Circadian Amplitude Regulation via FBXW7-Targeted REV-ERBα Degradation.

Defects in circadian rhythm influence physiology and behavior with implications for the treatment of sleep disorders, metabolic disease, and cancer. Although core regulatory components of clock rhythmicity have been defined, insight into the mechanisms underpinning amplitude is limited. Here, we show that REV-ERBα, a core inhibitory component of clock transcription, is targeted for ubiquitination and subsequent degradation by the F-box protein FBXW7. By relieving REV-ERBα-dependent repression, FBXW7 provides an unrecognized mechanism for enhancing the amplitude of clock gene transcription. Cyclin-dependent kinase 1 (CDK1)-mediated phosphorylation of REV-ERBα is necessary for FBXW7 recognition. Moreover, targeted hepatic disruption of FBXW7 alters circadian expression of core clock genes and perturbs whole-body lipid and glucose levels. This CDK1-FBXW7 pathway controlling REV-ERBα repression defines an unexpected molecular mechanism for re-engaging the positive transcriptional arm of the clock, as well as a potential route to manipulate clock amplitude via small molecule CDK1 inhibition.

SRF'ing around the clock.

Central circadian clock oscillators, located in the suprachiasmatic nucleus (SCN) of the hypothalamus, align peripheral clock systems with geosynchronous time. Gerber et al. (2013) identify actin polymerization and serum response factor (SRF) activation as key steps linking the central master clock to peripheral oscillators.

The comparative efficacy and safety of factor Xa inhibitors and warfarin for primary thromboprophylaxis in multiple myeloma patients undergoing immunomodulatory therapy.

There are limited data on the optimal choice of anticoagulation in multiple myeloma (MM) patients receiving immunomodulatory drugs (IMiDs). We conducted a propensity score-matched cohort study using the TriNetX database to compare the efficacy and safety of factor Xa inhibitors and warfarin in this patient population. Compared to warfarin, factor Xa inhibitors had a similar risk of deep vein thrombosis (hazard ratio [HR]: 1.11 [95% CI: 0.50-2.46]) or pulmonary embolism (HR: 1.08 [95% CI: 0.59-2.00]). There were no differences in the risk of gastrointestinal or intracranial bleeding. Factor Xa inhibitor-treated patients had lower all-cause mortality (HR: 0.56 [95% CI: 0.36-0.86]) compared with warfarin. These data suggest that factor Xa inhibitors had similar safety and efficacy compared with warfarin for MM patients on IMiDs.

Highly Emissive Lanthanide-Based 0D Metal Halide Nanocrystals for Efficient Ultraviolet Photodetector.

Recently, lanthanide-based 0D metal halides have attracted considerable attention for their applications in X-ray imaging, light-emitting diodes (LEDs), sensors, and photodetectors. Herein, lead-free 0D gadolinium-alloyed cesium cerium chloride (Gd3+-alloyed Cs3CeCl6) nanocrystals (NCs) are introduced as promising materials for optoelectronic application owing to their unique optical properties. The incorporation of Gd3+ in Cs3CeCl6 (CCC) NCs is proposed to increase the photoluminescence quantum yield (PLQY) from 57% to 96%, along with significantly enhanced phase and chemical stability. The structural analysis is performed by density functional theory (DFT) to confirm the effect of Gd3+ in Cs3Ce1- xGdxCl6 (CCGC) alloy system. Moreover, the CCGC NCs are applied as the active layer in UVPDs with different Gd3+ concentration. The excellent device performance is shown at 20% of Gd3+ in CCGC NCs with high detectivity (7.938 × 1011 Jones) and responsivity (0.195 A W-1) at -0.1 V at 310 nm. This study paves the way for the development of lanthanide-based metal halide NCs for next-generation UVPDs and other optoelectronic applications.

