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As fluoroscopy-guided interventional procedures gain popularity, the associated health threats from radiation exposure to interventionalists during these procedures are increasing. Therefore, an understanding of the potential risks of radiation and careful consideration on minimizing exposure to radiation during the procedures are of paramount importance. The Korean Pancreatobiliary Association has developed a clinical practice guideline to minimize radiation exposure during fluoroscopy-guided interventional procedures. This guideline provides recommendations to deal with the risk of radiation exposure to interventionalists who perform fluoroscopy-guided procedures, and emphasizes the importance of proper and practical approaches to avoid unnecessary radiation exposure.

Background: Mild cognitive impairment (MCI) is a growing concern among older adults, with limited effective pharmacological treatments available. Despite the potential of herbal medicine and acupuncture in managing MCI, there is a lack of research on their long-term effects on cognitive function and brain activity in clinical practice settings. This study aimed to address this gap by exploring the effects of a community-based program integrating herbal medicine and acupuncture on cognitive function and neural responses in older individuals with MCI., Methods: Nineteen individuals were enrolled from a pool of 250 individuals registered in the 2021 Busan Dementia Prevention & Care Program. Participants with MCI received herbal medicine, acupuncture, and pharmacopuncture treatments over a 6-month period. The Montreal Cognitive Assessment (MoCA) was administered at baseline and after 3 and 6 months to evaluate cognitive function. Functional near-infrared spectroscopy (fNIRS) was used to measure prefrontal cortex activity during cognitive task performance, including verbal fluency, Stroop color and word, and digit span backward tests., Results: Seventeen participants (13 female; mean age, 69.5 years) with MCI completed the study. Following the 6-month intervention, they exhibited a significant increase in the MoCA total score over time [F (2.32) =10.59, p < 0.0001]. Additionally, the deoxygenated hemoglobin beta coefficient in the left frontopolar prefrontal cortex significantly decreased during the Stroop task after the intervention., Conclusion: The Dementia Prevention & Care Program, which integrates herbal medicine and acupuncture, may enhance cognitive function in individuals with MCI. Moreover, the observed changes in prefrontal cortex activity after completion of the program suggest a need for further investigation of the underlying mechanisms., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Choi, Lee, Yang, Kwon, Keum and Jang.)

Background: Approximately half of the patients with advanced pancreatic ductal adenocarcinoma (PDAC) receive subsequent lines of chemotherapy. Recently, the liposomal irinotecan (nal-IRI) plus 5-fluorouracil/leucovorin (5-FU/LV) regimen is recommended as subsequent lines of chemotherapy. However, little is known about the predictive factors for the nal-IRI + 5-FU/LV regimen, especially in patients with previous irinotecan (IRI) exposure., Objectives: We investigated the predictive factors associated with nal-IRI + 5-FU/LV treatment in patients with PDAC., Design: Multicenter, retrospective cohort study., Methods: This study included patients with advanced PDAC who received the nal-IRI + 5-FU/LV regimen for palliative purposes., Results: Overall, 268 patients were treated with nal-IRI + 5-FU/LV. The median overall survival (OS) was 7.9 months (95% confidence interval (CI): 7.0-8.8), while the median progression-free survival (PFS) was 2.6 months (95% CI: 1.9-3.2). An albumin level of<4.0 g/dL, neutrophil-to-lymphocyte ratio (NLR) of ⩾3.5, liver or peritoneal metastasis, and a history of >3 lines of palliative chemotherapy were associated with worse OS. An NLR of ⩾3.5 and liver metastasis were significant predictive factors for worse PFS. Previous exposure to IRI was not a significant predictor. Patients without prior IRI (no-IRI) treatment showed relatively longer OS and PFS compared to IRI responders and nonresponders, but these differences were not significant when compared specifically to the responders (OS: 8.8 vs 8.1 months, p = 0.388; PFS: 3.6 vs 2.6 months, p = 0.126)., Conclusion: An NLR of ⩾3.5 and liver metastasis were associated with worse PFS. Prior IRI exposure was not a significant predictive factor for OS and PFS, especially in IRI responders., Competing Interests: Seungmin Bang received funding from Servier., (© The Author(s), 2024.)

A two-component liquid crystalline epoxy network (LCEN) with shape memory behavior was developed and evaluated as a candidate material for 3D printing. The cure kinetics of the uncured material and the shape memory properties of the cured LCEN were investigated by using parallel plate rheology and dynamic mechanical analysis, respectively. A commercially available fumed silica additive was introduced to the neat, uncured material to improve the rheological properties for 3D printing. The addition of fumed silica was found to increase the yield stress, shear-thinning behavior, and toughness of the uncured epoxy ink. Polarized light microscopy, differential scanning calorimetry, and wide-angle X-ray scattering measurements between the neat and additive-modified LCEN suggested a reduction in liquid crystalline alignment in the modified LCEN, owing to interactions between crystalline domains and fumed silica, which in turn influenced the mechanical behavior. Overall, the additive was found to be successful in preserving the shape memory properties of LCEN while improving its printability., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Inversion symmetry breaking is critical for many quantum effects and fundamental for spin-orbit torque, which is crucial for next-generation spintronics. Recently, a novel type of gigantic intrinsic spin-orbit torque is established in the topological van der Waals (vdW) magnet iron germanium telluride. However, it remains a puzzle because no clear evidence exists for interlayer inversion symmetry breaking. Here, the definitive evidence of broken inversion symmetry in iron germanium telluride directly measured by the second harmonic generation (SHG) technique is reported. The data show that the crystal symmetry reduces from centrosymmetric P6 3 /mmc to noncentrosymmetric polar P3m1 space group, giving the threefold SHG pattern with dominant out-of-plane polarization. Additionally, the SHG response evolves from an isotropic pattern to a sharp threefold symmetry upon increasing Fe deficiency, mainly due to the transition from random defects to ordered Fe vacancies. Such SHG response is robust against temperature, ensuring unaltered crystalline symmetries above and below the ferromagnetic transition temperature. These findings add crucial new information to the understanding of this interesting vdW metal, iron germanium telluride: band topology, intrinsic spin-orbit torque, and topological vdW polar metal states., (© 2023 Wiley‐VCH GmbH.)

