Recently, studies of 2D organic layered materials with unique electronic properties have generated considerable interest in the research community. However, the development of organic materials with ...functional electrical transport properties is still needed. Here, a 2D fused aromatic network (FAN) structure with a C5N basal plane stoichiometry is designed and synthesized, and thin films are cast from C5N solution onto silicon dioxide substrates. Then field‐effect transistors are fabricated using C5N thin flakes as the active layer in a bottom‐gate top‐contact configuration to characterize their electrical properties. The C5N thin flakes, isolated by polydimethylsiloxane stamping, exhibit ambipolar charge transport and extraordinarily high electron (996 cm2 V−1 s−1) and hole (501 cm2 V−1 s−1) mobilities, surpassing the performance of most pristine organic materials without doping. These results demonstrate their vast potential for applications in thin‐film optoelectronic devices.
A crystalline fused aromatic network with a basal plane stoichiometry of C5N exhibits exceptionally high carrier mobility. The thin flakes of C5N, obtained by poly(dimethylsiloxane) stamping, show ambipolar charge transport and remarkably high electron and hole mobilities, demonstrating their huge potential for applications in thin‐film electronics.
Background
Breast-conserving surgery (BCS) has been reported to have better survival rates when compared with total mastectomy (TM) in early breast cancer. We evaluated the long-term outcomes of ...Korean women with early breast cancer who underwent either BCS plus radiotherapy (RT) or TM.
Methods
In this population-based study, we evaluated 45,770 patients from the Korean Breast Cancer Registry (KBCR) who were diagnosed with early breast cancer, and divided them into the BCS + RT and TM groups. To minimize bias caused by factors other than the surgical method, we used exact match pairing of prognostic factors. We compared the 10-year overall survival (OS) and breast cancer-specific survival (BCSS) before and after exact matching. As the KBCR is a multicenter, online-based registry program, we used the Asan Medical Center (AMC) database, a single-center database, to validate the results from the KBCR database.
Results
In both the KBCR and AMC cohorts, the BCS + RT group showed better OS and BCSS than the TM group, before and after exact matching. For the KBCR cohort after exact matching, the hazard ratios for OS and BCSS were 1.541 (95% confidence interval CI 1.392–1.707,
p
< 0.001) and 1.405 (95% CI 1.183–1.668,
p
< 0.001), respectively, favoring the BCS + RT group. For the AMC cohort after exact matching, the hazard ratios for OS and BCSS were 1.854 (95% CI 1.476–2.328,
p
< 0.001) and 1.807 (95% CI 1.186–2.752,
p
= 0.006), respectively.
Conclusions
Our results suggest that BCS + RT is at least equivalent to TM in terms of OS and may affect treatment decisions in early breast cancer patients.
Background
Thymectomy is required for the treatment of thymoma‐associated myasthenia gravis (MG). However, MG may develop only after thymectomy, a condition known as post‐thymectomy MG. This study ...aimed to investigate the risk factors for post‐thymectomy MG in patients with thymoma.
Methods
We retrospectively identified 235 patients with thymoma who underwent thymectomy at a single hospital from January 2008 to December 2017: 44 with preoperatively diagnosed MG were excluded, leaving 191 patients in the final analysis. Univariable survival analyses using Cox proportional hazards regression model and Kaplan‐Meier estimate were conducted to identify risk factors for post‐thymectomy MG.
Results
Post‐thymectomy MG developed in 4.2% (8/191) of the patients with thymoma between 18 days and 108 mo after surgery. Hazard ratios (HRs) of pre‐ and postoperative anti‐acetylcholine receptor antibody (AChR‐Ab) titers were 2.267 (P = .002) and 1.506 (P < .001), respectively. Patients with extended thymectomy had a low chance of post‐thymectomy MG (HR 0.035, P = .007). Larger thymoma (HR, 1.359; P = .005) and type A or AB thymoma according to World Health Organization histological classification (HR, 11.92; P = .021) were associated with higher chances of post‐thymectomy MG. Within the subgroup of preoperatively AChR‐Ab seropositive patients, post‐thymectomy MG developed in 22.2% (6/27).
