Individuals with schizophrenia who are involuntarily admitted may have poorer prognosis, including higher readmission rates, than those voluntarily admitted. However, little is known about the risk ...factors for readmission in those schizophrenia patients who are involuntarily admitted.
We aim to explore the risk factors for readmission in this population.
We enrolled 138 schizophrenia patients with involuntary admission from July 2008 to June 2013 and followed those patients for readmission outcomes at 3 months and at 1 year.
The one-year and 3-months readmission rates were 33.3% and 15.2%, respectively. Unmarried status (adjusted odds ratio (aOR) = 6.28, 95% CI: 1.48-26.62), previous history of involuntary admission (aOR = 4.08, 95% CI: 1.19-14.02), longer involuntary admission days (aOR = 1.04, 95% CI: 1.01-1.07) and shorter total admission days (aOR = 1.03, 95% CI: 1.01-1.05) were associated with increased risk for 1-year readmission. Younger age (aOR = 1.10, 95% CI 1.02-1.18) was associated with increased risk for 3-months readmission.
Unmarried status, prior history of involuntary admission, longer involuntary admission days and shorter total admission days were associated with increased risk for 1-year readmission. Healthcare providers may need to focus on patients with these risk factors to reduce subsequent readmissions.
Hypoxia, the most commonly observed characteristic in cancers, is implicated in the establishment of an immunosuppressive niche. Recent studies have indicated that extracellular vesicle (EV)-mediated ...cancer-stroma interactions are considered to play a critical role in the regulation of various cellular biological functions, with phenotypic consequences in recipient cells. However, the mechanisms underlying the relationship between EVs and hypoxia during cancer progression remain largely unknown. In this study, we found that EVs derived from hypoxic lung cancers increased M2-type polarization by miR-103a transfer. Decreased PTEN levels caused by hypoxic cancer-cell-derived EV miR-103a increased activation of AKT and STAT3 as well as expression of several immunosuppressive and pro-angiogeneic factors. In contrast, inhibition of miR-103a by an miRNA inhibitor effectively decreased hypoxic cancer-mediated M2-type polarization, improving the cytokine prolife of tumor infiltration macrophages. Macrophages received cancer-cell-derived EV miR-103a feedback to further enhance cancer progression and tumor angiogenesis. Finally, circulating EV miR-103a levels were higher in patients with lung cancer and closely associated with the M2 polarization. In conclusion, our results delineate a novel mechanism by which lung cancer cells induce immunosuppressive and pro-tumoral macrophages through EVs and inspire further research into the clinical application of EV inhibition or PTEN restoration for immunotherapy.
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Extracellular vesicle (EV) miR-103 can be transferred from hypoxic cancer cells to macrophages, resulting in the enhancement of M2 polarization by the downregulation of miR-103a’s direct target PTEN. EV miR-103a increases the stimulatory effects of macrophages on cancer progression and angiogenesis.
Helicobacter pylori is recognised as a main risk factor for gastric cancer. However, approximately half of the patients with gastritis are negative for H. pylori infection, and the abundance of H. ...pylori decreases in patients with cancer. In the current study, we profiled gastric epithelium-associated bacterial species in patients with gastritis, intestinal metaplasia, and gastric cancer to identify additional potential pathogenic bacteria. The overall composition of the microbiota was similar between the patients with gastritis and those with intestinal metaplasia. H. pylori was present in half of the non-cancer group, and the dominant bacterial species in the H. pylori-negative patients were Burkholderia, Enterobacter, and Leclercia. The abundance of those bacteria was similar between the cancer and non-cancer groups, whereas the frequency and abundance of H. pylori were significantly lower in the cancer group. Instead, Clostridium, Fusobacterium, and Lactobacillus species were frequently abundant in patients with gastric cancer, demonstrating a gastric cancer-specific bacterial signature. A receiver operating characteristic curve analysis showed that Clostridium colicanis and Fusobacterium nucleatum exhibited a diagnostic ability for gastric cancer. Our findings indicate that the gastric microenvironment is frequently colonised by Clostridium and Fusobacterium in patients with gastric cancer.
