Search

Thirty-nine patients with chronic HBV infection and 38 normal persons were investigated by simultaneous assay of T suppressor cell function and enumeration of T-lymphocyte subsets by monoclonal antibodies. In patients with chronic active hepatitis B (CAH-B), T suppressor cell activity (17.8 +/- 8.8%) was significantly lower than in healthy HBsAg carriers (35.4 +/- 12.3%) and normal control persons (38.3 +/- 16.3%). The proportions of T-lymphocyte subsets in patients with CAH-B were not different from those of healthy HBsAg carriers and control persons. No correlation was observed in between percentage suppression and proportions of T-lymphocyte subsets. These findings suggest that in the absence of a simultaneous assay of function, enumeration of T-lymphocyte subsets by using monoclonal antibodies is an inadequate assessment of immune regulation.

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this fifth of 6 sections of the guidelines of care for psoriasis, we discuss the use of ultraviolet (UV) light therapy for the treatment of patients with psoriasis. Treatment should be tailored to meet individual patients' needs. We will discuss in detail the efficacy and safety as well as offer recommendations for the use of phototherapy, including narrowband and broadband UVB and photochemotherapy using psoralen plus UVA, alone and in combination with topical and systemic agents. We will also discuss the available data for the use of the excimer laser in the targeted treatment of psoriasis. Finally, where available, we will summarize the available data that compare the safety and efficacy of the different forms of UV light therapy. [ABSTRACT FROM AUTHOR]

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this first of 5 sections of the guidelines of care for psoriasis, we discuss the classification of psoriasis; associated comorbidities including autoimmune diseases, cardiovascular risk, psychiatric/psychologic issues, and cancer risk; along with assessment tools for skin disease and quality-of-life issues. Finally, we will discuss the safety and efficacy of the biologic treatments used to treat patients with psoriasis. [ABSTRACT FROM AUTHOR]

Introduction: Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5 years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers., Methods: Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years., Results: Over 5 years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported., Conclusion: Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals., (© 2024. The Author(s).)

The present study examined the clinical characteristics of patients with a final diagnosis of solitary large malignant lymphoma of the head and neck after surgery. Between January 2015 and December 2022, 13 patients with a final diagnosis of solitary large malignant lymphoma of the head and neck after surgery were enrolled. The most common symptom of solitary large malignant lymphoma was a neck mass (n=11; 84.6%). The most common sites of the head and neck were neck level II (eight patients), neck level IV (two patients), parotid glands (two patients) and the tongue (two patients). The number of malignant lymphomas was as follows: 11 patients had one large tumor and two patients had two large tumors. The mean tumor size was 4.0±1.3 cm (range; 2.7-6.8 cm). Among the two patients with two lymphomas, the size of the second neck mass was 3.2 cm in one patient and 2.7 cm in the other patient. The most common type of solitary large malignant lymphoma was diffuse large B-cell lymphoma (n=6, 46.2%). A total of 12 patients are currently under follow-up without disease recurrence after treatment completion and one patient diagnosed 1 month ago is currently undergoing radiation therapy. The follow-up period was 47.3±19.0 months (range; 1-62 months). The possibility of solitary large malignant lymphoma of the head and neck should be considered. As it is difficult to accurately diagnose solitary large malignant lymphoma before surgery, surgical resection is required for differentiation from other diseases., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Lee et al.)

Background: Sufficient alveolar housing is fundamental to ensure the favorable prognosis of autotransplanted teeth. However, little is known about the alveolar ridge profiles of the anterior maxilla in children. Therefore, this study aimed to investigate the alveolar ridge profiles of the anterior maxilla in growing children., Methods: A total of 169 Korean children aged 10-13 years old were included in this retrospective study. Demographic data and cone-beam computed tomography scans of 244 maxillary central incisors were collected. For each tooth, the alveolar ridge thickness was determined at 1-, 3-, and 5-mm levels below the cemento-enamel junction. The alveolar process height and labial concavity were also evaluated. Statistical analyses were performed to evaluate differences according to age and sex., Results: The alveolar ridge thickness did not differ according to age. The alveolar ridge thickness in males was significantly greater than that in females among those aged 10 and 11 years. The average alveolar process height was 17.43 ± 2.22 mm. The alveolar process height hardly changed with age from 10-13 years, whereas the alveolar process height of males was significantly greater compared with that of females among those aged 10 years. The labial concavity was approximately 150˚, with no significant differences between age and sex., Conclusions: Within the limits of this study, the anatomy of the alveolar ridge in the maxillary central incisors showed sufficient capacity as a recipient site for autotransplantation using mandibular premolars, especially in males. These findings serve as a valuable resource for facilitating autotransplantation in children., 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 © 2023 Elsevier GmbH. All rights reserved.)