Objectives: We aimed to investigate medication utilisation trends during pregnancy and identify factors associated with adverse pregnancy outcomes (APOs) in patients with rheumatoid arthritis (RA)., Methods: Female patients with RA aged 20-50 years were identified from the Korean national health insurance database between 2010 and 2020. Pregnancy episodes were divided into two groups according to pregnancy outcome: the delivery group and the APO group (abortion and stillbirth). The characteristics and medication utilisation patterns were compared between the two groups, and multivariable logistic regression analysis was conducted to identify the factors associated with APOs., Results: A total of 5728 pregnancy episodes were included, comprising 4576 delivery episodes and 1152 APO episodes. The mean maternal age for all pregnancy episodes was 33.7 years; 33.3 years in the delivery group and 33.7 years in the APO group. Hydroxychloroquine was the most commonly used conventional synthetic disease-modifying antirheumatic drug (DMARD) during the preconception period and pregnancy in both groups. The prescription rate of all DMARDs decreased rapidly during pregnancy. In the multivariable analysis, use of methotrexate (adjusted OR (aOR): 2.14, 95% CI 1.57 to 2.92) and leflunomide (aOR: 2.68, 95% CI 1.39 to 5.15) within 3 months before conception was associated with APOs., Conclusion: Methotrexate and leflunomide are associated with an increased possibility of APOs, emphasising the importance of appropriate medication adjustment when planning for pregnancy., Competing Interests: Competing interests: Y-KS has received research grants from Bristol-Myers Squibb, Eisai, Pfizer and JW Pharmaceutical. DHY has received research grants from Celltrion, has served as an outside board of Celltrion and is on the speakers’ bureau of Celltrion and Celltrion Healthcare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Perpendicular magnetic anisotropy (PMA) of magnets is paramount for electrically controlled spintronics due to their intrinsic potentials for higher memory density, scalability, thermal stability and endurance, surpassing an in-plane magnetic anisotropy (IMA). Nickel film is a long-lived fundamental element ferromagnet, yet its electrical transport behavior associated with magnetism has not been comprehensively studied, hindering corresponding spintronic applications exploiting nickel-based compounds. Here, we systematically investigate the highly versatile magnetism and corresponding transport behavior of nickel films. As the thickness reduces within the general thickness regime of a magnet layer for a memory device, the hardness of nickel films' ferromagnetic loop of anomalous Hall effect increases and then decreases, reflecting the magnetic transitions from IMA to PMA and back to IMA. Additionally, the square ferromagnetic loop changes from a hard to a soft one at rising temperatures, indicating a shift from PMA to IMA. Furthermore, we observe a butterfly magnetoresistance resulting from the anisotropic magnetoresistance effect, which evolves in conjunction with the thickness and temperature-dependent magnetic transformations as a complementary support. Our findings unveil the rich magnetic dynamics and most importantly settle down the most useful guiding information for current-driven spintronic applications based on nickel film: The hysteresis loop is squarest for the ∼8 nm-thick nickel film, of highest hardness with R xy r / R xy s ∼ 1 and minimum H s - H c , up to 125 K; otherwise, extra care should be taken for a different thickness or at a higher temperature., (© 2024 IOP Publishing Ltd.)

Background: Polycystic ovarian syndrome (PCOS) can be diagnosed when the anti-Müllerian hormone (AMH) levels are high, but in clinic, women who do not meet the diagnosis of PCOS but have elevated AMH levels are often seen. This study aimed to compare the differences in menstrual cycle patterns and hormone levels in women with regular menstrual cycles, but not PCOS, by dividing them into high and low AMH groups., Material and Methods: This multicenter prospective study included 68 healthy women. Participants with regular menstrual cycles were divided into two groups according to their AMH levels. The main outcome measures were menstrual cycle pattern, body mass index, and hormone levels (thyroid stimulating hormone, prolactin, testosterone, sex hormone-binding globulin, and free androgen index), which were compared between the groups according to AMH levels. The ovulation was assessed by performing pelvic ultrasound, and by assessing the hormone levels of the luteinizing hormone and progesterone., Results: The criteria for determining normal and high AMH levels were based on previous literatures. The participants were divided into normal (39 people) and high (29 people) AMH group. No differences were found in age or BMI between the two groups, and no other differences were observed in TSH, prolactin, testosterone, or free androgen index. However, the high AMH group had significantly higher SHBG levels than the normal group (normal group: 65.46 ± 25.78 nmol/L; high group: 87.08 ± 45.05 nmol/L) ( p = 0.025)., Conclusions: This study is the first to analyze the association between SHBG and AMH levels in women with regular menstrual cycles. Elevated AMH levels are associated with increased levels of SHBG levels.

Objectives: This study developed an algorithm for identifying pregnancy episodes and estimating the last menstrual period (LMP) in an administrative claims database and applied it to investigate the use of pregnancy-incompatible immunosuppressants among pregnant women with systemic lupus erythematosus (SLE)., Methods: An algorithm was developed and applied to a nationwide claims database in Korea. Pregnancy episodes were identified using a hierarchy of pregnancy outcomes and clinically plausible periods for subsequent episodes. The LMP was estimated using preterm delivery, sonography, and abortion procedure codes. Otherwise, outcome-specific estimates were applied, assigning a fixed gestational age to the corresponding pregnancy outcome. The algorithm was used to examine the prevalence of pregnancies and utilization of pregnancy-incompatible immunosuppressants (cyclophosphamide [CYC]/mycophenolate mofetil [MMF]/methotrexate [MTX]) and non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy in SLE patients., Results: The pregnancy outcomes identified in SLE patients included live births (67%), stillbirths (2%), and abortions (31%). The LMP was mostly estimated with outcome-specific estimates for full-term births (92.3%) and using sonography procedure codes (54.7%) and preterm delivery diagnosis codes (37.9%) for preterm births. The use of CYC/MMF/MTX decreased from 7.6% during preconception to 0.2% at the end of pregnancy. CYC/MMF/MTX use was observed in 3.6% of women within 3 months preconception and 2.5% during 0-7 weeks of pregnancy., Conclusions: This study presents the first pregnancy algorithm using a Korean administrative claims database. Although further validation is necessary, this study provides a foundation for evaluating the safety of medications during pregnancy using secondary databases in Korea, especially for rare diseases.

(1) Background: An investigation of the preoperative diagnostic clues used to identify ruptured endometrioma by comparing the ruptured and unruptured states in patients who underwent laparoscopic operations due to endometrioma. (2) Methods: Patients with ruptured endometriomas (14 patients) and unruptured endometriomas (60 patients) were included, and clinical symptoms, laboratory findings, and radiological findings were analyzed. (3) Results: There were no significant differences in age, parity, last menstrual cycle days, or median size of endometrioma between two groups (group A: ruptured; group B: unruptured). The median serum level of CA 125 was 345.1 U/mL in group A and 49.8 U/mL in group B ( p = 0.000). The median serum levels of CA 19-9 in group A and B were 46.0 U/mL and 19.1 U/mL, respectively ( p = 0.005). The median serum level of CRP in group A was 1.2 g/dL, whereas it was 0.3 in group B ( p = 0.000). ROC analysis showed that the optimal CA 125 cutoff value was 100.9 U/mL; the optimal CA 19-9 cutoff value was 27.7 U/mL; and the optimal CRP cutoff value was 1.0 g/dL. (4) Conclusions: Ruptured endometrioma can be diagnosed preoperatively using a combination of clinical symptoms, laboratory findings, and radiological findings. If a physician suspects a ruptured endometrioma, surgery should be performed to ensure optimal prognosis.

Inspired by spider silk's hierarchical diversity, we leveraged peptide motifs with the capability to tune structural arrangement for controlling the mechanical properties of a conventional polymer framework. The addition of nanofiller with hydrogen bonding sites was used as another pathway towards hierarchical tuning via matrix-filler interactions. Specifically, peptide-polyurea hybrids (PPUs) were combined with cellulose nanocrystals (CNCs) to develop mechanically-tunable nanocomposites via tailored matrix-filler interactions (or peptide-cellulose interactions). In this material platform, we explored the effect of these matrix-filler interactions on the secondary structure, hierarchical ordering, and mechanical properties of the peptide hybrid nanocomposites. Interactions between the peptide matrix and CNCs occur in all of the PPU/CNC nanocomposites, preventing α-helical ordering, but promoting inter-molecular hydrogen bonded β-sheet formation. Depending on peptide and CNC content, the Young's modulus varies from 10 to 150 MPa. Unlike conventional cellulose-reinforced polymer nanocomposites, the mechanical properties of these composite materials are dictated by a balance of CNC reinforcement, peptidic ordering, and microphase-separated morphology. This research highlights that leveraging peptide-cellulose interactions is a strategy to create materials with targeted mechanical properties for a specific application using a limited selection of building blocks.

