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Background: Extracellular vesicles (EVs) are derived from internal cellular compartments, and have potential as a diagnostic and therapeutic tool in degenerative disease associated with aging. Mesenchymal stem cells (MSCs) have become a promising tool for functional EVs production. This study investigated the efficacy of EVs and its effect on differentiation capacity. Methods: The characteristics of MSCs were evaluated by flow cytometry and stem cell differentiation analysis, and a production mode of functional EVs was scaled from MSCs. The concentration and size of EVs were quantitated by Nanoparticle Tracking Analysis (NTA). Western blot analysis was used to assess the protein expression of exosome-specific markers. The effects of MSC-derived EVs were assessed by chondrogenic and adipogenic differentiation analyses and histological observation. Results: The range of the particle size of adipose-derived stem cells (ADSCs)- and Wharton’s jelly -MSCs-derived EVs were from 130 to 150 nm as measured by NTA, which showed positive expression of exosomal markers. The chondrogenic induction ability was weakened in the absence of EVs in vitro. Interestingly, after EV administration, type II collagen, a major component in the cartilage extracellular matrix, was upregulated compared to the EV-free condition. Moreover, EVs decreased the lipid accumulation rate during adipogenic induction. Conclusion: The results indicated that the production model could facilitate production of effective EVs and further demonstrated the role of MSC-derived EVs in cell differentiation. MSC-derived EVs could be successfully used in cell-free therapy to guide chondrogenic differentiation of ADSC for future clinical applications in cartilage regeneration.

The objective of this study was to determine if hemodialysis patients who have undergone an invasive dental treatment are at risk of developing infective endocarditis.This study was a cohort case-control design and used secondary data collected from the National Health Insurance Research Database of Taiwan. The case group and the control group were each comprised of 19,602 hemodialysis patients. The control group was matched for four variables: age, gender, a medical history of diabetes mellitus, and a cerebrovascular event. After matching, the case group and the control group were each comprised of 19,602 hemodialysis patients. Cox regression analysis determined hazard ratios and 95% confidence intervals.Patients were followed up at 1 month and 3 months after receiving invasive dental treatment. The results showed the cohort case-control hazard ratio was 0.88 (95% CI, 0.49, 1.57) 1 month after receiving invasive dental treatment. Three months after receiving IDT, the cohort case-control hazard ratio was 1.04 (95% CI, 0.71, 1.52). Hazard ratios did not differ significantly between groups.Hemodialysis patients who received invasive dental treatment had no greater risk of developing infective endocarditis than matched control patients. The results of this study should alleviate concerns for hemodialysis patients and dentists about invasive dental treatment procedures. We recommend hemodialysis patients undergo invasive dental treatment when needed.The results of this study showed that invasive dental treatment did not increase their risk of developing infective endocarditis. Hemodialysis patients in need of an invasive dental procedure should be encouraged to undergo treatment if the dentist deems it necessary.

Patients with severe psoriasis are prone to deterioration of renal function. Whether biologics with potent anti-inflammatory action can prevent deterioration of renal function in psoriatic patients was unclear.To investigate the effects of different biologics on renal function in patients with severe psoriasis.By using the Chang Gung Research Database in Taiwan during 2006-2018, we analyzed the changes in renal function of psoriatic patients from 2 years before biologic treatments to baseline (start of biologic treatment) to after 2 years' treatment with different classes of biologics (anti-TNF, anti-IL-12/23, and anti-IL-17 agents). The renal function was evaluated by estimated glomerular filtration rate (eGFR) and the staging of chronic kidney disease (CKD). We further analyzed the risk factors of progression on the staging of CKD during biologics treatment.We included 601 patients with severe psoriasis receiving continuous use of biologics for ≥ 2 years. We detected no significant differences between pre-biologic treatment with conventional systemic treatment and post-biologic treatment in the levels of eGFR and progression of CKD staging among psoriatic patients receiving different classes of biologics. Most patients (97.8%) remained at stable CKD stage, while progression of CKD stage over time occurred in 13 patients (2.2%), with seven treated with anti-TNF biologics and six treated with anti-IL-12/23 biologics. Of note, all 52 patients receiving anti-IL-17 biologics had stable CKD. Progression of CKD during biologics use was associated with lower baseline levels of eGFR, higher baseline CKD stage, older age, diabetes, and dyslipidemia. Further multiple logistic regression analysis showed diabetes as an independent factor for the deterioration of renal function during biologic treatment.Biologic treatments failed to improve but did not worsen renal function of psoriatic patients during a 2-year follow-up period. Diabetes is an important risk factor for the deterioration of renal function.