Objectives: As a convenient and economical method of screening cervical cancer and precancerous pathologies, the Papanicolaou smear (Pap smear) has been most widely used. Nevertheless, it requires cytological changes for making diagnoses and reportedly has a high false-negative rate. In this study, the usefulness of the human papillomavirus (HPV) DNA chip test as a complementary method that can compensate for the defect of the Pap smear was investigated., Material and Methods: Of the 6516 patients who simultaneously underwent a Pap smear and an HPV DNA chip test at Chonnam National University Hospital between January 2015 and December 2016, 1897, an initial PAP smear-negative patients who had undergone an additional Pap smear during their 2-year follow-up period were selected for this study. Of the subject patients, 281 underwent a cervical biopsy., Results: The Pap smear follow-up of an initial Pap smear-negative subjects showed 53 (75.7%) HPV high-risk positive cases in the cytology low-grade lesion group (70 cases) and 46 (97.8%) HPV high-risk positive cases in the cytology high-grade lesion group (47 cases). The 281 biopsy cases included 67 biopsy low-grade lesion cases and 74 biopsy high-grade lesion cases, of which there were 45 (67.2%) and 67 (90.5%) HPV high-risk positive cases, respectively. The follow-up cytology on the high-risk HPV-positive subjects showed that the ratio of their high-grade lesions was 260.8 times greater than that of the high-risk HPV-negative subjects (OR = 260.8 and 95% CI: 36.1 and 1886.1); and their biopsy showed that the ratio of their high-grade lesions was 102.7 times greater than that of the HPV-negative subjects (OR = 102.7 and 95% CI: 14.0 and 753.3)., Conclusion: The complementary use of the HPV DNA chip test may be useful in increasing the accuracy of screening examinations for the early diagnosis of uterine cervix cancer when combined with the Pap smear., Competing Interests: The authors declare that they have no competing interest., (© 2023 Cytopathology Foundation Inc, Published by Scientific Scholar.)

Rationale: Neurenteric cysts are rare benign lesions that are usually located in the lower cervical and upper thoracic spine and extremely rare in the craniovertebral junction. It is generally challenging to completely remove the neurenteric cysts of the craniovertebral junction. We report the cases of 2 patients with neurenteric cyst in the ventral craniovertebral junction managed using different treatment strategies., Patient Concerns: The first patient was a 64-year-old man. He man was admitted with headache, posterior neck pain, and a tingling sensation in both the forearms. The second patient was a 53-year-old woman. She was admitted with tingling sensations and numbness in both the hands and feet., Diagnoses: Cervical spine magnetic resonance imaging showed 2 intradural extramedullary cystic lesions in case 1 and a C2 to C3 intradural extramedullary cystic mass in case 2., Interventions and Outcomes: The patient of the case 1 underwent a left C1 to C2 hemi-laminectomy and the cysts were completely removed. Eleven years after the surgery, there was no recurrence. In case 2, we performed a left C2 to C3 hemi-laminectomy and removed only a part of the outer membrane to enable sufficient communication with the surrounding normal subarachnoid space. After removing the cyst wall, the patient underwent C1 to 2 trans articular screw fixation to prevent cervical instability. Ten years after surgery, there was no recurrence of the cyst or new lesions., Lessons: Clinicians should consider neurenteric cyst in the differential diagnosis of arachnoid cyst or epidermoid cyst. If performing a complete surgical removal is difficult, partial surgical removal, using a cysto-subarachnoid shunt and stabilization, such as screw fixation, could be an alternative treatment option to reduce the risk of mortality and morbidity., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Neuroinflammation is one of the critical processes implicated in central nervous system (CNS) diseases. Therefore, alleviating neuroinflammation has been highlighted as a therapeutic strategy for treating CNS disorders. However, the complexity of neuroinflammatory processes and poor drug transport to the brain are considerable hurdles to the efficient control of neuroinflammation using small-molecule therapeutics. Thus, there is a significant demand for new chemical entities (NCEs) targeting neuroinflammation. Herein, we rediscovered benzopyran-embedded tubulin inhibitor 1 as an anti-neuroinflammatory agent via phenotype-based screening. A competitive photoaffinity labeling study revealed that compound 1 binds to tubulin at the colchicine-binding site. Structure-activity relationship analysis of 1's analogs identified SB26019 as a lead compound with enhanced anti-neuroinflammatory efficacy. Mechanistic studies revealed that upregulation of the tubulin monomer was critical for the anti-neuroinflammatory activity of SB26019. We serendipitously found that the tubulin monomer recruits p65, inhibiting its translocation from the cytosol to the nucleus and blocking NF-κB-mediated inflammatory pathways. Further in vivo validation using a neuroinflammation mouse model demonstrated that SB26019 suppressed microglial activation by downregulating lba-1 and proinflammatory cytokines. Intraperitoneal administration of SB26019 showed its therapeutic potential as an NCE for successful anti-neuroinflammatory regulation. Along with the recent growing demands on tubulin modulators for treating various inflammatory diseases, our results suggest that colchicine-binding site-specific modulation of tubulins can be a potential strategy for preventing neuroinflammation and treating CNS diseases., (© 2022. The Author(s).)

Typical amorphous aerogels pose great potential for CO 2 adsorbents with high surface areas and facile diffusion, but they lack well-defined porosity and specific selectivity, inhibiting utilization of their full functionality. To assign well-defined porous structures to aerogels, a hierarchical metal-organic aerogel (HMOA) is designed, which consists of well-defined micropores ( d ∼ 1 nm) by coordinative integration with chromium(III) and organic ligands. Due to its hierarchical structure with intrinsically flexible coordination, the HMOA has excellent porous features of a high surface area and a reusable surface with appropriate binding energy for CO 2 adsorption. The HMOA features high CO 2 adsorption capacity, high CO 2 /N 2 IAST selectivity, and vacuum-induced surface regenerability (100% through 20 cycles). Further, the HMOA could be prepared via simple ambient drying methods while retaining the microporous network. This unique surface-tension-resistant micropore formation and flexible coordination systems of HMOA make it a potential candidate for a CO 2 adsorbent with industrial scalability and reproducibility.