Magnetic transition metal chalcogenides form an emerging platform for exploring spin-orbit driven Berry phase phenomena owing to the nontrivial interplay between topology and magnetism. Here we show that the anomalous Hall effect in pristine Cr 2 Te 3 thin films manifests a unique temperature-dependent sign reversal at nonzero magnetization, resulting from the momentum-space Berry curvature as established by first-principles simulations. The sign change is strain tunable, enabled by the sharp and well-defined substrate/film interface in the quasi-two-dimensional Cr 2 Te 3 epitaxial films, revealed by scanning transmission electron microscopy and depth-sensitive polarized neutron reflectometry. This Berry phase effect further introduces hump-shaped Hall peaks in pristine Cr 2 Te 3 near the coercive field during the magnetization switching process, owing to the presence of strain-modulated magnetic layers/domains. The versatile interface tunability of Berry curvature in Cr 2 Te 3 thin films offers new opportunities for topological electronics., (© 2023. The Author(s).)

Context: Considering the absence of methods to find pancreatic cancer early, surveillance of high-risk groups is needed for early diagnosis., Objective: The study aimed to investigate the effect in the incidence of pancreatic cancer and the differences between new-onset diabetes mellitus (NODM) and long-standing DM (LSDM) since NODM group is a representative high-risk group., Methods: The Korean National Health Insurance Service-National Sample Cohort between 2002 and 2013 data were used. Regarding 88 396 people with DM (case group), we conducted a 1:1 propensity score matching to select a matched non-DM population (control group). To investigate the interaction between DM and the time variable distinguishing NODM and LSDM, we performed a multivariate time-dependent Cox regression analysis., Results: The incidence of pancreatic cancer was higher in the DM group compared to the non-DM group (0.52% vs 0.16%; P < .001). The DM group had shown different risk of pancreatic cancer development according to the duration since the DM diagnosis (NODM hazard ratio (HR): 3.81; 95% CI, 2.97-4.88; P < .001; LSDM HR: 1.53; 95% CI, 1.11-2.11; P < .001). When the NODM and the LSDM groups were compared, the risk of pancreatic cancer was higher in the NODM group than in the LSDM group (HR: 1.55; P = .020). In subgroup analysis, NODM group showed that men (HR = 4.42; 95% CI, 3.15-6.19; P < .001) and patients who were in their 50 seconds (HR = 7.54; 95% CI, 3.24-17.56; P < .001) were at a higher risk of developing pancreatic cancer than matched same sex or age control group (non-DM population), respectively., Conclusion: The risk of pancreatic cancer was greater in people with DM than in a non-DM population. Among people with DM, NODM showed a higher risk of pancreatic cancer than LSDM., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

This study aimed to evaluate the difference in gut microbiomes between preterm and term infants using third-generation long-read sequencing (Oxford Nanopore Technologies, ONT) compared with an established gold standard, Illumina (second-generation short-read sequencing). A total of 69 fecal samples from 51 term (T) and preterm (P) infants were collected at 7 and 28 days of life. Gut colonization profiling was performed by 16S rRNA gene sequencing using ONT. We used Illumina to validate and compare the patterns in 13 neonates. Using bioinformatic analysis, we identified features that differed between P and T. Both T1 and P1 microbiomes were dominated by Firmicutes ( Staphylococcus and Enterococcus ), whereas sequentially showed dominant transitions to Lactobacillus ( p  < 0.001) and Streptococcus in T2 ( p  = 0.001), and pathogenic bacteria ( Klebsiella ) in P2 ( p  = 0.001). The abundance of beneficial bacteria ( Bifidobacterium and Lactobacillus ) increased in T2 ( p  = 0.026 and p  < 0.001, respectively). These assignments were correlated with the abundance at the species-level. Bacterial α-diversity increased in T ( p  = 0.005) but not in P ( p  = 0.156), and P2 showed distinct β-diversity clustering than T2 ( p  = 0.001). The ONT reliably identified pathogenic bacteria at the genus level, and taxonomic profiles were comparable to those identified by Illumina at the genus level. This study shows that ONT and Illumina are highly correlated. P and T had different microbiome profiles, and the α- and β-diversity varied. ONT sequencing has potential for pathogen detection in neonates in clinical settings., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Cha, Kim, Keum, Kwak, Park, Hoh, Kim, Jeon and Park.)

Objective: We investigated the feasibility of laparoscopic restaging surgery in patients with unexpected uterine cancer., Methods: This retrospective study included eight patients who underwent laparoscopic restaging surgery for Iran University uterine cancer after a prior hysterectomy or myomectomy., Results: The median age of the patients and their body mass index were 55 years (range, 44-78) and 23.8 kg/m2 (range, 20.75- 31.89), respectively. The median interval between the prior hysterectomy and the restaging surgery was 21 days (range, 10-35). The median operating time and time for the return of bowel activity were 325 minutes (range, 200-475) and 35 hours (range, 18-50), respectively. The median numbers of harvested pelvic and para-aortic lymph nodes were 17.5 (range, 14-29) and 20.5 (range, 7-36), respectively. In seven of the eight patients, uterine extraction was performed with vaginal or electronic morcellation. The final International Federation of Gynecology and Obstetrics stage was IA in all patients. Intraoperative and postoperative complications did not occur in any of the patients, except for the need for transfusion. Patient 4 had synchronous primary cancer (stage IA) of the endometrium and left ovary. Two of the eight patients with clear cell carcinoma received chemotherapy, and none received radiotherapy. All patients survived without disease recurrence., Conclusion: Restaging surgery might be necessary for highly selective patients with unexpected uterine malignancies. This would be an alternative surgical modality for complete staging and planning tailored adjuvant treatments. However, lymphadenectomy might not be performed in patients with early uterine cancer.

Excretory-secretory products (ESP) of T. vaginalis have been shown to inhibit sperm motility, viability, and functional integrity, leading to a decreased fertilization rate in vitro. This study investigated whether T. vaginalis induce apoptosis and ultrastructural changes of sperm using flow cytometry and electron microscopy. Incubation of sperm with T. vaginalis ESP increased phosphatidylserine externalization and DNA fragmentation, and decreased mitochondrial membrane potential. Transmission electron microscopy of sperm incubated with ESP revealed abnormal features such as distorted heads, broken necks, and acrosomes exocytosis. This is the first report that demonstrates a direct impact of T. vaginalis ESP on sperm apoptosis and architecture in vitro.

Animal and human studies suggest that thyroid hormone may have critical roles in the development of the ovary. For example, thyroid deficiency disrupts the ovarian microarchitecture and menstrual cycle in neonate and adult women, respectively. Therefore, it is conceivable that thyroid deficiency might disrupt sexual maturation during the peri-pubertal period. To investigate the impact of radioactive iodine-induced thyroid deficiency on reproductive organs throughout puberty, immature female rats were given water containing radioactive iodine (0.37 MBq/g body weight) twice, on postnatal days 22 and 29. Radioactive iodine-induced hypothyroidism was revealed by low free thyroxin levels. Thyroid deficiency delayed the onset of vaginal opening, reduced ovarian weight and the number of medium-sized follicles and led to elongated uteri. However, there was no effect on the estrous cycle or absolute uterus weight. We conclude that radioactive iodine-induced thyroid deficiency delays sexual maturation and alters normal ovarian growth in peri-pubertal rats., Competing Interests: Conflict of interestAll authors state that they have no conflicts of interest with any financial organization regarding the material discussed in the manuscript., (© The Author(s) under exclusive licence to Korean Society of Toxicology 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

