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Objective We aimed to assess the efficacy of cefoperazone/sulbactam (CPZ/SUL) in extended-spectrum β-lactamase (ESBL)-producing Enterobacterales infections and identify factors influencing outcomes. Methods This retrospective multicentre study was conducted in Taiwan (January 2015 to December 2020) and examined the efficacy of CPZ/SUL treatment in ESBL-producing Enterobacterales bacteraemia. The minimum inhibitory concentrations (MICs) were determined using agar dilution; ESBL/AmpC genes were detected using polymerase chain reaction. The primary outcome was clinical success, whereas the secondary outcome was 30-day mortality. Clinical success was defined as the complete resolution of clinical signs and symptoms of K. pneumoniae or E. coli infection, with no evidence of persistent or recurrent bacteraemia. The factors influencing outcomes were identified using a multivariate analysis. Results CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia, with a 30-day mortality rate of 9.1% (10/110). Among 110 ESBL-producing isolates, a high clinical success rate was observed at an MIC of ≤32/32 mg/L. Multivariate analysis revealed that a Charlson comorbidity index (CCI) of ≥6 was associated with lower clinical success [odds ratio (OR): 5.80, 95% confidence interval (CI): 1.15–29.14, P = 0.033]. High Sequential Organ Failure Assessment scores (≥6) were significantly associated with increased 30-day mortality (OR: 14.34, 95% CI: 1.45–141.82, P = 0.023). Discussion CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia. Treatment success was evident when the CPZ and SUL MIC was ≤32/32 mg/L. Comorbidities (CCI ≥6) were associated with lower clinical success, while disease severity (Sequential Organ Failure Assessment score ≥6) correlated with higher mortality. [ABSTRACT FROM AUTHOR]

Although colloidal perovskite nanocrystal (PNC) solution has exhibited near‐unity photoluminescence quantum yield (PLQY), the luminance would be severely quenched when the PNC solution is assembled into thin films due to the agglomeration and fusion of NCs caused by the exfoliation of surface ligands and non‐radiative Förster resonance energy transfer (FRET) from small to large particle sizes, which seriously affected the performances of light‐emitting diodes (LEDs). Here, we used Guanidine thiocyanate (GASCN) and Sodium thiocyanate (NaSCN) to achieve effective CsPbI3 PNC surface reconstruction. Due to the strong coordination ability of these small molecules with the anions and cations on the surface of the PNCs, they can provide strong surface protection against PNC fusion during centrifugal purification process and repair the surface defects of PNCs, so that the original uniform size distribution of PNCs can be maintained and FRET between close‐packed PNC films is effectively suppressed, which allows the emission characteristics of the films to be preserved. As a result, highly oriented, smooth and nearly defect‐free high‐quality PNC thin films are obtained, with PLQY as high as 95.1 %, far exceeding that of the original film, and corresponding LEDs exhibit a maximum external quantum efficiency of 24.5 %. [ABSTRACT FROM AUTHOR]

Although colloidal perovskite nanocrystal (PNC) solution has exhibited near‐unity photoluminescence quantum yield (PLQY), the luminance would be severely quenched when the PNC solution is assembled into thin films due to the agglomeration and fusion of NCs caused by the exfoliation of surface ligands and non‐radiative Förster resonance energy transfer (FRET) from small to large particle sizes, which seriously affected the performances of light‐emitting diodes (LEDs). Here, we used Guanidine thiocyanate (GASCN) and Sodium thiocyanate (NaSCN) to achieve effective CsPbI3 PNC surface reconstruction. Due to the strong coordination ability of these small molecules with the anions and cations on the surface of the PNCs, they can provide strong surface protection against PNC fusion during centrifugal purification process and repair the surface defects of PNCs, so that the original uniform size distribution of PNCs can be maintained and FRET between close‐packed PNC films is effectively suppressed, which allows the emission characteristics of the films to be preserved. As a result, highly oriented, smooth and nearly defect‐free high‐quality PNC thin films are obtained, with PLQY as high as 95.1 %, far exceeding that of the original film, and corresponding LEDs exhibit a maximum external quantum efficiency of 24.5 %. [ABSTRACT FROM AUTHOR]

Cognitive impairment impacts the quality of life and increases morbidity and mortality rates. The prevalence of and factors associated with cognitive impairment have become important issues as the age of people living with HIV(PLWH) increases. In 2020, We conducted a cross-sectional study to survey the cognitive impairment among PLWH in three hospitals in Taiwan with Alzheimer Disease-8 (AD8) questionnaire. The average age of 1,111 individuals was 37.54 ± 10.46 years old, and their average duration to live with HIV was 7.12 ± 4.85 years. The rate of impaired cognitive function was 2.25% (N = 25) when AD8 score ≥ 2 was a positive finding for cognitive impairment. Aging (p =.012), being less educated (p = 0.010), and having a longer duration to live with HIV (p =.025) were significantly associated with cognitive impairment. Multivariate logistic regression analysis revealed that only the duration of living with HIV was a significant factor related to the tendency of cognitive impairment (p =.032). The risk of cognitive impairment increased by 1.098 times for every additional year to live with HIV. In conclusion, the prevalence of cognitive impairment among PLWH in Taiwan was 2.25%. Healthcare personnel should be sensitive to the changes in PLWH's cognitive function as they age. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) associated with TAR DNA-binding protein 43 (TDP-43) aggregation has been considered as a lethal and progressive motor neuron disease. Recent studies have shown that both C-terminal TDP-43 (C-TDP-43) aggregates and oligomers were neurotoxic and pathologic agents in ALS and frontotemporal lobar degeneration (FTLD). However, misfolding protein has long been considered as an undruggable target by applying conventional inhibitors, agonists, or antagonists. To provide this unmet medical need, we aim to degrade these misfolding proteins by designing a series of proteolysis targeting chimeras (PROTACs) against C-TDP-43. Methods: By applying filter trap assay, western blotting, and microscopy imaging, the degradation efficiency of C-TDP-43 aggregates was studied in Neuro-2a cells overexpressing eGFP-C-TDP-43 or mCherry-C-TDP-43. The cell viability was characterized by alarmarBlue assay. The beneficial and disaggregating effects of TDP-43 PROTAC were examined with the YFP-C-TDP-43 transgenic C. elegans by motility assay and confocal microscopy. The impact of TDP-43 PROTAC on C-TDP-43 oligomeric intermediates was monitored by fluorescence lifetime imaging microscopy and size exclusion chromatography in the Neuro-2a cells co-expressing eGFP-C-TDP-43 and mCherry-C-TDP-43. Results: Four PROTACs with different linker lengths were synthesized and characterized. Among these chimeras, PROTAC 2 decreased C-TDP-43 aggregates and relieved C-TDP-43-induced cytotoxicity in Neuro-2a cells without affecting endogenous TDP-43. We showed that PROTAC 2 bound to C-TDP-43 aggregates and E3 ligase to initiate ubiquitination and proteolytic degradation. By applying advanced microscopy, it was further shown that PROTAC 2 decreased the compactness and population of C-TDP-43 oligomers. In addition to cellular model, PROTAC 2 also improved the motility of transgenic C. elegans by reducing the C-TDP-43 aggregates in the nervous system. Conclusions: Our study demonstrated the dual-targeting capacity of the newly-designed PROTAC 2 against both C-TDP-43 aggregates and oligomers to reduce their neurotoxicity, which shed light on the potential drug development for ALS as well as other neurodegenerative diseases. [ABSTRACT FROM AUTHOR]

Introduction: The clinical efficiency of cefoperazone/sulbactam (CPZ/SUL) against Escherichia coli bacteremia was unknown. This study aimed to explore the relationship between CPZ/SUL MIC values and clinical outcomes in Escherichia coli bacteremia. Methods: A multicenter, retrospective, observational cohort study was conducted in Taiwan between January 2015 and December 2020. Patients treated with CPZ/SUL for E. coli bacteremia were enrolled in the analysis. The CPZ/SUL MICs were determined by using the agar dilution method. The primary outcome was 30-day mortality. Results: Among 247 isolates, 160 (64.8%) isolates were susceptible, 8 (3.2%) were intermediate, and 79 (32.0%) were resistant to cefoperazone. The activity of cefoperazone against cefoperazone-non-susceptible E. coli (n = 87) was restored upon combination with sulbactam, with susceptibility ranging from 0% to 97.7%. The 30-day mortality was 4.5% (11/247) and overall clinical success rate was 91.9% (227/247). Multivariate Cox proportional-hazards model revealed that heart failure [adjusted relative risk (ARR), 5.49; 95% confidence interval (CI) 1.31–23.02; p = 0.020], malignancy (ARR 7.50; 95% CI 2.02–27.80; p = 0.003), SOFA score (ARR 1.29; 95% CI 1.09–1.52; p = 0.003), and CPZ/SUL MIC ≥ 64 mg/L (ARR 11.31; 95% CI 1.34–95.52; p = 0.026) were independently associated with 30-day mortality. No statistically significant differences in 30-day mortality were found between groups with or without cefoperazone susceptibility (3.4% vs. 5.0%, p = 0.751, respectively). Conclusions: Patients with E. coli bacteremia who were treated with CPZ/SUL had a favorable outcome when the MICs of the isolates were ≤ 16 mg/L and a high risk of mortality with MICs ≥ 64 mg/L. [ABSTRACT FROM AUTHOR]

