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The study's objective is to assess the feasibility and utility of VSP for maxillary reconstruction with the scapular free flap.An open-source VSP platform was used to create the reconstruction models and simple guides. Clinical, operative, and postoperative data were collected.Ten patients in the VSP cohort and 18 in the non-VSP control cohort were included in the study. There was a significant reduction in operative time (256.0 ± 69.4 vs. 448.1 ± 108.2 min, p 0.01), tracheotomy rate (20% vs. 72%, p 0.01), increased two-team utilization rate (80% vs. 0%, p 0.01) and better reconstructive accuracy (7.5 ± 3.4 vs. 11.7 ± 7.6 mm, p = 0.048) for the VSP cohort.Maxillary reconstruction planned with an in-house open-source VSP platform and accompanied simple guides can facilitate a two-team approach, reduce operative time, and improve structural accuracy. This open-source technology has great potential to be readily applied in other institutions to improve efficiency and outcomes.

Genetic diseases affecting the skeletal system present with a wide range of symptoms that make diagnosis and treatment difficult. Genome-wide association and sequencing studies have identified genes linked to human skeletal diseases. Gene editing of zebrafish models allows researchers to further examine the link between genotype and phenotype, with the long-term goal of improving diagnosis and treatment. While current automated tools enable rapid and in-depth phenotyping of the axial skeleton, characterizing the effects of mutations on the craniofacial skeleton has been more challenging. The objective of this study was to evaluate a semi-automated screening tool can be used to quantify craniofacial variations in zebrafish models using four genes that have been associated with human skeletal diseases (meox1, plod2, sost, and wnt16) as test cases. We used traditional landmarks to ground truth our dataset and pseudolandmarks to quantify variation across the 3D cranial skeleton between the groups (somatic crispant, germline mutant, and control fish). The proposed pipeline identified variation between the crispant or mutant fish and control fish for four genes. Variation in phenotypes parallel human craniofacial symptoms for two of the four genes tested. This study demonstrates the potential as well as the limitations of our pipeline as a screening tool to examine multi-dimensional phenotypes associated with the zebrafish craniofacial skeleton.

OBJECTIVE The aim of this study is to investigate whether the number of metastatic lymph nodes (LNs) could be used as a basis in the radioactive iodine (RAI) dose selection for patients with papillary thyroid carcinoma (PTC). PATIENTS A total of 595 patients with PTC who received first RAI therapy after total or near-total thyroidectomy and had no evidence of disease in treatment response assessment were retrospectively enroled from five hospitals. The patients were classified into two subgroups based on the number of metastatic LNs (>5). The multivariate Cox-proportional hazard model was performed to identify the significant factors for recurrence prediction in each group as well as all enroled patients. RESULTS Overall, 22 (3.7%) out of 595 patients had the recurrent disease during the follow-up period. The number of metastatic LNs (>5) was only a significant factor for recurrence prediction in all enroled patients (odds ratio: 7.834, p

T and B lymphocytes are two major adaptive immune cells in the human defense system. To real-time monitor their diverse functions, a live-cell-selective probe for only one cell type is need to investigate the complex interaction of the immune cells. Herein, a small-molecule probe CDyB for live B cells is developed by an unbiased fluorescence library screening. The cell selectivity was confirmed by multiparametric single-cell analysis using CyTOF. Through a systematic SLC-CRISPRi library screening, the molecular target of CDyB was identified as SLC35C2 transporter based on a gating-oriented live-cell distinction (GOLD) mechanism. The gene expression analysis and knock-out experiments validated that the SLC35C2 transporter was the target for CDyB distinction. Interestingly, when CDyB was applied to study B cell development, the CDyB fluorescence and SLC35C2 expression were positively correlated with the B cell maturation process, and not involved in the T cell development.

As bromate removal and reduction can be also achieved using metals, aluminum (Al) appears as the most promising one for reduction of bromate because Al is abundant element and exhibits a high reduction power. Reactions between bromate and Al shall be even enhanced through ultrasound (US) process because US can facilitate mass transfer on liquid/solid interfaces and clean surfaces via generating microscale turbulence to facilitate reactions. Therefore, the aim of this study is for the first time to investigate the effect of US on bromate removal by Al metal. Specifically, Al particle would be treated by HCl to afford HCl-treated Al (HCTAL), which is capable of removing bromate and even reducing it to bromide. Such a mechanism is also validated by density function theory calculation through determining adsorption energy as -152.8 kJ/mole, and oxygen atoms of bromate would be extracted and reacted with Al atoms, releasing bromide ion. US not only facilitated bromate removal by further increasing removal capacity under the acidic condition but also suppressed the inhibitive effect from basicity at relatively high pH. The spent HCTAL could still remove bromate and convert it to bromide after regeneration. These features indicate that US considerably enhances bromate removal by Al. PRACTITIONER POINTS: Bromate removed by Al is elucidated by DFT calculation with E