The Effect of Exercise on Cardiotoxicity in Women with Breast Cancer Receiving Anthracycline-Based Chemotherapy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Breast cancer is the most common cancer in women with a 5-year survival over 90%. However, anthracycline-based chemotherapy causes significant cardiotoxicity often requiring discontinuation of chemotherapeutic regimen among breast cancer survivors. We conducted a systematic review and meta-analysis to evaluate the efficacy of exercise training in mitigating anthracycline-related cardiotoxicity among women with breast cancer. METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases. The outcomes of interest were left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), early to atrial filling velocity (E/A) ratio, maximal oxygen consumption (VO2 max), and cardiac output (CO). We used the Cochrane risk-of-bias tool for randomized trials (RoB 2) to assess the risk of bias in individual studies. RESULTS: We identified a total of 596 articles with 5 trials included in the final analysis. Exercise training was associated with an increase in VO2 max compared with no exercise training (mean difference, 3.95 [95% CI, 0.63-7.26]; I2 = 99.68%). Other cardiovascular outcomes such as LVEF (mean difference, 1.76 [95% CI, -1.95 to 5.46]; I2 = 99.44%), GLS (mean difference, 0.30 [95% CI, -0.49 to 1.10]; I2 = 96.63%), E/A ratio (mean difference, 0.05 [95% CI, -0.05 to 0.15]; I2 = 94.16%), and CO (mean difference, 0.38 [95% CI, -0.91 to 1.66]; I2 = 99.73%) are similar between patients who underwent exercise training and those who did not. CONCLUSIONS: Exercise was associated with an improvement in maximal oxygen uptake among women with breast cancer receiving anthracycline-based chemotherapy.

Aortic carboxypeptidase-like protein, a putative myokine, stimulates the differentiation and survival of bone-forming osteoblasts.

A new target that stimulates bone formation is needed to overcome limitations of current anti-osteoporotic drugs. Myokines, factors secreted from muscles, may modulate it. In this study, we investigated the role of aortic carboxypeptidase-like protein (ACLP), which is highly expressed in skeletal muscles, on bone formation. MC3T3-E1 cells and/or calvaria osteoblasts were treated with recombinant N-terminal mouse ACLP containing a signal peptide [rmACLP (N)]. The expression and secretion of ACLP were higher in skeletal muscle and differentiated myotube than in other tissues and undifferentiated myoblasts, respectively. rmACLP (N) increased bone formation, ALP activity, and phosphorylated p38 mitogen-activated protein (MAP) kinase in osteoblasts; reversal was achieved by pre-treatment with a TGF-ß receptor inhibitor. Under H2 O2 treatment, rmACLP (N) increased osteoblast survival, phosphorylated p38 MAP kinase, and the nuclear translocation of FoxO3a in osteoblasts. H2 O2 treatment caused rmACLP (N) to suppress its apoptotic, oxidative, and caspase-9 activities. rmACLP (N)-stimulated osteoblast survival was reversed by pre-treatment with a p38 inhibitor, a TGF-ß-receptor II blocking antibody, and a FoxO3a shRNA. Conditioned media (CM) from muscle cells stimulated osteoblast survival under H2 O2 treatment, in contrast to CM from ACLP knockdown muscle cells. rmACLP (N) increased the expressions of FoxO3a target anti-oxidant genes such as Sod2, Trx2, and Prx5. In conclusion, ACLP stimulated the differentiation and survival of osteoblasts. This led to the stimulation of bone formation by the activation of p38 MAP kinase and/or FoxO3a via TGF-ß receptors. These findings suggest a novel role for ACLP in bone metabolism as a putative myokine.

Dendritic cell vaccine for glioblastoma: an updated meta-analysis and trial sequential analysis.

BACKGROUND: Dendritic cell (DC) vaccine is an emerging immunotherapy that could potentially improve glioblastoma survival. The first phase III clinical trial of DC vaccine was recently published. This meta-analysis aims to update and reappraise existing evidence on the efficacy of DC vaccine in patients with glioblastoma. METHODS: We searched PubMed, Embase, and Cochrane Library for clinical trials of DC vaccine for glioblastoma. The quality of the studies was assessed using the RoB 2.0 and ROBINS-I tools. The results of overall survival (OS) and progression-free survival (PFS) were pooled using hazard ratios (HRs) with corresponding 95% confidence intervals (CI). Summary effects were evaluated using random effects models. Trial sequential analysis (TSA) was performed. RESULTS: Seven clinical trials involving 3,619 patients were included. DC vaccine plus standard care was associated with significantly improved OS (HR = 0.71; 95% CI, 0.57 - 0.88) and PFS (HR = 0.65; 95% CI, 0.43 - 0.98). In the subgroup of newly diagnosed glioblastoma, DC vaccine was associated with improved PFS (HR = 0.59; 95% CI, 0.39 - 0.90). TSA of OS showed that the cumulative z-score line for the DC vaccine crossed the benefit boundary and reached the required sample size. TSA of PFS and subgroup analysis of newly diagnosed glioblastoma showed that the required sample size was not reached. CONCLUSIONS: This updated meta-analysis, which included the first phase III trial of a DC vaccine for glioblastoma, demonstrated that the DC vaccine was associated with improved OS. Moreover, TSA showed that the required sample size was reached, indicating a true-positive result. Future studies are required for patient subgroups with newly diagnosed and recurrent glioblastoma.