Microreactor-Assisted Nanomaterial Deposition (MAND) process offers unique capabilities in achieving large size and shape control levels while providing a more rapid path for scaling via process intensification for nanomaterial production. This review highlights the application of continuous flow microreactors to synthesize, assemble, transform, and deposit nanostructured materials for Solar Photovoltaics, the capabilities of MAND in the field, and the potential outlook of MAND.Microreactor-Assisted Nanomaterial Deposition (MAND) is a promising technology that synthesizes reactive fluxes and nanomaterials to deposit nanostructured materials at the point of use. MAND offers precise control over reaction, organization, and transformation processes to manufacture nanostructured materials with distinct morphologies, structures, and properties. In synthesis, microreactor technology offers large surface-area-to-volume ratios within microchannel structures to accelerate heat and mass transport. This accelerated transport allows for rapid changes in reaction temperatures and concentrations, leading to more uniform heating and mixing in the deposition process. The possibility of synthesizing nanomaterials in the required volumes at the point of application eliminates the need to store and transport potentially hazardous materials. Further, MAND provides new opportunities for tailoring novel nanostructures and nano-shaped features, opening the opportunity to assemble unique nanostructures and nanostructured thin films. MAND processes control the heat transfer, mass transfer, and reaction kinetics using well-defined microstructures of the active unit reactor cell that can be replicated at larger scales to produce higher chemical production volumes. This critical feature opens a promising avenue in developing scalable nanomanufacturing. This paper reviews advances in microreactor-assisted nanomaterial deposition of nanostructured materials for solar photovoltaics. The discussions review the use of microreactors to tailor the reacting flux, transporting to substrate surfaces via controlling process parameters such as flow rates, pH of the precursor solutions, and seed layers on the formation and/or transformation of intermediary reactive molecules, nanoclusters, nanoparticles, and structured assemblies. In the end, the review discusses the use of an industrial scale MAND to apply anti-reflective and anti-soiling coatings on the solar modules in the field and details future outlooks of MAND reactors. Graphical abstract

Peritoneal contamination is a major concern during natural orifice specimen extraction after laparoscopic colorectal resection (LCR-NOSE), but few data are available. We explored the prevalence, risk factors, and association between clinical outcomes and infectious complications in patients with positive peritoneal drain fluid culture (PDFC) after LCR-NOSE.We retrospectively analyzed patient records in our prospectively maintained registry database who underwent LCR-NOSE between 2011and 2020. Peritoneal drain fluid was collected within 12 h post-operative and cultures for microorganisms were obtained. The relationships between PDFC, clinical variables, and infectious complications were examined by univariate and multivariable analysis.Of 241 consecutive patients who underwent LCR-NOSE and drainage fluid culture, 59 (24.5%) had PDFC. Anterior resection (Odds ratio OR 2.40) was identified as an independent predictor for PDFC. Twenty-eight patients (11.6%) developed infectious complications. Multivariable analysis identified low anterior resection (OR 2.74), prolonged operative time (OR 3.20), and PDFC (OR 5.14) as independent risk factors. Pseudomonas aeruginosa was the most frequently found microorganism (OR 5.19) responsible for infectious complications.Microorganisms are commonly present in the peritoneum after LCR-NOSE and play a critical role in the development of infectious complications and related morbidity. Specific caution is warranted in patients contaminated with specific types of microorganisms.

Augmentation rhinoplasty is one of the top three anesthetic surgeries in Asia. I-shaped silicone-polytetrafluoroethylene composite implants are feasible for both primary and secondary augmentation rhinoplasty in Asians. This series was to analyze and evaluated the effect of the rhinoplasty to the intercanthal distance and to compare the height of the implantation with those differences in ICD before and after rhinoplasty. We retrospectively reviewed data from a single medical center via a single surgeon (Hsiao YC), at Chang Gung Memorial Hospital, between 2011 and 2017 with follow-up through 2018. There were 223 patients who received augmentation rhinoplasty with an I-shaped composite silicone-polytetrafluoroethylene ePTFE-lined silicone dorsal composite implant (Implantech, Ventura, CA) with a glabellar component (chimeric technique) or without a glabellar component. There were 169 patients with the height of the I-shaped composite implant over 3 mm, and 15 patients were less than 3 mm. There was no distribution significance between two groups even in gender, age, type of surgery, or indication. The paired difference of ICD/IPD ratio was statistically significant in the group with the height of composite implant over 3 mm (1.04% ± 0.11, p lt; 0.005, 95%). The normalized ratio of the ICD to IPD is estimated to decrease by 1-2%. Appropriate candidates including those with a wide ICD should be informed about these data during preoperative decision-making.Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Numerous studies have found that repetitive transcranial magnetic stimulation (rTMS) modulates plasticity. rTMS has often been used to change neural networks underlying learning, often under the assumption that the mechanism of rTMS-induced plasticity should be highly similar to that associated with learning. The presence of visual perceptual learning (VPL) reveals the plasticity of early visual systems, which is formed through multiple phases. Hence, we tested how high-frequency (HF) rTMS and VPL modulate the effect of visual plasticity by investigating neurometabolic changes in early visual areas. We employed an excitatory-to-inhibitory (E/I) ratio, which refers to glutamate concentration divided by GABA+ concentration, as an index of the degree of plasticity. We compared neurotransmitter concentration changes after applying HF rTMS to the visual cortex with those after training in a visual task, in otherwise identical procedures. Both the time courses of the E/I ratios and neurotransmitter contributions to the E/I ratio significantly differed between HF rTMS and training conditions. The peak E/I ratio occurred 3.5 h after HF rTMS with decreased GABA+, whereas the peak E/I ratio occurred 0.5 h after visual training with increased glutamate. Furthermore, HF rTMS temporally decreased the thresholds for detecting phosphene and perceiving low-contrast stimuli, indicating increased visual plasticity. These results suggest that plasticity in early visual areas induced by HF rTMS is not as involved in the early phase of development of VPL that occurs during and immediately after training.