Conclusions
Pre‐ and postoperative AChR‐Ab levels should be measured in patients with thymoma. A large thymoma and partial thymectomy appear to be associated with a higher probability of post‐thymectomy MG.
Background
Diffuse large B‐cell lymphoma (DLBCL) harboring Epstein–Barr virus (EBV) primarily occurs in patients who have underlying immunodeficiency or in elderly patients but is also reported in ...young, immunocompetent patients. The authors investigated the pathologic differences in EBV‐positive DLBCL in these three groups of patients.
Methods
In total, 57 patients with EBV‐positive DLBCL were included in the study; of these, 16 patients had associated immunodeficiency, 10 were young (younger than 50 years), and 31 were elderly (aged 50 years or older). Immunostaining for CD8, CD68, PD‐L1, and EBV nuclear antigen 2, and panel‐based next‐generation sequencing was performed on formalin‐fixed, paraffin‐embedded blocks.
Results
Immunohistochemistry revealed EBV nuclear antigen 2 positivity in 21 of the 49 patients. The degree of CD8‐positive and CD68‐positive immune cell infiltration and PD‐L1 expression did not differ significantly in each group. Extranodal site involvement was more common in young patients (p = .021). In mutational analysis, the genes with the highest mutation frequency were PCLO (n = 14), TET2 (n = 10), and LILRB1 (n = 10). For the TET2 gene, all 10 mutations were found in elderly patients (p = .007). Compared with a validation cohort, both TET2 and LILRB1 showed a higher mutation frequency in EBV‐positive patients than in EBV‐negative patients.
Conclusions
EBV‐positive DLBCL occurring in three different age and immune status groups showed similar pathologic characteristics. Notably, a high frequency of TET2 and LILRB1 mutations was characteristic of this disease in elderly patients. Further studies are needed to determine the role of TET2 and LILRB1 mutations in the development of EBV‐positive DLBCL along with immune senescence.
Plain Language Summary
Epstein–Barr virus‐positive diffuse large B‐cell lymphoma occurring in three different groups (immunodeficiency‐associated, young, and elderly) showed similar pathologic characteristics.
The frequency of TET2 and LILRB1 mutations was high in elderly patients with Epstein–Barr virus‐positive diffuse large B‐cell lymphoma.
Epstein–Barr virus‐positive diffuse large B‐cell lymphoma occurring in three different age and immune status groups showed similar pathologic characteristics. Notably, the high frequency of TET2 and LILRB1 mutations was characteristic of this disease in elderly patients.
Partially epoxidized soybean oil (pESO) and fully epoxidized soybean oil (fESO) were used respectively to modify a diglycidyl ether of bisphenol A (DGEBA) resin system in this study. The pESO was ...prepared by epoxidizing soybean oil and the fESO was purchased as it was commercially available. DGEBA/ESO ratio of the epoxy resin system was changed from 100/0 to 70/30 and triethylenetetramine was used as a curing agent. Impact strength of the bio‐epoxy resin system with fESO increased with ESO content, but the system with pESO decreased with ESO content. The bio‐epoxy resin system with pESO showed higher tensile strength and elongation at break than the system with fESO at ESO 30 wt%. Tensile modulus and thermal degradation temperature decreased with ESO content and glass transition temperature was highest at 20 wt% ESO regardless of epoxide functionality of ESO. The performance of the DGEBA/ESO bio‐epoxy resin system could be tailored by changing ESO content and functionality.
