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BACKGROUND Atherosclerosis and vascular inflammatory response have been considered as risk factors for non-typhoidal Salmonella (NTS) vascular infection. The study aims to assess the risk of vascular infection by measuring atherosclerosis severity, NTS vascular infection (NTSVI) score, and serum levels of inflammatory markers in people with NTS bacteremia. METHODS A prospective observational study was conducted in two medical centers and two regional hospitals. Adults aged ≥50 years with NTS bacteremia who underwent computed tomography (CT) scan for revealing vascular infections were enrolled. The degree of atherosclerosis was scaled by a calcium score determined by a CT scan. Serum concentrations of inflammatory biomarkers were determined in the patients enrolled in a medical center. RESULTS Fourteen (20.3%) of 69 patients with NTS bacteremia had vascular infections. Calcium scores over the thoracic (12,540 vs. 3,261, P = 0.0005) and abdominal (9755 vs. 3,461, P = 0.0006) aorta of those with vascular infections were higher than those without vascular infection. All vascular infections were present in the high-risk group (NTSVI score ≥1), yielding a sensitivity of 100% and specificity of 30.9%. Among 17 low-risk patients (NTSVI score

Background Management of comorbidities of people living with HIV (PLHIV) involves different care models, including providing diabetes care and HIV care by the same infectious diseases physician (IDP) (“consolidated care”) or providing diabetes care by the physicians other than IDP (“shared care”). The impact of diabetes care model on PLHIV with diabetes mellitus (DM) has not been well-evaluated. Methods A nationwide cross-sectional sample in the Taiwan National Health Insurance Research Database was used to compare the performance rates of seven guideline-recommended tests provided by the different subspecialists. Results Of 523 PLHIV with DM, there were 54.88% (n = 287) in the consolidated care group and 45.12% (n = 236) in the shared care group. More patients in the consolidated care group received the tests of lipid profile (92.33% vs. 79.24%), creatinine (Cr) (93.73% vs. 78.39%), and alanine transaminase (ALT) (91.99% vs. 75.42%), but fewer received urine protein test (35.54% vs. 51.69%) and fundoscopic examination (8.01% vs. 33.90%). The two groups did not differ in the performance rates of serum fasting glucose and HbA1c. After controlling for demographic factors and diabetic severity, the consolidated group was less likely to miss the serum tests of lipid profile (odds ratio [OR]: 0.30), Cr (OR: 0.19), and ALT (OR: 0.23), but more often missed urine protein test (OR: 1.56) and fundoscopic examination (OR: 4.97). Conclusion These findings suggest the need to focus on different process indicators of diabetes cares in different care models to enhance the diabetes care for PLHIV.

Photodocumentation during endoscopy procedures is one of the indicators for endoscopy performance quality; however, this indicator is difficult to measure and audit in the endoscopy unit. Emerging artificial intelligence technology may solve this problem, which requires a large amount of material for model development. We developed a deep learning-based endoscopic anatomy classification system through convolutional neural networks with an accelerated data preparation approach. We retrospectively collected 8,041 images from esophagogastroduodenoscopy (EGD) procedures and labeled them using two experts for nine anatomical locations of the upper gastrointestinal tract. A base model for EGD image multiclass classification was first developed, and an additional 6,091 images were enrolled and classified by the base model. A total of 5,963 images were manually confirmed and added to develop the subsequent enhanced model. Additional internal and external endoscopy image datasets were used to test the model performance. The base model achieved total accuracy of 96.29%. For the enhanced model, the total accuracy was 96.64%. The overall accuracy improved with the enhanced model compared with the base model for the internal test dataset without narrowband images (93.05% vs. 91.25%, p

BACKGROUND Multidisciplinary meeting (MDM) discussion and early palliative care are recommended in lung cancer management. The literature is unclear whether MDM discussion leads to early palliative care and improved end-of-life care. AIMS To evaluate impacts of discussion at an Australian lung MDM on palliative care referral, and MDM and early palliative care on aggressive end-of-life care. METHODS A retrospective, cross-sectional study was conducted of 352 patients diagnosed with primary lung cancer from 2017 to 2019 at the Alfred Hospital, Melbourne. The primary question was whether MDM discussion influenced palliative care referrals. Secondary questions were whether MDM discussion and early palliative care reduced aggressive treatment (chemotherapy, hospitalisation, emergency department visits, intensive care admission and in-hospital death) during the last 30 days of life. Multivariable logistic regression was used to determine independent association between MDM discussion and palliative care referral. RESULTS MDM discussion did not independently impact palliative care referral. There was reduced likelihood of MDM presentation in patients with metastatic disease (P

Tissue microenvironment properties like blood flow, extracellular matrix, or proximity to immune-infiltrate are important regulators of cell biology. However, methods to study regional protein expression in the native tissue environment are limited. To address this need, we developed a novel approach to visualize, purify, and measure proteins in situ using automated spatially targeted optical microproteomics (AutoSTOMP). Here, we report custom codes to specify regions of heterogeneity in a tissue section and UV-biotinylate proteins within those regions. We have developed liquid chromatography-mass spectrometry (LC-MS)/MS-compatible biochemistry to purify those proteins and label-free quantification methodology to determine protein enrichment in target cell types or structures relative to nontarget regions in the same sample. These tools were applied to (a) identify inflammatory proteins expressed by CD68+ macrophages in rat cardiac infarcts and (b) characterize inflammatory proteins enriched in IgG4+ lesions in human esophageal tissues. These data indicate that AutoSTOMP is a flexible approach to determine regional protein expression in situ on a range of primary tissues and clinical biopsies where current tools and sample availability are limited.

