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Although concrete materials generally exhibit outstanding mechanical properties, it is susceptible against crack formation. It has been reported that narrow cracks (≤ 150 µm) could be naturally sealed in the cement matrix by externally supplied water-induced hydration. However, the crack width of larger than 150 µm is difficult to be sealed without using additional self-healing admixture. In this study, the self-healing cementitious mortar was successfully developed by using a combination of polyvinyl alcohol (PVA) fiber and superabsorbent polymer (SAP), aiming to heal the wide cracks. Although the mechanical properties were slightly reduced, it shows outstanding self-healing performance by using the dual admixtures. A self-healing rate of 60% was observed in the control sample with an initial crack width of 300 µm, while a self-healing rate of nearly 100% was confirmed with suitable SAP and PVA. In addition, it was confirmed that lower hydration degree of self-healing mortar in early stage contributes to the enhanced self-healing performance of developed composite system by internally supplied water from SAP. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to evaluate the impact of intravenous palonosetron compared to ondansetron on hypotension induced by spinal anesthesia in women undergoing cesarean section. Methods: Fifty-four women scheduled for elective cesarean section were, randomly allocated to ondansetron group (n = 27) or palonosetron group (n = 27). Ten minutes prior to the administration of spinal anesthesia, participants received an intravenous injection of either ondansetron or palonosetron. A prophylactic phenylephrine infusion was initiated immediately following the intrathecal administration of bupivacaine and fentanyl. The infusion rate was titrated to maintain adequate blood pressure until the time of fetal delivery. The primary outcome was total dose of phenylephrine administered. The secondary outcomes were nausea or vomiting, the need for rescue antiemetics, hypotension, bradycardia, and shivering. Complete response rate, defined as the absence of postoperative nausea and vomiting and no need for additional antiemetics, were assessed for up to 24 hours post-surgery. Results: No significant differences were observed in the total dose of phenylephrine used between the ondansetron and palonosetron groups (387.5 μg [interquartile range, 291.3–507.8 μg versus 428.0 μg [interquartile range, 305.0–507.0 μg], P = 0.42). Complete response rates also showed no significant differences between the groups both within two hours post-spinal anesthesia (88.9% in the ondansetron group versus 100% in the palonosetron group; P = 0.24) and at 24 hours post-surgery (81.5% in the ondansetron group versus 88.8% in the palonosetron group; P = 0.7). In addition, there was no difference in other secondary outcomes. Conclusion: Prophylactic administration of palonosetron did not demonstrate a superior effect over ondansetron in mitigating hemodynamic changes or reducing phenylephrine requirements in patients undergoing spinal anesthesia with bupivacaine and fentanyl for cesarean section. [ABSTRACT FROM AUTHOR]

Background: Patients with multiple myeloma exhibit malignant osteolytic bone disease due to excessive osteoclast formation and function. We recently identified that osteoclastogenic stimulator selenoprotein W (SELENOW) is upregulated via ERK signaling and downregulated via p38 signaling during receptor activator of nuclear factor (NF)-κΒ ligand (RANKL)-induced osteoclast differentiation. In the intrinsic physiological process, RANKL-induced downregulation of SELENOW maintains proper osteoclast differentiation; in contrast, forced overexpression of SELENOW leads to overactive osteoclast formation and function. Methods and results: We observed that SELENOW is highly expressed in multiple myeloma-derived peripheral blood mononuclear cells (PBMCs) and mature osteoclasts when compared to healthy controls. Also, the level of tumor necrosis factor alpha (TNFα), a pathological osteoclastogenic factor, is increased in the PBMCs and serum of patients with multiple myeloma. ERK activation by TNFα was more marked and sustained than that by RANKL, allowing SELENOW upregulation. Excessive expression of SELENOW in osteoclast progenitors and mature osteoclasts derived from multiple myeloma facilitated efficient nuclear translocation of osteoclastogenic transcription factors NF-κB and NFATc1, which are favorable for osteoclast formation. Conclusion: Our findings suggest a possibility that feedforward signaling of osteoclastogenic SELENOW by TNFα derived from multiple myeloma induces overactive osteoclast differentiation, leading to bone loss during multiple myeloma. [ABSTRACT FROM AUTHOR]

Electrical resistance measurement is central to materials characterization, circuit analysis and resistance-based sensing. Resistance measurement involving the two-probe method (involving two electrical connections) is known to overassess the resistance, due to the electrode-specimen contact resistance. Resistance measurement involving the four-probe method (involving four electrical connections) is advantageous in that it essentially excludes the contact resistance at the connection-specimen interface. Nevertheless, the two-probe method is widely used, because of the simplicity of having only two connections. In the two-probe method, the current passes through the specimen and connections. The connection-related stray inductance is found in this work to cause large additional overassessment of the two-probe resistance when the electrical connection configuration entails current direction changes. The connections pertain to electrical leads and clips. The inductance increase due to a current direction change is in line with Faraday's law. Mere constriction or spreading of the current due to the connections also increases the inductance, but it does not influence the two-probe resistance. The inductance and two-probe resistance increase with the lead length because of the connection-related inductance, not because of the negligible increase in the lead resistance. An inductance increase of ≤ 80% causes a two-probe resistance increase of ≤ 278%. The specimen in this work is aluminum. It does not need to be magnetic. The connections in this work are also not magnetic. This inductance-related source of two-probe resistance overassessment is reported here for the first time. [ABSTRACT FROM AUTHOR]

Background: Patients with multiple myeloma exhibit malignant osteolytic bone disease due to excessive osteoclast formation and function. We recently identified that osteoclastogenic stimulator selenoprotein W (SELENOW) is upregulated via ERK signaling and downregulated via p38 signaling during receptor activator of nuclear factor (NF)-κΒ ligand (RANKL)-induced osteoclast differentiation. In the intrinsic physiological process, RANKL-induced downregulation of SELENOW maintains proper osteoclast differentiation; in contrast, forced overexpression of SELENOW leads to overactive osteoclast formation and function. Methods and results: We observed that SELENOW is highly expressed in multiple myeloma-derived peripheral blood mononuclear cells (PBMCs) and mature osteoclasts when compared to healthy controls. Also, the level of tumor necrosis factor alpha (TNFα), a pathological osteoclastogenic factor, is increased in the PBMCs and serum of patients with multiple myeloma. ERK activation by TNFα was more marked and sustained than that by RANKL, allowing SELENOW upregulation. Excessive expression of SELENOW in osteoclast progenitors and mature osteoclasts derived from multiple myeloma facilitated efficient nuclear translocation of osteoclastogenic transcription factors NF-κB and NFATc1, which are favorable for osteoclast formation. Conclusion: Our findings suggest a possibility that feedforward signaling of osteoclastogenic SELENOW by TNFα derived from multiple myeloma induces overactive osteoclast differentiation, leading to bone loss during multiple myeloma. [ABSTRACT FROM AUTHOR]

Background: This study analyzed the predictive value of artificial intelligence (AI)‐powered tumor‐infiltrating lymphocyte (TIL) analysis in recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC) treated with axitinib. Methods: Patients from a multicenter, prospective phase II trial evaluating axitinib efficacy in R/M ACC were included in this study. H&E whole‐side images of archival tumor tissues were analyzed by Lunit SCOPE IO, an AI‐powered spatial TIL analyzer. Results: Twenty‐seven patients were included in the analysis. The best response was stable disease, and the median progression‐free survival (PFS) was 11.1 months (95% CI, 9.2–13.7 months). Median TIL densities in the cancer and surrounding stroma were 25.8/mm2 (IQR, 8.3–73.0) and 180.4/mm2 (IQR, 69.6–342.8), respectively. Patients with stromal TIL density >342.5/mm2 exhibited longer PFS (p = 0.012). Conclusions: Cancer and stromal area TIL infiltration were generally low in R/M ACC. Higher stromal TIL infiltration was associated with a longer PFS with axitinib treatment. [ABSTRACT FROM AUTHOR]