Polypropylene (PP), a promising engineering thermoplastic, possesses the advantages of light weight, chemical resistance, and flexible processability, yet preserving insulative properties. For the rising demand for cost-effective electronic devices and system hardware protections, these applications require the proper conductive properties of PP, which can be easily modified. This study investigates the thermal and electrical properties of isotactic polypropylene/copper nanowires (i-PP/CuNWs). The CuNWs were harvested by chemical reduction of CuCl2 using a reducing agent of glucose, capping agent of hexadecylamine (HDA), and surfactant of PEG-7 glyceryl cocoate. Their morphology, light absorbance, and solution homogeneity were investigated by SEM, UV-visible spectrophotometry, and optical microscopy. The averaged diameters and the length of the CuNWs were 66.4 ± 16.1 nm and 32.4 ± 11.8 µm, respectively. The estimated aspect ratio (L/D, length-to-diameter) was 488 ± 215 which can be recognized as 1-D nanomaterials. Conductive i-PP/CuNWs composites were prepared by solution blending using p-xylene, then melt blending. The thermal analysis and morphology of CuNWs were characterized by DSC, polarized optical microscopy (POM), and SEM, respectively. The melting temperature decreased, but the crystallization temperature increasing of i-PP/CuNWs composites were observed when increasing the content of CuNWs by the melt blending process. The WAXD data reveal the coexistence of Cu2O and Cu in melt-blended i-PP/CuNWs composites. The fit of the electrical volume resistivity (ρ) with the modified power law equation: ρ = ρo (V − Vc)−t based on the percolation theory was used to find the percolation concentration. A low percolation threshold value of 0.237 vol% and high critical exponent t of 2.96 for i-PP/CuNWs composites were obtained. The volume resistivity for i-PP/CuNWs composite was 1.57 × 107 Ω-cm at 1 vol% of CuNWs as a potential candidate for future conductive materials. [ABSTRACT FROM AUTHOR]

A photo quiz about the presence of lung and brain abscesses in a male patient who underwent upper extremity allotransplantatation is presented.

Background: Diabetic patients are at risk of severe urinary tract infections (UTIs). Due to the emerging resistance rates to fluoroquinolones and β-lactams, we aimed to evaluate the effectiveness of β-lactams versus fluoroquinolones as empirical therapy for diabetic patients hospitalized for UTIs. Methods: A retrospective cohort study was conducted in a medical center in Taiwan between 2016 and 2018. Patients with type 2 diabetes, aged ≥20 and hospitalized for UTIs were enrolled. Patients with UTI diagnosis within one year before the admission, co-infections at the admission, or ≥2 pathogens in the urine cultures were excluded. The primary outcome was empiric treatment failure. Results: 298 patients were followed for at least 30 days after the admission. Escherichia coli (61.07%) was the most common pathogen. The resistance rates of the pathogens to levofloxacin were 28.52% and 34.22% according to the historical Clinical and Laboratory Standards Institute (CLSI) breakpoints and the updated 2019 CLSI breakpoints, respectively. The resistance rates of ceftazidime and cefepime were 21.81% and 11.41%, respectively. Empirical β-lactams were associated with less treatment failure compared to fluoroquinolones (adjusted OR = 0.32, 95% CI = 0.17–0.60). Beta-lactams were associated with less treatment failure than fluoroquinolones when appropriatness was determined by the pre-2019 CLSI breakpoints but not the 2019 CLSI breakpoints. Conclusions: In diabetic patients hospitalized for UTIs, β-lactams were associated with less empiric treatment failure compared to fluoroquinolones when the resistance rate to fluoroquinolone is higher than β-lactams. The updated 2019 CLSI breakpoint for fluoroquinolone was better than pre-2019 CLSI breakpoints to correlate with treatment outcomes for hospitalized UTIs in diabetic patients. [ABSTRACT FROM AUTHOR]

UVB can induce inflammatory responses contributing to diverse skin damage. UVB-triggered inflammasome activation of human keratinocytes underlies UVB-induced skin sunburn reaction. Pleiotropic functions of spleen tyrosine kinase (Syk) have rendered it as a potential therapeutic target. In immunocytes, Syk modulates immunoreceptor signaling and NLRP3 inflammasome activation. In skin, Syk mediates EGFR signaling, regulates keratinocyte differentiation and is involved in inflammatory disorders. However, roles of Syk in UVB-induced inflammasome activation in keratinocytes remain elusive. We investigated roles of keratinocyte Syk in UVB-triggered photo-responses. Primary normal human epidermal keratinocytes (NHEKs) isolated from skin were used. Syk knockdown or Syk inhibitor R406 was applied to investigate functions of keratinocyte Syk in UVB photobiology. The possible in vivo role of Syk was evaluated by checking UVB-induced skin damage in R406-treated mice. UVB was able to induce Syk phosphorylation in NHEKs that could be regulated by reactive oxygen species (ROS) generation and EGFR. Syk knockdown or Syk inhibitor (R406) treatment reduced UVB-triggered apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC) crosslinking, procaspase-1 cleavage, active IL-1β formation, and gasdermin D activation, indicating roles of Syk in UVB-triggered inflammasome activation in keratinocytes. UVB-induced production of IL-8, TNF-α, ROS, and phosphorylation of JNK and p38 were attenuated after Syk knockdown or inhibition. R406 ameliorated UVB-induced mouse skin damage, including erythema and transepidermal water loss (TEWL). Thus, Syk participated in UVB-induced inflammasome activation and inflammatory response in vitro and in vivo , suggesting potential photo-protective effects of Syk inhibition in UVB-induced skin inflammation. [Display omitted] • UVB can induce Syk activation in human skin keratinocytes through ROS and EGFR. • Keratinocyte Syk participates in processes of UVB-activated NLRP1 inflammasome. • Keratinocyte Syk regulates UVB-induced inflammatory cytokines IL-8 and TNF-α. • Topical Syk inhibitor application mitigates UVB-induced inflammation in mouse skin. • Keratinocyte Syk can be regarded as a potential target in UVB photoprotection. [ABSTRACT FROM AUTHOR]

To achieve balanced carrier transport and further improve the device performances of CsPbI3 nanocrystals-based light-emitting diodes, the 1,1-bis-(4-bis(4-tolyl)-aminophenyl) cyclohexene (TCTA) with high hole mobility was doped into a 4,4,4″-tris(carbazol-9-yl) triphenylamine hole transport layer (HTL) by a coevaporation method. The introduction of TAPC reduced hole injection barrier and improved mobility of the HTL. By adjusting the doping ratio of TAPC, highly efficient charge injection and more balanced carrier transport were obtained. Consequently, the mixed HTL based device showed elevated device performances with a maximum luminance of 3308 cd m−2 and a peak external quantum efficiency of 10.7%. [ABSTRACT FROM AUTHOR]

Summary This paper examines the influence of field‐effect passivation (from a coating of aluminum oxide) in conjunction with up‐conversion (from multiple coatings containing Er/Yb‐doped phosphors) on the performance of silicon solar cells. Note that the phosphors were applied to the rear surface of the cells. The surface morphology of the coatings was characterized by scanning electron microscopy and the chemical composition of Er/Yb‐doped phosphors coating was examined using energy‐dispersive X‐ray spectroscopy. The fluorescence emissions of the coatings were examined using photoluminescence and optical image measurements. We examined the influence of field‐effect passivation on dark current‐voltage as well as photo‐current density and external quantum efficiency (EQE). Improvements in photovoltaic performance after applying coatings containing Er/Yb‐doped phosphors were estimated in terms of EQE and conversion efficiency. The field‐effect passivation of Al2O3 and up‐conversion provided by Er/Yb‐doped phosphors resulted in EQE enhancements over a wavelength range of 600 to 1050 nm. Field‐effect passivation was shown to enhance the conversion efficiency by 1.77% (from 16.91% to 17.21%), up‐conversion enhanced conversion efficiency by 2.9% (from 17.21% to 17.71%), and a combination of field‐effect passivation and up‐conversion enhanced conversion efficiency by 4.73% (from 16.91% to 17.71%). [ABSTRACT FROM AUTHOR]