Electromagnetic fields (EMFs) are widely used in a number of cell therapies and bone disorder treatments, and nanomagnetic particles (NMPs) also promote cell activity. In this study, we investigated the synergistic effects of EMFs and NMPs on the osteogenesis of the human Saos‐2 osteoblast cell line and in a rat calvarial defect model. The Saos‐2 cells and critical‐size calvarial defects of the rats were exposed to EMF (1 mT, 45 Hz, 8 h/day) with or without Fe3O4 NMPs. Biocompatibility was evaluated with MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) and LDH (lactate dehydrogenase) assays. This analysis showed that NMP and EMF did not induce cell toxicity. Quantitative reverse‐transcription polymerase chain reaction indicated that the osteogenesis‐related markers were highly expressed in the NMP‐incorporated Saos‐2 cells after exposure to EMF. Also, the expression of gene‐encoding proteins involved in calcium channels was activated and the calcium concentration of the NMP‐incorporated + EMF‐exposed group was increased compared with the control group. In particular, in the NMP‐incorporated + EMF‐exposed group, all osteogenic proteins were more abundantly expressed than in the control group. This indicated that the NMP incorporation + EMF exposure induced a signaling pathway through activation of p‐ERK and calcium channels. Also, in vivo evaluation revealed that rat calvarial defects treated with EMFs and NMPs had good regeneration results with new bone formation and increased mineral density after 6 weeks. Altogether, these results suggest that NMP treatment or EMF exposure of Saos‐2 cells can increase osteogenic activity and NMP incorporation following EMF exposure which is synergistically efficient for osteogenesis.

This study compared the topography of different titanium surface structures (TiO2 nanotube and grain) with similar elemental compositions (TiO2 and fluorine [F]) on the Ti surface. High magnification indicated that the surfaces of the control and etching groups were similar to each other in a flat, smooth form. The group anodized for 1 h was observed with TiO2 nanotubes organized very neatly and regularly. In the group anodized for 30 min after etching, uneven wave and nanopore structures were observed. In addition, MTT assay showed that the F of the surface did not adversely affect cell viability, and the initial cell adhesion was increased in the 2.8% F‐incorporated TiO2 nanograin. At the edge of adherent cells, filopodia were observed in spreading form on the surfaces of the anodizing and two‐step processing groups, and they were observed in a branch shape in the control and etching groups. Moreover, cell adhesion molecule and osteogenesis marker expression was increased at the F‐incorporated TiO2 nanostructure. In addition, it was found that the expression of p‐extracellular signal‐regulated kinase (ERK) and p‐cAMP response element‐binding protein (CREB) increased in the TiO2 nanograin with the nanopore surface compared to the micro rough and nanotube surfaces relative to the osteogenic‐related gene expression patterns. As a result, this study confirmed that the topographic structure of the surface is more affected by osteogenic differentiation than the pore size and that differentiation by specific surface composition components is by CREB. Thus, the synergy effect of osteogenic differentiation was confirmed by the simultaneous activation of CREB/ERK.

Here, we discovered that targeting cell cycle processes or protein ubiquitination pathways are promising treatment strategies for overcoming resistance to EGFR inhibitors in lung cancer using a genome‐scale CRISPR‐Cas9 screening. Combination therapies targeting each of these two processes such as nutlin‐3 and carfilzomib increased cancer cell death when combined with erlotinib in both in vitro and in vivo experiments., Erlotinib is highly effective in lung cancer patients with epidermal growth factor receptor (EGFR) mutations. However, despite initial favorable responses, most patients rapidly develop resistance to erlotinib soon after the initial treatment. This study aims to identify new genes and pathways associated with erlotinib resistance mechanisms in order to develop novel therapeutic strategies. Here, we induced knockout (KO) mutations in erlotinib‐resistant human lung cancer cells (NCI‐H820) using a genome‐scale CRISPR‐Cas9 sgRNA library to screen for genes involved in erlotinib susceptibility. The spectrum of sgRNAs incorporated among erlotinib‐treated cells was substantially different to that of the untreated cells. Gene set analyses showed a significant depletion of ‘cell cycle process’ and ‘protein ubiquitination pathway’ genes among erlotinib‐treated cells. Chemical inhibitors targeting genes in these two pathways, such as nutlin‐3 and carfilzomib, increased cancer cell death when combined with erlotinib in both in vitro cell line and in vivo patient‐derived xenograft experiments. Therefore, we propose that targeting cell cycle processes or protein ubiquitination pathways are promising treatment strategies for overcoming resistance to EGFR inhibitors in lung cancer.

