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Rheumatoid arthritis (RA) is of foremost concern among long-term autoimmune disorders, as it leads to inflammation, exudates, chondral degeneration, and painful joints. Because RA severity often fluctuates over time, a local drug delivery method that titrates release of therapeutics to arthritis bioactivity should represent a promising paradigm of RA therapy. Given the local nature of RA chronic illnesses, polysaccharide-drug delivering systems have the promise to augment therapeutic outcomes by offering controlled release of bioactive materials, diminishing the required frequency of administration, and preserving therapeutic levels in affected pathological regions. Herein, an intra-articular photothermal-laden injectable methylcellulose (MC) polymeric hydrogel carrier incorporating strontium ranelate (SrR) and sodium chloride was investigated to resolve these issues. Physicochemical and cellular characteristics of the MC carrier system were thoroughly evaluated. The slow release of SrR, enhancement of the material mechanical strength, and the potential of the non-invasive near-infrared photothermal gel to improve blood circulation and suppress inflammation in a mini-surgical model of RA were examined. Biocompatibility and suppression of intracellular ROS-induced inflammation were observed. This multifunctional photothermal MC hydrogel carrier is anticipated to be an alternative approach for future orthopedic disease treatment., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Protobothrops mucrosquamatus, also known as the brown spotted pit viper or Taiwanese habu, is a medically significant venomous snake in Taiwan, especially in the northern area. To more fully understand the proteome profile of P. mucrosquamatus, we characterized its venom composition using a bottom-up proteomic approach. Whole venom components were fractionated by RP-HPLC and then analyzed by SDS-PAGE. Each protein band in gels was excised and subjected to protein identification by LC-MS/MS. A subsequent proteomic analysis revealed the presence of 61 distinct proteins belonging to 19 families in P. mucrosquamatus venom. Snake venom metalloproteinase (SVMP; 29.4%), C-type lectin (CLEC; 21.1%), snake venom serine protease (SVSP; 17.6%) and phospholipase A 2 (PLA 2 ; 15.9%) were the most abundant protein families, whereas several low-abundance proteins, categorized into eight protein families, were demonstrated in P. mucrosquamatus venom for the first time. Because PLA 2 is known to make a major contribution to venom lethality, we evaluated whether the known PLA 2 inhibitor, varespladib, was capable of preventing the toxic effects of P. mucrosquamatus venom. This small-molecule drug demonstrated the ability to inhibit PLA 2 activity in vitro (IC 50  = 101.3 nM). It also blunted lethality in vivo, prolonging survival following venom injection in a mouse model, but it showed limited potency against venom-induced local hemorrhage in this model. Our findings provide essential biological and pathophysiological insights into the composition of P. mucrosquamatus venom and suggest PLA 2 inhibition as an adjunctive or alternative therapeutic strategy in the clinical management of P. mucrosquamatus envenoming in emergency medicine. SIGNIFICANCE: P. mucrosquamatus envenomation is a significant medical concern in Taiwan, especially in the northern region. Although antivenom is commonly used for rescuing P. mucrosquamatus envenoming, severe clinical events still occur, with more than 20% of cases requiring surgical intervention. Small-molecule therapy offers several advantages as a potential adjunctive, or even alternative, to antivenom treatment, such as heat stability, low antigenicity and ease of administration, among others. A deeper understanding of the venom proteome of P. mucrosquamatus would aid in the discovery of small-molecule drugs that could be repurposed to target specific venom proteins. Here, we applied a bottom-up proteomic approach to characterize the protein profile of P. mucrosquamatus venom. Varespladib, a small-molecule drug used to treat inflammatory disease, was repurposed to inhibit the toxicity of P. mucrosquamatus venom, and was shown to reduce the lethal effects of P. mucrosquamatus envenomation in a rodent model. Varespladib might be used as a first-aid therapeutic against P. mucrosquamatus envenoming in the pre-referral period and/or as an adjunctive agent administered together with anti-P. mucrosquamatus antivenom., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Congenital nephrogenic diabetes insipidus (CNDI) is a genetic disorder caused by mutations in arginine vasopressin receptor 2 ( AVPR2 ) or aquaporin 2 genes, rendering collecting duct cells insensitive to the peptide hormone arginine vasopressin stimulation for water reabsorption. This study reports a first identified AVPR2 mutation in Taiwan and demonstrates our effort to understand the pathogenesis caused by applying computational structural analysis tools. The CNDI condition of an 8-month-old male patient was confirmed according to symptoms, family history, and DNA sequence analysis. The patient was identified to have a valine 279 deletion-mutation in the AVPR2 gene. Cellular experiments using mutant protein transfected cells revealed that mutated AVPR2 is expressed successfully in cells and localized on cell surfaces. We further analyzed the pathogenesis of the mutation at sub-molecular levels via long-term molecular dynamics (MD) simulations and structural analysis. The MD simulations showed while the structure of the extracellular ligand-binding domain remains unchanged, the mutation alters the direction of dynamic motion of AVPR2 transmembrane helix 6 toward the center of the G-protein binding site, obstructing the binding of G-protein, thus likely disabling downstream signaling. This study demonstrated that the computational approaches can be powerful tools for obtaining valuable information on the pathogenesis induced by mutations in G-protein-coupled receptors. These methods can also be helpful in providing clues on potential therapeutic strategies for CNDI.

Formation of DNA adducts is a key event during carcinogenesis. DNA adducts, if not repaired properly, can lead to mutations and cancer. DNA adducts have been frequently used as biomarkers to evaluate chemical exposure. Vinyl acetate monomer (VAM) is widely used in the manufacture of various industrial polymers. Previous studies have documented that VAM induced nasal tumors in rodents exposed to high exposure levels of VAM. VAM is metabolized by carboxylesterase to acetaldehyde (AA), which subsequently results in DNA adducts. However, AA is also an endogenous metabolite in living cells, which impedes accurate assessment of the contribution of VAM exposure under the substantial endogenous background. To address this challenge, we exposed rats to stable isotope labeled [ 13 C 2 ]-VAM at 50, 200, and 400 ppm through inhalation for 6 h, followed by DNA adduct analysis in nasal respiratory and olfactory epithelia with highly sensitive mass spectrometry. Our results show that exogenous N 2 -ethyl-dG adducts were present in all rats exposed to [ 13 C 2 ]-VAM, with over 2-fold higher DNA adducts in nasal respiratory epithelium than olfactory epithelium. Our data also show that N 2 -ethyl-dG is a more sensitive biomarker to assess VAM exposure than 1, N 2 -propano-dG adducts. Moreover, a very low amount of exogenous N 2 -ethyl-dG adducts were detected in peripheral blood mononuclear cell samples of exposed rats, suggesting that only an extremely small percentage of [ 13 C 2 ]-VAM or its metabolite may enter into systemic circulation to potentially damage tissues beyond nasal epithelium. Furthermore, exogenous N 2 -ethyl-dG DNA adducts undergo rapid repair or spontaneous loss in nasal epithelium of exposed rats. Taken together, the results presented herein provide novel quantitative data and lay the foundation for future studies to improve risk assessment of VAM.

Background: The objective of this trial is to evaluate the flexibility of the cartilaginous component of the cleft nose after diced cartilage rhinoplasty by determining the degree of possible bending in relation to the vertical nasal dorsum axis and to compare with to a control group of the unaffected population., Patients and Methods: Fifteen cleft nose patients with diced cartilage rhinoplasty were included in this study, as well as a control group of 15 unaffected individuals. The angle of maximum nasal bending is measured between the basic and maximum bending axis and performed by the same rater twice at least 2 weeks apart to account for intrarater reliability. Study groups were compared with Fisher and independent t test., Results: The maximum bending to the left side was 16.10 ± 5.03 degrees for the study group and 23.95 ± 6.54 degrees for the control group (P = 0.001). The maximum bending to the right side were 16.54 ± 6.73 degrees for the study group and 23.00 ± 8.88 degrees for the control group (P = 0.034)., Conclusion: Diced cartilage graft injection for dorsal augmentation yields reproducible and esthetically pleasing outcomes with good flexibility and natural feel of the nasal tip. Although there is a significant difference compared with a nonaffected control group in maximum bending capacity, all patients in this study were satisfied with the results., Competing Interests: Conflicts of interest and sources of funding: This project is supported by Chang Gung Research Grant CMRPG5F0191. The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

[Figure: see text].