We demonstrated the synthesis of a conductive two-dimensional metal-organic framework (MOF) thin film by single-step all-vapor-phase chemical vapor deposition (CVD). The synthesized large-area thin film of Cu 3 (C 6 O 6 ) 2 has an edge-on-orientation with high crystallinity. Cu 3 (C 6 O 6 ) 2 thin film-based microdevices were fabricated by e-beam lithography and had an electrical conductivity of 92.95 S/cm. Synthesis of conductive MOF thin films by the all-vapor-phase CVD will enable fundamental studies of physical properties and may help to accomplish practical applications of conductive MOFs.

Hemangioblastoma (HB) is a rare benign tumor that most commonly occurs in the cerebellum. HB is composed of neoplastic stromal cells and abundant small vessels. However, the exact origin of stromal cells is controversial. Extraneural HBs have been reported in a small series, and peripheral HBs arising in the adrenal gland are extremely rare. Herein, we report a case of sporadic adrenal HB in a 54-year-old woman. The tumor was a well-circumscribed, yellow mass measuring 4.2 cm in diameter. Histologically, the tumor was composed of small blood vessels and vacuolated stromal cells with clear cytoplasm. On immunohistochemical stain, the stromal cells were positive for S-100 protein, neuron-specific enolase, and synaptophysin. The tumor did not reveal mutation of VHL alleles. We herein present a case of HB of the adrenal gland and review of the literature.

This study examines an intrinsic penalized smoothing method on the 2-sphere. We propose a method based on the spherical Bézier curves obtained using a generalized de Casteljau algorithm to provide a degree-based regularity constraint to the spherical smoothing problem. A smooth Bézier curve is found by minimizing the least squares criterion under the regularization constraint. The de Casteljau algorithm constructs higher-order Bézier curves in a recursive manner using linear Bézier curves. We introduce a local penalization scheme based on a penalty function that regularizes the velocity differences in consecutive linear Bézier curves. The imposed penalty induces sparsity on the control points so that the proposed method determines the number of control points, or equivalently the order of the Bézier curve, in a data-adaptive way. An efficient Riemannian block coordinate descent algorithm is devised to implement the proposed method. Numerical studies based on real and simulated data are provided to illustrate the performance and properties of the proposed method. The results show that the penalized Bézier curve adapts well to local data trends without compromising overall smoothness., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2022 Informa UK Limited, trading as Taylor & Francis Group.)

TTF 3 MCl 6 (M = In, Sb) series were developed for an ideal platform to investigate the effect of back charge transfer of MCl 6 3- on electrical conductivity depending on the metal ions. They were successfully synthesized by a UV light-induced one-pot reaction where TTF oxidation and formation of MCl 6 3- occurred sequentially. In isostructural TTF 3 InCl 6 and TTF 3 SbCl 6 , the intermolecular interaction between MCl 6 3- and TTF induces back charge transfer, which were confirmed by the crystal structure and spectroscopic analysis. Despite the similar crystal structure in terms of intermolecular distance, TTF 3 InCl 6 shows 3-orders of magnitude higher electrical conductivity compared to TTF 3 SbCl 6 . According to the cyclic voltammograms (CV) and electron spin resonance (ESR) spectra, increased conductivity is because of the higher degree of back charge transfer from MCl 6 3- in TTF 3 InCl 6 compared to TTF 3 SbCl 6 , which is due to the lower electronegativity of In, considering that the only difference between the two compounds is the center metal.

We generate paramagnetic centers on a heavily boron-doped Si(111) surface by using a scanning tunneling microscope and show that they mediate the spin-dependent recombination of the bound holes of the boron acceptor via direct visualization. This recombination is the intraband process and is significantly affected by the spin-orbit coupling effect. We also demonstrate that such a paramagnetic center with a boron acceptor at its neighbor site can be produced with atomic precision, which makes it a promising candidate for implementing position-controlled impurity qubits with an electrical readout mechanism in silicon.

Bismuth-based organic frameworks (BiOFs) can display interesting phosphorescent properties, but the relationship between structure and optical activity remains underexplored. The structure-dependent phosphorescence properties in the BiOFs are investigated using different multidentate ligands. In-depth analysis of the luminescence properties confirms that the densely packed framework shows long-lasting phosphorescence at room temperature, owing to an efficient electron-hole separation. The combination of spectroscopic analysis and single-crystal structural analysis provides important insights into the emission control through BiOFs structural change, which can be a useful strategy for modulating the optical properties of various metal organic frameworks. Furthermore, taking the advantage of long-lasting phosphorescence, the potential usage as an eco-friendly photocatalyst is demonstrated., (© 2021. The Author(s).)

