Elevated Expression of CCN3 in Articular Cartilage Induces Osteoarthritis in Hip Joints Irrespective of Age and Weight Bearing.

Osteoarthritis (OA) occurs not only in the knee but also in peripheral joints throughout the whole body. Previously, we have shown that the expression of cellular communication network factor 3 (CCN3), a matricellular protein, increases with age in knee articular cartilage, and the misexpression of CCN3 in cartilage induces senescence-associated secretory phenotype (SASP) factors, indicating that CCN3 promotes cartilage senescence. Here, we investigated the correlation between CCN3 expression and OA degenerative changes, principally in human femoral head cartilage. Human femoral heads obtained from patients who received total hip arthroplasty were categorized into OA and femoral neck fracture (normal) groups without significant age differences. Gene expression analysis of RNA obtained from femoral head cartilage revealed that CCN3 and MMP-13 expression in the non-weight-bearing part was significantly higher in the OA group than in the normal group, whereas the weight-bearing OA parts and normal cartilage showed no significant differences in the expression of these genes. The expression of COL10A1, however, was significantly higher in weight-bearing OA parts compared with normal weight-bearing parts, and was also higher in weight-bearing parts compared with non-weight-bearing parts in the OA group. In contrast, OA primary chondrocytes from weight-bearing parts showed higher expression of CCN3, p16, ADAMTS4, and IL-1ß than chondrocytes from the corresponding normal group, and higher ADAMTS4 and IL-1ß in the non-weight-bearing part compared with the corresponding normal group. Acan expression was significantly lower in the non-weight-bearing group in OA primary chondrocytes than in the corresponding normal chondrocytes. The expression level of CCN3 did not show significant differences between the weight-bearing part and non-weight-bearing part in both OA and normal primary chondrocytes. Immunohistochemical analysis showed accumulated CCN3 and aggrecan neoepitope staining in both the weight-bearing part and non-weight-bearing part in the OA group compared with the normal group. The CCN3 expression level in cartilage had a positive correlation with the Mankin score. X-ray analysis of cartilage-specific CCN3 overexpression mice (Tg) revealed deformation of the femoral and humeral head in the early stage, and immunohistochemical analysis showed accumulated aggrecan neoepitope staining as well as CCN3 staining and the roughening of the joint surface in Tg femoral and humeral heads. Primary chondrocytes from the Tg femoral head showed enhanced expression of Ccn3, Adamts5, p16, Il-6, and Tnfα, and decreased expression of Col2a1 and -an. These findings indicate a correlation between OA degenerative changes and the expression of CCN3, irrespective of age and mechanical loading. Furthermore, the Mankin score indicates that the expression level of Ccn3 correlates with the progression of OA.

Osimertinib-Associated Toxic Epidermal Necrolysis in a Lung Cancer Patient Harboring an EGFR Mutation-A Case Report and a Review of the Literature.

Toxic epidermal necrolysis (TEN) and Stevens-Johnson syndrome (SJS) are life-threatening dermatologic adverse events in the same category, caused by a delayed-type drug hypersensitivity reaction. Although skin toxicity is common during treatment with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), osimertinib-associated TEN is quite rare-thus far, only one report has been published from China. We report a case of an 80-year-old Japanese woman with lung adenocarcinoma harboring an EGFR-sensitizing mutation who was treated with osimertinib as the first-line treatment. Forty-six days after osimertinib induction, diffuse erythematous rash rapidly spread over the patient's trunk along with vesicles and purpuric macules; furthermore, she developed targetoid erythema on the face. Despite osimertinib discontinuation and corticosteroid treatment, diffuse erythema with Nikolsky's sign, general epidermal detachment, erosion and loose blisters developed over her entire body including the face. Based on her symptoms, TEN was diagnosed and thus, intravenous immunoglobulin was immediately administered for 4 days. The treatment ameliorated TEN-associated skin toxicity and caused epithelialization. Reports on osimertinib-associated SJS/TEN are scarce and only one report each on SJS and TEN from China is available. This is the first report of osimertinib-associated TEN from Japan. Cases of EGFR-TKI-associated SJS/TEN have been reported predominantly from Asian countries, suggesting ethnicity and genetic linkage play a role in the underlying mechanism.

A single-round selection of selective DNA aptamers for mammalian cells by polymer-enhanced capillary transient isotachophoresis.