Crizotinib, an inhibitor of anaplastic lymphoma kinase (ALK), MET, and ROS1, is approved for treatment of patients with ALK‐positive or ROS1‐positive advanced non‐small‐cell lung cancer (NSCLC). ...However, ALK rearrangements are also implicated in other malignancies, including anaplastic large‐cell lymphoma and inflammatory myofibroblastic tumors (IMTs). In this ongoing, multicenter, single‐arm, open‐label phase 1b study (PROFILE 1013; NCT01121588), patients with ALK‐positive advanced malignancies other than NSCLC were to receive a starting dose of crizotinib 250 mg twice daily. Primary endpoints were safety and objective responses based on Response Evaluation Criteria in Solid Tumors version 1.1 or National Cancer Institute International Response Criteria. Forty‐four patients were enrolled (lymphoma, n = 18; IMT, n = 9; other tumors, n = 17). The objective response rate was 53% (95% confidence interval CI, 28–77) for lymphoma, with 8 complete responses (CRs) and 1 partial response (PR); 67% (95% CI, 30–93) for IMTs, with 1 CR and 5 PRs; and 12% (95% CI, 2–36) for other tumors, with 2 PRs in patients affected by colon carcinoma and medullary thyroid cancer, respectively. The median duration of treatment was almost 3 years for patients with lymphoma and IMTs, with 2‐year progression‐free survival of 63% and 67%, respectively. The most common treatment‐related adverse events were diarrhea (45.5%) and vision disorders (45.5%), mostly grade 1. These findings indicate strong and durable activity of crizotinib in ALK‐positive lymphomas and IMTs. The safety profile was consistent with the known safety profile of crizotinib even with long‐term treatment.
Abstract Background Hepatitis B virus (HBV) reactivation is increasing, as rituximab has become widely used for B-cell lymphoma. Thus, prevention and management of HBV reactivation are important in ...HBV-endemic areas. Methods Hepatitis B virus (HBV) reactivation in HBV surface antigen (HBsAg)-positive patients and HBsAg-negative/HBV core antibody (HBcAb)-positive patients who received rituximab-containing chemotherapy was investigated by the Asia Lymphoma Study Group via retrospective ( n = 340), and the results were compared to cross-sectional analysis with patients who were prospectively monitored in a single institute ( n = 127). The goal of the study was to define the frequency of HBV reactivation and the efficacy of antiviral prophylaxis. Results HBV reactivation was found in 27.8% of HBsAg-positive patients (45/162) in the retrospective analysis, being significantly less frequent in patients receiving antiviral prophylaxis than those not (22.9%, 32/140 versus 59.1%, 13/22; p < 0.001). Lamivudine was most commonly used (96/162, 59.3%), but more than 20% of HBsAg-positive patients showed breakthrough HBV reactivation. In the cross-sectional analysis, a reduced rate of HBV reactivation occurred for entecavir as compared with lamivudine prophylaxis (6.3% versus 39.3%; p < 0.05). HBV DNA monitoring of HBsAg-negative/HBcAb-positive patients in the cross-sectional analysis showed HBV reactivation in only 2.4% of cases. Conclusions This is the largest study of HBV reactivation in patients receiving rituximab-containing chemotherapy to date, and we defined the probability of HBV reactivation in an HBV-endemic region.
Liposomal drug delivery system Kim, Jin-Seok
Journal of pharmaceutical investigation,
07/2016, Volume:
46, Issue:
4
Journal Article
Peer reviewed
Lipid-based self-assembling vesicles were first described in 1961 and reported in 1964 by Dr. Alec D. Bangham (Bangham and Horne in J Mol Biol 8:660–668,
1964
) at the Babraham Institute in ...Cambridge, UK, in which he wrote:
“
It is probable that at equilibrium each and every lipid bilayer forms an unbroken membrane-there being no exposed hydrocarbon/water interface-from which it follows that every aqueous compartment would be discrete and isolated from its neighbor, including a complete separation of the outermost compartment of the whole structure from the continuous phase in which it is suspended”. It is thermodynamically possible for each lipid bilayer to form a discrete membrane, separating the vesicle from the continuous aqueous phase in which it is suspended. These
“
unbroken membranes
”
were called as “liquid crystal” or “smectic mesophase”, “Bangasomes” after the name of Dr. Bangham, and finally “liposomes”. The word “liposome” derives from two Greek words of “
lipo
-meaning fat” and “
soma
-meaning body”. In the earlier days, these artificial vesicles (or liposomes) were used for the study of cell physiology such as ion (or drug) permeability, membrane fusion, membrane-bound enzyme properties or as a membrane model. More recently, much attention was brought to the uses of liposomes in medical fields as drug delivery systems and the first article of this kind was published in 1971 in FEBS Letters by Dr. George Gregoriadis and his co-workers, where amyloglucosidase and albumin were entrapped into liposome for the purpose of enzyme replacement therapy (Gregoriadis et al. in FEBS Lett 14(2):95–99,
1971
). Since then, tremendous amounts of papers were published on the uses of liposomes as a drug delivery system (DDS). So, this mini-review is mainly focused on the use of liposome as DDS.
