A nationwide case-referent study on elevated risks of adenocarcinoma lung cancer by long-term PM2.5 exposure in Taiwan since 1997.

BACKGROUND: The effects of long-term PM2.5 exposures since 1968 on adenocarcinoma lung cancer (AdLC) were not studied before. METHODS: This case-referent study used nationwide cancer registry data since 1997 and air pollution data since 1968 in Taiwan to estimate risks of 30-year PM2.5 exposures on AdLC. Cases were all AdLC, while references were all non-AdLC. Individuals' 30-year PM2.5 exposures were estimated by PM2.5 levels at their residence for 30 years prior their diagnosis dates. We applied multiple logistic regression analyses to estimate PM2.5 exposures on incidence rate ratios (IRRs) between cases and references, adjusting for sex, age, smoking, cancer stage, and EGFR mutation. RESULTS: Elevation in annual ambient PM2.5 concentrations since 1968 were associated with increase in annual age-adjusted AdLC incidence since 1997. AdLC incidences were higher among females, nonsmokers, the elderly aged above 65, cases of stages IIIB to IV, and EGFR mutation. Study subjects' PM2.5 exposures averaged at 33.7 ± 7.4 µg/m3 with 162 ± 130 high PM2.5 pollution days over 30 years. Multiple logistic models showed an increase in 10 µg/m3 of PM2.5 exposures were significantly associated with 1.044 of IRR between all AdLC and all non-AdLC cases during 2011-2020. Our models also showed that females and nonsmokers and adults less than 65 years had higher IRRs than their respective counterparts. Restricted analyses showed similar effects of PM2.5 exposures on IRRs between stage 0-IIIA and IIIB-IV cases and between EGFR+ and EGFR- cases. CONCLUSIONS: Long-term exposures to PM2.5 over 30 years were associated with elevated risks of AdLC against non-AdLC, regardless of gender, age, smoking status, cancer stage, or EGFR mutation.

Eat Better to Look Better: The Relationship between Food Availability, UV Brightness of the Major Claw, and Mating Success of the Fiddler Crab Austruca lactea.

Many factors affect male fiddler crab courting and female choice during underground mating, including claw-waving patterns, claw-waving frequency, hood structures, burrow quality, and visible and ultraviolet signals of the major claw. Under food-limited conditions, fiddler crabs decrease their investments in reproduction-e.g., lower their claw-waving frequency. However, the effect of food availability on the visible or ultraviolet signals important for courtship success is unknown, not only for fiddler crabs, but for crustaceans in general. This is the first study to explore the influence of food availability on the early stages of female choice in Austruca lactea. In the present study, we tested (1) the effect of food availability on the UV brightness of A. lactea's major claw and burrow quality and (2) the correlation between A. lactea courtship success and the UV brightness of its major claw. Our results showed that higher food availability increased the UV brightness of the major claw and enhanced the male's burrow quality. The UV component to the signal is important for courtship success. The males with a UV component of signal on their major claw had a higher courtship success. This is an indication that food availability may affect the attractiveness of male fiddler crabs.

Human Costars Family Protein ABRACL Modulates Actin Dynamics and Cell Migration and Associates with Tumorigenic Growth.

Regulation of cellular actin dynamics is pivotal in driving cell motility. During cancer development, cells migrate to invade and spread; therefore, dysregulation of actin regulators is often associated with cancer progression. Here we report the role of ABRACL, a human homolog of the Dictyostelium actin regulator Costars, in migration and tumorigenic growth of cancer cells. We found a correlation between ABRACL expression and the migratory ability of cancer cells. Cell staining revealed the colocalization of ABRACL and F-actin signals at the leading edge of migrating cells. Analysis of the relative F-/G-actin contents in cells lacking or overexpressing ABRACL suggested that ABRACL promotes cellular actin distribution to the polymerized fraction. Physical interaction between ABRACL and cofilin was supported by immunofluorescence staining and proximity ligation. Additionally, ABRACL hindered cofilin-simulated pyrene F-actin fluorescence decay in vitro, indicating a functional interplay. Lastly, analysis on a colorectal cancer cohort demonstrated that high ABRACL expression was associated with distant metastasis, and further exploration showed that depletion of ABRACL expression in colon cancer cells resulted in reduced cell proliferation and tumorigenic growth. Together, results suggest that ABRACL modulates actin dynamics through its interaction with cofilin and thereby regulates cancer cell migration and participates in cancer pathogenesis.