Considering the birefringence of the gain medium, we propose a selection rule for designing cavity configurations that enable the generation of radially and azimuthally polarized laser beams with a low beam quality factor, i.e., high beam quality. Using this rule, all stable regions can support cylindrical vector (CV) beams by using the position of the end mirror as the tuning parameter to vary the cavity configuration. Such cavity configurations tend to sustain the fundamental or lowest-order CV beam, and radially or azimuthally polarized beams can be obtained simply by varying the tuning parameter. Based on experimental measurements of the beam quality factor and polarization characteristics, we verified our analyses and simulations for a four-element laser system.

Snake envenomation is a serious public health issue in many tropical and subtropical countries. Accurate diagnosis and immediate antivenom treatment are critical for effective management. However, the venom concentration in the victims' plasma is usually low, representing one of the bottlenecks in developing clinically applicable assays for venom detection and snakebite diagnosis. In this study, we attempted to develop a simple method for rapid enrichment of venom proteins from human plasma to facilitate detection. Our experiments showed that several major protein components of both Naja atra ( N. atra ) and Bungarus multicinctus ( B. multicinctus ) venoms have higher isoelectric point (pI) values relative to high-abundance human plasma proteins and could be separated via strong cation exchange-high-performance liquid chromatography (SCX-HPLC). Based on this principle, we developed an SCX tip column-based protocol for rapid enrichment of N. atra and B. multicinctus venom proteins from human plasma. Application of liquid chromatography-tandem mass spectrometry (LC-MS/MS) led to the identification of cytotoxin and beta-bungarotoxin as the major proteins enriched by the SCX tip column in each venom sample. The entire process of venom enrichment could be completed within 10-15 min. Combination of this method with our previously developed lateral flow strip assays (rapid test) significantly enhanced the sensitivity of the rapid test, mainly via depletion of the plasma protein background, as well as increase in venom protein concentration. Notably, the SCX tip column-based enrichment method has the potential to efficiently enrich other Elapidae snake venoms containing proteins with higher pI values, thereby facilitating venom detection with other assays. This simple and rapid sample preparation method should aid in improving the clinical utility of diagnostic assays for snakebite.

Objective: This study aimed to investigate the contribution of high body mass index (BMI) to growth velocity among school-aged children who remained in the same BMI categories for a 6-year period. Methods: This retrospective cohort study included children who enrolled in the school year 2009 and remained in the same BMI categories during their 1st, 4th, and 7th grades (6-7, 9-10, 12-13 years of age). Annual linear growth velocity and weight gain were calculated and compared between sexes, BMI groups, and different times. Risk analysis and repeated measures analysis of variance were performed to identify the impact of BMI on growth velocity. Results: Of the 1,637 subjects, 53.0% were male, and 2.5% and 10.9% belonged to BMI groups of overweight and obese, respectively. In students between 6 and 13 years of age, obesity was associated with higher annual weight gain and height gain. Risk analysis showed that obese subjects had higher linear growth velocity than normal BMI groups of both sexes between 6 and 9 years of age. Unexpectedly, overweight and obese girls between 9 and 13 years of age had less linear growth velocity than underweight girls at the same interval. Repeated measures analysis of variance in both sexes showed a significant statistical association between BMI and different times of growth. However, the effect was less in girls between 9 and 13 years of age. Conclusion: Puberty may dominate over BMI as the main contributor to high growth velocity in girls with underweight BMI emerging into pubertal age., 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 © 2021 Hsiao, Wang, Chu, Chang, Chen, Jan, Yang, Chen, Chou, Chu, Lai, Cheng, Chiu, Liu and Chang.)

Background: Many Asian patients desire a narrower nasal base with less flaring of the alar lobules. However, patients who underwent multiple rhinoplasty surgeries with nostril contracture or an overreduction of the alar base may experience nostril contracture and deformity, which may lead to further airway obstruction. We present a technique that combines paranasal augmentation with composite chondrocutaneous graft transfer to overcome this problem., Methods: Nine patients underwent composite chondrocutaneous graft transfer to the soft triangle or alar base combined with paranasal augmentation using preshaped porous polyethylene implants to correct nostril contracture and airway obstruction between September of 2014 and May of 2018. Preoperative and postoperative alar base distances and cross-sectional areas of the nostrils were measured and compared., Results: The average thickness of paranasal augmentation was 5.5 mm (range, 4.0-7.0 mm). Eighteen composite grafts were located over the soft triangle (n = 3) and the alar base (n = 15). The average number of composite grafts for each person was 2 (range, 1-4). All composite grafts survived totally or partially, and no graft failed. The average follow-up was 10.9 months (range, 3-28 months). The alar base increased 13.9% (range, 2.2%-23.9%), and the nostril area increased an average of 78.1% (range, 4.5%-316.8%) postoperatively. Patients had satisfactory aesthetic and functional outcomes., Conclusions: Combining paranasal augmentation and composite graft transfer increased the cross-sectional area of the external valve and improved nostril contracture and airway obstruction after the overresection of the alar base or nose contracture after multiple rhinoplasty surgeries., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Smoker patients with non-small cell lung cancer (NSCLC) have poorer prognosis and survival than those without smoking history. However, the mechanisms underlying the low response rate of those patients to EGFR tyrosine kinase inhibitors (TKIs) are not well understood. Here we report that exposure to cigarette smoke extract enhances glycolysis and attenuates AMP-activated protein kinase (AMPK)-dependent inhibition of mTOR; this in turn reduces the sensitivity of NSCLC cells with wild-type EGFR (EGFR WT ) to EGFR TKI by repressing expression of liver kinase B1 (LKB1), a master kinase of the AMPK subfamily, via CpG island methylation. In addition, LKB1 expression is correlated positively with sensitivity to TKI in patients with NSCLC. Moreover, combined treatment of EGFR TKI with AMPK activators synergistically increases EGFR TKI sensitivity. Collectively, the current study suggests that LKB1 may serve as a marker to predict EGFR TKI sensitivity in smokers with NSCLC carrying EGFR WT and that the combination of EGFR TKI and AMPK activator may be a potentially effective therapeutic strategy against NSCLC with EGFR WT .

Influenza, pneumonia, and pathogenic infection of the respiratory system are boosted in cold environments. Low temperatures also result in vasoconstriction, restraint of blood flow, and decreased oxygen to the heart, and the risk of a heart attack would increase accordingly. The present face mask fabric fails to preserve its air-filtering function as its electrostatic function vanishes once exposed to water. Therefore, its filtering efficacy would be decreased meaningfully, making it nearly impracticable to reuse the disposable face masks. The urgent requirement for photothermal fabrics is also rising. Nanobased polyethyleneimine-polypyrrole nanopigments (NPP NPs) have been developed and have strong near-infrared spectrum absorption and exceptional photothermal convertible performance. Herein, the mask fabric used PE-fiber-constructed membrane (PEFM) was coated by the binding affinity of the cationic polyethyleneimine component of NPP NPs forming NPP NPs-PEFM. To the best of our knowledge, no study has investigated NPP NP-coated mask fabric to perform infrared red (solar or body) photothermal conversion efficacy to provide biocompatible warming, remotely photothermally captured antipathogen, and antivasoconstriction in vivo . This pioneering study showed that the developed NPP NPs-PEFM could be washable, reusable, breathable, biocompatible, and photothermal conversable for active eradication of pathogenic bacteria. Further, it possesses warming preservation and antivasoconstriction.

