Association of non-steroidal anti-inflammatory drug use with encephalopathy development: An analysis using the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases.

Encephalopathy is the most severe complication of various common infections, including influenza and herpes, and it often results in death or severe neurological disability. The risk factors for viral encephalopathy include non-steroidal anti-inflammatory drug (NSAID) use; however, studies on NSAID-related encephalopathy are limited. In this study, we aimed to investigate the characteristics of NSAID-related encephalopathy. We investigated the incidence of NSAID-related encephalopathy using data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases containing reports on spontaneous adverse effects (AEs) published by the Pharmaceuticals and Medical Devices Agency. We used these databases to detect AEs based on reported odds ratios. By separating suspicious drugs, concomitant drugs, and drug interactions involving NSAIDs, we investigated the relationship between encephalopathy pathology and AEs of NSAIDs. Significant encephalopathy signals were detected for loxoprofen and etodolac in the FAERS database and loxoprofen in the JADER database. In the JADER database, significant encephalopathy signals in loxoprofen-treated patients were detected in 70-79-year-old, ≥80-year-old, influenza viral infection, and herpes virus infection groups. Significant encephalopathy signals in patients with herpes virus infection were detected in the ≥80-year-old and loxoprofen-treated groups. Regarding the involvement of loxoprofen in the development of encephalopathy, the JADER database listed loxoprofen as a suspect drug, without indicating any concomitant drug interactions. In conclusion, our findings suggest that loxoprofen and etodolac may be associated with viral encephalopathy. Accordingly, prudence is recommended when using loxoprofen in older individuals with viral infections.

POST-COVID-19 INFLAMMATORY RHEUMATOID ARTHRITIS REMISSION.

People infected with the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) are at a higher risk of developing autoimmune inflammatory rheumatic disease. However, clinical studies have shown that, unlike bacterial infections, inflammatory rheumatoid arthritis is rarely triggered by viral infections. Generally, adult females have a higher incidence of rheumatoid arthritis compared to males (a female/male ratio of approximately 3:1). The secretion of female hormones is presumed to be deeply involved in the onset of rheumatoid arthritis. Furthermore, there is a definitive role of genetic factors in rheumatoid arthritis. Typically, rheumatoid arthritis is treated with steroids and antibody drugs, such as anti-tumor necrosis factor-α (TNF-α) antibodies and anti-interleukin-6 (IL-6) antibodies; however, although the symptoms of autoimmune diseases are alleviated by these drugs, the underlying pathology cannot be completely cured. Meanwhile, immunosuppressive treatment with steroids is effective against inflammatory rheumatoid arthritis associated with coronavirus disease (COVID-19). Therefore, the pathogenesis, symptoms, and pathological findings of inflammatory rheumatoid arthritis associated with COVID-19 are presumably different from those of autoimmune rheumatoid arthritis. Since COVID-19-related autoimmune-like diseases, such as COVID-19-related inflammatory rheumatoid arthritis, have pathological conditions that are different from inherited autoimmune diseases, it is possible to establish treatments that aim at remission. Further pathological analyses of patients with post-COVID-19 inflammatory rheumatoid arthritis are essential to the development of treatments for this type of arthritis.

Impact of COVID-19 on the mental health of primary schoolchildren during the later phase of the pandemic: A case report of an 18-month longitudinal survey in a Japanese primary school.

Background: Drastic changes such as school closures and stay-at-home measures due to the global COVID-19 pandemic, may have long-term negative effects on children's mental health; however, longitudinal studies after 2021 are limited. This study aimed to observe the long-term effects of the COVID-19 pandemic on children's mental health by exploring changes in their mental health over a period of 18 months. Study design: We conducted a longitudinal study at Chiba Prefecture in Japan, focusing on schoolchildren's mental health changes. Methods: Data were obtained from the Strengths and Difficulties Questionnaire (SDQ) questionnaire conducted at single primary school three times from October 2021 to March 2023 which and included 183 participants. This study adopted a linear-mixed model to evaluate changes in children's SDQ scores, with sex and grade as the independent variables, and participants as a random effect. Results: Regarding changes in SDQ scores, there were no significant changes in the total difficulty scores or in each subscale; Emotional Symptoms, Conduct Problems, Hyperactivity/Inattention, Peer Problems, and Prosocial Behavior. There was no statistically significant interaction between changes in SDQ scores and sex. Conclusions: This report indicates that the impact of the COVID-19 pandemic on the mental health of Japanese primary schoolchildren was negligible in the later phase of the pandemic. However, the impact may differ from country to country owing to factors such as social restrictions during the COVID-19 pandemic.

