Search

Liquid mobility is ubiquitous in nature, with droplets emerging at all size scales, and artificial surfaces have been designed to mimic such mobility over the past few decades. Meanwhile, millimeter-sized droplets are frequently used for wettability characterization, even with facial mask applications, although these applications have a droplet-size target range that spans from millimeters to aerosols measuring less than a few micrometers. Unlike large droplets, microdroplets can interact sensitively with the fibers they contact with and are prone to evaporation. However, wetting behaviors at the single-microfiber level remain poorly understood. Herein, we characterized the wettability of fibrous layers, which revealed that a multiscale landscape of droplets ranged from the millimeter to the micrometer scale. The contact angle (CA) values of small droplets on pristine fibrous media showed sudden decrements, especially on a single microfiber, owing to the lack of air cushions for the tiny droplets. Moreover, droplets easily adhered to the pristine layer during droplet impact tests and then yielding widespread areas of contamination on the microfibers. To resolve this, we carved nanowalls on the pristine fibers by plasma etching, which effectively suppressed such wetting phenomena. Significantly, the resulting topographies of the microfibers managed the dynamic wettability of droplets at the multiscale, which reduced the probability of contamination with impact droplets and suppressed the wetting transition upon evaporation. These findings for the dynamic wettability of fibrous media will be useful in the fight against infectious droplets.

The increasing advances in thermal radiation regulators have attracted growing interest, particularly in infrared sources, thermal management, and camouflage. Despite many advances in dynamic thermal emitters with great controllability, sustained external energy is required to maintain the desired emission. In this study, we present a polarization-driven thermal emission regulator based on a two-way control: i) phase change and ii) polarization tuning. Based on a conventional, non-volatile phase change material, i . e ., Ge 2 Sb 2 Te 5 (GST), we newly introduce an anisotropic medium for facile emissivity regulation without heat energy consumption. A rigorous coupled-wave analysis method provides design guidelines for finding optimal structural parameters. We utilized a simple glancing angle deposition process which induces tilted self-aligned nanocolumns with anisotropic properties. The fabricated sample shows polarization-sensitive thermal regulation through thermal imaging spectroscopic measurement. Additionally, we manufactured a multispectral visibly/thermally camouflaged patch that identifies encrypted information at a specific polarization state for a proof-of-concept demonstration., Competing Interests: The author declares no competing interests. The author does not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (© 2022 The Author(s).)

Grignard reagents featuring carbanion characteristics are mostly unreactive toward alkyl halides and require a catalyst for the coupling reaction. With the need to prepare p -(CH 2 =CH)C 6 H 4 CH 2 CH 2 CH 2 Cl on a large scale, the coupling reaction of p -(CH 2 =CH)C 6 H 4 MgCl with BrCH 2 CH 2 CH 2 Cl was attempted to screen the catalysts, and CuCN was determined to be the best catalyst affording the desired compound in 80% yield with no formation of Wurtz coupling side product CH 2 =CHC 6 H 4 -C 6 H 4 CH=CH 2 . The p -(CH 2 =CH)C 6 H 4 Cu(CN)MgCl species was proposed as an intermediate based on the X-ray structure of PhCu(CN)Mg(THF) 4 Cl. p -ClC 6 H 4 MgCl did not react with sterically encumbered R 3 SiCl (R = n -Bu or n -octyl). However, the reaction took place with the addition of 3 mol % CuCN catalyst, affording the desired compound p -ClC 6 H 4 SiR 3 . The structures of p -(CH 2 =CH)C 6 H 4 CH 2 CH 2 CH 2 MgCl and p -ClC 6 H 4 MgCl were also elucidated, which existed as an aggregate with MgCl 2 , suggesting that some portion of the Grignard reagents were possibly lost in the coupling reaction due to coprecipitation with the byproduct MgCl 2 . R 3 SiCl (R = n -Bu or n -octyl) was also prepared easily and economically with no formation of R 4 Si when SiCl 4 was reacted with 4 equiv of RMgCl. Using the developed syntheses, [ p -(CH 2 =CH)C 6 H 4 CH 2 CH 2 CH 2 ] 2 Zn and iPrN[P(C 6 H 4 - p -SiR 3 ) 2 ] 2 , which are potentially useful compounds for the production of PS- block -PO- block -PS and 1-octene, respectively, were efficiently synthesized with substantial cost reductions., Competing Interests: The authors declare no competing financial interest., (© 2022 The Authors. Published by American Chemical Society.)

Raman spectroscopy was applied to MAPbCl 3 single crystals in a wide frequency range from 10 to 3500 cm -1 over a broad temperature range from -196 °C to 200 °C including both two structural phase transitions and a thermal degradation range. Low-frequency lattice modes of MAPbCl 3 were revealed for the first time, which showed discontinuous anomalies along with the change in the number of Raman modes at the transition points of -114 °C and -110 °C. Several Raman modes related to the C-N stretching and MA rocking modes in addition to the lattice modes displayed temperature dependences similar to those of MAPbBr 3 in both Raman shifts and half widths, indicating that the MA cation arrangement and H-halide bond interactions behave similarly in both systems during the phase transition. The substantial increase in the half widths of nearly all Raman modes especially suggests that the dynamic disorder caused by the free rotational motions of MA cations induces significant anharmonicity in the lattice and thus, reduces the phonon lifetimes. High-temperature Raman and Brillouin scattering measurements showed that the spectral features changed drastically at ~200 °C where the thermal decomposition of MAPbCl 3 into PbCl 2 began. This result exhibits that combined Raman and Brillouin spectroscopic techniques can be a useful tool in monitoring temperature-induced or temporal changes in lead-based halide perovskite materials.

Tumor heterogeneity plays a critical role in tumor development and response to treatment. In small-cell lung cancer (SCLC), intratumoral heterogeneity is driven in part by the Notch signaling pathway, which reprograms neuroendocrine cancer cells to a less/non-neuroendocrine state. Here we investigated the atypical Notch ligand DLL3 as a biomarker of the neuroendocrine state and a regulator of cell-cell interactions in SCLC. We first built a mathematical model to predict the impact of DLL3 expression on SCLC cell populations. We next tested this model using a single-chain variable fragment (scFv) to track DLL3 expression in vivo and a new mouse model of SCLC with inducible expression of DLL3 in SCLC tumors. We found that high levels of DLL3 promote the expansion of a SCLC cell population with lower expression levels of both neuroendocrine and non-neuroendocrine markers. This work may influence how DLL3-targeting therapies are used in SCLC patients., Competing Interests: J.S. received research funding from StemCentrx/AbbVie for the development of the new Dll3 allele. J.S. has equity in, and is an advisor for, DISCO Pharmaceuticals. The authors declare no other competing interests., (© 2022 The Author(s).)

Bile duct surgeries are conventionally considered to promote bacterial contamination of the surgical field. However, liver transplantation recipients' bile produced by the newly implanted liver graft from healthy living donors may be sterile. We tested bacterial contamination of autologous blood salvaged before and after bile duct anastomosis (BDA) during living donor liver transplantation (LDLT). In 29 patients undergoing LDLT, bacterial culture was performed for four blood samples and one bile sample: two from autologous blood salvaged before BDA (one was nonleukoreduced and another was leukoreduced), two from autologous blood salvaged after BDA (one was nonleukoreduced and another was leukoreduced), and one from bile produced in the newly implanted liver graft. The primary outcome was bacterial contamination. The risk of bacterial contamination was not significantly different between nonleukoreduced autologous blood salvaged before BDA and nonleukoreduced autologous blood salvaged after BDA (44.8% and 31.0%; odds ratio 0.33, 95% confidence interval 0.03-1.86; p = 0.228). No bacteria were found after leukoreduction in all 58 autologous blood samples. All bile samples were negative for bacteria. None of the 29 patients, including 13 patients who received salvaged autologous blood positive for bacteria, developed postoperative bacteremia. We found that bile from the newly implanted liver graft is sterile in LDLT and BDA does not increase the risk of bacterial contamination of salvaged blood, supporting the use of blood salvage during LDLT even after BDA. Leukoreduction converted all autologous blood samples positive for bacteria to negative. The clinical benefit of leukoreduction for salvaged autologous blood on post-LDLT bacteremia needs further research., (© 2022 American Association for the Study of Liver Diseases.)