A dielectric thermal smart glass (DTSG) based on the dielectric heating optical (DHO) effect in tunable helical polymer-based superstructures-cholesteric liquid crystals (CLCs)-was exhibited in this study. Field-induced dielectric heating can strongly affect the orientation of liquid crystals and change its optical properties. The purpose of this research focuses on dual-frequency CLC materials characterized by their specific properties on dielectric relaxation and demonstrates their potential for antibacterial biosensor applications. The developed DTSG is driven by voltages with modulated frequencies. The principal of DTSG in transparent states are a planar (P) state and a heated planar (HP) state reflecting infrared light, operated with the voltage at low and high frequencies, respectively. The scattering states are a focal conic (FC) state and a heated FC (HFC) state, with an applied frequency near the crossover frequency. The biomolecule detection of the antibacterial property was also demonstrated. The detection limitation of the DTSG biosensor was found to be about 0.5 µg/mL. The DTSG material has many potential industrial applications, such as in buildings, photonic devices, and biosensor applications.

The current state of the COVID-19 pandemic is a global health crisis. To fight the novel coronavirus, one of the best-known ways is to block enzymes essential for virus replication. Currently, we know that the SARS-CoV-2 virus encodes about 29 proteins such as spike protein, 3C-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), Papain-like protease (PLpro), and nucleocapsid (N) protein. SARS-CoV-2 uses human angiotensin-converting enzyme 2 (ACE2) for viral entry and transmembrane serine protease family member II (TMPRSS2) for spike protein priming. Thus in order to speed up the discovery of potential drugs, we develop DockCoV2, a drug database for SARS-CoV-2. DockCoV2 focuses on predicting the binding affinity of FDA-approved and Taiwan National Health Insurance (NHI) drugs with the seven proteins mentioned above. This database contains a total of 3,109 drugs. DockCoV2 is easy to use and search against, is well cross-linked to external databases, and provides the state-of-the-art prediction results in one site. Users can download their drug-protein docking data of interest and examine additional drug-related information on DockCoV2. Furthermore, DockCoV2 provides experimental information to help users understand which drugs have already been reported to be effective against MERS or SARS-CoV. DockCoV2 is available at https://covirus.cc/drugs/., (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The global outbreak of COVID-19 since January 2020 has forced the closure of schools and universities in over 180 countries to control the pandemic, affecting approximately 90% of students worldwide. Distance teaching has been adopted during school closures to suspend classes without suspending learning. Scholars have claimed that distance teaching is more effective than face-to-face teaching and can replace face-to-face courses. However, further investigation is required to confirm whether distance learning is suitable for all types of courses and all students. Thanks to the effective containment of COVID-19 outbreaks in Taiwan, universities in Taiwan face a less problematic situation than do those in other countries; however, plans and preparations remain essential. The present study recruited 18,085 students from a technology university in Taiwan and used the baseline data of the past three academic years before COVID-19 (2016-2018) to explore the influences of course type and gender on distance learning performance. The results revealed that compulsory courses are more suitable for distance learning courses, whereas face-to-face teaching is more suitable for elective and general education courses. The learning performance of males and females is also different: face-to-face courses are more suitable for males, whereas no significant difference between teaching methods was observed in females. This result suggests that not all courses offered by the university are suitable for distance learning courses, and not all students are adept at distance learning. Based on these results, it is recommended that a new teaching model be established for the post-COVID-19 era., Competing Interests: Competing interestsThe author declares that there is not competing interests., (© The Author(s) 2021.)

Peptide hormones play pivotal roles in many physiological processes through coordinating developmental and environmental cues among different cells. Peptide hormones are recognized by their receptors that convey signals to downstream targets and interact with multiple pathways to fine-tune plant growth. Extensive research has illustrated the mechanisms of peptides in shoots but functional studies of peptides in roots are scarce. Reactive oxygen species (ROS) are known to be involved in stress-related events. However, recent studies have shown that they are also associated with many processes that regulate plant development. Here, we focus on recent advances in understanding the relationships between peptide hormones and their receptors during root growth including outlines of how ROS are integrated with these networks.

Purpose: Antibiotic resistance issues associated with microbial pathogenesis are considered to be one of the most serious current threats to health. Fortunately, TiO 2 , a photoactive semiconductor, was proven to have antibacterial activity and is being widely utilized. However, its use is limited to the short range of absorption wavelength., Methods: In this work, heterostructured TiO 2 -FeS 2 nanocomposites (NCs) were successfully prepared by a facile solution approach to enhance light-induced antibacterial activity over a broader absorption range., Results: In TiO 2 -FeS 2 NCs, FeS 2 NPs, as light harvesters, can effectively increase light absorption from the visible (Vis) to near-infrared (NIR). Results of light-induced antibacterial activities indicated that TiO 2 -FeS 2 NCs had better antibacterial activity than that of only TiO 2 nanoparticles (NPs) or only FeS 2 NPs. Reactive oxygen species (ROS) measurements also showed that TiO 2 -FeS 2 NCs produced the highest relative ROS levels. Unlike TiO 2 NPs, TiO 2 -FeS 2 NCs, under light irradiation with a 515-nm filter, could absorb light wavelengths longer than 515 nm to generate ROS. In the mechanistic study, we found that TiO 2 NPs in TiO 2 -FeS 2 NCs could absorb ultraviolet (UV) light to generate photoinduced electrons and holes for ROS generation, including ⋅O 2 - and ⋅OH; FeS 2 NPs efficiently harvested Vis to NIR light to generate photoinduced electrons, which then were transferred to TiO 2 NPs to facilitate ROS generation., Conclusion: TiO 2 -FeS 2 NCs with superior light-induced antibacterial activity could be a promising antibacterial agent against bacterial infections., Competing Interests: The authors declare no conflicts of interest., (© 2020 Mutalik et al.)

The study aimed to determine the impact of an elective spiritual education course for nursing students on spiritual competencies. A convenience sample of nursing students (N = 92) was recruited from a baccalaureate school of nursing between February and July 2016. The intervention group (n = 45) was comprised of students enrolled in the elective spiritual education course which integrated non-Christian Eastern cultural beliefs; the control group was comprised of students not enrolled in the elective (n = 47). A quasi-experimental design examined pretest, posttest, and follow-up data from students' self-administered questionnaires. The intervention effect of the course was analyzed using generalized estimation equation. The results indicated posttest scores among nursing students in the intervention group were significantly better than the comparison group for spiritual health. Practicum stress and professional commitment were significantly better at follow-up. Spiritual care attitudes, caring behavior, and religious belief were significantly improved from pretest to posttest, and at follow-up for the intervention group compared with the control group. In conclusion, a spiritual education course should be considered as a regular course in the nursing curriculum, which could improve students' spiritual competencies, individual spiritual growth, and the ability to care for patients., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

The highly sensitive interfacial effects between liquid crystal (LC) and alignment layers make LC-bioinspired sensors an important technology. However, LC-bioinspired sensors are limited by quantification requiring a polarized microscope and expensive equipment, which makes it difficult to commercialize LC-bioinspired sensors. In this report, we first demonstrate that dye-doped LC (DDLC) chips coated with vertically aligned layers can be employed as a new LC-bioinspired sensing technology. The DDLC-bioinspired sensor was tested by detecting bovine serum albumin (BSA) and immunocomplexes of BSA pairs. The intensities of the dye color of the DDLC-bioinspired sensor can be changed with the concentrations of biomolecules and immunocomplexes. A detection limit of 0.5 µg/mL was shown for the color-indicating DDLC-bioinspired sensors. We also designed a new method to use the quantitative DDLC-bioinspired sensor with a smart-phone for potential of home test. The novel DDLC-bioinspired sensor is cheap, label-free, and easy to use, furthering the technology for home and field-based disease-related detection.