Rational Design of an ICT-Based Chemodosimeter with Aggregation-Induced Emission for Colorimetric and Ratiometric Fluorescent Detection of Cyanide in a Wide pH Range.

An alkoxy-substituted 1,3-indanedione-based chemodosimeter 1 with an aggregation-induced emission (AIE) characteristic was rationally designed and synthesized for the ultrasensitive and selective sensing of cyanide in a wide pH range of 3.0-12.0. The nucleophilic addition of cyanide to the ß-conjugated carbon of the 1,3-indanedione group obstructs intramolecular charge transfer (ICT) and causes a significant change in the absorption and fluorescence spectra, enabling colorimetric and ratiometric fluorescent detection of cyanide in a 90% aqueous solution. The cyanide-sensing mechanism is supported by single-crystal X-ray diffraction analysis, time-dependent density functional theory (TD-DFT) calculations, and 1H NMR titration experiments. Sensor 1 exhibits strong yellow fluorescence in the solid state due to the AIE effect, and the paper probes containing 1 can be conveniently used to sense cyanide by the naked eye. Furthermore, chemodosimeter 1 was successfully used for sensing cyanide in real environmental water samples.

Diagnosis of ventilator-associated pneumonia using electronic nose sensor array signals: solutions to improve the application of machine learning in respiratory research.

BACKGROUND: Ventilator-associated pneumonia (VAP) is a significant cause of mortality in the intensive care unit. Early diagnosis of VAP is important to provide appropriate treatment and reduce mortality. Developing a noninvasive and highly accurate diagnostic method is important. The invention of electronic sensors has been applied to analyze the volatile organic compounds in breath to detect VAP using a machine learning technique. However, the process of building an algorithm is usually unclear and prevents physicians from applying the artificial intelligence technique in clinical practice. Clear processes of model building and assessing accuracy are warranted. The objective of this study was to develop a breath test for VAP with a standardized protocol for a machine learning technique. METHODS: We conducted a case-control study. This study enrolled subjects in an intensive care unit of a hospital in southern Taiwan from February 2017 to June 2019. We recruited patients with VAP as the case group and ventilated patients without pneumonia as the control group. We collected exhaled breath and analyzed the electric resistance changes of 32 sensor arrays of an electronic nose. We split the data into a set for training algorithms and a set for testing. We applied eight machine learning algorithms to build prediction models, improving model performance and providing an estimated diagnostic accuracy. RESULTS: A total of 33 cases and 26 controls were used in the final analysis. Using eight machine learning algorithms, the mean accuracy in the testing set was 0.81 ± 0.04, the sensitivity was 0.79 ± 0.08, the specificity was 0.83 ± 0.00, the positive predictive value was 0.85 ± 0.02, the negative predictive value was 0.77 ± 0.06, and the area under the receiver operator characteristic curves was 0.85 ± 0.04. The mean kappa value in the testing set was 0.62 ± 0.08, which suggested good agreement. CONCLUSIONS: There was good accuracy in detecting VAP by sensor array and machine learning techniques. Artificial intelligence has the potential to assist the physician in making a clinical diagnosis. Clear protocols for data processing and the modeling procedure needed to increase generalizability.

Heterogeneous influences of emotional disturbances on multi-domain quality of life after anterior cervical spine surgery: A prospective study.

OBJECTIVE: Quality of life (QoL) has been identified as one of the most important outcome measurements following cervical spine surgery. The contributing factors to post-operative QoL remain limited. This study thus aimed to prospectively examine the QoL and related pre-operative emotional factors in patients who underwent anterior cervical spine surgery. PATIENTS AND METHODS: A total of 124 patients who underwent anterior cervical spine surgery were recruited. All participants were prospectively evaluated for their QoL and 2 aspects of emotion, depression and anxiety, before and after surgery, respectively. RESULTS: Pre-operatively, 13% of patients showed signs of depression and 31% of patients reported symptoms of anxiety. Post-operatively 14% of patients reported depression, but 41% reported symptoms of anxiety. A significant association between depression, anxiety and different domains of QoL were identified, and specific cut-off points of pre-operatively depressive and/or anxiety levels to predict unfavorable post-operative QoL were further established. CONCLUSIONS: This prospective study demonstrated specific emotional factors, specifically depression and anxiety, influence patients' QoL following surgery. These results suggest clinicians should also monitor patients' emotional adjustments with their physical conditions.