Objectives: This retrospective study aimed to analyze data on nerve damage in patients who complained of sensory changes after dental implant surgery, the clinical results according to proximity of the implant fixture to the inferior alveolar nerve (IAN) canal, and the factors affecting recovery of sensation., Materials and Methods: The electronic medical records of 64 patients who had experienced sensory change after implant surgery were reviewed. Patients were classified by sex, age, implant installation sites, recovery rate and the distance between the implant fixture and IAN canal on computed tomography (CT). The distance was classified into Group I (D>2 mm), Group II (2 mm≥D>0 mm), and Group III (D≤0 mm)., Results: The 64 patients were included and the mean age was 57.3±7.3 years. Among the 36 patients who visited our clinic more than two times, 21 patients (58.3%) reported improvement in sensation, 13 patients (36.1%) had no change in sensation, and 2 patients (5.6%) reported worsening sensation. In Group II, symptom improvement was achieved in all patients regardless of the removal of the implant fixture. In Group III, 8 patients (40.0%) had reported symptom improvement with removal of the implant fixture, and 2 patients (33.3%) of recovered patients showed improvement without removal. Removal of the implant fixture in Group III did not result in any significant difference in recovery ( P =0.337), although there was a higher possibility of improvement in sensation in removal cases., Conclusion: Clinicians first should consider removing the fixture when it directly invades the IAN canal. However, in cases of sensory change after dental implant surgery where the drill or implant fixture did not invade the IAN canal, other indirect factors such as flap elevation and damage due to anesthesia should be considered as causes of sensory change. Removal of the implant should be considered with caution in these situations.

Splicing factor B subunit 4 (SF3B4), a component of the U2-pre-mRNA spliceosomal complex, contributes to tumorigenesis in several types of tumors. However, the oncogenic potential of SF3B4 in lung cancer has not yet been determined. The in vivo expression profiles of SF3B4 in non-small cell lung cancer (NSCLC) from publicly available data revealed a significant increase in SF3B4 expression in tumor tissues compared to that in normal tissues. The impact of SF3B4 deletion on the growth of NSCLC cells was determined using a siRNA strategy in A549 lung adenocarcinoma cells. SF3B4 silencing resulted in marked retardation of the A549 cell proliferation, accompanied by the accumulation of cells at the G0/G1 phase and increased expression of p27, p21, and p53. Double knockdown of SF3B4 and p53 resulted in the restoration of p21 expression and partial recovery of cell proliferation, indicating that the p53/p21 axis is involved, at least in part, in the SF3B4-mediated regulation of A549 cell proliferation. We also provided ubiquitination factor E4B (UBE4B) is essential for p53 accumulation after SF3B4 depletion based on followings. First, co-immunoprecipitation showed that SF3B4 interacts with UBE4B. Furthermore, UBE4B levels were decreased by SF3B4 depletion. UBE4B depletion, in turn, reproduced the outcome of SF3B4 depletion, including reduction of polyubiquitinated p53 levels, subsequent induction of p53/p21 and p27, and proliferation retardation. Collectively, our findings indicate the important role of SF3B4 in the regulation of A549 cell proliferation through the UBE4B/p53/p21 axis and p27, implicating the therapeutic strategies for NSCLC targeting SF3B4 and UBE4B.

Abnormal formation of solid thrombus inside a blood vessel can cause thrombotic morbidity and mortality. This necessitates early stage diagnosis, which requires quantitative assessment with a small volume, for effective therapy with low risk to unwanted development of various diseases. We propose a micro-ultrasonic diagnosis using an all-optical ultrasound-based spectral sensing (AOUSS) technique for sensitive and quantitative characterization of early stage and whole blood coagulation. The AOUSS technique detects and analyzes minute viscoelastic variations of blood at a micro-ultrasonic spot (<100 μm) defined by laser-generated focused ultrasound (LGFU). This utilizes (1) a uniquely designed optical transducer configuration for frequency-spectral matching and wideband operation (6 dB widths: 7-32 MHz and d.c. ∼ 46 MHz, respectively) and (2) an empirical mode decomposition (EMD)-based signal process particularly adapted to nonstationary LGFU signals backscattered from the spot. An EMD-derived spectral analysis enables one to assess viscoelastic variations during the initiation of fibrin formation, which occurs at a very early stage of blood coagulation (1 min) with high sensitivity (frequency transition per storage modulus increment = 8.81 MHz/MPa). Our results exhibit strong agreement with those obtained by conventional rheometry (Pearson's R > 0.95), which are also confirmed by optical microscopy. The micro-ultrasonic and high-sensitivity detection of AOUSS poses a potential clinical significance, serving as a screening modality to diagnose early stage clot formation (e.g., as an indicator for hypercoagulation of blood) and stages of blood-to-clot transition to check a potential risk for development into thrombotic diseases.

We describe a reliable approach for double nerve transfer of the medial triceps branch and thoracodorsal nerve to the axillary nerve to increase axonal input. We present a review of outcomes for both end-to-end and reverse end-to-side nerve transfer., Methods: A retrospective review of patients who underwent nerve transfer for improvement of shoulder abduction at Harborview Medical Center and Northwestern Memorial Hospital between 2012 and 2021 was conducted. Patients were prospectively contacted to fill out a 30 item Disabilities of the Arm, Shoulder and Hand questionnaire, with an option to upload a video demonstrating active range of motion., Results: Twenty-one patients with 23 affected extremities were included in the final analysis. Fifteen patients completed the prospective arm of the study (71% response rate). Seventy-nine percent of patient limbs achieved a Medical Research Council Motor Scale (MRC-MS) of 4 or greater, and measured shoulder abduction active range of motion (AROM) was 139.2 degrees (range, 29-174 degrees) and 140.9 degrees (range, 60-180 degrees) ( P = 0.95) for end-to-end and reverse end-to-side, respectively. Comparing end-to-end with reverse end-to-side neurorrhaphy, outcomes, including follow-up, mean postoperative MRC-MS, mean change in MRC-MS, Disabilities of the Arm, Shoulder and Hand, abduction AROM, and flexion AROM, were not statistically different., Conclusions: We showed improvements in shoulder abduction with the thoracodorsal nerve, in addition to the medial triceps branch, to increase axonal donation and power the axillary nerve without sacrificing the spinal accessory nerve. Furthermore, we demonstrated improvements with reverse end-to-side coaptation when intraoperative stimulation of the axillary nerve revealed residual function., (Copyright © 2022 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of The American Society of Plastic Surgeons.)

BackgroundCognitive impairment is a common symptom of Parkinson's disease (PD) that increases in risk and severity as the disease progresses. An accurate prediction of the risk of progression from the mild cognitive impairment (MCI) stage to the dementia (PDD) stage is an unmet clinical need.MethodsWe investigated the use of a supervised learning algorithm called the support vector machine (SVM) to retrospectively stratify patients on the basis of brain fluorodeoxyglucose-PET (FDG-PET) scans. Of 43 patients with PD-MCI according to the baseline scan, 23 progressed to PDD within a 5-year period, whereas 20 maintained stable MCI. The baseline scans were used to train a model, which separated patients identified as PDD converters versus those with stable MCI with 95% sensitivity and 91% specificity.ResultsIn an independent validation data set of 19 patients, the AUC was 0.73, with 67% sensitivity and 80% specificity. The SVM model was topographically characterized by hypometabolism in the temporal and parietal lobes and hypermetabolism in the anterior cingulum and putamen and the insular, mesiotemporal, and postcentral gyri. The performance of the SVM model was further tested on 2 additional data sets, which confirmed that the model was also sensitive to later-stage PDD (17 of 19 patients; 89% sensitivity) and dementia with Lewy bodies (DLB) (16 of 17 patients; 94% sensitivity), but not to normal cognition PD (2 of 17 patients). Finally, anti-PD medication status did not change the SVM classification of the other set of 10 patients with PD who were scanned twice, ON and OFF medication.ConclusionsThese results potentially indicate that the proposed FDG-PET-based SVM classifier has utility for providing an accurate prognosis of dementia development in patients with PD-MCI.