Large-Scale Mechanochemical Synthesis of Cesium Lanthanide Chloride for Radioluminescence.

Cesium lanthanide chloride (Cs3LnCl6), a recently developed class of lanthanide-based zero-dimensional metal halides, has garnered a significant amount of interest because of its potential applications in scintillators, light-emitting diodes, and photodetectors. Although cesium lanthanide chloride demonstrates exceptional scintillator properties, conventional synthesis methods involving solid-state and solution-phase techniques are complex and limited on the reaction scale. This study presents a facile mechanochemical synthesis method for producing Cs3CeCl6, Cs3TbCl6, and Cs3EuCl6 metal halides on a 5 g scale. These materials exhibit intense blue-violet, green, and red emissions upon ultraviolet excitation, with high photoluminescence quantum yields ranging from 54% to 93%. Furthermore, Cs3CeCl6, Cs3TbCl6, and Cs3EuCl6 metal halides exhibit intense radioluminescence spanning from the ultraviolet to the visible region. This research shows the potential of the scalable mechanochemical synthesis of lanthanide-based metal halides for the advancement of luminescent materials for scintillators.

The impact of sodium-glucose cotransporter-2 inhibitors on outcome of patients with diabetes mellitus and colorectal cancer.

BACKGROUND AND AIM: Patients with type 2 diabetes mellitus (T2DM) have a higher risk of colorectal cancer (CRC), and those with diagnosed CRC have a poorer prognosis compared with individuals with normal glucose levels. The inhibition of sodium-glucose cotransporter 2 (SGLT2) channels has been associated with a reduction in tumor proliferation in preclinical studies. We aimed to investigate the impact of sodium-glucose cotransporter 2 inhibitors (SGLT2i) on the outcome of T2DM patients with colorectal cancer. METHODS: We performed a retrospective cohort study comprising adult patients with T2DM and colorectal adenocarcinoma. SGLT2i recipients were matched to non-SGLT2i recipients in a 1:1 ratio based on age, sex, and cancer stage. The primary outcome was overall survival (OS) and progression-free survival (PFS), and the secondary outcomes were previously reported serious adverse events associated with SGLT2i. RESULTS: We identified 1347 patients with T2DM and colorectal adenocarcinoma, from which 92 patients in the SGLT2i cohort were matched to the non-SGLT2i cohort. Compared to non-SGLT2i recipients, SGLT2i recipients had a higher rate of 5-year OS (86.2% [95% CI: 72.0-93.5] vs 62.3% [95% CI: 50.9-71.8], P = 0.013) and 5-year PFS (76.6% [95% CI: 60.7-86.7] vs 57.0% [95% CI: 46.2-66.4], P = 0.021). In Cox proportional hazard analyses, SGLT2i were associated with a 50-70% reduction in all-cause mortality and disease progression. SGLT2i were not associated with an increased risk of serious adverse events. CONCLUSION: SGLT2i were associated with a higher rate of survival in T2DM patients with colorectal cancer.

Ingestion of fishing gear and Anisakis sp. infection in a beached Indo-Pacific finless porpoise (Neophocaena phocaenoides) in the Jeju Island, Republic of Korea: findings from post-mortem computed tomography and necropsy.

