Risk Factors and Incidence Rates of Self-Reported Short-Term Adverse Events of COVID-19 Vaccine Booster Dose.

With the spread of the new SARS-CoV-2 variants, many countries have begun COVID-19 vaccine booster programs with the mix-and-match strategy. However, research on the adverse events (AE) of booster doses is still scarce. The aim of our study was to analyze the reported incidence rate (IR), and factors associated with AE, including short-term serious adverse events (SAE) and short-term non-serious adverse events (NSAE), among different vaccine products through the hospital-based Vaccine Adverse Event Reporting System (VAERS). A total of 7432 records were collected during the three-month study period. While more than half of the responses (52.2%) reported the presence of AE after receiving a booster dose, only a few AE were considered SAE (2.4%). AE were significantly higher among women and people of younger age, and the brand of vaccines is the strongest factor associated with post-booster dose AE. The incidence of AE in mRNA1273 is higher than in BNT162b2 and MVC-COV1901 (IRR mRNA1273 vs. BNT162b2: 1.22, 95% CI: 1.11-1.34; BNT162b2 vs. MVC-COV1901: 2.77, 95% CI: 2.27-3.39). The IR of different groups were calculated to support the decision making of the booster vaccine. Although AE were not uncommon for booster vaccines, almost all AE were not serious and predictable using estimated IR. This result can be used to optimize booster vaccine decision making.

The effect of facial expression intensity on emotion recognition and psychosocial performance in patients with frontal or temporal lobe epilepsy.

PURPOSE: No studies have examined the relationship between the intensity of facial emotion expression and theory of mind (ToM) ability in people with epilepsy. This study aimed to explore facial emotion recognition in a group of patients with frontal (FLE) or temporal lobe epilepsy (TLE) and its relationship with the intensities of perceived facial emotion expressions, ToM, and social functioning. METHODS: Twenty-six patients with FLE or TLE and 30 matched controls were included in the study. All participants completed the facial emotion recognition test, Faux Pas Recognition (FPR) test measuring advanced ToM, Symptom Checklist-90-Revised, Social and Occupational Functioning Scale for Epilepsy (SOFSE), and background neuropsychological tests. RESULTS: The patient group was significantly worse than the control group in recognizing facial expressions of negative emotions, particularly for medium-intensity facial expression of fear. There was no significant difference between the groups in recognizing high-intensity fear facial expressions. The scores of FPR (overall and affective ToMs) in the patient group were significantly lower than those in the control group. Additionally, the facial emotion recognition was significantly associated with the total score of FPR, and the FPR total score remarkably correlated with the Communication subscale score of the SOFSE. CONCLUSIONS: Patients with FLE or TLE had impaired ability to recognize medium-intensity facial expressions of fear. Moreover, patients' ToM deficit significantly correlated not only with their emotion recognition problem but also with their social-communicative competence. Nevertheless, we also found that increasing the intensity of expression can improve the accuracy of emotion recognition in patients with epilepsy. These findings may provide considerations for further longitudinal studies and interventions on the social difficulties of people with epilepsy.

Personalized and Self-Management: Systematic Search and Evaluation Quality Factors and User Preference of Drug Reference Apps in Taiwan.

BACKGROUND: Drug reference apps promote self-management and improve the efficiency and quality of work for physicians, nurses, pharmacists, and patients. This study aimed to describe a systematic and stepwise process to identify drug reference apps in Taiwan, assess the quality of these apps, and analyze the influential factors for user ratings. METHODS: A two-step algorithm (KESS) consisting of keyword growing and systematic search was proposed. Seven independent reviewers were trained to evaluate these apps using Mobile App Rating Scale (MARS). A logistic regression model was fitted and average marginal effects (AME) were calculated to identify the effects of factors for higher user ratings. RESULTS: A total of 23 drug reference apps in Taiwan were identified and analyzed. Generally, these drug reference apps were evaluated as acceptable quality with an average MARS score of 3.23. Higher user engagement, more functionality, better aesthetics, and more information associated with higher user ratings. Navigation is the most influential factor on higher user ratings (AME: 13.15%) followed by performance (AME: 11.03%), visual appeal (AME: 10.87%), credibility (AME: 10.67%), and quantity of information (AME: 10.42%). CONCLUSIONS: User experience and information clearly affect user ratings of drug reference apps. Five key factors should be considered when designing drug reference apps.

Higher Periwound Temperature Associated with Wound Healing of Pressure Ulcers Detected by Infrared Thermography.