Purpose Tumor metastasis is the main cause of death from breast cancer patients and cell migration plays a critical role in cancer metastasis. Recent studies have shown long non-coding RNAs (lncRNAs) play an essential role in the initiation and progression of cancer. In the present study, the role of an LncRNA, Rho GTPase Activating Protein 5- Antisense 1 (ARHGAP5-AS1) in breast cancer was investigated. Methods RNA sequencing was performed to find out dysregulated LncRNAs in MDA-MB-231-LM2 cells. Transwell migration assays and F-actin staining were utilized to estimate cell migration ability. RNA pulldown assays and RNA immunoprecipitation were used to prove the interaction between ARHGAP5-AS1 and SMAD7. Western blot and immunofluorescence imaging were used to examine the protein levels. Dual luciferase reporter assays were performed to evaluate the activation of TGF-β signaling. Results We analyzed the RNA-seq data of MDA-MB-231 and its highly metastatic derivative MDA-MB-231-LM2 cell lines (referred to as LM2) and identified a novel lncRNA (NR_027263) named as ARHGAP5-AS1, which expression was significantly downregulated in LM2 cells. Further functional investigation showed ARHGAP5-AS1 could inhibit cell migration via suppression of stress fibers in breast cancer cell lines. Afterwards, SMAD7 was further identified to interact with ARHGAP5-AS1 by its PY motif and thus its ubiquitination and degradation was blocked due to reduced interaction with E3 ligase SMURF1 and SMURF2. Moreover, ARHGAP5-AS1 could inhibit TGF-β signaling pathway due to its inhibitory role on SMAD7. Conclusion ARHGAP5-AS1 inhibits breast cancer cell migration via stabilization of SMAD7 protein and could serve as a novel biomarker and a potential target for breast cancer in the future.

Purpose Metastasis of lung adenocarcinoma (LADC) is a crucial factor determining patient survival. Repurposing of the antipsychotic agent penfluridol has been found to be effective in the inhibition of growth of various cancers. As yet, however, the anti-metastatic effect of penfluridol on LADC has rarely been investigated. Herein, we addressed the therapeutic potential of penfluridol on the invasion/metastasis of LADC cells harboring different epidermal growth factor receptor (EGFR) mutation statuses. Methods MTS viability, transwell migration and invasion, and tumor endothelium adhesion assays were employed to determine cytotoxic and anti-metastatic effects of penfluridol on LADC cells. Protease array, Western blot, immunohistochemistry (IHC), immunofluorescence (IF) staining, and expression knockdown by shRNA or exogenous overexpression by DNA plasmid transfection were performed to explore the underlying mechanisms, both in vitro and in vivo. Results We found that nontoxic concentrations of penfluridol reduced the migration, invasion and adhesion of LADC cells. Protease array screening identified matrix metalloproteinase-12 (MMP-12) as a potential target of penfluridol to modulate the motility and adhesion of LADC cells. In addition, we found that MMP-12 exhibited the most significantly adverse prognostic effect in LADC among 39 cancer types. Mechanistic investigations revealed that penfluridol inhibited the urokinase plasminogen activator (uPA)/uPA receptor/transforming growth factor-β/Akt axis to downregulate MMP-12 expression and, subsequently, reverse MMP-12-induced epithelial-mesenchymal transition (EMT). Subsequent analysis of clinical LADC samples revealed a positive correlation between MMP12 and mesenchymal-related gene expression levels. A lower survival rate was found in LADC patients with a SNAl1high/MMP12high profile compared to those with a SNAl1low/MMP12low profile. Conclusions Our results indicate that MMP-12 may serve as a useful biomarker for predicting LADC progression and as a promising penfluridol target for treating metastatic LADC.

The factor structure, measurement invariance, and internal consistency of the Patient Health Questionnaire for Depression and Anxiety (PHQ-4) was examined with a rural, predominately Hispanic sampl...

The adaptation of tumour cells to hypoxic microenvironment is one of the most significant characteristics of many malignant tumour diseases including hepatocarcinoma. Recently, long non-coding RNAs (lncRNAs) have been reported to play important roles in the various levels of gene regulation thus functioning in growth and survival of tumour cells. Here, new hypoxia-related lncRNAs in hepatocarcinoma cells were screened and validated by lncRNA chip-array as well as real-time RT-PCR. Among them, a hypoxia-activated lncRNA that we identified and termed Hypoxia-Activated BNIP3 Overlapping Non-coding RNA (HABON), was not only regulated by hypoxic-induced factor-1α (HIF-1α) but its expression increased significantly under hypoxia in tumour cells. We deciphered the biological characteristics of HABON including its cell localization, genomic location, as well as its full-length sequence, and proved HABON could promote growth, proliferation and clone-formation of hepatocarcinoma cells under hypoxia. Then, we revealed that HABON was transcriptionally activated by HIF-1α in hypoxic cells, furthermore, it could interact with HIF-1α and promote its protein degradation, thus affecting transcription of HIF-1α’s target genes to exert its effects on cells. Besides, the elevated expression of HABON under hypoxia could promote the transcriptional activation of BNIP3 through HIF-1α, and increasing the expression level of BNIP3. This research provides a novel clue for the adaptive survival and growth mechanism of tumour under hypoxia, and gives a way to reveal the nature of tumour cells’ resistance characteristics to harsh microenvironment.