Using detailed data for fieldwork hours and audit hours by rank from audit engagements in Korea, we examine whether audits conducted under workload imbalance, proxied by busy‐season audits, impair audit quality, and how auditors adjust staff assignments for busy‐season audits. We generally find that busy‐season audits are associated with lower audit quality, and that audit firms reduce the involvement of senior auditors during busy‐season audits. In addition, the greater the involvement of senior auditors and junior auditors, the lesser the deterioration in audit quality. Finally, although there is no increase in interim audits in response to workload imbalance during busy seasons, increasing interim audits can mitigate the negative impact of busy‐season audits on audit quality. Our results are relevant to auditors and regulators, who have expressed concerns about the adverse effects of workload imbalance on audit quality. Desequilibre de la charge de travail : reactions des auditeurs et incidence sur la qualite de l'audit Les auteurs analysent des donnees exhaustives concernant les heures de travail sur le terrain et les heures d'audit selon le rang, tirees de missions d'audit realisees en Coree, afin de determiner, d'une part, si la realisation d'audits en situation de desequilibre de la charge de travail — selon la variable substitutive des audits de la periode de pointe — est prejudiciable a la qualite de l'audit et, d'autre part, comment les auditeurs ajustent les affectations de personnel aux audits de la periode de pointe. De facon generale, les auteurs constatent que les audits de la periode de pointe sont associes a une qualite inferieure de l'audit et que les cabinets d'audit reduisent la participation des responsables de mission aux audits de la periode de pointe. En outre, plus la participation des responsables de mission et des assistants d'audit est grande, moins la deterioration de la qualite de l'audit est marquee. Enfin, meme si aucune augmentation des audits intermediaires n'est observee en reaction au desequilibre de la charge de travail au cours des periodes de pointe, la multiplication des audits intermediaires peut attenuer l'incidence negative des audits de la periode de pointe sur la qualite de l'audit. Les resultats de l’etude interesseront les auditeurs et les autorites de reglementation, qui se sont dits preoccupes par les repercussions nefastes du desequilibre de la charge de travail sur la qualite de l'audit.

Approximately half of lung cancer patients (LCP) receiving chemotherapy are experiencing cancer-related fatigue (CRF). In East Asia, herbal medicines (HMs) have been used as tonics due to their anti-fatigue effect. This systematic review evaluated the effectiveness and safety of HMs for CRF in LCP. We comprehensively searched 12 electronic medical databases to search randomized controlled trials (RCTs) and quasi-RCTs investigating HMs for CRF in LCP, published up to September 2019. The primary outcome was the fatigue severity. Secondary outcomes included patients' quality of life (QOL), activities of daily life (ADL), and incidence of adverse events. Cochrane's risk of bias tool assessed the methodological quality of included RCTs. The risk ratio or mean difference was estimated with 95% confidence intervals by performing a meta-analysis. Twelve RCTs with 861 participants were included. Compared to conventional medicine alone, HM combined with conventional medicine significantly improved fatigue level, QOL, and ADL. As monotherapy, HM significantly improved ADL compared with megestrol. No serious HM-related adverse events were reported. Limited evidence suggests that HM could be effective and safe for CRF in LCP. However, further high-quality RCTs are needed to confirm these findings owing to the small number and low methodological quality of the included studies.

Although previous studies have shown that the administration of fibroblast growth factor 21 (FGF21) reverses hepatic steatosis, the mechanism by which FGF21 exerts a therapeutic effect on nonalcoholic fatty liver disease (NAFLD) is not yet entirely understood. We previously demonstrated that hepatic six transmembrane protein of prostate 2 (STAMP2) may represent a suitable target for NAFLD. We investigated the mechanism underlying the therapeutic effect of recombinant FGF21 on NAFLD, focusing on the involvement of hepatic STAMP2. In this study, we used human nonalcoholic steatosis patient pathology samples, C57BL/6 mice for a high-fat diet (HFD)-induced in vivo NAFLD model, and used human primary hepatocytes and HepG2 cells for oleic acid (OA)-induced in vitro NAFLD model. We observed that recombinant FGF21 treatment ameliorated hepatic steatosis and insulin resistance through the upregulation of STAMP2 expression. We further observed hepatic iron overload (HIO) and reduced iron exporter, ferroportin expression in the liver samples obtained from human NAFLD patients, and HFD-induced NAFLD mice and in OA-treated HepG2 cells. Importantly, recombinant FGF21 improved HIO through the hepatic STAMP2-mediated upregulation of ferroportin expression. Our data suggest that hepatic STAMP2 may represent a suitable therapeutic intervention target for FGF21-induced improvement of NAFLD accompanying HIO.

