Superior outcomes and high-risk features with carfilzomib, lenalidomide, and dexamethasone combination therapy for patients with relapsed and refractory multiple myeloma: Results of the multicenter KMMWP2201 study.

Carfilzomib, lenalidomide, and dexamethasone (KRd) combination therapy improves the survival of patients with relapsed and/or refractory multiple myeloma (RRMM). Nonetheless, evidence on the use of KRd in Asian populations remains scarce. Accordingly, this study aimed at investigating this regimen's efficacy in a large group of patients. This retrospective study included patients with RRMM who were treated with KRd at 21 centers between February 2018 and October 2020. Overall, 364 patients were included (median age: 63 years). The overall response rate was 90% in responseevaluable patients, including 69% who achieved a very good partial response or deeper responses. With a median follow-up duration of 34.8 months, the median progression-free survival (PFS) was 23.4 months and overall survival (OS) was 59.5 months. Among adverse factors affecting PFS, highrisk cytogenetics, extramedullary disease, and doubling of monoclonal protein within 2 to 3 months prior to start of KRd treatment significantly decreased PFS and overall survival (OS) in multivariate analyses. Patients who underwent post-KRd stem cell transplantation (i.e.delayed transplant) showed prolonged PFS and OS. Grade 3 or higher adverse events (AEs) were observed in 56% of the patients, and non-fatal or fatal AE's that resulted in discontinuation of KRd were reported in 7% and 2% of patients, respectively. Cardiovascular toxicity was comparable to that reported in the ASPIRE study. In summary, KRd was effective in a large real-world cohort of patients with RRMM with long-term follow-up. These findings may further inform treatment choices in the treatment of patients with RRMM.

PTK2 is a potential biomarker and therapeutic target for EGFR- or TLRs-induced lung cancer progression via the regulation of the cross-talk between EGFR- and TLRs-mediated signals.

Protein tyrosine kinase 2 (PTK2), epidermal growth factor receptor (EGFR), and toll-like receptor (TLRs) are amplified in non-small cell lung cancer (NSCLC). However, the functional and clinical associations between them have not been elucidated yet in NSCLC. By using microarray data of non-small cell lung cancer (NSCLC) tumor tissues and matched normal tissues of 42 NSCLC patients, the genetic and clinical associations between PTK2, EGFR, and TLRs were analyzed in NSCLC patients. To verify the functional association, we generated PTK2-knockout (PTK2-KO) lung cancer cells by using CRISPR-Cas9 gene editing method, and performed in vitro cancer progression assay, including 3D tumor spheroid assay, and in vivo xenografted NSG (NOD/SCID/IL-2Rγnull) mouse assay. Finally, therapeutic effects targeted to PTK2 in lung cancer in response to EGF and TLR agonists were verified by using its inhibitor (Defactinib). In summary, we identified that up-regulated PTK2 might be a reliable marker for EGFR- or TLRs-induced lung cancer progression in NSCLC patients via the regulation of the cross-talk between EGFR- and TLRs-mediated signaling. This study provides a theoretical basis for the therapeutic intervention of PTK2 targeting EGFR- or TLRs-induced lung cancer progression.

Transition of Carbon Nanotube Sheets from Hydrophobicity to Hydrophilicity by Facile Electrochemical Wetting.

The present study delves into the transformative effects of electrochemical oxidation on the hydrophobic-to-hydrophilic transition of carbon nanotube (CNT) sheets. The paper elucidates the inherent advantages of CNT sheets, such as high electrical conductivity and mechanical strength, and contrasts them with the limitations posed by their hydrophobic nature. A comprehensive investigation is conducted to demonstrate the efficacy of electrochemical oxidation treatment in modifying the surface properties of CNT sheets, thereby making them hydrophilic. The study reveals that the treatment not only is cost-effective and time-efficient compared to traditional plasma treatment methods but also results in a significant decrease in water contact angle. Mechanistic insights into the hydrophilic transition are provided, emphasizing the role of oxygen-containing functional groups introduced during the electrochemical oxidation process.

Cancer organoid-based diagnosis reactivity prediction (CODRP) index-based anticancer drug sensitivity test in ALK-rearrangement positive non-small cell lung cancer (NSCLC).