Background The impact of sex-related differences in patients receiving extracorporeal membrane oxygenation support (ECMO) support is still inconclusive. This population-based study aimed to investigate sex differences in short- or long-term outcomes in order to improve clinical practice. Methods Patients who received ECMO between 2001 to 2017 were identified from the Taiwan National Health Insurance Research Database. Propensity score matching with a 1:1 ratio was conducted in female-to-male groups, to reduce confounding of baseline covariates. Outcomes included in-hospital mortality, all-cause mortality, all-cause readmission, and ECMO-related complications. Logistic regression analysis, Cox proportional hazard model, and join point regression were used to compare sex differences in both short- or long-term outcomes. Results In total, 7,010 matched patients from 11,734 ECMO receivers were included for analysis. The use of ECMO increased dramatically in past years, although the proportion of females was still lower than males. There was a decreasing trend of females undergoing ECMO over time. Female patients have lower risks of in-hospital mortality (64.08% in females vs 66.48% in males; P = 0.0352) and ECMO-related complications compared with males. Furthermore, females also had favorable long-term late outcomes such as all-cause mortality (73.35% in females vs 76.98% in males; P = 0.009) and readmission rate (6.99% in females vs 9.19% in males; P = 0.001). Conclusions Female patients had more favorable in-hospital and long-term survival outcomes. Despite improvement in modern ECMO technique and equipment, ECMO remains underutilized in eligible female patients. Thus, females should undergo ECMO treatment if available and indicated. Trial registration The institutional review board of Chang Gung Memorial Hospital approved all data usage and the study protocol (registration number: 202100151B0C502; date of registration: 23/08/2021).

There is scarce evidence about the surgeon learning curve of acute type A aortic dissection surgery and whether the optimal procedure number exists when training a cardiovascular surgeon. A total of 704 patients with acute type A aortic dissection surgery performed by 17 junior surgeons who can identify their first career surgery from January 1, 2005, to December 31, 2018, are included. The surgeon experience volume is defined as the cumulative number of acute type A aortic dissection surgery of the surgeon since January 1, 2005. The primary outcome was in-hospital mortality. The possibility of non-linearity and cutoffs for surgeon experience volume level was explored using a restricted cubic spline model. The results revealed that more surgeon experience volume is significantly correlated to a lower in-hospital mortality rate (r = − 0.58, P = 0.010). The RCS model shows for an operator who reaches 25 cumulative volumes of acute type A aortic dissection surgery, the average in-hospital mortality rate of the patients can be below 10%. Furthermore, the longer duration from the 1st to 25th operations of the surgeon is significantly correlated to a higher average in-hospital mortality rate of the patients (r = 0.61, p = 0.045). Acute type A aortic dissection surgery has a prominent learning curve in terms of improving clinical outcomes. The findings suggest fostering high-volume surgeons at high-volume hospitals can achieve optimal clinical outcomes.

Background Atrial fibrillation is the most common cardiac arrythmia and causes many complications. Sinus rhythm restoration could reduce late mortality of atrial fibrillation patients. The Maze procedure is the gold standard for surgical ablation of atrial fibrillation. Higher surgical volume has been documented with favorable outcomes of various cardiac procedures such as mitral valve surgery and aortic valve replacement. We aimed to determine the volume–outcome relationship (i.e., association between surgical volume and outcomes) for the concomitant Maze procedure during major cardiac surgeries. Methods This nationwide population-based cohort study retrieved data from the Taiwan National Health Insurance Research Database. Adult patients undergoing concomitant Maze procedures during 2010–2017 were identified; consequently, 2666 patients were classified into four subgroups based on hospital cumulative surgery volumes. In-hospital outcomes and late outcomes during follow-up were analyzed. Logistic regression and Cox proportional hazards model were used to analyze the volume–outcome relationship. Results Patients undergoing Maze procedures at lower-volume hospitals tended to be frailer and had higher comorbidity scores. Patients in the highest-volume hospitals had a lower risk of in-hospital mortality than those in the lowest-volume hospitals [adjusted odds ratio, 0.30; 95% confidence interval (CI), 0.15–0.61; P Conclusions A positive hospital volume–outcome relationship for concomitant Maze procedures was demonstrated for in-hospital and late follow-up mortality. The consequence may be attributed to physician skill/experience, experienced multidisciplinary teams, and comprehensive care processes. We suggest referring patients with frailty or those requiring complicated cardiac surgeries to high-volume hospitals to improve clinical outcomes. Trial registration: the institutional review board of Chang Gung Memorial Hospital approved all data usage and the study protocol (registration number: 202100151B0C502).

The forces of drag, tire and road surface friction resistance, the drive motor characteristics, the hill climbing angle, and other non-linear dynamic factors affect the performance of electric vehicles (EV) tremendously. The proposed self-construction of type-2 fuzzy neural network (SCT2FNN) controller was based on the robust typical type-2 fuzzy neural network (T2FNN) controller. T2FNN with the self-construct parameter and online learning could estimate the angular velocity of the motor operation to control the EV. Hence, SCT2FNN with the self-construct parameter and online learning could promptly track the speed of EV. SCT2FNN also could estimate the torque control of DC motor. The simulation results showed that SCT2FNN controller was more efficient than PID controller, while the speed was controlled by considering the difference of the climbing slope.