POTENTIAL LIFE PROGNOSTIC MARKER FOR MESENCHYMAL TUMOR RESEMBLING UTERINE LEIOMYOSARCOMA.

Benign uterine leiomyoma (U.LMA) and malignant uterine leiomyosarcoma (U.LMS), both uterine mesenchymal tumors, are distinguished by the number of cells exhibiting mitotic activity. However, uterine mesenchymal tumors contain tumor cells with various cell morphologies; therefore, making a diagnosis, including differentiating between benign and malignant tumors, is difficult. For example, cotyledonoid dissecting leiomyoma (CDL) or uterine smooth muscle tumors of uncertain malignant potential (STUMPs) are a group of uterine mesenchymal tumors for which a differential diagnosis is challenging. To date, a standardized classification system for uterine mesenchymal tumors has not yet been established. Furthermore, definitive preoperative imaging techniques or hematological examinations for the potential inclusion of CDL or STUMP in the differential diagnosis have not been defined. Several clinical studies have reported that there is no correlation between biomarker expression and mitotic rate or tumor recurrence. The immunohistochemical biomarkers reported so far cannot effectively help determine the malignant potential of CDL or STUMPs in patients who wish to become pregnant in the future. The establishment of gene expression profiles or detection of pathogenic variants by using next-generation molecular techniques can facilitate disease prediction, diagnosis, treatment, and prognosis. We examined the oncological properties of STUMP in adults using molecular pathological techniques on tissue excised from patients with uterine mesenchymal tumor. In a clinical study conducted by our medical team, the results of gene expression profiling indicated factors that may be associated with malignancy of uterine mesenchymal tumors. We herein describe the problems in diagnosing uterine mesenchymal tumors along with the results of the latest clinical studies. It is expected that the establishment of a diagnostic method targeting the characteristics of mesenchymal tumor cells will lead to the treatment of malignant tumors with a low risk of recurrence and metastasis.

EFFECT OF RBD MUTATIONS IN SPIKE GLYCOPROTEIN OF SARS-COV-2 ON NEUTRALIZING IGG AFFINITY.

Certain mutant strains of SARS-CoV-2 are known to spread widely among humans, including the receptor binding domain (RBD) mutant, Y453F, from farmed minks, and the RBD mutant, N501Y, a mutation common to three major SARS-CoV-2 subvariants (B.1.1.7, B.1.351, and B.1.1.248) and omicron type SARS-CoV-2 BQ.1.1 and XBB.1.16 subvariants. We investigated the characteristics of the RBD mutants, Y453F and N501Y, using three-dimensional structural analysis. We also investigated the effect of Y453F, N501Y or the mutants of RBD of omicron type SARS-CoV-2 BQ.1.1 and XBB.1.16 subvariants on neutralizing antibodies in serum derived from individuals including children (aged 5-11 years) inoculated with mRNA based COVID-19 vaccine (BNT162b2: Pfizer/BioNTech) or COVID-19-positive patients or children (aged 5-11 years) after vaccination with BNT162b2. Our results suggest that SARS-CoV-2 subspecies with the RBD mutations Y453F or N501Y partially escaped detection by 4 neutralizing monoclonal antibodies and 21 neutralizing antibodies in serums derived from COVID-19-positive patients. The significantly low antibody titer of children against Omicron type SARS-CoV-2 BQ.1.1 subvariant and XBB.1.16 subvariant in Japan. Infection with SARS-CoV-2 subspecies that causes serious symptoms in humans may spread globally. In particular, since the antibody titer against the omicron type is low in children (aged 5-11 years) who have been vaccinated with conventional vaccines, therefore it is important for children to receive vaccines specific for the omicron type.

Influence of using history of immune checkpoint inhibitor therapy for neutropenia caused by combination therapy of ramucirumab and docetaxel.