Objectives: This study aimed to evaluate the prognostic factors of reoperation after plate fixation for midshaft clavicle fracture and compare outcomes of dynamic compression plates (DCP) and pre-contoured locking plates., Design: Retrospective comparative study., Setting: Level I trauma center., Patients/participants: We recruited 274 consecutive patients who underwent plate fixation for midshaft clavicle fracture from 2007 to 2017 and completed at least 1 year of follow-up., Intervention: 235 patients underwent surgery with DCP, while 39 patients were treated with locking plate., Main Outcome Measurements: We reviewed the possible variables of secondary surgeries, and documented complications from the medical records. Patients with a DCP or locking plate were further divided for outcome comparisons., Results: 150 (54.7%) patients underwent reoperation after the initial surgery, and plate removal represented the major etiology. On multivariate analysis, superficial wound infection and prominent implant were identified as significant risk factors for reoperation, while aging, locking plate usage, and higher body mass index (BMI) were protective factors (all P < 0.05). The locking plate featured a significantly decreased implant removal rate (7.7% vs. 60.9%, P < 0.05)., Conclusions: Patients with risk factors for superficial wound infection or a prominent implant tended to require a secondary operation after surgery for midshaft clavicle fracture, while aging, pre-contoured locking plate usage, and higher BMI decreased the risk. Compared with DCP, patients with locking plates tended to have better prognosis and significantly lower implant removal rates., Level of Evidence: Prognostic III., Competing Interests: Declaration of Competing Interest There is no conflict of interest of the study., (Copyright © 2020. Published by Elsevier Ltd.)

Cleft lip and/or cleft palate are the most common congenital craniofacial anomalies. Philtral ridge morphology is an important aesthetic component of unilateral cleft lip (UCL) repair. To this end, we have developed two techniques of philtral ridge reconstruction: (1) asymmetric mattress muscle sutures, and (2) overlapping mattress muscle sutures. The objective of this retrospective cohort study was to compare their outcomes in UCL repairs. Group I patients (n=30) underwent UCL repair before August 2003, including philtral ridge reconstruction by asymmetric mattress muscle sutures. Group II patients (n=30) underwent UCL repair after August 2003, including philtral ridge reconstruction by overlapping mattress muscle sutures. Philtral morphology was evaluated by ultrasonographic and three-dimensional photographic measurements, examining cleft side philtral projection and philtral ridge symmetry. These demonstrated that group II patients had better philtral column symmetry and projection on the cleft side when compared to group I. Overlapping mattress muscle sutures produced better philtral morphology in UCL repairs than asymmetric mattress muscle sutures., (Copyright © 2020 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Gold nanoclusters (AuNCs) and liquid crystals (LCs) have shown great potential in nanobiotechnology applications due to their unique optical and structural properties. Herein, the hardcore of the 4-cyano biphenyl group for commonly used LCs of 4-cyano-4'-pentylbiphenyl (5CB) was utilized to synthesize 4'-(2-mercaptoethyl)-(1,1'-biphenyl)-4-carbonitrile (TAT-12) based on Suzuki coupling and Appel reaction. The structural and optical properties of thiol-modified TAT-12 LCs were demonstrated by nuclear magnetic resonance (NMR) spectroscopy, ultraviolet-visible (UV-vis) spectroscopy and differential scanning calorimetry (DSC). By one-pot synthesis, thiol-modified TAT-12 LCs were used as the ligands to prepare fluorescent gold nanoclusters (AuNCs@TAT-12) according to the Au-S bond between AuNCs and TAT-12. The spectra of UV-vis absorption and X-ray photoelectron spectroscopy (XPS) of AuNCs@TAT-12 indicated that the core of gold of AuNCs@TAT-12 exhibited high gold oxidation states. The fluorescence of AuNCs@TAT-12 was observed with a maximum intensity at ~352 nm coming from TAT-12 on AuNCs@TAT-12 and the fluorescence quantum yield of AuNCs@TAT-12 was calculated to be 10.1%. Furthermore, the fluorescence with a maximum intensity at ~448 nm was attributed to a ligand-metal charge transfer between the ligands of TAT-12 LCs and the core of AuNCs. The image of transmission electron microscopy (TEM) further demonstrated an approximately spherical shape of AuNCs@TAT-12 with an average size of 2.3 nm. A combination of UV-vis absorption spectra, XPS spectra, fluorescence spectra and TEM image, fluorescent AuNCs@TAT-12 were successfully synthesized via one-pot synthesis. Our work provides a practical approach to the synthesis of LCs conjugated AuNCs for future applications in nanobiotechnology.

The forehead flap is a dependable option for nasal reconstruction owing to its reliability and anatomic likeness to nasal skin. For patients with low hairlines, the vertical design of the paramedian forehead flap can intrude into the scalp, thus incorporating hair into the nasal reconstruction. The inadequate length of the forehead flap or shift to an oblique design may result in eyebrow elevation and asymmetry. Therefore, laser hair removal (epilation) on the forehead flap has been proposed to improve esthetic results. An alexandrite laser (755 nm, 10 to 20 ms, 18-mm spot size) with a Dynamic Cooling Device ™ (DCD ™ ) cooling system was used for hair removal in 22 patients (16 male and 6 female patients) after nasal reconstructions using forehead flaps from December 2011 to September 2016. All patients received cryogen spray cooling laser treatment (CSC-LT). The mean follow-up period was 24 months, with a range between 18 and 50 months. The average duration of treatment was 1.8 months (range, 1-5 months). The energy density ranged from 14 to 18 J/cm 2 with an average of 17.2 J/cm 2 . The number of treatments ranged from 2 to 4 (mean 2.8). Patients had satisfactory esthetic results over 11.1 months (range, 8-18 months). Residual white hairs were observed in 3 patients, and 4 patients had tiny black residual hairs without deteriorating cosmesis. Using an alexandrite laser to remove hair on the forehead is safe and reliable in nasal reconstruction with superior recipient site cosmesis.

The human intestine is host to a vast microbial community: the gut microbiome (GM). The GM has been considered as a key modulator of human health in the past decade. In particular, several studies have supported that altered GM is associated with cancer, such as colorectal cancer, adenocarcinoma, and pancreatic cancer. The formation of a DNA adduct is one of the key events in carcinogenesis, and whether GM can influence DNA adducts has yet to be examined. This study analyzed 10 DNA adducts (N 2 -Me-dG, N 6 -Me-dA, N 2 -Et-dG, OH-Me-dG, OH-Me-dA, N 2 -EtD-dG, O 6 -Me-dG, 1,N 2 -ε-dG, 8-oxo-dG, and 5-Cl-dC), attributed to various endogenous processes and physiological stressors, using highly sensitive LC-MS/MS in germ-free (GF) and conventionally raised (CONV-R) mice. Our results showed that significant differences in specific DNA adducts appeared in liver, colon, and small intestine samples between GF and CONV-R mice. The differences in adduct levels may indicate that GM can locally or systemically regulate endogenous processes including neutrophil bactericidal activity (represented by 5-Cl-dC), lipid peroxidation (1,N 2 -ε-dG), oxidative stress generation (8-oxo-dG), and endogenous aldehyde metabolism (OH-Me-dA). Further studies are warranted to elucidate how the GM influences endogenous process, DNA damage, and the risks of developing cancer.

