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Aims and objectives: To assess the concurrent validity between logbooks and a single‐item rehabilitation adherence measurement for patients with stroke. Agreement between caregivers and patients and between caregivers and physical therapists regarding a single‐item measurement was investigated, and its predictive validity was explored. Background: Adherence to therapy is a primary determinant of treatment success. There are no standard instruments for measuring rehabilitation adherence available for stroke patients. Design: Prospective longitudinal study. Methods: Seventy‐five patients with stroke were recruited, measured four times and followed for 6 months. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist was used to ensure comprehensive reporting. Adherence was documented in logbooks, and single‐item measurements were compared. Predictive validity was explored by assessing associations between adherence levels, self‐care ability and health‐related quality of life. The Spearman's correlation coefficients, weighted kappa, and generalised estimating equations statistics were used to explore the concurrent validity, measurement agreement, and predictive validity, respectively. Results: Logbook records had a fair correlation (rs =.23, p =.04) with the single‐item rehabilitation adherence measurements. There was moderate agreement (kappa = 0.42, p <.001) between caregiver and patient assessments and fair agreement (kappa = 0.29, p =.017) between caregiver and physical therapist assessments of patients' rehabilitation adherence levels. Perfect rehabilitation adherence, based on the logbook and single‐item measurements, predicted better scores for self‐care ability and quality of life than imperfect rehabilitation adherence during 6 months after inclusion. Conclusions: There was fair concurrent validity between logbooks and single‐item rehabilitation adherence measurements and moderate and fair adherence measure agreement between caregivers and patients and caregivers and physical therapists, respectively. Logbooks and single‐item rehabilitation adherence measurements had adequate predictive validity. Relevance to clinical practice: Single‐item rehabilitation adherence measurement is a workable and straightforward method to assess stroke patients' rehabilitation adherence in busy clinical care settings. Caregivers can represent stroke patients regarding their reported rehabilitation adherence. Patient or public contribution: Patients were diagnosed with stroke in the study hospital. Rehabilitation physicians transferred patients to a research nurse who then screened them for the inclusion criteria and invited them and their family caregivers to participate in this study if they met the requirements. We also recruited seven physical therapists responsible for the physical therapy of the study participants. After participants signed informed consent, the research nurse encouraged participants to respond to research questions face to face, including rehabilitation adherence data, daily physical function, and quality of life. Each participant was measured four times at baseline and at 1, 3, and 6 months after inclusion in this study. Physical therapists had to score their patients' rehabilitation adherence levels before discharge. Trial registration details: Not applicable. [ABSTRACT FROM AUTHOR]

Background: Castration-resistant prostate cancer (CRPC) patients frequently develop neuroendocrine differentiation, with high mortality and no effective treatment. However, the regulatory mechanism that connects neuroendocrine differentiation and metabolic adaptation in response to therapeutic resistance of prostate cancer remain to be unravelled.Methods: By unbiased cross-correlation between RNA-sequencing, database signatures, and ChIP analysis, combining in vitro cell lines and in vivo animal models, we identified that PCK1 is a pivotal regulator in therapy-induced neuroendocrine differentiation of prostate cancer through a LIF/ZBTB46-driven glucose metabolism pathway.Results: Upregulation of PCK1 supports cell proliferation and reciprocally increases ZBTB46 levels to promote the expression of neuroendocrine markers that are conducive to the development of neuroendocrine characteristic CRPC. PCK1 and neuroendocrine marker expressions are regulated by the ZBTB46 transcription factor upon activation of LIF signalling. Targeting PCK1 can reduce the neuroendocrine phenotype and decrease the growth of prostate cancer cells in vitro and in vivo.Conclusion: Our study uncovers LIF/ZBTB46 signalling activation as a key mechanism for upregulating PCK1-driven glucose metabolism and neuroendocrine differentiation of CRPC, which may yield significant improvements in prostate cancer treatment after ADT using PCK1 inhibitors. [ABSTRACT FROM AUTHOR]

Background and Purpose: Intra-islet heparan sulfate (HS) plays an important role in the maintenance of pancreatic islet function. The aim of this study was to investigate the effect mechanism of HS loss on the functioning of islets in diabetic mice.Experimental Approach: The hypoglycaemic effect of a heparanase inhibitor, OGT2115, was tested in a streptozotocin-induced diabetic mouse model. The islets in pancreatic sections were also stained to reveal their morphology. An insulinoma cell line (MIN6) and primary isolated murine islets were used to investigate the effect of OGT2115 in vitro.Key Results: Intra-islet HS was clearly lost in streptozotocin-induced diabetic mice due to the increased heparanase expression in damaged islets. OGT2115 prevented intra-islet HS loss and improved the glucose profile and insulin secretion in streptozotocin-treated mice. The apoptosis of pancreatic beta cells and the infiltration of mononuclear macrophages, CD4- and CD8-positive T-cells in islets was reduced by OGT2115 in streptozotocin-treated mice, but OGT2115 did not alter the direct streptozotocin-induced damage in vitro. The expression of heparanase was increased in high glucose-treated isolated islets but not in response to direct streptozotocin stimulation. Further experiments showed that high glucose stimuli could decreased expression of PPARγ in cultured islets, thereby relieving the PPARγ-induced inhibition of heparanase gene expression.Conclusion and Implications: Hyperglycaemia could cause intra-islet HS loss by elevating the expression of heparanase, thereby aggravating inflammatory cell infiltration and islet damage. Inhibition of heparanase might provide benefit for pancreatic beta cell protection in Type 1 diabetes. [ABSTRACT FROM AUTHOR]