Recently, pretreatment with immune checkpoint inhibitors (ICIs) has been shown to enhance the therapeutic effects of the combination therapy of ramucirumab (RAM) and docetaxel (DTX); however, its influence on the drug's side effects remains unclear. This study investigated the influence of pretreatment with ICIs on the incidence of neutropenia caused by RAM + DTX therapy in patients with non-small cell lung cancer (NSCLC). Patients with NSCLC who received RAM + DTX therapy at Gifu Prefectural General Medical Center between April 2016 and December 2020 were enrolled. Retrospective data regarding age, sex, performance status and detailed treatment history, among others, at treatment initiation were collected from the patients' electronic medical records. Additionally, data on the course number of RAM + DTX therapy, supportive therapy and blood biochemical parameters, including leukocyte and neutrocyte counts, during the treatment period were collected. We identified 41 patients receiving RAM + DTX therapy. Among the more than grade 3 adverse events caused by this therapy, neutropenia was the most common (78.1%). Despite the fact that all previous risk factors influencing this incidence rate had corresponded, the only factor influencing the incidence rate of neutropenia more than grade 3 was ICI treatment history. A difference in the incidence of neutropenia more than grade 3 in the Kaplan-Meier curve was observed between patients with and without ICI pretreatment history (p = 0.037). The pretreatment history of ICI therapy affects the incidence of neutropenia caused by RAM + DTX therapy in patients with NSCLC.

Measurements of Strong-Interaction Effects in Kaonic-Helium Isotopes at Sub-eV Precision with X-Ray Microcalorimeters.

We have measured the 3d→2p transition x rays of kaonic ^{3}He and ^{4}He atoms using superconducting transition-edge-sensor microcalorimeters with an energy resolution better than 6 eV (FWHM). We determined the energies to be 6224.5±0.4(stat)±0.2(syst) eV and 6463.7±0.3(stat)±0.1(syst) eV, and widths to be 2.5±1.0(stat)±0.4(syst) eV and 1.0±0.6(stat)±0.3(stat) eV, for kaonic ^{3}He and ^{4}He, respectively. These values are nearly 10 times more precise than in previous measurements. Our results exclude the large strong-interaction shifts and widths that are suggested by a coupled-channel approach and agree with calculations based on optical-potential models.

Association between Decreased Social Participation and Depressive Symptom Onset among Community-Dwelling Older Adults: A Longitudinal Study during the COVID-19 Pandemic.

OBJECTIVES: The coronavirus disease (COVID-19) pandemic has imposed restrictions on people's social behavior. However, there is limited evidence regarding the relationship between changes in social participation and depressive symptom onset among older adults during the pandemic. We examined the association between changes in social participation and the onset of depressive symptoms among community-dwelling older adults during the COVID-19 pandemic. DESIGN: This was a longitudinal study. SETTING: Communities in Minokamo City, a semi-urban area in Japan. PARTICIPANTS: We recruited community-dwelling older adults aged ≥ 65 years using random sampling. Participants completed a questionnaire survey at baseline (March 2020) and follow-up (October 2020). MEASUREMENTS: Depressive symptoms were assessed using the Two-Question Screen. Based on their social participation status in March and October 2020, participants were classified into four groups: "continued participation," "decreased participation," "increased participation," and "consistent non-participation." RESULTS: A total of 597 older adults without depressive symptoms at baseline were analyzed (mean age = 79.8 years; 50.4% females). Depressive symptoms occurred in 20.1% of the participants during the observation period. Multivariable Poisson regression analysis showed that decreased social participation was significantly associated with the onset of the depressive symptoms, compared to continued participation, after adjusting for all covariates (incidence rate ratio = 1.59, 95% confidence interval = 1.01-2.50, p = 0.045). CONCLUSION: Older adults with decreased social participation during the COVID-19 pandemic demonstrated a high risk of developing depressive symptoms. We recommend that resuming community activities and promoting the participation of older adults, with sufficient consideration for infection prevention, are needed to maintain mental health among older adults.

Autophagy and glycolysis independently attenuate silibinin-induced apoptosis in human hepatocarcinoma HepG2 and Hep3B cells.