Damage to the myelin sheath and the neuroaxonal unit is a cardinal feature of multiple sclerosis; however, a detailed characterization of the interaction between myelin and axon damage in vivo remains challenging. We applied myelin water and multi-shell diffusion imaging to quantify the relative damage to myelin and axons (i) among different lesion types; (ii) in normal-appearing tissue; and (iii) across multiple sclerosis clinical subtypes and healthy controls. We also assessed the relation of focal myelin/axon damage with disability and serum neurofilament light chain as a global biological measure of neuroaxonal damage. Ninety-one multiple sclerosis patients (62 relapsing-remitting, 29 progressive) and 72 healthy controls were enrolled in the study. Differences in myelin water fraction and neurite density index were substantial when lesions were compared to healthy control subjects and normal-appearing multiple sclerosis tissue: both white matter and cortical lesions exhibited a decreased myelin water fraction and neurite density index compared with healthy (P < 0.0001) and peri-plaque white matter (P < 0.0001). Periventricular lesions showed decreased myelin water fraction and neurite density index compared with lesions in the juxtacortical region (P < 0.0001 and P < 0.05). Similarly, lesions with paramagnetic rims showed decreased myelin water fraction and neurite density index relative to lesions without a rim (P < 0.0001). Also, in 75% of white matter lesions, the reduction in neurite density index was higher than the reduction in the myelin water fraction. Besides, normal-appearing white and grey matter revealed diffuse reduction of myelin water fraction and neurite density index in multiple sclerosis compared to healthy controls (P < 0.01). Further, a more extensive reduction in myelin water fraction and neurite density index in normal-appearing cortex was observed in progressive versus relapsing-remitting participants. Neurite density index in white matter lesions correlated with disability in patients with clinical deficits (P < 0.01, beta = -10.00); and neurite density index and myelin water fraction in white matter lesions were associated to serum neurofilament light chain in the entire patient cohort (P < 0.01, beta = -3.60 and P < 0.01, beta = 0.13, respectively). These findings suggest that (i) myelin and axon pathology in multiple sclerosis is extensive in both lesions and normal-appearing tissue; (ii) particular types of lesions exhibit more damage to myelin and axons than others; (iii) progressive patients differ from relapsing-remitting patients because of more extensive axon/myelin damage in the cortex; and (iv) myelin and axon pathology in lesions is related to disability in patients with clinical deficits and global measures of neuroaxonal damage. [ABSTRACT FROM AUTHOR]

What is known and objective: Gut microbiota plays an important role in shaping immune responses. Several studies have reported that antibiotics may alter gut microbiota diversity and compromise the therapeutic response to immune checkpoint inhibitors (ICIs). Nevertheless, the impact of a specific class of antibiotics on ICIs therapy is still not known. The aim of this study was to analyse the influence of antibiotics on the clinical outcomes of non‐small cell lung cancer (NSCLC) patients treated with ICIs and to compare the effects of fluoroquinolones vs. other broad‐spectrum antibiotics. Methods: This retrospective cohort study (n = 340) analysed data from Chang Gung Research Database, which comprises work from seven medical institutions in Taiwan. Patients with NSCLC who received ICIs between January 2016 and March 2019 were evaluated. The data of patients who received antibiotics (ie fluoroquinolone) within 30 days prior to ICIs therapy were analysed. Overall survival (OS) was the goal of our study and was calculated from the time the ICIs therapy start. Survival analysis was estimated using the Kaplan‐Meier and Cox statistics. Results: A total of 340 patients were identified for analysis. Of the 340 patients, only over one third (38%) of patients received antibiotics 30 days prior to ICI therapy. These patients exhibited a shorter OS compared with those not receiving antibiotics (median OS, 266 days vs. 455 days; hazard ratio (HR), 2.9; 95% confidence interval (CI), 1.1–8.1, p = 0.003). In this study, 127 out of 128 patients who were exposed to antibiotics had received at least one broad‐spectrum antibiotic. We observed patients who had received fluoroquinolone had a shorter OS compared with those receiving other broad‐spectrum antibiotics (median OS, 121 days vs. 370 days; HR, 1.582; 95% CI 1.007–2.841; p = 0.047). What is new and conclusion: Antibiotic treatment, especially fluoroquinolone, prior to ICIs therapy was associated with poorer clinical efficacy in NSCLC patients. Antibiotics should not be withheld when there is a clear need for them despite the possibility of interfering with the microbiome, which may, in turn, adversely affect the ICI's effectiveness. However, one should consider avoiding the use of fluoroquinolones antibiotics. [ABSTRACT FROM AUTHOR]

Background and Purpose: The interleukin (IL)‐36 pathway is a critical player in the pathogenesis of pustular psoriasis. However, therapies targeting this pathway are limited or unaffordable (e.g. the anti‐IL‐36 receptor antibody). AMP‐activated protein kinase (AMPK), a regulator of cellular energy and metabolism, is known to participate in inflammatory diseases. However, its role in IL‐36‐induced skin inflammation remains unclear. Therefore, we sought to investigate the role of AMPK signals in regulating IL‐36‐induced responses in the skin. Experimental Approach: IL‐36‐stimulated primary normal human epidermal keratinocytes (NHEKs) and IL‐36‐injected (intradermally) BALB/c mice served as the cell and animal models, respectively. Additionally, 5‐aminoimidazole‐4‐carboxamide riboside (AICAR) and A769662 served as AMPK activators. Key Results: AICAR and A769662 significantly suppressed the IL‐36‐induced IL‐8 (CXCL8) and CCL20 production from NHEKs. IL‐36‐induced IκBζ protein expression was prominently reduced and IKK/IκBα phosphorylation was attenuated by AICAR and A769662. Conversely, AMPKα knockdown increased IκBζ protein expression and IKK/IκBα phosphorylation in IL‐36‐treated NHEKs. Furthermore, AICAR and A769662 enhanced IL‐36‐induced‐IκBζ protein degradation via the proteasome‐dependent but not the lysosome‐dependent pathway. Pretreatment of NHEKs with IL‐36 slightly suppressed the AICAR‐ and A769662‐triggered phosphorylation of AMPK and acetyl‐CoA carboxylase. In the mouse model, topical application of AICAR significantly reduced ear swelling, redness, epidermal thickening, neutrophil infiltration and inflammatory and antimicrobial peptide gene expression. Conclusion and Implications: AMPK activation suppresses IL‐36‐induced IL‐8 and CCL20 release by regulating IκBζ expression in keratinocytes and reduces IL‐36‐induced skin inflammation in mice, suggesting that AMPK activation is a potential strategy for treating patients with IL‐36‐mediated inflammatory skin disorders. [ABSTRACT FROM AUTHOR]

[Display omitted] • Photocatalytic degradation of microplastics (MPs) by Ruthenium-incorporated g-C 3 N 4 was proposed. • Photocatalytic degradation of LDPE was studied for different pH values (1–6) at 0, 35, 50, and 70 °C using Ru-g-C 3 N 4. • The degradation efficiency was 74.51 % after 24 h at pH 3 and 50 °C. • Formation of macroradicals played an important role in the photocatalytic degradation and followed the Norrish mechanism. Microplastics (MPs) are pollutants generated by plastic debris of diameters ≤ 5 mm and are a global concern that can pose severe threats to human and environmental health in both aquatic and terrestrial areas. In this study, low-density polyethylene (LDPE, MW = ∼35000) blended with Ru-incorporated g-C 3 N 4 (Ru-gCN) was fabricated to examine its degradation efficiency. Plastic film (Ru-gCN@PE) degradation was performed by adding an aqueous medium with pH values ranging from 1 to 6 and at different temperatures (0, 35, 50, and 70 °C). The Ru-gCN@PE showed a significant weight loss of approximately 66.04, 74.51, and 69.64 wt% in pH 3 at 0, 50, and 70 °C, respectively, upon light irradiation for 24 h. The high activity of Ru-gCN can result from the formation of a heterojunction of Ru and g-C 3 N 4 (Ru-gCN), which facilitates the transfer of the photoinduced π electrons of g-C 3 N 4. Moreover, H+ is produced at an appropriate pH and temperature to further convert into hydroperoxides and accelerate the formation of macroradicals (∙ROO, ∙RO, and ∙OH) for plastic degradation, which follows the Norrish Type I and II mechanisms. Our study demonstrated the outstanding efficacy of the photocatalytic degradation of LDPE. [ABSTRACT FROM AUTHOR]

Process for reducing the iron content in 356 secondary aluminum alloy is developed in the current study. The Fe-rich intermetallic compounds (or sludge) were removed by sedimentation of liquid aluminum through alloy addition. Effects of alloy additions were first surveyed by thermodynamic evaluation. The sedimentation temperature and time were designed according to the solidification curves of the secondary aluminum alloys. In this study, combinations of 0–2 wt% of manganese (Mn) and chromium (Cr) were added to the melts for isothermal sedimentation. Fe-rich sludges of Al(FeMn)Si, Al(FeCr)Si, and Al(FeMnCr)Si compounds were formed, and sedimented. Mn tends to increase the sludge particle size, while Cr addition has the effects of refining the precipitates and increasing aspect ratios of the precipitate morphology. Although chromium demonstrated higher iron removal capability than manganese, when more than 1 wt% Cr is added, the Al13Cr4Si4 phase forms without further removing Fe. When both Mn and Cr additions are excessive, Mn- and Cr-rich phases are formed at the center of the sludge phase. Therefore, excessive Mn and Cr cannot further increase iron removal rate. For optimum iron removal conditions, 1 wt% Mn- and 1 wt% Cr-added melts can remove 73.8% of Fe from the 356 secondary alloy and recover 77.3% secondary alloy by gravity separation method. [ABSTRACT FROM AUTHOR]