Case: A 19-year-old woman presented with bilateral mangled upper extremities after jumping in front of a moving train. After revascularization, osteocutaneous free vascularized fibula flap was performed to reconstruct the right humerus. The left forearm required transradial amputation with acute targeted muscle reinnervation. Finally, staged bilateral bipolar latissimus dorsi functional muscle flaps were performed to restore elbow flexion., Conclusion: Staged orthoplastic reconstruction of the upper extremities is an effective treatment approach for traumatic bone and soft-tissue defects. This patient's recovery demonstrates improved quality of life after severe upper extremity trauma., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B922)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: The impact of nirmatrelvir/ritonavir treatment on shedding of viable virus in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is unclear., Methods: A prospective cohort study evaluating mildly ill COVID-19 patients was conducted. Virologic responses were compared between nirmatrelvir/ritonavir-treatment and supportive care groups. Risk factors and relevant clinical factors for shedding of viable virus were investigated., Results: A total of 80 COVID-19 patients were enrolled and 222 sputum specimens were collected. Ten patients were dropped during follow-up, and 33 patients in the nirmatrelvir/ritonavir and 37 in the supportive care groups were compared. The median age was 67 years, and 67% were male. Clinical characteristics were similar between groups. Viral loads decreased significantly faster in the nirmatrelvir/ritonavir group compared with the supportive care group ( P < 0.001), and the slope was significantly steeper (-2.99 ± 1.54 vs. -1.44 ± 1.52; P < 0.001). The duration of viable virus shedding was not statistically different between groups. In the multivariable analyses evaluating all collected specimens, male gender (OR 2.51, 95% CI 1.25-5.03, P = 0.010), symptom score (OR 1.41, 95% CI 1.07-1.87, P = 0.015), days from symptom onset (OR 0.72, 95% CI 0.59-0.88, P = 0.002), complete vaccination (OR 0.09, 95% CI 0.01-0.87, P = 0.038), and BA.2 subtype (OR 0.49, 95% CI 0.26-0.91, P = 0.025) were independently associated with viable viral shedding, while nirmatrelvir/ritonavir treatment was not., Conclusion: Nirmatrelvir/ritonavir treatment effectively reduced viral loads of SARS-CoV-2 Omicron variants but did not decrease the duration of viable virus shedding., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Kim, Yang, Ko, Lee, Lee, Park, Kim, Shin, Lee, Na, Park, Kim, Lee, Yang, Huh, Cho, Kang, Chung and Peck.)

A facile approach for improving color purity is explored by the introduction of an angle-robust selective absorber (ARSA) into bottlebrush block copolymer (BBCP)-based one-dimensional (1D) photonic crystals (PCs). The BBCPs of poly[(3-(12-( cis -5-norbornene- exo -2,3-dicarboximido)dodecanoylamino)propyl POSS)- block -(norbornene- graft -styrene)], P x ( x = 1-4), with ultrahigh molecular weights ( M n ∼ 2260 kDa) and low dispersities ( D̵ ∼ 1.07) are synthesized by ring-opening metathesis polymerization. The 1D PCs of the lamellar structure are fabricated by self-assembly of the BBCP with different periodicities for full color-generation (blue, green, and red). The optically tailored substrate (i.e., ARSA) is used to modulate the spectral line shape with selective absorption in the near-infrared range. Optical simulation proposes the optimized 1D PC structures on the ARSA, and it provides the reproducibility of the predictable color. The simulated structures are well matched with the experimental results, verifying the enhancement of color saturation even at various incident angles (0-70°).

Optical losses in photovoltaic (PV) systems cause nonradiative recombination or incomplete absorption of incident light, hindering the attainment of high energy conversion efficiency. The surface of the PV cells is encapsulated to not only protect the cell but also control the transmission properties of the incident light to promote maximum conversion. Despite many advances in elaborately designed photonic structures for light harvesting, the complicated process and sophisticated patterning highly diminish the cost-effectiveness and further limit the mass production on a large scale. Here, we propose a robust/comprehensive strategy based on the hybrid disordered photonic structure, implementing multifaceted light harvesting with an affordable/scalable fabrication method. The spatially segmented structures include (i) nanostructures in the active area for antireflection and (ii) microstructures in the inactive edge area for redirecting the incident light into the active area. A lithography-free hybrid disordered structure fabricated by the thermal dewetting method is a facile approach to create a large-area photonic structure with hyperuniformity over the entire area. Based on the experimentally realized nano-/microstructures, we designed a computational model and performed an analytical calculation to confirm the light behavior and performance enhancement. Particularly, the suggested structure is manufactured by the elastomeric stamps method, which is affordable and profitable for mass production. The produced hybrid structure integrated with the multijunction solar cell presented an improved efficiency from 28.0 to 29.6% by 1.06 times.

Objectives: We assessed humoral responses and reactogenicity following the heterologous vaccination compared to the homologous vaccination groups., Methods: We enrolled healthcare workers (HCWs) who were either vaccinated with ChAdOx1 followed by BNT162b2 (heterologous group) or 2 doses of ChAdOx1 (ChAdOx1 group) or BNT162b2 (BNT162b2 group). Immunogenicity was assessed by measuring antibody titers against receptor-binding domain (RBD) of SARS-CoV-2 spike protein in all participants and neutralizing antibody titer in 100 participants per group. Reactogenicity was evaluated by a questionnaire-based survey., Results: We enrolled 499 HCWs (ChAdOx1, n = 199; BNT162b2, n = 200; heterologous ChAdOx1/BNT162b2, n = 100). The geometric mean titer of anti-receptor-binding domain antibody at 14 days after the booster dose was significantly higher in the heterologous group (11 780.55 binding antibody unit (BAU)/mL [95% CI, 10 891.52-12 742.14]) than in the ChAdOx1 (1561.51 [95% CI, 1415.03-1723.15]) or BNT162b2 (2895.90 [95% CI, 2664.01-3147.98]) groups (both p < 0.001). The neutralizing antibody titer of the heterologous group (geometric mean ND 50 , 2367.74 [95% CI, 1970.03-2845.74]) was comparable to that of the BNT162b2 group (2118.63 [95% CI, 1755.88-2556.32]; p > 0.05) but higher than that of the ChAdOx1 group (391.77 [95% CI, 326.16-470.59]; p < 0.001). Compared with those against wild-type SARS-CoV-2, the geometric mean neutralizing antibody titers against the Delta variant at 14 days after the boosting were reduced by 3.0-fold in the heterologous group (geometric mean ND 50 , 872.01 [95% CI, 685.33-1109.54]), 4.0-fold in the BNT162b2 group (337.93 [95% CI, 262.78-434.57]), and 3.2-fold in the ChAdOx1 group (206.61 [95% CI, 144.05-296.34]). The local or systemic reactogenicity after the booster dose in the heterologous group was higher than that of the ChAdOx1 group but comparable to that of the BNT162b2 group., Discussion: Heterologous ChAdOx1 followed by BNT162b2 vaccination with a 12-week interval induced a robust humoral immune response against SARS-CoV-2, including the Delta variant, that was comparable to the homologous BNT162b2 vaccination and stronger than the homologous ChAdOx1 vaccination, with a tolerable reactogenicity profile., (Copyright © 2022 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Interaction between dipoles often emerges intriguing physical phenomena, such as exchange bias in the magnetic heterostructures and magnetoelectric effect in multiferroics, which lead to advances in multifunctional heterostructures. However, the defect-dipole tends to be considered the undesired to deteriorate the electronic functionality. Here, deterministic switching between the ferroelectric and the pinched states by exploiting a new substrate of cubic perovskite, BaZrO 3 is reported, which boosts the square-tensile-strain to BaTiO 3 and promotes four-variants in-plane spontaneous polarization with oxygen vacancy creation. First-principles calculations propose a complex of an oxygen vacancy and two Ti 3+ ions coins a charge-neutral defect-dipole. Cooperative control of the defect-dipole and the spontaneous polarization reveals ternary in-plane polar states characterized by biased/pinched hysteresis loops. Furthermore, it is experimentally demonstrated that three electrically controlled polar-ordering states lead to switchable and nonvolatile dielectric states for application of nondestructive electro-dielectric memory. This discovery opens a new route to develop functional materials via manipulating defect-dipoles and offers a novel platform to advance heteroepitaxy beyond the prevalent perovskite substrates., (© 2022 Wiley-VCH GmbH.)