PURPOSE: The mechanism of cytotoxicity of silibinin on two human hepatocellular carcinoma (HCC) cell lines, HepG2 (p53 wild-type) and Hep3B cells (p53 null), is examined in relation with the induction of autophagy and phosphorylation of AMP-activated protein kinase (p-AMPK). MATERIALS AND METHODS: Levels of apoptosis in relation to the levels of autophagy and those of glycolysis-related proteins, glucose transporter 1/4 (Glut1/4) and hexokinase-II (HK2), in HepG2 and Hep3B cells were examined. RESULTS: Silibinin-induced apoptosis was incomplete for HCC cell death in that up-regulated autophagy and/or reduced level of glycolysis, which are induced by silibinin treatment, antagonized silibinin-induced apoptosis. Inhibition of autophagy with 3-methyl adenine (3MA) or blocking of AMP-activated protein kinase (AMPK) activation with Compound C (CC) enhanced silibinin-induced apoptosis. The results confirm that AMPK involved in autophagy as well as in glycolysis remaining with silibinin is responsible for attenuation of silibinin-induced apoptosis. Blocking of AMPK or autophagy contributes to the enhancement of silibinin's cytotoxicity to HepG2 and Hep3B cells. CONCLUSION: This study shows that incomplete apoptosis of HCC by silibinin treatment becomes complete by repression of autophagy and/or glycolysis.

[Descemet membrane endothelial keratoplasty (DMEK) for graft failure after penetrating keratoplasty and in vascularized high-risk eyes]. / "Descemet membrane endothelial keratoplasty" (DMEK) bei Transplantatversagen nach perforierender Keratoplastik und in vaskularisierten Hochrisikoaugen.

BACKGROUND: Descemet membrane endothelial keratoplasty (DMEK) is considered the gold standard for the treatment of corneal endothelial dysfunction and generally leads to good postoperative results. Recently, studies have also analyzed the outcome of DMEK in so-called high-risk eyes. MATERIAL AND METHODS: The relevant literature and own data on DMEK for graft failure after penetrating keratoplasty and in vascularized high-risk eyes are presented and discussed. RESULTS: A DMEK for the treatment of transplant failure after penetrating keratoplasty can be considered for eyes without stromal scars and without high astigmatism. A retrospective analysis of 52 patients with failed penetrating grafts showed that DMEK leads to a significant increase in visual acuity, albeit to a lesser extent than after primary DMEK. Rejection and transplant failure rates seem to be similar those seen after penetrating re-keratoplasty and are thus higher than after primary DMEK. A DMEK might also be a feasible option for eyes with corneal neovascularization and stromal edema without stromal scars. A retrospective analysis of 24 eyes with at least 2 vascularized corneal quadrants demonstrated that DMEK leads to a significant improvement in visual acuity and regression of corneal neovascularization. The rejection rate in this cohort was 4.2% and is therefore slightly higher than after low-risk DMEK in eyes without corneal neovascularization but still much better compared to penetrating keratoplasty. CONCLUSION: Indications for DMEK are expanding and it can be a therapeutic option for transplant failure after penetrating keratoplasty with acceptable outcomes. Furthermore, DMEK seems to be a good option for the treatment of endothelial dysfunction in vascularized high-risk eyes without stromal scars.

Lymph node dissection for gastric cancer: Establishment of D2 and the current position of splenectomy in Europe and Japan.

Two European phase III trials comparing D1 and D2 demonstrated that D2 did not improve the overall survival and was associated with a high mortality related to splenectomy. However, a long-term follow-up study showed that the gastric cancer-related death rate was significantly higher in D1 than D2. Based on these findings, the standard surgery in Europe became D2 without pancreatico-splenectomy to prevent mortality. In contrast, the JCOG9501 phase III comparing D2 and D2 plus para-aortic nodal dissection did not showed a survival efficacy of extended lymphadenectomy, but the mortality rate was quite low in both surgeries. Subsequently, the JCOG0110 phase III study comparing D2 and spleen-preserving D2 for upper gastric cancer not invading the greater curvature clearly showed the non-inferiority of spleen preservation. Thus, spleen-preserving D2 was made the standard surgery for these tumors in Japan. However, splenectomy is often selected for complete dissection of the splenic-hilar nodes, a frequent metastatic site for upper gastric tumors invading the greater curvature. Recently, an approach involving splenic hilar nodal dissection without splenectomy has been developed.

Genetic characterization of Shigatoxigenic and enteropathogenic Escherichia coli O80:H2 from diarrhoeic and septicaemic calves and relatedness to human Shigatoxigenic E. coli O80:H2.