The European Confederation of Medical Mycology (ECMM) Quality of Clinical Candidaemia Management (EQUAL) score is a tool designed by the ECMM to measure guideline adherence. The current study investigated the association between EQUAL scores and clinical outcomes. This retrospective study was conducted in three hospitals in Taiwan. Patients with candidaemia between January 2014 and July 2018 were enrolled. Guideline adherence was evaluated using EQUAL score indicators. Clinical outcomes and predictors of 30-day mortality were investigated. A total of 384 patients were enrolled. The overall mean EQUAL score was 8.91 ± 3.42 (9.42 ± 3.60 in survivors vs. 8.10 ± 2.94 in non-survivors, p < 0.001). Higher scores were positively correlated with survival (p < 0.001). Scores of 16–22 indicated the highest survival rates (p for trend <0.001). The Kaplan–Meier plot revealed that patients with EQUAL scores ≥10 exhibited significantly higher survival rates (p < 0.001) than those with scores <10. Multivariable analysis revealed that EQUAL scores ≥10 (odds ratio (OR) 0.37, 95% confidence interval (CI) 0.19–0.74), advanced age (OR 1.02, 95% CI 1.00–1.04), septic shock (OR 4.42, 95% CI 2.09–9.36), high sequential organ failure assessment scores (OR 4.28, 95% CI 2.15–8.52), intravascular catheter-related source (OR 0.42, 95% CI 0.19–0.94) and central venous catheter retention (OR 5.41, 95% CI 2.06–14.24) were independent predictors of 30-day mortality. Greater guideline adherence with a higher EQUAL score was significantly associated with survival. An EQUAL score cutoff point <10 predicted 30-day mortality. [ABSTRACT FROM AUTHOR]

2D transition metal carbides, nitrides, and carbonitrides called MXenes show outstanding performance in many applications due to their superior physical and chemical properties. Herein, a ZnO–MXene mixture with different contents of Ti3C2 is applied as electron transport layers (ETLs) and the influence of the Ti3C2 MXene in all‐inorganic metal halide perovskite nanocrystal light‐emitting diodes (perovskite NC LEDs) is explored. The addition of Ti3C2 makes more balanced charge carrier transport in LEDs by changing the energy level structure and electron mobility of ETL. Moreover, lower surface roughness is obtained for the ETL, thus guaranteeing uniform distribution of the perovskite NCs layer and further reducing leakage current. As a result, a 17.4% external quantum efficiency (EQE) with low efficiency roll‐off is achieved with 10% Ti3C2, which is a 22.5% improvement compared to LEDs without Ti3C2. [ABSTRACT FROM AUTHOR]

• Galectin-3 in human keratinocytes positively regulates UVB-induced activation of IL-1β and caspase-1. • Galectin-3 modulates UVB-induced expression of reactive oxygen species and COX2 in human keratinocytes. • UVB-induced skin inflammation is alleviated in galectin-3 knockout mice compared to wild type mice. Galectin-3 is widely expressed in many immunocytes and epithelial cells including skin keratinocytes. Galectin-3 can regulate immunological or inflammatory processes and plays a proinflammatory role in some disease models. Galectin-3 has a role in disorders related to ultraviolet (UV) photodamage such as apoptosis, skin squamous cell carcinoma and basal cell carcinoma. However, the evidence of galectin-3 in UVB-induced skin inflammation is still limited and the underlying molecular mechanism remains elusive. We aimed to investigate the effects of galectin-3 in human epidermal keratinocytes and in mice after UVB irradiation. Primary human epidermal keratinocytes with galectin-3 knockdown were used as the in vitro model. ELISA, QPCR, and western blotting were applied to evaluate the released cytokine, mRNA and protein expression. Histologic analysis, measurement of erythema and transepidermal water loss (TEWL) were applied to evaluate UVB-induced skin damage in galectin-3 knockout mice. In UVB-irradiated human keratinocytes, galectin-3 knockdown downregulated the UVB-induced ASC crosslinking, cleavage of caspase-1, and formation of active IL-1β. Galectin-3 knockdown also decreased UVB-induced production of reactive oxygen species, p38 phosphorylation, and COX2 expression in human keratinocytes. After four days of UVB irradiation, galectin-3 knockout mice showed reduced gross erythema, histologic features of tissue inflammation, quantified levels of erythema and TEWL compared to wild type mice. The skin tissue lysate also showed less expression of active IL-1β and COX2 in galectin-3 knockout mice. Galectin-3 may play a positive regulatory role in UVB-induced skin inflammation. [ABSTRACT FROM AUTHOR]

H1N1, a subtype of influenza A virus, has emerged as a global threat in the past decades. Due to its highly infectious nature, an accurate and rapid detection assay is urgently required. Therefore, this study presents a new type of digital microfluidic platform for H1N1 virus detection by utilizing a one-aptamer/two-antibodies assay on magnetic beads. The droplets containing magnetic beads were driven by electromagnetic forces on a structure-free, super-hydrophobic surface to automate the entire assay within 40 min. With different levels of hydrophobic modification, the droplets could be easily controlled and positioned without any assisted microstructure. The tunable electromagnetic forces could be adjusted for three kinds of operating modes for the manipulations of beads and droplets, including movement of droplets containing magnetic beads, mixing of two droplets and beads extraction out of droplets. When compared with previous studies, the manipulations of droplets and magnetic particles in this study are more flexible as they can be easily adjusted by fine-tuning the magnetic flux density. Furthermore, the magnetic beads also served as three-dimensional substrates for the new enzyme-linked immunosorbent assay (ELISA)-like assay. The magnetic beads were conjugated with aptamers, which have high specificity towards H1N1 viruses such that they could be specifically captured and detected. The horseradish peroxidase-conjugated secondary antibody was then used to activate tyramide-tetramethylrhodamine (TTMR) such that fluorescent signals could be amplified. With this approach, the limit of detection was experimentally found to be 0.032 hemagglutination units/reaction, which is sensitive enough for clinical diagnostics. This kind of digital microfluidic platform with the ELISA-like assay could effectively reduce the consumption of samples and reagents such that the volume of all droplets including the H1N1 sample, antibodies, TTMR and wash buffers was only 20 μL. This is the first time that a digital microfluidic platform was demonstrated such that the entire diagnostic process for influenza A H1N1 viruses could be performed by using electromagnetic forces, which could be promising for rapid and accurate diagnosis of influenza. [ABSTRACT FROM AUTHOR]

[Display omitted] • Novel Dialysis-Free Process to Produce Silk Fibroin Nano-Fibrils (SFNF) • SFNF was Prepared by Shear-Induced Phase Separation Process. • Results SFNFs with high crystalline index (CI) and degree of crystallinity (DC) • Good Biocompatibility and Hemostatic efficacy of SFNFs as a potential alternative hemostatic agent. The objectives of this study were to investigate the biocompatibility and hemostatic efficacy of silk fibroin nanofibrils (SFNFs). Unlike a conventional dialysis/freeze-drying process, SFNFs were prepared using a novel shear-induced phase-separation method. The morphology, particle size distribution, protein secondary structures, and crystalline structures of the resulting SFNFs were respectively investigated by scanning electron microscopy (SEM), transmission electron microscopy (TEM), laser diffraction (LD), Fourier-transform infrared (FTIR) spectroscopy, and x-ray diffraction (XRD) deconvolution analyses. Polar and non-polar extractants of SFNFs under a bath ratio of 0.2 g/mL were collected after individually soaking them into 0.9% normal saline and cottonseed oil. In vitro hemolysis ratios, biocompatibility, and sensitization tests were carried out. Then, the hemostatic efficacy was assayed using a rat liver punch biopsy model. Compared to dialyzed/freeze-dried SF, the harvested SFNFs revealed high surface area in morphology. The median particle size distribution, D50, was 294 μm for SFNFs. Shear-induced hydrogen bonding, crystallization, and phase separation tended to give the SFNFs a high crystalline index (CI) and degree of crystallinity (DC). The hemolysis ratio of SFNFs was 0.86 ± 0.40%, and it was classified as being non-hemolytic (0%∼2%). The test results of toxicity and skin sensitization were both negative. The hemostasis time for SFNFs (2.8 ± 0.6 min) was statistically less than that of oxidized cellulose (4.3 ± 0.9 min) (p < 0.05). The high biocompatibility and hemostatic efficacy of SFNFs revealed their potential as an alternative hemostatic agent. [ABSTRACT FROM AUTHOR]

Summary: Background: Current guidelines recommend echinocandins as first‐line therapy for candidemia. However, several non‐Candida yeast are non‐susceptible to echinocandins (echinocandin non‐susceptible yeast, ENSY), including Cryptococcus, Geotrichum, Malassezia, Pseudozyma, Rhodotorula, Saprochaete, Sporobolomyces and Trichosporon. In laboratories that are not equipped with rapid diagnostic tools, it often takes several days to identify yeast, and this may lead to inappropriate presumptive use of echinocandins in patients with ENSY fungemia. The aim of this study was to determine the distribution of ENSY species during a 1‐year, laboratory surveillance programme in Asia. Methods: Non‐duplicate yeast isolated from blood or bone marrow cultures at 25 hospitals in China, Hong Kong, India, Singapore, Taiwan and Thailand were analysed. Isolates were considered to be duplicative if they were obtained within 7 days from the same patient. Results: Of 2155 yeast isolates evaluated, 175 (8.1%) were non‐Candida yeast. The majority of non‐Candida yeast were ENSY (146/175, 83.4%). These included Cryptococcus (109 isolates), Trichosporon (23), Rhodotorula (10) and Malassezia (4). The proportion of ENSY isolates (146/2155, 6.7%) differed between tropical (India, Thailand and Singapore; 51/593, 8.6%) and non‐tropical countries/regions (China, Hong Kong and Taiwan; 95/1562, 6.1%, P = 0.038). ENSY was common in outpatient clinics (25.0%) and emergency departments (17.8%) but rare in intensive care units (4.7%) and in haematology‐oncology units (2.9%). Cryptococcus accounted for the majority of the non‐Candida species in emergency departments (21/24, 87.5%) and outpatient clinics (4/5, 80.0%). Conclusions: Isolation of non‐Candida yeast from blood cultures was not rare, and the frequency varied among medical units and countries. [ABSTRACT FROM AUTHOR]