Aim Predictive accuracy of cervical funneling for successful vaginal delivery prior to labor induction was compared to that of conventional methods such as Bishop score and cervical length. Methods Prospective observational study was conducted on nulliparous women at 38 gestational weeks or more with intact membranes who delivered vaginally following labor induction. Transvaginal ultrasound was performed prior to labor induction to evaluate the cervix, to determine the cervical length and to check for the presence of funneling. Following pelvic examinations, the Bishop score was calculated. Predictive accuracy of the three different methods, namely cervical funneling, cervical length and Bishop, were compared. Results A total of 235 nulliparous women with intact membranes were recruited. Of these, 194 women (82.6%) had successful vaginal deliveries following induction. Cervical funneling was observed in 105 women (44.7%). The rate of successful vaginal delivery was significantly higher in women with cervical funneling than in those without funneling (90.5% vs 76.2%, P

Background and objectives Ablative fractional laser (AFL) systems are commonly used to treat various scars, and recent research has indicated that early treatment with AFL may have a preventive effect on scars. This study was designed to evaluate the efficacy of early treatment with a 10,600 nm carbon dioxide (CO2 ) AFL on thyroidectomy scars and compare it to late (conventional) treatment for the same and untreated controls. Study design/materials and methods We performed a prospective, evaluator-blinded, split-scar study on fresh thyroidectomy scars between July 2014 and July 2017. Scars were divided into two equal portions. Early AFL treatment had begun 1 month after surgery; five sessions on the right half of the scar was performed at 1-month intervals. Late AFL treatment followed for 1 month after the final early treatment session on the left half of the scar at the same interval. The scars were evaluated at 6 and 11 months postoperatively using scar analysis scales and patient questionnaires. Results Twenty-four out of 28 patients completed the study. The mean decrease in Vancouver Scar Scale (VSS) scores was significantly higher for the early treated right halves of the scars both at the 6th month (vs. untreated controls) and at the 11th month (vs. late treated controls). The VSS subset analysis showed that the early treated sides had significantly greater improvement in pliability and height than the control sides at each point of evaluation. Conclusions Early postoperative AFL treatment is safe and effective in improving linear surgical scars, such as thyroidectomy scars, and may be a promising option for scar prevention. Lasers Surg. Med. © 2020 Wiley Periodicals, Inc.

Prompt recognition and treatment for thrombotic thrombocytopenic purpura (TTP) are critical to prevent the irreversible manifestations of this rare and quickly fatal hematologic disorder. Untreated TTP is typically a rapid‐onset disease with mortality exceeding 90% within days in the absence of appropriate treatment. In the current report, we describe a case of immune‐mediated TTP (iTTP) in a 62‐year‐old man manifesting as longstanding thrombocytopenia, recurrent cardioembolic strokes, and valvular thrombogenesis over a period of 3 years. We provide correlative evidence to support the potential contribution of adalimumab, a TNFα inhibitor, to the development of iTTP. We offer several educational insights regarding the identification of atypical presentations of iTTP owing to the longstanding disease course and numerous clinical comorbidities seen in this patient., We report an atypical manifestation of immune‐mediated thrombotic thrombocytopenic purpura (TTP) that we hypothesize represents a longstanding, or “smoldering,” process. As typified by this case, the prompt recognition and treatment for immune‐mediated TTP are often confounded by clinical comorbidities. Thus, TTP should be considered in cases of unremitting thrombocytopenia of unknown origin in patients with stroke or other thrombosis.

Numerical generation of physical states is essential to all scientific research fields. The role of a numerical generator is not limited to understanding experimental results; it can also be employed to predict or investigate characteristics of uncharted systems. A variational autoencoder model is devised and applied to a magnetic system to generate energetically stable magnetic states with low local deformation. The spin structure stabilization is made possible by taking the explicit magnetic Hamiltonian into account to minimize energy in the training process. A significant advantage of the model is that the generator can create a long‐range ordered ground state of spin configuration by increasing the role of stabilization even if the ground states are not necessarily included in the training process. It is expected that the proposed Hamiltonian‐guided generative model can bring about great advances in numerical approaches used in various scientific research fields., An energy‐minimization variational autoencoder model is devised to generate energetically stable physical states by taking the explicit Hamiltonian into the training process. A significant advantage of the model is that the generator can produce the ground states of various systems even if the ground states are not necessarily included in the training process.