With the continuous increase of global plastics production, there is a demand to develop energy efficient processes to transform mixed plastic wastes into new products with enhanced utility - a concept that is often referred to as upcycling. Compatibilization is one of the most promising strategies to upcycle communal waste plastics. In this work, poly(ethylene terephthalate) (PET) and high-density polyethylene (HDPE), both widely used semicrystalline packaging polymers, are used as the target polymer blend. We systematically evaluate and compare three commercial ethylene copolymer based compatibilizers, ELVALOY™ AC 2016 Acrylate Copolymer (EAA), ELVALOY™ PTW Copolymer (PTW), and SURLYN™ 1802 Ionomer (Surlyn). They represent different compatibilization mechanisms. Furthermore, this work tackles a challenging question: where the compatibilizers are located in the blend. We discover that the location of the compatibilizer molecules can be predicted by comparing the crystallinity change of PET and HDPE in binary and ternary systems. Gaining this knowledge will facilitate root cause analysis of an ineffective compatibilizer and guide the design strategy to upcycle commingled waste plastics., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

FOLFIRINOX (oxaliplatin, leucovorin, irinotecan, and 5-fluorouracil) is a first-line chemotherapy for metastatic pancreatic cancer (PC). Chemotherapy-induced neutropenia is one of the most serious adverse events associated with advanced PC. Although UGT1A1 polymorphisms are associated with the metabolism of irinotecan, their role as surrogate markers for FOLFIRINOX-induced neutropenia has not been confirmed. We investigated risk factors for FN-in particular, UGT1A1 polymorphisms-in PC patients receiving FOLFIRINOX, using a single-center cohort registry. To investigate the association between UGT1A1 polymorphisms and FN, we divided patients into three groups based on the predicted UGT1A1 phenotype: extensive metabolizer (EM) vs. intermediate metabolizer (IM) vs. poor metabolizer (PM). A total of 154 patients (FN group ( n = 31) vs. non-FN group ( n = 123)) receiving first-line FOLFIRINOX were identified between December 2017 and July 2020. The Cox regression analysis showed that female sex (HR: 2.20; p = 0.031), Eastern Cooperative Oncology Group performance status = 1 (HR: 2.83; p = 0.008), UGT1A1 IM (HR: 4.30; p = 0.004), and UGT1A1 PM (HR: 4.03; p = 0.028) were statistically significant risk factors for FN. We propose that UGT1A1 is the strongest predictive factor for FN and that this gene should be screened prior to the administration of chemotherapy.

Background/aims: : Controversy regarding the effectiveness of neoadjuvant therapy for resectable pancreatic ductal adenocarcinoma (PDAC) still exists. Here, we aimed to identify the potential benefits of neoadjuvant therapy followed by surgery for resectable PDAC., Methods: We reviewed radiologically resectable PDAC patients who received resection with curative intent at a tertiary hospital in South Korea between January 2012 and August 2019. A total of 202 patients underwent curative resection for resectable PDAC: 167 underwent surgical resection first during this period, and 35 received neoadjuvant chemotherapy/chemoradiation therapy followed by surgery. Resectable PDAC patients were subdivided, and 1:3 propensity score matching (PSM) was performed to reduce selection bias., Results: Compared with the group that received surgery first, the group that received neoadjuvant treatment followed by surgery had significantly smaller tumors (22.0 mm vs 27.0 mm, p=0.004), a smaller proportion of patients with postoperative pathologic T stage (p=0.026), a smaller proportion of patients with lymphovascular invasion (20.0% vs 40.7%, p=0.022), and a larger proportion of patients with negative resection margins (74.3% vs 51.5%, p=0.049). After PSM, the group that received neoadjuvant therapy had a significantly longer progression-free survival than those in the group that underwent surgery first (29.6 months vs 15.1 months, p=0.002). Overall survival was not significantly different between the two groups after PSM analysis., Conclusions: We observed significantly better surgical outcomes and progression-free survival with the addition of neoadjuvant therapy to the management of resectable PDAC. However, despite PSM, there was still selection bias due to the use of different regimens between the groups receiving surgery first and neoadjuvant therapy. Large homogeneous samples are needed in the future prospective studies.

In this study, we describe a novel kinase inhibitor AX-0085 which can suppress the induction of PD-L1 expression by Interferon-γ (IFN-γ) in lung adenocarcinoma (LUAD) cells. AX-0085 effectively blocks JAK2/STAT1 signaling initiated by IFN-γ treatment and prevents nuclear localization of STAT1. Importantly, we demonstrate that AX-0085 reverses the IFN-γ-mediated repression of T cell activation in vitro and enhances the anti-tumor activity of anti-PD-1 antibody in vivo when used in combination. Finally, transcriptomic analyses indicated that AX-0085 is highly specific in targeting the IFN-γ-pathway, thereby raising the possibility of applying this reagent in combination therapy with checkpoint inhibitor antibodies. It may be particularly relevant in cases in which PD-L1-mediated T cell exhaustion leads to immunoevasive phenotypes.

With the cationic transference number close to unity, single-ion conducting polymer electrolytes (SICPEs) are recognized as an advanced electrolyte system with improved energy efficiency for battery application. The relatively low ionic conductivity for most of the SICPEs in comparison with liquid electrolytes remains the major "bottleneck" for their practical applications. Polyethylene oxide (PEO) has been recognized as a benchmark for solid polymer electrolytes due to its high salt solubility and reasonable ionic conductivity. PEO has two advantages: (i) the polar ether groups coordinate well with lithium ions (Li + ) providing good dissociation from anions, and (ii) the low T g provides fast segmental dynamics at ambient temperature and assists rapid charge transport. These properties lead to active use of PEO as neutral plasticizing units in SICPEs. Herein, we present a detailed comparison of new SICPEs copolymerized with PEO units vs SICPEs copolymerized with other types of neutral units possessing either flexible or polar structures. The presented analysis revealed that the polarity of side chains has a limited influence on ion dissociation for copolymer-type SICPEs. The Li + -ion dissociation seems to be controlled by the charge delocalization on the polymerized anion. With good miscibility between plasticizing neutral units and ionic conductive units, the ambient ionic conductivity of synthesized SICPEs is still mainly controlled by the T g of the copolymer. This work sheds light on the dominating role of PEO in SICPE systems and provides helpful guidance for designing polymer electrolytes with new functionalities and structures. Furthermore, based on the presented results, we propose that designing polyanions with a highly delocalized charge may be another promising route for achieving sufficient lithium ionic conductivity in solvent-free SICPEs.