A new oxo-bridged chromium-molybdenum heterometallic complex, O-CrMoHC ([Cr 4 (MoO 4 ) 2 O 2 (OAc) 4 (DMF) 4 ]·2DMF), was synthesized by using a simple solvothermal reaction. In this complex, the octahedrally coordinated Cr(III) and tetrahedrally coordinated Mo(VI) metal centers are bridged by oxo ligands. O-CrMoHC has in-plane π-conjugation systems, which are interconnected by noncoordinating DMF molecules. The crystals show anisotropic conductivity with respect to the crystal planes, and theoretical calculations were used to study their origins. The O-CrMoHC single crystals exhibited that a relatively high electrical conductivity with an average value of 5.37 × 10 -7 S/cm was observed along the [01-1] direction, but the current level was very low along the [100] direction. This is the first report of anisotropic conductivity observed in the single crystal of a monomeric heterometallic complex.

A kinetic overgrowth allowing organic molecular crystals in various morphologies is induced by temperature-dependent viscosity change of crystallization solution. By this strategy, concave cube and octapod fullerene C 70 crystals were successfully obtained by antisolvent crystallization (ASC). The structural analysis of fullerene C 70 crystals indicates that the morphological difference is the result of kinetic processes, which reveals that viscosity, the only variable that can change dynamics of solutes, has a significant influence on determining the morphology of crystals. The effect of solvent viscosity in the stage of crystal growth was investigated through time-dependent control experiments, which led to the proposal of a diffusion rate-based mechanism. Our findings suggest morphology control of organic crystals by diffusion rate control, which is scarcely known compared to inorganic crystals. This strategic method will promote the morphology controls of various organic molecular crystals, and boost the morphology-property relationship study., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Producing more than one structure from the same set of metal and ligand precursors will grant structural diversity in metal-organic framework (MOF) systems. One of the biggest obstacles of getting structural diversity for the late transition metals is that the coordination mode is pretty much fixed by nature. Herein, we show that two different coordination modes to Cu(II) are possible for flexible ligands containing hydrophilic terminal groups through solvent guidance. It is demonstrated that trans , trans -muconic acid (H 2 muco) ligands coordinate to Cu(II) to form Cu(II) muconate MOFs having a 1D chain structure and a 2D plane structure in water-rich and DMF-rich water-DMF mixed solvent systems, respectively. It is suggested that the interaction between ligands and solvent is responsible for the selective coordination. A similar result was observed from the attempts using the fumaric acid ligand. Our results provide a new direction to obtain diverse secondary building units for the construction of diverse MOFs.

Poor nutritional status in children with cancer can impact treatment outcomes and mortality. Nutrition screening is a simple yet effective approach to identify malnutrition risk for early intervention. We aim to improve the identification of children with cancer at high risk of malnutrition, so that nutritional intervention and rehabilitation can commence early for these children. Our multidisciplinary team conducted a root cause analysis and concluded that the generic screening tool did not differentiate malnutrition risk for different cancer types, stage and intensity of treatment. Hence, a screening tool that considered the identified factors was tested for reliability and validity first. Subsequently, we used the Plan, Do, Study, Act model with two improvement cycles to put in place a systematic process to facilitate the implementation. The interventions included (1) instituting the tool in the electronic medical records and (2) direct referral to dietitian based on screening score.We compared pre- and post-implementation cohorts and demonstrated better identification of nutritionally at-risk patients (36.4%-85.7%, p<0.001) with the new tool as well as improved timeliness of nutritional intervention (3 days to 1 day from admission, p=0.010). A lower malnutrition rate (17.4%-6.5%, p<0.001) in the postimplementation cohort was also demonstrated. Nutritional intervention within 48 hours of admission led to an overall positive weight change at 3 months (+2.68%, IQR: -1.14 to 9.09 vs -0.43%, -6.60 to 2.29; p=0.036) in the malnourished patients from both cohorts. Further studies will be conducted to evaluate the scale of the effectiveness of early intervention and close nutritional monitoring, in improving the nutritional status of children with cancer. The collaborative partnership among the doctors, nurses and dietitians has helped to streamline and simplify nutrition screening, making it an efficient and sustainable system in our hospital., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Chiral organic optoelectronics using circularly polarized light (CPL) as the key element in the photonic signal has recently emerged as a next-generation photonic technology. However, it remains challenging to simultaneously achieve high polarization selectivity and superior optoelectronic performance. Supramolecular two-dimensional (2D) chiral organic single crystals may be good candidates for this purpose due to their defect-free nature, molecular diversity, and morphologies. Here, quasi-2D single crystals of chiral perylene diimides with parallelogram and triangle/hexagon morphologies have been selectively fabricated via self-assembly using different cosolvent systems. These materials exhibit amplified circular dichroism (CD) spectral signals, due to their molecular packing modes and supramolecular chirality. Through molecular surface n-doping using hydrazine, chiral single crystals exhibit electron mobility surpassing 1.0 cm 2 V -1 s -1 , which is one of the highest among chiral organic semiconductors, and excellent optoelectronic functions. Theoretical calculations reveal that the radical anions formed by n-doping increase the electron affinity and/or reduce the energy gap, thus facilitating electron transport. More importantly, the doped organic chiral crystals selectively discriminate CPL handedness with a high anisotropy factor of photoresponsivity (∼0.12). These results demonstrate that surface-doped quasi-2D chiral organic single crystals are highly promising for chiral optoelectronics.