A single-round DNA aptamer selection for mammalian cells was successfully achieved for the first time using a capillary electrophoresis (CE)-based methodology called polymer-enhanced capillary transient isotachophoresis (PectI). The PectI separation yielded a single peak for the human lung cancer cell line (PC-9) complexed with DNA aptamer candidates, which was effectively separated from a free randomized DNA library peak, ensuring no contamination from free DNA in the PC-9-DNA aptamer complex fraction. The DNA aptamer candidates obtained after a single-round selection employing counter selection with HL-60 were proven to bind selectively and form kinetically stable complexes with PC-9 cells. Interestingly, most aptamer candidates showed high binding ability (Kd = 70-350 nM) with different extents of binding on the cell surface. These facts proved that a single-round selection for mammalian cells by PectI is feasible to obtain various types of aptamer candidates, which have high-affinity even for non-overexpressed but unique targets on the cell surface in addition to overexpressed targets.

Determination of 90Sr in highly radioactive aqueous samples via conversion to a kinetically stable 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid complex followed by concentration-separation-fractionation based on capillary electrophoresis-liquid scintillation.

BACKGROUND: The Fukushima Daiichi Nuclear Power Plant accident (2011) released large amounts of radioactive substances into the environment and generated highly radioactive debris. Post-accident countermeasures are currently in the phase of fuel debris removal, which requires the analysis of radioactive contaminants in the environment and fuel. The spectra of solely ß-emitting nuclides, such as 90Sr, overlap; thus, an effective method for nuclide separation is desired. Since conventional methods for high-dose sample analysis pose substantial exposure risks and generate large amounts of secondary radioactive waste, faster procedures allowing for decreased radiation emission are highly desirable. RESULTS: In this study, we developed a 90Sr2+ quantitation technique based on liquid scintillation counting (LSC)-coupled capillary transient isotachophoresis (ctITP), along with two-point detection and relying on the rapid concentration, separation, and fractionation of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-complexed 90Sr2+ in a single run. The applicability of our method for the analysis of real-world samples was verified by conducting addition-recovery experiments using a seawater reference material and radioactive liquid waste obtained from the radioactive waste treatment facility at the Japan Atomic Energy Agency. The recovery determined by LSC was 95-113%, indicating successful quantitative analysis. 90Sr recovery was determined to be 90.1% from a contaminated water sample obtained from the Fukushima Daiichi Nuclear Power Plant, which was analyzed using the standard addition of 90Sr. The sensitivity (detection limit = 0.016 Bq) of the proposed method on a radioactivity basis was equal to or higher than that of the conventional method using ion exchange-LSC (0.012-0.07 Bq). SIGNIFICANCE AND NOVELTY: Our method allows for the handling of high-dose radioactive samples at the microliter level and is substantially faster than conventional ion exchange protocols, whereas ctITP has not been used for practical applications due to inaccurate collection and lack of a suitable chemical system. The concentration-separation-fractionation protocol in ctITP is successful due to the existence of a rare inert Sr2+ complex and precise fractionation. This study establishes a pathway toward safer and more practical analysis of radionuclides.

Early responders within seven days of dupilumab treatment for severe asthma evaluated by patient-reported outcome: a pilot study.

BACKGROUND: The management of severe asthma-associated symptoms is essential since they are distressing to the affected patients, and also greatly impair their quality of life. Dupilumab, a monoclonal antibody, blocks interleukin (IL)-4 and IL-13 signaling, both of which are crucial in acquired and innate immunity pathways through fast signal transduction, leading to an early response to treatment. Although rapid improvement within 1-3 days after dupilumab treatment was observed in moderate-to-severe atopic dermatitis, an early response within 7 days of dupilumab treatment in severe asthma has not been reported. METHODS: Twelve consecutive patients with severe asthma who were newly treated with dupilumab between July 2019 and April 2020 were retrospectively investigated. We evaluated the early response (within 7 days) of patients with severe asthma receiving dupilumab therapy. Asthma control test (ACT) and the daily ACT, which was modified from the ACT to evaluate daily symptoms associated with asthma, were adopted as patient-reported outcomes (PROs) at week 8 and within 7 days, respectively. Patients were stratified into early responders (7 days), late responders (week 8), and non-responders without significant improvement in PROs. Descriptive statistics were adopted due to the limited number of patients. RESULTS: Four of these 12 patients were early responders, with the following baseline characteristics: body mass index, <25 kg/m2; without depression; baseline forced expiratory volume in 1 second, <1.50 L; and more than one exacerbation in 1 year. On the other hand, five were late responders, and 44.4% of the nine responders were early responders. The higher the eosinophilic count and/or FeNO did not show any relationship between the early responder and nonresponder. CONCLUSIONS: The effect of dupilumab on severe asthma in patients with atopic features could be started earlier than 2 weeks, similar to atopic dermatitis. Daily ACT may be useful in monitoring the early efficacy of dupilumab in treating severe asthma.