Metastatic tumors have been shown to establish a supportive pre-metastatic niche (PMN) in distant organs, which in turn determines disseminated tumor cells' targeting of such organs. PMN is formed ...through the recruitment of bone-marrow-derived cells (BMDCs); however, the role of BMDCs in PMN formation is not fully understood. On the basis of RNA-seq data and bioinformatic analysis, secretion of extracellular vesicle (EV) miR-92a by BMDCs of lung cancer-bearing mice contributes to the establishment of liver PMN. Both BMDC-derived EVs and miR-92a mimics potentiate the activation of hepatic stellate cells (HSCs), subsequently increasing extracellular matrix (ECM) deposition in mice. Consequently, remodeling of the liver microenvironment enhanced immunosuppressive cell accumulation and cancer cell attachment. EVs miR-92a directly suppressed its target SMAD7, leading to the enhancement of transforming growth factor-β signaling in HSC. Elevated levels of circulating miR-92a are found in the sera of lung cancer patients, and EVs isolated from these patients have a similar ability to increase HSCs activation and ECM protein expression. Our study reveals the sequential steps of liver PMN formation in lung cancer, providing critical mediators that prepare PMN in the liver, and identifies new targets that offer valuable options for diagnosis and therapeutic intervention.
Objective
Quantitative sensory testing is widely used in clinical and research settings to assess the sensory functions of healthy subjects and patients. It is of importance to establish normative ...values in a healthy population to provide reference for studies involving patients. Given the absence of normative values for pain thresholds in Taiwan, the aim of this study was to report the normative values for future reference in the Taiwanese population and compare the differences between male and female participants.
Methods
Healthy adults without any chronic or acute pain condition were recruited. The pain thresholds were assessed over the cephalic (supraorbital area and masseter muscle) and extracephalic (medio‐volar forearm and thenar eminence) areas. The heat, cold, mechanical punctate, and pressure pain thresholds were measured with a standardized protocol. Comparisons between male and female participants were performed.
Results
One hundred and thirty healthy participants (55 males: 30.4 ± 7.4 years; 75 females: 30.5 ± 8.1 years) finished the assessments. Male participants were less sensitive to mechanical stimuli, including pressure over masseter muscle (male vs. female: 178.5 ± 56.7 vs. 156.6 ± 58.4 kPa, p = .034) and punctate over medio‐volar forearm (male vs. female: 116.4 ± 45.2 vs. 98.7 ± 65.4 g, p = .011), compared to female participants. However, female participants were less sensitive to cold stimuli, indicated by lower cold pain thresholds over the supraorbital area (male vs. female: 18.6 ± 8.4 vs. 13.6 ± 9.3°C, p = .004), compared to male participants. No significant differences were found between sexes in other pain threshold parameters.
Conclusions
We provided the normative values of healthy male and female adults in Taiwan. This information is crucial for comparison in future pain‐related studies to identify potential hypoalgesia or hyperalgesia of tested subjects.
This is the first study that reports the normative values of pain thresholds following a standardized protocol of quantitative sensory testings among a large healthy cohort without any pain conditions in East Asia. These results are crucial as a comparison for future pain‐related research.
Extensive exposure to UVB (280–320 nm) is the major risk responsible for various skin injuries. Numerous reports have shown that natural products could demonstrate photochemopreventive efficacy ...against UVB damage. We investigated the preventive effects and associated molecular mechanisms of red raspberry extract upon UVB-caused damage in human epidermal keratinocytes and a nude mouse model. The protein profiles and immunohistological study on a nude mouse skin indicated that red raspberry extract could prevent UVB-caused cell death and protect the skin against UVB-exposed injury manifested by wrinkling, scaling, tanning, and water loss as well as epidermal thickening. In addition, red raspberry extract application effectively abolished oxidative damage in DNA and attenuated the carbonylation level of proteins, which attributed to the activation of SOD, Nrf2 and its target genes, and HO-1. Red raspberry extract also altered the cells’ apoptotic signaling pathways including caspase-3 as well as the inflammatory cascade such as c-jun and attenuated UVB-induced activation of NF-κB and COX-2. Red raspberry extract could alleviate direct photodamage to the skin caused by UVB exposure through the ROS scavenger and protection against inflammatory responses, which may allow the development of novel strategies in protecting the skin subjected to UVB radiation.