BACKGROUND: Recently, cancer organoid-based drug sensitivity tests have been studied to predict patient responses to anticancer drugs. The area under curve (AUC) or IC50 value of the dose-response curve (DRC) is used to differentiate between sensitive and resistant patient's groups. This study proposes a multi-parameter analysis method (cancer organoid-based diagnosis reactivity prediction, CODRP) that considers the cancer stage and cancer cell growth rate, which represent the severity of cancer patients, in the sensitivity test. METHODS: On the CODRP platform, patient-derived organoids (PDOs) that recapitulate patients with lung cancer were implemented by applying a mechanical dissociation method capable of high yields and proliferation rates. A disposable nozzle-type cell spotter with efficient high-throughput screening (HTS) has also been developed to dispense a very small number of cells due to limited patient cells. A drug sensitivity test was performed using PDO from the patient tissue and the primary cancer characteristics of PDOs were confirmed by pathological comparision with tissue slides. RESULTS: The conventional index of drug sensitivity is the AUC of the DRC. In this study, the CODRP index for drug sensitivity test was proposed through multi-parameter analyses considering cancer cell proliferation rate, the cancer diagnosis stage, and AUC values. We tested PDOs from eight patients with lung cancer to verify the CODRP index. According to the anaplastic lymphoma kinase (ALK) rearrangement status, the conventional AUC index for the three ALK-targeted drugs (crizotinib, alectinib, and brigatinib) did not classify into sensitive and resistant groups. The proposed CODRP index-based drug sensitivity test classified ALK-targeted drug responses according to ALK rearrangement status and was verified to be consistent with the clinical drug treatment response. CONCLUSIONS: Therefore, the PDO-based HTS and CODRP index drug sensitivity tests described in this paper may be useful for predicting and analyzing promising anticancer drug efficacy for patients with lung cancer and can be applied to a precision medicine platform.

Electrochemically Oxidized Carbon Nanotube Sheets for High-Performance and Flexible-Film Supercapacitors.

The development of flexible, high-performance supercapacitors has been a focal point in energy storage research. While carbon nanotube (CNT) sheets offer promising mechanical and electrical properties, their low electrical double-layer capacitance significantly limits their practicability. Herein, we introduce a novel approach to address this challenge via the electrochemical oxidation treatment of CNT sheets stacked on a polyethylene terephthalate substrate. This introduces oxygen-containing functional groups onto the CNT surface, thereby dramatically enhancing the pseudocapacitive effect and improving ion adsorption. Consequently, using the material in a two-electrode system increased the capacitance by 54 times compared to pristine CNT. The results of electrochemical performance characterization, including cyclic voltammograms, galvanostatic charge/discharge curves, and capacitance retention testing data, confirm the efficacy of the electrochemical oxidation approach. Furthermore, the mechanical flexibility of the electrochemically wetted CNT sheets was validated through resistance and discharge retention testing under repetitive bending (98% capacitance retention after 1000 bending cycles). The results demonstrate that electrochemically wetted CNT sheets retain their intrinsic mechanical and electrical properties while significantly enhancing the electrochemical performance (0.59 mF/cm2 or 97.8 F/g). This work represents a significant advancement in the development of flexible, high-performance supercapacitors with potential applicability to wearable electronics, flexible displays, and next-generation energy storage solutions.

Cryobiopsy: A Breakthrough Strategy for Clinical Utilization of Lung Cancer Organoids.

One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer (n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer.

Changes of drinking behavior in Korean pregnant women for the last 20 year.

BACKGROUND: The purpose of this study is to investigate the drinking behavior of Korean pregnant women in 2017 and to compare the changes of drinking status with the results of the research conducted in 1997 and 2008. METHODS: Pregnant women at one obstetrics and gynecology hospital and one university hospital were the subjects of the study. They were filled out questionnaire. RESULTS: The rate of positive responses to CAGE increased 16.0% in 2008 and 16.3% in 2017 compared to 11.8% in 1997 (P = 0.046). Blackout history rate was keep increasing from 1997 to 2017 (8.8% versus 27.7% versus 36.3%, P < 0.001). The rate of family history of alcohol was nearly doubled in 2017 (30.3%) compared to 1997 (17.6%) and 2008 (16.3) (P < 0.001). The rate of pregnant women who drink alcohol during pregnancy decreased from 57.5% in 1997 to 39.5% in 2008 and decreased to 25.6% in 2017 (P < 0.001). The rate of pregnant women who drink alcohol after knowing the pregnancy was decreased in 2017 (6.9%) compared to 2008 (23.5%) (P < 0.001). CONCLUSION: According to the results of the study in 2017, the rate of pregnant women who drink alcohol after pregnancy was decreased compared to 1997 and 2008. However drinking behavior severity has increased in 2017.