Background and aim Guidelines for selecting the eradication regimen for Helicobacter pylori reinfection remain unclear. This study aimed to evaluate the eradication rate of H. pylori reinfection in patients with a previous infection successfully eradicated with index triple therapy. Methods This was a single-center, retrospective case-control study. A total of 10 468 H. pylori-infected patients treated with proton-pump inhibitor-based triple eradication therapy at a tertiary medical institution between 2005 and 2016 were enrolled. We reviewed the medical records of the enrolled patients and compared the treatment outcomes in those with H. pylori reinfection after a successful eradication. Results Helicobacter pylori infection was successfully eradicated with the index triple therapy in 7770 patients (74.2%). Among 3567 patients followed up for > 1 year, H. pylori reinfection occurred in 420 (11.8%; 3.06% per person-year) during a median follow-up of 39.1 months (interquartile range, 23.5-58.7 months). Of these patients, 164 received eradication therapy for reinfection (triple therapy in 102 and quadruple therapy in 62) and had follow-up data. Triple therapy showed an eradication rate of 78.4% for H. pylori reinfection, which was not significantly different from that of the index triple therapy (P = 0.394). Quadruple therapy for reinfection exhibited a better eradication rate (87.1%) than triple therapy but without statistical significance (P = 0.237). Conclusions Retreatment with triple therapy for H. pylori reinfection after successful eradication of prior infection showed comparable outcomes to the index triple therapy. Bismuth-containing quadruple therapy for reinfection tended to have a better eradication rate than did triple therapy.

INTRODUCTION The objective of this study was to determine whether patients with carpal tunnel syndrome (CTS) manifest changes in early-stage motor function and to investigate the utility of a gyrosensor for quantitative evaluation of motor function. METHODS Angular velocity signal was measured during finger tapping in 52 patients with mild-to-moderate CTS and 45 controls. Four finger-tapping performance (FTP) values-root-mean-squared (RMS) velocity, RMS angle, peak power, and total power-were derived from the signal. RESULTS All FTP values were significantly lower in patients with CTS than in controls (P = 0.001 or P

Background Currently, diagnosis of equine coronavirus (ECoV) relies on the exclusion of other infectious causes of enteric disease along with molecular detection of ECoV in feces or tissue. Although this approach is complete, it is costly and may not always be achievable. Objective We hypothesized that the overall fecal shedding of ECoV in hospitalized horses is low. Our objective was to determine whether systemically healthy horses and horses with gastrointestinal disorders shed ECoV in their feces at the time of admission to a referral hospital and after 48 hours of stress associated with hospitalization. Animals One-hundred thirty adult horses admitted to the Washington State University Veterinary Teaching Hospital for gastrointestinal disease (n = 65) or for imaging under anesthesia (n = 65) that were hospitalized for 48 hours. Owner consent was obtained before sampling. Methods Fecal samples were collected at admission and 48 hours later. Polymerase chain reaction (PCR) for ECoV and electron microscopy (EM) were performed on all samples. Results Only 1 of 258 fecal samples was PCR-positive for ECoV. Electron microscopy identified ECoV-like particles in 9 of 258 samples, parvovirus-like particles in 4 of 258 samples, and rotavirus-like particles in 1 of 258 samples. Conclusions and clinical importance The presence of ECoV in feces of hospitalized adult horses was low. Thus, fecal samples that are PCR-positive for ECoV in adult horses that have clinical signs consistent with this viral infection are likely to be of diagnostic relevance. The clinical relevance of the viruses observed using EM remains to be investigated.

Ginsenoside Rd is a saponin from ginseng and has been reported to have various biological activities. However, the effect of ginsenoside Rd on the metastasis of colorectal cancer (CRC) remains unknown. Here, we found that ginsenoside Rd decreased the colony-forming ability, migration, invasion, and wound-healing abilities of CRC cells, although it did not affect cell proliferation. In addition, using an inverse-docking assay, we found that ginsenoside Rd bound to epidermal growth factor receptor (EGFR) with a high binding affinity, inducing the downregulation of stemness- and epithelial-mesenchymal transition-related genes; these were partially rescued by either exogenous EGF treatment or ectopic expression of SOX2. Furthermore, ginsenoside Rd significantly decreased the number and size of tumor metastasis nodules in the livers, lungs, and kidneys of mouse model of metastasis. © 2018 IUBMB Life, 71(5):601-610, 2019.