Kekulé distortion in graphene is a subject of extensive theoretical studies due to its non-trivial material properties. Yet, experimental observation of its formation mechanism and electronic structures is still elusive. Here, we used scanning tunneling microscopy to visualize two different phases of the Kekulé distortion in graphene along with experimental evidence that local strain is responsible for the formation of such distortions. In addition, we directly measured the electronic structures of the two phases of the Kekulé distortion in graphene revealing that one opens an energy gap whereas the other maintains a linear density profile. These are consistent with the calculated band structures of the two phases of the Kekulé distortion, respectively, providing a direct verification of the theoretical predictions.

Together with high conductivity, high flexibility is an important property required for next generation organic electronic components. Both properties are difficult to achieve together especially when the components are crystalline because of the intrinsic high brittleness of organic molecular crystals. We report an organic radical crystal system that has both high flexibility and high conductivity. The crystal consists of 9,10-bis(phenylethynyl)anthracene radical cation (BPEA .+ ) units, and shows flexibility under pressure with high conductivity in ambient condition exhibiting average conductivity of 2.68 S cm -1 when normal linear shape, as well as 2.43 S cm -1 when bent. The structural analysis reveals that both a short π-π distance (3.290 Å) between BPEA .+ units that are aligned along the crystal length direction, and the presence of PF 6 - counter ions induce flexibility and high electrical conductivity., (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objectives: Bronchial brushing (BB) is often used to obtain supplementary samples for diagnosing lung cancer. We examined the possibility of epidermal growth factor receptor (EGFR) testing on BB samples and compared them with bronchial biopsy samples., Material and Methods: We used 150 BB samples with non-small cell carcinoma submitted to our department within 2 years. Biopsy samples were concurrently submitted for histologic diagnosis. We used the peptide nucleic acid clamping method for EFGR mutation test. Histologic diagnosis identified 137 cases of adenocarcinomas and 13 cases of non-small cell lung carcinoma, not otherwise specified. Each sample was assessed for adequacy and DNA content for EGFR mutation test., Results: Among BB samples, 28 had exon 19 deletion, 21 had mutations in exon 21, 99 were wild type, and analysis of two failed. The EGFR mutation rate in BB samples was 33.1% (49/148). Among bronchial biopsy samples, 26 had exon 19 deletion, 20 had mutations in exon 21, 92 were wild type, and analysis of 12 failed. The EGFR mutation rate using biopsy sample was 33.8% (46/136). The mutation detection results were nearly identical in both groups of samples (131/138, 94.9%). However, in two cases, an exon 21 mZutation was detected in biopsy samples but not in BB samples. In five cases, exon 19 deletion (two cases) and exon 21 mutation (three cases) were detected in BB but not in biopsy samples. The median DNA content was 58.83 ng for BB samples and 48.47 ng for biopsy samples. The failure rate for BB samples was lower than for biopsy samples. Overall, the BB samples were comparable to bronchial biopsy samples in terms of DNA quantity and mutation detection results., Conclusion: We conclude that in case of inadequate biopsy samples, BB samples can be used as a substitute material for EGFR mutation test., Competing Interests: All authors declare that this study was supported by a grant (CRI 14028-1) from the Chonnam National University Hospital Biomedical Research Institute., (©2020 Cytopathology Foundation Inc, Published by Scientific Scholar.)

Herein, we report the use of two-photon fluorogenic probes using tetrazine-based bioorthogonal reactions with multicolor emissions that cover nearly all of the visible region. New fluorogenic probes were designed based on donor-acceptor-type naphthalene structures conjugated with a fluorescence-quenching tetrazine moiety for turn-on properties in one- and two-photon fluorescence. Our fluorescent probes showed a moderate to good turn-on ratio after bioorthogonal inverse electron demand Diels-Alder cycloaddition with trans- cyclooctenol in one- and two-photon fluorescence. We successfully applied our probes to mitochondria- and lysosome-selective bioorthogonal imaging in live cells with one-/two-photon and one-photon microscopy, respectively.

Pancreatic cancer is the worst exocrine gastrointestinal cancer leading to the highest mortality. Recent studies reported that aberrant expression of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is involved in uncontrolled cell growth. However, the molecular mechanism of APE1 biological role remains unrevealed in pancreatic cancer progression. Here, we demonstrate that APE1 accelerates pancreatic cancer cell proliferation through glial cell line-derived neurotrophic factor (GDNF)/glial factor receptor α1 (GFRα1)/Src/ERK axis-cascade signaling. The proliferation of endogenous APE1 expressed-MIA PaCa-2, a human pancreatic carcinoma cell line, was increased by treatment with GDNF, a ligand of GFRα1. Either of downregulated APE1 or GFRα1 expression using small interference RNA (siRNA) inhibited GDNF-induced cancer cell proliferation. The MEK-1 inhibitor PD98059 decreased GDNF-induced MIA PaCa-2 cell proliferation. Src inactivation by either its siRNA or Src inhibitor decreased ERK-phosphorylation in response to GDNF in MIA PaCa-2 cells. Overexpression of GFRα1 in APE1-deficient MIA PaCa-2 cells activated the phosphorylation of Src and ERK. The expression of both APE1 and GFRα1 was gradually increased as progressing pancreatic cancer grades. Our results highlight a critical role for APE1 in GDNF-induced pancreatic cancer cell proliferation through APE1/GFRα1/Src/ERK axis-cascade signaling and provide evidence for future potential therapeutic drug targets for the treatment of pancreatic cancer.