AIM: The purpose of this work was to identify and genetically characterize enterohemorrhagic Escherichia coli (EHEC) and enteropathogenic E. coli (EPEC) O80:H2 from diarrhoeic and septicaemic calves in Belgium and to comparing them with human EHEC after whole genome sequencing. METHODS AND RESULTS: Ten EHEC and 21 EPEC O80 identified by PCR between 2009 and 2018 from faeces, intestinal content and a kidney of diarrhoeic or septicaemic calves were genome sequenced and compared to 19 human EHEC identified between 2008 and 2019. They all belonged to the O80:H2 serotype and ST301, harboured the eaeξ gene, and 23 of the 29 EHEC contained the stx2d gene. Phylogenetically, they were distributed in two major sub-lineages: one comprised a majority of bovine EPEC whereas the second one comprised a majority of stx2d bovine and human EHEC. CONCLUSIONS: Not only EPEC but also EHEC O80:H2 are present in diarrhoeic and septicaemic calves in Belgium and are genetically related to human EHEC. SIGNIFICANCE AND IMPACT OF THE STUDY: These findings support the need to assess cattle as potential source of contamination of humans by EHEC O80:H2 and to understand the evolution of bovine and human EHEC and EPEC O80:H2.

Long-term outcomes and recurrence-free interval after the treatment of keloids with a standardized protocol.

BACKGROUND: Recurrence rates of keloids have generally been reported at one time point. However, the longer the duration after treatment, the greater the likelihood that such lesions will recur. In this study, we analysed the time to recurrence during long-term follow-up. MATERIAL AND METHODS: We retrospectively reviewed recurrence-free interval in 52 patients with keloid (age 8-79 years) who had been treated between June 2006 and January 2011 using a standardised protocol developed by our group. RESULTS: Mean duration of follow-up was 37.5 (range, 7-120) months in patients with keloid. Kaplan-Meier survival curves revealed a statistically significant difference in recurrence-free interval between ear keloids and keloids excluding ear keloids. Recurrence rate for keloids was high in the first 2 years after treatment. CONCLUSIONS: Kaplan-Meier analysis was useful for understanding the tendency of recurrence of keloids after treatment using a standardised protocol.

Anti-PD1 checkpoint inhibitor therapy in acral melanoma: a multicenter study of 193 Japanese patients.

BACKGROUND: Acral melanoma (AM) is an epidemiologically and molecularly distinct entity that is underrepresented in clinical trials on immunotherapy in melanoma. We aimed to analyze the efficacy of anti-programmed cell death 1 (anti-PD-1) antibodies in advanced AM. PATIENTS AND METHODS: We retrospectively evaluated unresectable stage III or stage IV AM patients treated with an anti-PD-1 antibody in any line at 21 Japanese institutions between 2014 and 2018. The clinicobiologic characteristics, objective response rate (ORR, RECIST), survival estimated using Kaplan-Meier analysis, and toxicity (Common Terminology Criteria for Adverse Events 4.0.) were analyzed to estimate the efficacy of the anti-PD-1 antibodies. RESULTS: In total, 193 patients (nail apparatus, 70; palm and sole, 123) were included in the study. Anti-PD-1 antibody was used as first-line therapy in 143 patients (74.1%). Baseline lactate dehydrogenase (LDH) was within the normal concentration in 102 patients (52.8%). The ORR of all patients was 16.6% (complete response, 3.1%; partial response, 13.5%), and the median overall survival (OS) was 18.1 months. Normal LDH concentrations showed a significantly stronger association with better OS than abnormal concentrations (median OS 24.9 versus 10.7 months; P < 0.001). Although baseline characteristics were similar between the nail apparatus and the palm and sole groups, ORR was significantly lower in the nail apparatus group [6/70 patients (8.6%) versus 26/123 patients (21.1%); P = 0.026]. Moreover, the median OS in this group was significantly poorer (12.8 versus 22.3 months; P = 0.03). CONCLUSIONS: Anti-PD-1 antibodies have limited efficacy in AM patients. Notably, patients with nail apparatus melanoma had poorer response and survival, making nail apparatus melanoma a strong candidate for further research on the efficacy of novel combination therapies with immune checkpoint inhibitors.

Combined Impact of Physical Frailty and Social Isolation on Rate of Falls in Older Adults.