Perovskite light‐emitting diodes (PeLEDs) can be a promising technology for next‐generation display and lighting applications due to their excellent optoelectronic properties. However, a systematical overview of luminescence and degradation mechanism of perovskite materials and PeLEDs is lacking. Therefore, it is crucial to fully understand these mechanisms and further improve device performances. In this work, the fundamental photophysical processes of perovskite materials, electroluminescence mechanism of PeLEDs including carrier kinetics and efficiency roll‐off as well as device degradation mechanism are discussed in detail. In addition, the strategies to improve device performances are summarized, including optimization of photoluminescence quantum yield, charge injection and recombination, and light outcoupling efficiency. It is hoped that this work can provide guidance for future development of PeLEDs and ultimately realize industrial applications. [ABSTRACT FROM AUTHOR]

Diverse nanoparticles have been widely applied in different fields, including industries and biomedical sciences. Recent developments in nanotechnology have broadened the potential applications of nanotechnology in clinical diagnosis and medical therapy of malignant and non-malignant diseases. Gold nanoparticles (AuNPs) have been reported to possess unique physico-chemical properties; they have been investigated in studies on tumor growth and metastasis. Here, we explored the possible pharmacological functions of AuNPs on the mouse melanoma cell line, B16F10. We demonstrated that AuNPs of sizes 1-3, 3-5, and 10-15 nm exerted dose-dependent cytotoxic effects after 72-h treatments. AuNPs (4 and 10 ppm) of 1-3 and 3-5 nm were more cytotoxic than those of 10-15 nm. However, AuNPs of 1-3 nm were more cytotoxic against benign HaCaT keratinocytes than those of 3-5 nm. Thus, 4 ppm of AuNPs of 3-5 nm was considered relatively safe and an ideal candidate for this study. Further investigations revealed that AuNPs could induce sub-G1 phase accumulation, cleavage of caspase-3 and poly-(ADP-ribose) polymerase, and activation of JNK/p38. The expression of pro-apoptotic protein, Bax, was also induced. Furthermore, platelet-derived growth factor BB-induced migration and motility of melanoma cells were reduced after pretreatment with AuNPs of 3-5 nm. Adhesion assay showed that AuNPs of 3-5 nm could significantly suppress the adhesion of melanoma cells to collagen. In summary, AuNPs of 3-5 nm might be potential anti-tumor agents, as they were selectively cytotoxic against and inhibited motility of melanoma cells. [ABSTRACT FROM AUTHOR]

BiInO3 is a potentially polar oxide with distinct optical properties whose origin could result from a surface that has not been well characterized. The surface properties of BiInO3 thin films have been characterized here by temperature dependent angle-resolved x-ray photoemission spectroscopy. A large surface to bulk core-level binding energy shift for the In 3d5/2 core-level is identified, indicating a surface very different from the bulk. BiInO3 terminates in indium oxide and loses bismuth from the surface of the film at T = 573 K. The Debye–Waller plots suggest effective Debye temperatures of 263 ± 10 and 556 ± 27 K for the surface and bulk components of In 3d core-level, respectively. [ABSTRACT FROM AUTHOR]

Although fosfomycin is a treatment option for infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae, fosfomycin resistance has been documented. To our knowledge, fosfomycin resistance mechanisms in Klebsiella pneumoniae have not been systematically investigated. A total of 108 ESBL-producing K. pneumoniae isolates collected from Kaohsiung Medical University Hospital, Taiwan, from August 2012 to May 2013 were analysed in this study. Pulsed-field gel electrophoresis (PFGE) revealed 64 pulsotypes and six non-typeable isolates, indicating high genetic diversity. Moreover, pulsotypes V ( n  = 6), VII ( n  = 11) and LI ( n  = 4) belonging to ST11 were major types. Among 30 (27.8%) fosfomycin-non-susceptible isolates, 21 (70%) had a MurA amino acid substitution, and seven new variations increased the fosfomycin minimum inhibitory concentration (MIC) by 8- to 16-fold compared with wild-type MurA in Escherichia coli DH5α.strain. Functionless transporters (GlpT and UhpT) with various mutations were found in 29 isolates (97%). No known fosfomycin-modifying enzymes were detected in this study. The major resistance mechanisms to fosfomycin in K. pneumoniae were amino acid variations in the drug target and transporters. [ABSTRACT FROM AUTHOR]

This study aims to examine the properties of the small-diameter vascular grafts that are made by incorporating polyester (PET) yarns and spandex fibers. PET and spandex fibers are warp-knitted or weft-knitted into tubular knits. These two tubular knits are combined with polyvinyl alcohol (PVA) by applying a freezing-thawing method in order to create vascular grafts. The physical properties of vascular grafts are tested by performing tensile tests and a compliance test. The test results indicate that the incorporation of spandex fibers increases the deformation level along the axial direction of the warp-knitted tubular knits. In addition, the vascular grafts that are made of spandex fibers have a greater compliance than that of the commercially available vascular grafts (i.e., ePTFE) and natural blood vessels. [ABSTRACT FROM AUTHOR]

Objective: To assess the benefits of regular exercise in reducing harms associated with betel quid (BQ) chewing. Methods: The study cohort, 419,378 individuals, participated in a medical screening program between 1994 and 2008, with 38,324 male and 1,495 female chewers, who consumed 5–15 quids of BQ a day. Physical activity of each individual, based on “MET-hour/week”, was classified as “inactive” or “active”, where activity started from a daily 15 minutes/day or more of brisk walking (≥3.75 MET-hour/week). Hazard ratios for mortality and remaining years in life expectancy were calculated. Results: Nearly one fifth (18.7%) of men, but only 0.7% of women were chewers. Chewers had a 10-fold increase in oral cancer risk; and a 2-3-fold increase in mortality from lung, esophagus and liver cancer, cardiovascular disease, and diabetes, with doubling of all-cause mortality. More than half of chewers were physically inactive (59%). Physical activity was beneficial for chewers, with a reduction of all-cause mortality by 19%. Inactive chewers had their lifespan shortened by 6.3 years, compared to non-chewers, but being active, chewers improved their health by gaining 2.5 years. The improvement, however, fell short of offsetting the harms from chewing. Conclusions: Chewers had serious health consequences, but being physically active, chewers could mitigate some of these adverse effects, and extend life expectancy by 2.5 years and reduce mortality by one fifth. Encouraging exercise, in addition to quitting chewing, remains the best advice for 1.5 million chewers in Taiwan. [ABSTRACT FROM AUTHOR]

An outbreak of adenovirus has been surveyed in Taiwan in 2011. To better understand the evolution and epidemiology of adenovirus in Taiwan, full-length sequence of hexon and fiber coapsid protein was analyzed using series of phylogenetic and dynamic evolution tools. Six different serotypes were identified in this outbreak and the species B was predominant (HAdV-3, 71.50%; HAdV-7, 15.46%). The most frequent diagnosis was acute tonsillitis (54.59%) and bronchitis (47.83%). Phylogenetic analysis revealed that hexon protein gene sequences were highly conserved for HAdV-3 and HAdV-7 circulation in Taiwan. However, comparison of restriction fragment length polymorphism (RFLP) analysis and phylogenetic trees of fiber gene in HAdV-7 clearly indicated that the predominant genotype in Taiwan has shifted from 7b to 7d. Several positive selection sites were observed in hexon protein. The estimated nucleotide substitution rates of hexon protein of HAdV-3 and HAdV-7 were 0.234×10-3 substitutions/site/year (95% HPD: 0.387~0.095×10-3) and 1.107×10-3 (95% HPD: 0. 541~1.604) respectively; those of the fiber protein of HAdV-3 and HAdV-7 were 1.085×10-3 (95% HPD: 1.767~0.486) and 0.132×10-3 (95% HPD: 0.283~0.014) respectively. Phylodynamic analysis by Bayesian skyline plot (BSP) suggested that using individual gene to evaluate the effective population size might possibly cause miscalculation. In summary, the virus evolution is ongoing, and continuous surveillance of this virus evolution will contribute to the control of the epidemic. [ABSTRACT FROM AUTHOR]

