response, and embryonic development. Several endogenous ligands were also identified by high-throughput screening techniques. However, the mechanism by which these molecules mediate AHR signaling in certain functions is still elusive. In this study, we investigated the possible pathway through which AHR and its endogenous ligands regulate neural development. We first identified two neuroactive steroids, 3α,5α-tetrahydrocorticosterone and 3α,5β-tetrahydrocorticosterone (5α- and 5β-THB), as novel AHR endogenous ligands through the use of an ultrasensitive dioxin-like compound bioassay and liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS). We then treated zebrafish embryos with 5α- and 5β-THB, which enhance the expression of neurogenesis marker HuC. Furthermore, 5α- and 5β-THB both enhanced the expression of myelinating glial cell markers, sex determining region Y-box 10 (Sox10), and myelin-associated proteins myelin basic protein (Mbp) and improved the mobility of zebrafish larvae via the Ahr2 pathway. These results indicated that AHR mediates zebrafish neurogenesis and gliogenesis, especially the differentiation of oligodendrocyte or Schwann cells. Additionally, we showed that these molecules may induce neuroblastoma (NB) cell differentiation suggesting therapeutic potential of 5α- and 5β-THB in NB treatment. In summary, our results reveal that 5α- and 5β-THB are endogenous ligands of AHR and have therapeutic potential for NB treatment. By the interaction with THB, AHR signaling regulates various aspects of neural development.