Background: Approximately 80% of pancreatic ductal adenocarcinoma (PDAC) patients suffer from anorexia, weight loss, and asthenia. Most PDAC patients receive chemotherapy, which often worsens their nutritional status owing to the adverse effects of chemotherapy. Malnutrition of PDAC patients is known to be associated with poor prognosis; therefore, nutritional management during chemotherapy is a key factor influencing the outcome of the treatment. Mobile apps have the potential to provide readily accessible nutritional support for patients with PDAC., Objective: We aimed to evaluate the efficacy of a mobile app-based program, Noom, in patients receiving chemotherapy for PDAC., Methods: We prospectively enrolled 40 patients who were newly diagnosed with unresectable PDAC from a single university-affiliated hospital in South Korea, and randomly assigned them into a Noom user group (n=20) and a non-Noom user group (n=20). The 12-week in-app interventions included meal and physical activity logging as well as nutritional education feedback from dietitians. The non-Noom user group did not receive any nutrition intervention. The primary outcomes were the changes in the nutritional status and quality of life (QoL) from the baseline to 12 weeks. The secondary outcomes included the changes in the skeletal muscle index (SMI) from the baseline to 12 weeks. The European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire (QLQ-C30) and the Patient-Generated Subjective Global Assessment (PG-SGA) were used as paper questionnaires to assess the QoL and nutritional status of the patients. Intention-to-treat and per-protocol analyses were conducted. Regarding the study data collection time points, we assessed the nutritional status and QoL at the baseline (T0), and at 4 (T1), 8 (T2), and 12 (T3) weeks. Abdominal computed tomography (CT) imaging was conducted at the baseline and after 8 weeks for tumor response and SMI evaluation. The skeletal muscle area (cm 2 ) was calculated using routine CT images. The cross-sectional areas (cm 2 ) of the L3 skeletal muscles were analyzed., Results: Between February 2017 and January 2018, 48 patients were assessed for eligibility. Totally 40 patients with pancreatic cancer were included by random allocation. Only 17 participants in the Noom user group and 16 in the non-Noom user group completed all follow-ups. All the study participants showed a significant improvement in the nutritional status according to the PG-SGA score regardless of Noom app usage. Noom users showed statistically significant improvements on the global health status (GHS) and QoL scales compared to non-Noom users, based on the EORTC QLQ (P=.004). The SMI decreased in both groups during chemotherapy (Noom users, 49.08±12.27 cm 2 /m 2 to 46.08±10.55 cm 2 /m 2 ; non-Noom users, 50.60±9.05 cm 2 /m 2 to 42.97±8.12 cm 2 /m 2 ). The decrement was higher in the non-Noom user group than in the Noom user group, but it was not statistically significant (-13.96% vs. -3.27%; P=.11)., Conclusions: This pilot study demonstrates that a mobile app-based approach is beneficial for nutritional and psychological support for PDAC patients receiving chemotherapy., Trial Registration: ClinicalTrials.gov NCT04109495; https://clinicaltrials.gov/ct2/show/NCT04109495., (©Jiyoung Keum, Moon Jae Chung, Youngin Kim, Hyunyoung Ko, Min Je Sung, Jung Hyun Jo, Jeong Youp Park, Seungmin Bang, Seung Woo Park, Si Young Song, Hee Seung Lee. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 31.08.2021.)

Understanding the feasibility to couple semiconducting and magnetic properties in metal halide perovskites through interface design opens new opportunities for creating the next generation spin-related optoelectronics. In this work, a fundamentally new phenomenon of optically induced magnetization achieved by coupling photoexcited orbital magnetic dipoles with magnetic spins at perovskite/ferromagnetic interface is discovered. The depth-sensitive polarized neutron reflectometry combined with in situ photoexcitation setup, constitutes key evidence of this novel effect. It is demonstrated that a circularly polarized photoexcitation induces a stable magnetization signal within the depth up to 7.5 nm into the surface of high-quality perovskite (MAPbBr 3 ) film underneath a ferromagnetic cobalt layer at room temperature. In contrast, a linearly polarized light does not induce any detectable magnetization in the MAPbBr 3 . The observation reveals that photoexcited orbital magnetic dipoles at the surface of perovskite are coupled with the spins of the ferromagnetic atoms at the interface, leading to an optically induced magnetization within the perovskite's surface. The finding demonstrates that perovskite semiconductor can be bridged with magnetism through optically controllable method at room temperature in this heterojunction design. This provides the new concept of utilizing spin and orbital degrees of freedom in new-generation spin-related optoelectronic devices., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

A quantum magnetic state due to magnetic charges is never observed, even though they are treated as quantum mechanical variables in theoretical calculations. Here, the occurrence of a novel quantum disordered state of magnetic charges in a nanoengineered magnetic honeycomb lattice of ultra-small connecting elements is demonstrated. The experimental research, performed using spin resolved neutron scattering, reveals a massively degenerate ground state, comprised of low integer and energetically forbidden high integer magnetic charges, that manifests cooperative paramagnetism at low temperature. The system tends to preserve the degenerate configuration even under large magnetic field application. It exemplifies the robustness of disordered correlation of magnetic charges in a 2D honeycomb lattice. The realization of quantum disordered ground state elucidates the dominance of exchange energy, which is enabled due to the nanoscopic magnetic element size in nanoengineered honeycomb. Consequently, an archetypal platform is envisaged to study quantum mechanical phenomena due to emergent magnetic charges., Competing Interests: The authors declare no conflict of interest., (© 2021 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

In this study, we describe a novel function of TNNC1 (Troponin C1, Slow Skeletal and Cardiac Type), a component of actin-bound troponin, as a tumor suppressor of lung adenocarcinoma (LUAD). First, the expression of TNNC1 was strongly down-regulated in cancer tissues compared to matched normal lung tissues, and down-regulation of TNNC1 was shown to be strongly correlated with increased mortality among LUAD patients. Interestingly, TNNC1 expression was enhanced by suppression of KRAS , and ectopic expression of TNNC1 in turn inhibited KRAS G12D -mediated anchorage independent growth of NIH3T3 cells. Consistently, activation of KRAS pathway in LUAD patients was shown to be strongly correlated with down-regulation of TNNC1 . In addition, ectopic expression of TNNC1 inhibited colony formation of multiple LUAD cell lines and induced DNA damage, cell cycle arrest and ultimately apoptosis. We further examined potential correlations between expression levels of TNNC1 and various clinical parameters and found that low-level expression is significantly associated with invasiveness of the tumor. Indeed, RNA interference-mediated down-regulation of TNNC1 led to significant enhancement of invasiveness in vitro . Collectively, our data indicate that TNNC1 has a novel function as a tumor suppressor and is targeted for down-regulation by KRAS pathway during the carcinogenesis of LUAD.

Polydopamine (PDA) is an emerging nature-inspired biopolymer material that possesses many interesting properties including self-assembly and universal adhesion. PDA is also able to form coordination bonds with various metal ions, which can be reduced to metal nanoparticles (NPs) as a result of thermal annealing under protective environment. In this study, PDA has been utilized as a support material to synthesize Pt NPs in an aqueous solution at room temperature. The catalytic performance of the resulting PDA-Pt nanocomposite was evaluated using an electrochemical workstation which showed comparable activity to Pt/C material for hydrogen evolution reaction (HER). Furthermore, Cu, Ni, and Cu-Ni NPs supported on PDA were also obtained using this strategy with assistance of subsequent thermal annealing. The phase evolution of the NPs was studied by in-situ X-ray diffraction while the morphology of the nanoparticles was investigated using electron microscopic techniques. Preliminary results showed the NPs supported on PDA also possessed HER activity. This work demonstrates that PDA can be utilized as a potential support for synthesis of metal NPs that can be exploited in engineering applications such as catalysts.

Polar phonon modes associated with room temperature ferroelectricity are observed in SrTiO 3 single crystals irradiated with Ti ions. Quantitative strain analysis reveals that irradiation-induced out-of-plane strain drives the centrosymmetric cubic SrTiO 3 to a tetragonal-like structure in the maximum damaged region. Energy transfer from ions to electrons during ion irradiation yields defects in SrTiO 3 that also plays an important role for the room temperature ferroelectricity. Different from thin film techniques, the ferroelectricity in the ion irradiated SrTiO 3 can occur for much larger thicknesses, depending on the energy and type of ion., (© 2020 IOP Publishing Ltd.)