Arabidopsis inositol phosphate kinases IPK1 and ITPK1 constitute a metabolic pathway in maintaining phosphate homeostasis.

Emerging studies have suggested that there is a close link between inositol phosphate (InsP) metabolism and cellular phosphate (Pi ) homeostasis in eukaryotes; however, whether a common InsP species is deployed as an evolutionarily conserved metabolic messenger to mediate Pi signaling remains unknown. Here, using genetics and InsP profiling combined with Pi -starvation response (PSR) analysis in Arabidopsis thaliana, we showed that the kinase activity of inositol pentakisphosphate 2-kinase (IPK1), an enzyme required for phytate (inositol hexakisphosphate; InsP6 ) synthesis, is indispensable for maintaining Pi homeostasis under Pi -replete conditions, and inositol 1,3,4-trisphosphate 5/6-kinase 1 (ITPK1) plays an equivalent role. Although both ipk1-1 and itpk1 mutants exhibited decreased levels of InsP6 and diphosphoinositol pentakisphosphate (PP-InsP5 ; InsP7 ), disruption of another ITPK family enzyme, ITPK4, which correspondingly caused depletion of InsP6 and InsP7 , did not display similar Pi -related phenotypes, which precludes these InsP species from being effectors. Notably, the level of d/l-Ins(3,4,5,6)P4 was concurrently elevated in both ipk1-1 and itpk1 mutants, which showed a specific correlation with the misregulated Pi phenotypes. However, the level of d/l-Ins(3,4,5,6)P4 is not responsive to Pi starvation that instead manifests a shoot-specific increase in the InsP7 level. This study demonstrates a more nuanced picture of the intersection of InsP metabolism and Pi homeostasis and PSRs than has previously been elaborated, and additionally establishes intermediate steps to phytate biosynthesis in plant vegetative tissues.

Reversible glycosidic switch for secure delivery of molecular nanocargos.

Therapeutic drugs can leak from nanocarriers before reaching their cellular targets. Here we describe the concept of a chemical switch which responds to environmental conditions to alternate between a lipid-soluble state for efficient cargo loading and a water-soluble state for stable retention of cargos inside liposomes. A cue-responsive trigger allows release of the molecular cargo at specific cellular sites. We demonstrate the utility of a specific glycosidic switch for encapsulation of potent anticancer drugs and fluorescent compounds. Stable retention of drugs in liposomes allowed generation of high tumor/blood ratios of parental drug in tumors after enzymatic hydrolysis of the glycosidic switch in the lysosomes of cancer cells. Glycosidic switch liposomes could cure mice bearing human breast cancer tumors without significant weight loss. The chemical switch represents a general method to load and retain cargos inside liposomes, thereby offering new perspectives in engineering safe and effective liposomes for therapy and imaging.

Iatrogenic Effect? Cautions when Utilizing an Early Health Education for Post-concussion Symptoms.

OBJECTIVE: Patients with mild traumatic brain injury (MTBI) usually suffer from the post-concussion symptoms (PCS). PCS could recover by 3 months post-injury, but some patients still persistently complain of those symptoms for years. Accordingly, the Chang-Gung University Brief Intervention for Post-Concussion Symptoms (CGU-BIPCS) was developed to intervene PCS based on the established advantages of health education. This prospective study thus aims to evaluate the effectiveness of CGU-BIPCS for patients with MTBI. METHODS: A total of 130 participants, which included 53 healthy participants and 77 patients with MTBI. Patients were further subdivided as two groups: "regular intervention" (RI) and "health education intervention" (EI). PCS of patients with MTBI were respectively evaluated at 2 weeks and 3 months post-injury, and symptoms of healthy participants were also examined. RESULTS: Both patients in RI and EI reported significantly more PCS than healthy participants did at 2 weeks and 3 months post-injury but less PCS at 3 months than at 2 weeks post-injury. However, the PCS endorsement of patients in RI and EI were not significantly different. In addition, more patients in EI reported significantly PCS deterioration than patients in RI did at 3 months post-injury. CONCLUSIONS: Although establishing the effectiveness of CGU-BIPCS was unsuccessful in this study, it is further suggested that a potential iatrogenic effect from this kind of early interventions should never be overlooked.