Visual and empirical assessments do not enable the early detection of wound deterioration or necroses. No suitable objective indicator for predicting poor wound-healing is currently available. We used infrared thermography to determine the association between wound temperature and pressure-wound healing. We examined patients with grades 2-4 pressure ulcers from a medical center in southern Taiwan and recorded the temperatures of the wound bed, periwound, and normal skin using infrared thermographic cameras. A total of 50 pressure ulcers and 248 infrared-thermography temperature records were analyzed. Normal skin temperature was not related to pressure ulcer wound healing. In a multivariate analysis, higher malnutrition universal-screening-tool scores were associated with poor wound-healing (p = 0.020), and higher periwound-temperature values were associated with better wound-healing (p = 0.028). In patients who had higher periwound-skin temperature than that of the wound bed, that result was also associated with better wound-healing (p = 0.002). Wound-bed and periwound temperatures differed significantly with the grade of the pressure ulcer, and a high periwound temperature was positively correlated with wound healing. Infrared thermography can objectively serve as indicators for assessing pressure-ulcer healing.

LACE Score-Based Risk Management Tool for Long-Term Home Care Patients: A Proof-of-Concept Study in Taiwan.

BACKGROUND: Effectively predicting and reducing readmission in long-term home care (LTHC) is challenging. We proposed, validated, and evaluated a risk management tool that stratifies LTHC patients by LACE predictive score for readmission risk, which can further help home care providers intervene with individualized preventive plans. METHOD: A before-and-after study was conducted by a LTHC unit in Taiwan. Patients with acute hospitalization within 30 days after discharge in the unit were enrolled as two cohorts (Pre-Implement cohort in 2017 and Post-Implement cohort in 2019). LACE score performance was evaluated by calibration and discrimination (AUC, area under receiver operator characteristic (ROC) curve). The clinical utility was evaluated by negative predictive value (NPV). RESULTS: There were 48 patients with 87 acute hospitalizations in Pre-Implement cohort, and 132 patients with 179 hospitalizations in Post-Implement cohort. These LTHC patients were of older age, mostly intubated, and had more comorbidities. There was a significant reduction in readmission rate by 44.7% (readmission rate 25.3% vs. 14.0% in both cohorts). Although LACE score predictive model still has room for improvement (AUC = 0.598), it showed the potential as a useful screening tool (NPV, 87.9%; 95% C.I., 74.2-94.8). The reduction effect is more pronounced in infection-related readmission. CONCLUSION: As real-world evidence, LACE score-based risk management tool significantly reduced readmission by 44.7% in this LTHC unit. Larger scale studies involving multiple homecare units are needed to assess the generalizability of this study.

Branched I antigen regulated cell susceptibility against natural killer cytotoxicity through its N-linked glycosylation and overall expression.

Cell surface glycosylation has been known as an important modification process that can be targeted and manipulated by malignant cells to escape from host immunosurveillance. We previously showed that the blood group branched I antigen on the leukemia cell surface can regulate the cell susceptibility against natural killer (NK) cell-mediated cytotoxicity through interfering target-NK interaction. In this work, we first identified N-linkage as the major glycosylation linkage type for branched I glycan formation on leukemia cells, and this linkage was responsible for cell sensitivity against therapeutic NK-92MI targeting. Secondly, by examining different leukemia cell surface death receptors, we showed death receptor Fas had highest expressions in both Raji and TF-1a cells. Mutations on two Fas extracellular N-linkage sites (118 and 136) for glycosylation impaired activation of Fas-mediated apoptosis during NK-92MI cytotoxicity. Last, we found that the surface I antigen expression levels enable leukemia cells to respond differently against NK-92MI targeting. In low I antigen expressing K-562 cell, reduction of I antigen presence greatly reduced leukemia cell susceptibility against NK-92MI targeting. But in other high I antigen expressing leukemia cells, similar reduction in I antigen expression did not affect cell susceptibility.

DNA methylation-mediated Siglec-7 regulation in natural killer cells via two 5' promoter CpG sites.

First discovered on the natural killer (NK) cell, the cell surface inhibitory receptor sialic acid-binding immunoglobulin-like lectin-7 (Siglec-7) is known for regulating many important biological activities. However, the detail regulatory mechanism for Siglec-7 expression in NK cells currently remains unclear. In this study, we aimed to investigate how cell surface Siglec-7 expression is regulated and found that, in both NK cell lines and peripheral NK cells, transcription was the main regulatory step. Furthermore, when NK-92MI and peripheral NK cells were treated with DNA methyltransferase (DNMT) inhibitor, the CpG island, with 9 CpG sites, in 5' Siglec-7 promoter became noticeably hypomethylated, and Siglec-7 expression increased in both RNA transcript and surface protein. Within this CpG island, we identified both CpG 8 and CpG 9 as two key regulators responsible for Siglec-7 expression. Additionally, by using histone deacetylases (HDAC) inhibitor, butyric acid, we showed that Siglec-7 expression was also subjected to the histone modification. And a combined treatment with both 5-azacytidine and butyric acid showed an additive effect on Siglec-7 transcript expression in peripheral NK cells.