This study aimed to propose a novel four-type deformity and treatment-oriented classification of the lower eyelids that directs the therapeutic combination of three-step lower blepharoplasty for Asian populations. We reviewed 183 patients who underwent a therapeutic combination of three steps of lower blepharoplasty after being diagnosed with four types of lower eyelid deformities between July 2018 and April 2021. The three-step lower blepharoplasty includes: (1) mid-face and lower eyelid augmentation, (2) transconjunctival eye bag removal, and (3) skin pinch removal. Consecutive digital images, detailed fat graft volume, fat removal amount, skin pinch removal amount, complications, and patient’s satisfaction and aesthetic improvement score were recorded. The overall patient’s satisfy score is 91. Aesthetic improvement score is 80.2 and 83.3 among lay persons and experts, respectively. The volume of the fat graft ranges from 2 to 3 mL per orbit according to the severity of the deformity. The amount of fat removed was 0.53 ± 0.36 and 0.61 ± 0.40 mL per orbit in types II and III patients, respectively. There is no lower lid malposition. Eleven patients had over-correction of fat grafting, and they need steroid injection; 20 patients had under-correction of fat grafting, and they need secondary fat grafting. Ten patients need secondary skin pinch excision due to post-op skin redundancy. Two patients had conjunctiva wound granuloma. The combination of three-step lower blepharoplasty according to the novel classification is a straightforward and effective method to correct lower eyelid deformities. The complication rate was low with high patient satisfaction. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

BACKGROUND Several materials can serve as spacer grafts in the repair of retracted lower eyelids. However, previous studies did not reveal any of these to be superior to the others. From our perspective, autologous dermal grafts are ideal because they are biologically compatible and abundantly available. However, the absorption of these grafts is an issue, and the thickness of the dermal grafts is crucial. We evaluated the dermal thickness at five potential donor sites using ultrasonography and the efficacy and safety of the posterior neck dermis as a spacer graft in the correction of retracted lower eyelids. METHODS In 20 healthy volunteers, the dermal thickness was assessed using ultrasonography and compared between the posterior neck, upper arm, inguinal area, intergluteal cleft, and gluteal sulcus. Between January 2018 and June 2021, eight retracted lower eyelids in eight patients were repaired using a posterior neck dermal graft. The surgical results of these grafts were also evaluated. RESULTS The mean age of the volunteers was 37.8 years, and the mean body mass index was 24.45 kg/m2. The intergluteal cleft provided the thickest dermis followed by the posterior neck and gluteal sulcus, which were not significantly different. The upper arm and inguinal area had the thinnest dermis without significant differences between them. The mean marginal reflex distance 2/iris ratio decreased by 0.15 (p=0.008). The mean cosmetic score (0-10) for evaluation of lower eyelid reconstruction increased by 3.38 (p=0.011). The mean Vancouver Scar Scale score for evaluation of donor site scarring was 3.21. CONCLUSIONS Although the posterior neck dermis is the second thickest, it is an ideal spacer graft in the reconstruction of retracted lower eyelids. Adequate thickness, uncomplicated methods, and a closer surgical field are its advantages. Additionally, donor site morbidity is minimal, with acceptable scarring. LEVEL OF EVIDENCE IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Background Impaired renal function is frequently observed in patients with heart failure and reduced ejection fraction (HFrEF). The differential effect of sacubitril/valsartan and angiotensin-converting enzyme inhibitors/angiotensin-receptor blockers (ACEIs/ARBs) on the clinical and renal outcomes in patients with HFrEF and chronic kidney disease (CKD) remains unknown. Aims This study aimed to explore the differential effect of sacubitril/valsartan and ACEI/ARB on the clinical and renal outcomes as well as renal function over a 12-month follow-up period in HFrEF patients with and without CKD. Methods Patients with HfrEF (LVEF ≤35%) and NYHA class ≥II were enrolled from the Chang Gung Research Database between 2017 and 2020. Baseline characteristics were compared between patients prescribed sacubitril/valsartan and ACEI/ARB. After propensity score matching, the following clinical and renal outcomes were compared between the two groups in patients with and without CKD over a 12-month follow-up period: acute kidney injury (AKI), emergent dialysis/renal death, HF hospitalization, cardiovascular mortality, and all-cause mortality. Results This study enrolled 3735 HFrEF patients with a mean left ventricular EF of 27.56 ± 5.86%, who had been prescribed sacubitril/valsartan (N = 1708) or ACEI/ARB (N = 2027). After propensity score matching, the clinical and renal outcomes did not differ between the sacubitril/valsartan and ACEI/ARB groups in patients without CKD. In patients with CKD, the ACEI/ARB group had a significantly higher incidence of all-cause mortality than the sacubitril/valsartan group (14.89% vs. 10.50%; hazard ratio 1.46; 95% confidence interval 1.06–2.00; p = 0.02), and the incidence of AKI, HF hospitalization, and CV mortality did not differ between the two groups. Conclusions Sacubitril/valsartan had a lower all-cause mortality compared to ACEI/ARB in symptomatic HFrEF patients with CKD. Further prospective randomized studies are warranted to confirm our findings.