Objectives Simultaneous transplantation of a solid organ and bone marrow from the same donor is a possible means of achieving transplant tolerance. Here, we attempted to identify biomarkers that indicate transplant tolerance for discontinuation of immunosuppressants in combined kidney and bone marrow transplantation (CKBMT). Methods Conventional kidney transplant (KT) recipients (n = 20) and CKBMT recipients (n = 6) were included in this study. We examined various immunological parameters by flow cytometry using peripheral blood mononuclear cells (PBMCs), including the frequency and phenotype of regulatory T (Treg) cell subpopulations. We also examined the suppressive activity of the Treg cell population in the setting of mixed lymphocyte reaction (MLR) with or without Treg cell depletion. Results Among six CKBMT recipients, three successfully discontinued immunosuppressants (tolerant group) and three could not (non‐tolerant group). The CD45RA−FOXP3++ Treg cell subpopulation was expanded in CKBMT recipients compared to conventional kidney transplant patients, and this was more obvious in the tolerant group than the non‐tolerant group. In addition, high suppressive activity of the Treg cell population was observed in the tolerant group. The ratio of CD45RA−FOXP3++ Treg cells to CD45RA−FOXP3+ cells indicated good discrimination between the tolerant and non‐tolerant groups. Conclusion Thus, our findings propose a biomarker that can distinguish CKBMT patients who achieve transplant tolerance and are eligible for discontinuation of immunosuppressants and may provide insight into tolerance mechanisms in CKBMT.

OBJECTIVE When conservative therapy fails for chronic parotitis, sialendoscopic treatment or surgical excision can be considered. However, these are financially costly or invasive. Thus, this study aimed to evaluate the clinical efficacy and safety of botulinum toxin (BTX) injection and to further analyze its effect on parotid gland function and volume using salivary single-photon emission computed tomography (SPECT)-computed tomography (CT). METHODS This clinical trial has been registered in the Clinical Research Information Service, Republic of Korea. Fourteen patients with chronic parotitis received BTX injections into the parotid glands. Pain, postprandial pain, swelling, aesthetic discomfort, and salivary flow rate were assessed before injection, at 2 weeks, and at 1, 3, and 6 months. Salivary SPECT-CT was performed before injection and again 3 and 6 months after to assess the volume and uptake changes. RESULTS All subjective symptoms decreased significantly until 1 month and then increased. However, at 6 months, all subjective symptoms were determined to be better than before injection. The unstimulated and stimulated salivary flow rate did not show a significant difference over time. No significant difference was noted in parotid gland volume or uptake on salivary SPECT-CT over time. CONCLUSION BTX injection can be an alternative treatment option for chronic parotitis. LEVEL OF EVIDENCE 4 Laryngoscope, 131:E1903-E1909, 2021.

Melanocytes in hair are located around dermal papilla cells at the tip of the hair follicle. In this study, we examined the melanogenesis of a three-dimensional (3D) hair dermal papilla model treated with natural extracts and electromagnetic fields (EMFs). The 3D model involved dermal papilla-like tissue (DPLT), an aggregation of a mixture of dermal papilla cells, and melanocytes in microwells. Rice bran extract (RBE), an EMF, and RBE/EMF were applied to different DPLT groups. The LDH assay indicated no cell stress in all experimental groups, and detection of tyrosinase activity demonstrated high activity in the RBE/EMF group. Western blot analysis of the RBE, EMF, and RBE/EMF groups revealed increased MITF, TRP-1, and tyrosinase expression. In addition, the mRNA expression of ET-1, laminin, bFGF, β-catenin, MITF, and tyrosinase was increased in the RBE/EMF group, as demonstrated by RT-qPCR analysis. HMB45 and Fontana-Masson immunostaining showed that the RBE/EMF group had the highest melanin content. Therefore, RBE and EMF may be used as a material and therapy, respectively, for the treatment of vitiligo and white hair, through activation of melanogenesis in melanocytes. Bioelectromagnetics. 39:595-603, 2018. © 2018 The Authors. Bioelectromagnetics Published by Wiley Periodicals, Inc..

Bronchoalveolar lavage is a common diagnostic test for dogs with suspected pulmonary disease, however there is no published information on whether this procedure could affect the imaging characteristics of the lungs. Aims of this prospective experimental study were to describe computed tomography (CT) and radiographic features of the lungs after bronchoalveolar lavage in a sample of healthy dogs. Thoracic CT and radiographic images of eight healthy Beagles were acquired at the following time points: before bronchoalveolar lavage, immediately following bronchoalveolar lavage, and at 2, 4, 8, 12, and 24 h following bronchoalveolar lavage. Lung consolidation or interstitial patterns were seen in CT and radiographic images immediately after the procedure. Radiographic lung patterns resolved within 2 h and CT patterns resolved within 24 h. Resolution of the CT pulmonary patterns in the ventral areas of the lungs was delayed compared to the dorsal areas. Mean CT imaging scores differed over time (P < 0.001), while mean radiographic imaging scores did not differ over time. This study suggests that thoracic radiography and CT imaging assessments should precede bronchoalveolar lavage procedures if possible, or be performed at least 24 h afterward.