Objective: This study sought to develop a decision aid with cartoon pictures and evaluate its effectiveness in increasing consistency between elderly individuals and their surrogates regarding end-of-life care.Methods: A pre-post quasi-experimental design was adopted using the Life Support Preferences Questionnaire. The intervention had two components: (1) increasing participants' knowledge of medical treatments related to end-of-life care, and (2) sharing their end-of-life wishes. The experimental group received an intervention, whereas the control group received usual care.Results: A total of 110 participants in 55 pairs of elderly individuals with average aged 86.4 and their surrogates (27 in the experimental group, 28 in the control group) were recruited from a veterans hospital in northern Taiwan. Nearly 90 % of elderly individuals were male. The multiple linear regression showed that the inconsistent gap between elderly individuals and their surrogates in the experimental group decreased 12 points than the control group after controlling the covariances (B = -12.116, p = 0.032).Conclusion: The intervention improved the consistency between elderly individuals and their surrogates regarding end-of-life care.Practice Implications: A decision aid with cartoon pictures may support the discussion of end-of-life care in older Asian populations. [ABSTRACT FROM AUTHOR]

The strength of high-strength steel butt-welded joints with a similar steel grade may be quite different due to their discrepancies in the processing methods of high-strength steel. The process methods mainly include quenching and tempering (QT) and thermo-mechanically controlled process (TMCP). These differences in the strength of high-strength steel butt-welded joints with different processing methods of steel have not been quantitatively determined and considered in several design codes, which may lead to the unsafe design for the high-strength steel butt-welded joints. This research demonstrated a comparative and quantitative study on the strength of double-V butt-welded joints made of QT550, QT690, TMCP 550, and TMCP690. The true stress-strain behavior of various zones within these welded joints, including the hardened heat affected zone (HHAZ), softened HAZ (SHAZ), weld metal (WM), and base metal (BM), were investigated based on the test and simulation results of the round notched specimens and the flat grooved specimens in tension. The developed true stress-strain models were validated against the test results of high-strength steel butt-welded joints. The strength of QT and TMCP high-strength steel butt-welded joints were then numerically analyzed considering the effect of different heat inputs of 1.0, 1.5 and 1.9 kJ/mm. The results show that strength ratios of SHAZ to BM of butt-welded joints made of TMCP steel were lower than those made of QT steel when the heat input was <1.9 kJ/mm. The strength of each zone in the TMCP high-strength steel butt-welded joint may not necessarily decrease with increasing heat inputs. • The material properties of the heat-affected zone of butt-welded joints made of QT and TMCP steel were determined. • A comparative study of the true stress-strain relationship of each zone of the butt welds of QT and TMCP steels was performed. • The effect of the heat input during welding on the strength of butt welds of QT and TMCP steels was studied. • The discrepancy in the strength of high-strength steel butt-welded joints due to the different processing methods of steel was quantitatively determined. [ABSTRACT FROM AUTHOR]

Objectives: While the NCCN guidelines maintain that T4b oral cavity squamous cell carcinoma (OCSCC) should undergo either non-surgical treatments or clinical trials, promising outcomes of T4b OCSCC having surgical excision have been reported. We analyzed and compared the clinical outcomes of Taiwanese patients with pT4a and pT4b OCSCC who had undergone surgical treatment.Methods: From 2011 to 2017, a total of 4031 and 355 patients with first primary pT4a and pT4b OCSCC were identified. A propensity score (PS)-matched analysis of patients (n = 351 each) for pT4a and pT4b tumors was also performed.Results: The 5-year disease-specific and overall survival (DSS/OS) rates were more favorable in patients with pT4a than in those with pT4b OCSCC (64%/55%, p < 0.0001; 55%/43%, p < 0.0001, respectively). Compared with pT4a, those with pT4b tumors had a higher burden of the following risk factors: buccal/retromolar/hard palate subsite, male sex, depth ≥ 10 mm, and positive margins. Before PS matching, multivariable analyses revealed that pT4b tumors (versus pT4a) were an adverse prognosticator for both 5-year DSS and OS (hazard ratios: 1.32 and 1.39, respectively). However, in the PS-matched cohort, no significant differences in 5-year DSS and OS rates were observed between pT4a and pT4b OCSCC (57%/56%, p = 0.4024; 48%/44%, p = 0.1807, respectively) CONCLUSIONS: No significant outcome differences were evident between pT4b and pT4a OCSCC after PS matching. The most plausible hypothesis for the observed survival difference between T4a and T4b tumors is that it was driven by positive margins. We suggest that T4b OCSCC should undergo initial surgical excision if adequate resection is possible. [ABSTRACT FROM AUTHOR]

Abstract: We present a systematic investigation on the mechanical properties of platinum nanowires with single-crystalline and fivefold twinned structures by means of atomistic simulations. The results show that the Young’s moduli of both types of nanowires are significantly higher than that of bulk counterpart. Furthermore, the fivefold twinned nanowire generally exhibits a higher elastic modulus than the single-crystalline one. The introduction of the twinned structures enhances the yielding strength of the nanowires but remarkably lowers their ductility. The initiation of the yielding mechanism of the two types of nanowires is through a nucleation process and the activity of Shockley partial dislocations under external stress. However, due to the obstacle to partial dislocations, the twin boundaries have been found to be simultaneously destructive, initiating the fracture of twinned nanowire. A comparison of the results with those of other fcc nanowires has indicated that the nonlinear elasticity and the yielding strain should also be responsible for the yielding strength of the nanowires. [Copyright &y& Elsevier]