This study aimed to compare survival of patients with advanced major salivary gland cancers treated with adjuvant chemoradiation therapy (CRT) versus radiotherapy (RT) alone, after surgical resection. The Taiwan Cancer Registry database was used to identify patients (2009–2017) with advanced (T3–4 or nodal positivity) major salivary gland cancers, treated post-surgically with adjuvant CRT or RT alone. Overall survival (OS) and disease-specific survival (DSS) evaluated using Kaplan–Meier. Stratified analyses conducted on clinicopathological features. A total of 395 patients were analyzed: 178 (45.1%) received adjuvant CRT; 217 (54.9%) received adjuvant RT alone. Median radiation dose was 66 Gy in 33 fractions. Cisplatin was most common chemotherapy regimen. After a median follow-up of 3.37 years, there was no significant difference in OS or DSS (p = 0.1354 and 0.3361, respectively) between groups. Adding chemotherapy to adjuvant RT was not significantly associated with improved OS (adjusted hazard ratio [aHR] 0.94; 95% CI 0.72–1.23) and DSS (aHR 0.96; 95% CI 0.72–1.28). Stratified analysis of clinicopathological features found no significant advantages for improved OS or DSS from adding chemotherapy to adjuvant RT. Thus, in this population database, the use of chemotherapy provided limited survival benefits in advanced major salivary gland cancers after surgical resection.

This study evaluated the risk of major bleeding associated with concomitant use of direct oral anticoagulant (DOAC) and anticancer drugs (ACDs), which share metabolic pathways, in patients with atrial fibrillation (AF) and cancer. We performed a retrospective cohort study using Taiwan’s National Health Insurance database and included patients with AF and cancer who received DOAC prescriptions from 1 to 2012 to 31 December 2017. The incidence of major bleeding in person-quarters with concomitant use of DOAC and any of 15 ACDs with inhibitory or competitive effects of CYP3A4 or P-gp activity (docetaxel, vinorelbine, methotrexate, irinotecan, etoposide, doxorubicin, cyclophosphamide, imatinib, nilotinib, abiraterone, bicalutamide, tamoxifen, anastrozole, cyclosporine, tacrolimus) was compared with that in person-quarters with DOAC alone. Adjusted incidence-rate differences between DOAC use with and without concurrent ACDs were estimated using Poisson regression models weighted by the inverse probability of treatment. In 13,158 patients with AF and cancer (76.9 ± 8.9 years; male 60%), 1545 major bleeding events occurred during 90,540 DOAC-exposed person-quarters. Concurrent use of DOAC and any of 15 ACDs occurred in only 18% of patients. Compared with use of DOAC alone, concomitant use of DOAC and these ACDs was not associated with an increased risk of major bleeding. Co-medication with DOAC and ACDs with inhibitory or competitive effects on CYP3A4 or P-gp activity was not associated with a higher risk of major bleeding than DOAC alone. Our findings may provide clinicians with confidence regarding the safety of concurrent use of DOAC and ACDs in patients with AF and cancer.

Miliary lung metastasis is a unique feature of lung metastasis in non-small cell lung cancer (NSCLC), indicating hematogenous dissemination. Some studies reported more frequency of epidermal growth factor receptor (EGFR) mutation and worse prognosis in these patients. Cases were identified from Chi-Mei medical center cancer registry for the period 2015–2019. Inclusion criteria were NSCLC with contra-lateral lung metastasis harboring EGFR mutation, under tyrosine kinase inhibitor (TKI) prescription. Patients with miliary or non-miliary lung metastasis were enrolled for survival analysis. 182 NSCLC patients were enrolled for assessing time to discontinuation of TKI (TD-TKI), progression-free survival (PFS) and overall survival (OS). 54 patients with miliary lung metastasis had average 13.2 months [95% confidence interval (CI) 10.7–15.6] of TD-TKI, 11.4 months (95% CI 9.3–13.6) of PFS, and 21.3 months (95% CI 16.8–25.8) of OS, which were shorter than non-miliary group with marginally statistical significance. In multivariate analysis, miliary lung metastasis had no statistical significance, and other strong prognostic indicators were found including performance status, liver metastasis, EGFR type, and generation of TKI. In NSCLC patients harboring EGRF mutation under TKI prescription, miliary lung metastasis was not a dominant indicator for outcomes evaluation.

Background Vitamin K antagonists and different direct oral anticoagulants (DOACs) have different renal clearance rates. However, the impact of different stages of chronic renal impairment on the efficacy and safety of warfarin, dabigatran, rivaroxaban, apixaban, and edoxaban in atrial fibrillation (AF) patients remains unclear. Methods This study enrolled AF patients from the Chang Gung Research Database. The study endpoints included thromboembolic events, major/fatal bleeding, gastrointestinal (GI) bleeding and intracranial hemorrhage (ICH). The risks of time to study endpoints between groups were compared using a Cox proportional hazards regression model with adjustment. Results This study enrolled 3525 patients with moderate renal impairment (30 ≤ creatinine clearance (CrCl) Conclusion There did not appear to be major differences in bleeding or thromboembolic risk compared to warfarin in AF patients across a range of degree of renal failure when appropriate dose reductions of the DOACs are made.