Counterplotting the Mechanosensing-Based Fouling Mechanism of Mussels against Fouling.

Marine organisms react to various factors when building colonies for survival; however, severe accumulation of diverse organisms on artificial structures located close to water causes large industrial losses. Herein, we identify a concept in the development of antifouling surfaces based on understanding the surface stiffness recognition procedure of mussel adhesion at the genetic level. It was found that on a soft surface the combination of decreased adhesive plaque size, adhesion force, and plaque protein downregulation synergistically weakens mussel wet adhesion and sometimes prevents mussels from anchoring, mainly due to transcriptional changes within the mechanosensing pathway and the adhesive proteins in secretory glands. In addition, the use of soft substrates or antagonists of surface mechanosensing behavior suppresses mussel fouling significantly.

Remifentanil-based propofol-supplemented vs. balanced sevoflurane-sufentanil anesthesia regimens on bispectral index recovery after cardiac surgery: a randomized controlled study.

BACKGROUND: The present study was to compare the potential impact of remifentanil-based propofol-supplemented anesthesia regimen vs. conventional sevoflurane-sufentanil balanced anesthesia on postoperative recovery of consciousness indicated by bispectral index (BIS) values in patients undergoing cardiac surgery. METHODS: Patients undergoing cardiac surgery were randomly allocated to get the remifentanil-based propofol-supplemented anesthesia employing target-controlled infusion (TCI) of remifentanil and propofol (Group-PR, n = 15) or a balanced-anesthesia employing sevoflurane-inhalation and TCI-sufentanil (Group-C, n = 19). In Group-PR, plasma concentration (Cp) of TCI-remifentanil was fixed at 20 ng/ml, and the effect-site concentration of TCI-propofol was adjusted within 0.8-2.0 µg/ml to maintain BIS value of 40-60. In Group-C, sevoflurane dosage was adjusted within 1-1.5 minimum alveolar concentration to maintain BIS of 40-60, and Cp of TCI-sufentanil was fixed at 0.4 ng/ml. The inter-group difference in the time for achieving postoperative BIS > 80 (T-BIS80) in the intensive care unit was determined as the primary outcome. The inter-group difference in the extubation time was determined as the secondary outcome. RESULTS: T-BIS80, was shorter in Group-PR than Group-C (121.4 ± 64.9 min vs. 182.9 ± 85.1 min, respectively; the difference of means -61.5 min; 95% CI -115.7 to -7.4 min; effect size 0.812; P = 0.027). The extubation time was shorter in Group-PR than in Group-C (434.7 ± 131.3 min vs. 946.6 ± 393.3 min, respectively, P < 0.001). CONCLUSIONS: Compared with the conventional sevoflurane-sufentanil balanced anesthesia, the remifentanil-based propofol-supplemented anesthesia showed significantly faster postoperative conscious recovery in patients undergoing cardiac surgery.

A sugar-lectin rich interface between soft tissue and the stiff byssus of Atrina pectinata.

Maintaining durable adhesion between soft tissues and relatively hard implant materials is one of the most elusive technological difficulties in bionic devices due to contact damage between mechanically mismatched materials. Although there are many examples of coexistence of soft and hard tissues in living organisms, relatively little is known about the mechanisms used to overcome mechanical mismatches occurring at the interface between soft and hard tissues. Among the various creatures possessing mechanically mismatched biological tissues, Atrina pectinata is a good model system where the interface between stiff byssal threads and soft tissues is distributed all over an extended organ. In this study, we found a wide distribution of various types of carbohydrates and lectins at the mechanically mismatched interface of the byssus of Atrina using histological methods and proteomics. Reversible and robust interactions between the carbohydrate and lectins at the interface would play a major role in mitigating the contact damage at the Atrina interface. Based on these results, the adhesion between sugar and lectin would be useful to overcome a wide range of contact damage observed in research studies on bionic devices.

The profiles of microRNAs from urinary extracellular vesicles (EVs) prepared by various isolation methods and their correlation with serum EV microRNAs.