Chemotherapy, in combination with immune checkpoint blockade (ICB) targeting to programmed death‐1 (PD‐1) or its ligand PD‐L1, is one of the first‐line treatments for patients with advanced ...non–small‐cell lung cancer (NSCLC). However, a large proportion of patients, especially those with PD‐L1 negative tumors, do not benefit from this treatment. This may be due to the existence of multiple immunosuppressive mechanisms other than the PD‐1/PD‐L1 axis. Human leukocyte antigen‐G (HLA‐G) has been identified as an immune checkpoint protein (ICP) and a neoexpressed tumor‐associated antigen (TAA) in a large proportion of solid tumors. In this study, we evaluated the induction of HLA‐G as well as PD‐L1 using sublethal doses of chemotherapeutics including pemetrexed in different NSCLC cell lines. Except for gefitinib, most of the chemotherapeutic agents enhanced HLA‐G and PD‐L1 expression in a dose‐dependent manner, whereas pemetrexed and carboplatin treatments showed the most consistent upregulation of PD‐L1 and HLA‐G in each cell line. In addition to protein levels, a novel finding of this study is that pemetrexed enhanced the glycosylation of HLA‐G and PD‐L1. Pemetrexed potentiated the cytotoxicity of cytotoxic T lymphocytes (CTLs) to treat NSCLC. Both in vitro and in vivo experiments revealed that CTL‐mediated cytotoxicity was most pronounced when both anti‐PD‐L1 and anti‐HLA‐G ICBs were combined with pemetrexed treatment. In conclusion, anti‐HLA‐G could be an intervention strategy in addition to the anti‐PD‐1/PD‐L1 pathway for NSCLC. Moreover, dual targeting of PD‐L1 and HLA‐G combined with pemetrexed might have a better extent of CTL‐based immunotherapy.
Pemetrexed might enhance the expression and glycosylation of HLA‐G and PD‐L1, which could provide a beneficial TME for CTL cytotoxicity against NSCLC. Dual targeting of PD‐L1 and HLA‐G combined with pemetrexed might have a better extent of CTL‐based immunotherapy.
5G Multicast Broadcast Services (MBS) are viewed as a promising 5G New Radio (NR) application, as standardization begins in 3GPP Release 17. With MBS, one next generation Node B (gNB) delivers data ...to multiple user equipments (UE) simultaneously, thus improving spectrum efficiency. Millimeter wave (mmWave) beamforming further enhances system performance by focusing signals in a dedicated direction. However, despite the advantages, we identify three issues of multicast with beamforming techniques. First, link directionality causes the gNB to transmit data over the beams sequentially, resulting in a combinatorial resource allocation problem. Confronting this beam scheduling issue, we develop an optimization algorithm that obtains an optimal solution in polynomial time. Second, UEs may falsely report their valuations over beam resources to gain more utility. Under this scenario, the gNB cannot allocate the resources to those in need due to the lack of accurate UE information. Therefore, we propose a Vickrey-Clarke-Groves (VCG) auction-based mechanism to incentivize the UEs to reveal their valuations over resources truthfully. This mechanism guarantees solution efficiency and maximizes social welfare. Third, as 3GPP standards allow for different priorities for different multicast flows, and video content providers distinguish between ordinary and premium UEs, we take UE priority into account. In this regard, we extend the valuation-based mechanism to a multi-priority one. Finally, the mathematical analysis validates some desirable properties of the proposed scheme, such as incentive-compatibility. Simulation results also justify our superior performance in the 5G MBS system compared with other resource allocation schemes.