Skin photoaging induced by ultraviolet (UV) irradiation contributes to the formation of thick and coarse wrinkles. Humans are exposed to UV light throughout their lives. Therefore, it is crucial to determine the time-sequential effects of UV on the skin. In this study, we irradiated the mouse back skin with UV light for eight weeks and observed the changes in gene expressions via microarray analysis every week. There were more downregulated genes (514) than upregulated genes (123). The downregulated genes had more functional diversity than the upregulated genes. Additionally, the number of downregulated genes did not increase in a time-dependent manner. Instead, time-dependent kinetic patterns were observed. Interestingly, each kinetic cluster harbored functionally enriched gene sets. Since collagen changes in the dermis are considered to be a major cause of photoaging, we hypothesized that other gene sets contributing to photoaging would exhibit kinetics similar to those of the collagen-regulatory genes identified in this study. Accordingly, co-expression network analysis was conducted using 11 well-known collagen-regulatory seed genes to predict genes with similar kinetics. We ranked all downregulated genes from 1 to 504 based on their expression levels, and the top 50 genes were suggested to be involved in the photoaging process. Additionally, to validate and support our identified top 50 gene lists, we demonstrated that the genes (FN1, CCDC80, PRELP, and TGFBR3) we discovered are downregulated by UV irradiation in cultured human fibroblasts, leading to decreased collagen levels, which is indicative of photoaging processes. Overall, this study demonstrated the time-sequential genetic changes in chronically UV-irradiated skin and proposed 50 genes that are involved in the mechanisms of photoaging. [ABSTRACT FROM AUTHOR]

Workplace bullying is a prevalent issue with a significant impact on employees' mental health. This study aimed to explore the relationship between workplace bullying and the prevalence of depression, with a particular focus on the role of gender. A total of 12,344 Korean employees aged 19–65 years were included in the study. They completed the Center for Epidemiologic Studies Depression Scale (CES-D) and a score of 16 or higher in CES-D indicated depression. The association between workplace bullying and depression was analyzed using logistic regression analyses. The average CES-D scores were higher for both male and female employees who experienced bullying than for those who did not (p < 0.001). The association between the experience of workplace bullying and the prevalence of depression was statistically significant for both genders, with a stronger correlation observed among male employees (p for interaction < 0.001). Organizations are urged to address workplace bullying, particularly for male employees, through the implementation of anti-bullying strategies and policies, as well as the provision of mental health resources and support. [ABSTRACT FROM AUTHOR]

The analgesia nociception index (ANI) has emerged as a potential measurement for objective pain assessment during general anesthesia. This systematic review and meta-analysis aimed to evaluate the accuracy and effectiveness of ANI in assessing intra- and post-operative pain in patients undergoing general anesthesia. We conducted a comprehensive search of Ovid-MEDLINE, Ovid-EMBASE, Cochrane Central Register of Controlled Trials, Google Scholar, public clinical trial databases (ClinicalTrials and Clinical Research Information Service), and OpenSIGLE to identify relevant studies published prior to May 2023 and included studies that evaluated the accuracy and effectiveness of ANI for intra- or post-operative pain assessment during general anesthesia. Among the 962 studies identified, 30 met the eligibility criteria and were included in the systematic review, and 17 were included in the meta-analysis. For predicting intra-operative pain, pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under curve of ANI were 0.81 (95% confidence interval [CI] = 0.79–0.83; I2 = 68.2%), 0.93 (95% CI = 0.92–0.93; I2 = 99.8%), 2.32 (95% CI = 1.33–3.30; I2 = 61.7%), and 0.77 (95% CI = 0.76–0.78; I2 = 87.4%), respectively. ANI values and changes in intra-operative hemodynamic variables showed statistically significant correlations. For predicting post-operative pain, pooled sensitivity, specificity, and DOR of ANI were 0.90 (95% CI = 0.87–0.93; I2 = 58.7%), 0.51 (95% CI = 0.49–0.52; I2 = 99.9%), and 3.38 (95% CI = 2.87–3.88; I2 = 81.2%), respectively. ANI monitoring in patients undergoing surgery under general anesthesia is a valuable measurement for predicting intra- and post-operative pain. It reduces the use of intra-operative opioids and aids in pain management throughout the perioperative period. [ABSTRACT FROM AUTHOR]

Background: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2‐targeted agents. Docetaxel‐PM (polymeric micelle) is a low‐molecular‐weight, nontoxic, biodegradable, and docetaxel‐loaded micellar formulation. Trastuzumab‐pkrb is a biosimilar to trastuzumab. Methods: This was a multicenter, single‐arm, open‐label phase 2 study. Patients with HER2‐positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel‐PM (75 mg/m2) and trastuzumab‐pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR). Results: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9–82.8) and a disease control rate of 93.0% (80.9–98.5). Median progression‐free survival, duration of response, and overall survival were 7.9 (6.3–9.5), 6.7 (5.1–8.4), and 23.3 (19.9–26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty‐eight (88.4%) patients experienced treatment‐related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively. Conclusions: The combination of docetaxel‐PM and trastuzumab‐pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2‐positive advanced SDC. Plain Language Summary: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas.SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC.In this study, patients with HER2‐positive SDC were enrolled and treated with combination of docetaxel‐polymeric micelle and trastuzumab‐pkrb.Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression‐free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months. In this multicenter, single‐arm, phase 2 study, the authors evaluate efficacy and safety of docetaxel‐polymeric micelle and trastuzumab‐pkrb in patients with recurrent/metastatic human epidermal growth factor receptor 2 (HER2)‐positive salivary gland carcinoma. The data show that the combination therapy demonstrates promising antitumor activity with a manageable toxicity profile in patients with HER2 immunohistochemistry of 3+. [ABSTRACT FROM AUTHOR]

As global temperatures have steadily increased over past decades, studying of the impacts of heat stress on morpho-physiological traits and economic yields of horticultural crops have been increasingly gained attentions by many scientists and farmers. Hot pepper (Capsicum annuum L.) is an important vegetable crop mostly grown in open-fields in South Korea. In this study, the impacts of prolonged heat stress on three hot pepper genotypes differing by levels of stress susceptibility were evaluated. The study was conducted in two different temperature-controlled greenhouses for 75 days. 48 days old plants were grown in control and heat-treated greenhouses where the temperatures had been set at 30 °C and 35 °C during the day for 75 days, respectively. Morphological, physiological, and nutrient characteristics of three accessions were measured. All hot pepper accessions were enabled to recover from prolonged heat stress exposures within approximately a month. The phenomenon of recovery was observed in some significant morphological and physiological characteristics. For example, the plant growth rate and photosynthesis rate significantly increased after 40th days of heat treatment. The heat stress sensitivity varied between genotypes. The plants that produced more fruits over biomass at early stage of heat treatment had relatively slow recovery, resulting in the largest yield loss. This key morphological characteristic can be used for future breeding program to adapt the prolonged heat stress. [ABSTRACT FROM AUTHOR]