Background: Previous cross-sectional studies suggest that assessments of instrumental activities of daily living (IADLs) may be useful for operationalizing the differences in functional deficits seen in mild cognitive impairment (MCI) and dementia. However, their utility for longitudinal changes in IADLs in the transition between MCI and dementia remains unclear. Methods: We analyzed longitudinal IADL data with the Functional Activities Questionnaire (FAQ) in stable (MCI-S; n = 1,318) or progressive (MCI-P; n = 1,108) MCI patients. Results: Larger increases in FAQ scores were seen in the MCI-P group across a 14.5-month interval, but overlapping distributions in the two groups yielded poorer discriminatory power than prior cross-sectional reports. Conclusion: Our findings emphasize the difficulties in operationalizing the criterion of ‘essentially intact' IADLs in MCI, which may complicate the interpretation of disease progression in MCI treatment trials. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Emotional blunting is a characteristic feature of behavioral variant frontotemporal dementia (bvFTD) and can help discriminate between patients with bvFTD and other forms of younger-onset dementia. Objective: We compared the presence of emotional blunting symptoms in patients with bvFTD and early-onset Alzheimer's disease (AD), and investigated the neuroanatomical associations between emotional blunting and regional brain volume. Methods: Twenty-five individuals with bvFTD (n = 11) and early-onset AD (n = 14) underwent magnetic resonance imaging (MRI) and were rated on symptoms of emotional blunting using the Scale for Emotional Blunting (SEB). The two groups were compared on SEB ratings and MRI-derived brain volume using tensor-based morphometry. Voxel-wise linear regression was performed to determine neuroanatomical correlates of SEB scores. Results: The bvFTD group had significantly higher SEB scores compared to the AD group. On MRI, bvFTD patients had smaller bilateral frontal lobe volume compared to AD patients, while AD patients had smaller bilateral temporal and left parietal volume than bvFTD patients. In bvFTD, SEB ratings were strongly correlated with right anterior temporal volume, while the association between SEB and the right orbitofrontal cortex was non-significant. Conclusions: Symptoms of emotional blunting were more prevalent in bvFTD than early-onset AD patients. These symptoms were particularly associated with right-sided atrophy, with significant involvement of the right anterior temporal region. Based on these findings, the SEB appears to measure symptoms of emotional blunting that are localized to the right anterior temporal lobe. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is a major risk factor for tuberculosis (TB). Evidence has linked the DM-related dysbiosis of gut microbiota to modifiable host immunity to Mycobacterium tuberculosis infection. However, the crosslinks between gut microbiota composition and immunological effects on the development of latent TB infection (LTBI) in DM patients remain uncertain. Methods: We prospectively obtained stool, blood samples, and medical records from 130 patients with poorly-controlled DM (pDM), defined as ever having an HbA1c > 9.0% within previous 1 year. Among them, 43 had LTBI, as determined by QuantiFERON-TB Gold in-Tube assay. The differences in the taxonomic diversity of gut microbiota between LTBI and non-LTBI groups were investigated using 16S ribosomal RNA sequencing, and a predictive algorithm was established using a random forest model. Serum cytokine levels were measured to determine their correlations with gut microbiota. Results: Compared with non-LTBI group, the microbiota in LTBI group displayed a similar alpha-diversity but different beta-diversity, featuring decrease of Prevotella_9, Streptococcus, and Actinomyces and increase of Bacteroides, Alistipes, and Blautia at the genus level. The accuracy was 0.872 for the LTBI prediction model using the aforementioned 6 microbiome-based biomarkers. Compared with the non-LTBI group, the LTBI group had a significantly lower serum levels of IL-17F (p = 0.025) and TNF-α (p = 0.038), which were correlated with the abundance of the aforementioned 6 taxa. Conclusions: The study results suggest that gut microbiome composition maybe associated with host immunity relevant to TB status, and gut microbial signature might be helpful for the diagnosis of LTBI. [ABSTRACT FROM AUTHOR]

• Projecting the voxel myelin index on bundles using tractometry provides biased results when more than one bundle crosses a voxel. • Microstructure informed tractography can deconvolve myelin markers derived from voxel-wise maps on bundles to provide Bundle-specific myelin fractions (BMFs). • Myelin streamline decomposition (MySD) derived values projected on cortex show a pattern in line with literature. • BMFs estimated with MySD are consistent across two different myelin sensitive maps. To date, we have scarce information about the relative myelination level of different fiber bundles in the human brain. Indirect evidence comes from postmortem histology data but histological stainings are unable to follow a specific bundle and determine its intrinsic myelination. In this context, quantitative MRI, and diffusion MRI tractography may offer a viable solution by providing, respectively, voxel-wise myelin sensitive maps and the pathways of the major tracts of the brain. Then, "tractometry" can be used to combine these two pieces of information by averaging tissue features (obtained from any voxel-wise map) along the streamlines recovered with diffusion tractography. Although this method has been widely used in the literature, in cases of voxels containing multiple fiber populations (each with different levels of myelination), tractometry provides biased results because the same value will be attributed to any bundle passing through the voxel. To overcome this bias, we propose a new method - named "myelin streamline decomposition" (MySD) - which extends convex optimization modeling for microstructure informed tractography (COMMIT) allowing the actual value measured by a microstructural map to be deconvolved on each individual streamline, thereby recovering unique bundle-specific myelin fractions (BMFs). We demonstrate the advantage of our method with respect to tractometry in well-studied bundles and compare the cortical projection of the obtained bundle-wise myelin values of both methods. We also prove the stability of our approach across different subjects and different MRI sensitive myelin mapping approaches. This work provides a proof-of-concept of in vivo investigations of entire neuronal pathways that, to date, are not possible. [ABSTRACT FROM AUTHOR]

Utilizing wastewaters as feedstock for microalgal cultivation has the dual benefits of water-saving and low nutrient costs, with simultaneous remediation of pollutants and generation of value-added biochemical products. This study employed two different strategies to treat raw dairy wastewaters with moderate and high chemical oxygen demand (COD) levels. For moderate-COD dairy wastewater, the wastewater was directly utilized as feedstock for algal cultivation, in which the effects of wastewater dilution ratios and algal inoculum sizes were investigated. The results show that the microalga strain used (Chlorella sorokiniana SU-1) was capable of obtaining a high biomass concentration of 3.2 ± 0.1 g/L, accompanied by 86.8 ± 6%, 94.6 ± 3%, and 80.7 ± 1%, removal of COD, total phosphorus (TP) and total nitrogen (TN), respectively. Meanwhile, the obtained microalgal biomass has lipids content of up to 12.0 ± 0.7% at a wastewater dilution ratio of 50% and an inoculum size of 2 g/L. For high-COD dairy wastewater, an integrated process of anaerobic digestion and microalgal phycoremediation was employed, and the effect of inoculum sizes was also studied. The inoculum size of 2 g/L gave highest biomass production of 4.25 ± 0.10 g/L with over 93.0 ± 2.0% removal of COD, TP, and TN. The harvested microalgal biomass has lipids and protein content of 12.5 ± 2.2% and 18.0 ± 2.2%, respectively. The present study demonstrated potential microalgal phycoremediation strategies for the efficient COD removal and nutrients recovery from dairy wastewater of different COD levels with simultaneous production of microalgal biomass which contains valuable components, such as protein and lipids. [Display omitted] • C. sorokiniana SU-1 can treat dairy wastewater with simultaneous biomass production. • High-strength dairy wastewater was treated by combining AD and algal cultivation. • 4.25 g/L biomass concentration and 93% pollutants removal was obtained. • Highest biomass productivity of 0.37 g/L/d was obtained at 1 g/L inoculums size. • The harvested microalgal biomass had 12% lipids and 18% proteins content. [ABSTRACT FROM AUTHOR]

Background: White matter abnormalities have been associated with both behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD). Objective: Using MRI diffusion tensor imaging (DTI) measures, we compared white matter integrity between patients with bvFTD and those with early-onset AD and correlated these biomarkers with behavioral symptoms involving emotional blunting. Methods: We studied 8 bvFTD and 12 AD patients as well as 12 demographically-matched healthy controls (NCs). Using four DTI metrics (fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity), we assessed the frontal lobes (FWM) and genu of the corpus callosum (GWM), which are vulnerable late-myelinating regions, and a contrasting early-myelinating region (splenium of the corpus callosum). The Scale for Emotional Blunting Scale (SEB) was used to assess emotional functioning of the study participants. Results: Compared to AD patients and NCs, the bvFTD subjects exhibited significantly worse FWM and GWM integrity on all four DTI metrics sensitive to myelin and axonal integrity. In contrast, AD patients showed a numerical trend toward worse splenium of the corpus callosum integrity than bvFTD and NC groups. Significant associations between SEB ratings and GWM DTI measures were demonstrated in the combined bvFTD and AD sample. When examined separately, these relationships remained robust for the bvFTD group but not the AD group. Conclusions: The regional DTI alterations suggest that FTD and AD are each associated with a characteristic distribution of white matter degradation. White matter breakdown in late-myelinating regions was associated with symptoms of emotional blunting, particularly within the bvFTD group. [ABSTRACT FROM AUTHOR]