Background Traditionally, the central nervous system (CNS) has been viewed as an immune-privileged environment with no lymphatic vessels. This view was partially overturned by the discovery of lymphatic vessels in the dural membrane that surrounds the brain, in contact with the interior surface of the skull. We here examine the distribution and developmental timing of these lymphatic vessels. Results Using the Prox1-GFP BAC transgenic reporter and immunostaining with antibodies to lymphatic markers LYVE-1, Prox1, and Podoplanin, we have carried out whole-mount imaging of dural lymphatic vasculature at postnatal stages. We have found that between birth and postnatal day (P) 13, lymphatic vessels extend alongside dural blood vessels from the side of the skull toward the midline. Between P13 and P20, lymphatic vessels along the transverse sinuses reach the superior sagittal sinus (SSS) and extend along the SSS toward the olfactory bulb. Conclusions Compared with the embryonic developmental timing of lymphatic vessels in other tissues, e.g. skin, dural lymphatic vessel development is dramatically delayed. This study provides useful anatomical data for continuing investigations of the fundamental mechanisms that underlie dural lymphatic vessel development. Developmental Dynamics 247:741-753, 2018. © 2018 Wiley Periodicals, Inc.

BACKGROUND AND AIM Naturally occurring hepatitis B virus variants carrying a deletion in the preS1 start codon region may evolve during long-lasting virus-host interactions in chronic hepatitis B (CHB). The aim of this study was to determine the immune phase-specific prevalent patterns of preS1 start codon deletion variants and related factors during the natural course of CHB. METHODS A total of 399 CHB patients were enrolled. Genotypic analysis of three different preS1 start codon deletion variants (classified by deletion size: 15-base pair [bp], 18-bp, and 21-bp deletion variants) was performed. RESULTS PreS1 start codon deletion variants were detected in 155 of 399 patients (38.8%). The predominant variant was a 15-bp deletion in the immune-tolerance phase (18/50, 36%) and an 18-bp deletion in the immune-clearance phase (69/183, 37.7%). A 21-bp deletion was the predominant variant in the low replicative phase (3/25, 12.0%) and reactivated hepatitis Be antigen (HBeAg)-negative phase (22/141, 15.6%). The 15-bp and 18-bp deletion variants were more frequently found in HBeAg-positive patients (P

SummaryAim Noninvasive encapsulated follicular variant of papillary thyroid carcinoma (FVPTC) has been managed as low-risk malignancy. Recently, a proposal was made to reclassify this tumor type as a premalignant lesion and rename it noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP). However, a comprehensive study on molecular genotype-phenotype correlations of encapsulated FVPTC is lacking. Methods and results This study consisted of 177 consecutive FVPTCs from January 2014 to April 2016. These were classified into noninvasive (n=74), invasive (n=51) encapsulated FVPTC, and infiltrative FVPTC (n=52) according to standard criteria by two independent pathologists. Genetic alterations and other clinicopathologic information were compared. A BRAFV600E mutation was found in 12.2% (noninvasive) and 11.8% (invasive) of encapsulated FVPTCs and 34.6% of infiltrative FVPTCs (P=0.001). Mutation in encapsulated FVPTCs was limited to cases with rare or abortive papillae. RET/PTC1 and RET/PTC3 rearrangements were present (11.5%) only in infiltrative FVPTC. In contrast, N-, H-, and KRAS mutations were observed predominantly in encapsulated FVPTCs (48.6% in noninvasive and 66.7% in invasive) compared to infiltrative FVPTCs (15.4%) (P

Background The purpose of this study was to determine an appropriate cutoff value for the resection margin according to the initial T classification. Methods The medical records of 151 patients treated by surgery for tongue cancer were retrospectively reviewed to identify the significant perioperative parameters and appropriate cutoff value associated with disease-specific survival (DSS) and recurrence-free survival (RFS). Results The posterior resection margin was significantly correlated with survival and local recurrence (P = .020 and .016, respectively), whereas the deep resection margin was correlated with overall recurrence (P = .047). The cutoff values of the posterior and deep resection margins for survival and recurrence were different and larger in the advanced-stage T classification group (0.45 cm vs 0.95 cm and 0.25 cm vs 0.80 cm, respectively). Conclusion Posterior and deep resection margins are significant prognosticators in tongue cancer. A larger resection margin may be needed in advanced-stage T classification.