BACKGROUND: Human fishing activities have significantly affect environmental concern for marine ecosystems, conservation of marine mammals, and human health. Coastal cetaceans are highly vulnerable to ingestion of fishing gear, bycatching, or entanglement, all of which can be fatal for these animals. In particular, certain coastal dolphins and porpoises are heavily impacted by fishing gear such as angling gear or stownet, as their food often overlap with the target fish species of human fisheries. CASE PRESENTATION: This study presents a case of an Indo-Pacific finless porpoise (Neophocaena phocaenoides) beached on the coast of Jeju Island, Republic of Korea, with ingestion of fishing gear and severe Anisakis infection. Although this species inhabits waters ranging from the Persian Gulf to Taiwan, several stranded carcasses have been reported on Jeju Island in recent years. Post-mortem computed tomography revealed a bundle of four fishing hooks in the forestomach, along with nylon lines and steel lines with connectors, which were assumed to be angling gear for Jeju hairtail (Trichiurus lepturus). Further necroscopic investigation revealed that the forestomach contained a large number of Anisakis spp. (Nematoda: Anisakidae). Histological examination revealed a thickened forestomach wall with pinpoint and volcanic ulcerations, a thickened layer of stratified squamous epithelium, and infiltrated stroma in the squamous epithelium. CONCLUSIONS: This study emphasizes the urgent need to address the impact of fishing activities on marine mammals, marine litter pollution, and the bycatch problem in Korean seawater. In addition, the occurrence of N. phocaenoides in seawater around Jeju Island should be raised in future geographical ecology or veterinary pathology studies and when its distribution is updated.

Thromboprophylaxis for outpatients with COVID-19: a Systematic Review and Meta-analysis.

Patients with COVID-19 develop an increased risk of thromboembolism. Thromboprophylaxis is recommended for hospitalized COVID-19 patients, but the role of thromboprophylaxis in outpatients with COVID-19 is less well defined. We conducted a systematic review and meta-analysis to evaluate the safety and efficacy of thromboprophylaxis among outpatients with COVID-19. We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus from inception to August 2023. The outcomes of interest were venous thromboembolic events including deep venous thrombosis and pulmonary embolism, all-cause mortality, cardiovascular events, hospitalization, major bleeding events, and non-major bleeding events. We included 6 trials comprising 3352 patients. Patients who received thromboprophylaxis had an approximately 70% reduction in venous thromboembolism (RR, 0.28 [95% CI, 0.08 to 0.93]) compared to patients who did not receive thromboprophylaxis. The risk of mortality (RR, 0.79 [95% CI, 0.35 to 1.77]), cardiovascular events (RR, 0.91 [95% CI, 0.30 to 2.73]), and hospitalization (RR, 1.09 [95% CI, 0.81 to 1.47]) were similar between the two groups. Patients who received thromboprophylaxis had a higher risk of non-major bleeding (RR, 3.48 [95% CI, 1.72 to 7.05) compared to patients who did not receive thromboprophylaxis. Thromboprophylaxis reduced the risk of venous thromboembolism but not mortality, cardiovascular events, or hospitalization among outpatients with COVID-19.

Factors associated with the development of exudation in treatment-naive eyes with nonexudative macular neovascularization.

PURPOSE: To identify the predictive factors for development of exudation in patients with treatment-naïve nonexudative macular neovascularization (MNV). METHODS: We retrospectively analyzed 61 treatment-naïve patients with nonexudative MNV who had not received treatment for nonexudative MNV before the exudation developed. Baseline characteristics and changes in MNV were evaluated using multivariate modeling to determine the potential risk factors for exudative conversion. RESULTS: Exudation development was identified in 31.1% (19/61 eyes) of the study eyes during the 46.2 ± 8.2-month mean follow-up period. The mean period of development of exudation from the baseline was 21.5 ± 6.7 months. Multivariate Cox regression analysis identified that older age (hazard ratio [HR] of 1.380, 95% confidence interval [CI] 1.129-1.688, P = 0.008), larger MNV area at baseline (HR of 1.715, CI 1.288-2.308; P = 0.006), increase of MNV area by doubling (HR of 4.992, CI 1.932-9.246; P = 0.002), and retinal pigment epithelium (RPE) elevation more than 100 µm (HR of 1.017, CI 1.006-1.233; P = 0.015) were associated with increased risk of the development of exudation. CONCLUSION: Older age, larger MNV area, increasing MNV area, and higher RPE elevation were associated with an increased risk of exudative conversion in patients with treatment-naïve nonexudative MNV. Identifying these risk factors may be helpful in establishing treatment strategies and monitoring patients.

YouTube as a source of information for pressure injury: Quality assessment and content analysis.