Reliable animal models are invaluable for monitoring the extent of pollution in the aquatic environment. In this study, we demonstrated the potential of huORFZ, a novel transgenic zebrafish line that harbors a human upstream open reading frame of the chop gene fused with GFP reporter, as an animal model for monitoring environmental pollutants and stress-related cellular processes. When huORFZ embryos were kept under normal condition, no leaked GFP signal could be detected. When treated with hazardous chemicals, including heavy metals and endocrine-disrupting chemicals near their sublethal concentrations (LC50), huORFZ embryos exhibited different tissue-specific GFP expression patterns. For further analysis, copper (Cu2+), cadmium (Cd2+) and Chlorpyrifos were applied. Cu2+ triggered GFP responses in skin and muscle, whereas Cd2+ treatment triggered GFP responses in skin, olfactory epithelium and pronephric ducts. Moreover, fluorescence intensity, as exhibited by huORFZ embryos, was dose-dependent. After surviving treated embryos were returned to normal condition, survival rates, as well as TUNEL signals, returned to pretreatment levels with no significant morphological defects observed. Such results indicated the reversibility of treatment conditions used in this study, as long as embryos survived such conditions. Notably, GFP signals decreased along with recovery, suggesting that GFP signaling of huORFZ embryos likely reflected the overall physiological condition of the individual. To examine the performance of the huORFZ line under real-world conditions, we placed huORFZ embryos in different river water samples. We found that the huORFZ embryos correctly detected the presence of various kinds of pollutants. Based on these findings, we concluded that such uORFchop-based system can be integrated into a first-line water alarm system monitoring the discharge of hazardous pollutants. [ABSTRACT FROM AUTHOR]

Background: Emotional blunting is a characteristic feature of behavioral variant frontotemporal dementia (bvFTD) and can help discriminate between patients with bvFTD and other forms of younger-onset dementia.Objective: We compared the presence of emotional blunting symptoms in patients with bvFTD and early-onset Alzheimer's disease (AD), and investigated the neuroanatomical associations between emotional blunting and regional brain volume.Methods: Twenty-five individuals with bvFTD (n = 11) and early-onset AD (n = 14) underwent magnetic resonance imaging (MRI) and were rated on symptoms of emotional blunting using the Scale for Emotional Blunting (SEB). The two groups were compared on SEB ratings and MRI-derived brain volume using tensor-based morphometry. Voxel-wise linear regression was performed to determine neuroanatomical correlates of SEB scores.Results: The bvFTD group had significantly higher SEB scores compared to the AD group. On MRI, bvFTD patients had smaller bilateral frontal lobe volume compared to AD patients, while AD patients had smaller bilateral temporal and left parietal volume than bvFTD patients. In bvFTD, SEB ratings were strongly correlated with right anterior temporal volume, while the association between SEB and the right orbitofrontal cortex was non-significant.Conclusions: Symptoms of emotional blunting were more prevalent in bvFTD than early-onset AD patients. These symptoms were particularly associated with right-sided atrophy, with significant involvement of the right anterior temporal region. Based on these findings, the SEB appears to measure symptoms of emotional blunting that are localized to the right anterior temporal lobe. [ABSTRACT FROM AUTHOR]

Background: White matter abnormalities have been associated with both behavioral variant frontotemporal dementia (bvFTD) and Alzheimer's disease (AD).Objective: Using MRI diffusion tensor imaging (DTI) measures, we compared white matter integrity between patients with bvFTD and those with early-onset AD and correlated these biomarkers with behavioral symptoms involving emotional blunting.Methods: We studied 8 bvFTD and 12 AD patients as well as 12 demographically-matched healthy controls (NCs). Using four DTI metrics (fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity), we assessed the frontal lobes (FWM) and genu of the corpus callosum (GWM), which are vulnerable late-myelinating regions, and a contrasting early-myelinating region (splenium of the corpus callosum). The Scale for Emotional Blunting Scale (SEB) was used to assess emotional functioning of the study participants.Results: Compared to AD patients and NCs, the bvFTD subjects exhibited significantly worse FWM and GWM integrity on all four DTI metrics sensitive to myelin and axonal integrity. In contrast, AD patients showed a numerical trend toward worse splenium of the corpus callosum integrity than bvFTD and NC groups. Significant associations between SEB ratings and GWM DTI measures were demonstrated in the combined bvFTD and AD sample. When examined separately, these relationships remained robust for the bvFTD group but not the AD group.Conclusions: The regional DTI alterations suggest that FTD and AD are each associated with a characteristic distribution of white matter degradation. White matter breakdown in late-myelinating regions was associated with symptoms of emotional blunting, particularly within the bvFTD group. [ABSTRACT FROM AUTHOR]

This study investigates the effects of argument stance on knowledge inquiry skills. Sixty-two participants were assigned to three argument stance conditions (proponent, opponent, or control) to receive scaffolded argumentation practice on two science issues in random order. After the argumentation treatment, participants were asked to write down their own opinions regarding the claim. Their responses were analysed according to argument structure, argument content, methods of refutation, and number of new propositions. Results revealed that taking a proponent's stance increased the use of evidence in argumentation, while taking an opponent's stance enhanced both the use of evidence and alternative-based refutations to the claim, number of falsifications, and number of new propositions. This implies that arguing from an opponent's stance may increase the search for multiple causes behind observed phenomena and the need for evidence, thereby alleviating the confirmation bias in thinking. [ABSTRACT FROM PUBLISHER]

Background: Iron can catalyze damaging free radical reactions. With age, iron accumulates in brain gray matter regions and may contribute to the risk of developing age-related diseases such as Alzheimer's disease (AD). Prior MRI studies demonstrated increased iron deposits in basal ganglia regions; however, the hippocampus (Hipp), which is heavily damaged in AD, and comparator regions that are resistant to AD damage, such as thalamus (Th), have rarely been examined. Objective: To assess iron levels and evidence of tissue damage in Hipp and Th of AD subjects and healthy controls. Methods: Thirty-one AD and sixty-eight healthy control subjects participated in this study. High- and low-field strength MRI instruments were used in combination to quantify iron content of ferritin molecules (ferritin iron) using the field dependent relaxation rate increase (FDRI) method. Decreased transverse relaxation rate (R2) was used as an index of tissue damage. Results: Compared with healthy controls, AD subjects had increased ferritin iron in Hipp (p = 0.019) but not Th (p = 0.637), and significantly decreased R2 in Hipp (p < 0.001) but not Th (p = 0.37). In the entire sample, FDRI and R2 were negatively correlated. Conclusion: The data shows that in AD, Hipp damage occurs in conjunction with ferritin iron accumulation. Prospective studies are needed to evaluate how increasing iron levels may influence the trajectory of tissue damage and cognitive and pathologic manifestations of AD. [ABSTRACT FROM AUTHOR]

The trailing effect of Candida species is a phenomenon characterized by reduced but persistent growth at antifungal concentrations above the MIC. We assessed the impact of trailing growth on the persistence of Candida albicans candidemia in patients receiving fluconazole (FLC) therapy. We retrospectively investigated candidemia isolates at three hospitals in southern Taiwan between 2013 and 2020. Patients treated with FLC for FLC-susceptible C. albicans candidemia were enrolled. The degree of trailing was determined as the average growth above the MIC divided by the measured growth at the lowest drug concentration using the EUCAST method and classified into four categories: residual (0.1–5%), slight (6–10%), moderate (11–15%), and heavy trailers (>15%). Among isolates from 190 patients, the proportions of heavy trailers at 24 hours, 48 hours, and 72 hours were 63.7% (121/190), 63.2% (120/190), and 74.7% (142/190), respectively. Persistent candidemia was observed in 17 (8.9 %) patients. The proportion of persistent C. albicans candidemia in heavy trailing isolates at 48 hours was higher than in isolates without heavy trailing (13.3% [16/120] vs. 1.4% [1/70], p = 0.007). A multivariate analysis showed that immunosuppression (OR = 7.92; 95% CI: 2.38–26.39, p = 0.001), hospitalization days after the index date of C. albicans identification (OR = 1.03; 95% CI: 1.01–1.05, p = 0.011), and heavy trailing isolates at 48 hours (OR = 10.04; 95% CI: 1.27–79.88, p = 0.029) were independent factors for persistent candidemia. The current study revealed that heavy trailing in C. albicans isolates is associated with persistent candidemia in patients receiving FLC treatment. [ABSTRACT FROM AUTHOR]

Background Real-world experience with combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor–containing antiretroviral therapy (ART) in management of latent tuberculous infection (LTBI) is limited among people with human immunodeficiency virus (PWH). Methods From August 2019 to October 2022, PWH receiving 3 months of weekly rifapentine plus isoniazid (3HP) or 1 month of daily rifapentine plus isoniazid (1HP) in combination with ART were included. The primary outcome was virologic response within 12 months after LTBI treatment; secondary outcomes included treatment completion rate and safety of LTBI regimens. Results During the study period, 479 PWH (94.6% male; median age, 43 years) were included: 142 received 1HP and bictegravir (BIC)-containing regimens (1HP/BIC group), 46 1HP and dolutegravir (DTG)-containing regimens (1HP/DTG group), 38 3HP and BIC-containing regimens (3HP/BIC group), 214 3HP and DTG-containing regimens (3HP/DTG group), 17 1HP and other ART regimens (1HP/others group), and 22 3HP/other ART regimens (3HP/others group). In the intention-to-treat analysis, the proportions of PWH maintaining plasma HIV-1 RNA <200 copies/mL within 12 months after LTBI treatment completion were 96.5% (1HP/BIC), 100% (1HP/DTG), 100% (3HP/BIC), 95.8% (3HP/DTG), 100% (1HP/others), and 100% (3HP/others). The overall completion rates were >80% for all treatment groups, whereas >50% of the included PWH experienced any adverse event. LTBI regimens and ART combinations were not associated with virologic response and completion rate. Conclusions Combinations of short-course rifapentine-based regimens and integrase strand-transfer inhibitor-containing ART maintained viral suppression for most PWH within 12 months of LTBI treatment completion with low rates of grade 3 or higher adverse events. [ABSTRACT FROM AUTHOR]