Aim: To investigate the protective behaviours of longer near work distance, discontinuing near work and more time outdoors in recess from parent self-report in the myopia prevalence and progression among myopic children aged 9-11 years., Methods: Myopia Investigation study in Taipei is a longitudinal population-based study that enrolled elementary school students in Taipei. We provided vision and refraction examination every 6 months. Spherical equivalent (SE) of cycloplegic refraction ≤-0.50 Diopter (D) is defined as myopia. Total 10 743 (70.4%) students completed 2-year refraction data and questionnaire. The myopia prevalence and progression (difference of SE) in baseline, 6, 12, 18 and 24 months were compared by generalised estimating equations., Results: Children with persistent protective behaviour had significant lower prevalence of myopia. The protective impact was statistically significant from 6 to 24 months. In 2 years follow-up, risk ratio after adjusting the background variables and the other two behaviours in near work distance, near work time and outdoor time were 0.71, 0.89 and 0.77. In SE analysis, after adjusting the other two behaviours, near work distance >30 cm (-0.7 vs -1.04 D; p < 0.001), discontinuing near work every 30 min (-0.77 vs -0.96 D, p=0.005) and more time outdoors in recess from parent self-report (-0.75 vs -0.98 D; p=0.012) revealed protective impacts on diminishing myopia progression from 6 to 24 months., Conclusion: In myopic children aged around 10 years in Taipei, longer distance in near work, discontinuing near work every 30 min and more outdoor time from parent self-report are protective behaviours in myopia prevalence and progression in 6-24 months., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Infrared thermography can be applied in different medical systems, for example it can be used to catch the images of living blood vessels. Far infrared rays can be used in a heating machine, which can be applied in the clinical hemodialysis patients. Infrared electronically sensitized images, which are generated by near-infrared Charge-coupled Device (CCD), are used to detect blood vessels, and used as a long-wavelength external stimulating therapeutic tissue repair system. When an infrared sensor detection and actuator treatment is applied during hemodialysis, a missing needle can be detected, and far infrared rays have a therapeutic effect on blood vessels. Because a far-infrared actuated light source can improve blood circulation, it is currently used to prevent fistula embolism in hemodialysis (HD) patients and reduce vascular occlusion after hemodialysis. Sensors used for sudden changes in heart rate variability (HRV) are used as predictive and evaluation indicators for our new method. Far-infrared actuated radiation can increase sympathetic nerve activity and regulation of parasympathetic and sympathetic nerves. We performed baseline measurements of the low-frequency/high-frequency ratio of autonomic nerve activity before hemodialysis (low frequency (LF), high frequency (HF), LF/HF, before HD) and after hemodialysis (LF/HF, after-HD). Based on data from the HRV continuity tracking report, 35 patients with autonomic nerve activation were treated and evaluated. We have demonstrated that the resulting near-infrared (NIR) sensor imaging and far-infrared actuator illumination can be used for the detection and treatment of hemodialysis patients.

Background: Religion is an important cultural asset that is known to affect the thoughts, behaviors, and lifestyles of individuals. However, the impact of religious affiliation, religious activities, and religious beliefs on the attitudes of nurses toward providing spiritual care to their patients is an issue that has been inadequately explored., Purposes: The aim of this study was to explore the relationship between religion (including religious affiliation, religious activities, and religious beliefs) and attitude toward spiritual care in clinical nurses., Methods: This study used a cross-sectional correlation study design. Six hundred nineteen nurses were included as participants. The measurements used included a questionnaire on religious affiliation, religious activities, and religious beliefs; the Spiritual Health Scale-Short Form; the Spiritual Care Attitude Scale; and a sociodemographic datasheet. The study employed hierarchical regression modeling to establish the relationships between the aspects and degrees of religious belief and practice as well as the attitudes of participants toward spiritual care., Results: Most of the participants participated infrequently in religious activities. After controlling for demographic variables and spiritual health, religious belief was found to be an important factor impacting participants' attitudes toward providing spiritual care., Conclusions/implications for Practice: The findings indicate that religious belief is an important factor impacting the attitudes of nurses toward providing spiritual care and that the religious/spiritual beliefs of nurses may impact on their fitness to provide spiritual care to patients. Education on religion may be needed to improve the attitude of nurses toward providing spiritual care.

Oral microbes are a contributing factor to hyperglycemia by inducing an increase in insulin resistance resulting in uncontrolled blood glucose levels. However, the relationship between the distribution of oral flora and hyperglycemia is still controversial. Combining the power of MALDI-Biotyper with anaerobic bacterial culture, this study explores the correlation between anaerobic bacteria in the oral cavity and blood glucose levels. The results demonstrated that altered blood glucose levels contributed to a varied bacterial distribution in the oral cavity. Specifically, Veillonella spp. and Prevotella spp. were identified in a higher proportion in people with elevated blood glucose levels. Six bacterial species identified in this study (Prevotella melaninogenica, Campylobacter rectus, Streptococcus gordonii, Streptococcus mitis, Streptococcus salivarius, and Veillonella parvula) not only demonstrated a positive association with higher blood glucose levels, but also likely contribute to the development of the condition. The data demonstrated MALDI-TOF MS to be a simpler, faster, and more economical clinical identification tool that provides clarity and depth to the research on blood glucose and oral microbiota., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)

When the cartilage on the prominent ears is reshaped, the arising stress returns the tissue to its initial configuration. Laser irradiation of areas of maximal stress leads to stress relaxation and results in a stable configuration. Sixty auricles were harvested from 30 New Zealand white rabbits and cut into a rectangle measuring 50 mm by 25 mm with an average thickness of approximately 1.3 mm. Bilateral skin was included for ex vivo studies. Continuous cryogen spray cooling (CSC) with laser energy was delivered to the exposed cartilage for reshaping. In clinical applications, from January 2006 to December 2016, a total of 50 patients with 100 bat ears who underwent CO 2 laser reshaping (otoplasty) were assessed. A continuous cooling system (4 °C) in conjunction with a CO 2 laser was applied to make a retroauricular-approached incision and reshape the ear cartilage. The well cartilage bending correlated with the different parameters demonstrated in the continuous CSC protected group. All 100 (100%) of the subjects experienced early complications (≤ 1 month) related to laser exposure with swelling, while 5 (5%) experienced ecchymosis, 2 (2%) minimal hematoma, 2 (2%) scarring, 1 (1%) minor infection, 1 (1%) under correction, 1 (1%) overcorrection, and 1 (1%) relapse. These problems were corrected and/or had resolved after 3 months. All patients achieved good to excellent results in our final outcome assessment (> 6 months). Laser reshaping has a potential use in certain surgical procedures involving the cartilage. The appropriate conditions for laser ear reshaping clearly depend on the laser wavelength used, energy controlling, and tissue optical properties.

Background: Lymphatic malformations remain a challenge for patients and plastic surgeons. Promising results have been reported using intralesional laser photocoagulation (ILP) for treating vascular anomalies., Background Data: The objective of our study is to review the long-term results of a large series of lymphatic malformations in patients treated with ILP., Materials and Methods: A retrospective review of 190 head and neck lymphatic malformations in patients were treated by ILP with an neodymium-yttrium-aluminum-garnet (Nd:YAG) laser (1064 nm) over a period of 20 years (January 1997-January 2016). Patients' ages ranged from 10 months to 12 years and 6 months (mean, 1 year and 11 months). The patient group consisted of 98 female and 92 male patients., Results: Patients were treated with an Nd:YAG laser (Sharplan Inc, Allendale, New Jersey) delivered through a 600-μm optical fiber. Laser power was set at 7 to 15 W and delivered with a pulse duration of 7 to 15 seconds. All patients demonstrated improvement as judged by clinical assessment of the reduction in lesion size (range, 65%-100%; mean reduction, 85%). One hundred fifty-two (80%) patients had a more than 65% reduction of the volume in lymphatic malformations at 3 months after 1 treatment, and 171 (90%) patients had a more than 85% reduction of the volume after 2 treatments. Excellent results were seen in 19 (10%) patients after 3 treatments. Postoperative complications were related to photocoagulation that was delivered too extensively or superficially, with resultant ulceration, infection, induration, and scarring., Conclusions: Throughout the course of our long-term study, ILP using an Nd:YAG laser is an effective treatment modality for lymphatic malformations. Complications can be avoided if the potential for harm is kept in mind.