This study reveals an uncovered mechanism for the regulation of polyamine homeostasis through protein arginyl citrullination of antizyme (AZ), a natural inhibitor of ornithine decarboxylase (ODC). ODC is critical for the cellular production of polyamines. AZ binds to ODC dimers and promotes the degradation of ODC via the 26S proteasome. This study demonstrates the protein citrullination of AZ catalyzed by peptidylarginine deiminase type 4 (PAD4) both in vitro and in cells. Upon PAD4 activation, the AZ protein was citrullinated and accumulated, leading to higher levels of ODC proteins in the cell. In the PAD4-overexpressing and activating cells, the levels of ODC enzyme activity and the product putrescine increased with the level of citrullinated AZ proteins and PAD4 activity. Suppressing cellular PAD4 activity reduces the cellular levels of ODC and downregulates cellular polyamines. Furthermore, citrullination of AZ in the C-terminus attenuates AZ function in the inhibition, binding, and degradation of ODC. This paper provides evidence to illustrate that PAD4-mediated AZ citrullination upregulates cellular ODC and polyamines by retarding ODC degradation, thus interfering with the homeostasis of cellular polyamines, which may be an important pathway regulating AZ functions that is relevant to cancer biology.

Background: The geriatric nutritional risk index (GNRI) calculated as 1.489 × albumin (g/dL) +41.7× (current body weight/ideal body weight) is useful in identifying high-risk for malnutrition in elderly patients with subacute or chronic diseases. Given that trauma patients have sustained injuries in an acute condition, this study is designed to explore the association between GNRI on admission and outcomes in elderly and young adult patients with trauma. Materials and Methods: From January 01, 2009, to December 31, 2019, a total of 1772 elderly and 2194 young adult trauma patients were categorized into four nutritional risk groups according to GNRI: high-risk group (GNRI 98). Propensity score-matched patient cohorts were created in different nutritional risk groups against the no-risk group to minimize the confounding effects of sex, age, pre-existing comorbidities, Glasgow Coma Scale score, and Injury Severity Score on outcome measurements. Primary outcome was in-hospital mortality, and secondary outcome was the length of hospital stay. Results: Young adult patients with trauma were comparable in pattern of mortality outcomes and hospital stays to that in elderly patients. Analysis of the selected propensity score-matched patient cohorts revealed that both elderly and young adult patients in the high-risk group had significantly higher odds of mortality (elderly, odds ratio [OR], 6.5; 95% confidence interval [CI], 3.00-14.03; P < 0.009; young adult, OR, 2.7; 95% CI, 1.45-5.11; P = 0.001) and longer hospital stay (elderly, 21.5 days vs. 12.4 days, respectively, P < 0.001; young adults, 22.5 days vs. 14.1 days, respectively, P < 0.001) than those of the no-risk group. Conclusion: This study demonstrated that the GNRI could serve as a useful screening method to identify high-risk malnutrition in acutely injured trauma patients, including not only the elderly trauma patients but also the young adult trauma patients.

Gastric cancer is common, especially in East Asian countries, and is associated with high recurrence and mortality rates. Currently, there is no standard third-line treatment for metastatic gastric cancer. In this report, we present the case of a 69-year-old man with advanced gastric cancer, whose tumor was negative for human epidermal growth factor receptor 2 (HER2) according to immunohistochemical analysis. Next-generation sequencing performed on paraffin sections of the postoperative tumor samples indicated the presence of the ERBB3 V104L mutation. The patient received irinotecan plus pyrotinib as a third-line therapy and achieved a progression-free survival of 7.6 months with a high quality of life. Therefore, the combined administration of irinotecan and pyrotinib may improve the clinical condition of patients with gastric cancer harboring an ERBB3 mutation. Moreover, ERBB3 could be a potential therapeutic target for gastric cancer.

This paper proposes a gait detection model that can recognize important gait events in real time. Human gaits are periodic, with each gait cycle containing the important gait events of mid-swing, heel-strike (HS), and toe-off. The correct identification of different gait patterns caused by stroke or progressive neurodegenerative Parkinson’s disease could ensure that the patients receive appropriate treatment and rehabilitation strategies. However, online detection of gait events can be challenging because each person has their own walking patterns and speeds. This paper applies recurrent neural networks (RNNs) to develop a model that can instantly detect important gait events in any subject. We collected clinical gait data and used them to develop an RNN model for real-time detection of HS. The model correctly recognized HS events with an average success rate of 98.84% and an average delay of 0.024 s in the laboratory environment. We then applied the model to three different groups of subjects: healthy elderly subjects, stroke patients, and patients with Parkinson’s disease. The developed RNN model also correctly recognized HS events in all three groups with an average accuracy of more than 99.65%, even though the subjects had very different walking patterns. In the future, the developed gait detection model can be integrated with real-time rehabilitation systems to provide patients with repetitive guidance using clinician-determined cures for enhanced clinical gait training.

Food allergy is often understood as an IgE-mediated hypersensitivity, characterized by allergic symptoms which occur "immediately" after the ingestion of a relevant food allergen. Increasingly, however, other food-related immune-mediated disorders are recognized in which symptoms can have a delayed onset and IgE does not play a central role. One of the described examples of the latter is eosinophilic esophagitis (EoE) - a disease defined pathologically by local eosinophilic inflammation in the esophagus in the setting of symptoms of esophageal dysfunction. The evidence that EoE is a food-mediated allergic disease includes i) almost all patients respond to an elemental diet and many respond to a diet in which dairy, wheat, eggs and/or soy are eliminated, ii) the presence of food-specific IgE and Th2 cells are consistent with a loss of tolerance to trigger foods and iii) many EoE patients have concomitant IgE-mediated food allergy and other allergic co-morbidities. This narrative review focuses on the hypothesis that EoE is a form of chronic food allergy. The goal is to describe similarities and differences in EoE and IgE-mediated food allergy, and to consider ways that these two increasingly common forms of food allergy are related to each other.