Self-compassion (SC) involves taking an emotionally positive attitude towards oneself when suffering. Although SC has positive effects on mental well-being as well as a protective role in preventing symptoms in healthy individuals, few studies on white matter (WM) microstructures in neuroimaging studies of SC has been studied. Brain imaging data were acquired from 71 healthy participants. WM regions of mirroring network were analyzed using tract-based spatial statistics. After the WM regions associated with SC were extracted, exploratory correlation analysis with the self-forgiveness scale, the coping scale, and the world health organization quality of life scale abbreviated version was performed. We found that self-compassion scale total scores were negatively correlated with the fractional anisotropy (FA) values of the superior longitudinal fasciculus (SLF) in healthy individuals. The self-kindness and mindfulness subscale scores were also negatively correlated with FA values of the same regions. These FA values were negatively correlated with the total scores of self-forgiveness scale, and self-control coping strategy and confrontation coping strategy. Our findings suggest levels of SC may be associated with WM microstructural changes of SLF in healthy individuals. These lower WM microstructures may be associated with positive personal attitudes, such as self-forgiveness, self-control and active confrontational strategies. [ABSTRACT FROM AUTHOR]

As global warming increases day/night temperatures as well as frequencies of heat waves, studying physiological responses in long-term heat stress is required for sustainable yield production in the future. In this study, effects of long-term heat stress on photosynthetic, morphological, and yield parameters of three cherry tomato accessions, HR17, HR22, and HR24, were evaluated. The experiment was conducted under two temperature greenhouse conditions, where temperature set-point for ventilation was 30 °C and 35 °C during the day for 57 days, respectively. Plants were harvested on the 35th days and 57th days after heat treatments, and their physiological and morphological characteristics and yield traits were measured. Under control conditions, HR17 and HR22 had 0.5–0.6 harvest index, while HR24 had 0.3 harvest index. On 35th days after heat treatment, although yield loss percentage of HR17 was high (43%), it produced the highest fruit yield among all three accessions. However, after longer heat treatment, HR24 produced the highest fruit yields among all accessions with the smallest yield loss (34%). Furthermore, yield loss was highly associated with reductions in nitrogen use efficiency and water content in plant body under heat stress. The results of this study will provide breeders with a new insight into selecting heat-tolerant genotypes in cherry tomatoes. [ABSTRACT FROM AUTHOR]

Several guidelines classify autologous stem cell transplantation (ASCT) as a low to intermediate risk group for infection. In a nationwide population-based study, using the Korean Health Insurance Review and Assessment Service database, patients with lymphoma and multiple myeloma (MM) who underwent ASCT from 2002 to 2016 were retrospectively analyzed. Cumulative incidence rates (CIRs) and risk factors of opportunistic infections were investigated. CIRs of fungal, Varicella zoster virus (VZV), cytomegalovirus (CMV), and Pneumocystis jirovecii infections in lymphoma were 7.9%, 16.0%, 7.4%, and 5.1%, respectively, and CIRs in MM were 6.3%, 19.1%, 4.2%, and 5.6%, respectively. Fungal infection was significantly higher in patients with previous infection (Hazard ratio (HR) 2.003, p = 0.005) in lymphoma. Incidence of CMV infection was significantly higher in patients with prior CMV infection: HR 4.920, p < 0.001 (lymphoma); HR 3.022, p = 0.030 (MM). VZV infection was significantly lower in patients receiving prophylaxis: HR 0.082, p < 0.001 (lymphoma); HR 0.096, p < 0.001 (MM). For P. jirovecii infection, busulfex and melphalan conditioning (HR 1.875, p = 0.032) and previous P. jirovecii infection (HR 4.810, p < 0.001) had a higher incidence in MM. Patients who underwent ASCT should receive VZV prophylaxis and prophylaxis for fungal and P. jirovecii may be considered in patients with previous same infection. [ABSTRACT FROM AUTHOR]

Simple Summary: Though women account for approximately 30% of newly diagnosed head and neck cancer, women have comprised only 17% of the study population in landmark clinical trials so far. Caution is therefore required when applying research outcomes directly to women in actual clinical practice. We hypothesized that there is no difference in treatment strategies and their effect on survival in treating locally advanced head and neck squamous cell carcinoma (LA-HNSCC) in the real world. We aimed to compare multidisciplinary treatment modalities and their outcomes by sex in 445 patients with stage III to IVB LA-HNSCC. In our overall and propensity-matched cohorts, there were no significant differences in the treatment strategy or OS by gender. In the present era, in which a multidisciplinary approach is emphasized, we conclude that there is no apparent sex-based disparity in the treatment modalities and outcomes in treating LA-HNSCC. We aimed to compare treatment modalities and outcomes by gender in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). We characterized the sex-specific differences and compared the overall survival (OS) between male and female patients in a multicenter cohort of LA-HNSCC. To minimize the observed confounding, propensity score matching was utilized. The study included 445 patients; 385 (86.5%) were men and 60 (13.5%) were women. In terms of age, smoking habits, drinking habits, and primary tumor locations, there was a significant imbalance in sex before the matching. Propensity score matching yielded 60 patient pairs, with no statistical difference between the sexes in terms of their characteristics. As for the treatment strategies, there were no significant differences between the sexes before (p = 0.260) and after (p = 0.585) the propensity score matching. When comparing the survival probabilities between the sexes, OS was not significantly different in the overall (HR 1.02; 95% CI 0.59–1.76; p = 0.938) and propensity-score-matched population (HR 1.46; 95% CI 0.68–3.17; p = 0.331). These results suggest that there was no difference in prognosis by gender in the treatment modalities and outcomes of LA-HNSCC in real-world practice. [ABSTRACT FROM AUTHOR]

Scientific regulatory systems with suitable analytical methods for monitoring quality, safety, and efficacy are essential in medicinal plant drug discovery. There have been only few attempts to adopt the analytical quality by design (AQbD) strategy in medicinal plants analysis over the last few years. AQbD is a holistic method and development approach that understands analytical procedure, from risk assessment to lifecycle management. The enhanced AQbD approach reduces the time and effort necessary to develop reliable analytical methods, leads to flexible change control through the method operable design region (MODR), and lowers the out-of-specification (OOS) results. However, it is difficult to follow all the AQbD workflow steps in the field of medicinal plants analysis, such as defining the analytical target profiles (ATPs), identifying critical analytical procedure parameters (CAPPs), among others, because the complexity of chemical and biological properties in medicinal plants acts as a barrier. In this review, various applications of AQbD to medicinal plant analytical procedures are discussed. Unlike the analysis of a single compound, medicinal plant analysis is characterized by analyzing multiple components contained in biological materials, so it will be summarized by focusing on the following points: Analytical methods showing correlations within analysis parameters for the specific medicinal plant analysis, plant raw material diversity, one or more analysis targets defined for multiple phytochemicals, key analysis attributes, and analysis control strategies. In addition, the opportunities available through the use of design-based quality management techniques and the challenges that coexist are also discussed. [ABSTRACT FROM AUTHOR]