We aimed to assess the quality and reliability of pressure injury-related videos uploaded on YouTube, analyse the sources and contents, and examine the correlation between video parameters. We searched YouTube using two keywords, "pressure ulcer" and "pressure sore", on August 20, 2022. We sorted the videos according to their number of views and included the top 100 videos for each keyword. The quality of videos was assessed using the Global Quality Scale (GQS), while their reliability was evaluated by the modified DISCERN (mDISCERN) tool. In addition, we evaluated the videos in which content was included, analysed the correlations and differences between GQS, mDISCERN, and video parameters. We initially found a total of 100 videos for each keyword and finally included and analysed 77 videos. The mean scores for the mDISCERN and GQS were 2.35 ± 0.98 and 3.09 ± 0.99, respectively. Both GQS and mDISCERN showed statistically significant correlations with each other (rho = 0.54, p < 0.0001*) and with the length of the videos, respectively (rho = 0.36, p = 0.001*), (rho = 0.29, p = 0.01*). Of the videos created by physicians, 8 (57.1%) included content related to treatment, while of the videos created by nonphysician health personnel, 22 (57.9%) included content related to prevention. Analysing whether there were differences in video parameters based on the sources, we observed significant differences between sources in GQS (p < 0.0001*), mDISCERN (p < 0.0001*), and video length (p = 0.001*). In the post-hoc analysis, videos uploaded by physicians or nonphysician health personnel showed higher quality and reliability than videos uploaded by other sources. Therefore, the results of this study could be useful for healthcare providers, as well as patients and caregivers, to search for high-quality and reliable YouTube videos related to pressure injury.

Cancer Prediction With Machine Learning of Thrombi From Thrombectomy in Stroke: Multicenter Development and Validation.

BACKGROUND: We aimed to develop and validate machine learning models to diagnose patients with ischemic stroke with cancer through the analysis of histopathologic images of thrombi obtained during endovascular thrombectomy. METHODS: This was a retrospective study using a prospective multicenter registry which enrolled consecutive patients with acute ischemic stroke from South Korea who underwent endovascular thrombectomy. This study included patients admitted between July 1, 2017 and December 31, 2021 from 6 academic university hospitals. Whole-slide scanning was performed for immunohistochemically stained thrombi. Machine learning models were developed using transfer learning with image slices as input to classify patients into 2 groups: cancer group or other determined cause group. The models were developed and internally validated using thrombi from patients of the primary center, and external validation was conducted in 5 centers. The model was also applied to patients with hidden cancer who were diagnosed with cancer within 1 month of their index stroke. RESULTS: The study included 70 561 images from 182 patients in both internal and external datasets (119 patients in internal and 63 in external). Machine learning models were developed for each immunohistochemical staining using antibodies against platelets, fibrin, and erythrocytes. The platelet model demonstrated consistently high accuracy in classifying patients with cancer, with area under the receiver operating characteristic curve of 0.986 (95% CI, 0.983-0.989) during training, 0.954 (95% CI, 0.937-0.972) during internal validation, and 0.949 (95% CI, 0.891-1.000) during external validation. When applied to patients with occult cancer, the model accurately predicted the presence of cancer with high probabilities ranging from 88.5% to 99.2%. CONCLUSIONS: Machine learning models may be used for prediction of cancer as the underlying cause or detection of occult cancer, using platelet-stained immunohistochemical slide images of thrombi obtained during endovascular thrombectomy.

Effect of metformin on outcomes of patients treated with immune checkpoint inhibitors: a retrospective cohort study.

BACKGROUND: Immune checkpoint inhibitors have transformed the treatment landscape of cancer treatment, but only a fraction of patients responds to treatment, leading to an increasing effort to repurpose clinically approved medications to augment ICI therapy. Metformin has been associated with improved survival outcomes in patients undergoing conventional chemotherapy. However, whether metformin provides survival benefits in patients receiving immune checkpoint inhibitors (ICIs) is unknown. METHODS: We performed a retrospective cohort study at two tertiary referral centers in Taiwan. All adult diabetes mellitus patients who were treated with ICIs between January 2015 and December 2021 were included. The primary and secondary outcomes were overall survival (OS) and progression-free survival (PFS), respectively. RESULTS: In total, 878 patients were enrolled in our study, of which 86 patients used metformin and 78 patients used non-metformin diabetes medications. Compared with non-users, metformin users had a longer median OS (15.4 [IQR 5.6-not reached] vs. 6.1 [IQR, 0.8-21.0] months, P = 0.003) and PFS (5.1 [IQR 2.0-14.3] vs. 1.9 [IQR 0.7-8.6] months, P = 0.041). In a univariate Cox proportional hazard analysis, the use of metformin was associated with a reduction in the risk of mortality (HR: 0.53 [95% confidence interval: 0.35-0.81], P = 0.004) and disease progression (HR: 0.69 [95% CI 0.49-0.99], P = 0.042). The use of metformin remained associated with a lower risk of mortality after adjusting for baseline variables such as age, cancer stage, and underlying comorbidities (OS, HR: 0.55 [95% CI 0.34-0.87], P = 0.011). Similarly, the use of metformin was associated with a lower risk of disease progression. Importantly, the use of metformin before ICI initiation was not associated with a reduction in mortality (HR: 0.61 [95% CI 0.27-1.42], P = 0.25) or disease progression (HR: 0.69 [95% CI 0.33-1.43], P = 0.32). CONCLUSION: The use of metformin is associated with survival benefits in patients undergoing immunotherapy. Prospective clinical trials are warranted to define the role of metformin in augmenting immunotherapy.