Purpose: FOLFIRINOX is the standard therapy in patients with unresectable pancreatic cancer (PC). However, FOLFIRINOX frequently induces febrile neutropenia (FN) and neutropenia. The purpose of this study was to explore risk factors for FN and grade 4 neutropenia (NP G4) in patients receiving FOLFIRINOX for PC., Methods: We collected data on 106 patients with PC treated with first-line FOLFIRINOX between 2015 and 2017 using the Pancreatic Cancer Cohort Registry of Severance Hospital in Seoul, Korea., Results: Multivariate logistic regression analysis showed that female (OR, 3.24; P = 0.023), Eastern Cooperative Oncology Group performance status (OR, 3.70; P = 0.024), overweight (OR, 4.25; P = 0.022), and initial biliary stent insertion (OR, 4.22; P = 0.008) were significantly related to a high risk of FN. Time-dependent bias was reduced using Cox regression analysis, which revealed that female (OR, 2.29; P = 0.041), overweight (OR, 2.67; P = 0.022), and initial biliary stent insertion (OR, 2.59; P = 0.016) were statistically significant predictors. Regarding NP G4, female sex (OR, 2.90; P = 0.016) and overweight (OR, 4.07; P = 0.033) were identified as risk factors in multivariate analysis; however, in Cox regression analysis, tumor in the head of the pancreas (OR, 1.96; P = 0.027) and hemoglobin (g/dL < 12) (OR, 1.87; P = 0.049) were also identified as risk factors., Conclusion: Female sex, overweight, and initial biliary stent insertion were independent risk factors for the occurrence of FN in patients with unresectable PC treated with FOLFIRINOX.

Identification of drug-target interactions (DTIs) plays a key role in drug discovery. The high cost and labor-intensive nature of in vitro and in vivo experiments have highlighted the importance of in silico-based DTI prediction approaches. In several computational models, conventional protein descriptors have been shown to not be sufficiently informative to predict accurate DTIs. Thus, in this study, we propose a deep learning based DTI prediction model capturing local residue patterns of proteins participating in DTIs. When we employ a convolutional neural network (CNN) on raw protein sequences, we perform convolution on various lengths of amino acids subsequences to capture local residue patterns of generalized protein classes. We train our model with large-scale DTI information and demonstrate the performance of the proposed model using an independent dataset that is not seen during the training phase. As a result, our model performs better than previous protein descriptor-based models. Also, our model performs better than the recently developed deep learning models for massive prediction of DTIs. By examining pooled convolution results, we confirmed that our model can detect binding sites of proteins for DTIs. In conclusion, our prediction model for detecting local residue patterns of target proteins successfully enriches the protein features of a raw protein sequence, yielding better prediction results than previous approaches. Our code is available at https://github.com/GIST-CSBL/DeepConv-DTI., Competing Interests: No authors have competing interests.

The effects of deuterium isotope substitution on conjugated polymer chain stacking of poly(3-hexylthiophene) is studied experimentally by X-ray diffraction (XRD) in combination with gel permeation chromatography and theoretically using density functional theory and quantum molecular dynamics. For four P3HT materials with different levels of deuteration (pristine, main-chain deuterated, side-chain deuterated, and fully deuterated), the XRD measurements show that main-chain thiophene deuteration significantly reduces crystallinity, regardless of the side-chain deuteration. The reduction of crystallinity due to the main-chain deuteration is a quantum nuclear effect resulting from a static zero-point vibrational energy combined with a dynamic correlation of the dipole fluctuations. The quantum molecular dynamics simulations confirm the interchain correlation of the proton-proton and deuteron-deuteron motions but not of the proton-deuteron motion. Thus, isotopic purity is an important factor affecting stability and properties of conjugated polymer crystals, which should be considered in the design of electronic and spintronic devices.

Nature has achieved diverse functionality via hierarchical organization driven by physical interactions such as hydrogen bonding. Synthetically, polymer-peptide hybrids have been utilized to achieve these architectural arrangements and obtain diverse mechanical properties, stimuli responsiveness, and bioactivity. Here, we explore the impact of peptide ordering and soft/hard phase interactions in PEG-based non-chain extended and chain extended peptidic polyurea (PU) and polyurea/polyurethane (PUU) hybrids towards tunable mechanics. Increasing the peptide content of poly(ε-carbobenzyloxy-l-lysine) (PZLY) revealed an increase in α-helical formation and modulation in amine/ether hydrogen bonding, suggesting enhanced intermolecular hydrogen bonding between peptide segments and soft/hard blocks. A balance of phase mixing and microphase segregation was observed depending on competitive hydrogen bonding and the hybrid architecture. This phase behaviour strongly modulated the mechanical response, particularly modulus and extensibility. We anticipate that this solid-state, synthetic framework will expand the reach of our peptide hybrids into biointerfacing materials, including scaffolds and responsive actuators via peptide selection.

Objective: To analyze the preoperative diagnostic clues to ovarian pregnancy (OP)., Methods: This study conducted a retrospective chart review of 23 patients with OP and 46 patients with tubal pregnancy (TP) from October 1, 2003 to September 31, 2016 in Hanyang University Hospital., Results: There were no significant differences in demographic and clinical characteristics between the two groups. The presence of an ectopic gestational sac and hemoperitoneum was significantly higher in the TP group (13.0% vs. 95.7%, P =0.000; 13.0% vs. 54.3%, P =0.001, respectively) in preoperative ultrasonogram. The OP group had more ruptured ectopic gestational sacs than the TP group (73.9% vs. 45.7%, P =0.039) in surgical findings., Conclusion: For the patients in whom a gestational sac is not detected in the uterus or the fallopian tubes, it is important to be aware of the possibility of OP and rupture of an ovarian gestational sac to promote early diagnosis and surgical intervention., Competing Interests: Conflict of interest: No potential conflict of interest relevant to this article was reported.

Predicting drug-target interactions is important for the development of novel drugs and the repositioning of drugs. To predict such interactions, there are a number of methods based on drug and target protein similarity. Although these methods, such as the bipartite local model (BLM), show promise, they often categorize unknown interactions as negative interaction. Therefore, these methods are not ideal for finding potential drug-target interactions that have not yet been validated as positive interactions. Thus, here we propose a method that integrates machine learning techniques, such as self-training support vector machine (SVM) and BLM, to develop a self-training bipartite local model (SELF-BLM) that facilitates the identification of potential interactions. The method first categorizes unlabeled interactions and negative interactions among unknown interactions using a clustering method. Then, using the BLM method and self-training SVM, the unlabeled interactions are self-trained and final local classification models are constructed. When applied to four classes of proteins that include enzymes, G-protein coupled receptors (GPCRs), ion channels, and nuclear receptors, SELF-BLM showed the best performance for predicting not only known interactions but also potential interactions in three protein classes compare to other related studies. The implemented software and supporting data are available at https://github.com/GIST-CSBL/SELF-BLM., Competing Interests: The authors have declared that no competing interests exist.

Nature has achieved controlled and tunable mechanics via hierarchical organization driven by physical and covalent interactions. Polymer-peptide hybrids have been designed to mimic natural materials utilizing these architectural strategies, obtaining diverse mechanical properties, stimuli responsiveness, and bioactivity. Here, utilizing a molecular design pathway, peptide-polyurea hybrid networks were synthesized to investigate the role of architecture and structural interplay on peptide hydrogen bonding, assembly, and mechanics. Networks formed from poly(β-benzyl-l-aspartate)-poly(dimethylsiloxane) copolymers covalently cross-linked with a triisocyanate yielded polyurea films with a globular-like morphology and parallel β-sheet secondary structures. The geometrical constraints imposed by the network led to an increase in peptide loading and ∼7x increase in Young's modulus while maintaining extensibility (∼160%). Thus, the interplay of physical and chemical bonds allowed for the modulation of resulting mechanical properties. This investigation provides a framework for the utilization of structural interplay and mechanical tuning in polymer-peptide hybrids, which offers a pathway for the design of future hybrid biomaterial systems.