The International Myeloma Working Group has recently revised the diagnostic criteria for primary plasma cell leukemia (PCL) to circulating plasma cells (CPCs) ≥ 5% in a peripheral blood smear. The present study validated new criteria in patients with multiple myeloma or PCL diagnosed using the previous diagnostic criteria, who were administered immunomodulatory drugs or proteasome inhibitors as induction therapy. We analyzed the medical records of 1357 patients from eight hospitals in South Korea. The median age of the all patients was 64 years, and 187 (13.8%) had CPCs at diagnosis. Only 79 (5.8%) of the patients had ≥ 5% CPCs. The median overall survival (OS) of patients with CPCs ≥ 5% and ≥ 20% was similar, but had significantly inferior median progression-free survival (PFS) and median OS than those with CPCs < 5% (13.1 vs. 21.5 months, P < 0.001, and 21.5 vs. 60.9 months, P < 0.001, respectively). Primary PCL diagnosed using the revised criteria presented with higher total calcium levels and serum creatinine levels, lower platelet counts and frequent organomegaly and plasmacytoma at diagnosis. Univariate and multivariate analyses demonstrated that the presence of plasmacytoma and elevated serum β2-microglobulin were significantly associated with OS in primary PCL. In conclusion, the revised criterion of CPCs ≥ 5% in a peripheral blood smear is appropriate for PCL diagnosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALToma) is a slow-growing lymphoma with a good prognosis. This study was designed to evaluate the effectiveness of radiotherapy at a very low dose of 4 Gy (2 Gy × 2 fractions) in stage I orbital MALToma. Patients with complete remission after a very low dose of 4 Gy (2 Gy × 2 fractions) radiotherapy were closely monitored, and those who did not achieve remission received an additional 24 Gy radiotherapy. Using 4 Gy radiotherapy for orbital MALToma, 11 out of 17 lesions achieved complete remission. There was no transformation of diffuse large B-cell lymphoma, and there was only one local failure. Radiation therapy at a low dose of 4 Gy could be performed effectively and safely with a planned second-line treatment. External beam radiotherapy is effective for stage I orbital mucosa-associated lymphoid tissue lymphoma (MALToma). Hence, very-low-dose radiotherapy is increasingly being investigated. We conducted a single-center prospective phase II trial to evaluate the effectiveness of very-low-dose radiotherapy of 4 Gy (2 Gy × 2 fractions) in pathologically confirmed stage I orbital MALToma. In this first prospective trial, patients with complete response were observed after 3–6 months of follow-up. For patients without complete remission, a radiation dose of 24 Gy/12 fractions was additionally delivered. The primary endpoint was complete response rate; secondary endpoints were overall survival, local control, and progression-free survival. Seventeen patients were screened and three patients refused enrollment during October 2018–October 2021. Thus, 14 patients (17 eyes) were analyzed (median follow-up, 28.2 months). The overall response rate was 100% (complete remission: 11 lesions; partial remission: six lesions). In all lesions with residual disease, additional radiation therapy (dose: 24 Gy) was performed. One local failure was observed. Therefore, 4 Gy ultralow-dose radiation therapy for orbital MALToma was safely performed with a planned second-line treatment in patients without complete remission. This is the first prospective study to report the effectiveness of ultralow-dose radiotherapy of 4 Gy for stage I orbital MALToma treatment. [ABSTRACT FROM AUTHOR]

Although mesoporous silica materials have been widely investigated for many applications, most silica materials are made by calcination processes. We successfully developed a convenient method to synthesize mesoporous materials at room temperature. Although the silica materials made by the two different methods, which are the calcination process and the room-temperature process, have similar specific surface areas, the silica materials produced with the room-temperature process have a significantly larger pore volume. This larger pore volume has the potential to attach to functional groups that can be applied to various industrial fields such as CO2 adsorption. This mesoporous silica with a larger pore volume was analyzed by TEM, FT-IR, low angle X-ray diffraction, N2-adsorption analysis, and CO2 adsorption experiments in comparison with the mesoporous silica synthesized with the traditional calcination method. [ABSTRACT FROM AUTHOR]

Asherman's syndrome (AS) is caused by intrauterine adhesions and inactive endometrium from repeated curettage of the uterine endometrium. AS is a major cause of recurrent implantation failure and miscarriage and is very difficult to treat because of the poor recovery of endometrial basal cells. Platelet-rich plasma (PRP) has abundant growth factors that may induce angiogenesis and cell proliferation. Here, we demonstrate that human PRP (hPRP) significantly enhances angiogenesis to restore embryo implantation, leading to successful pregnancy in mice with AS. In mice with AS, hPRP treatment considerably reduced the expression of fibrosis markers and alleviated oligo/amenorrhea phenotypes. Mice with AS did not produce any pups, but the hPRP therapy restored their infertility. AS-induced abnormalities, such as aberrantly delayed embryo implantation and intrauterine growth retardation, were considerably eliminated by hPRP. Furthermore, hPRP significantly promoted not only the elevation of various angiogenic factors, but also the migration of endometrial stromal cells. It also increased the phosphorylation of STAT3, a critical mediator of wound healing, and the expression of tissue remodeling genes in a fibrotic uterus. PRP could be a promising therapeutic strategy to promote angiogenesis and reduce fibrosis in impaired uterine environments, leading to successful embryo implantation for better clinical outcomes in patients with AS. [ABSTRACT FROM AUTHOR]

The flower buds of Daphne genkwa have been reported as a potent resource associated with anti-angiogenic, anti-tumor, anti-rheumatoid arthritis activities, as well as immunoregulation. This paper aimed to establish an optimal extraction method for flavonoids, as active phytochemicals, and to conduct a comparative analysis by profiling the different blooming stages. Optimized shaking extraction conditions from the design of experiments (DoE), such as minutely mixture design, 23 full factorial design, and polynomial regression analysis, involved an agitation speed of 150 rpm and temperature of 65 °C for 12 h in 56% (v/v) acetone solvent. After, a comparative analysis was performed on three blooming stages, juvenile bud, mature purple bud, and complete flowering, by ultra-high-performance liquid chromatography-photodiode array-mass spectrometry (UHPLC-PDA-MS). Most flavonoids increased during bud growth and then decreased when the bud opened for blooming. In particular, apigenin 7-O-glucuronide, genkwanin 5-O-primeveroside, and genkwanin strikingly showcased this pattern. Furthermore, the raw spectrometric dataset was subjected to orthogonal projection to latent structures discriminant analysis (OPLS-DA) to find significant differences in the flavonoids from the juvenile bud, mature purple bud, and complete flowering. In conclusion, the present study facilitates an understanding of flavonoid change at different blooming stages and provides a momentous reference in the research of D. genkwa. [ABSTRACT FROM AUTHOR]

Background: Worldwide, children are increasingly being diagnosed with autism spectrum disorder (ASD). The case of South Korea is not exceptional. One of the core symptoms of children with ASD is sensory reactivity issues, such as an unusual interest in the sensory aspects of the environment. One promising development in sensory enrichment for individuals with ASD is a multisensory environment (MSE). Objectives: This study investigated the influence of MSE on the target behaviors of children with ASD with different sensory characteristics in the case of South Korea. Methods: A multiple treatment design {A-B-C-D (B + C) phases} was implemented to observe the six target behaviors of three children with ASD. The sensory environmental intervention focusing on visual and auditory stimuli was manipulated as a stimulating MSE or a relaxing MSE depending on the sensory profile of each participant. The analysis was undertaken using visual inspection with data patterns and graph slopes, which is a customary method of analyzing the single-subject design data. In addition, the means and standard deviations of the two target behaviors of each participant were analyzed together. Results: The findings reveal that MSE interventions positively affected the target behaviors of children with ASD with diverse sensory characteristics. The stimulating MSE created by the integration of visual and auditory stimuli was the most effective intervention for the participants with hypo-visual and hypo-auditory sensitivities in this study. Conclusions: The MSE could be meaningful as a nonpharmaceutical therapy that could influence the daily behaviors of children with ASD. [ABSTRACT FROM AUTHOR]