Sequential Phosphorylation of Hepatitis C Virus NS5A Protein Requires the ATP-Binding Domain of NS3 Helicase.

The propagation of the hepatitis C virus (HCV) is regulated in part by the phosphorylation of its nonstructural protein NS5A that undergoes sequential phosphorylation on several highly conserved serine residues and switches from a hypo- to a hyperphosphorylated state. Previous studies have shown that NS5A sequential phosphorylation requires NS3 encoded on the same NS3-NS4A-NS4B-NS5A polyprotein. Subtle mutations in NS3 without affecting its protease activity could affect NS5A phosphorylation. Given the ATPase domain in the NS3 COOH terminus, we tested whether NS3 participates in NS5A phosphorylation similarly to the nucleoside diphosphate kinase-like activity of the rotavirus NSP2 nucleoside triphosphatase (NTPase). Mutations in the NS3 ATP-binding motifs blunted NS5A hyperphosphorylation and phosphorylation at serines 225, 232, and 235, whereas a mutation in the RNA-binding domain did not. The phosphorylation events were not rescued with wild-type NS3 provided in trans. When provided with an NS3 ATPase-compatible ATP analog, N6-benzyl-ATP-γ-S, thiophosphorylated NS5A was detected in the cells expressing the wild-type NS3-NS5B polyprotein. The thiophosphorylation level was lower in the cells expressing NS3-NS5B with a mutation in the NS3 ATP-binding domain. In vitro assays with a synthetic peptide and purified wild-type NS3 followed by dot blotting and mass spectrometry found weak NS5A phosphorylation at serines 222 and 225 that was sensitive to an inhibitor of casein kinase Iα but not helicase. When casein kinase Iα was included in the assay, much stronger phosphorylation was observed at serines 225, 232, and 235. We concluded that NS5A sequential phosphorylation requires the ATP-binding domain of the NS3 helicase and that casein kinase Iα is a potent NS5A kinase. IMPORTANCE For more than 20 years, NS3 was known to participate in NS5A sequential phosphorylation. In the present study, we show for the first time that the ATP-binding domain of NS3 is involved in NS5A phosphorylation. In vitro assays showed that casein kinase Iα is a very potent kinase responsible for NS5A phosphorylation at serines 225, 232, and 235. Our data suggest that ATP binding by NS3 probably results in conformational changes that recruit casein kinase Iα to phosphorylate NS5A, initially at S225 and subsequently at S232 and S235. Our discovery reveals intricate requirements of the structural integrity of NS3 for NS5A hyperphosphorylation and HCV replication.

Efficacy of Lipophilic Statins on Outcomes of Patients Treated with Immune Checkpoint Inhibitors.

BACKGROUND: Statins are associated with improved survival outcomes in patients receiving immune checkpoint inhibitors (ICIs), but the impact of lipophilic and hydrophilic statin properties on patient outcomes is unknown. OBJECTIVES: We aim to investigate if statins with lipophilic properties are associated with clinical outcomes in patients receiving ICIs. METHOD: We conducted a retrospective cohort study at two tertiary referral centers in Taiwan comprising patients receiving ICIs between January 2015 and December 2021. We compared the comparative effect of lipophilic and hydrophilic statins on patient outcomes. The primary outcome was overall survival (OS) and the secondary outcome was progression-free survival (PFS). RESULTS: Among 734 patients receiving ICIs, there were 51 lipophilic statin users, 25 hydrophilic statin users, and 658 nonusers. Lipophilic statin users had a longer median OS (38.0 [IQR, 16.7-not reached] vs. 15.2 [IQR, 8.2-not reached] months vs. 18.9 [IQR, 5.4 51.6] months) and PFS (13.0 [IQR, 4.7-41.5] vs. 8.2 [IQR, 2.2-14.7] months vs. 5.6 [2.3-18.7] months) than hydrophilic statin users and non-statin users. In Cox proportional hazard analyses, the use of lipophilic statins was associated with a 40-50% lower risk of mortality and disease progression compared with hydrophilic statin or non-statin users. CONCLUSIONS: The use of lipophilic statins seems to be associated with survival benefits in patients undergoing immunotherapy.