Objectives: Neuropathological studies have shown that multiple sclerosis (MS) lesions are heterogeneous in terms of myelin/axon damage and repair as well as iron content. However, it remains a challenge to identify specific chronic lesion types, especially remyelinated lesions, in vivo in patients with MS.Methods: We performed 3 studies: (1) a cross-sectional study in a prospective cohort of 115 patients with MS and 76 healthy controls, who underwent 3 T magnetic resonance imaging (MRI) for quantitative susceptibility mapping (QSM), myelin water fraction (MWF), and neurite density index (NDI) maps. White matter (WM) lesions in QSM were classified into 5 QSM lesion types (iso-intense, hypo-intense, hyperintense, lesions with hypo-intense rims, and lesions with paramagnetic rim legions [PRLs]); (2) a longitudinal study of 40 patients with MS to study the evolution of lesions over 2 years; (3) a postmortem histopathology-QSM validation study in 3 brains of patients with MS to assess the accuracy of QSM classification to identify neuropathological lesion types in 63 WM lesions.Results: At baseline, hypo- and isointense lesions showed higher mean MWF and NDI values compared to other QSM lesion types (p < 0.0001). Further, at 2-year follow-up, hypo-/iso-intense lesions showed an increase in MWF. Postmortem analyses revealed that QSM highly accurately identifies (1) fully remyelinated areas as hypo-/iso-intense (sensitivity = 88.89% and specificity = 100%), (2) chronic inactive lesions as hyperintense (sensitivity = 71.43% and specificity = 92.00%), and (3) chronic active/smoldering lesions as PRLs (sensitivity = 92.86% and specificity = 86.36%).Interpretation: These results provide the first evidence that it is possible to distinguish chronic MS lesions in a clinical setting, hereby supporting with new biomarkers to develop and assess remyelinating treatments. ANN NEUROL 2022;92:486-502. [ABSTRACT FROM AUTHOR]

Abstract: Molecular identification of mycobacteria in positive Mycobacteria Growth Indicator Tube (MGIT) cultures can accelerate mycobacterial diagnosis. A membrane hybridization array (Blue Point) was evaluated for this purpose in 284 positive MGIT cultures. Discrepant results were resolved by testing with the GenoType Mycobacterium kit, TBc ID test, sequencing of the 16S rRNA gene and internal transcribed spacer. Total recovery from culture and the array (if confirmed) was considered 100%. The sensitivity, specificity, positive, and negative predictive values of the array for detection of Mycobacterium tuberculosis complex were 99.4%, 100%, 100%, and 99.2%, respectively, while the corresponding values of culture were 95.1%, 100%, 100%, and 93.8%, respectively, with significant differences in sensitivity and negative predictive value being found between the 2 methods. The recoveries of nontuberculous mycobacteria and mixed cultures of the array were also significantly higher than those of culture. The array can be adopted in routine mycobacteriology laboratory. [Copyright &y& Elsevier]

Abstract: Differences between the left and right sides of the brain are present in many animal species. For instance, in humans the left cerebral hemisphere is largely responsible for language and tool use and the right for processing spatial information. Zebrafish have prominent left–right asymmetries in their epithalamus that have been associated with differential left and right eye use and navigational behavior. In wild-type (WT) zebrafish embryos, Nodal pathway genes are expressed in the left side of the pineal anlage. Shortly thereafter, a parapineal organ forms to the left of the pineal. The parapineal organ causes differences in gene expression, neuropil density, and connectivity of the left and right habenula nuclei. In embryos that have an open neural tube, such as embryos that are deficient in Nodal signaling or the cell adhesion protein N-cadherin, the left and right sides of the developing epithalamus remain separated from one another. We find that the brains of these embryos often become left isomerized: both sides of the brain develop morphology and gene expression patterns that are characteristic of the left side. However, other aspects of epithalamic development, such as differentiation of specific neuronal cell types, are intact. We propose that there is a mechanism in embryos with closed neural tubes that prevents both sides from developing like the left side. This mechanism fails when the two sides of the epithalamus are widely separated from one another, suggesting that it is dependent upon a signaling protein with limited range. [Copyright &y& Elsevier]

Abstract: Background: To assess the hypothesis that in a sample of very healthy elderly men selected to minimize risk for Alzheimer’s disease (AD) and cerebrovascular disease, myelin breakdown in late-myelinating regions mediates age-related slowing in cognitive processing speed (CPS). Materials and methods: The prefrontal lobe white matter and the genu of the corpus callosum myelinate later in brain development (late-myelinating white matter; LMWM) and are more vulnerable to breakdown due to the effects of normal aging. An in vivo MRI biomarker of myelin integrity (transverse relaxation rates; R 2) of LMWM was obtained for 38 very healthy elderly adult men (mean age=66.3years; SD=6.0; range=55–76). To evaluate regional specificity, we also assessed a contrasting early-myelinating region (splenium of the corpus callosum; SWM), which primarily contains axons involved in visual processing. CPS was assessed using the Trail Making Test. Results: LMWM R 2 and CPS measures were significantly correlated (r =.515, p =.0009), but no significant association between R 2 and CPS was detected in the splenium (p =.409). LMWM R 2, but not SWM R 2, was a significant mediator of the relationship between age and CPS (p =.037). Conclusions: In this very healthy elderly sample, age-related slowing in CPS is mediated by myelin breakdown in highly vulnerable late-myelinating regions but not in the splenium. [Copyright &y& Elsevier]

Background Mutations in the presenilin (PSEN1, PSEN2) and amyloid precursor protein (APP) genes cause familial Alzheimer's disease (FAD) in a nearly fully penetrant, autosomal dominant manner, providing a unique opportunity to study presymptomatic individuals who can be predicted to develop Alzheimer's disease (AD) with essentially 100% certainty. Using tensor-based morphometry (TBM), we examined brain volume differences between presymptomatic and symptomatic FAD mutation carriers and non-carrier (NC) relatives. Methods Twenty-five mutation carriers and 10 NC relatives underwent brain MRI and clinical assessment. Four mutation carriers had dementia (MUT-Dem), 12 had amnestic mild cognitive impairment (MUT-aMCI) and nine were cognitively normal (MUT-Norm). TBM brain volume maps of MUT-Norm, MUT-aMCI and MUT-Dem subjects were compared to NC subjects. Results MUT-Norm subjects exhibited significantly smaller volumes in the thalamus, caudate and putamen. MUT-aMCI subjects had smaller volumes in the thalamus, splenium and pons, but not in the caudate or putamen. MUT-Dem subjects demonstrated smaller volumes in temporal, parietal and left frontal regions. As non-demented carriers approached the expected age of dementia diagnosis, this was associated with larger ventricular and caudate volumes and a trend towards smaller temporal lobe volume. Conclusions Cognitively intact FAD mutation carriers had lower thalamic, caudate and putamen volumes, and we found preliminary evidence for increasing caudate size during the predementia stage. These regions may be affected earliest during prodromal stages of FAD, while cortical atrophy may occur in later stages, when carriers show cognitive deficits. Further studies of this population will help us understand the progression of neurobiological changes in AD. [ABSTRACT FROM AUTHOR]

Background/Aims: The clinical syndromes of frontotemporal lobar degeneration include behavioral variant frontotemporal dementia (bvFTD) and semantic (SV-PPA) and nonfluent variants (NF-PPA) of primary progressive aphasia. Using magnetic resonance imaging (MRI), tensor-based morphometry (TBM) was used to determine distinct patterns of atrophy between these three clinical groups. Methods: Twenty-seven participants diagnosed with bvFTD, 16 with SV-PPA, and 19 with NF-PPA received baseline and follow-up MRI scans approximately 1 year apart. TBM was used to create three-dimensional Jacobian maps of local brain atrophy rates for individual subjects. Results: Regional analyses were performed on the three-dimensional maps and direct comparisons between groups (corrected for multiple comparisons using permutation tests) revealed significantly greater frontal lobe and frontal white matter atrophy in the bvFTD relative to the SV-PPA group (p < 0.005). The SV-PPA subjects exhibited significantly greater atrophy than the bvFTD in the fusiform gyrus (p = 0.007). The NF-PPA group showed significantly more atrophy in the parietal lobes relative to both bvFTD and SV-PPA groups (p < 0.05). Percent volume change in ventromedial prefrontal cortex was significantly associated with baseline behavioral symptomatology. Conclusion: The bvFTD, SV-PPA, and NF-PPA groups displayed distinct patterns of progressive atrophy over a 1-year period that correspond well to the behavioral disturbances characteristic of the clinical syndromes. More specifically, the bvFTD group showed significant white matter contraction and presence of behavioral symptoms at baseline predicted significant volume loss of the ventromedial prefrontal cortex. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]