Purpose: The aim of the study was to determine the effectiveness of dignity therapy for end-of-life patients with cancer. Methods: This study used a quasi-experimental study design with a nonrandomized controlled trial. Dignity therapy was used as an intervention in the experimental group, and general visit was used in the control group. Thirty end-of-life patients with cancer were recruited, with 16 in the experimental group and 14 in the control group. Outcome variables were the participants' dignity, demoralization, and depression. Measurements were taken at the following time points: pre-test (before intervention), post-test 1 (the 7th day), and post-test 2 (the 14th day). The effectiveness of the intervention in the two groups was analyzed using the generalized estimating equation, with the p value set to be less than .05. Results: After dignity therapy, the end-of-life patients with cancer reflected increased dignity significantly [β = −37.08, standard error (SE) = 7.43, Wald χ2 = 24.94, p

Microtissue engineering root canal dentin with biopolymeric nanoparticles has the potential to improve mechanical properties of iatrogenically compromised root dentin. This study aims to characterize the surface mechanical property, bulk biomechanical response, and fatigue resistance of microtissue-engineered root dentin using photodynamically (photodynamic-activated [PDA]) cross-linked chitosan nanoparticles (CSnps).Experiments were conducted in 3 parts: part 1, root canal dentin sections were subjected to nanoindentations before/after treatment with CSnps and chemically (1-ethyl-3-[3-dimethylaminopropyl]carbodiimide [EDC] cross-linked CSnps) and photodynamically cross-linked CSnps to determine the properties of treated surfaces (n = 84 points/group); part 2, root canal dentin specimens treated with PDA cross-linked CSnps were subjected to strain analysis using customized moiré interferometry (n = 5/group); and part 3, root canal dentin specimens treated with EDC cross-linked CSnps, PDA cross-linked CSnps, and instrumented controls were tested using an accelerated fatigue loading protocol to evaluate the sustained loads and cycles at failure (n = 15/group). Data were analyzed using the paired sample t test, trend analysis, and Kaplan-Meier with log-rank tests at a significance of .05 in each experiment.Root dentin microtissue engineered with PDA cross-linked CSnps showed a 16.8% increase in elastic modulus and a conspicuous decrease in strain distribution in cervical root dentin (P.01). There was a significant reduction in the tensile strain formed at the apical region of the instrumented root dentin after treatment (P.05). Survival analysis showed a statistically significant difference (P.05) among evaluated conditions in fatigue resistance (ie, PDA cross-linked CSnpsEDC cross-linked CSnpscontrol).This study highlighted the potential of root canal dentin microtissue engineering with PDA cross-linked CSnps to diminish radicular strain distribution and improve resistance to fatigue loads in endodontically treated teeth.

Background/aim We aimed to examine the association of the genotypes of Nijmegen breakage syndrome 1 (NBS1), a critical gene in DNA double strand break repair machinery, with bladder cancer risk in Taiwan. Materials and methods NBS1 rs1805794 genotypes among 375 bladder cancer patients and 375 non-cancer healthy controls were determined via the polymerase chain reaction-restriction fragment length polymorphism methodology and their association with bladder cancer risk were evaluated. Results The results showed that the percentages of GG, CG and CC of NBS1 rs1805794 genotypes were 45.4%, 43.7% and 10.9% in the bladder cancer patient group and 47.2%, 43.2% and 9.6% in the non-cancer control group, respectively (p for trend=0.7873). The analysis of allelic frequency distributions showed that the variant C allele of NBS1 rs1805794 does not contribute to an increased bladder cancer susceptibility (p=0.5066). Conclusion The genotypes of NBS1 rs1805794 are not closely associated with personal susceptibility to bladder cancer.

Background The temporal and spatial scales of exposure assessment may influence observed associations between fine particulate air pollution (PM2.5) and mortality, but few studies have systematically examined this question. Methods We followed 2.4 million adults in the 2001 Canadian Census Health and Environment Cohort for nonaccidental and cause-specific mortality between 2001 and 2011. We assigned PM2.5 exposures to residential locations using satellite-based estimates and compared three different temporal moving averages (1, 3, and 8 years) and three spatial scales (1, 5, and 10 km) of exposure assignment. In addition, we examined different spatial scales based on age, employment status, and urban/rural location, and adjustment for O3, NO2, or their combined oxidant capacity (Ox). Results In general, longer moving averages resulted in stronger associations between PM2.5 and mortality. For nonaccidental mortality, we observed a hazard ratio of 1.11 (95% CI = 1.08, 1.13) for the 1-year moving average compared with 1.23 (95% CI = 1.20, 1.27) for the 8-year moving average. Respiratory and lung cancer mortality were most sensitive to the spatial scale of exposure assessment with stronger associations observed at smaller spatial scales. Adjustment for oxidant gases attenuated associations between PM2.5 and cardiovascular mortality and strengthened associations with lung cancer. Despite these variations, PM2.5 was associated with increased mortality in nearly all of the models examined. Conclusions These findings support a relationship between outdoor PM2.5 and mortality at low concentrations and highlight the importance of longer-exposure windows, more spatially resolved exposure metrics, and adjustment for oxidant gases in characterizing this relationship.

Embryonic stem cells (ESCs) are pluripotent stem cells capable of self-renewal and differentiation into all types of embryonic cells. Like many other cell types, ESCs release small membrane vesicles, such as exosomes, to the extracellular environment. Exosomes serve as essential mediators of intercellular communication and play a basic role in many (patho)physiological processes. Granulocyte-macrophage colony-stimulating factor (GM-CSF) functions as a cytokine to modulate the immune response. The presence of GM-CSF in exosomes has the potential to boost their immune regulatory function. Here, GM-CSF was stably overexpressed in the murine ESC cell line ES-D3. A protocol was developed to isolate high-quality exosome-enriched extracellular vesicles (EVs) from ES-D3 cells overexpressing GM-CSF. Isolated exosome-enriched EVs were characterized by a variety of experimental approaches. Importantly, significant amounts of GM-CSF were found to be present in exosome-enriched EVs. Overall, GM-CSF-bearing exosome-enriched EVs from ESCs might function as cell-free vesicles to exert their immune regulatory activities.