TGF-ß regulated leukemia cell susceptibility against NK targeting through the down-regulation of the CD48 expression.

Transforming growth factor-ß (TGF-ß) is known to function as a dual role regulatory cytokine for being either a suppresser or promoter during tumor initiation and progression. In solid tumors, TGF-ß secreted from tumor microenvironment acts as a suppresser against host immunity, like natural killer (NK) cells, to favor tumor evasion. However, besides solid tumors, the underlying mechanism of how TGF-ß regulates leukemogenesis, tumor progression, immunoediting, and NK function is still not clear in detail. In this study, we found that TGF-ß induced leukemia MEG-01 and U937 cells to become less sensitive to NK-92MI targeting by down-regulating CD48, a ligand for NK activating receptor 2B4, but not down-regulating other tumor-associated carbohydrate antigens (TACAs). In CD48-knockdown cells, cells responding to NK-92MI targeting displayed a phenotype of less NK susceptibility and cell conjugation. On the other hand, when NK cells were treated with TGF-ß, TGF-ß suppressed NK recognition, degranulation, and killing activity in time-dependent manner by regulating ICAM-1 binding capacity instead of affecting expressions of activating and inhibitory receptors. Taken together, both leukemia cells and immune NK cells could be regulated by TGF-ß through suppressing leukemia cell surface CD48 to escape from host surveillance and down-regulating NK cell surface ICAM-1 binding activity to impair NK functions, respectively. Our results suggested that TGF-ß had effect in leukemia similar to that observed in solid tumors but through different regulatory mechanism.

A Developed NK-92MI Cell Line with Siglec-7neg Phenotype Exhibits High and Sustainable Cytotoxicity against Leukemia Cells.

Altered sialic acid processing that leads to upregulation of cell surface sialylation is recognized as a key change in malignant tissue glycosylation. This cancer-associated hypersialylation directly impacts the signaling interactions between tumor cells and their surrounding microenvironment, especially the interactions mediated by immune cell surface sialic acid-binding immunoglobulin-like lectins (Siglecs) to relay inhibitory signals for cytotoxicity. First, we obtained a Siglec-7neg NK-92MI cell line, NK-92MI-S7N, by separating a group of Siglec-7neg cell population from an eight-month-long-term NK-92MI in vitro culture by fluorescence-activated cell sorting (FACS). The effect of Siglec-7 loss on NK-92MI-S7N cells was characterized by the cell morphology, proliferation, and cytotoxic activity via FACS, MTS assay, cytotoxic assay, and natural killer (NK) degranulation assay. We found the expression levels of Siglec-7 in NK-92MI were negatively correlated with NK cytotoxicity against leukemia cells. This NK-92MI-S7N cell not only shared very similar phenotypes with its parental cells but also possessed a high and sustainable killing activity. Furthermore, this Siglec-7neg NK line was unexpectedly capable of eliminating a NK-92MI-resistant leukemia cell, THP-1, through enhancing the effector-target interaction. In this study, a NK cell line with high and sustainable cytotoxicity was established and this cell may provide a potential application in NK-based treatment for leukemia patients.

A thermal sensor and switch based on a plasma polymer/ZnO suspended nanobelt bimorph structure.

The combination of design and subsequent fabrication of organic/inorganic nanostructures creates an effective way to combine the favorable traits of both to achieve a desired device performance. We demonstrate a miniature electrical read-out, and a sensitive temperature sensor/switch, based on a ZnO nanobelt/plasma-polymerized benzonitrile bimorph structure. A new read-out technique based on the change in the electric current flowing through the bimorph and the contact pad has been employed, replacing the conventional cumbersome piezoresistive method or tedious optical alignment. The thermal sensor demonstrated here has great prospects for thermal switching and triggered detection owing to the relative ease in the fabrication of arrays and the direct electrical read-out.

Robust, fluorescent, and nanoscale freestanding conjugated films.

The fabrication of free-standing structures of nanoscale thickness is technically challenging because of the poor mechanical stability of conventional polymers. Conjugated polymers (CP) composed of rod-like chains with much stronger mechanical properties are exploited here for layer-by-layer assembly. We successfully fabricated ultrathin freestanding layer-by-layer conjugated films (under 20 nm thick) which are flexible, easily fabricated, and demonstrated excellent mechanical properties combined with high fluorescence. This unique combination of properties can be considered for new applications such as flexible, lightweight displays and large luminescent panels.