Introduction: Despite vaccine development, the COVID-19 pandemic is ongoing due to immunity-escaping variants of concern (VOCs). Estimations of vaccine-induced protective immunity against VOCs are essential for setting proper COVID-19 vaccination policy., Methods: We performed plaque-reduction neutralizing tests (PRNTs) using sera from healthcare workers (HCWs) collected from baseline to six months after COVID-19 vaccination and from convalescent COVID-19 patients. The 20.2% of the mean PRNT titer of convalescent sera was used as 50% protective value, and the percentage of HCWs with protective immunity for each week (percent-week) was compared among vaccination groups. A correlation equation was deduced between a PRNT 50% neutralizing dose (ND 50 ) against wild type (WT) SARS-CoV-2 and that of the Delta variant., Results: We conducted PRNTs on 1,287 serum samples from 297 HCWs (99 HCWs who received homologous ChAdOx1 vaccination (ChAd), 99 from HCWs who received homologous BNT162b2 (BNT), and 99 from HCWs who received heterologous ChAd followed by BNT (ChAd-BNT)). Using 365 serum samples from 116 convalescent COVID-19 patients, PRNT ND 50 of 118.25 was derived as 50% protective value. The 6-month cumulative percentage of HCWs with protective immunity against WT SARS-CoV-2 was highest in the BNT group (2297.0 percent-week), followed by the ChAd-BNT (1576.8) and ChAd (1403.0) groups. In the inter-group comparison, protective percentage of the BNT group (median 96.0%, IQR 91.2-99.2%) was comparable to the ChAd-BNT group (median 85.4%, IQR 15.7-100%; P =0.117) and significantly higher than the ChAd group (median 60.1%, IQR 20.0-87.1%; P < 0.001). When Delta PRNT was estimated using the correlation equation, protective immunity at the 6-month waning point was markedly decreased (28.3% for ChAd group, 52.5% for BNT, and 66.7% for ChAd-BNT)., Conclusion: Decreased vaccine-induced protective immunity at the 6-month waning point and lesser response against the Delta variant may explain the Delta-dominated outbreak of late 2021. Follow-up studies for newly-emerging VOCs would also be needed., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Nham, Ko, Song, Choi, Kim, Kim, Kim, Lim, Kim, Jang, Lee, Song, Baek, Ahn, Choi, Kim, Park, Choi, Bae, Kim, Kang, Jeong, Kim, Kwon, Kim and Peck.)

The genus Nephelobotys is newly recorded from Laos and two new species Nephelobotys denticulatus sp. nov. and Nephelobotys forcipatus sp. nov. are newly described. Nephelobotys evenoralis (Walker, 1859) comb. nov., is also newly reported from Korea. Illustrations of adults and genitalia are provided. The differences with related genus Torulisquama Zhang & Li, 2010 are briefly discussed.

Objective: Although endovascular treatment for intracranial aneurysms is considered effective and safe, its durability is still debated. Also, few studies have described angiographic follow-up plan after endovascular treatment of intracranial aneurysm, especially in ruptured cases. Hence, we report the long-term results of follow-up angiography protocol., Methods: Radiological records of 639 cases of coil embolization with ruptured aneurysms from March 2003 to December 2016 were retrospectively reviewed. Patients who received treatment of a saccular aneurysm less than 7 mm resulted with near complete occlusion were included. Two hundred thirty-eight aneuryms which received the follow-up angiography at least once were enrolled. We classified four periods of follow-up as follows : post-treatment 1 year (defined as the first period), from 1 to 2 years (the second period), 2 to 5 years (the third period), and over 5 years (long-term)., Results: We identified 14 cases (6.4%) of recurrence from 218 aneurysms in follow-up angiography in the first period. Among 143 aneurysms in the second period, five cases (3.5%) of recurrence were identified. There were no findings suspicious of recanalization in 97 patients in the third period. Of the total 238 cases, there were 19 recurrences, for a recurrence rate of 8.0%. Six (31.6%) out of 19 recurrences showed a tendency toward repeat recurrences even after additional treatment. Twenty-eight received long-term follow-up over 5 years and there was no recurrence., Conclusion: Most of the recurrence were found during the first and the second year. We suggest that at least one digital subtraction angiography examination may be necessary around post-treatment 2 years, especially in ruptured cases. If the angiographic results are favorable at 2 years post-treatment, long-term result should be favorable.

Transposon-associated transposase B (TnpB) is deemed an ancestral protein for type V, Cas12 family members, and the closest ancestor to UnCas12f1. Previously, we reported a set of engineered guide RNAs supporting high indel efficiency for Cas12f1 in human cells. Here we suggest a new technology whereby the engineered guide RNAs also manifest high-efficiency programmable endonuclease activity for TnpB. We have termed this technology TaRGET (TnpB-augment RNA-based Genome Editing Technology). Having this feature in mind, we established TnpB-based adenine base editors (ABEs). A Tad-Tad mutant (V106W, D108Q) dimer fused to the C terminus of dTnpB (D354A) showed the highest levels of A-to-G conversion. The limited targetable sites for TaRGET-ABE were expanded with engineered variants of TnpB or optimized deaminases. Delivery of TaRGET-ABE also ensured potent A-to-G conversion rates in mammalian genomes. Collectively, the TaRGET-ABE will contribute to improving precise genome-editing tools that can be delivered by adeno-associated viruses, thereby harnessing the development of clustered regularly interspaced short palindromic repeats (CRISPR)-based gene therapy., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Case: Distal radius reconstruction after giant cell tumor (GCT) resection is typically performed with free fibular flaps when a vascularized bone is needed. However, vascularized fibular flaps are contraindicated in patients with peroneal artery variants. We present 2 patients with GCTs of the radius and bilateral peronea arteria magna who underwent resection with wrist fusion using an allograft bone and vascularized free medial femoral condyle periosteal flaps. Both patients had excellent outcomes with minimal postoperative morbidity., Conclusion: Allograft bone with vascularized medial femoral condyle periosteal flaps is an effective option for reconstructing distal radius defects after GCT resection when conventional methods fail., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/B909)., (Copyright © 2022 by The Journal of Bone and Joint Surgery, Incorporated.)

Objectives: Vancomycin and teicoplanin are glycopeptides with activity against Enterococcus faecium. However, studies on the clinical efficacy of teicoplanin are limited. This study aimed to compare the therapeutic efficacy of teicoplanin and vancomycin in E. faecium bacteremia., Methods: We identified patients with bloodstream infections prospectively from July 2015 to December 2016 in 14 hospitals as part of a multicenter nationwide surveillance. Patients with E. faecium monomicrobial bacteremia were selected. Teicoplanin and vancomycin groups included patients treated with either agent for ≥48 hours. The primary outcome was 30-day all-cause in-hospital mortality. The Cox proportional hazards model with inverse probability weighting was used to account for the imbalance in baseline characteristics between the two groups., Results: Among 97 patients with E. faecium bacteremia, 33 (34%) were treated with teicoplanin and 64 (66%) with vancomycin. There were no significant differences in 30-day in-hospital mortality (18.2% vs 26.6%, P = 0.358) and 7-day mortality (6.1% vs 15.6%, P = 0.212). Furthermore, multivariable analysis confirmed that the use of teicoplanin was not significantly associated with mortality (adjusted odds ratio, 0.72; 95% confidence interval, 0.28-1.86; P = 0.494)., Conclusion: We found no significant differences in the clinical outcomes. These findings suggest teicoplanin as a useful alternative to vancomycin., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study aimed to analyze the treatment outcomes and to evaluate the clinicopathological prognostic factors of oral tongue cancer. Patients and., Methods: We retrospectively analyzed treatment results and prognostic factors in 205 patients with oral tongue squamous cell carcinoma who were admitted to the National Cancer Center, South Korea, between January 2001 and December 2020. The patients were treated with surgery and postoperative, definitive radiotherapy (RT) or chemoradiotherapy (CRT)., Results: Eighteen patients (8.8%) were treated with curative RT or CRT, while the rest (91.2%) were treated with surgery with or without postoperative RT or CRT. The median follow-up period was 30 months (range, 0-234 months). The 5-year overall survival (OS) and 5-year disease-free survival (DFS) were 72% and 63%, respectively. Multivariate analysis revealed that a positive neck nodal status (N1, N2-3) was significantly associated with poorer 5-year OS and DFS, while perineural invasion was associated with poorer 5-year DFS., Conclusion: Cervical metastasis and perineural invasion are significant prognostic predictors, and combination treatments are necessary for improving OS and DFS in patients with these factors.