Background: Laparoscopic liver resection (LLR) remains to be established as a safe and effective alternative to open liver resection (OLR) for hepatocellular carcinoma (HCC). Aims: The aim of this meta-analysis is to compare laparoscopic versus open resection for HCC with regard to perioperative and oncologic outcomes. Methods: A literature search was performed to identify comparative studies reporting outcomes for both laparoscopic and open resection for HCC. Pooled odds ratios (OR) and weighted mean differences (WMD with 95% confidence intervals (95% CI) were calculated using either the fixed effects model or random effects model. Results: Ten nonrandomized controlled studies matched the selection criteria and reported on 494 subjects, of whom 213 underwent LLR and 281 underwent OLR for HCC. Compared with the perioperative results of open surgery, reports on laparoscopic resection indicate potentially favourable outcomes in terms of operative blood loss (WMD: −160.57, 95% CI: −246.49 to −74.66), blood transfusion requirement (OR: 0.39, 95% CI: 0.18 to 0.86), postoperative morbidity (OR: 0.48, 95% CI: 0.29 to 0.78), and length of hospital stay (WMD: −5.53, 95% CI: −7.89 to −3.16). Concerning the oncologic outcomes, there was no difference between groups in surgical margin, overall survival and disease-free survival. Conclusions: LLR for HCC is superior to the OLR in terms of its perioperative results and does not compromise the oncological outcomes. Therefore, LLR may be an alternative choice for treatment of HCC. [ABSTRACT FROM AUTHOR]

This paper uses a molecular static approach with a many-body potential to investigate the surface energetic and bonding characteristics of tetrahexahedral platinum nanocrystals enclosed by high-index facets such as {210}, {310}, {410}, {520} and {730}. It mainly focuses on the effect of crystal size and surface Miller index on these characteristics. The results show that the surface energy and dangling bond density increase with decreasing diameter of tetrahexahedral nanocrystals and generally show an order of {210} > {730} > {520} > {310} > {410}. However, this order is not valid at crystal sizes below 7 nm or so. The results of corresponding surfaces are also presented for comparison. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association between restless legs syndrome (RLS) and hypertension in men and women based on a community-based cohort of middle-aged and elderly participants.Methods: This cross-sectional observational study enrolled 4080 participants from the Sleep Heart Health study (SHHS). RLS was defined by positive responses on a self-administered questionnaire assessing the four diagnostic criteria, with symptoms occurring at least five times per month and associated with at least moderate distress. Hypertension was defined as SBP ≥140 mmHg, DBP ≥90 mmHg, or current use of antihypertensive medication. Propensity score-matched (PSM) inverse probability treatment weighting (IPTW) analyses and multivariable logistic regression were used to examine the relationship between RLS and hypertension.Results: RLS was present in 6.8% of women (n = 152) and 3.2% of men (n = 59). In the primary cohort analysis, the odds ratio (OR) for hypertension was 1.60 [95% confidence interval (CI) 1.19-2.16, p < 0.001] for participants with RLS compared to those without RLS. In the PSM analyses, the OR for hypertension was 1.66 (95% CI 1.09-2.54, p = 0.019) for participants with RLS compared to those without RLS. In sex subgroup analyses, the association between RLS and hypertension persisted in women. In the PSM cohort, the ORs for hypertension were 1.67 (95% CI 1.01-2.81, p = 0.048) and 1.85 (95% CI 0.75-4.75, p = 0.191) in women and men, respectively. Similar results were found in IPTW cohort.Conclusions: This study revealed a positive association between RLS and hypertension in a community-based population; in sex subgroup analyses, the association persisted in women. [ABSTRACT FROM AUTHOR]

Alteration of visual scanpaths under emotional facial expression in schizophrenia patients has been described in recent years; however, it is not clear whether such results are different when they transfer to faces in natural social scenes. The present study was designed to investigate the effects of emotional faces in natural social scenes on the gaze patterns of patients with schizophrenia, compared to gaze at isolated faces. A novel theme identification task was used where participants selected a positive, neutral or negative word to describe an emotional picture. Participants were 29 patients with schizophrenia and 31 healthy controls. The Positive and Negative Syndrome Scale (PANSS) and the Scale of Social Function in Psychosis Inpatients (SSPI) were used to assess symptoms and social functioning. In total, patients with schizophrenia showed significantly fewer fixations, saccades numbers and decreased fixations in areas of interest. As expected, patients showed shorter scanpath length, but only in the pictures with social settings. Furthermore, the effect size of scanpaths parameters under social scene was all greater than isolated face. In addition, patients compared to controls showed more abnormal scanpath parameters processing negative and neutral faces than positive faces, especially in social scene. The present study suggests that scanpath length for social scene faces may be more sensitive than for isolated face pictures. Our findings further support restricted scanpath whilst recognizing emotional facial expressions in natural social scenes as a favorable topic for further investigation as a trait marker. [ABSTRACT FROM AUTHOR]

Androgen receptor (AR) targeting is an important therapeutic strategy for treating prostate cancer. Most tumors progress to castration-resistant prostate cancer (CRPC) and develop the neuroendocrine (NE) phenotype under androgen deprivation therapy (ADT). The molecular basis for NE transdifferentiation after ADT remains incompletely understood. Herein, we show that an immunocyte expression protein, ZBTB46, induces inflammatory response gene expression and contributes to NE differentiation of prostate cancer cells. We demonstrated a molecular mechanism whereby ZBTB46 can be regulated by the androgen-responsive gene, SPDEF, and is associated with NE prostate cancer (NEPC) differentiation. In addition, ZBTB46 acts as a transcriptional coactivator that binds to the promoter of prostaglandin-endoperoxide synthase 1 (PTGS1) and transcriptionally regulated PTGS1 levels. Overexpression of ZBTB46 decreases the sensitivity of the combination of enzalutamide and a PTGS1 inhibitor; however, knockdown of ZBTB46 sensitizes the PTGS1 inhibitor and reduces tumor malignancy. ZBTB46 is inversely correlated with SPDEF and is increased in higher tumor grades and small-cell NE prostate cancer (SCNC) patients, which are positively associated with PTGS1. Our findings suggest that the induction of ZBTB46 results in increased PTGS1 expression, which is associated with NEPC progression and linked to the dysregulation of the AR-SPDEF pathway. [ABSTRACT FROM AUTHOR]