Introduction/Aims
Patients with amyotrophic lateral sclerosis (ALS) inevitably visit the emergency department (ED) due to their increased risk of respiratory failure and mobility limitations. ...However, nationwide data on ED visits by patients with ALS are limited. This study investigated the characteristics of patients with ALS‐related ED visits.
Methods
We conducted a cross‐sectional study from 2016 to 2020, utilizing a nationwide ED database. The total number of patients with ALS who visited the ED and their primary reasons for visiting/diagnoses were analyzed.
Results
In total, 6036 visits to the ED were made by patients with ALS. Of these, 41.8% arrived by ambulance and 27.7% spent >9 h in the ED. Following ED treatment, 57.4% were hospitalized, including 19.3% admitted to the intensive care unit (ICU) and 5.4% who died in the hospital. The primary reasons for ALS‐related ED visits were dyspnea (35.2%), feeding tube problems (10.1%), fever (7.8%), and mental status changes (3.6%). The most common diagnoses were pneumonia (14.5%), respiratory failure (5.7%), dyspnea (5.5%), aspiration pneumonia (4.3%), and tracheostomy complications (3.4%).
Discussion
Reasons for ED visits for patients with ALS include acute respiratory distress, as well as concerns related to tube feeding and tracheostomy. To reduce the risk of patients with ALS requiring ED visits, it is essential to ensure the provision of timely respiratory support and high‐quality home‐based medical care teams that can support and address patients before their condition deteriorates.
ABSTRACT
Cancerstem‐like cells (CSLCs) contribute to the initiation and recurrence of tumors and to their resistance to conventional therapies. In this study, small interfering RNA (siRNA)‐based ...screening of ~4800 druggable genes in 3‐dimensional CSLC cultures in comparison to 2‐dimensional bulk cultures of U87 glioma cells revealed 3 groups of genes essential for the following: survival of the CSLC population only, bulk‐cultured population only, or both populations. While diverse biologic processes were associated with siRNAs reducing the bulk‐cultured population, CSLC‐eliminating siRNAs were enriched in a few functional categories, such as lipid metabolism, protein metabolism, and gene expression. Interestingly, siRNAs that selectively reduced CSLC only were found to target genes for cholesterol and unsaturated fatty acid synthesis. The lipidomic profile of CSLCs revealed increased levels of monounsaturated lipids. Pharmacologic blockage of these target pathways reduced CSLCs, and this effect was eliminated by addition of downstream metabolite products. The present CSLC‐sensitive target categories provide a useful resource that can be exploited for the selective elimination of CSLCs.—Song, M., Lee, H., Nam, M.‐H., Jeong, E., Kim, S., Hong, Y., Kim, N., Yim, H. Y., Yoo, Y.‐J., Kim, J.S., Kim, J.‐S., Cho, Y.‐Y., Mills, G. B., Kim, W.‐Y., Yoon, S. Loss‐offunction screens of druggable targetome against cancer stem‐like cells. FASEB J. 31, 625–635 (2017). www.fasebj.org
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