Background: There is currently no method to predict tyrosine kinase inhibitor (TKI) -induced hepatotoxicity. The purpose of this study was to propose a risk scoring system for hepatotoxicity induced within one year of TKI administration using machine learning methods. Methods: This retrospective, multi-center study analyzed individual data of patients administered different types of TKIs (crizotinib, erlotinib, gefitinib, imatinib, and lapatinib) selected in five previous studies. The odds ratio and adjusted odds ratio from univariate and multivariate analyses were calculated using a chi-squared test and logistic regression model. Machine learning methods, including five-fold cross-validated multivariate logistic regression, elastic net, and random forest were utilized to predict risk factors for the occurrence of hepatotoxicity. A risk scoring system was developed from the multivariate and machine learning analyses. Results: Data from 703 patients with grade II or higher hepatotoxicity within one year of TKI administration were evaluated. In a multivariable analysis, male and liver metastasis increased the risk of hepatotoxicity by 1.4-fold and 2.1-fold, respectively. The use of anticancer drugs increased the risk of hepatotoxicity by 6.0-fold. Patients administered H2 blockers or PPIs had a 1.5-fold increased risk of hepatotoxicity. The area under the receiver-operating curve (AUROC) values of machine learning methods ranged between 0.73-0.75. Based on multivariate and machine learning analyses, male (1 point), use of H2 blocker or PPI (1 point), presence of liver metastasis (2 points), and use of anticancer drugs (4 points) were integrated into the risk scoring system. From a training set, patients with 0, 1, 2-3, 4-7 point showed approximately 9.8%, 16.6%, 29.0% and 61.5% of risk of hepatotoxicity, respectively. The AUROC of the scoring system was 0.755 (95% CI, 0.706-0.804). Conclusion: Our scoring system may be helpful for patient assessment and clinical decisions when administering TKIs included in this study. [ABSTRACT FROM AUTHOR]

Compared to ocular adnexal lymphoma of mucosa-associated lymphoid tissue-type (OAML) patients with symptoms related invasion beyond the ocular adnexa, the different approaches to staging assessment may be required in OAML patients with symptoms limited to the ocular adnexa. Seventy-six patients to be diagnosed with OAML and performed bone marrow biopsy and imaging study at Yeungnam University Hospital in 1995–2014 were enrolled. Patients with symptoms limited to the ocular adnexa were included. Computed tomography, magnetic resonance imaging, positron emission tomography (PET), and bone marrow biopsies were performed for diagnosis, NM staging and follow up evaluation. Most patients were treated with external beam irradiation (median dose, 30 Gray (Gy)). The relapse-free survival (RFS) was analyzed according to the tumor laterality and TNM stage. The median follow-up period was 72 months. The 5-year RFS and overall survival rates were 82.1% and 95.6% respectively. Of all 76 patients, lymph node and bone marrow involvement was identified in 1 patient, respectively. Among the 3 patients with T4 stage as tumor invasion beyond ocular adnexa, bone marrow involvement was confirmed in a patient with left cheek invasion. Only 11 of the 43 patients who underwent PET showed positive uptakes in orbital lesion. The patients with advanced stage were alive without recurrences. Bone marrow examination is useful in OAML patients with T4 for extended stage assessment. The AJCC TNM staging system was not significantly predictive factor for relapse, but may contribute to clarifying the patient group that needs bone marrow study. [ABSTRACT FROM AUTHOR]

Aim: Long‐acting injectable antipsychotic agents (LAIs) including paliperidone palmitate (PP) have shown promising results in preventing relapse and rehospitalization in schizophrenia. This study aimed to ascertain the comparative real‐world effectiveness between the early and late administration of PP and oral formulations of risperidone and paliperidone (ORPs) in patients experiencing a first episode or relapse of schizophrenia. Methods: We identified patients with schizophrenia admitted to a psychiatric ward at least once and treated with ORPs or PP using the Korea National Insurance Claims Database. Patients were divided into three groups based on the clinical data: (1) patients treated with PP within 30 days of the initiation of treatment (early‐PP), (2) patients treated with PP after 30 days of the initiation of therapy (late‐PP) and (3) patients treated with only ORPs and not received PP (only‐ORP). The primary outcomes were determined as psychiatric rehospitalization during the entire duration of treatment after the first discharge. Results: A total of 3790 patients (1096 early‐PP, 799 late‐PP and 1895 only‐ORP) were finally included in the analysis. The mean of number and total length of rehospitalization stays during the entire duration in early‐PP group were significantly lower than those of late‐PP group and only‐ORP group (number: 2.32 stays/year, 3.24 stays/year and 4.23 stays/year, p <.001; total length: 50.34 days/year, 72.26 days/year and 105.14 days/year, p <.001). Conclusions: Early treatment with PP was associated with a greater reduction in psychiatric rehospitalization during the treatment period than late treatment with PP and ORP in schizophrenia. [ABSTRACT FROM AUTHOR]

For affordance-based design, which is especially lacking in the architecture field, this study investigates the relationships between affordances and interior elements in the built environment by understanding intrinsic affordances by users. The ethnographic case study was conducted by unobtrusively observing participant behaviours during given tasks using video recordings, voice recordings and photographs. The 32 affordances were identified in a public space containing 22 observed affordances and 10 issue affordances. The paper defines the hierarchical nature of the interior elements, including area-level, set-level, object-level and detailed attribute-level elements. An awareness of human-based affordances, where humans can create specific affordances using their bodies and belongings, was significant in the current research. The affordance-interior design element map can be used to support the identification of interior elements that are relevant to certain affordances and to distinguish which affordances are demanded by occupants in the built environment. Overall, designers could embed the affordance concept in the early stages of the design process by choosing more critical affordances and interior elements. The affordance-interior design element matrix and the map may be developed as an initial data repository for affordance-based interior design. [ABSTRACT FROM AUTHOR]

Objectives: Soy and hop extracts have been investigated as alternatives for hormone replacement therapy. However, their combined efficacy is not known. We investigated the efficacy and safety of a combined soy and hop extract on postmenopausal symptoms. Design: Double-blinded, randomized controlled trial. Settings/Location: Gynecological outpatient clinic of tertiary hospital. Subjects: Seventy-eight women with moderate or severe menopausal symptoms assessed as modified Kupperman Menopoausal Index (KMI) scores >20. Interventions: They received either a combined soy and hop extract (n = 38) or placebo (n = 40). Outcome measures: Menopausal symptoms were evaluated through self-reporting of modified Kupperman Menopausal Index (KMI) scores at baseline and after 6 and 12 weeks. We assessed serum levels of bone metabolism biomarkers, ultrasonographic parameters, hormone profiles, compliance, and safety. Results: After 12 weeks of the treatment, treatment group scores decreased by 20.61 points compared with 14.80 points in the placebo group (p < 0.05). Fatigue, paresthesia, arthralgia, and myalgia, palpitation and vaginal dryness significantly improved more in the treatment group compared with the placebo group after 12 weeks (p < 0.05). Urine N-telopeptide in participants ≥50 years in the treatment group showed a reduced increase. Endometrial thickness and hormonal profiles did not show significant changes in either group. No serious adverse events were reported. Conclusion: The results suggest that 190 mg of combined soy and hop extract is safe and effective for improvement of menopausal symptoms. CRIS No.: KCT0006019. [ABSTRACT FROM AUTHOR]

Purpose: This observational study aimed to evaluate the safety and efficacy of pegteograstim prophylaxis in patients with lymphoma and solid malignancies. Methods: This study was conducted at 18 sites in Korea between November 2015 and August 2018. Results: In total, 611 patients (female, 61.2%) with a median age of 58 (range, 18–88) years were included. Most patients had lymphomas (n = 371, 60.7%) and breast cancer (n = 230, 37.6%) and were administered R-CHOP21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone per 21 days) (n = 284, 46.5%) and AC (doxorubicin and cyclophosphamide) (n = 177, 29.0%). The total pegteograstim dose in the 611 patients was 14,970 mg (2495 doses), with each patient receiving an average daily dose of 6.0 mg. Neutropenia grade 4 occurred in 97 patients (15.9%), and febrile neutropenia (FN) occurred in 31 patients (5.1%). Among the 611 patients, 267 patients (43.7%) developed 882 adverse events (AEs), and 11 patients (1.8%) experienced 18 adverse drug reactions (ADRs). There were 62 patients (10.2%) who experienced 81 cases of serious adverse events (SAEs), with FN and pneumonia being the most frequent at 14 and 13 episodes, respectively, in 13 patients (2.1%). Meanwhile, 1 patient (0.2%) developed 2 episodes of serious ADRs (grade 1 and grade 2 hypotension). No safety concerns in the elderly and patients with liver and/or renal disease were identified. Conclusion: The prophylactic use of pegteograstim might have good overall safety and efficacy in patients with lymphomas and solid malignancies in routine clinical practice, even in those who are elderly and have liver and renal diseases. [ABSTRACT FROM AUTHOR]