AIMS: MicroRNAs (miRNAs) that circulate in biological fluids are frequently enclosed in extracellular vesicles (EVs). However, urinary EVs and their cargo miRNAs have not been systematically studied according to their EV isolation methods. METHODS: In type 2 diabetes mellitus persons with diabetic nephropathy (n = 4), we compared miRNA species in urine EVs prepared by ultracentrifugation (UC), qEV original size exclusion column (qEV), ExoQuick-TC Plus (ExoQuick), and ultrafiltration using Amicon Ultra centrifugal filter devices (Amicons) 10 K and 100 K. EV miRNAs were profiled by next-generation sequencing (NGS). Additionally, we evaluated the correlations of EV miRNA expression between the urine and serum samples isolated by UC. RESULTS: From each of 100 ml of urine, the UC method yielded the highest number of EV miRNA species (233 ± 37.3), with the ExoQuick yielded the lowest (103 ± 17.4). Urine EV miRNA profiles were highly correlated between UC, qEV, ExoQuick and Amicon 10 K methods. EV miRNA profiles between the urine and serum samples showed variable correlations between the patients (paired sample number = 3, r = 0.39-0.72). CONCLUSIONS: UC, qEV, ExoQuick, and Amicon 10 K are acceptable for urinary EV isolation to profile miRNAs. Urine- and serum-derived EV miRNA profiles have variable correlations depending on specific patients.

Charge-Transfer-Modulated Transparent Supercapacitor Using Multidentate Molecular Linker and Conductive Transparent Nanoparticle Assembly.

One of the most critical issues in preparing high-performance transparent supercapacitors (TSCs) is to overcome the trade-off between areal capacitance and optical transmittance as well as that between areal capacitance and rate capability. Herein, we introduce a TSC with high areal capacitance, fast rate capability, and good optical transparency by minimizing the charge transfer resistance between pseudocapacitive nanoparticles (NPs) using molecular linker- and conductive NP-mediated layer-by-layer (LbL) assembly. For this study, bulky ligand-stabilized manganese oxide (MnO) and indium tin oxide (ITO) NP multilayers are LbL-assembled through a ligand exchange reaction between native ligands and small multidentate linkers (tricarballylic acid). The introduced molecular linker substantially decreases the separation distance between neighboring NPs, thereby reducing the contact resistance of electrodes. Moreover, the periodic insertion of ITO NPs into the MnO NP-based electrodes can lower the charge transfer resistance without a meaningful loss of transmittance, which can significantly improve the areal capacitance. The areal capacitances of the ITO NP-free electrode and the ITO NP-incorporated electrode are 24.6 mF cm-2 (at 61.6% transmittance) and 40.5 mF cm-2 (at 60.8%), respectively, which outperforms state of the art TSCs. Furthermore, we demonstrate a flexible symmetric solid-state TSC that exhibits scalable areal capacitance and optical transmittance.

Highly Conductive Paper/Textile Electrodes Using Ligand Exchange Reaction-Induced in Situ Metallic Fusion.

Here, we report that metal nanoparticle (NP)-based paper/textile electrodes with bulk metallic conductivity can be prepared via organic linker-modulated ligand exchange reaction and in situ room-temperature metallic fusion without additional chemical or thermal treatments. For this study, amine-functionalized molecule linkers instead of bulky polymer linkers were layer-by-layer (LbL)-assembled with tetraoctylammonium bromide (TOABr)-stabilized Au NPs to form Au NP multilayered films. By conversion of the amine groups of the organic molecule linkers from -NH3+ to the -NH2 groups, as well as by a decrease in the size of the organic linkers, the LbL-assembled Au NPs became highly interconnected and fused during LbL deposition, resulting in Au NP multilayers with adjustable conductivity and transport behavior. These phenomena were also predicted by a density functional theory investigation for the model system. Particularly, LbL-assembled films composed of TOABr-Au NPs and diethylenetriamine ( Mw: ∼104) exhibited a remarkable electrical conductivity of 2.2 × 105 S·cm-1, which was higher than the electrical conductivity of the metal NP-based electrodes as well as the carbon material-based electrodes reported to date. Furthermore, based on our approach, a variety of insulating flexible papers and textiles were successfully converted into real metal-like paper and textile electrodes with high flexibility preserving their highly porous structure. This approach can provide a basis for further improving and controlling the electrical properties of flexible electrodes through the control of organic linkers.

Associations Among Plasma Stress Markers and Symptoms of Anxiety and Depression in Patients with Breast Cancer Following Surgery.