Predictors of survival among Japanese patients receiving first-line chemoimmunotherapy for advanced non-small cell lung cancer.

BACKGROUND: First-line chemoimmunotherapy (CIT) has improved overall survival (OS) and progression-free survival (PFS) outcomes among patients with non-small cell lung cancer (NSCLC). The immunological and nutritional statuses of patients fluctuate during treatment using immune checkpoint inhibitors, and are closely related to treatment outcomes. However, it is unclear whether these markers are significant in patients who are receiving CIT. METHODS: This retrospective single-center study evaluated 34 consecutive Japanese patients with NSCLC who were treated using first-line CIT. Previously reported markers that reflect immunological and nutritional statuses were evaluated at three time points: at the start of CIT, after three weeks, and at the end of induction therapy. RESULTS: The median PFS was 7.2 months (95% confidence interval: 6.3 months-not reached) and the median OS was not reached (95% confidence interval: 9.6 months-not reached). The PFS duration was significantly associated with the baseline neutrophil-to-lymphocyte ratio and the three-week values for the modified Glasgow prognostic score, C-reactive protein-albumin ratio, prognostic nutrition index, and advanced lung cancer inflammation index. The OS duration was significantly associated with the pre-treatment values for the neutrophil-to-lymphocyte ratio and advanced lung cancer inflammation index, as well as the prognostic nutrition index at the end of induction therapy. CONCLUSIONS: Immunological and nutritional markers could be useful for predicting the outcomes of CIT for Japanese patients with advanced non-small cell lung cancer. The timing of their evaluation may also be important. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Overall survival in patients receiving first-line chemoimmunotherapy for advanced lung cancer were associated with pretreatment values of neutrophil-to-lymphocyte ratio, advanced lung cancer inflammation index, and the prognostic nutrition index at the end of induction therapy. WHAT THIS STUDY ADDS: Repetitive evaluation of immunological and nutritional markers may be useful for guiding prognostication and treatment selection for Japanese patients with advanced lung cancer.

Association between habitual coffee consumption and normal or increased estimated glomerular filtration rate in apparently healthy adults.

Habitual coffee consumption is associated with the prevention of type 2 diabetes, which often accompanies diabetic nephropathy. However, the relationship between coffee consumption and kidney function is unclear. Therefore, we investigated the associations between habitual coffee consumption and kidney function and damage assessed by the estimated glomerular filtration rate (eGFR) and proteinuria using dipstick urinalysis, respectively, in a cross-sectional study of 342 apparently healthy adults. Habitual coffee consumption was defined as drinking one or more cups of coffee per d. eGFR in coffee consumers (n 182; 80.1 (sd 15.0) ml/min per 1.73 m(2)) was significantly higher than that in non-coffee consumers (n 160; 76.9 (sd 12.6) ml/min per 1.73 m(2)) (P < 0.05). Multivariate logistic analysis showed that, compared with non-coffee consumption, coffee consumption was significantly associated with normal or increased eGFR (NIGFR) ( >or= 90 ml/min per 1.73 m(2)), but not proteinuria, which was not attenuated, even after adjustment for age, sex, smoking, tea consumption and other cardiovascular risks (OR 2.91; 95 % CI 1.51, 5.61; P = 0.001). When we took into account eGFR measured 1 year before in a subgroup of the subjects (n 262), coffee consumption (n 142) had a significant relationship with eGFR, which was consistently higher with a difference of 4.0 ml/min per 1.73 m(2) compared with non-coffee consumption (P = 0.01; two-way repeated ANOVA). Similar associations were observed in both sexes when data were reanalysed according to sex. In conclusion, our findings suggest that habitual coffee consumption is associated with NIGFR independently of clinical confounders. Further studies are needed to confirm this association and to explore whether the effect of coffee consumption on eGFR is beneficial for the kidney.

Bioconversion From Docosahexaenoic Acid to Eicosapentaenoic Acid in the Marine Bacterium Shewanella livingstonensis Ac10.

Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which belong to the same class of long chain ω-3 polyunsaturated fatty acids (PUFAs), are present in marine γ-proteobacteria. In contrast to their de novo biosynthesis that has been intensively studied, their metabolic fates remain largely unknown. Detailed information regarding bacterial ω-3 PUFA metabolism would be beneficial for understanding the physiological roles of EPA/DHA as well as the industrial production of EPA, DHA, and other PUFAs. Our previous studies revealed that the EPA-producing marine bacterium Shewanella livingstonensis Ac10 produces EPA from exogenous DHA independently of de novo EPA biosynthesis, indicating the presence of an unidentified metabolic pathway that converts DHA into EPA. In this study, we attempted to reveal the molecular basis for the bioconversion through both in vivo and in vitro analyses. Mutagenesis experiments showed that the gene disruption of fadH, which encodes an auxiliary ß-oxidation enzyme 2,4-dienoyl-CoA reductase, impaired EPA production under DHA-supplemented conditions, and the estimated conversion rate decreased by 86% compared to that of the parent strain. We also found that the recombinant FadH had reductase activity toward the 2,4-dienoyl-CoA derivative of DHA, whereas the intermediate did not undergo ß-oxidation in the absence of the FadH protein. These results indicate that a typical ß-oxidation pathway is responsible for the conversion. Furthermore, we assessed whether DHA can act as a substitute for EPA by using an EPA-less and conversion-deficient mutant. The cold-sensitive phenotype of the mutant, which is caused by the lack of EPA, was suppressed by supplementation with EPA, whereas the DHA-supplementation suppressed it to a lesser extent. Therefore, DHA can partly substitute for, but is not biologically equivalent to, EPA in S. livingstonensis Ac10.

Vogt-Koyanagi-Harada disease during chemoimmunotherapy for non-small cell lung cancer.

Vogt-Koyanagi-Harada disease (VKHD) is a rare systemic granulomatous autoimmune disease that affects melanocyte-rich organs such as eye, inner ear, meninges, skin, and hair. VKHD leads to chronic uveal inflammation accompanied by a decline in visual acuity in some patients when appropriate corticosteroid treatment was not initiated in an early phase. Immune checkpoint inhibitors (ICIs) are widely used in the treatment of several kinds of cancers and chemoimmunotherapy has become the standard of care in the first-line treatment of non-small cell lung cancer (NSCLC). While ICIs induce immune-related adverse events, drug-induced VKHD is quite rare with only four reports in the ICI monotherapy; three patients with melanoma and one patient with NSCLC. We describe the first case of VKHD during chemoimmunotherapy including pembrolizumab in a patient with NSCLC, which was successfully treated with corticosteroid without any sequela.

Improvement in Subjective Symptoms and Tolerability in Response to Nintedanib Treatment in Elderly Patients with Idiopathic Pulmonary Fibrosis.

The efficacy of nintedanib treatment in patients with idiopathic pulmonary fibrosis (IPF) was demonstrated in phase III trials. However, there is limited data on the significance of nintedanib in elderly patients aged ≥75 years. We have retrospectively evaluated 54 newly nintedanib-treated patients including 32 elderly individuals. Potential changes in modified medical research council (mMRC) grade and COPD (chronic obstructive pulmonary disease) assessment test (CAT) score, as well as in forced vital capacity (FVC) were obtained 6 months before, at the time of, and 6 and 12 months after initiation of nintedanib treatment. Significant differences were observed in CAT scores between 6 months before treatment and baseline (p < 0.001), and between baseline and 6 months (p < 0.001) and 12 months (p < 0.001) after treatment. If subjective improvement is defined as an improvement in mMRC grade or CAT score by 1 or 3 points, respectively, 25 patients (46.3%) have significantly improved after 6 months of treatment. Out of these, all have improved in CAT score. The tolerability of nintedanib was similar in elderly and younger patients. These findings suggest that CAT scores could be useful in the subjective assessment during nintedanib treatment, and that nintedanib is safe and efficient for the treatment of the elderly population.

Drug-induced interstitial lung disease associated with dasatinib coinciding with active tuberculosis.