The present study introduces a systematic approach using analytical quality by design (AQbD) methodology for the development of a qualified liquid chromatographic analytical method, which is a challenge in herbal medicinal products due to the intrinsic complex components of botanical sources. The ultra-high-performance liquid chromatography-photodiode array-mass spectrometry (UHPLC-PDA-MS) technique for 11 flavonoids in Genkwa Flos was utilized through the entire analytical processes, from the risk assessment study to the factor screening test, and finally in method optimization employing central composite design (CCD). In this approach, column temperature and mobile solvent slope were found to be critical method parameters (CMPs) and each of the eleven flavonoid peaks' resolution values were used as critical method attributes (CMAs) through data mining conversion formulas. An optimum chromatographic method in the design space was calculated by mathematical and response surface methodology (RSM). The established chromatographic condition is as follows: acetonitrile and 0.1% formic acid gradient elution (0–13 min, 10–45%; 13–13.5 min, 45–100%; 13.5–14 min, 100–10%; 14–15 min, 10% acetonitrile), column temperature 28℃, detection wavelength 335 nm, and flow rate 0.35 mL/min using C18 (50 × 2.1 mm, 1.7 μm) column. A validation study was also performed successfully for apigenin 7-O-glucuronide, apigenin, and genkwanin. A few important validation results were as follows: linearity over 0.999 coefficient of correlation, detection limit of 2.87–22.41, quantitation limit of 8.70–67.92, relative standard deviation of precision less than 0.22%, and accuracy between 100.13 and 102.49% for apigenin, genkwanin, and apigenin 7-O-glucuronide. In conclusion, the present design-based approach provide a systematic platform that can be effectively applied to ensure pharmaceutically qualified analytical data from complex natural products based botanical drug. [ABSTRACT FROM AUTHOR]

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL)-a new category of anaplastic large cell lymphoma associated with textured breast implants-has a distinct variation in incidence and is especially rare in Asia. We report the first case of BIA-ALCL in Korea and present its histological and genetic characteristics. A 44-year-old female patient presented with a typical clinical course and symptoms, including breast augmentation with textured breast implants, late-onset peri-implant effusion, and CD30+ALK- histology, followed by bilateral implant removal and total capsulectomy. For histological analysis, we performed immunohistochemistry of the bilateral breast capsules. For transcriptome analysis, we identified highly upregulated gene sets employing RNA-sequencing and characterized the lymphoma immune cell components. In the lymphoma-associated capsule, CD30+ cells infiltrated not only the lymphoma lesion but also the peritumoral lesion. The morphologies of the myofibroblasts and vessels in the peritumoral lesion were similar to those in the tumoral lesion. We observed strong activation of the JAK/STAT3 pathway and expression of programmed death ligand-1 in the lymphoma. Unlike the molecular profiles of BIA-ALCL samples from Caucasian patients-all of which contained activated CD4+ T cells-the Asian patient's profile was characterized by more abundant CD8+ T cells. This study contributes to a better understanding of the pathogenesis and molecular mechanisms of BIA-ALCL in Asian patients that will ultimately facilitate the development of clinical therapies.Level Of Evidence:5: [ABSTRACT FROM AUTHOR]

Mistletoe extracts (Viscum album L.) have been widely used as complementary and alternative medicines for the treatment of cancer, and their cytotoxic effects have been reported on various types of cancer. However, the molecular targets of mistletoe extracts have not been well studied. Herein, we investigated molecules associated with the in vitro and in vivo anticancer effects of mistletoe extract using 4T1 murine breast cancer cells. Mistletoe extract induced apoptosis and inhibited the signal transducer and activator of transcription3 (STAT3) phosphorylation. This inhibition was accompanied by the downregulations of forkhead box M1 (FOXM1) and the DNA repair proteins, RAD51 and survivin. Mistletoe extract simultaneously increased the expression of the DNA damage marker proteins, phosphorylated H2A histone family member X (H2A.X), and phosphorylated p38. Furthermore, mistletoe extract effectively suppressed tumor growth in 4T1 tumor-bearing BALB/c mice. In addition to tumor growth inhibition, mistletoe extract inhibited lung metastasis in the tumor-bearing mice and cell invasiveness by downregulating the expressions of matrix metalloproteinases (MMPs), urokinase-type plasminogen activator (uPA), uPA receptor, and markers of epithelial-mesenchymal transition (snail and fibronectin). Taken together, our results suggest that mistletoe extract targets the STAT3-FOXM1 pathway for its cytotoxic effects, and that mistletoe extracts might be useful for the treatment of patients with cancers highly expressing the STAT3-FOXM1 pathway. [ABSTRACT FROM AUTHOR]

Background: Some sea anemone toxins cause renal injuries resembling hemolytic uremic syndrome (HUS). To date, only a few cases of HUS caused by sea anemone stings have been reported. In this case report, we have described an HUS case caused by a sea anemone sting.Case Presentation: In November 2019, a 37-year-old man with no underlying disease was admitted to our hospital. He presented with intense pain, a rash on, and swelling in his right thigh. Two days prior, he had been stung by a sea anemone while scuba diving in Cebu, Philippines. His blood tests revealed renal dysfunction, and his platelet count was normal. However, on day three, the platelet count decreased rapidly. His blood haptoglobin level decreased, and schistocytes were identified on the peripheral blood smear. We suspected thrombotic microangiopathy and started the conventional treatment, comprising hemodialysis, blood transfusion, and antibiotic administration. ADAMTS-13 and genetic test results associated with atypical HUS were normal. Therefore, the patient was diagnosed with HUS caused by a sea anemone toxin.Conclusions: HUS caused by a sea anemone toxin is rare, but it is a serious medical disease. Clinicians should consider HUS in patients with such clinical presentations, and they should make prompt treatment-related decisions. [ABSTRACT FROM AUTHOR]

We compared efficacy and safety, according to frailty, of elderly patients with relapsed and refractory multiple myeloma (RRMM) treated with lenalidomide and dexamethasone (Rd), for whom bortezomib treatment had failed. Patients, 164 (52.9%) and 146 (47.1%), were classified as non-frail and frail using a simplified frailty scale. The overall response rates (ORR) and survival outcomes were lower in frail than in non-frail patients (ORR: 56.2% vs. 67.7%, P = 0.069; median progression free survival: 13.17 vs. 17.80 months, P = 0.033; median overall survival: 23.00 vs. 36.27 months, P = 0.002, respectively). The number of treatment emergent adverse events in grade 3 or worse was higher in frail than in non-frail patients (41.8% vs. 24.4%, P = 0.002, respectively). In frail patients, independent poor prognostic factors for survival were two or more Charlson comorbidity index (CCI) score, prior to exposure to both bortezomib and thalidomide, and achieved less than partial response In conclusion, frailty could predict clinical outcomes of Rd treatment in elderly patients with RRMM who had failed prior bortezomib. In frail patients, lower CCI in addition to less previous treatment exposure and deep response were associated with better survival. [ABSTRACT FROM AUTHOR]