The nanocone-shaped carbon nanotubes field-emitter array (NCNA) is a near-ideal field-emitter array that combines the advantages of geometry and material. In contrast to previous methods of field-emitter array, laser ablation is a low-cost and clean method that does not require any photolithography or wet chemistry. However, nanocone shapes are hard to achieve through laser ablation due to the micrometer-scale focusing spot. Here, we develop an ultraviolet (UV) laser beam patterning technique that is capable of reliably realizing NCNA with a cone-tip radius of ≈300 nm, utilizing optimized beam focusing and unique carbon nanotube–light interaction properties. The patterned array provided smaller turn-on fields (reduced from 2.6 to 1.6 V/μm) in emitters and supported a higher (increased from 10 to 140 mA/cm2) and more stable emission than their unpatterned counterparts. The present technique may be widely applied in the fabrication of high-performance CNTs field-emitter arrays.

This prospective study aimed to investigate the clinical and microbiological characteristics of different Aeromonas species. Clinical isolates of Aeromonas species between 2016 to 2018 were collected in a university hospital in southern Taiwan. The species was determined by rpoD or gyrB sequencing. A total of 222 Aeromonas isolates from 160 patients in 164 episodes were identified. The crude in-hospital mortality was 17.2%. The most frequently isolated species was Aeromonas veronii (30.6%), followed by A. caviae (24.8%), A. hydrophila (23%), and A. dhakensis (16.7%). The major clinical manifestations were primary bacteremia (31.1%), skin and soft tissue infection (22.6%), and biliary tract infection (18.3%). The most common underlying diseases were malignancy (45.1%), diabetes mellitus (27.4%), and liver cirrhosis or chronic hepatitis (26.2%). A. hydrophila and A. dhakensis predominated in the skin and soft tissue infection (pA. vernoii and A. caviae prevailed in primary bacteremia and biliary tract infections (p=0.012). Pneumonia, malignancy, and ascF-ascG genotype were independent factors associated with mortality. Ertapenem susceptibility was decreased in A. sobria (42.9%), A. veronii (66.7%), A. dhakensis (73%), and A. hydrophila (84.3%). Cefotaxime resistance was found in 30.9% of A. caviae and 18.9% of A. dhakensis isolates, much more prevalent than the other species. The metallo-β-lactamase blaCphA was almost invariably present in A. dhakensis, A. hydrophila, and A. veronii (100%, 100% and 89.9%, respectively). Amp-C β-lactamases such as blaMOX and blaAQU-1 were identified in all A. caviae and 91.9% of A. dhakensis isolates. Cefepime, fluoroquinolones and tigecycline showed good in vitro activity against aeromonads.

Background: Sepsis remains a common but fatal complication among patients with immune suppression. We aimed to investigate the performance of metagenomic next-generation sequencing (mNGS) compared with standard microbiological diagnostics in patients with hematologic malignancies. Methods: We performed a prospective study from June 2019 to December 2019. Adult patients with hematologic malignancies and a clinical diagnosis of sepsis were enrolled. Conventional diagnostic methods included blood cultures, serum galactomannan for Aspergillus, cryptococcal antigen and cytomegalovirus (CMV) viral loads. Blood samples for mNGS were collected within 24 h after hypotension developed. Results: Of 24 patients enrolled, mNGS and conventional diagnostic methods (blood cultures, serology testing and virus RT-PCR) reached comparable positive results in 9 cases. Of ten patients, mNGS was able to identify additional pathogens compared with conventional methods, most of the pathogens were virus. Conclusion: Our results show that mNGS may serve as adjunctive diagnostic tool for the identification of pathogens of hematologic patients with clinically sepsis.

(1) Background: This study aimed to determine the association between the use of efavirenz and depressive disorders among human immunodeficiency virus (HIV)-infected patients. (2) Methods: A retrospective cohort study was conducted using Taiwan’s National Health Insurance Database. We identified patients receiving anti-retroviral therapy (ART) between 2000 and 2009; these patients were followed until 2010 for diagnoses of depressive disorders using the Cox proportional hazard model to estimate hazard ratios. (3) Results: After up to 11 years of follow-up, the incidence of depressive disorders for the efavirenz-treated group was estimated at 12.2/1000 person-years (PYs), and the control group was at 12.5/1000 PY (p = 0.822). The independent risk factors for depressive disorders included an insurance premium of less than NTD 17,820 (New Taiwan Dollars—NTD) (adjusted hazard ratio (aHR) 2.59, 95% confidence interval (CI), 1.79–3.76, p < 0.001), and between NTD 17,821 and NTD 26,400 (aHR 1.55, 95% CI, 1.04–2.31, p = 0.030), living in Southern Taiwan (aHR 1.49, 95% CI, 1.21–1.84, p = 0.002), and with a psychiatric history (excluding depressive disorders) (aHR 4.59, 95% CI, 3.51–6.01, p = 0.030). (4) Conclusions: This study concluded that ART-treated patients with a past history of psychiatric disorders, lower insurance premium, and living in Southern Taiwan have an increased risk of depressive disorders, which are not associated with the use of efavirenz.