Objectives The purpose of this study was to assess the intraobserver and interobserver variability in ultrasound (US) measurements of thyroid nodules. Methods We performed a prospective study of the US examinations of 73 patients with 122 thyroid nodules greater than 5 mm in size. Ultrasound measurements in 4 dimensions (anteroposterior, transverse, longitudinal, and maximum diameters) and measurement of the estimated volume (using the ellipsoid formula) of each thyroid nodule were performed twice by 2 independent radiologists (A and B, with 10 years and 6 months of experience, respectively). The intraobserver and interobserver variability in measurements of thyroid nodules was assessed by a Bland-Altman analysis of agreement. The absolute values for intraobserver and interobserver variability were compared by a paired t test. Results The 95% intraobserver and interobserver limits of agreement for the anteroposterior, transverse, longitudinal, and maximum diameters and estimated volume of thyroid nodules were ±18.2%, ± 14.3%, and ±21.0%; ± 17.2%%, ± 17.3%, and 18.2%; ± 14.6%, ± 15.5%, and ±22.3%; ± 13.8%, ± 15.5%, and ±19.6%; and ±30.2%, ± 27.7%, and ±44.1%, respectively. The absolute values for intraobserver variability were lower than those for interobserver variability for all measurements. Conclusions There was considerable intraobserver and interobserver variability in US measurement of thyroid nodules, which must be taken into account during follow-up US examinations of patients with thyroid nodules.

Background and aims To evaluate the efficacy and safety of evogliptin, a newly developed dipeptidyl peptidase-4 inhibitor, in patients with type 2 diabetes (T2D) inadequately controlled by diet and exercise. Materials and methods In this randomized, double-blind, placebo-controlled, parallel-group, multicenter, phase III study, 160 patients with T2D were assigned to either an evogliptin 5 mg or placebo group for 24 weeks. The primary endpoint was the mean change in glycated hemoglobin (HbA1c) from baseline to week 24. Results The mean baseline HbA1c levels were similar between the evogliptin and the placebo groups (7.20 ± 0.56 vs. 7.20 ± 0.63%, respectively). At week 24, evogliptin significantly reduced HbA1c levels from baseline compared to placebo (−0.23 vs. 0.05%, respectively, P < .0001). Additionally, the proportion of patients achieving HbA1c < 6.5% was significantly higher in the evogliptin group than that in the placebo group (33.3 vs. 15.2%, respectively, P = .008). The overall incidence of adverse events, including hypoglycemia, was similar between the two groups. Conclusions In this 24-week study, once daily evogliptin monotherapy significantly improved glycemic control and was well tolerated in patients with T2D.

In this work, an octadecylamine-modified graphene oxide (ODA-GO)-MgCl-supported Ziegler–Natta catalyst was synthesized by reacting ODA-GO with a Grignard reagent, followed by anchoring TiCl4 to the structure. The effect of the ODA-GO on the catalyst morphology and ethylene polymerization behavior was examined. The resultant polyethylene (PE)/ODA-GO nanocomposites directly mirrored the catalyst morphology by forming a layered morphology, and the ODA-GO fillers were well dispersed in the PE matrix and showed strong interfacial adhesion with it. The resultant PE/ODA-GO nanocomposites exhibited better thermal stability and mechanical properties than neat PE, even with a small amount of ODA-GO added. Thus, this work provides a facile approach to the production of high-performance PE. © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2017, 55, 855–860

Biophysical wave stimulus has been used as an effective tool to promote cellular maturation and differentiation in the construction of engineered tissue. Pulsed electromagnetic fields (PEMFs) and sound waves have been selected as effective stimuli that can promote neural differentiation. The aim of this study was to investigate the synergistic effect of PEMFs and sound waves on the neural differentiation potential in vitro and in vivo using human bone marrow mesenchymal stem cells (hBM-MSCs). In vitro, neural-related genes in hBM-MSCs were accelerated by the combined exposure to both waves more than by individual exposure to PEMFs or sound waves. The combined wave also up-regulated the expression of neural and synaptic-related proteins in a three-dimensional (3-D) culture system through the phosphorylation of extracellular signal-related kinase. In a mouse model of photochemically induced ischemia, exposure to the combined wave reduced the infarction volume and improved post-injury behavioral activity. These results indicate that a combined stimulus of biophysical waves, PEMFs and sound can enhance and possibly affect the differentiation of MSCs into neural cells. Our study is meaningful for highlighting the potential of combined wave for neurogenic effects and providing new therapeutic approaches for neural cell therapy. © 2016 American Institute of Chemical Engineers Biotechnol. Prog., 33:201-211, 2017.