LIMCH1 regulates nonmuscle myosin-II activity and suppresses cell migration.

Nonmuscle myosin II (NM-II) is an important motor protein involved in cell migration. Incorporation of NM-II into actin stress fiber provides a traction force to promote actin retrograde flow and focal adhesion assembly. However, the components involved in regulation of NM-II activity are not well understood. Here we identified a novel actin stress fiber-associated protein, LIM and calponin-homology domains 1 (LIMCH1), which regulates NM-II activity. The recruitment of LIMCH1 into contractile stress fibers revealed its localization complementary to actinin-1. LIMCH1 interacted with NM-IIA, but not NM-IIB, independent of the inhibition of myosin ATPase activity with blebbistatin. Moreover, the N-terminus of LIMCH1 binds to the head region of NM-IIA. Depletion of LIMCH1 attenuated myosin regulatory light chain (MRLC) diphosphorylation in HeLa cells, which was restored by reexpression of small interfering RNA-resistant LIMCH1. In addition, LIMCH1-depleted HeLa cells exhibited a decrease in the number of actin stress fibers and focal adhesions, leading to enhanced cell migration. Collectively, our data suggest that LIMCH1 plays a positive role in regulation of NM-II activity through effects on MRLC during cell migration.

Retrospectively evaluated preinjury personality traits influence postconcussion symptoms.

Postconcussion symptoms (PCS) are not uncommon following mild traumatic brain injury (mTBI). Personality traits have always been viewed as one of the most important explanations for persistent postconcussion symptoms (PPCS). Unfortunately, studies on the association between preinjury personality traits and the PPCS are still limited. This study thus aimed to examine the relationship between the preinjury personality and PCS in patients with mTBI. A total of 106 participants including 53 healthy participants were recruited. All participants complete the modified Checklist of Postconcussion Symptoms and the Health, Personality, & Habit Scale. Participants were evaluated within 4 weeks and at 4 months, respectively, after injury. The results showed patients reported significantly more PCS than healthy participants did within 4 weeks postinjury. A significant positive association between PCS and retrospectively evaluated preinjury personality was found. Specifically, patients who reported that their preinjury personality was depressive or anxious-related presented more PCS. This study might be the first to directly demonstrate that preinjury personality traits are closely linked to PCS reporting in patients with mTBI. Importantly, PCS reporting might be associated with different personality traits at different periods after injuries, and thus, a careful evaluation for personality characteristics is merited after mTBI.

Electrical impedance tomography monitoring in acute respiratory distress syndrome patients with mechanical ventilation during prolonged positive end-expiratory pressure adjustments.

BACKGROUND/PURPOSE: The time required to reach oxygenation equilibrium after positive end-expiratory pressure (PEEP) adjustments in mechanically ventilated patients with acute respiratory distress syndrome (ARDS) is unclear. We used electrical impedance tomography to elucidate gas distribution and factors related to oxygenation status following PEEP in patients with ARDS. METHODS: Nineteen mechanically ventilated ARDS patients were placed on baseline PEEP (PEEPB) for 1 hour, PEEPB - 4 cmH2O PEEP (PEEPL) for 30 minutes, and PEEPB + 4 cmH2O PEEP (PEEPH) for 1 hour. Tidal volume and respiratory rate were similar. Impedance changes, respiratory parameters, and arterial blood gases were measured at baseline, 5 minutes, and 30 minutes after PEEPL, and 5 minutes, 15 minutes, 30 minutes, and 1 hour after PEEPH. RESULTS: PaO2/fraction of inspired oxygen (P/F ratio) decreased quickly from PEEPB to PEEPL, and stabilized 5 minutes after PEEPL. However the P/F ratio progressively increased from PEEPL to PEEPH, and a significantly higher P/F ratio and end-expiratory lung impedance were found at 60 minutes compared to 5 minutes after PEEPH. The end-expiratory lung impedance level significantly correlated with P/F ratio (p < 0.001). With increasing PEEP, dorsal ventilation significantly increased; however, regional ventilation did not change over time with PEEP level. CONCLUSION: Late improvements in oxygenation following PEEP escalation are probably due to slow recruitment in ventilated ARDS patients. Electrical impedance tomography may be an appropriate tool to assess recruitment and oxygenation status in patients with changes in PEEP.