Defects in the {beta}-cells secretion system are well-described in Type 2 diabetes (T2D), including reduced insulin storage and impaired proinsulin processing; however, the cellular mechanisms underlying these secretory defects and the contribution of chronic hyperglycemia to this process remain poorly understood. In this study, we provide evidence that oxidative protein folding in the endoplasmic reticulum (ER) is perturbed in models of {beta}-cell dysfunction, leading to delays in proinsulin trafficking and insulin granule formation. Using an in situ fluorescent pulse-chase labeling strategy and APEX2-based proximity labeling, we demonstrate that enriched interactions of proinsulin with ER oxidoreductases coincides with a delay in proinsulin ER export. Furthermore, our data show that proinsulin ER export can be regulated by metabolically derived NADPH and reducing equivalent (glutathione) availability. Together, these data highlight an emerging role for nutrient metabolism and mitochondrial dysfunction in the maladaptive remodeling of the {beta}-cells secretory pathway during the decline of {beta}-cell function in T2D.

Purpose: this study investigated the effects of the intensity of machine-based bicep curl resistance exercise on ultrafast ultrasound-derived muscle strain rate and carotid ultrafast pulse wave velocity (ufPWV), and examined the association between muscle strain rate, ufPWV, and established carotid function measures in habitual resistance-trained individuals. Methods: twenty-three young habitual resistance-trained males (age: 24 ± 1 year, body mass index = 24 ± 1 kg/m2) were recruited to participate in two bouts of acute bicep curl exercise. After one-repetition maximum determination (1RM), the participants were randomly assigned to engage in bicep curls at 40 or 80%1RM intensity (10 reps × five sets) by a crossover study design. The muscle strain rate of bicep muscle, carotid ufPWV during systole(ufPWV-sys), and diastole (ufPWV-dia) were obtained pre- and post-exercise. In addition, carotid function measures were calculated by obtained carotid diameter and central blood pressure changes. Results: compared with pre-exercise, the reduction in post-exercise muscle strain rate and its area under the curve of 80%1RM was greater than those of 40%1RM. Both ufPWV-sys and ufPWV-dia increased regardless of exercise intensity. Baseline bicep muscle strain rate correlated not only with ufPWV-sys (r = −0.71, p = 0.001), ufPWV-dia (r = −0.74, p = 0.001), but also carotid compliance (r = 0.49, p = 0.02), distensibility (r = 0.54, p = 0.01) and ß stiffness (r= −0.84, p &lt, 0.0001). The ufPWVs also correlated with ß stiffness (r = 0.64–0.76, p = 0.01). Conclusion: muscle stiffness measured by ultrafast ultrasound elastography increases positively with resistance exercise intensity, and it appears to correlate with carotid ufPWV and established carotid function measures in habitual resistance-trained individuals.

Myocardial fibrosis is a pathological change in the progress of modern heart disease. It is mainly characterized by dysregulation or marked increase of collagen volume in myocardial components. The physiological mechanism of fibrosis in different pathologies is very diverse. It has been proved that the use of MRI for the detection of heart failure patients can provide accurate measurements of left ventricle and right ventricle and assessment of myocardial function, but the accurate segmentation of myocardial contour is still an important prerequisite for the detection of fibrosis. This study uses Mask R-CNN on the ACDC challenge Database to repeatedly adjust the characteristics of the boundary of the Bounding box, and separately divided the left ventricular area and the right ventricular area. The proposed method can achieve up to 95% hit rate with 0.89 IoU.

Aim There is very little literature reporting the association of matrix metalloproteinase-1 (MMP1) with personal susceptibility to bladder cancer. In the current study, we carried out the first examination of the contribution of MMP1 rs1799750 to bladder cancer risk in Taiwanese. Materials and methods A total of 375 bladder cancer cases and 375 healthy controls were genotyped for MMP1 rs1799750 via polymerase chain reaction-restriction fragment length polymorphism methodology and this was evaluated for association with clinicopathological factors. Results The frequencies of MMP1 rs1799750 2G/2G, 1G/2G, and 1G/1G genotypes were 35.7%, 44.8% and 19.5% in the group with bladder cancer and 32.5%, 46.4%, and 21.1% in the healthy control group (p for trend=0.6362). The odds ratios (ORs) for bladder cancer risk after adjusting for age and gender for those carrying 1G/2G and 1G/1G genotypes at MMP1 rs1799750 were 0.88 (95% CI=0.62-1.24, p=0.4357) and 0.83 (95% CI=0.61-1.26, p=0.3990), respectively, compared with the wild-type 2G/2G genotype. In allelic frequency analysis, the adjusted OR for those carrying the 1G allele at MMP1 rs1799750 was 0.87 (95% CI=0.71-1.23, p=0.3479) compared to those people carrying a 2G allele. Conclusion Our findings indicated that the genotypes at MMP1 rs1799750 appear to play little role in determining personal susceptibility to bladder cancer for Taiwanese.

This paper investigates the potential of detecting stroke gaits by Deep Neural Network (DNN) models based on data from different sensor systems. Stroke survivors usually experience partial disability and need long-term rehabilitation. Because correct evaluation of stroke gaits is crucial for clinics to apply suitable medical treatments and rehabilitation strategies, we propose a method to detect stroke gaits by generalized gait data that might be obtained from different measurement systems. In this paper, we measure the subjects’ gait data by two equipment: an IMU system and a motion capture system. Then, we apply the IMU data to develop DNN models, which achieve an accuracy of 99.04% in detecting the stroke gaits by k-fold validation. Last, we applied the data measured by the motion capture system to test the DNN models. The results showed that the model could successfully detect stroke gaits with an average accuracy of 98.68%. In addition, we also applied a public dataset, where the gait data was measured by different IMU systems, to evaluate the model performance. The results show that the DNN models achieve an average accuracy of 98.25% in distinguishing normal gaits. These results confirm the possibility of detecting abnormal gaits based on data measured at different locations by assorted sensor systems.