Polymeric nanolayers as actuators for ultrasensitive thermal bimorphs.

Polymeric nanolayers are introduced here as active, thermal-stress mediating structures facilitating extremely sensitive thermal detection based upon the thermomechanical response of a bimaterial polymer-silicon microcantilever. To maximize the bimaterial bending effect, the microcantilever bimorph is composed of stiff polysilicon, with a strongly adhered polymer deposited via plasma-enhanced chemical vapor deposition. The polymer layers with thickness ranging from 20 to 200 nm possess a rapid and pronounced response to temperature fluctuations due to intrinsic sensitive thermal behavior. We show that by taking advantage of the thermal stresses generated by the huge mismatch of material properties in the polymer-silicon bimorph, unprecedented thermal sensitivities can be achieved. In fact, the temperature resolution of our bimaterial microcantilevers approaches 0.2 mK with thermal sensitivity reaching 2 nm/mK; both parameters are more than an order of magnitude better than the current metal-ceramic design. This new hybrid platform overcomes the inherently limited sensitivity of current sensor designs and provides the basis to develop the ultimate uncooled IR microsensor with unsurpassable sensitivity.

In-situ observation of switchable nanoscale topography for y-shaped binary brushes in fluids.

Direct, in-fluid observation of the surface morphology and nanomechanical properties of the mixed brushes composed of Y-shaped binary molecules PS-PAA revealed nanoscale network-like surface topography formed by coexisting stretched soluble PAA arms and collapsed insoluble PS chains in water. Placement of Y-shaped brushes in different fluids resulted in dramatic reorganization ranging from soft repellent layer covered by swollen PS arms in toluene to an adhesive, mixed layer composed of coexisting swollen PAA and collapsed PS arms in water. These binary layers with the overall nanoscale thickness can serve as adaptive nanocoatings with stimuli-responsive properties.

Ultrathin binary grafted polymer layers with switchable morphology.

Polymer surface layers comprised of mixed chains grafted to a functionalized silicon surface with a total layer thickness of only 1-3 nm are shown to exhibit reversible switching of their structure. Carboxylic acid-terminated polystyrene (PS) and poly (butyl acrylate) (PBA) were chemically attached to a silicon surface that was modified with an epoxysilane self-assembled monolayer by a "grafting to" routine. While one-step grafting resulted in large, submicron microstructures, a refined, two-step sequential grafting procedure allowed for extremely small spatial dimensions of PS and PBA domains. By adjusting the grafting parameters, such as concentration of each phase and molecular weight, very finely structured surfaces resulted with roughly 10-nm phase domains and less than 0.5-nm roughness. Combining the glassy PS and the rubbery PBA, we implemented a design approach to fabricate a mixed brush from two immiscible polymers so that switching of the surface nanomechanical properties is possible. Post-grafting hydrolysis converted PBA to poly(acrylic acid) to amplify this switching in surface wettability. Preliminary tribological studies showed a difference in wear behavior of glassy and rubbery surface layers. Such switchable coatings have practical applications as surface modifications of complex nanoscale electronic devices and sensors, which is why we restricted total thickness for potential nanoscale gaps.

Y-shaped amphiphilic brushes with switchable micellar surface structures.

We observed novel nanoscale surface structures of segregated pinned micelles and craterlike micelles formed by grafted Y-shaped molecules and their reversible reorganization in selective solvents. The Y-shaped molecules have two incompatible polymer chains (polystyrene and poly(tert-butyl acrylate)) attached to a functional stemlike segment capable of covalent grafting to a functionalized silicon surface. Postgrafting hydrolysis of poly(tert-butyl acrylate) arms imparts amphiphilicity to the brush. We demonstrated that spatial constraints induced by a chemical junction of two relatively short (6-10 nm) dissimilar arms in such Y-shaped molecules lead to the formation of segregated micellar surface nanostructures in the grafted layer. We proposed a model of these segregated pinned micelles and the corresponding reverse micelles (craterlike structures) featuring different segregation states of hydrophobic polystyrene and hydrophilic poly(acrylic acid) arms. The arms undergo conformational rearrangements in selective solvents in a controlled and reversible fashion. These nanoscale structural reorganizations define adaptive macroscopic wetting surface properties of the amphiphilic Y-shaped brushes. This surface structure and switchable behavior can be considered as a promising way toward the patterning of solid substrates with adaptive nanowells, which could be used for trapping of adsorbing nanoscale objects.