Introduction Laparoscopic colectomy is rarely performed for ischemic colitis. The aim of this propensity score-matched study was to compare preoperative characteristics, intraoperative details and short-term outcomes for emergent laparoscopic colectomy versus the traditional open approach for patients with ischemic colitis. Methods Retrospective review of 96 patients who underwent emergent colectomy for ischemic colitis between January 2011 and December 2020 (39 via laparoscopy, 57 via laparotomy) was performed. We compared short-term outcomes after using a one-to-one ratio and nearest-neighbor propensity score matching to obtain similar preoperative and intraoperative parameters in each group. Results Patients in the open group experienced more surgical site complications (52.6% vs. 23.0%, p = 0.004), more intra-abdominal abscesses (47.3% vs. 17.9%, p = 0.003), longer need for ventilator support (20 days vs. 0 days, p p = 0.001), higher mortality (49.1% vs. 20.5%, p = 0.004), and longer hospital stay (32 days vs. 19 days, p = 0.001). After propensity score matching (31 patients in each group), patients undergoing open (vs. laparoscopy) had more surgical site complications (45.1% vs. 19.4%, p = 0.030) and required longer ventilator support (14 vs. 3 days, p = 0.039). After multivariate analysis, Charlson Comorbidity Index (p = 0.024), APACHE II score (p = 0.001), and Favier’s classification (p = 0.023) were independent predictors of mortality. Conclusions Laparoscopic emergent colectomy for ischemic colitis is feasible and is associated with fewer surgical site complications and better respiratory function, compared to the open approach.

Current methods of fabric dyeing have a significant negative effect on the environment via toxic effluent emissions, high water usage, and high energy consumption. We demonstrate, for the first time, low-energy inkjet printing of an ecofriendly and biodegradable pigment derived from widely available spalting fungi with synthesis by-products that are fully biodegradable. Vivid and stable coloration is achieved on polyester and cotton using benign acetone-based and ethanol-based biopigment inks, with no liquid effluent or runoff, and without any synthetic dyes or mordants. We investigate the influence of fabric type, solvent type, and the number of printing passes on the color type, intensity, and uniformity, pigment crystallization, and environmental stability. Greater spatial definition of the printed pigment in inkjet printing effects greater crystallization and more vivid and uniform coloration as compared to drop-casting, the primary method used till date to color fabrics with such fungal biopigments. pH-driven interactions between the fabric, solvent, and biopigment cause solvent-driven changes in color type (from bluish to reddish) and fabric-governed changes in color intensity. The impact of our findings on minimizing the environmental impact of fabric dyeing is discussed.

Machine health monitoring systems are vital components of modern manufacturing industries. As advanced sensors collecting machine health-related data become commonplace, such systems have started adopting data-driven approaches to harness the collected data. However, dealing with noisy data and gleaning the spatial and temporal correlation within the data is a challenge. Extant literature focuses on the use of feature extraction to judge the state of normal and worn tools. However, the process of detecting the features of worn tools can often damage the workpiece material and result in machine downtime, which increases costs. Using recent developments in artificial intelligence, data features can be used to gauge the condition of tools in real-time. This paper proposes Holistic–Local Long Short-Term Memory (HLLSTM), a deep learning approach that adopts Long Short-Term Memory to predict tool wear based on holistic and local features. The data is divided into segments to learn short-term data features and further divided into holistic training and local training data to extract more implicit feature information to improve the accuracy of tool wear prediction. Experimental results indicate that HLLSTM can reduce the mean absolute error of real tool wear value two-fold and accurately predict tool wear.

Although reduced port laparoscopic surgery (RPLS), defined as laparoscopic surgery performed with the minimum possible number of ports and/or small-sized ports, is less invasive than conventional laparoscopic surgery by reducing the number of surgical wounds, an extension of the incision is still needed for specimen extraction, which can undermine the merits of RPLS. To determine the impact of natural orifice specimen extraction (NOSE) in patients undergoing RPLS for colorectal cancer. The endpoints were perioperative outcome and oncologic safety at 3 years. Single-center experience (2013–2019). We retrospectively analyzed our prospectively collected patient records (American Joint Committee on Cancer (AJCC) stage I–III sigmoid or upper rectal cancer (tumor diameter ≤ 5 cm) who underwent curative anterior resection via RPLS. We excluded patients who did not undergo intestinal anastomosis. Perioperative and oncologic outcomes were compared between patients undergoing natural orifice (RPLS-NOSE) or conventional (mini-laparotomy) specimen extraction (RPLS-CSE). Patients were matched by propensity scores 1:1 for tumor diameter, AJCC stage, American Society of Anesthesiologists score and tumor location. Of 119 eligible patients, 104 were matched (52 RPLS-NOSE; 52 RPLS-CSE) by propensity scores. Compared with RPLS-CSE, RPLS-NOSE was associated with longer operative time (223.9 vs. 188.7 min; p = 0.003), decreased use of analgesics (morphine dose 33.9 vs. 43.4 mg; p = 0.011) and duration of hospital stay (4.2 vs. 5.1 days; p = 0.001). No statistically significant difference was found in morbidity or wound-related complication rates between the two groups. After a median follow-up of 34.3 months, no local recurrence was observed in RPLS-NOSE. The 3-year disease-free survival did not differ statistically significantly between groups (90.9 vs. 90.5%; p = 0.610). NOSE enhances the advantages of RPLS by avoiding the need for abdominal wall specimen extraction in patients with tumor diameter ≤ 5 cm. Surgical and oncologic safety are comparable to RPLS with CSE.