Detailed analysis of the static structure factor S(Q) in several glass-forming liquids reveals that the temperature variations of the width of the main diffraction peak ΔQ(T) correlate with the fragility of these liquids. This observation suggests a direct connection between rather subtle structural changes and sharp slowing down of structural relaxation in glass-forming liquids. We show that this observation can be rationalized using the Adam-Gibbs approach, through a connection between temperature variations of structural correlation length, l&#95;{c}∼2π/ΔQ, and the size of cooperatively rearranging regions.

Background: Verifying the proteins that are targeted by compounds of natural herbs will be helpful to select natural herb-based drug candidates. However, this entails a great deal of effort to clarify the interaction throughout in vitro or in vivo experiments. In this light, in silico prediction of the interactions between compounds and target proteins can help ease the efforts., Results: In this study, we performed in silico predictions of herbal compound target identification. First, data related to compounds, target proteins, and interactions between them are taken from the DrugBank database. Then we characterized six classes of compound-target interaction in humans including G-protein-coupled receptors (GPCRs), ion channel, enzymes, receptors, transporters, and other proteins. Also, classification-prediction models that predict the interactions between compounds and target proteins through a machine learning method were constructed using these matrices. As a result, AUC values of six classes are 0.94, 0.93, 0.90, 0.89, 0.91, and 0.76 respectively. Finally, the interactions of compounds from natural products were predicted using the constructed classification models. Furthermore, from our predicted results, we confirmed that several important disease related proteins were predicted as targets of natural herbal compounds., Conclusions: We constructed classification-prediction models that predict the interactions between compounds and target proteins. The constructed models showed good prediction performances, and numbers of potential natural compounds target proteins were predicted from our results.

Organometallic halide perovskites (OHPs) hold great promise for next-generation, low-cost optoelectronic devices. During the chemical synthesis and crystallization of OHP thin films, a major unresolved question is the competition between multiple halide species (e.g., I(-), Cl(-), Br(-)) in the formation of the mixed-halide perovskite crystals. Whether Cl(-) ions are successfully incorporated into the perovskite crystal structure or, alternatively, where they are located is not yet fully understood. Here, in situ X-ray diffraction measurements of crystallization dynamics are combined with ex situ TOF-SIMS chemical analysis to reveal that Br(-) or Cl(-) ions can promote crystal growth, yet reactive I(-) ions prevent them from incorporating into the lattice of the final perovskite crystal structure. The Cl(-) ions are located in the grain boundaries of the perovskite films. These findings significantly advance our understanding of the role of halogens during synthesis of hybrid perovskites and provide an insightful guidance to the engineering of high-quality perovskite films, essential for exploring superior-performing and cost-effective optoelectronic devices.

A two-step solution processing approach has been established to grow void-free perovskite films for low-cost high-performance planar heterojunction photovoltaic devices. A high-temperature thermal annealing treatment was applied to drive the diffusion of CH3NH3I precursor molecules into a compact PbI2 layer to form perovskite films. However, thermal annealing for extended periods led to degraded device performance owing to the defects generated by decomposition of perovskite into PbI2. A controllable layer-by-layer spin-coating method was used to grow "bilayer" CH3NH3I/PbI2 films, and then drive the interdiffusion between PbI2 and CH3NH3I layers by a simple air exposure at room temperature for making well-oriented, highly crystalline perovskite films without thermal annealing. This high degree of crystallinity resulted in a carrier diffusion length of ca. 800 nm and a high device efficiency of 15.6%, which is comparable to values reported for thermally annealed perovskite films., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

SLC22A18, solute carrier family 22, member 18, has been proposed to function as a tumor suppressor based on its chromosomal location at 11p15.5, mutations and aberrant splicing in several types of cancer and down-regulation in glioblastoma. In this study, we sought to demonstrate the significance of SLC22A18 as a tumor suppressor in colorectal cancer (CRC) and provide mechanistic bases for its function. We first showed that the expression of SLC22A18 is significantly down-regulated in tumor tissues using matched normal-tumor samples from CRC patients. This finding was also supported by publically accessible data from The Cancer Genome Atlas (TCGA). Functionally, SLC22A18 inhibits colony formation and induces of G2/M arrest consistent with being a tumor suppressor. Interestingly, suppression of KRAS by RNA interference promotes SLC22A18 expression, and expression of SLC22A18 in turn inhibits KRAS(G12D)-mediated anchorage independent growth of NIH3T3 cells indicating a mutual negative interaction. Finally, we evaluated diagnostic and prognostic values of SLC22A18 using clinical and gene expression data from TCGA which revealed a significantly worse long-term prognosis for patients with low level SLC22A18 expression. In sum, we established SLC22A18 as a tumor suppressor in colon epithelial cells and propose that SLC22A18 is potentially a marker of diagnostic and prognostic values.

Imperfections in organometal halide perovskite films such as grain boundaries (GBs), defects, and traps detrimentally cause significant nonradiative recombination energy loss and decreased power conversion efficiency (PCE) in solar cells. Here, a simple layer-by-layer fabrication process based on air exposure followed by thermal annealing is reported to grow perovskite films with large, single-crystal grains and vertically oriented GBs. The hole-transport medium Spiro-OMeTAD is then infiltrated into the GBs to form vertically aligned bulk heterojunctions. Due to the space-charge regions in the vicinity of GBs, the nonradiative recombination in GBs is significantly suppressed. The GBs become active carrier collection channels. Thus, the internal quantum efficiencies of the devices approach 100% in the visible spectrum range. The optimized cells yield an average PCE of 16.3 ± 0.9%, comparable to the best solution-processed perovskite devices, establishing them as important alternatives to growing ideal single crystal thin films in the pursuit toward theoretical maximum PCE with industrially realistic processing techniques.

The number of water quality monitoring stations in the USA has decreased over the past few decades. Scarcity of observations can easily produce prediction uncertainty due to unreliable model calibration. An effective water quality monitoring network is important not only for model calibration and water quality prediction but also for resources management. Redundant or improperly located monitoring stations may cause increased monitoring costs without improvement to the understanding of water quality in watersheds. In this work, a decision-making methodology is proposed to design a water quality monitoring network by providing an adequate number of monitoring stations and their approximate locations at the eight-digit hydrologic unit codes (HUC8) scale. The proposed methodology is demonstrated for an example at the Upper Colorado River Basin (UCRB), where salinity is a serious concern. The level of monitoring redundancy or scarcity is defined by an index, station ratio (SR), which represents a monitoring density based on water quality load originated within a subbasin. By comparing the number of stations from a selected target SR with the available number of stations including the actual and the potential stations, the suggested number of stations in each subbasin was decided. If monitoring stations are primarily located in the low salinity loading subbasins, the average actual SR tends to increase, and vice versa. Results indicate that the spatial distribution of monitoring locations in 2011 is concentrated on low salinity loading subbasins, and therefore, additional monitoring is required for the high salinity loading subbasins. The proposed methodology shows that the SR is a simple and a practical indicator for monitoring density.