A ratiometric chemodosimeter for highly selective naked-eye and fluorogenic detection of cyanide.

A simple indole-based chemosensor (1) with a very low molecular weight of 207 g mol(-1) has been synthesized for the highly reactive and selective detection of CN(-) in aqueous media, even in the presence of other anions, such as F(-), Cl(-), Br(-), AcO(-), [Formula: see text] , SCN(-), [Formula: see text] , [Formula: see text] , [Formula: see text] , BzO(-), [Formula: see text] , and [Formula: see text] . The sensor achieves rapid detection of cyanide anion in 2 min, and the pseudo-first-order rate constant is estimated as 1.576 min(-1). The colorimetric and ratiometric fluorescent response of the sensor to CN(-) is attributable to the addition of CN(-) to the electron-deficient dicyanovinyl group of 1, which prevents intramolecular charge transfer. The sensing mechanism is supported by density functional theory and time-dependent density functional theory calculations. Moreover, sensor 1 exhibits both high accuracy in determining the concentration of CN(-) in real samples and 1-based test strips can conveniently detect CN(-) without any additional equipment. The detection limit of the sensor 1 (1.1 µM) for cyanide is lower than the maximum permissible level of CN(-) (1.9 µM) in drinking water.

Actin-binding protein G (AbpG) participates in modulating the actin cytoskeleton and cell migration in Dictyostelium discoideum.

Cell migration is involved in various physiological and pathogenic events, and the complex underlying molecular mechanisms have not been fully elucidated. The simple eukaryote Dictyostelium discoideum displays chemotactic locomotion in stages of its life cycle. By characterizing a Dictyostelium mutant defective in chemotactic responses, we identified a novel actin-binding protein serving to modulate cell migration and named it actin-binding protein G (AbpG); this 971-amino acid (aa) protein contains an N-terminal type 2 calponin homology (CH2) domain followed by two large coiled-coil regions. In chemoattractant gradients, abpG(-) cells display normal directional persistence but migrate significantly more slowly than wild-type cells; expressing Flag-AbpG in mutant cells eliminates the motility defect. AbpG is enriched in cortical/lamellipodial regions and colocalizes well with F-actin; aa 401-600 and aa 501-550 fragments of AbpG show the same distribution as full-length AbpG. The aa 501-550 region of AbpG, which is essential for AbpG to localize to lamellipodia and to rescue the phenotype of abpG(-) cells, is sufficient for binding to F-actin and represents a novel actin-binding protein domain. Compared with wild-type cells, abpG(-) cells have significantly higher F-actin levels. Collectively our results suggest that AbpG may participate in modulating actin dynamics to optimize cell locomotion.

Ratiometric fluorescent/colorimetric cyanide-selective sensor based on excited-state intramolecular charge transfer-excited-state intramolecular proton transfer switching.

A novel salicylideneaniline-based fluorescent sensor, SB1, with a unique excited-state intramolecular charge transfer-excited-state intramolecular proton transfer (ESICT-ESIPT) coupled system was synthesized and demonstrated to fluorescently sense CN(-) with specific selectivity and high sensitivity in aqueous media based on ESICT-ESIPT switching. A large blue shift (96 nm) was also observed in the absorption spectra in response to CN(-). The bleaching of the color could be clearly observed by the naked eye. Moreover, SB1-based test strips were easily fabricated and low-cost, and could be used in practical and efficient CN(-) test kits. Density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations further support the cyanide-induced ESICT-ESIPT switching mechanism. The results provide the proof of concept that the colorimetric and ratiometric fluorescent cyanide-selective chemodosimeter can be created based on an ESICT-ESIPT coupled system.

"Good-old-days" bias: a prospective follow-up study to examine the preinjury supernormal status in patients with mild traumatic brain injury.