Background: Since 2012, the senior author has incorporated the natural curvature of rib cartilage as an alar rim graft in addition to the diced cartilage technique for unilateral cleft rhinoplasty. The aim of this study is to describe this modification and evaluate its long-term results regarding nasal symmetry using three-dimensional stereophotogrammetric assessment (3dMDface system)., Methods: From 2012 to 2018, 47 consecutive patients that underwent secondary unilateral cleft rhinoplasty were reviewed retrospectively. Sixteen patients with both preoperative and postoperative three-dimensional photographs taken at least 6 months after the operation were included. SimPlant O&O software was used to measure parameters on three-dimensional photographs: nostril heights, nostril widths, nasal dorsum heights, alare width, nostril areas, overlapping nostril area, nasal tip protrusion, nasal length, and nasal height before and after surgery. The ratios between cleft and noncleft sides were calculated. In addition, the overlapping nostril area ratio, tip protrusion-width index, and nasal index were compared before and after surgery., Results: The preoperative nostril height ratio (0.79), nostril width ratio (1.24), and nasal dome height ratio (0.84) between cleft and noncleft sides were significantly improved after surgery to 0.93, 1.06, and 0.97, respectively. The preoperative overlapping nostril area ratio (72.33 percent), nasal tip protrusion-width index (0.48), and nasal index (0.81) also showed significant improvement postoperatively to 83.91 percent, 0.57, and 0.74, respectively., Conclusion: This preliminary study supports the use of natural curvature of rib cartilage as alar rim graft in secondary unilateral cleft rhinoplasty, with long-term improvement regarding nasal symmetry and nasal profile., Clinical Question/level of Evidence: Therapeutic, IV.

Oral cavity cancer is a common cancer type that presents an increasingly serious global problem. Oral squamous cell carcinoma (OSCC) accounts for >90% oral cancer cases. No biomarker tests are currently available for management of this cancer type in clinical practice. Previously, we validated matrix metalloproteinase-1 (MMP1) as one of the most promising salivary biomarkers for OSCC detection. Development of a convenient, rapid and high-throughput assay should further facilitate application of salivary MMP1 measurement for early detection of OSCC. The present study aimed to develop a workflow comprising dry saliva spot (DSS) sampling and immunoenrichment-coupled MALDI-TOF MS (immuno-MALDI) analysis to quantify salivary MMP1. We generated recombinant MMP1 protein and anti-peptide antibodies against MMP1, which were used to optimize the procedures of the entire workflow, including DSS sampling, on-paper protein digestion and elution, KingFisher magnetic particle processor-assisted immuno-enrichment and MALDI-TOF MS analysis. The established workflow was applied to measure salivary MMP1 levels in DSS samples from 5 healthy donors and 9 OSCC cases. The newly developed workflow showed good precision (intra-day and inter-day variations <10%) and accuracy (80-100%) in quantification of MMP1 in DSS samples, with the limit of quantification at 3.07 ng/ml. Using this assay, we successfully detected elevated salivary MMP1 levels (ranging from 5.95 to 242.52 ng/ml) in 7 of 9 OSCC cases while MMP1 was not detectable in samples from the 5 healthy donors. In comparison, the traditional immunoassay was not effective in measuring MMP1 in DSS samples, highlighting the significant advantage of our immuno-MALDI assay. The DSS sampling format confers high flexibility and convenience of collection, storage and delivery of saliva specimens and the KingFisher-assisted immuno-MALDI analysis renders the assay as suitable for high-throughput screening. By combining the two features, the workflow developed in this study should facilitate improvement of molecular diagnostic tests for OSCC using salivary MMP1 as a biomarker., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We developed a new format for liquid crystal (LC)-based multi-microfluidic immunoassays, hosted on a polydimethylsiloxane substrate. In this design, the orientations of the LCs were strongly affected by the interface between the four microchannel walls and surrounding LCs. When the alignment layer was coated inside a microchannel, the LCs oriented homeotropically and appeared dark under crossed polarizers. After antigens bound to the immobilized antibodies on the alignment layer were coated onto the channel walls, the light intensity of the LC molecules changed from dark to bright because of disruption of the LCs. By employing pressure-driven flow, binding of the antigen/antibody could be detected by optical signals in a sequential order. The multi-microfluidic LC biosensor was tested by detecting bovine serum albumin (BSA) and an immunocomplex of BSA antigen/antibody pairs, a protein standard commonly used in labs. We show that this multi-microfluidic immunoassay was able to detect BSA and antigen/antibody BSA pairs with a naked-eye detection limitation of -0.01 µg/mL. Based on this new immunoassay design, a simple and robust device for LC-based label-free microfluidic immunodetection was demonstrated.

A system comprising a gold nanoisland film (Au NIF) covered with a liquid crystal (LC) material is introduced. By applying a voltage across the LC bulk, we demonstrate that changes in the refractive-index and orientation significantly modified the hybrid plasmonic-photonic resonances of the Au NIF. The hybrid structure enabled active control of the spectrum of the resonance wavelength of the metallic nanoisland by means of an externally applied electric field. Our modeling supports the observed results in LC/Au NIF. In a combination of the nanostructured surface with birefringent LCs, nonpolarized wavelength tunability of ~15 nm and absorbance tunability of ~0.024 were achieved in the visible wavelength, opening the door to optical devices and nanoscale sensors.

Background: The relationship between constipation and childhood nocturnal enuresis (NE) has been previously reported; however, this relationship remains controversial. The present study aimed to evaluate the association between constipation and childhood NE., Methods: Data from the Longitudinal Health Insurance Database 2000 (LHID 2000) of Taiwan National Health Insurance Research Database from 2000 to 2013 were collected. A total of 2286 children were enrolled in this study: a case group of 1143 children aged 5-18 years who were diagnosed with NE (NE group) and an age- and sex-matched control group of 1143 children without NE. Conditional logistic regression and odds ratio (OR) for NE were used to examine the association between constipation and childhood NE., Results: The prevalence of NE in the case group (NE group, aged 5-18 years) was 1.03% from 2000 to 2013. The NE group had a higher percentage of constipation in 1 year before the diagnosis of NE. After stratification for sex, both boys and girls with constipation had higher OR for NE. With stratification for age, children aged 5-12 and 7-12 years had a higher OR for NE., Conclusions: Constipation is associated with childhood NE in Taiwan, particularly in children aged 5-7 and 7-12 years.

For oral cancer, numerous saliva- and plasma-derived protein biomarker candidates have been discovered and/or verified; however, it is unclear about the behavior of these candidates as saliva or plasma biomarkers. In this study, we developed two targeted assays, MRM and SISCAPA-MRM, to quantify 30 potential biomarkers in both plasma and saliva samples collected from 30 healthy controls and 30 oral cancer patients. Single point measurements were used for target quantification while response curves for assay metric determination. In comparison with MRM assay, SISCAPA-MRM effectively improved (>1.5 fold) the detection sensitivity of 11 and 21 targets in measurement of saliva and plasma samples, respectively. The integrated results revealed that the salivary levels of these 30 selected biomarkers weakly correlated (r < 0.2) to their plasma levels. Five candidate biomarkers (MMP1, PADI1, TNC, CSTA and MMP3) exhibited significant alterations and disease-discriminating powers (AUC = 0.914, 0.827, 0.813, 0.77, and 0.753) in saliva sample; nevertheless, no such targets could be found in plasma samples. Our data support the notion that saliva may be more suitable for the protein biomarker-based detection of oral cancer, and the newly developed SISCAPA-MRM assay could be applied to verify multiple oral cancer biomarker candidates in saliva samples. SIGNIFICANCE: In this work we systematically determined the abundance of 30 selected targets in the paired saliva and plasma samples to evaluate the utility of saliva and plasma samples for protein biomarker-based detection of oral cancer. Our study provides significant evidence to support the use of saliva, but not blood samples, offer more opportunity to achieve the success of protein biomarker discovery for oral cancer detection., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Hepatocellular carcinoma (HCC) is among the most common causes of cancer death in men. Whether or not a longitudinal follow-up of circulating tumor cells (CTCs) before and at different time points during systemic/targeted therapy is useful for monitoring the treatment response of patients with locally advanced or metastatic HCC has been evaluated in this study. Blood samples ( n = 104) were obtained from patients with locally advanced or metastatic HCC ( n = 30) for the enrichment of CTCs by a negative selection method. Analysis of the blood samples from patients with defined disease status ( n = 81) revealed that those with progressive disease (PD, n = 37) had significantly higher CTC counts compared to those with a partial response (PR) or stable disease (SD; n = 44 for PR + SD, p = 0.0002). The median CTC count for patients with PD and for patients with PR and SD was 50 (interquartile range 21-139) and 15 (interquartile range 4-41) cells/mL of blood, respectively. A longitudinal analysis of patients ( n = 17) after a series of blood collections demonstrated that a change in the CTC count correlated with the patient treatment response in most of the cases and was particularly useful for monitoring patients without elevated serum alpha-fetoprotein (AFP) levels. Sequential CTC enumeration during treatment can supplement standard medical tests and benefit the management of patients with locally advanced or metastatic HCC, in particular for the AFP-low cases.