Two-dimensional (2D) semiconducting monolayers such as transition metal dichalcogenides (TMDs) are promising channel materials to extend Moore’s Law in advanced electronics. Synthetic TMD layers from chemical vapor deposition (CVD) are scalable for fabrication but notorious for their high defect densities. Therefore, innovative endeavors on growth reaction to enhance their quality are urgently needed. Here, we report that the hydroxide W species, an extremely pure vapor phase metal precursor form, is very efficient for sulfurization, leading to about one order of magnitude lower defect density compared to those from conventional CVD methods. The field-effect transistor (FET) devices based on the proposed growth reach a peak electron mobility ~200 cm2/Vs (~800 cm2/Vs) at room temperature (15 K), comparable to those from exfoliated flakes. The FET device with a channel length of 100 nm displays a high on-state current of ~400 µA/µm, encouraging the industrialization of 2D materials.

Whether direct oral anticoagulants (DOACs) are more effective and safer than warfarin among Asian patients with non-valvular atrial fibrillation (NVAF) undergoing dialysis remains unclear. We first compared the risks of ischemic stroke/systemic embolism (IS/SE) and major bleeding associated with DOACs compared with warfarin, in NVAF Asians undergoing dialysis using the Taiwan National Health Insurance Research Database (NHIRD) (Aim 1). Next, we searched PubMed and Medline from January 1, 2010 until January 31, 2020, to perform a systematic review and meta-analysis of all observational real-world studies comparing DOACs with warfarin specifically focused on NVAF patients with stage 4 or 5 chronic kidney disease undergoing dialysis (Aim 2). Finally, we tested the hypothesis whether AF patients undergoing dialysis treated with OACs (warfarin and DOACs) would be associated with lower risk of adverse clinical outcomes as compared to those without OACs using the Taiwan NHIRD (Aim 3). From June 1, 2012, to December 31, 2017, a total of 3237 and 9263 NVAF patients comorbid with ESRD receiving oral anticoagulant (OACs) (490 on DOAC, 2747 on warfarin) or no OACs, respectively, were enrolled. Propensity score matching was used to balance covariates across the study groups. For the comparison of DOAC vs. warfarin (Aim 1), DOACs had comparable risks of IS/SE and major bleeding to warfarin in our present cohort. From the original 85 results retrieved, nine studies (including our study) with a total of 6490 and 22,494 patients treated with DOACs and warfarin were included in the meta-analysis, respectively. There were 5343 (82%) and 20,337 (90%) patients treated with DOACs and warfarin undergoing dialysis, respectively. The pooled meta-analysis also indicated no difference of the effectiveness (HR:0.90; [95%CI:0.74–1.10]; P = 0.32) and safety outcomes (HR:0.75; [95%CI:0.54–1.05]; P = 0.09) between DOACs and warfarin (Aim 2). For the comparison of OAC (+) vs. OAC (−) (Aim 3), OAC-treatment was associated with a higher risk of IS/SE (hazard ratio (HR):1.54; [95% confidential interval (CI):1.29–1.84];P

Purpose A near-infrared spectroscopy system was developed to evaluate peripheral arterial occlusive disease (PAOD). The wireless device can take measurements when patients are doing rehabilitation exercise. Methods Two LED modules with wavelengths of 740 nm, 808 nm and 850 nm were placed over 32 mm away from the photodiode to detect the deep backscattering from muscle tissue. The absorbance difference from the extent of tissue oxygenation was extracted using a modified Beer’s law. Measurements taken on different muscle groups were applied to determine which branch of artery is occluded. Results The changes in oxygenation of gastrocnemius and tibialis anterior muscle were recorded when PAOD patients were riding a stationary bicycle. The drop in oxygenation with exercise generally should recover within 15 min of continuing exercise. Otherwise, the artery is not capable to provide enough blood supply to the exercising muscles. Since gastrocnemius is the primary muscle used in biking exercise, the compensatory vasodilation in gastrocnemius leads to hypoperfusion in tibialis anterior muscle. Conclusion This NIRS system is helpful for detecting the changes in tissue oxygenation during exercise. Muscle hypoxia was more obvious during exercise when the artery had some degree of occlusion.

Given the speculation of the market economy causing an epidemic of depression, this study aimed to examine the influence of international trade on the prevalence of depressive disorders. We used panel data from 1993 to 2015 covering 170 countries (n = 3787) and applied fixed effects regression models. We modeled the prevalence of depressive disorders as a function of international trade, adjusting for economic development, economic growth, and population size. Regime types, media freedom, and capital–labor ratio were included as moderators. A 100% point increase in the value of international trade indicated a 0.09% point decrease in the prevalence of depressive disorders (− 0.09, confidence interval [CI] − 0.01 to − 0.18). However, this effect existed only for democratic countries (− 0.15, CI − 0.03 to − 0.28). The effect was more prevalent when the governments allowed the media more freedom (score of 100, − 0.31, CI − 0.17 to − 0.45) or when a country’s capital–labor ratio of endowments was high (50,000, − 0.22, CI − 0.08 to − 0.35). Trade brings about positive mental health outcomes in democracies, countries having free media, or capital-abundant economies.