PRIMARY OBJECTIVE: Postconcussion symptoms (PCS) are common following mild traumatic brain injury (mTBI). A psychological misperception, the "good-old-days" bias, has been indicated as one of the influencing factors on symptom reporting after injury. To date, this response bias has only been examined in a small number of cross-sectional studies. This study thus prospectively evaluated the "good-old-days" bias in patients with mTBI. RESEARCH DESIGN: A prospective follow-up study. METHOD AND PROCEDURES: Fifty-three patients with mTBI were recruited in this study. The PCS was evaluated by the modified Checklist of Postconcussion Symptoms (mCPCS) at 1 month post injury. Twenty-five patients were evaluated again at 3 months after injuries. In addition, 53 healthy participants were also evaluated for the PCS, and 23 of them underwent a second evaluation at 2 months after the first one. MAIN OUTCOMES AND RESULTS: Patients with mTBI showed significantly higher PCS reporting at 1 month post injury than healthy participants did, but not at 3 months post injury. Consistent with the "good-old-days" bias, patients remarkably underestimated their preinjury PCS at 1 month post injury. Interestingly, our results further revealed that this response bias diminished more at 3 months than at 1 month after mTBI. CONCLUSIONS: This study thus might be the first one to prospectively reveal the progression of the "good-old-days" bias in patients with mTBI.

Divergent manifestations of irritability in patients with mild and moderate-to-severe traumatic brain injury: perspectives of awareness and neurocognitive correlates.

PRIMARY OBJECTIVES: To evaluate irritability in patients with mild traumatic brain injury (mTBI) and moderate-to-severe traumatic brain injury (msTBI), respectively. RESEARCH DESIGN: A prospective study was conducted at a level I trauma centre. METHODS AND PROCEDURES: A total of 160 participants, which included 80 healthy subjects and 80 patients with TBI, were recruited. Irritability was assessed by the National Taiwan University Irritability Scale and other cognitive functions, which included memory, executive function and information processing, were also evaluated. MAIN OUTCOMES AND RESULTS: The results showed post-injury self-reported irritability in patients with mTBI and family-reported irritability in patients with msTBI were significantly higher than irritability reported by healthy participants. Irritability was significantly associated with information processing ability in patients with mTBI, but it was not associated with any cognitive functions in patients with msTBI. CONCLUSIONS: Irritability was found to be prominent after TBI. Divergent causes of irritability seemed apparent in patients with mTBI and msTBI. Irritability after mTBI appeared might be related to the cognitive functions disrupted after the injury, whereas irritability after msTBI appeared to result directly from the brain lesions involved.

Penta-cyclo-[8.2.1.1(4,7).0(2,9).0(3,8)]tetra-deca-5,11-diene.

The title compound, C(14)H(16), was prepared through [2 + 2] cyclo-addition of norbornadiene. There are two independent mol-ecules in the asymmetric unit: each is centrosymmetric with the centroid of the four-membered ring located about an inversion center. Each mol-ecule possesses an exo-trans-exo conformation.

Irritability following traumatic brain injury: divergent manifestations of annoyance and verbal aggression.

PRIMARY OBJECTIVES: To evaluate irritability following traumatic brain injury. RESEARCH DESIGN: A prospective study was conducted at a level I trauma centre. METHODS AND PROCEDURES: One hundred and forty-four participants, which included 80 healthy subjects and 64 patients suffering from TBI, were recruited. Irritability was assessed by the National Taiwan University Irritability Scale (NTUIS) from patients themselves and their families. MAIN OUTCOMES AND RESULTS: the results showed 14.8% of patients and 29.4% of their families reported patients' problems of irritability. Meanwhile, both self-reported and family-reported irritability post-injury were significantly higher than those reported by the healthy subjects. When evaluating two sub-components of irritability, respectively, both family- and self-reported post-injury annoyance were significantly higher than the pre-injury one, while the self-reported post-injury verbal aggression was not. CONCLUSIONS: TBI patients have remarkable problems of irritability after injuries. Specifically, the results showed that annoyance might be the main characteristic of irritability in TBI patients and patients themselves might be unaware of their verbal aggression post-injury. Hence, it is merited to pay more attention to the annoyance of the patients with TBI and to the reports from significant caregivers when evaluating TBI patients' irritability in clinical settings.