Antibodies from B-cell clonal lineages share sequence and structural properties as well as epitope specificity. Clonally unrelated antibodies can similarly share sequence and specificity properties and are said to be convergent. Convergent antibody responses against several antigens have been described in humans and mice and include different classes of shared sequence features. In particular, some antigens and epitopes can induce convergent responses of clonally unrelated antibodies with restricted heavy (V H ) and light (V L ) chain variable region germline segment usage without similarity in the heavy chain third complementarity-determining region (CDR H3), a critical specificity determinant. Whether these V germline segment-restricted responses reflect a general epitope specificity restriction of antibodies with shared V H /V L pairing is not known. Here, we investigated this question by determining patterns of antigen binding competition between clonally unrelated antigen-specific rat antibodies from paired-chain deep sequencing datasets selected based solely on V H /V L pairing. We found that antibodies with shared V H /V L germline segment pairings but divergent CDR H3 sequences almost invariably have restricted epitope specificity indicated by shared binding competition patterns. This epitope restriction included 82 of 85 clonally unrelated antibodies with 13 different V H /V L pairings binding in 8 epitope groups in 2 antigens. The corollary that antibodies with shared V H /V L pairing and epitope-restricted binding can accommodate widely divergent CDR H3 sequences was confirmed by in vitro selection of variants of anti-human epidermal growth factor receptor 2 antibodies known to mediate critical antigen interactions through CDR H3. Our results show that restricted epitope specificity determined by V H /V L germline segment pairing is a general property of rodent antigen-specific antibodies.

This article presents a high-voltage (HV) pulse driver based on silicon-on-insulator (SOI) technology for biomedical ultrasound actuators and multi-channel portable imaging systems specifically. The pulse driver, which receives an external low-voltage drive signal and produces high-voltage pulses with a balanced rising and falling edge, is designed by synthesizing high-speed, capacitor-coupled level-shifters with a high-voltage H-bridge output stage. In addition, an on-chip floating power supply has also been developed to simplify powering the entire system and reduce static power consumption. The electrical and acoustic performance of the integrated eight-channel pulse driver has been verified by using medical-grade ultrasound probes to acquire the transmit/echo signals. The driver can produce pulse signals >100 Vpp with rise and fall times within 18.6 and 18.5 ns, respectively. The static power required to support the overall system is less than 3.6 mW, and the power consumption of the system during excitation is less than 50 mW per channel. The second harmonic distortion of the output pulse signal is as low as -40 dBc, indicating that the integrated multi-channel pulse driver can be used in advanced portable ultrasonic imaging systems., Competing Interests: The authors declare no conflict of interest.

Background: The philtrum plays an important role in determining the shape and form of the upper lip and creates individual identity. Postburn scar contracture in this area often leads to severe functional and aesthetic disfigurement. In this report, we present a novel method of philtrum reconstruction using full-thickness skin grafts (FTSGs) after burn injury., Methods: Between August 2011 and October 2017, 8 patients with postburn philtrum deformity who underwent FTSG for replacement of the whole upper lip unit with a silastic tube for creation of the philtral dimple were included. A review of photographic documentation was used to evaluate the aesthetic results., Results: The size of FTSG ranged from 4 × 9 to 6 × 17 cm. No patient had immediate postoperative complications, such as hematoma, infection, or necrosis. The crests of the ridges preserved their height and length, and the dimple remained visible after an average follow-up of 30.4 months (range, 3-69 months). All patients were satisfied with both functional and aesthetic results., Conclusions: This technique of single-stage reconstruction of the upper lip and philtrum with FTSG and silastic tube produced favorable results in the formation of the philtral ridges and the dimple. Through thoughtful preoperative design, meticulous scar release, and skin grafting, satisfactory functional and aesthetic results are achievable.

Background: Silicone-polytetrafluoroethylene composite implants are fast gaining popularity in Asian rhinoplasty. Nonetheless, implant displacement, erythematous reactions, and infections still occur in the authors' patient group during long-term follow-up., Objectives: The authors reported successful experience of combining the utilization of silicone-polytetrafluoroethylene composite implants with onlay temporal fascial grafts to circumvent these complications., Methods: Sixty-four patients of Asian ethnicity underwent augmentation rhinoplasty utilizing an I-shaped composite implant with an onlay fascial graft from January 2015 to June 2018, with a mean follow-up period of 13.5 months. This patient group was compared with a control group of 177 Asian patients who underwent augmentation rhinoplasty utilizing the same composite implant but without the addition of a fascial graft; the control group was treated from February 2012 to June 2015, with a mean follow-up of 42.0 months. Complications were compared between these 2 patient groups, specifically focusing on malposition/deviations, erythema, and infections., Results: There was a marked decrease in complication rates with the addition of an onlay temporal fascial graft to cover the composite implant in augmentation rhinoplasty (7.8% vs 14.7%) as well as the rate of erythematous reactions (0% vs 6.2%, P = 0.04), infection (1.6% vs 1.1%), and implant malposition/deviation (0% vs 4.5%). Harvesting the temporal fascia and fashioning the onlay graft added an additional 33 minutes on average per procedure. No donor site morbidity was encountered., Conclusions: Although the operative time increased, the benefits of adding onlay fascial grafts to silicone-polytetrafluoroethylene implants in alloplastic augmentation rhinoplasty outweigh the drawbacks, as evidenced by the decrease in erythematous reactions., (© 2019 The American Society for Aesthetic Plastic Surgery, Inc. Reprints and permission: journals.permissions@oup.com.)

Background/purpose: HIV-infected patients have a high prevalence of low bone mineral density (BMD), but BMD changes remain unclear. This cross-sectional retrospective observational study aimed to characterize the prevalence and associated factors of low BMD in HIV patients., Methods: Between 1 January 2015 and 31 December 2016, all patients aged 20 years or greater who sought for HIV care were included. BMD was measured by dual-energy X-ray absorptiometry. Multivariable analyses of the association with HIV disease status, treatment and anthropometric parameters were performed. Circulating fibroblast growth factor 23 and intact parathyroid hormone were measured., Results: A total of 137 patients was included; their median age was 39 years old; 97.8% were treated with combination antiretroviral therapy (cART); Body mass index (BMI) was 21.97 kg/m 2 . Sixty-one patients (44.5%) showed low BMD (osteopenia and osteoporosis) based on the WHO criteria. The median BMD was -0.80 g/cm 2 (IQR, -1.5 to -0.2). The prevalence rate of low BMD was 37% in those who were aged 20-29 years, 45.2% in those who were aged 30-39 years, 45.2% in those who were aged 40-49 years, 45.8% in those who were aged 50-59 years, and 53.8% in those who were aged ≧60 years. More than half of patients (50.4%, 69/137) were younger than 40 years. Compared with normal BMD group, the low BMD group has a higher proportion of secondary hyperparathyroidism (18.0% vs 5.3%, p: 0.026) and a lower median C-terminal FGF23 level (48.92 vs 62.61 pg/ml, p: 0.008). Univariate and multivariate analyses of the factors associated with low BMD. We found that only serum intact-parathyroid hormone (iPTH) > 69 pg/ml (OR, 3.86; 95% CI, 1.14-13.09) was statistically significant associated with low BMD in multivariate analysis., Conclusions: This cohort-based survey showed a high prevalence of low BMD among HIV-infected adults which included young-age patient in an university hospital. Secondary hyperparathyroidism was significantly associated with low BMD. There was no association between FGF23 and low BMD., (Copyright © 2018. Published by Elsevier B.V.)