Background: When older nursing home residents and their families are faced with end-of-life care decisions in Taiwan, they make them in the context of traditional cultural norms and socioeconomic changes. Both parties (residents and their family members) are often unwilling to broach the topic, leading to a decisional impasse. The aim of this study was to understand difficult-to-raise issues related to end-of-life care by investigating the perspectives of older nursing home residents and their family members. Methods: This qualitative descriptive study was conducted using content analysis based on the Consolidated Criteria for Reporting Qualitative Research. Purposive sampling was used to select the participants, and sampling continued until data saturation. Data were collected using semi structured interviews, and related analyses were conducted using an inductive approach. Results: Ten residents and twelve family members were interviewed individually. Six main themes were identified: (1) the inevitability of a goodbye; (2) a good death; (3) going with or against traditional culture; (4) better a good death than a bad life; (5) abiding by the residents' decisions; and (6) being willing but unable to take care of residents. Conclusion: Nursing home residents and their family members' thoughts on end-of-life care shifted toward the concept of a good death, and they even regarded death as a form of liberation. Health care providers may serve as mediators to counsel a resident and their family members separately, enabling them to speak up and understand each other's thoughts on end-of-life care before a decision is made so that neither party has regrets. [ABSTRACT FROM AUTHOR]

Background: Remodeling of the extracellular matrix (ECM) is a hallmark of heart failure (HF). Our previous analysis of the secretome of murine cardiac fibroblasts returned ADAMTS5 (a disintegrin and metalloproteinase with thrombospondin motifs 5) as one of the most abundant proteases. ADAMTS5 cleaves chondroitin sulfate proteoglycans such as versican. The contribution of ADAMTS5 and its substrate versican to HF is unknown.Methods: Versican remodeling was assessed in mice lacking the catalytic domain of ADAMTS5 (Adamts5ΔCat). Proteomics was applied to study ECM remodeling in left ventricular samples from patients with HF, with a particular focus on the effects of common medications used for the treatment of HF.Results: Versican and versikine, an ADAMTS-specific versican cleavage product, accumulated in patients with ischemic HF. Versikine was also elevated in a porcine model of cardiac ischemia/reperfusion injury and in murine hearts after angiotensin II infusion. In Adamts5ΔCat mice, angiotensin II infusion resulted in an aggravated versican build-up and hyaluronic acid disarrangement, accompanied by reduced levels of integrin β1, filamin A, and connexin 43. Echocardiographic assessment of Adamts5ΔCat mice revealed a reduced ejection fraction and an impaired global longitudinal strain on angiotensin II infusion. Cardiac hypertrophy and collagen deposition were similar to littermate controls. In a proteomics analysis of a larger cohort of cardiac explants from patients with ischemic HF (n=65), the use of β-blockers was associated with a reduction in ECM deposition, with versican being among the most pronounced changes. Subsequent experiments in cardiac fibroblasts confirmed that β1-adrenergic receptor stimulation increased versican expression. Despite similar clinical characteristics, patients with HF treated with β-blockers had a distinct cardiac ECM profile.Conclusions: Our results in animal models and patients suggest that ADAMTS proteases are critical for versican degradation in the heart and that versican accumulation is associated with impaired cardiac function. A comprehensive characterization of the cardiac ECM in patients with ischemic HF revealed that β-blockers may have a previously unrecognized beneficial effect on cardiac chondroitin sulfate proteoglycan content. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the outcome of vertebroplasty or kyphoplasty (VK), in comparison with non-VK treatment, among patients hospitalized for first-ever vertebral compression fractures (VCFs). Design: A population-based retrospective cohort study. Setting: Taiwan’ s National Health Insurance claims data. Participants: All individuals aged ≥60 years who were newly discharged after hospitalization for a primary VCF diagnosis. Intervention: Percutaneous vertebroplasty or kyphoplasty. Measurements: Study outcomes were discharge outcome (re-hospitalization within 1 week, 1 month or 6 months, categorized by diagnosis) and the prescription of anti-osteoporosis medication for secondary fracture prevention. Potential selection bias was adjusted by using propensity score matching to select one conservatively treated patient (e.g. lumbar brace, analgesics, or physical therapy) matched to one patient receiving VK. Results: The study cohort consisted of 9238 patients who had been discharged after hospitalization for a first-ever VCF between 2004 and 2007. During the index hospitalization, 1018 patients received VK, compared with 8,220 patients who did not receive VK. Patients receiving percutaneous procedure group had a consistently lower incidence of 7-day re-hospitalization for any of the three outcomes (OR = 0.48; 95% CI: 0.32–0.72). Considering the cause of re-hospitalization separately, the vertebroplasty/kyphoplasty group had a significantly lower risk of 7-day re-hospitalization for fracture-related diagnosis (OR = 0.28, 95% CI: 0.12–0.68) and musculoskeletal diagnosis (OR = 0.08, 95% CI: 0.01–0.88) as well as a significantly lower risk of 1-month re-hospitalization (OR = 0.74; 95% CI: 0.59–0.93). Conclusions: VK may protect patients with VCFs from short-term re-hospitalization and a greater need exists for anti-osteoporosis medication as secondary prevention for this at-risk patient group. [Copyright &y& Elsevier]