Insulin, the oldest U.S. Food and Drug Administration (FDA)-approved recombinant protein and a World Health Organization (WHO) essential medicine for treating diabetes globally, faces challenges due to its storage instability. One approach to stabilize insulin is the addition of poly(trehalose methacrylate) (pTrMA) as an excipient. The polymer increases the stability of the peptide to heat and mechanical agitation and has a low viscosity suitable for injection and pumps. However, the safety and stabilizing mechanism of pTrMA is not yet known and is required to understand the potential suitability of pTrMA as an insulin excipient. Herein is reported the immune response, biodistribution, and insulin plasma lifetime in mice, as well as investigation into insulin stabilization. pTrMA alone or formulated with ovalbumin did not elicit an antibody response over 3 weeks in mice, and there was no observable cytokine production in response to pTrMA. Micropositron emission tomography/microcomputer tomography of 64 Cu-labeled pTrMA showed excretion of 78-79% ID/cc within 24 h and minimal liver accumulation at 6-8% ID/cc when studied out to 120 h. Further, the plasma lifetime of insulin in mice was not altered by added pTrMA. Formulating insulin with 2 mol equiv of pTrMA improved the stability of insulin to standard storage conditions: 46 weeks at 4 °C yielded 87.0% intact insulin with pTrMA present as compared to 7.8% intact insulin without the polymer. The mechanism by which pTrMA-stabilized insulin was revealed to be a combination of inhibiting deamidation of amino acid residues and preventing fibrillation, followed by aggregation of inactive and immunogenic amyloids all without complexing insulin into its hexameric state, which could delay the onset of insulin activity. Based on the data reported here, we suggest that pTrMA stabilizes insulin as an excipient without adverse effects in vivo and is promising to investigate further for the safe formulation of insulin.

Presepsin is a highly specific biomarker for diagnosing bacterial infections, but its clinical usefulness is not well validated. A retrospective cross-sectional study was conducted. Among the patients suspected bacterial infection or fulfilled the criteria of systemic inflammatory response syndrome (SIRS) and patients who underwent blood culture, presepsin, procalcitonin (PCT), and C-reactive protein (CRP) at the same time were included. Receiver operating characteristic (ROC) curve analysis and logistic regression were used to compare performance of three biomarkers. A total of 757 patients were enrolled, including 256 patients (33.8%) with culture-proven bacterial infection and 109 patients (14.4%) with bacteremia. The 28-day mortality rate was 8.6%. ROC curve analysis revealed that the area under the curve (AUC) of PCT was higher than that of presepsin for both culture-proven bacterial infection (0.665 and 0.596, respectively; p = 0.003) and bacteremia (0.791 and 0.685; p < 0.001). In contrast, AUC of PCT for 28-day mortality was slower than presepsin (0.593 and 0.720; p = 0.002). In multivariable logistic regression analysis, PCT showed the highest ORs for culture-proven bacterial infection (OR 2.23, 95% CI 1.55-3.19; p < 0.001) and for bacteremia (OR 5.18, 95% CI 3.13-8.56; p < 0.001), while presepsin showed the highest OR for 28-day mortality (OR 3.31, 95% CI 1.67-6.54; p < 0.001). CRP did not show better performance than PCT or presepsin in any of the analyses. PCT showed the best performance predicting culture-proven bacterial infection and bacteremia, while presepsin would rather be useful as a prognostic marker., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Park, Yoon, Ki, Ko and Moon.)

To investigate the effect of fucosyltransferase (FUT) 1-mediated fucosylation on meibomian glands (MG), we first confirmed that FUT1 and its fucosylated products were expressed in the eyelid, conjunctiva and skin in wild-type (WT) mice, whereas their mRNA and protein levels were downregulated in Fut1 knock-out (KO) mice. We then evaluated age-dependent changes in the total and acinar areas of MG, meibocyte differentiation, lipid synthesis, and eyelid inflammation and oxidative stress in Fut1 KO and WT mice. Results show that both the total and acinar areas of MG were smaller in Fut1 KO mice than in WT mice in all evaluated age groups. Meibocyte differentiation, lipid-producing capacities and the enzyme levels responsible for lipid synthesis were reduced in Fut1 KO mice, compared to WT controls. The levels of pro-inflammatory cytokines and oxidative-stress-related markers were elevated in the eyelids and MG of FUT1 KO mice. These findings demonstrate the physiologic function of FUT1-mediated fucosylation in MG development and function, and indicate its potential role in ocular surface homeostasis.

A remote-type white light-emitting diode (LED) consisting of a red quantum-dot (QD) film and a yellow phosphor plate was studied by both experiment and optical simulation. The sequence of the two color-conversion films had a substantial effect on the color-rendering properties of the vertically-stacked white LED, and the optimized configuration exhibited a high color rendering index of more than 90 thanks to the enhanced red component via the QD film. For the design of high-power white LED devices of a remote type, it was necessary to locate the color-conversion films below the diffuser plate to remove the substantial color dispersion depending on the viewing angle. The present study shows that high power and high color-rendering white LED devices can be realized in terms of two vertically-stacked color-conversion materials, which would provide long-term stability due to the remote design.

Objective: Obturator nerve injury can occur as a complication of gynecologic surgeries, occurring most frequently in patients with endometriosis and genitourinary malignancies. The resulting injury causes paresthesia and major weakness in adduction and atrophy of the adductor group of lower extremity muscles. The objective of this study was to conduct a systematic review and meta-analysis of the effectiveness of end-to-end repair, nerve grafting, and nerve transfer in improving motor function in patients with obturator nerve injury., Methods: PubMed, Cochrane, Medline, and Embase libraries were searched from May 1994 to August 2020 according to the PRISMA guidelines for articles that present functional outcomes after obturator nerve injury in patients treated with nerve grafting, end-to-end repair, or nerve transfer., Results: A total of 25 patients from 22 studies were included in the study, 15 of whom were treated with end-to-end repair (60%), nine with nerve grafting (36%), and one with nerve transfer (4%). Of the 15 patients with transection data, two had incomplete (13%) and 13 had complete (87%) nerve transections. The patients underwent pelvic lymphadenectomy (n=24) and radical cystectomy (n=1) operations. The mean Medical Research Council (MRC) score was 2.95±1.7 immediately after treatment and 4.77±0.6 at the final follow-up. All patients achieved good outcomes (MRC ≥3) at the final follow-up. The mean MRC score for end-to-end repair (n=15), nerve grafting (n=9), and nerve transfer (n=1) was 4.8±0.6, 4.7±0.8, and 5, respectively. Patients with end-to-end repair had higher immediate post-operative strength than those treated with nerve grafting (p=0.03) and tended to achieve full functional recovery after shorter periods of time (rho=-0.65, p=0.049). Other parameters did not correlate with MRC., Conclusion: End-to-end repair, nerve grafting, and nerve transfer are equally effective in restoring function in patients with obturator nerve injury. However, patients treated with end-to-end repair had higher immediate post-operative strength than those treated with nerve grafting., Competing Interests: Competing interests: JHK is on the Scientific Advisory Board for Mesh Suture Inc and Checkpoint Surgical Inc. He is also a Consultant for Integra Lifesciences Inc and Neuraptive Therapeutics Inc. No disclosures are reported by any of the other authors., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: To find pharmacokinetic/pharmacodynamic parameters of vancomycin associated with the optimal outcome of severe infection due to Enterococcus species., Methods: We retrospectively reviewed enterococcal bacteremia cases treated with vancomycin from January 2015 to December 2020. The primary outcome was 30-day mortality. We calculated cutoff values of the ratio of vancomycin area under the concentration-time curve over 24 h to the minimum inhibitory concentration (AUC 24 /MIC) and trough concentration (C trough ) during the initial 72 h of treatment. The optimal cutoff value was determined using the Youden index. Binary variables created based on these cutoffs were further assessed using multivariable analysis., Results: A total of 65 patients were included. The majority (87.7%) had solid or hematologic malignancies. Thirty-day mortality and nephrotoxicity occurred in nine (13.4%) and 14 (21.5%) patients, respectively. Both vancomycin AUC 24 /MIC and C trough showed fair performance in predicting 30-day mortality (AUC of receiver-operator curve for AUC 24 /MIC, 0.712; 95% confidence interval [CI] 0.539-0.886; AUC for C trough , 0.760; 95% CI 0.627-0.892; pairwise AUC comparison: p = 0.570). C trough  ≥ 13.94 μg/mL, but not AUC 24 /MIC ≥ 504, had a significant association with 30-day mortality after adjusting for confounders (odds ratio, 8.40; 95% CI 1.60-86.62; p = 0.010)., Conclusion: Mean C trough  ≥ 13.94 μg/mL during the initial 72 h was associated with higher 30-day mortality in enterococcal bacteremia. Further studies are warranted to elucidate optimal pharmacokinetic targets for enterococcal bacteremia., (© 2022. The Author(s).)