Background: The frail elderly are prone to falls and fractures, which can result in dependency, disability, admission to institutions, and even death. They are at increased risk of frailty due to decreased physical activity, cognitive decline, and depression. Some evidence suggests that music therapy with physical activities may be particularly beneficial. Objective: This study aimed to investigate the intervention effect of music therapy with physical activities (MTPA) on frail elderly in the community. Methods: A quasi-experimental design was adopted. We selected 10 community care centers in southern Taiwan, in which elderly people over the age of 65 were assigned to a MTPA group and a comparison group after obtaining their informed consent. The MTPA group performed group music activities once a week for 120 min for 12 weeks, while the comparison group only continued with their daily activities. Instruments in this study included the Kihon Checklist, Senior Fitness Test (with Body Mass Index (BMI) and seven physical fitness items), Mini-Mental Status Examination (MMSE), and Geriatric Depression Scale Short Form (GDS-SF). Results: A total of 132 community elders agreed to participate in this study, and 122 completed both the pretest and posttest, with 62 in the music therapy group and 60 in the comparison group. The results of ANCOVA showed that after intervention, except for BMI, the Kihon frailty assessment, seven fitness scores individually and in total, MMSE, and depression showed significant improvements in the music therapy group relative to the comparison group (all p &lt, 0.05). Conclusion: MTPA can improve the frailty index, cognitive function, depression, and physical fitness index in the community elderly. The results of this study can be used as a reference for the design of activities for the community elderly, to provide them with appropriate activities, improve their physical functions, and improve or delay their disability.

Purpose: Detection of early glaucoma remains limited with the conventional analysis of the retinal nerve fiber layer (RNFL). This study assessed whether compensating the RNFL thickness for multiple demographic and anatomic factors improves the detection of glaucoma. Design: Cross-sectional study. Participants: Three hundred eighty-seven patients with glaucoma and 2699 healthy participants. Methods: Two thousand six hundred ninety-nine healthy participants were enrolled to construct and test a multivariate compensation model, which then was applied in 387 healthy participants and 387 patients with glaucoma (early glaucoma, n = 219; moderate glaucoma, n = 97; and advanced glaucoma, n = 71). Participants underwent Cirrus spectral-domain OCT (Carl Zeiss Meditec) imaging of the optic disc and macular cubes. Compensated RNFL thickness was generated based on ethnicity, age, refractive error, optic disc (ratio, orientation, and area), fovea (distance and angle), and retinal vessel density. The RNFL thickness measurements and their corresponding areas under the receiver operating characteristic curve (AUCs) were obtained. Main Outcome and Measures: Measured and compensated RNFL thickness measurements. Results: After applying the Asian-specific compensation model, the standard deviation of RNFL thickness reduced, where the effect was greatest for Chinese participants (16.9%), followed by Malay participants (13.9%), and Indian participants (12.1%). Multivariate normative comparison outperformed measured RNFL for discrimination of early glaucoma (AUC, 0.90 vs. 0.85; P < 0.001), moderate glaucoma (AUC, 0.94 vs. 0.91; P < 0.001), and advanced glaucoma (AUC, 0.98 vs. 0.96; P < 0.001). Conclusions: The multivariate normative database of RNFL showed better glaucoma discrimination capability than conventional age-matched comparisons, suggesting that accounting for demographic and anatomic variance in RNFL thickness may have usefulness in improving glaucoma detection. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version Supported by the National Medical Research Council, Singapore, Republic of Singapore (grant nos.: CG/C010A/2017, OFIRG/0048/2017, OFLCG/004c/2018, TA/MOH-000249-00/2018, and MOH-OFIRG20nov-0014); the National Research Foundation, Singapore, Republic of Singapore (grant nos.: NRF-CRP24-2020-0001 and NRF2019-THE002-0006); A*STAR (grant no.: A20H4b0141); the Singapore Eye Research Institute & Nanyang Technological University (SERI-NTU Advanced Ocular Engineering [STANCE] Program); the Duke-NUS Medical School (grant no. Duke-NUS-KP(Coll)/2018/0009A); and the SERI-Lee Foundation, Singapore, Republic of Singapore (grant no.: LF1019-1).

Fat embolism syndrome (FES) is a complication of long bone fractures that often occurs within 72 hours of injury. Early-onset isolated cerebral fat embolism is catastrophic and rarely reported. We herein present a rare case of delayed-onset isolated cerebral FES that developed 10 days after definite fixation of a left tibial plateau fracture. A 70-year-old woman was injured in a traffic accident and diagnosed with a left tibial plateau fracture. However, she developed sudden loss of consciousness (E4V1M1) and quadriplegia 10 days after fracture fixation. Her vital signs showed no respiratory distress. Diagnosis of isolated cerebral FES was made based on magnetic resonance imaging of the brain, the findings of which were compatible with the clinical neurological findings. After supportive care and rehabilitation, her consciousness became clear on the second day of admission, and her consciousness changed to E4V5M6. She gradually regained strength in her right limbs but had residual left limb paraplegia. Isolated cerebral FES should always be considered for patients who develop a change in consciousness, even beyond 72 hours after injury. Imaging may not initially show definitive abnormalities. Repeated magnetic resonance imaging should be considered if the initial clinical presentation does not fully meet Gurd’s criteria.

