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The purpose of this study was to prepare and evaluate the feasibility and biocompatibility of a new composite as a bone substitute. The new composite (GTGC) was mainly composed of tricalcium phosphate ceramics and gelatin to which Chi-Li-Saan, a Chinese medicinal remedy was added. The GTGC composite was manually packed into cylindrical Teflon molds, dried overnight in an oven and sterilized by γ-ray prior to use. Mature New Zealand rabbits, weighting 3–3.5 kg, underwent full-thickness excision of the parietal bone. In the experimental group, bone defects of 12 animals were filled with the GTGC composites and another 12 unreconstructed rabbits were considered as controls. Three rabbits were examined for each group in every time period at 2, 4, 8 and 12 weeks after operation. There was no evidence of adverse tissue reaction to the GTGC composite. In addition, examination with light and fluorescent microscopy revealed a significantly greater amount of new bone ingrowth in the GTGC group at the same implantion time as compared with the controls. Therefore, the GTGC composite could serve as a useful substitute when repairing bone defects.

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...

Coronavirus Disease-19 (COVID-19) has been in a global pandemic currently and relating symptoms were reported variously around the world. We reported a previously healthy man of COVID-19 presenting with anosmia as the obvious symptom with relevant radiological findings on brain magnetic resonance imaging.

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.

Purpose Infections caused by carbapenemase-producing Klebsiella pneumoniae are emerging causes of morbidity and mortality worldwide. Optimal treatment for non–carbapenemase-producing carbapenem-resistant K pneumoniae (nCP-CRKP) bacteremia remains undefined. The goal of this study was to assess the clinical outcome, predictors of mortality, and therapeutic strategy of carbapenems for nCP-CRKP bacteremia. Methods A retrospective study of monomicrobial bacteremia caused by nCP-CRKP, at a medical center between 2010 and 2015 was conducted. CRKP which was defined as a minimum inhibitory concentration (MIC) of ≥ 2 for ertapenem or ≥ 4 mg/L for meropenem, or imipenem. Multiplex polymerase chain was applied to detect carbapenemase genes. The patients definitively treated with combination therapy were compared with monotherapy using a propensity score–matched analysis to assess therapeutic effectiveness. The primary end point was the 30-day crude mortality and clinical prognostic factors were assessed. Findings Overall 171 patients met criteria were eligible for the study and their overall 30-day mortality rate was 38.6%. The multivariate logistic regression analysis showed that combination therapy was associated with a lower 30-day mortality rate (adjusted odds ratio [aOR], 0.11; 95% CI, 0.03–0.43; P = 0.001) and less clinical (aOR, 0.21; 95% CI, 0.08–0.58; P = 0.003) and microbiologic (aOR, 0.36; 95% CI, 0.19–0.71; P = 0.003) failure. However, the 30-day mortality rate in the cases infected by a pathogen with a meropenem MIC ≤8 mg/L receiving carbapenem-containing or carbapenem-sparing combination regimens was similar (15 of 58 [25.9%] vs 5 of 20 [23.3%]; P = 1.0). Implications Combination therapy, regardless of carbapenem-containing or carbapenem-sparing, with one or more active agents improved survival more than monotherapy and was more effective in patients with critical illness. (Clin Ther. 2020; 42:XXX–XXX) © 2020 Elsevier HS Journals, Inc.

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.