Poly(styrenyl acetal trehalose) (pSAT), composed of trehalose side chains linked to a polystyrene backbone via acetals, stabilizes a variety of proteins and enzymes against fluctuations in temperature. A promising application of pSAT is conjugation of the polymer to therapeutic proteins to reduce renal clearance. To explore this possibility, the safety of the polymer was first studied. Investigation of acute toxicity of pSAT in mice showed that there were no adverse effects of the polymer at a high (10 mg/kg) concentration. The immune response (antipolymer antibody and cytokine production) in mice was also studied. No significant antipolymer IgG was detected for pSAT, and only a transient and low level of IgM was elicited. pSAT was also safe in terms of cytokine response. The polymer was then conjugated to a granulocyte colony stimulating factor (GCSF), a therapeutic protein that is approved by the Federal Drug Administration, in order to study the biodistribution of a pSAT conjugate. A site-selective, two-step synthesis approach was developed for efficient conjugate preparation for the biodistribution study resulting in 90% conjugation efficiency. The organ distribution of GCSF-pSAT was measured by positron emission tomography and compared to controls GCSF and GCSF-poly(ethylene glycol), which confirmed that the trehalose polymer conjugate improved the in vivo half-life of the protein by reducing renal clearance. These findings suggest that trehalose styrenyl polymers are promising for use in therapeutic protein-polymer conjugates for reduced renal clearance of the biomolecule.

Background: We investigated the trend change in vancomycin-intermediate Staphylococcus aureus (VISA)/heterogeneous VISA (hVISA) prevalence among methicillin-resistant S. aureus (MRSA) bacteremia strains and antistaphylococcal antibiotic use together with mutation studies of vancomycin resistance-related gene loci to evaluate the impact of changes in antibiotic use after new antistaphylococcal antibiotics became available., Methods: Among 850 healthcare-associated MRSA isolates from 2006 to 2019 at a tertiary hospital in South Korea, hVISA/VISA was determined by modified PAP/AUC analysis, and the identified hVISA/VISA strains were genotyped. Gene mutations at vraSR, graSR, walKR, and rpoB were studied by full-length sequencing. Antistaphylococcal antibiotic use in 2005-2018 was analyzed., Results: Two VISA and 23 hVISA strains were identified. The prevalence rate ratio of hVISA/VISA carrying mutations at the two-component regulatory systems among MRSA was 0.668 (95% CI 0.531-0.841; P = 0.001), and the prevalence rate ratio of hVISA/VISA carrying rpoB gene mutations was 1.293 (95% CI 0.981-1.702; 174 P = 0.068). Annual vancomycin use density analyzed by days of therapy (DOT) per 1,000 patient-days did not decrease significantly, however the annual average length of time analyzed by the number of days vancomycin was administered for each case showed a significantly decreasing trend., Conclusions: During the 14-year period when the average length of vancomycin therapy decreased every year with the availability of alternative antibiotics, the prevalence of hVISA/VISA did not decrease significantly. This seems to be because the resistant strains carrying the rpoB mutations increased despite the decrease in the strains carrying the mutations at the two-component regulatory systems., (© 2022. The Author(s).)

Brillouin light scattering experiments were performed for lead zirconate single crystals doped with niobium. Special attention was paid to the elastic mode softening near phase transition temperatures. The results are compared with data obtained by Raman light scattering experiments. We observed that the interaction between acoustic and optic modes is responsible for symmetry breaking far above T C , leading to polar regions' appearance. No changes in the acoustic mode frequency and its damping are observed at T C , where ε(T) exhibits a maximum value. The absence of these changes and the central peak observed in Raman experiments suggest that the phase transition at T C is mainly of the order-disorder type. The origin of other phase transitions is discussed as well., (© 2022. The Author(s).)

With the emergence and rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta and Omicron variants, escaping vaccine-induced immunity is a concern. Three vaccination schedules, homologous or heterologous, have been initially applied due to an insufficient supply of vaccines in Korea. We investigated neutralizing activities against Omicron and Delta variants in each schedule. Three schedules using three doses of the BNT162b2 (BNT) or the ChAdOx1 (ChAd) vaccines include ChAd-ChAd-BNT, ChAd-BNT-BNT, and BNT-BNT-BNT. Neutralizing activities were evaluated using plaque-reduction neutralization test (PRNT) against wild type (WT) SARS-CoV-2, Delta variant, and Omicron variant. A total of 170 sera from 75 participants were tested, and the baseline characteristics of participants were not significantly different between groups. After the 2nd vaccine dose, geometric mean titers of PRNT ND 50 against WT, Delta, and Omicron were highest after ChAd-BNT vaccination (2,463, 1,097, and 107) followed by BNT-BNT (2,364, 674, and 38) and ChAd-ChAd (449, 163, and 25). After the 3rd dose of BNT, the increase of PRNT ND 50 against WT, Delta, and Omicron was most robust in ChAd-ChAd-BNT (4,632, 988, and 260), while the BNT-BNT-BNT group showed the most augmented neutralizing activity against Delta and Omicron variants (2,315 and 628). ChAd-BNT-BNT showed a slight increase of PRNT ND 50 against WT, Delta, and Omicron (2,757, 1,279, and 230) compared to the 2nd dose. The results suggest that a 3rd BNT booster dose induced strengthened neutralizing activity against Delta and Omicron variants. The waning of cross-reactive neutralizing antibodies after the 3rd dose and the need for additional boosting should be further investigated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Choi, Lee, Ko, Kim, Kim, Lee, Jeong, Kim, Jang, Hong, Kim, Lee, Kim, Chung, Lim, Jang, Kim, Kim, Ahn, Choi, Kim, Park, Peck and Kim.)

Inflammation is an indispensable biological process stimulated by infection and injuries. Inflammatory mechanisms related to extracellular vesicles (EVs), which are small membrane structures carrying various molecules, were summarized in this review. Emerging evidence from animal studies has highlighted the role of EVs in modulating inflammatory responses, by transporting various molecules involved in host defense. In this review, we have discussed the role of EV miRNAs in inflammation. Rodent studies associated with extracellular miRNAs in inflammatory diseases, published from 2012 to 2022, were explored from PUBMED, EMBASE, and MEDLINE. A total of 95 studies were reviewed. In summary, EV-associated miRNAs play a key role in various diseases, including organ injury, immune dysfunction, neurological disease, metabolic syndrome, vesicular disease, arthritis, cancer, and other inflammatory diseases. Diverse EV-associated miRNAs regulate inflammasome activation and pro- and anti-inflammatory cytokine levels by targeting genes.