OBJECTIVES: The aim of this study was to examine the impact of the combination of physical frailty and social isolation on falling in community-dwelling older adults. DESIGN: A cross-sectional study of data obtained at registration in a randomized control trial. SETTING: Community-based study of participants recruited from Toyota, Japan. PARTICIPANTS: 380 community-dwelling older adults (47.9% women, mean age = 72.3 ± 4.6 years). MEASUREMENTS: Participants were categorized as non-frail or pre-frail/frail based on the Fried frailty criteria (slowness, weakness, exhaustion, low activity, and weight loss). Social isolation was examined using the Lubben Social Network Scale (LSNS-6), and scores lower than 12 points indicated social isolation. Participants were divided into four groups depending on pre-frail/frail status and social isolation, and experiences of multiple falls over the past year were compared between the groups. RESULTS: Participants were classified into robust (n = 193), physical frailty (PF; n = 108), social isolation (SI; n = 43), and PF with SI (PF+SI; n = 36) groups. A total of 38 (10.0%) participants reported multiple falls. Logistic regression analysis showed that PF and SI groups were not independently associated with falling (PF: OR 1.64, 95% CI 0.65-4.16, SI: OR 2.25, 95% CI 0.77-6.58), while PF+SI group was significantly associated with falling compared with the robust group (OR 3.06, 95% CI 1.00-9.34, p = 0.049) after controlling for confounding factors. CONCLUSION: Our findings support the assertion that coexistence with physical frailty and social isolation were associated with falling in the older adults.

Quantum Criticality inside the Anomalous Metallic State of a Disordered Superconducting Thin Film.

The field-induced superconductor-insulator transition (SIT) in two-dimensional (2D) systems is a famous example of a quantum phase transition. However, an emergence of an anomalous metallic state induced by field has been a long-standing problem in 2D superconductors. While theories predicted that the emergence is attributed to strong phase fluctuations of the superconducting order parameter due to quantum fluctuations, usual resistance measurements have not probed them directly. Here, using Nernst effect measurements, we uncover superconducting fluctuations in the vicinity of the field-induced metallic state in an amorphous Mo_{x}Ge_{1-x} thin film. The field range where the vortex Nernst signals are detectable remains nonzero toward zero temperature, and it locates inside the metallic state defined by the magnetoresistance, indicating that the metallic state results from quantum vortex liquid (QVL) with phase fluctuations due to quantum fluctuations. Slow decay of transport entropy of vortices in the QVL with decreasing temperature suggests that the metallic state originates from broadening of a quantum critical point in SIT.

Energy of the

The low-lying isomeric state of ^{229}Th provides unique opportunities for high-resolution laser spectroscopy of the atomic nucleus. We determine the energy of this isomeric state by taking the absolute energy difference between the excitation energy required to populate the 29.2-keV state from the ground state and the energy emitted in its decay to the isomeric excited state. A transition-edge sensor microcalorimeter was used to measure the absolute energy of the 29.2-keV γ ray. Together with the cross-band transition energy (29.2 keV→ground) and the branching ratio of the 29.2-keV state measured in a recent study, the isomer energy was determined to be 8.30±0.92 eV. Our result is in agreement with the latest measurements based on different experimental techniques, which further confirms that the isomeric state of ^{229}Th is in the laser-accessible vacuum ultraviolet range.

Development of QSAAR and QAAR models for predicting fish early-life stage toxicity with a focus on industrial chemicals.

We developed models for predicting fish early-life stage (ELS) toxicities oriented to industrial chemicals. The training set was constructed without data from the Office of Pesticide Programs Pesticide Ecotoxicity Database, the main source for the pesticide-biased training set used in our previous work (SAR QSAR Environ. Res. 29:9, 725-742). In addition to the descriptors from the previous study, we also used water solubility to develop the new models, which were evaluated against the test set used in our previous study so that we could focus on the effects of the different training set and the additional descriptor. The statistics for the new models were hardly better than those for the previous models, which suggests, contrary to our expectations, that pesticide-biased data can successfully be used to develop models for predicting the fish ELS toxicities oriented to industrial chemicals. Acute Daphnia magna toxicity was important for the predictive QSAARs in both studies. A distance-based method for defining the applicability domains indicated that water solubility was a key indicator for detecting underestimated chemicals. The comparison of fish ELS toxicities for chemicals presented in different literatures revealed the uncertainty of the experimental data, which may lead to the low predictivity.

Correction: Signal peptidase complex 18, encoded by SEC11A, contributes to progression via TGF-α secretion in gastric cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.