Cation segregation, particularly Sr segregation, toward a perovskite surface has a significant effect on the performance degradation of a solid oxide cell (solid oxide electrolysis/fuel cell). Among the number of key reasons generating the instability of perovskite oxide, surface-accumulated positively charged defects (oxygen vacancy, V o ·· ) have been considered as the most crucial drivers in strongly attracting negatively charged defects (Sr A - site ' ) toward the surface. Herein, we demonstrate the effects of a heterointerface on the redistribution of both positively and negatively charged defects for a reduction of V o ·· at a perovskite surface. We took Sm 0.5 Sr 0.5 CoO 3-δ (SSC) as a model perovskite film and coated Gd 0.1 Ce 0.9 O 2-δ (GDC) additionally onto the SSC film to create a heterointerface (GDC/SSC), resulting in an ∼11-fold reduction in a degradation rate of ∼8% at 650 °C and ∼10-fold higher surface exchange ( k q ) than a bare SSC film after 150 h at 650 °C. Using X-ray photoelectron spectroscopy and electron energy loss spectroscopy, we revealed a decrease in positively charged defects of V o ·· and transferred electrons in an SSC film at the GDC/SSC heterointerface, resulting in a suppression of negatively charged Sr (Sr Sm ' ) segregation. Finally, the energetic behavior, including the charge transfer phenomenon, O p-band center, and oxygen vacancy formation energy calculated using the density functional theory, verified the effects of the heterointerface on the redistribution of the charged defects, resulting in a remarkable impact on the stability of perovskite oxide at elevated temperatures.

Alkali metal doping is an essential process for developing organic superconductors. The conventional vapor-phase alkali metal doping, however, frequently suffers from low efficiency and poor reproducibility mainly due to the inhomogeneous reaction between alkali metal vapor and target organic molecule powder. To overcome this issue, here we developed a facile and highly reproducible solution-phase alkali metal doping (SPD) and successfully applied it to prepare potassium-doped fullerene (K 3 C 60 ) superconductors. Different from the conventional vapor-phase alkali metal doping, the SPD method resulted in almost perfect diamagnetism with an unprecedented high shielding fraction (∼99.5%) with high reproducibility (>80%). It works well with popular commercially available solvents, like ammonia solution in THF, methylamine solution in THF, and even pure THF at room temperature. We believe that our highly facile and efficient SPD approach will be a great help for the finding of next-generation organic superconductors, especially searching for high- T c organic superconductors.

We demonstrate an effective and facile method for the deposition of gold nanoparticles (AuNPs) on graphene by using spontaneous galvanic reaction. Despite the interest and importance of the hybrid structure of noble metal-deposited graphene has been considerably increased for its fundamental knowledge in chemical and physical sciences and for its various applications, the progress of this subject is very slow mainly because of the lack of synthetic methods for such structures, especially that are not free from chemical contamination and usage of complex and expensive equipment. Therefore, we developed a new method allowing chemically pure AuNPs/graphene hybrid structures employing galvanic reaction. The spontaneous galvanic reaction was derived from reductant/graphene/oxidant sandwich structures, such as Au ions/graphene/Ge wafer and Au ions/graphene/copper foil, by placing Au ion solution droplets on graphene transferred on a germanium wafer or as made graphene on Cu foil, respectively. According to scanning electron microscopy and atomic force microscopy results, it was confirmed that AuNPs were successfully formed on the graphene surface. This result implies two important points. One is that the formation of pure AuNPs on graphene is possible without using other chemicals frequently required for conventional NP preparation. The other one is that it was experimentally demonstrated that there are electronic communications between the oxidant and reductant that are separated by graphene, through which electrons can pass freely., Competing Interests: The authors declare no competing financial interest., (Copyright © 2019 American Chemical Society.)

Pancreatic islet transplantation has been known as the best cure for patients suffering from severe type 1 diabetes mellitus (T1DM). Despite meaningful advances in human allogeneic islet transplantation field, significant amounts of islet loss in early post-transplantation periods is still a big concern for clinicians. One of the major factors determining the fate of the islets is the danger-associated molecular patterns (DAMPs) secreted by activated immune cells or islets themselves under hypoxic stress. High mobility group box 1 (HMGB1) protein is one of the best characterized DAMP molecules associated with islets. HMGB1 is known to be passively released by transplanted murine islet cells after taking damages from cytokines, reactive oxygen species, and other DAMPS, and the released HMGB1 harms neighboring islet cells by interacting with receptors expressed on murine islets such as toll-like receptor 2 (TLR2) and TLR4, thereby forming a vicious cycle. Here, we show that a small molecule inhibitor inflachromene (ICM) was capable of blocking the secretion of HMGB1 from murine islet cells during the normoxic and hypoxic post-isolation period. Notably, the treatment of ICM during the islet isolation process resulted in decreased HMGB1 levels during the subsequent cell culture. ICM's in vivo efficacy was evaluated in murine syngeneic islet transplantation model, and it significantly reduced the serum and graft level of HMGB1. Ultimately, the intraperitoneal administration of ICM prevented the loss of marginal-mass islet grafts and reversed the diabetes in mice., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Chiral self-sorting has great potential for constructing new complex structures and determining chirality-dependent properties in multicomponent mixtures. However, it is still of great challenge to achieve high fidelity chiral self-discrimination. Besides, the researches on the coordination polymers or metal-organic frameworks for micro/nanooptoelectronics are still rare due to their low conductivity and difficulty in developing a rapid and simple scale-up synthetic method. Here, heterochiral supramolecular coordination networks (SCNs) were synthesized by the solvothermal reaction of naphthalene diimide enantiomers and cadmium iodide, using the chirality as a synthetic tuning parameter to control the morphologies. Intriguingly, heterochiral micro/nanocrystals exhibited photochromic and photodetecting properties. Furthermore, we also developed a simple and efficient doping method to enhance the conductivity and photoresponsivity of micro/nanocrystals using hydrazine. From experimental and theoretical studies, the mechanism was suggested as follows: the radicals in the singly occupied molecular orbital level of the ligands provide charge carriers that can undergo "through-space" transport between π-π stacked ligands and the electron transfer from adsorbed hydrazine to the SCNs results in reduction of energy gap, leading to increased conductivity. Our findings demonstrate a simple and powerful strategy for implementing coordination networks with redox ligands for micro/nanooptoelectronic applications.