Background: In the past two decades, biologists have been able to identify the gene signatures associated with various phenotypes through the monitoring of gene expressions with high-throughput biotechnologies. These gene signatures have in turn been successfully applied to drug development, disease prevention, crop improvement, etc. However, ignoring the interactions among genes has weakened the predictive power of gene signatures in practical applications. Gene regulatory networks, in which genes are represented by nodes and the associations between genes are represented by edges, are typically constructed to analyze and visualize such gene interactions. More specifically, the present study sought to measure gene-gene associations by using the coefficient of intrinsic dependence (CID) to capture more nonlinear as well as cause-effect gene relationships., Results: A stepwise procedure using the CID along with the partial coefficient of intrinsic dependence (pCID) was demonstrated for the rebuilding of simulated networks and the well-known CBF-COR pathway under cold stress using Arabidopsis microarray data. The procedure was also applied to the construction of bHLH gene regulatory pathways under abiotic stresses using rice microarray data, in which OsbHLH104, a putative phytochrome-interacting factor (OsPIF14), and OsbHLH060, a positive regulator of iron homeostasis (OsPRI1) were inferred as the most affiliated genes. The inferred regulatory pathways were verified through literature reviews., Conclusions: The proposed method can efficiently decipher gene regulatory pathways and may assist in achieving higher predictive power in practical applications. The lack of any mention in the literature of some of the regulatory event may have been due to the high complexity of the regulatory systems in the plant transcription, a possibility which could potentially be confirmed in the near future given ongoing rapid developments in bio-technology.

The purpose of this study was to examine the effectiveness of a stage-matched intervention performed at outpatient clinics. Participants were randomly assigned to an intervention group (IG) or usual care group (UCG). The trial was targeted on smoking patients with coronary heart disease or diabetes. After completing the 3-month intervention, both groups received a telephone follow-up at 6 months. This analysis showed that the outcomes of the IG for the 7-day point prevalence (PP) of abstinence (odds ratio [OR] = 2.00; p = .001) and 30-day PP (OR = 2.27; p = .004) at 6 months were significantly better than the UCG. Stage of change (OR = 4.06; p < .001) and decreased daily cigarette consumption by 50% at 6 months (OR = 2.26; p = .019) outcomes also improved significantly. The preliminary results showed that a nurse-led cessation intervention in clinics may be an effective approach to help outpatients quit smoking.

Self-healing technology promises a generation of innovation in cross-cutting subjects ranging from electronic skins, to wearable electronics, to point-of-care biomedical sensing modules. Recently, scientists have successfully pulled off significant advances in self-healing components including sensors, energy devices, transistors, and even integrated circuits. Lasers, one of the most important light sources, integrated with autonomous self-healability should be endowed with more functionalities and opportunities; however, the study of self-healing lasers is absent in all published reports. Here, the soft and self-healable random laser (SSRL) is presented. The SSRL can not only endure extreme external strain but also withstand several cutting/healing test cycles. Particularly, the damaged SSRL enables its functionality to be restored within just few minutes without the need of additional energy, chemical/electrical agents, or other healing stimuli, truly exhibiting a supple yet robust laser prototype. It is believed that SSRL can serve as a vital building block for next-generation laser technology as well as follow-on self-healing optoelectronics.

Biosensors based on liquid crystal (LC) materials can be made by employing the sensitive interfacial effect between LC molecules and alignment layers on substrates. In the past, the optical texture observation method was used in the LC biosensor field. However, the method is limited by a complicated fabrication process and quantitative reproducibility of results that bv evidence that both the reliability and accuracy of LC biosensors need to be improved. In this report, we demonstrate that cholesteric LC (CLC) cells in which one substrate is coated with a vertically aligned layer can be used as a new sensing technology. The chirality of the single vertically anchored (SVA)/CLC biosensor was tested by detecting bovine serum albumin (BSA), a protein standard commonly used in the lab. The colors and corresponding spectrum of the SVA/CLC biosensor changed with the BSA concentrations. A detection limit of 1 ng/ml was observed for the SVA/CLC biosensor. The linear optical properties of the SVA/CLC biosensor produced cheap, inexpensive, and color-indicating detection of biomolecules, and may promote the technology of point-of-care devices for disease-related biomarker detection., Competing Interests: The authors declare that there are no conflicts of interest related to this article., (© 2019 Optical Society of America under the terms of the OSA Open Access Publishing Agreement.)

Obtaining full-length antibody heavy- and light-chain variable regions from individual B cells at scale remains a challenging problem. Here we use high-throughput single-cell B-cell receptor sequencing (scBCR-seq) to obtain accurately paired full-length variable regions in a massively parallel fashion. We sequenced more than 250,000 B cells from rat, mouse and human repertoires to characterize their lineages and expansion. In addition, we immunized rats with chicken ovalbumin and profiled antigen-reactive B cells from lymph nodes of immunized animals. The scBCR-seq data recovered 81% ( n  = 56/69) of B-cell lineages identified from hybridomas generated from the same set of B cells subjected to scBCR-seq. Importantly, scBCR-seq identified an additional 710 candidate lineages not recovered as hybridomas. We synthesized, expressed and tested 93 clones from the identified lineages and found that 99% ( n  = 92/93) of the clones were antigen-reactive. Our results establish scBCR-seq as a powerful tool for antibody discovery., Competing Interests: Competing interestsThe authors as noted in the authors section are employees of Genentech or SciGenom Labs. Genentech authors hold shares in Roche. The authors declare no nonfinancial conflicts of interest.

In the present study, we intended to examine the temporal association between loneliness and depression among community-based older adults. We analyzed data on 3,920 persons with a mean age of 67.6 years at baseline from the Taiwan Longitudinal Study on Aging. Structural equation modeling was used to investigate the temporal association between loneliness and depression over a period of 14 years. The results showed that the temporal association between loneliness and depression was bidirectional but stronger and more robust for depression as the initial symptom. Loneliness at Time 1 and 3, respectively, significantly predicted depression at Time 2 and 4. Depression at each time point had a significant effect on subsequent loneliness, even considering covariates. Future prevention programs for older adults with depression should also target at dealing with their loneliness, and vice versa. This study also highlights the need to assess and to manage the two symptoms simultaneously.

Background: Symmetry and balance in nasal reconstruction can be hard to achieve. Traditionally, a foil template modeled after the unaffected contralateral side is used in the design of a forehead flap. Crude two-dimensional models often generate underwhelming results. To better simulate complex nasal topography, three-dimensional printing technology was applied to nasal reconstruction., Methods: Between May 2012 and October 2016, twenty patients underwent forehead flap nasal reconstruction for heminasal deformities. Ten reconstructions were guided with prefabricated three-dimensional templates (CAD/CAM), and ten patients underwent traditional nasal reconstruction without CAD/CAM. In the CAD/CAM group, two templates were printed: contour guide and framework guide. These were a reference for skin flap design and cartilage framework design, respectively. Photographic records and photogrammetry was used to evaluate results., Results: The mean follow-up time was 19.3 months (range, 6 months to 38 months) in the control group and 17.4 months (range, 7 months to 35 months) in the CAD/CAM group. Without CAD/CAM, there was asymmetry in alar width, alar area, nostril height, width and area (p < 0.05) between reconstructed and native structures. In the CAD/CAM group, there were asymmetries of nostril-related parameters only. After quantifying asymmetries as a percentage, the CAD/CAM group demonstrated more symmetric reconstructions, particularly in alar width (p = 0.043) and alar area (p = 0.003)., Conclusions: When CAD/CAM guidance and three-dimensional printing was used, there was greater symmetry between reconstructed and native structures of the nose., (Copyright © 2019 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)