Background: The objective of the current study was to investigate the clinical activity of, safety of, and predictive biomarkers for afatinib, an irreversible pan‐ErbB kinase inhibitor, in patients with recurrent and/or metastatic esophageal squamous cell carcinoma (R/M‐ESCC). Methods: Patients with R/M‐ESCC that was refractory to platinum‐based chemotherapy were enrolled in the current multicenter, single‐arm, phase 2 study and received afatinib at a dose of 40 mg/day. The primary endpoint was the objective response rate. Secondary endpoints included progression‐free survival, overall survival, the disease control rate, and the safety profile. To identify predictive biomarkers, single‐nucleotide variations, short insertions/deletions, and somatic copy number alterations were assessed using whole‐exome sequencing and their associations with clinical outcomes were analyzed. Results: Among 49 enrolled patients, the objective response rate and disease control rate were 14.3% and 73.3%, respectively. With a median follow‐up of 6.6 months, the median progression‐free survival and overall survival were 3.4 months and 6.3 months, respectively. Treatment‐related adverse events were noted to have occurred in 33 patients (67.3%), with the majority being of grade 1 to 2 (adverse events were graded and recorded based on the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.03]). Whole‐exome sequencing demonstrated that the ESCC genomes of patients who demonstrated a response to afatinib were enriched with genomic alterations of TP53 and epidermal growth factor receptor (EGFR). As a predictive marker, a score derived from TP53 disruptive mutations and EGFR amplifications and/or missense mutations demonstrated a significant association with the response to afatinib. The score based on the mutational status of EGFR and TP53 achieved a performance of an area under the curve of 0.86 in predicting the sensitivity of afatinib. Conclusions: The results of the current study demonstrated that afatinib can confer modest clinical benefits with manageable toxicity in patients with platinum‐resistant R/M‐ESCC. Identification of TP53 alterations and EGFR amplifications may serve as predictive markers with which to identify patients with R/M‐ESCC who may benefit from afatinib. Lay Summary: Esophageal squamous cell carcinoma (ESCC) is a type of cancer with a dismal prognosis and very limited treatment options.The clinical efficacy of afatinib was evaluated in patients with recurrent and/or metastatic ESCC, with adverse events demonstrating the modest efficacy with manageable toxicity of this irreversible, pan‐ErbB kinase inhibitor. Whole‐exome sequencing analysis of 41 cases of ESCC further revealed that the patients harboring epidermal growth factor receptor (EGFR) amplifications and disruptive TP53 mutations are more likely to benefit from treatment with afatinib.The results of the current study have highlighted the clinical value of EGFR and TP53 as predictive biomarkers of platinum‐resistant recurrent and/or metastatic ESCC for afatinib sensitivity. Patients with recurrent and/or metastatic esophageal squamous cell carcinoma have a dismal prognosis with very limited treatment options. The results of the current phase 2 trial demonstrate that afatinib has modest efficacy and manageable toxicity, but the exploratory analyses using whole‐exome sequencing indicate that EGFR amplification and TP53 disruption might serve as predictive biomarkers for treatment with afatinib. [ABSTRACT FROM AUTHOR]

Polyunsaturated fatty acids (PUFAs) have important functions in biological systems. The beneficial effects of dietary PUFAs against inflammatory diseases, cardiovascular diseases, and metabolic disorders have been shown. Studies using cancer cells have presented the anti-tumorigenic effects of docosahexaenoic acid (DHA), an n-3 PUFA, while arachidonic acid (AA), an n-6 PUFA, has been shown to elicit both pro- and anti-tumorigenic effects. In the current study, the anti-tumorigenic effects of AA were evaluated in HT-29 human colon cancer cells. Upon adding AA in the media, more than 90% of HT-29 cells died, while the MCF7 cells showed good proliferation. AA inhibited the expression of SREBP-1 and its target genes that encode enzymes involved in fatty acid synthesis. As HT-29 cells contained lower basal levels of fatty acid synthase, a target gene of SREBP-1, than that in MCF7 cells, the inhibitory effects of AA on the fatty acid synthase levels in HT-29 cells were much stronger than those in MCF-7 cells. When oleic acid (OA), a monounsaturated fatty acid that can be synthesized endogenously, was added along with AA, the HT-29 cells were able to proliferate. These results suggested that HT-29 cells could not synthesize enough fatty acids for cell division in the presence of AA because of the suppression of lipogenesis. HT-29 cells may incorporate more AA into their membrane phospholipids to proliferate, which resulted in ER stress, thereby inducing apoptosis. AA could be used as an anti-tumorigenic agent against cancer cells in which the basal fatty acid synthase levels are low. [ABSTRACT FROM AUTHOR]

Purpose: Although several studies have examined tyrosine kinase inhibitor (TKI)-induced hepatotoxicity, the majority of patients in those studies displayed low-grade (grade I–II) hepatotoxicity. The purpose of this study was to investigate factors affecting high-grade (grade III–IV) hepatotoxicity of TKIs. Methods: This multi-center, retrospective study used individual patient data from five studies that examined factors affecting hepatotoxicity by TKIs (crizotinib, erlotinib, gefitinib, imatinib, and lapatinib). Odds ratio (OR) and adjusted OR (AOR) were estimated from univariate and multivariate analyses, respectively. Results: Data from 1279 patients treated with TKIs were analyzed. The rate of patients who experienced high-grade hepatotoxicity after TKI administration was 5.5%. In multivariable analysis, H2 blockers and CYP3A4 inducers increased high-grade hepatotoxicity 2.2- (95% CI 1.255–3.944) and 3.3-fold (95% CI 1.260–8.698), respectively. Patients with liver metastasis revealed a 3.4-fold (95% CI 1.561–7.466) higher risk of high-grade hepatotoxicity. Among underlying malignancies, pancreatic cancer and other cancers including acute lymphoblastic leukemia increased the risk of high-grade hepatotoxicity by 2.6- and 24.3-fold, respectively, whereas breast cancer decreased the risk (AOR 0.3, 95% CI 0.106–0.852), compared to non-small cell lung cancer. In patients who administrated TKIs which form reactive metabolites, use of CYP3A4 inducers and liver metastasis increased incidence of high-grade hepatotoxicity by 3.0- and 2.3-fold, respectively. In patients with EGFR mutation, exon 19 deletion and use of proton pump inhibitors were risk factors for high-grade hepatotoxicity in addition to liver metastasis and use of H2 blockers. Conclusion: The use of H2 blockers, presence of liver metastasis, and CYP3A4 inducers were associated with high-grade hepatotoxicity of TKIs. In subgroup analyses, presence of exon 19 deletion, and/or proton pump inhibitors, was additional risk factors for high-grade hepatotoxicity in special patients and use of specific TKIs. Close liver function monitoring is recommended, especially in patients with liver metastasis or using H2 blockers or CYP3A4 inducers. [ABSTRACT FROM AUTHOR]