Abstract: The soft deposition of Cu13 and Co13 clusters and their subsequent diffusion behaviors on the Cu(001) surface have been studied via molecular dynamics simulations with many-body potential based on the tight-binding model. Terrace-step-kink structures are used for the description of the substrate geometries. The results show that the final morphologies and the binding energies of the deposited clusters depend sensitively on the substrate surface geometries. The diffusion behaviors of the clusters on the substrate are investigated via annealing the cluster–substrate systems at 300K, 500K and 800K. It is shown that the significantly different diffusion behaviors of Cu13 and Co13 clusters are associated with different interactions between Cu–Cu, Co–Co, and Cu–Co atoms. Our results also reveal that the Cu13 and Co13 clusters collapse on the terrace at 800K via the solid-on-solid settling mechanism. A new collapse mechanism is also discovered during the collapse process of Co13 cluster, which suspends the transformation from a three-dimensional adsorbed cluster to a two-dimensional one. [Copyright &y& Elsevier]

This study evaluates the effects of glucagon 30 mug/kg (maximal 1 mg) on beta-cell function in children by C-peptide determined before and 6 min after intravenous administration. From 1990 to 2005, 118 Taiwanese children with newly diagnosed diabetes mellitus (98 children with type 1 and 20 children with type 2) and 29 normal Taiwanese children were enrolled in this study. Fasting and 6-min post-glucagon C-peptide levels were analyzed. In the pre-pubertal group, the median fasting serum C-peptide levels were 0.2 and 0.8 nmol/l in type 1 diabetes and normal children, respectively. These levels rose to 0.3 and 1.9 nmol/l after glucagon stimulation. In the pubertal group, the median fasting serum C-peptide levels were 0.3, 1.0 and 0.9 nmol/l in type 1 diabetes, type 2 diabetes and normal children, respectively. They rose to 0.4, 2.5 and 2.7 nmol/l after glucagon stimulation. Both fasting and post-glucagon C-peptide levels in type 1 diabetes patients were significantly lower than those of normal children and children with type 2 diabetes. The optimal cut-off values to distinguish type 1 diabetes patients from those with type 2 as determined by the receiving operating characteristic curve were 0.7 and 1.1 nmol/l, respectively. The sensitivities of both C-peptide values were 93%. The post-glucagon C-peptide level was more powerful in distinguishing type 1 diabetes from type 2 diabetes with higher specificity (95% vs. 85%). The 6-min glucagon test is valuable in assessing beta-cell function in children and can help pediatricians in the differential diagnoses of diabetes mellitus in children. [ABSTRACT FROM AUTHOR]

Purpose: The evidence for adjuvant therapy of oral cavity squamous cell carcinoma (OCSCC) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. Here, we examined whether adjuvant therapy should be guided by a detailed analysis of pathologic risk factors in patients with pure OCSCC.Methods and Materials: Between 2004 and 2016, we retrospectively reviewed 1200 consecutive patients with OCSCC who underwent radical surgery and neck dissection in the Chang-Gung Memorial Hospital (CGMH). Patients were divided into 3 prognostic groups. High-risk patients were those with extranodal extension (ENE) and/or positive margins (ENE/margins+, n = 267). Intermediate-risk patients were further divided into 3 subgroups: (1) patients in whom adjuvant therapy was indicated according to the CGMH but not the NCCN guidelines (NCCN[-]/CGMH[+], n = 14); (2) patients in whom adjuvant therapy was indicated by the NCCN but not the CGMH guidelines (NCCN[+]/CGMH[-], n = 160); and (3) patients in whom adjuvant therapy was indicated according to both guidelines (NCCN[+]/CGMH[+], n = 411). Low-risk patients were those for whom adjuvant therapy was not suggested in light of either guideline (NCCN[-]/CGMH[-], n = 348).Results: According to NCCN guidelines, postoperative adjuvant therapy was indicated in 69.8% of the participants. However, only 57.7% of patients were in need of adjuvant therapy by CGMH guidelines. The following 5-year outcomes were observed in the NCCN(-)/CGMH(-), NCCN(-)/CGMH(+), NCCN(+)/CGMH(-), NCCN(+)/CGMH(+), and ENE/margins+ subgroups: locoregional control, 88%/70%/83%/79%/68%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P = .576); distant metastases, 2%/7%/2%/9%/36%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P = .003); disease-specific survival, 97%/86%/94%/84%/56%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P < .001); and overall survival, 92%/86%/87%/68%/42%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P < .001), respectively.Conclusions: Patients in the NCCN(+)/CGMH(-) subgroup, 28% (160/571[160 + 411]) of NCCN intermediate-risk patients, had more favorable 5-year disease-specific and overall survival (94% and 87%) than the NCCN(+)/CGMH(+) subgroup. The former are unlikely to derive clinical benefits from NCCN guidelines. The 70% adjuvant therapy rate required by NCCN guidelines after radical surgery might be too high, ultimately leaving room for improvement. [ABSTRACT FROM AUTHOR]