The next frontier of photonics is evolving into reconfigurable platforms with tunable functions to realize the ubiquitous application. The dynamic control of optical properties of photonics is highly desirable for a plethora of applications, including optical communication, dynamic display, self-adaptive photonics, and multi-spectral camouflage. Recently, to meet the dynamic response over broad optical bands, optically active materials have been integrated with the diverse photonic platforms, typically in the dimension of micro/nanometer scales. Here, we review recent advances in tunable photonics with controlling optical properties from visible to terahertz (THz) spectral range. We propose guidelines for designing tunable photonics in conjunction with optically active materials, inherent in wavelength characteristics. In particular, we devote our review to their potential uses for five different applications: structural coloration, metasurface for flat optics, photonic memory, thermal radiation, and terahertz plasmonics. Finally, we conclude with an outlook on the challenges and prospects of tunable photonics., Competing Interests: The author declares no competing interests. The author does not have any commercial or associative interest that represents a conflict of interest in connection with the work submitted., (© 2022 The Author(s).)

Toll-like receptor 4 (TLR4)-mediated changes in macrophages reshape intracellular lipid pools to coordinate an effective innate immune response. Although this has been previously well-studied in different model systems, it remains incompletely understood in primary human macrophages. Here we report time-dependent lipidomic and transcriptomic responses to lipopolysaccharide (LPS) in primary human macrophages from healthy donors. We grouped the variation of ~200 individual lipid species measured by LC-MS/MS into eight temporal clusters. Among all other lipids, glycosphingolipids (glycoSP) and cholesteryl esters (CE) showed a sharp increase during the resolution phase (between 8h or 16h post LPS). GlycoSP, belonging to the globoside family (Gb3 and Gb4), showed the greatest inter-individual variability among all lipids quantified. Integrative network analysis between GlycoSP/CE levels and genome-wide transcripts, identified Gb4 d18:1/16:0 and CE 20:4 association with subnetworks enriched for T cell receptor signaling ( PDCD1 , CD86 , PTPRC , CD247 , IFNG ) and DC-SIGN signaling ( RAF1 , CD209 ), respectively. Our findings reveal Gb3 and Gb4 globosides as sphingolipids associated with the resolution phase of inflammatory response in human macrophages., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Muralidharan, Torta, Lin, Olona, Bagnati, Moreno-Moral, Ko, Ji, Burla, Wenk, Rodrigues, Petretto and Behmoaras.)

Type 2 diabetes (T2D) has long been regarded as an incurable and chronic disease according to conventional management methods. Clinical and pathophysiological studies on the natural course of T2D have shown that blood glucose control worsens with an increase in the number of required anti-hyperglycemic agents, as β-cell function progressively declines over time. However, recent studies have shown remission of T2D after metabolic surgery, intensive lifestyle modification, or medications, raising the possibility that β-cell function may be preserved or the decline in β-cell function may even be reversible. The World Health Organization as well as the American Diabetes Association and the European Association for the Study of Diabetes recognize remission as an appropriate management aim. In the light of the state of evidence for T2D reversal, physicians need to be educated on treatment options to achieve T2D remission so that they can actively play a part in counseling patients who may wish to explore these approaches to their disease. This review will introduce each of these approaches, summarizing their beneficial effects, supporting evidence, degree of sustainability, and challenges to be addressed in the future.

Unlike herbaceous plants, woody plants undergo volumetric growth (a.k.a. secondary growth) through wood formation, during which the secondary xylem (i.e., wood) differentiates from the vascular cambium. Wood is the most abundant biomass on Earth and, by absorbing atmospheric carbon dioxide, functions as one of the largest carbon sinks. As a sustainable and eco-friendly energy source, lignocellulosic biomass can help address environmental pollution and the global climate crisis. Studies of Arabidopsis and poplar as model plants using various emerging research tools show that the formation and proliferation of the vascular cambium and the differentiation of xylem cells require the modulation of multiple signals, including plant hormones, transcription factors, and signaling peptides. In this review, we summarize the latest knowledge on the molecular mechanism of wood formation, one of the most important biological processes on Earth.

Lead zirconate PbZrO 3 has been the subject of research interest for several dozen years. Recently, even its antiferroelectric properties have started to be questioned, and many researchers still deal with the so-called intermediate phase below Curie temperature (T C ), whose existence is not fully understood. It turns out that PbZrO 3 doped with Nb exhibits below T C phases with complex domain structures. One of them undergoes self-organization taking place at a constant temperature, and transforms, after several minutes, into a lower phase. This isothermal transition was investigated through dielectric, pyroelectric current and Raman scattering measurements. Discontinuities accompanied it in the permittivity and pyroelectric current. The obtained Raman spectra proved that those discontinuities are strictly linked with the isothermal transition between two intermediate phases. The ordering process in lead sublattice stimulated by thermal fluctuations is discussed as a driving force for this peculiar phenomenon.

Microbiota promotes or inhibits the pathogenesis of a range of immune-mediated disorders. Although recent studies have elucidated the role of gut microbiota in ocular disease, the effect of ocular microbiota remains unclear. Herein, we explored the role of ocular commensal bacteria in non-infectious corneal inflammation and angiogenesis in a mouse model of suture-induced corneal neovascularization. Results revealed that the ocular surface harbored a microbial community consisting mainly of Actinobacteria, Firmicutes and Proteobacteria. Elimination of the ocular commensal bacteria by oral broad-spectrum antibiotics or topical fluoroquinolone significantly suppressed corneal inflammation and neovascularization. Disease amelioration was associated with reduced numbers of CD11b + Ly6C + and CD11b + Ly6G + myeloid cells, not Foxp3 + regulatory T cells, in the spleen, blood, and draining lymph nodes. Therapeutic concentrations of fluoroquinolone, however, did not directly affect immune cells or vascular endothelial cells. In addition, data from a clinical study showed that antibiotic treatment in combination with corticosteroids, as compared with corticosteroid monotherapy, induced faster remission of corneal inflammation and new vessels in pediatric patients with non-infectious marginal keratitis. Altogether, our findings demonstrate a pathogenic role of ocular microbiota in non-infectious inflammatory disorders leading to sight-threatening corneal neovascularization, and suggest a therapeutic potential of targeting commensal microbes in treating ocular inflammation., (© 2022. The Author(s), under exclusive licence to Society for Mucosal Immunology.)

Inelastic light scattering spectra of organic-inorganic halide perovskite MAPbCl 3 single crystals were investigated by using Brillouin spectroscopy. Sound velocities and acoustic absorption coefficients of longitudinal and transverse acoustic modes propagating along the cubic [100] direction were determined in a wide temperature range. The sound velocities exhibited softening upon cooling in the cubic phase, which was accompanied by the increasing acoustic damping. The obtained relaxation time showed a critical slowing-down behavior, revealing the order-disorder nature of the phase transition, which is consistent with the growth of strong central peaks upon cooling toward the phase transition point. The temperature dependences of the two elastic constants C 11 and C 44 were obtained in the cubic phase for the first time. The comparison of C 11 and C 44 with those of other halide perovskites showed that C 11 of MAPbCl 3 is larger and C 44 is slightly smaller compared to the values of MAPbBr 3 and MAPbI 3 . It suggests that MAPbCl 3 has a more compact structure (smaller lattice constant) along with stronger binding forces, causing larger C 11 and bulk modulus in this compound, and that the shear rigidity is exceedingly small similar to other halide perovskites. The reported elastic constants in this study may serve as a testbed for theoretical and calculational approaches for MAPbCl 3 .