Objectives: Conventional guided bone regeneration (GBR) limits the amount of bone graft due to limited soft tissue expansion. We hypothesize that the use of tissue expander will successfully augment soft tissue prior to bone graft, allowing for sufficient amount of grafting which will lead to a more stable and effective vertical bone graft. The authors aimed to evaluate effectiveness of the novel self‐inflating tissue expander for vertical augmentation in terms of soft tissue expansion, clinical outcomes, and related complications. Material and methods: A prospective, multicenter, randomized controlled trial was performed on patients requiring vertical augmentation. For experimental group patients, the tissue expander was subperiosteally implanted and followed by a tunneling bone graft without full flap reflection. Control patients underwent conventional vertical GBR. Primary objectives were to evaluate the dimensional changes of soft tissue and radiographic vertical bone gain and retention. As a secondary outcome, clinical complications and thickness changes of expanded overlying tissue were assessed and analyzed. Results: Twenty‐three patients in each group were included. During a 4‐week expansion, two of the experimental group showed over‐expansion and one showed mucosal perforation associated with previous severe scars. The other patients showed uneventful expansion and mean tissue augmentation was 6.88 ± 1.64 mm vertically. Ultrasonographic measurements of overlying gingiva revealed no thinning after tissue expansion (p >.05). Significantly higher vertical bone gain was shown in the experimental group (5.12 ± 1.25 mm) compared with that in the control patients (4.22 ± 1.15 mm; p <.05). After a 6‐month retention period, the mean vertical bone measurement of the controls had decreased to 1.90 mm (55.0% reduction), which was a significantly greater decrease than that in the experimental group (mean 3.55 mm, 30.7% reduction; p <.05). Conclusion: Our results demonstrated the effectiveness of tissue expanders followed by tunneling bone graft for vertical augmentation; however, studies comparing the two techniques without tissue expanders are needed to elucidate the net effect of tissue expansion. [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV) positivity in diffuse large B cell lymphoma (DLBCL) provokes a critical oncogenic mechanism to activate intracellular signaling by LMP1. LMP1 specifically mimics the role of BTK-dependent B cell receptor. Therefore, a trial considering RCHOP therapy along with ibrutinib (I-RCHOP) in combination was conducted among patients with EBV-positive DLBCL. This study was an open-label, single-arm, prospective multicenter phase II clinical trial. Patients received 560 mg of ibrutinib with RCHOP every 3 weeks until 6 cycles were completed or progression or unacceptable toxicity was observed. The primary endpoint was objective response, while secondary endpoints included toxicity, progression-free survival, and overall survival. A matched case-control analysis was completed to compare the efficacy and toxicity of I-RCHOP and RCHOP, respectively, in EBV-positive DLBCL patients. From September 2016 to August 2019, 24 patients proven to have EBV-positive DLBCL in the tissue were enrolled and received I-RCHOP. Their median age was 58 years (range, 28-84 years). The objective overall response was 66.7%, including 16 patients who achieved complete response after 6 cycles. Patients aged younger than 65 years presented a superior OR (87.5%) as compared with those older than 65 years (25.0%; p = 0.01). In a matched case-control study, I-RCHOP therapy provoked a more favorable complete response rate (87.3%) than did RCHOP (68.8%) in those younger than 65 years. Treatment-related mortality was linked most frequently with I-RCHOP therapy (four patients presented with unusual infection without Gr3/4 neutropenia) in the older age group (age ≥ 65 years). In conclusion, in this phase II trial for EBV-positive DLBCL, I-RCHOP was effective but did not show a significant improvement in response and survival in comparison with RCHOP. Also, I-RCHOP promoted serious toxicity and treatment-related death in older patients. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the effect of stem cell source and dose on the survival of various donor subgroups, such as matched sibling donor (MSDs) and alternative donors (ADs), upon bone marrow (BM) or peripheral blood stem cell (PBSC) infusion in aplastic anemia (AA). Methods: We retrospectively investigated the effects of stem cell source and dose on allogeneic hematopoietic stem cell transplantation (alloHSCT) in AA. Results: A total of 267 patients were included in this analysis. The BM-treated group showed an association with low incidence of any-grade acute graft versus host disease (GvHD) (p < 0.001). A higher stem cell dose was related with a low incidence of extensive chronic GvHD in MSDs (p = 0.025). Multivariate analysis for overall survival (OS) revealed that only age at alloHSCT <31 years (p = 0.010) and prior platelet transfusion <86 U (p = 0.046) in MSDs and higher stem cell dose (hazard ratio = 2.596, p = 0.045) in ADs were favorable prognostic factors. Conclusion: PBSCs could be preferred in AD because high stem cell dose may be easily achieved to improve the OS at the expense of acute GvHD. However, BM stem cells are preferred in MSDs. [ABSTRACT FROM AUTHOR]

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr < 40 mL/min; 10.4%), comorbid conditions (≥ 2; 12.0%), and poor performance status (≥ 2; 25.1%) were included. The overall response rate was 64.2%: complete response (13.1%), very good partial response (VGPR 19.9%). With median follow-up duration of 18.6 months, median PFS and OS were 11.2 months and 25.2 months, respectively. In multivariate analysis, less than 2 comorbid conditions, normal LDH, failed one chemotherapy prior to RD, and ≥ 10 cycles of RD therapy had significantly prolonged PFS (P = 0.007, P = 0.011, P = 0.007, and P < 0.001, respectively). Adverse events were acceptable. RD is effective and safe in real-life clinical practice, including patients with comorbidities. RD is an effective and safe treatment in a real clinical setting which includes patients with comorbidities. Early and continual use of RD treatment may improve RRMM survival outcomes. [ABSTRACT FROM AUTHOR]

This trial was designed to investigate the efficacy and toxicity of bendamustine, carboplatin, and dexamethasone (BCD) for relapsed or refractory peripheral T-cell lymphomas (PTCLs), which would be expected to exhibit more promising clinical outcomes compared with bendamustine therapy alone. After treatments with BCD, eight patients exhibited a complete response (CR; 29%) and seven exhibited a partial response (PR; 25%). The overall response rate (ORR) was 54%. Five patients proceeded to ASCT and three patients finally achieved CR. The median progression-free survival (PFS) was 4.4 months (2.8–6.0, 95% CI). For a total of 85 cycles of BCD, grade 3 or 4 neutropenia, thrombocytopenia, and anemia occurred in 17.6, 38.8, and 16.5% of cycles, respectively. Only one patient experienced febrile neutropenia. BCD was a considerable salvage regimen for relapsed or refractory PTCLs with acceptable toxicity; AITL or ASCT eligible patients were more effective to BCD. ClinicalTrials.gov Identifier: NCT02424045 [ABSTRACT FROM AUTHOR]

We demonstrate fluorescent chemosensing for biologically important aromatic compounds by a supramolecular system consisting of tin(IV) porphyrin, viologen, and cucurbit[8]uril. The detection is successfully achieved by the inclusion of an aromatic analyte through the charge-transfer interaction with the viologen unit in the cavity of cucurbit[8]uril, in which the strong charge-transfer interaction interrupts the photo-induced electron transfer from the tin(IV) porphyrin core to the viologen ligands to lead to the efficient emission of the fluorescence from the porphyrin ring. [ABSTRACT FROM AUTHOR]

The synthesis of (porphyrinato)Sn-viologen, 1, and its supramolecular complexation with cucurbit[7]uril (CB[7]) were studied. 1H NMR spectroscopic studies obviously reveal that 1 forms a 1 : 2 supramolecular complex with CB[7] through the inclusion of viologen moieties of 1 into the cavity of CB[7]. The cyclic voltammetric study supports that the binding affinity of the radical cation forms is comparable to that of the di-cation viologen toward CB[7]. The fluorescence arising from the porphyrin moiety is significantly quenched upon the complexation of 1 with CB[7]. The ps-time-resolved fluorescence and ns-transient absorption spectroscopic studies reveal that the photoinduced electron transfer (PET) between viologen and Sn(iv) porphyrin of 1 takes place from the first excited singlet (S1) state and the second excited triplet (T2) state of the porphyrin moiety upon complexation with CB[7], while the PET from the S1 state is negligible in the absence of CB[7]. [ABSTRACT FROM AUTHOR]