Background and Aims: The Child-Pugh (CP) score is a widely used method to assess liver function and predict postoperative outcomes in patients with hepatocellular carcinoma (HCC). Recently, the fibrosis index (FIB-4) has been demonstrated to be closely associated with liver fibrosis and cirrhosis. This study aimed to compare the capability of FIB-4 index with CP score in predicting the outcomes for HCC patients after hepatectomy.Methods: A total of 495 HCC patients who underwent hepatectomy were enrolled. The performance of the FIB-4 index in predicting postoperative liver failure (PHLF) and overall survival was compared with that of the CP score.Results: Of them, 9.3% (46/495) patients developed PHLF. The area under the receiver operating characteristic (ROC) curve of the FIB-4 index for predicting PHLF was greater than that of the CP score (0.744 versus 0.621; P = 0.044). The optimal cutoff value of the FIB-4 index for predicting PHLF was 4.16. Multivariable analyses revealed that the FIB-4 index was an independent predictor of PHLF regardless of the hepatectomy subgroups, but the CP grade was only a significant predictor of PHLF in the minor hepatectomy subgroup. The FIB-4 index (4.16) stratified patients into two distinct overall survival cohorts (P = 0.006). The FIB-4 index also classified patients with the Barcelona Clinical Liver Cancer (BCLC) stages 0 and A into two distinct overall survival cohorts (P = 0.001 and P = 0.034, respectively).Conclusion: The FIB-4 index may be a better predictor of PHLF and overall survival in HCC patients with hepatectomy than CP score. [ABSTRACT FROM AUTHOR]

Background: Extranodal natural killer T-cell lymphoma (NKTCL; nasal type) is an aggressive malignancy with a particularly high prevalence in Asian and Latin American populations. Epstein-Barr virus infection has a role in the pathogenesis of NKTCL, and HLA-DPB1 variants are risk factors for the disease. We aimed to identify additional novel genetic variants affecting risk of NKTCL.Methods: We did a genome-wide association study of NKTCL in multiple populations from east Asia. We recruited a discovery cohort of 700 cases with NKTCL and 7752 controls without NKTCL of Han Chinese ancestry from 19 centres in southern, central, and northern regions of China, and four independent replication samples including 717 cases and 12 650 controls. Three of these independent samples (451 cases and 5301 controls) were from eight centres in the same regions of southern, central, and northern China, and the fourth (266 cases and 7349 controls) was from 11 centres in Hong Kong, Taiwan, Singapore, and South Korea. All cases had primary NKTCL that was confirmed histopathologically, and matching with controls was based on geographical region and self-reported ancestry. Logistic regression analysis was done independently by geographical regions, followed by fixed-effect meta-analyses, to identify susceptibility loci. Bioinformatic approaches, including expression quantitative trait loci, binding motif and transcriptome analyses, and biological experiments were done to fine-map and explore the functional relevance of genome-wide association loci to the development of NKTCL.Findings: Genetic data were gathered between Jan 1, 2008, and Jan 23, 2019. Meta-analysis of all samples (a total of 1417 cases and 20 402 controls) identified two novel loci significantly associated with NKTCL: IL18RAP on 2q12.1 (rs13015714; p=2·83 × 10-16; odds ratio 1·39 [95% CI 1·28-1·50]) and HLA-DRB1 on 6p21.3 (rs9271588; 9·35 × 10-26 1·53 [1·41-1·65]). Fine-mapping and experimental analyses showed that rs1420106 at the promoter of IL18RAP was highly correlated with rs13015714, and the rs1420106-A risk variant had an upregulatory effect on IL18RAP expression. Cell growth assays in two NKTCL cell lines (YT and SNK-6 cells) showed that knockdown of IL18RAP inhibited cell proliferation by cell cycle arrest in NKTCL cells. Haplotype association analysis showed that haplotype 47F-67I was associated with reduced risk of NKTCL, whereas 47Y-67L was associated with increased risk of NKTCL. These two positions are component parts of the peptide-binding pocket 7 (P7) of the HLA-DR heterodimer, suggesting that these alterations might account for the association at HLA-DRB1, independent of the previously reported HLA-DPB1 variants.Interpretation: Our findings provide new insights into the development of NKTCL by showing the importance of inflammation and immune regulation through the IL18-IL18RAP axis and antigen presentation involving HLA-DRB1, which might help to identify potential therapeutic targets. Taken in combination with additional genetic and other risk factors, our results could potentially be used to stratify people at high risk of NKTCL for targeted prevention.Funding: Guangdong Innovative and Entrepreneurial Research Team Program, National Natural Science Foundation of China, National Program for Support of Top-Notch Young Professionals, Chang Jiang Scholars Program, Singapore Ministry of Health's National Medical Research Council, Tanoto Foundation, National Research Foundation Singapore, Chang Gung Memorial Hospital, Recruitment Program for Young Professionals of China, First Affiliated Hospital and Army Medical University, US National Institutes of Health, and US National Cancer Institute. [ABSTRACT FROM AUTHOR]