Introduction: Neuregulin 1 (NRG1) has been discovered as the tail moiety of fusion genes with several distinct partner head genes in lung cancers. These fusion genes activate ERBB2/ERBB3 receptor-mediated cell signaling and thereby function as oncogenic drivers., Methods: We have carried out whole-transcriptome sequencing of 100 non-small-cell lung carcinoma tumors and isolated a novel fusion gene consisting of vesicle-associated membrane protein 2 (VAMP2) and NRG1. Reverse transcription-polymerase chain reaction and genomic DNA analysis were used to demonstrate interchromosomal translocation. Immunoblotting and soft agar assays were used to examine stimulating activity of the fusion gene through ERBB2/ERBB3 signaling pathway., Results: The most highly expressed splice variant of VAMP2-NRG1 fusion gene was shown to be membrane bound and display EGF-like domain of NRG1 extracellularly. VAMP2-NRG1 promotes anchorage-independent colony formation of H1568 lung adenocarcinoma cells. Ectopic expression of the fusion gene stimulates phosphorylation of ERBB2 and ERBB3 as well as downstream targets, AKT and ERK, confirming activation of the signaling pathway., Conclusion: VAMP2-NRG1 is a novel oncogenic fusion gene representing a new addition to the list of NRG1 fusion genes, which together may form an important diagnostic and clinical category of lung adenocarcinoma cases.

When water molecules are confined to nanoscale spacings, such as in the nanometer-size pores of activated carbon fiber (ACF), their freezing point gets suppressed down to very low temperatures (∼150K), leading to a metastable liquid state with remarkable physical properties. We have investigated the ambient pressure diffusive dynamics of water in microporous Kynol ACF-10 (average pore size ∼11.6Å, with primarily slit-like pores) from temperature T=280 K in its stable liquid state down to T=230 K into the metastable supercooled phase. The observed characteristic relaxation times and diffusion coefficients are found to be, respectively, higher and lower than those in bulk water, indicating a slowing down of the water mobility with decreasing temperature. The observed temperature-dependent average relaxation time 〈τ〉 when compared to previous findings indicate that it is the width of the slit pores-not their curvature-that primarily affects the dynamics of water for pore sizes larger than 10 Å. The experimental observations are compared to complementary molecular dynamics simulations of a model system, in which we studied the diffusion of water within the 11.6 Å gap of two parallel graphene sheets. We find generally a reasonable agreement between the observed and calculated relaxation times at the low momentum transfer Q(Q≤0.9Å(-1)). At high Q, however, where localized dynamics becomes relevant, this ideal system does not satisfactorily reproduce the measurements. Consequently, the simulations are compared to the experiments at low Q, where the two can be best reconciled. The best agreement is obtained for the diffusion parameter D associated with the hydrogen-site when a representative stretched exponential function, rather than the standard bimodal exponential model, is used to parametrize the self-correlation function I(Q,t).

The attractive optoelectronic properties of conducting polymers depend sensitively upon intra- and inter-polymer chain interactions, and therefore new methods to manipulate these interactions are continually being pursued. Here, we report a study of the isotopic effects of deuterium substitution on the structure, morphology and optoelectronic properties of regioregular poly(3-hexylthiophene)s with an approach that combines the synthesis of deuterated materials, optoelectronic properties measurements, theoretical simulation and neutron scattering. Selective substitutions of deuterium on the backbone or side-chains of poly(3-hexylthiophene)s result in distinct optoelectronic responses in poly(3-hexylthiophene)/[6,6]-phenyl-C61-butyric acid methyl ester (PCBM) photovoltaics. Specifically, the weak non-covalent intermolecular interactions induced by the main-chain deuteration are shown to change the film crystallinity and morphology of the active layer, consequently reducing the short-circuit current. However, side-chain deuteration does not significantly modify the film morphology but causes a decreased electronic coupling, the formation of a charge transfer state, and increased electron-phonon coupling, leading to a remarkable reduction in the open circuit voltage.

Background: Deep sequencing techniques provide a remarkable opportunity for comprehensive understanding of tumorigenesis at the molecular level. As omics studies become popular, integrative approaches need to be developed to move from a simple cataloguing of mutations and changes in gene expression to dissecting the molecular nature of carcinogenesis at the systemic level and understanding the complex networks that lead to cancer development., Results: Here, we describe a high-throughput, multi-dimensional sequencing study of primary lung adenocarcinoma tumors and adjacent normal tissues of six Korean female never-smoker patients. Our data encompass results from exome-seq, RNA-seq, small RNA-seq, and MeDIP-seq. We identified and validated novel genetic aberrations, including 47 somatic mutations and 19 fusion transcripts. One of the fusions involves the c-RET gene, which was recently reported to form fusion genes that may function as drivers of carcinogenesis in lung cancer patients. We also characterized gene expression profiles, which we integrated with genomic aberrations and gene regulations into functional networks. The most prominent gene network module that emerged indicates that disturbances in G2/M transition and mitotic progression are causally linked to tumorigenesis in these patients. Also, results from the analysis strongly suggest that several novel microRNA-target interactions represent key regulatory elements of the gene network., Conclusions: Our study not only provides an overview of the alterations occurring in lung adenocarcinoma at multiple levels from genome to transcriptome and epigenome, but also offers a model for integrative genomics analysis and proposes potential target pathways for the control of lung adenocarcinoma.

Background and Objectives: Sinomenine is an alkaloid compound and a prominent anti-inflammatory agent found in the root of the climbing plant Sinomenium acutum. However, its effects on the mechanism of human mast cell line (HMC)-1-mediated inflammation remained unknown., Materials and Methods: To provide insight into the biological effects of sinomenine, we examined its influence on the pro-inflammatory cytokine production in HMC-1 cells stimulated by phorbol 12-myristate-13-acetate (PMA) plus A23187 by evaluating the stimulated cells in the presence or absence of sinomenine. In the present study, the pro-inflammatory cytokine production was measured using ELISA, Reverse Transcription-polymerase chain reaction (RT-PCR) and nuclear factor (NF)-kappaB, mitogen-activated protein kinases (MAPKs) pathway activation, as determined by Western blot analysis. Also, cyclooxygenase (COX)-2 expression was measured through Western blot and RT-PCR analysis., Results: Sinomenine inhibited the pro-inflammatory cytokine production induced by PMA plus A23187 in a dose-dependent manner. Furthermore, sinomenine inhibited the phosphorylations of extracellular signal-regulated kinase (ERK) and p38 MAPKs as well as the translocation of NF-kappaB p65 through reduced IkappaBalpha degradation. In addition, sinomenine suppressed COX-2 protein and mRNA expression dose-dependently., Conclusions: Taken together, the results of this study indicate that the anti-inflammatory effects of sinomenine may occur via the inhibition of pro-inflammatory cytokine and COX-2 production through the inhibition of MAPKs and NF-kappaB pathway activation by PMA plus A23187 stimulation in HMC-1 cells.

Background and Objectives: Papaveraceae serve as a rich source of various alkaloids which have anti-inflammatory effect., Materials and Methods: In this study, we investigated the effect of Hylomecon hylomeconoides ethanol extract (HHE) on lipopolysaccharide (LPS)-induced NO and interleukin-6 (IL-6) production in RAW 264.7 cells., Results: HHE inhibited LPS-induced NO and IL-6 production. Moreover, HHE suppressed the phosphorylation of ERK1/2 and p38 in LPS-induced RAW 264.7 in a dose-dependent manner. Furthermore, major constituents, dihydrosanguinarine and 6-methoxydihydrosanguinarine, of the chloroform-soluble extract were analyzed., Conclusions: Taken together, the results of this study indicate that the anti-inflammatory effects of HHE may occur via the inhibition of NO and IL-6 expression through the down-regulation of MAP kinase (ERK1/2, p38) phosphorylation in RAW 264.7 cells.