A 69-year-old woman was diagnosed with a breakpoint cluster region-Abelson-positive chronic myeloid leukaemia and treated with dasatinib for 14 months. She presented with one month of high-grade fever and persistent dry cough. Chest computed tomography revealed non-segmental subpleural consolidation, ground-glass opacities, and interlobular septal thickening. The bronchoalveolar lavage (BAL) and transbronchial lung biopsy confirmed a diagnosis of drug-induced interstitial lung disease (ILD) associated with dasatinib. Then, systemic corticosteroid treatment was initiated, which was effective and the interstitial shadow disappeared after two weeks. The acid-fast bacilli culture test of BAL fluid after three weeks was positive for Mycobacterium tuberculosis, and combination therapy with four antituberculosis drugs was added. It is known that drug-induced ILD and susceptibility to infection associated with dasatinib occur in a dose-dependent manner. This is the first case of dasatinib-induced ILD which coincided with active tuberculosis.

IgG4-related lung disease progressing to respiratory failure.

Immunoglobulin G4 (IgG4)-related disease (IgG4-RD) is a systemic immune-mediated, fibroinflammatory disorder categorized as proliferative or fibrotic depending on the responsiveness of corticosteroid treatment. IgG4-related lung disease (IgG4-RLD) accounts for 13-14% of IgG4-RD cases, but respiratory failure is quite rare. A 71-year-old man diagnosed with interstitial lung disease was referred to our department after a 10-month observational period. He presented with respiratory failure at the first visit, with significant elevations in serum IgG4 levels and histopathological findings meeting the criteria of IgG4-positive plasma cells and IgG4/IgG-positive plasma cell ratio in transbronchial lung biopsy and inguinal lymph node biopsy, resulting in a diagnosis of IgG4-RD. Systemic corticosteroid treatment promptly ameliorated the respiratory failure. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography showed significant FDG accumulation in the lung fields, indicating the proliferative and reversible status of IgG4-RLD, which responded well to corticosteroid treatment. The patient recovered from respiratory failure even after a 10-month observational period.

Atezolizumab in combination with carboplatin and etoposide for heavily treated small cell lung cancer.

Atezolizumab was the first immune checkpoint inhibitor (ICI) to be introduced as a first-line treatment option for extensive-stage small cell lung cancer (ES-SCLC), in combination with carboplatin and etoposide (CE) chemotherapy. However, SCLC treatment options after progression to first-line chemotherapy are limited, warranting the readministration of previously used drugs. In combination with atezolizumab, CE readministration may theoretically be effective, based on two tentative mechanisms: its additive and synergistic effects on cytotoxic chemotherapy. The additive effect is based on the IFCT-1603 trial in which the Kaplan-Meier estimates of both progression-free survival (PFS) and overall survival (OS) in the atezolizumab group exhibited a tail plateau in the selected population. Conversely, an anti-PD-L1 antibody synergistic effect on platinum compounds was assessed in a preclinical study, which was reinforced by clinical data. Thus, atezolizumab in combination with CE may be a treatment option in heavily treated patients. Here, we describe the first case of a heavily treated ES-SCLC patient treated with chemoimmunotherapy, resulting in a partial response and a durable PFS. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY AND WHAT THIS STUDY ADDS: CE readministration with atezolizumab may be effective based on two tentative mechanisms. Additive and synergistic effects of atezolizumab on CE have been previously suggested via a clinical trial and preclinical study, respectively. This is reflected in the current case in clinical settings.

Significance of inflammatory indexes in atezolizumab monotherapy outcomes in previously treated non-small-cell lung cancer patients.

Cancer immunotherapy, including atezolizumab monotherapy, is a promising alternative strategy for patients with advanced non-small-cell lung cancer (NSCLC). Several inflammatory indices have been reported as potential biomarkers regarding the effectiveness of various treatments. This study aimed to analyze the efficacy of atezolizumab monotherapy using baseline inflammatory markers in NSCLC patients. We retrospectively enrolled 81 NSCLC patients who received atezolizumab monotherapy at six different medical institutions in Japan. The Cox proportional hazards model was used to assess the impact of the clinical variables, including inflammatory indexes, on clinical outcomes. Median progression-free survival (PFS) and overall survival (OS) were 60 days and 252 days, respectively. The objective response rate was 7.4%, and the disease control rate was 54.3%. Patients with high neutrophil to lymphocyte ratio (NLR), low lymphocyte to monocyte ratio (LMR), and/or high platelet to lymphocyte ratio (PLR), at baseline, demonstrated substantially shorter PFS and OS compared to those with a low NLR, high LMR, and/or low PLR. The multivariate analysis demonstrated that a high baseline NLR was substantially associated with short PFS and short OS. Our retrospective observations suggest that inflammatory indices may be a potential negative prognostic factor of atezolizumab monotherapy outcomes in NSCLC patients.