Abstract: Background: A link between the use of alendronate and atypical diaphyseal femoral fracture has been suggested. Objective: The goal of this study was to evaluate the benefits of alendronate in preventing rehospitalization due to hip fractures and whether its use increases risk of hospitalization for atypical diaphyseal femoral fractures in Taiwan. Methods: Using Taiwan''s National Health Insurance database, we identified women with osteoporosis with a first-ever hospitalization for vertebral or hip fractures between 2001 and 2007, which consisted of all patients receiving alendronate, raloxifene, calcitonin salmon, or teriparatide after the index fracture hospitalization. Data of untreated women were obtained as the untreated cohort. Study outcomes were defined as a rehospitalization due to hip fracture or a new hospitalization for subtrochanteric or diaphyseal femoral fracture. Results: Among 11,278 women identified (mean age, 77 years), 2425 (21.5%) received alendronate, 2694 (23.9%) received other antiosteoporosis drugs, and 6159 (54.6%) were untreated. Patients in each group were comparable in fracture history and major comorbidities; untreated patients were more likely to have stroke (11.2%; P = 0.01) and those treated with alendronate were more likely to have a history of hyperlipidemia (16.2%; P = 0.03). Compared with the untreated patient cohort, our analysis suggested that patients prescribed alendronate were associated with decreased risk of rehospitalization due to hip fracture (hazard ratio = 0.67 [95% CI, 0.54–0.82]). Neither patients prescribed alendronate, nor those prescribed other antiosteoporosis drugs, differed significantly from the untreated patient cohort in terms of risk of hospitalization for atypical femoral fracture (adjusted hazard ratios = 0.77 and 0.49 [95% CI, 0.40–1.47 and 0.22–1.12], respectively). Consistent with these data, short- or long-term alendronate use was not found to be significantly associated with higher risk of atypical femoral fractures. Conclusions: This study in Taiwanese patients suggests that alendronate use was associated with a reduction in risk of rehospitalization due to hip fracture. We did not find a significant association between alendronate use and risk of hospitalization for atypical femoral fracture. [Copyright &y& Elsevier]

Background and Purpose: Recent evidence has suggested that nicotine decreases blood pressure (BP) and heart rate (HR) in the nucleus tractus solitarii (NTS), indicating that nicotinic acetylcholine receptors (nAChRs) play an important role in BP control in the NTS. However, the signalling mechanisms involved in nAChR-mediated depressor effects in the NTS are unclear. Hence, the aim of this study was to investigate these signalling mechanisms.Experimental Approach: Depressor responses to nicotine microinjected into the NTS of Wistar-Kyoto rats were elicited in the absence and presence of an antagonist of α7 nAChR, the calcium chelator ethylene glycol tetraacetic acid, a calmodulin-specific inhibitor, nitric oxide (NO) synthase (NOS) inhibitor, endothelial NOS (eNOS)-selective inhibitor or neuronal NOS (nNOS)-specific inhibitor.Key Results: Microinjection of nicotine into the NTS produced a dose-dependent decrease in BP and HR, and increased nitrate levels. This depressor effect of nicotine was attenuated after pretreatment with a nAChR antagonist or blockers of the calmodulin-eNOS pathway. In contrast, N5-(1-Imino-3-butenyl)-L-ornithine (vinyl-L-NIO), nNOS-specific inhibitor, did not diminish these nicotine-mediated effects. Calmodulin was found to bind eNOS after nicotine injection into NTS. However, nicotine did not affect the eNOS phosphorylation level or eNOS upstream extracellular signal-regulated kinases (ERK)1/2 and Akt phosphorylation levels. Furthermore, pretreatment with an ERK1/2 or Akt inhibitor did not attenuate nicotine-induced depressor effects in the NTS.Conclusions and Implications: These results suggest that the nAChR-Ca(2+) -calmodulin-eNOS-NO signalling pathway, but not nNOS, plays a significant role in central BP regulation, and neither the ERK1/2 nor Akt signalling pathway are significantly involved in the activation of eNOS by nAChRs in the NTS. [ABSTRACT FROM AUTHOR]

Abstract: Currently, there are various approaches for developing therapeutic vaccines for chronic hepatitis B patients. Previously, an antigen–antibody-based therapeutic vaccine (YIC) has been conducted in a double-blind placebo controlled phase IIb clinical trial in 242 chronic hepatitis B patients. At the end of follow-up for 24 weeks, HBeAg sero-conversion rate was 21.6% in the 60μg immunized group, compared to 9% in the alum immunized control group (p =0.03). To analyze the correlation between HBeAg-seroconversion, and decrease of serum HBsAg and HBV DNA, serum samples were back quantified for serum HBsAg and HBV DNA collected at baseline, end of treatment, and end of follow-up from patients who were treated either with 60μg of YIC, or with placebo. Patients were dichotomized to HBeAg sero-converted and non-converted groups in comparison with patients in the placebo group. The correlations between HBeAg seroconversion and the decrease of HBsAg, HBV DNA and ALT levels during study period were analyzed using a logistic regression model. Results showed marked and sustained reduction of HBsAg, HBV DNA and ALT level in HBeAg sero-converted patients compared to those in patients of HBeAg non-converted and placebo groups. Reduction of HBV DNA and elevation of ALT was markedly associated with HBeAg seroconversion with an adjusted OR of 0.09 (95%CI: 0.01–0.62) and 0.08 (95%CI: 0.02–0.37) respectively after adjusted by age and sex, while reduction of HBsAg level was close to of significance (p =0.054). Analysis indicated that HBeAg sero-conversion was a reasonable endpoint for therapeutic vaccination. [ABSTRACT FROM AUTHOR]