We studied whether the extent of exertional oxygen desaturation and emphysema could cause greater mortality in COPD and asthma independent of airflow obstruction.
We performed a 5-year longitudinal ...observational study in COPD and asthma patients who matched for airflow obstruction severity. All subjects performed a 6-min walk test (6MWT) and high-resolution computed tomography (HRCT) and followed spirometry and oxygen saturation (SpO
) during the 6MWT every 3-6 months. Overall survival was recorded. Cumulative survival curves were performed according to the Kaplan-Meier method and compared with the log-rank test.
The COPD group had higher emphysema scores, higher Δinspiratory capacities (ICs) and lower SpO
during the 6MWT, which showed a greater yearly decline in FEV
(40.6 mL) and forced vital capacity (FVC) (28 mL) than the asthma group (FEV
, 9.6 mL; FVC, 1.2 mL;
< 0.05). The emphysema-predominant COPD group had an accelerated annual decline in lung function and worse survival. The nadir SpO
≤ 80% and a higher emphysema score were the strong risk factors for mortality in COPD patients.
The greater structural changes with a higher emphysema score and greater desaturation during the 6MWT in COPD may contribute to worse yearly decline in FEV
and higher five-year mortality than in asthma patients with a similar airflow obstruction. The lowest SpO
≤ 80% during the 6MWT and emphysema-predominant COPD were the strong independent factors for mortality in chronic obstructive airway disease patients.
Abstract
Aims
Given the concerns of health inequality associated with mental illnesses, we aimed to reveal the extent of which general mortality and life expectancy at birth in people with ...schizophrenia, bipolar disorder and depressive disorder varied in the 2005 and 2010 nationally representative cohorts in Taiwan.
Methods
Two nationally representative samples of individuals with schizophrenia, bipolar disorder and depressive disorder were identified from Taiwan's national health insurance database in 2005 and 2010, respectively, and followed-up for consecutive 3 years. The database was linked to nationwide mortality registry to identify causes and date of death. Age-, gender- and cause-specific mortality rates were generated, with the average follow-up period of each age- and gender-band applied as ‘weighting’ for the calculation of expected number of deaths. Age- and gender-standardised mortality ratios (SMRs) were calculated for these 3-year observation periods with Taiwanese general population in 2011/2012 as the standard population. The SMR calculations were then stratified by natural/unnatural causes and major groups of death. Corresponding life expectancies at birth were also calculated by gender, diagnosis of mental disorders and year of cohorts for further elucidation.
Results
The general differential in mortality rates for people with schizophrenia and bipolar disorder remained wide, revealing an SMR of 3.65 (95% confidence interval (CI): 3.55–3.76) for cohort 2005 and 3.27 (3.18-3.36) for cohort 2010 in schizophrenia, and 2.65 (95% CI: 2.55–2.76) for cohort 2005 and 2.39 (2.31-2.48) for cohort 2010 in bipolar disorder, respectively. The SMRs in people with depression were 1.83 (95% CI: 1.81–1.86) for cohort 2005 and 1.59 (1.57-1.61) for cohort 2010. SMRs due to unnatural causes tended to decrease in people with major mental illnesses over the years, but those due to natural causes remained relatively stable. The life expectancies at birth for schizophrenia, bipolar disorder and depression were all significantly lower than the national norms, specifically showing 14.97–15.50 years of life lost for men and 15.15–15.48 years for women in people with schizophrenia.
Conclusions
Compared to general population, the differential in mortality rates for people with major mental illnesses persisted substantial. The differential in mortality for unnatural causes of death seemed decreasing over the years, but that due to natural causes remained relatively steady. Regardless of gender, people with schizophrenia, bipolar disorder and depression were shown to have shortened life expectancies compared to general population.
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