Morphology-retained solid-state photoconversion of anthracene (AN) to 9,10-anthraquinone (PC-ANQ) and dipara-anthracene (PC-DPA) was accomplished by irradiating mercury lamp light to plate-shaped AN single crystal in oxygen and argon atmosphere, respectively. The photoconverted crystals retained the original plate shape morphology of the starting AN crystal, whereas the emission profile and crystal structure were significantly changed. The electrical conductivity of PC-ANQ crystal is 5 orders of magnitude greater than that of the starting AN crystal, whereas the PC-DPA crystal exhibits a decreased conductivity. The AN/PC-ANQ/PC-DPA heterostructures with smooth interface were successfully obtained by inducing the photoconversion only at the desired area.

Background and Aims: No consensus has been established regarding optimal long-term maintenance therapy in symptomatic gastroesophageal reflux disease (GERD). The aim of this study was to compare the efficacies of on-demand and continuous therapy with esomeprazole as maintenance treatments for GERD., Methods: Patients with upper gastrointestinal (GI) endoscopy-proven GERD who received initial proton pump inhibitor (PPI) therapy for 8 weeks were randomized to an on-demand group (esomeprazole 40 mg) or a continuous group (esomeprazole 20 mg). Intensities and frequencies of heartburn and acid regurgitation were assessed using a 6-point Likert scale (0 = no symptoms; 5 = very severe symptoms) and a 6-point frequency scale (0 = none; 5 = symptoms for > 5 days per week) at baseline (start of maintenance treatment) and after 12 weeks of treatment. Alleviation of symptoms was quantified using percentages of patients with a Likert scale or frequency scale of 0 or 1., Results: Of the 88 patients enrolled, 8 patients were excluded due to follow-up loss in early period of this study, and finally, 39 in the on-demand group and 41 in the continuous group were analyzed. No significant intergroup difference was found between Likert scale or frequency scale of heartburn or regurgitation at baseline. Percentages of symptom alleviations in the on-demand and continuous groups for intensity of heartburn were 56.4%/48.8% at baseline (P = .523) and 82.1%/87.8% at 12 weeks (P = .471), for frequency of heartburn were 61.5%/46.3% at baseline (P = .173) and 76.9%/87.8% at 12 weeks (P = .200), for intensity of regurgitation was 53.8%/43.9% at baseline (P = .374) and 82.1%/87.8% at 12 weeks (P = .471), and for frequency of regurgitation was 61.5%/56.1% at the baseline (P = .621) and 82.1%/82.9% at 12 weeks (P = .918), respectively. Furthermore, no significant intergroup difference was found for convenience of medication or subjective satisfaction., Conclusions: Intensities and frequencies of heartburn and regurgitation responded well to maintenance treatment in patients in the on-demand and continuous groups. On-demand therapy with esomeprazole 40 mg appears to be sufficient for maintenance treatment in GERD patients.

Chiral supramolecules have great potential for use in chiral recognition, sensing, and catalysis. Particularly, chiral supramolecular biocoordination polymers (SBCPs) provide a versatile platform for characterizing biorelated processes such as chirality transcription. Here, we selectively synthesize homochiral and heterochiral SBCPs, composed of chiral naphthalene diimide ligands and Zn ions, from enantiomeric and mixed R-ligands and S-ligands, respectively. Notably, we find that the chiral self-sorted SBCPs exhibit multifunctional properties, including photochromic, photoluminescent, photoconductive, and chemiresistive characteristics, thus can be used for various sensors. Specifically, these materials can be used for detecting hazardous amine materials due to the electron transfer from the amine to the SBCP surface and for enantioselectively sensing a chiral species naproxen due to the different binding energies with regard to their chirality. These results provide guidelines for the synthesis of chiral SBCPs and demonstrate their versatility and feasibility for use in various sensors covering photoactive, chemiresistive, and chiral sensors.