OBJECTIVE: The objective of present study is to analyze the prevalence of depression and anxiety following breast cancer surgery and to assess the factors that affect postoperative psychological symptoms. METHODS: The Hamilton Rating Scale for Depression (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), Body Image Scale (BIS), and Rosenberg Self Esteem Scale (RSES) were used to assess the psychological states of patients who had been diagnosed with and had undergone surgery for breast cancer. Blood concentrations of the stress markers adrenocorticotropic hormone, cortisol, arginine-vasopressin, and angiotensin-converting enzyme were measured. Pearson's correlation analysis and multilinear regression analysis were used to analyse the data. RESULTS: At least mild depressive symptoms were noted in 50.5% of patients, while 42.4% of patients exhibited at least mild anxiety symptoms. HAM-D score was positively correlated with HAM-A (r=0.83, p<0.001) and BIS (r=0.29, p<0.001) scores and negatively correlated with RSES score (r=-0.41, p<0.001). HAM-A score was positively correlated with BIS score (r=0.32, p<0.001) and negatively correlated with RSES score (r=-0.27, p<0.001). There were no statistically significant associations between stress markers and depression/anxiety. CONCLUSION: Patients with breast cancer frequently exhibit postoperative depression and anxiety, which are related to low levels of self-esteem and distorted body image.

A mechanical and electrical transistor structure (METS) with a sub-2 nm nanogap for effective voltage scaling.

A mechanical and electrical transistor structure (METS) is proposed for effective voltage scaling. The sub-2 nm nanogap by atomic layer deposition (ALD) without stiction and the application of a dielectric with high-permittivity allowed the pull-in voltage of sub-2 V, showing the strength of the mechanical actuation that is hard to realize in a typical complementary metal-oxide-semiconductor (CMOS) transistor. The results are verified by simulation and interpreted by the numerical equation. Therefore the METS can pave a new way to make a breakthrough to overcome the limits of CMOS technology.

CRP detection from serum for chip-based point-of-care testing system.

Most of point-of-care testing (POCT) to improve facilitates in diagnosis, treatment, and monitoring of patients. POCT technique has still remained a quantitatively and accurately detective effect. In this article, we demonstrated that real human C-reactive protein (CRP) in serum was detected for a chip-based point-of-care testing application based on a nanogap-embedded field effect transistor (FET), and the results were compared with those obtained via the enzyme-linked immunosorbent assay (ELISA) method. The limit of detection (LOD), determined from the standard curve, was 0.1 ng/ml, which is comparable to that of commercialized ELISAs. We evaluated that an improved detection range (0.1 ng/ml to 100 ng/ml) was achieved by comparing with commercialized ELISA. Control experiments to determine selectivity and to discern false-positive/false-negative rates were also performed. This report is the first description of the detection of CRP in human serum using a silicon-based biosensor.

Self-aligned nanoforest in silicon nanowire for sensitive conductance modulation.

A self-aligned and localized nanoforest structure is constructed in a top-down fabricated silicon nanowire (SiNW). The surface-to-volume ratio (SVR) of the SiNW is enhanced due to the local nanoforest formation. The conductance modulation property of the SiNWs, which is an important characteristic in sensor and charge transfer based applications, can be largely enhanced. For the selective modification of the channel region, localized Joule-heating and subsequent metal-assisted chemical etching (mac-etch) are employed. The nanoforest is formed only in the channel region without misalignment due to the self-aligned process of Joule-heating. The modified SiNW is applied to a porphyrin-silicon hybrid device to verify the enhanced conductance modulation. The charge transfer efficiency between the porphyrin and the SiNW, which is caused by external optical excitation, is clearly increased compared to the initial SiNW. The effect of the local nanoforest formation is enhanced when longer etching times and larger widths are used.

Hybrid porphyrin-silicon nanowire field-effect transistor by opto-electrical excitation.

A porphyrin-silicon nanowire (Si-NW) hybrid field-effect transistor is introduced. The hybrid device has separate electrical and optical gates surrounding the Si-NW channel. Porphyrin, a component of chlorophyll, is employed as an optical gate to modulate the potential of the Si-NW channel. Due to the independently formed hybrid gates, both optical and electrical excitation can effectively modulate the device. The exposed porphyrin optical gate responds to the optical excitation, and independently formed electrical gates respond to the electrical excitation. Charge transfer characteristics between a semiconductor channel and the porphyrin optical gate are deeply investigated. Optical, electrical, and opto-electrical excitation methods are employed to analyze the charging and discharging behaviors. Of these methods, opto-electrical excitation enables the strongest charge transfer because the inversion electron formation by an electrical pulse and the photoinduced charge transfer by an optical stimulus are affected simultaneously. Discharging processes, such as rapid discharging, exponential detrapping, and the formation of metastable states are also analyzed.