Observation and Characterization of the Hg-O Diatomic Molecule: A Matrix-Isolation and Quantum-Chemical Investigation.

Mercuric oxide is a well-known and stable solid, but the diatomic molecule Hg-O is very fragile and does not survive detection in the gas phase. However, laser ablation of Hg atoms from a dental amalgam alloy target into argon or neon containing about 0.3 % of 16 O2 or of 18 O2 during their condensation into a cryogenic matrix at 4 K allows the formation of O atoms which react on annealing to make ozone and new IR absorptions in solid argon at 521.2 cm-1 for Hg-16 O or at 496.4 cm-1 for Hg-18 O with the oxygen isotopic frequency ratio 521.2/496.4=1.0499. Solid neon gives a 529.0 cm-1 absorption with a small 7.8 cm-1 blue shift. CCSD(T) calculations found 594 cm-1 for Hg16 O and 562 cm-1 for Hg18 O (frequency ratio=1.0569). Such calculations usually produce harmonic frequencies that are slightly higher than the anharmonic (observed) values, which supports their relationship. These observed frequencies have the isotopic shift predicted for Hg-O and are within the range of recent high-level frequency calculations for the Hg-O molecule. Spectra for the related mercury superoxide and ozonide species are also considered for the first time.

Virus detection of measles-negative cases in Gyeonggi Province, South Korea, from 2017 to 2019.

To investigate viruses in measles-negative cases, 221 measles-suspected samples collected in Gyeonggi Province, South Korea were tested using a real-time PCR assay. Rubella virus was not detected. However, 11 cases of parvovirus B19 (5.0%), 47 cases of human herpesvirus 6 (21.3%), 25 cases of human herpesvirus 7 (11.3%), and one case of co-infection with parvovirus B19 and human herpesvirus 7 were confirmed, as were eight cases of co-infection with human herpesvirus 6 and human herpesvirus 7. This study showed that parvovirus B19, human herpesvirus 6, and human herpesvirus 7 should be considered by physicians for the diagnosis of measles-suspected patients.

SUBRETINAL FLUID ASSOCIATED WITH DRUSENOID PIGMENT EPITHELIAL DETACHMENT.

PURPOSE: To analyze the clinical characteristics of drusenoid pigment epithelial detachment (PED) with subretinal fluid (SRF) and to evaluate the impact of SRF on the long-term visual and anatomical outcomes. METHODS: Forty-seven eyes with drusenoid PED (47 patients) who completed >24 months of follow-up were retrospectively analyzed. Intergroup comparisons of the visual and anatomical outcomes with and without SRF were made. RESULTS: The mean duration of follow-up was 32.9 ± 18.7 months. The group with drusenoid PED with SRF (14 eyes) showed significantly higher PED height (468 ± 130 µ m vs. 313 ± 88 µ m, P < 0.001), larger PED diameter (2,328 ± 953 µ m vs. 1,227 ± 882 µ m, P < 0.001), and larger PED volume (1.88 ± 1.73 mm 3 vs. 1.12 ± 1.35 mm 3 , P = 0.021) than that in the group with drusenoid PED without SRF (33 eyes) at baseline. No significant intergroup difference was found regarding the best-corrected visual acuity at the final visit. In addition, the incidence of complete retinal pigment epithelial and outer retinal atrophy (cRORA; 21.4%) and the development of macular neovascularization (MNV; 7.1%) for the group with drusenoid PED with SRF showed no difference compared with those (39.4% for cRORA development and 9.1% for MNV development) with drusenoid PED without SRF. CONCLUSION: The size, height, and volume of drusenoid PED were associated with the development of SRF. The SRF in drusenoid PED did not affect the visual prognosis or the development of macular atrophy during long-term follow-up.