In genomic data analysis, it is commonplace that underlying regulatory relationship over multiple genes is hardly ascertained due to unknown genetic complexity and epigenetic regulations. In this paper, we consider a joint mean and constant covariance model (JMCCM) that elucidates conditional dependent structures of genes with controlling for potential genotype perturbations. To this end, the modified Cholesky decomposition is utilized to parametrize entries of a precision matrix. The JMCCM maximizes the likelihood function to estimate parameters involved in the model. We also develop a variable selection algorithm that selects explanatory variables and Cholesky factors by exploiting the combination of the GCV and BIC as benchmarks, together with Rao and Wald statistics. Importantly, we notice that sparse estimation of a precision matrix (or equivalently gene network) is effectively achieved via the proposed variable selection scheme and contributes to exploring significant hub genes shown to be concordant to a priori biological evidence. In simulation studies, we confirm that our model selection efficiently identifies the true underlying networks. With an application to miRNA and SNPs data from yeast (a.k.a. eQTL data), we demonstrate that constructed gene networks reproduce validated biological and clinical knowledge with regard to various pathways including the cell cycle pathway.

In this paper, we report an efficient alkali metal doping system for organic single crystals. Our system employs an enhanced diffusion method for the introduction of alkali metal into organic single crystals by controlling the sample temperature to induce secondary thermal activation. Using this system, we achieved intercalation of potassium into picene single crystals with closed packed crystal structures. Using optical microscopy and Raman spectroscopy, we confirmed that the resulting samples were uniformly doped and became K 2 picene single crystal, while only parts of the crystal are doped and transformed into K 2 picene without secondary thermal activation. Moreover, using a customized electrical measurement system, the insulator-to-semiconductor transition of picene single crystals upon doping was confirmed by in situ electrical conductivity and ex situ temperature-dependent resistivity measurements. X-ray diffraction studies showed that potassium atoms were intercalated between molecular layers of picene, and doped samples did not show any KH- nor KOH-related peaks, indicating that picene molecules are retained without structural decomposition. During recent decades, tremendous efforts have been exerted to develop high-performance organic semiconductors and superconductors, whereas as little attention has been devoted to doped organic crystals. Our method will enable efficient alkali metal doping of organic crystals and will be a resource for future systematic studies on the electrical property changes of these organic crystals upon doping.

The multistate redox-active/multi-interactive ligand 5,5',8,8'-tetra(4-pyridyl)-2,2'-(1,4-phenylene)bis-1H-perimidine (H 2 TPP) was designed and synthesized. H 2 TPP undergoes four one-electron oxidation steps, and was used for the preparation of a multistate redox-active coordination network in a solid-liquid interface reaction using molten Cd 2+ salts. The multiple redox states of H 2 TPP were confirmed spectroscopically by stepwise four-electron oxidation. Spectroscopic analysis indicated that the mixed-valence states of the ligand are class II on the UV/Vis/NIR timescale and borderline class II/class III on the ESR timescale., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Strontium segregation at perovskite surfaces deteriorates the oxygen reduction reaction kinetics of cathodes and therefore the long-term stability of solid oxide fuel cells (SOFCs). For the systematic and quantitative assessment of the elastic energy in perovskite oxides, which is known to be one of the main origins for dopant segregation, we report the fractional free volume as a new descriptor for the elastic energy in the perovskite oxide system. To verify the fractional free volume model, three samples were prepared with different A-site dopants: La 0.6 Sr 0.4 CoO 3-δ , La 0.6 Sr 0.2 Ca 0.2 CoO 3-δ , and La 0.6 Ca 0.4 CoO 3-δ . A combination of the theoretical calculations of the segregation energy and oxide formation energy and experimental measurements of the structural, chemical, and electrochemical degradation substantiated the validity of using the fractional free volume to predict the dopant segregation. Furthermore, the dopant segregation could be significantly suppressed by increasing the fractional free volume in the perovskite oxides with dopant substitution. Our results provide insight into dopant segregation from the elastic energy perspective and offer a design guideline for SOFC cathodes with enhanced stability at elevated temperatures.

By changing the rate of evaporation, two kinds of crystalline films composed of redox-active porous coordination networks (1 and 2) were selectively prepared on a gold-patterned substrate using a DMF solution of 2,5,8-tri(4-pyridyl)1,3-diazaphenalene and Cd(NO 3 ) 2 . We found the highly sensitive humidity sensing ability of film 1. Single crystal structures and infrared spectroscopic analyses before and after hydration of a single crystal of 1 revealed the sensing mechanism: exchange of nitrate ions with water on Cd atoms occurred in hydrated conditions to generate a conductive cationic network.

Synthesis of morphologically well-defined crystals of metalloporphyrin by direct crystallization based on conventional anti-solvent crystallization method without using any additives has been rarely reported. Herein, we demonstrate an unconventional and additive-free synthetic method named reverse anti-solvent crystallization method to achieve well-defined zinc-porphyrin cube crystals by reversing the order of the addition of solvents. The extended first solvation shell effect mechanism is therefore suggested to support the synthetic process by providing a novel kinetic route for reaching the local supersaturation environment depending on the order of addition of solvents, which turned out to be critical to achieve clean cube morphology of the crystal. We believe that our work not only extends fundamental knowledge about the kinetic process in binary solvent systems, but also enables great opportunities for shape-directing crystallization of various organic and organometallic compounds.