The 2019 Asian Working Group on Sarcopenia in Older People (AWGS 2019) recommends using either calf circumference or the strength, assistance in walking, rising from a chair, climbing stairs, and falls (SARC-F) or SARC-F combined with calf circumference (SARC-CalF) questionnaires for sarcopenia screening. The aim of this study was to compare the ability and applicability of calf circumference, SARC-F, and SARC-CalF for screening sarcopenia among community-dwelling older adults. Cross-sectional study. A total of 1050 community-dwelling older people were enrolled. Sarcopenia was diagnosed according to the AWGS 2019 criteria: bioimpedance analysis for appendicular skeletal muscle index, hand grip, and 6-m gait speed test. Participants also completed the SARC-F questionnaire and calf circumference measurement. The screening tools' performances were evaluated through receiver operating characteristic (ROC) curves, area under the ROC curves (AUC), and sensitivity/specificity analyses. Sarcopenia was identified in 263 (25.0%) participants by the AWGS 2019 criteria. Calf circumference had a sensitivity of 81.4% and a specificity of 77.0%. Sensitivity and specificity of SARC-F for screening sarcopenia were 17.9% and 93.7%, respectively. SARC-CalF improved the sensitivity of SARC-F (47.5%) while keeping similar specificity (92.0%). The AUCs of calf circumference, SARC-F, and SARC-CalF were 0.79 [95% confidence interval (CI), 0.77–0.82], 0.56 (95% CI, 0.52–0.59), and 0.70 (95% CI, 0.67–0.73), respectively. The differences across ROC curves were statistically significant among 3 screening tools (P <.001). The overall screening ability of calf circumference was better than that of SARC-F and SARC-CalF for sarcopenia in community-dwelling older persons despite gender, age, and cognitive function. SARC-F and SARC-CalF have high specificity but are susceptible to the preceding factors. [ABSTRACT FROM AUTHOR]

• Maize photosynthesis responds differently to light heterogeneity between cultivars. • Systemic regulation of carbon assimilation determines photosynthetic performance. • Carbohydrate export is closely related to photosynthesis under light heterogeneity. Photosynthetic performance of a leaf is widely recognized to be systemically regulated by distal parts within the same plant. However, the effects of systemic regulation on different plant materials cannot be generalized. In this work, two cultivars of maize (Zea mays L.), 'Rongyu 1210' (RY) and 'Zhongdan 808' (ZD), were selected for a comparative study on the different responses of photosynthesis to light-dependent systemic regulation. After the growth of plants in heterogeneous light, the net photosynthetic rate of newly developed leaves increased in RY but decreased in ZD. A distinct capacity of CO 2 fixation and assimilation between these two cultivars is also suggested. In ZD, the area of vascular bundles declined obviously, suggesting a restriction on carbohydrate export, which is also indicated by an increase in starch content. Resulting excessive accumulation of carbohydrates is proposed to inhibit the carbon assimilation, and eventually the photosynthesis. A decline in the area of bundle sheath cells also suggests a restriction on carbon assimilation. In contrast, these restrictions were unlikely to present in RY. This study reveals that the response of leaf photosynthetic performance to light heterogeneity is largely dependent on the systemic regulation of carbon assimilation, as well as carbohydrate export in maize. [ABSTRACT FROM AUTHOR]

Background: The prevalence and incidence of end-stage renal disease (ESRD) in Taiwan are the highest of any country in the world. The different renal replacement therapies that are adopted by patients with ESRD significantly affect their social roles and daily life. However, because of the complexities of different renal replacement therapies, patients may be unsure of which to choose. Purpose: The aim of this study was to explore the effectiveness of a shared decision-making (SDM) program regarding different renal replacement therapies for patients with chronic kidney disease. Methods: A quasi-experimental design was conducted at two similar regional hospitals in Miaoli County, Taiwan. One hospital hosted the intervention group, and the other hospital hosted the control group. The 31 participants in the intervention group took part in a SDM program. The 36 control group participants took part in the pre-ESRD care program. Data collection included demographic and disease characteristics, decisional conflict scale, and decision self-efficacy scale. Results were analyzed using independent t test, Fisher's exact test, generalized estimating equation, and paired t tests. Results: The study results revealed that the intervention group experienced a significant increase in decision self-efficacy and a significant decrease in decisional conflict at 1 month after receiving the SDM intervention in comparison to before and immediately after receiving the intervention. Moreover, the intervention group had higher decision self-efficacy and lower decisional conflict than the control group. Conclusions/Implications for Practice: The SDM program may be an effective intervention for complex decision-making processes, such as the process involved in making renal replacement treatment decisions. The SDM program group intervention improved decisional conflict and decision self-efficacy. Thus, to improve patients' decision-making processes, the application of an SDM program focused on the personal values and opinions of patients with ESRD will be necessary. Physicians and case managers of patients with ESRD should act in complementary and cooperative roles in SDM programs. [ABSTRACT FROM AUTHOR]

Background: Nursing professionals have received comprehensive medical education and training. However, whether these medical professionals exhibit positive patient care attitudes and behaviors and thus reduce mortality risks when they themselves are diagnosed with chronic diseases is worth exploring. This study compared the mortality risks of female nurses and general patients with diabetes and elucidated factors that caused this difference.Methods: A total of 510,058 female patients newly diagnosed with diabetes between 1998 and 2006 as recorded in the National Health Insurance Research Database were the participants in this study. Nurses with diabetes and general population with diabetes were matched with propensity score method in a 1:10 ratio. The participants were tracked from the date of diagnosis to 2009. The Cox proportional hazards model was utilized to compare the mortality risks in the two groups.Results: Nurses were newly diagnosed with diabetes at a younger age compared with the general public (42.01 ± 12.03 y vs. 59.29 ± 13.11 y). Nevertheless, the matching results showed that nurses had lower mortality risks (HR: 0.53, 95 % CI: 0.38-0.74) and nurses with diabetes in the < 35 and 35-44 age groups exhibited significantly lower mortality risks compared with general patients (HR: 0.23 and 0.36). A further analysis indicated that the factors that influenced the mortality risks of nurses with diabetes included age, catastrophic illnesses, and the severity of diabetes complications.Conclusion: Nurses with diabetes exhibited lower mortality risks possibly because they had received comprehensive medical education and training, may had more knowledge regarding chronic disease control and change their lifestyles. The results can serve as a reference for developing heath education, and for preventing occupational hazards in nurses. [ABSTRACT FROM AUTHOR]