Clinical Characteristics of Osimertinib Responder in Non-Small Cell Lung Cancer Patients with EGFR-T790M Mutation.

Osimertinib is a mutant-selective EGFR inhibitor that is effective against non-small cell lung cancer (NSCLC) in patients with the EGFR-T790M mutation, who are resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, the factors affecting response to osimertinib treatment are unknown. In this retrospective study, 27 NSCLC patients with the EGFR-T790M mutation were enrolled at five institutions in Japan. Among several parameters tested, the progression-free survival (PFS) associated with the initial EGFR-TKIs was positively correlated with the PFS after osimertinib treatment (p = 0.021). The median PFS following osimertinib treatment and the overall survival (OS) were longer in patients who responded to osimertinib than in those who did not (17.7 months versus 3.5 months, p = 0.009 and 24.2 months versus 13.5 months, p = 0.021, respectively). A multivariate analysis demonstrated that the PFS with initial EGFR-TKIs was significantly related to the PFS with osimertinib treatment (p = 0.035), whereas osimertinib response was significantly related to the PFS and OS with osimertinib treatment (p = 0.016 and p = 0.006, respectively). Our retrospective observations indicate that PFS following the initial EGFR-TKI treatment and the response rate to osimertinib might be promising predictors for effective osimertinib treatment in NSCLC patients with the EGFR-T790M mutation.

Retrospective efficacy analysis of immune checkpoint inhibitors in patients with EGFR-mutated non-small cell lung cancer.

BACKGROUND: Treatment with epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) leads to initial response in most patients with EGFR-mutated non-small cell lung cancer (NSCLC). In contrast, little is known of the subpopulation of patients with NSCLC with EGFR mutations who exhibit clinical outcomes that require treatment with immune checkpoint inhibitors (ICIs). Therefore, to identify eligible cases to treat with ICIs, we retrospectively analyzed the correlation between clinical features and the efficacy of ICIs in patients with EGFR mutations. PATIENTS AND METHODS: We retrospectively analyzed patients with advanced NSCLC harboring EGFR mutations who were treated with ICIs after developing resistance to EGFR-TKIs between February 2016 and April 2018 at 6 institutions in Japan. The association between clinical outcomes and the efficacy of ICIs was investigated. RESULTS: We enrolled 27 patients who harbored EGFR-activating mutations. The objective response and disease control rates were higher in patients with uncommon EGFR mutations than in those with common EGFR mutations (71% vs 35.7% and 57% vs 7%, P = 0.14 and P < 0.01, respectively). Patients with uncommon EGFR mutations or without T790M mutations exhibited a significantly longer median progression-free survival than those with common EGFR mutations or with T790M mutations (P = 0.003 and P = 0.03, respectively). CONCLUSION: Patients with uncommon EGFR mutations and without T790M mutations are associated with the best outcomes for treatment with immunotherapy among those with EGFR-mutated NSCLC, based on retrospective analysis. Further research is needed to validate the clinical biomarkers involved in ICI responders with EGFR mutations.

Cerebral Salt-wasting Syndrome and Inappropriate Antidiuretic Hormone Syndrome after Subarachnoid Hemorrhaging.

Hyponatremia is a common finding after subarachnoid hemorrhaging (SAH) and can be caused by either cerebral salt-wasting syndrome (CSWS) or syndrome of inappropriate antidiuretic hormone (SIADH). Distinguishing between these two entities can be difficult because they have similar manifestations, including hyponatremia, serum hypo-osmolality, and high urine osmolality. We herein report the case of a 60-year-old man who suffered from SAH complicated by hyponatremia. During his initial hospitalization, he was diagnosed with CSWS. He was readmitted one week later with hyponatremia and was diagnosed with SIADH. This is the first report of SAH causing CSWS followed by SIADH. These two different sources of hyponatremia require different treatments.

Rapid acquisition of high-affinity DNA aptamer motifs recognizing microbial cell surfaces using polymer-enhanced capillary transient isotachophoresis.

We present a polymer-enhanced capillary transient isotachophoresis (PectI) selection methodology for acquisition of high-affinity (kinetically inert) DNA aptamers capable of recognizing distinct microbial cell surfaces, which requires only a single electrophoretic separation between particles (free cells and cells bound with aptamers) and molecules (unbound or dissociated DNA) in free solution.