Recycled poly(ethylene terephthalate) (r-PET) is a thermoplastic polyester. Repeated heat processing of r-PET may negatively affect physical properties due to thermal degradation. Therefore, to improve the physical properties of r-PET, poly(glycidyl methacrylate) (PGMA) samples with different molecular weights (low, medium, and high) were synthesized using atom transfer radical polymerization. The synthesized PGMA polymer was then subjected to 1H-NMR characterization and gel permeation chromatography for the analysis of molecular weight and its distribution. The intrinsic viscosity values of the r-PET/PGMA blend were increased from 0.61 to 0.8 dL g− 1 using high-molecular-weight PGMA at 2 wt%, and the glass transition temperature was increased from 71.8 °C for r-PET to 82.2 °C using high-molecular-weight PGMA at 1 wt%. Young’s modulus was increased by 1.1 times using 2 wt% high-molecular-weight PGMA compared with raw r-PET. All r-PET/PGMA blends samples exhibited notable shear thinning behavior and high viscosity compared with raw r-PET, and r-PET/PGMA blends are found with medium-molecular-weight PMGA polymers observing optimal physical properties. With these enhanced properties, the r-PET/PGMA blends can be applied in the recycling of PET, such as in eco-friendly yarn, packaging materials, and melt-brown non-woven fabric applications.

Following hematuria, it is uncertain to what extent a vitamin K antagonist (VKA) or non-VKA oral anticoagulant (NOAC) is resumed, and the risks of ischemic stroke/systemic embolism and major bleeding associated with NOAC and VKA resumption are unknown. A cohort study was conducted using electronic medical records collected from 2009 to 2017 at a multicenter healthcare provider in Taiwan. The cohort included 4155 atrial fibrillation patients receiving anticoagulant therapy with hematuria (age: 71.4 ± 11.2 years; 48.8% female). Within 90 days following hematuria, 3287 patients (79.1%) resumed oral anticoagulants including VKA (n = 1554, 37.4%) and NOACs (n = 1733, 41.7%), whereas 868 patients did not resume anticoagulant. Follow-up was initiated 90 days after the occurrence of hematuria, and time-varying multiple Cox regression analyses were used for comparisons between the resumption of NOAC and VKA. The event rates per 100 person-years in the VKA resumption and NOAC resumption groups were 3.04 and 3.28 for ischemic stroke/systemic embolism, and 2.63 and 2.92 for major bleeding, respectively. Patients resuming NOAC had similar risks of ischemic stroke/systemic embolism (hazard ratio 1.14, 95% CI 0.75–1.74) and major bleeding (hazard ratio 1.12, 95% CI 0.72–1.74) compared with those resuming VKA. Since 2011, the proportion of NOAC resumption has increased, whereas the proportions of VKA resumption and non-resumption have decreased. In conclusion, more and more patients who suffer a hematuria while on oral anticoagulant therapy resume NOAC. Patients resuming NOAC have similar risks of ischemic stroke/systemic embolism and major bleeding compared with those resuming VKA.

Let $$G=\left\langle S|R_{A}\right\rangle $$ be a semigroup with generating set S and equivalences $$R_{A}$$ among S determined by a matrix A. This paper investigates the complexity of G-shift spaces by yielding the Petersen–Salama entropies [defined in Petersen and Salama (Theoret Comput Sci 743:64–71, 2018)]. After revealing the existence of Petersen–Salama entropy of G-shift of finite type (G-SFT), the calculation of Petersen–Salama entropy of G-SFT is equivalent to solving a system of nonlinear recurrence equations. The complete characterization of Petersen–Salama entropies of G-SFTs on two symbols is addressed, which extends (Ban and Chang in On the topological entropy of subshifts of finite type on free semigroups, 2018. arXiv:1702.04394 ) in which G is a free semigroup.

Zirconia (ZrO2) has been widely used in clinical applications, such as bone and dental implantation, because of its favorable mechanical properties and resistance to fracture. However, the poor cell affinity of ZrO2 for bone regeneration and tissue binding, as well as its shrinkage due to crystal phase transformation during heat treatment, limits its clinical use and processing plasticity. This study aims to investigate an appropriate ZrO2–SiO2 composite recipe for ceramic 3D printing processes that can strike a balance between the mechanical properties and cell affinity needed in clinical applications. Specimens with different ZrO2–SiO2 composite recipes were fabricated by a selective laser gelling method and sintered at temperatures ranging from 900 to 1500 °C. The S5Z5 composite, which consists of 50 wt% ZrO2, 35 wt% SiO2 and 15 wt% SiO2 sol, showed an appropriate compressive strength and bending strength of 82.56 MPa and 55.98 MPa, respectively, at a sintering temperature of 1300 °C. The shrinkage rate of the S5Z5 composite was approximately 5% when the sintering temperature was increased from 900 to 1500 °C. All composites exhibited no cytotoxicity after 144 h of MG63 cell incubation, and the S5Z5 composite exhibited the most obvious cell affinity among the composite recipes. From these results, compared with other composites, the S5Z5 composite was shown to possess mechanical properties and a cell affinity more comparable to those of natural human bone.