Lipoteichoic acid (LTA) stimulates pleural mesothelial cell (PMC) to overproduce plasminogen activator inhibitor-1 (PAI-1), and thus may promote pleural fibrosis in Gram-positive bacteria (GPB) parapneumonic effusion (PPE). Histone deacetylase inhibitor (HDACi) was found to possess anti-fibrotic properties. However, the effects of HDACi on pleural fibrosis remain unclear. The effusion PAI-1 was measured among 64 patients with GPB PPE. Pleural fibrosis was measured as radiographical residual pleural thickening (RPT) and opacity at a 12-month follow-up. The LTA−stimulated human PMCs and intrapleural doxycycline−injected rats were pretreated with or without the pan-HDACi, m-carboxycinnamic acid bis-hydroxamide (CBHA), then PAI-1 and collagen expression and activated signalings in PMCs, and morphologic pleural changes in rats were measured. Effusion PAI-1 levels were significantly higher in GPB PPE patients with RPT &gt, 10 mm (n = 26) than those without (n = 38), and had positive correlation with pleural fibrosis shadowing. CBHA significantly reduced LTA−induced PAI-1 and collagen expression via inhibition of JNK, and decreased PAI-1 promoter activity and mRNA levels in PMCs. Furthermore, in doxycycline−treated rats, CBHA substantially repressed PAI-1 and collagen synthesis in pleural mesothelium and minimized pleural fibrosis. Conclusively, CBHA abrogates LTA−induced PAI-1 and collagen expression in PMCs and attenuates experimental pleural fibrosis. PAI-1 inhibition by HDACi may confer potential therapy for pleural fibrosis.

We used a large national cohort in Canada to assess the incidence of acute myocardial infarction (AMI) and stroke hospitalizations in association with long-term exposure to fine particulate matter (PM2.5), nitrogen dioxide (NO2), and ozone (O3). The study population comprised 2.7 million respondents from the 2006 Canadian Census Health and Environment Cohort (CanCHEC), followed for incident hospitalizations of AMI or stroke between 2006 and 2016. We estimated 10-year moving average estimates of PM2.5, NO2, and O3, annually. We used Cox proportional hazards models to examine the associations adjusting for various covariates. For AMI, each interquartile range (IQR) increase in exposure was found to be associated with a hazard ratio of 1.026 (95% CI: 1.007-1.046) for PM2.5, 1.025 (95% CI: 1.001-1.050) for NO2, and 1.062 (95% CI: 1.041-1.084) for O3, respectively. Similarly, for stroke, an IQR increase in exposure was associated with a hazard ratio of 1.078 (95% CI: 1.052-1.105) for PM2.5, 0.995 (95% CI: 0.965-1.030) for NO2, and 1.055 (95% CI: 1.028-1.082) for O3, respectively. We found consistent evidence of positive associations between long-term exposures to PM2.5, and O3, and to a lesser degree NO2, with incident AMI and stroke hospitalizations.

A 46-year-old woman presented to the emergency department with 2-day fever and cough at seven days after returning from Macau. COVID-19 and pneumonia was diagnosed based on the positive real-time RT-PCR tests for oropharyngeal swab samples and the presence of anti-SARS-COV-2 IgG starting from the illness day 11 and post-exposure 18–21 days.

In times like these, appreciating the essential nature of palliative and end-of-life care is perhaps more critical than ever. At the time of writing, more than 2.8 million confirmed cases and nearl...

Background and aim Antibiotic prophylaxis should be instituted for cirrhotic patients with upper gastrointestinal bleeding (UGIB), but the benefit on compensated patients remains undetermined. We aimed to compare the clinical outcomes between cirrhotic patients without major complications with UGIB with and without antibiotic prophylaxis. Methods We conducted this population-based cohort study by using Taiwanese Longitudinal Health Insurance Database 2000 (LHID2000, between 1997 to 2013), aged 18 years or older with a hospital discharge diagnosis of cirrhosis (n = 64,506), UGIB (n = 7,784), and endoscopic therapy (n = 2,292). After strict exclusions, 1205 patients were enrolled and were divided into antibiotic exposure (n = 558) and non-exposure (n = 647) groups. The outcomes were rebleeding and mortality. Results After completing the analysis adjusted by death, the rebleeding rates within 4 weeks were significantly lower in patients with antibiotic prophylaxis (3.05% versus 6.03%, P = 0.0142) and those with endoscopic therapy (0.72% vs 3.09%, P = 0.0033) but not significant after 3 months and onwards. Male patients aged > 55, high CCI score ≧ 4, and UGIB of variceal etiologies were benefited from rebleeding. The use of antibiotics did not significantly impact 6-week mortality (adjusted hazard ratio: 1.07, 95%CI: 0.41~2.75; P = 0.8943). Old age, multiple comorbidities, and UGIB of variceal etiologies were risk factors of all-cause mortality. Conclusions The current study suggested that cirrhotic patients without major complications who suffered from UGIB were benefited by the use of antibiotics to prevent rebleeding within 4 weeks after endoscopic treatment of UGIB especially for those with age > 55, high CCI score ≧ 4, and UGIB of variceal etiologies.

AIMS: The aim of this study was to improve medication reconciliation and reduce the occurrence of duplicate prescriptions by pharmacists and physicians within 72 hours of hospital admission using an intelligent prescription system combined with the National Health Insurance PharmaCloud system to integrate the database with the medical institution computerized physician order entry (CPOE) system. METHODS: This 2‐year intervention study was implemented in the geriatric ward of a hospital in Taiwan. We developed an integrated CPOE system linked with the PharmaCloud database and established an electronic platform for coordinated communication with all healthcare professionals. Patients provided written informed consent to access their PharmaCloud records. We compared the intervention effectiveness within 72 hours of admission for improvement in pharmacist medication reconciliation, increased at‐home medications documentation and decreased costs from duplicated at‐home prescriptions. RESULTS: The medication reconciliation rate within 72 hours of admission increased from 44.0% preintervention to 86.8% postintervention (relative risk = 1.97, 95% confidence interval [CI]: 1.69–2.31; P