Background: Coronavirus disease 2019 (COVID-19) is often accompanied by secondary infections, such as invasive aspergillosis. In this study, risk factors for developing COVID-19-associated pulmonary aspergillosis (CAPA) and their clinical outcomes were evaluated., Methods: This multicenter retrospective cohort study included critically ill COVID-19 patients from July 2020 through March 2021. Critically ill patients were defined as patients requiring high-flow respiratory support or mechanical ventilation. CAPA was defined based on the 2020 European Confederation of Medical Mycology and the International Society for Human and Animal Mycology consensus criteria. Factors associated with CAPA were analyzed, and their clinical outcomes were adjusted by a propensity score-matched model., Results: Among 187 eligible patients, 17 (9.1%) developed CAPA, which is equal to 33.10 per 10,000 patient-days. Sixteen patients received voriconazole-based antifungal treatment. In addition, 82.4% and 53.5% of patients with CAPA and without CAPA, respectively, received early high-dose corticosteroids ( P = 0.022). In multivariable analysis, initial 10-day cumulative steroid dose > 60 mg of dexamethasone or dexamethasone equivalent dose) (adjusted odds ratio [OR], 3.77; 95% confidence interval [CI], 1.03-13.79) and chronic pulmonary disease (adjusted OR, 4.20; 95% CI, 1.26-14.02) were independently associated with CAPA. Tendencies of higher 90-day overall mortality (54.3% vs. 35.2%, P = 0.346) and lower respiratory support-free rate were observed in patients with CAPA (76.3% vs. 54.9%, P = 0.089)., Conclusion: Our study showed that the dose of corticosteroid use might be a risk factor for CAPA development and the possibility of CAPA contributing to adverse outcomes in critically ill COVID-19 patients., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Purpose: Real-world experience with tocilizumab in combination with dexamethasone in patients with severe coronavirus disease (COVID-19) needs to be investigated., Materials and Methods: A retrospective cohort study was conducted to evaluate the effect of severity-adjusted dosing of dexamethasone in combination with tocilizumab for severe COVID-19 from August 2020 to August 2021. The primary endpoint was 30-day clinical recovery, which was defined as no oxygen requirement or referral after recovery., Results: A total of 66 patients were evaluated, including 33 patients in the dexamethasone (Dexa) group and 33 patients in the dexamethasone plus tocilizumab (DexaToci) group. The DexaToci group showed a statistically significant benefit in 30-day clinical recovery, compared to the Dexa group ( p =0.024). In multivariable analyses, peak FiO 2 within 3 days and tocilizumab combination were consistently significant for 30-day recovery (all p <0.05). The DexaToci group showed a significantly steeper decrease in FiO 2 (-4.2±2.6) than the Dexa group (-2.7±2.6; p =0.021) by hospital day 15. The duration of oxygen requirement was significantly shorter in the DexaToci group than the Dexa group (median, 10.0 days vs. 17.0 days; p =0.006). Infectious complications and cellular and humoral immune responses against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the convalescence stage were not different between the two groups., Conclusion: A combination of severity-adjusted dexamethasone and tocilizumab for the treatment of severe COVID-19 improved clinical recovery without increasing infectious complications or hindering the immune response against SARS-CoV-2., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

Bright-field imaging of nanoscale bioparticles is a challenging task for optical microscopy because the light-matter interactions of bioparticles are weak on conventional surfaces due to their low refractive index and small size. Alternatively, advanced imaging techniques, including near-field microscopy and phase microscopy, have enabled visualization and quantification of the bioparticles, but they require assistance of sophisticated/customized systems and post-processing with complex established algorithms. Here, a simple and fast immunoassay device, Gires-Tournois immunoassay platform (GTIP) is presented, which provides unique color dynamics in response to optical environment changes and thus enables the label-free bright-field imaging and facile quantification of bioparticles using conventional optical microscopy. Bioparticles on GTIP slow down the velocity of reflected light, leading to vivid color change according to the local particle density and maximizing chromatic contrast for high spatial distinguishability. The particle distribution and density on the surface of the resonator are readily analyzed through 2D raster-scanning-based chromaticity analysis. GTIP offers multiscale sensing capability for target analytes that possess different refractive indices and sizes., (© 2022 The Authors. Advanced Materials published by Wiley-VCH GmbH.)

Objective: Step 1 will transition to a pass/fail system in 2022. This study aimed to characterize the effects of this change on integrated plastic surgery program directors' selection criteria and assess whether Step 2 Clinical Knowledge (CK) can replace Step 1 as an application selection metric., Design: Online survey that was administered to a collaborative group of ten plastic surgery program directors collecting USMLE Step 1, Step 2 CK, In-Service, and written board scores for 3 years of graduated integrated residents., Setting: Ten academic integrated plastic surgery programs., Participants: Data from 80 graduated integrated plastic surgery residents., Results: Across 80 included integrated residents, mean (SD) Step 1 score was 247 (13), Step 2 CK was 249 (13), PGY1-6 In-Service percentiles varied from 45 to 53 percentile, and written board pass rate was 98.3%. Both Step 1 and Step 2 CK correlated highly with In-Service percentiles (both p < 0.001), with Step 2 CK scores correlating similarly with In-Service performance compared to Step 1 (rho 0.359 vs. 0.355, respectively). Across applicant characteristics, program directors reported the highest relative increase in Step 2 CK importance after Step 1 transitions to pass/fail., Conclusions: Step 2 CK correlates similarly with plastic surgery In-Service performance compared to Step 1. While Step scores do not necessarily correlate with residency performance, Step 2 CK may also be used as an application screening metric for programs seeking objective data to differentiate plastic surgery applicants., (Copyright © 2021 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Cardiac glycosides inhibit Na + /K + -ATPase and are used to treat heart failure and arrhythmias. They can induce inflammasome activation and pyroptosis in macrophages, suggesting cytotoxicity, which remains to be elucidated in human tissues., Experimental Approach: To determine the cell-type specificity of this cytotoxicity, we used human monocyte-derived macrophages and non-adherent peripheral blood cells from healthy donors, plus omental white adipose tissue, stromal vascular fraction-derived pre-adipocytes and adipocytes from obese patients undergoing bariatric surgery. All these cells/tissues were treated with nanomolar concentrations of ouabain (50, 100, 500 nM) to investigate the level of cytotoxicity and the mechanisms leading to cell death. In white adipose tissue, we investigated ouabain-mediated cytotoxicity by measuring insulin sensitivity, adipose tissue function and extracellular matrix deposition ex vivo., Key Results: Ouabain induced cell death through pyroptosis and apoptosis, and was more effective in monocyte-derived macrophages compared to non-adherent peripheral blood mononuclear cell populations. This cytotoxicity is dependent on K + flux, as ouabain causes intracellular depletion of K + and accumulation of Na + and Ca 2+ . Consistently, the cell death caused by these ion imbalances can be rescued by addition of potassium chloride to human monocyte-derived macrophages. Remarkably, when white adipose tissue explants from obese patients are cultured with nanomolar concentrations of ouabain, this causes depletion of macrophages, down-regulation of type VI collagen levels and amelioration of insulin sensitivity ex vivo., Conclusion and Implications: The use of nanomolar concentration of cardiac glycosides could be an attractive therapeutic treatment for metabolic syndrome, characterized by pathogenic infiltration and activation of macrophages., Linked Articles: This article is part of a themed issue on Inflammation, Repair and Ageing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.9/issuetoc., (© 2021 The Authors. British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Dysphagia is the most common complication of anterior cervical discectomy and fusion (ACDF). Several studies have reported dysphagia's incidence, severity, and prognosis after ACDF; however, few have investigated the objective effects of dysphagia management. We aimed to elucidate the efficacy of laryngeal rehabilitation therapy for dysphagia following ACDF. This prospective randomized control trial included 20 patients who underwent more than two-level ACDF. Laryngeal rehabilitation therapy was performed on 10 patients for 7 days, whereas the remaining 10 comprised the control group. Pharyngeal transit time (PTT) by videofluoroscopic swallowing study (VFSS) was performed to evaluate the objective state of swallowing. We analyzed Bazaz scale and total variance of prevertebral soft tissue swelling (PSTS) from C2 to C7 on lateral cervical radiographs during hospitalization and at 4 and 8 weeks post-surgery. The PTT of the rehabilitation group was shorter than that of the control group at 7 days and 4 weeks post-surgery ( p -value; POD 7D = 0.003, POD 4W = 0.042, POD 8W = 0.097). Perioperative laryngeal rehabilitation therapy effectively reduces postoperative dysphagia after ACDF.