A multimodal atlas of hepatocellular carcinoma reveals convergent evolutionary paths and 'bad apple' effect on clinical trajectory.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a highly fatal cancer characterized by high intra-tumor heterogeneity (ITH). A panoramic understanding of its tumor evolution, in relation to its clinical trajectory, may provide novel prognostic and treatment strategies. METHODS: Through the Asia-Pacific Hepatocellular Carcinoma trials group (NCT03267641), we recruited one of the largest prospective cohorts of patients with HCC, with over 600 whole genome and transcriptome samples from 123 treatment-naïve patients. RESULTS: Using a multi-region sampling approach, we revealed seven convergent genetic evolutionary paths governed by the early driver mutations, late copy number variations and viral integrations, which stratify patient clinical trajectories after surgical resection. Furthermore, such evolutionary paths shaped the molecular profiles, leading to distinct transcriptomic subtypes. Most significantly, although we found the coexistence of multiple transcriptomic subtypes within certain tumors, patient prognosis was best predicted by the most aggressive cell fraction of the tumor, rather than by overall degree of transcriptomic ITH level - a phenomenon we termed the 'bad apple' effect. Finally, we found that characteristics throughout early and late tumor evolution provide significant and complementary prognostic power in predicting patient survival. CONCLUSIONS: Taken together, our study generated a comprehensive landscape of evolutionary history for HCC and provides a rich multi-omics resource for understanding tumor heterogeneity and clinical trajectories. IMPACT AND IMPLICATIONS: This prospective study, utilizing comprehensive multi-sector, multi-omics sequencing and clinical data from surgically resected hepatocellular carcinoma (HCC), reveals critical insights into the role of tumor evolution and intra-tumor heterogeneity (ITH) in determining the prognosis of HCC. These findings are invaluable for oncology researchers and clinicians, as they underscore the influence of distinct evolutionary paths and the 'bad apple' effect, where the most aggressive tumor fraction dictates disease progression. These insights not only enhance prognostic accuracy post-surgical resection but also pave the way for personalized treatment strategies tailored to specific tumor evolutionary and transcriptomic profiles. The coexistence of multiple subtypes within the same tumor prompts a re-appraisal of the utilities of depending on single samples to represent the entire tumor and suggests the need for clinical molecular imaging. This research thus marks a significant step forward in the clinical understanding and management of HCC, underscoring the importance of integrating tumor evolutionary dynamics and multi-omics biomarkers into therapeutic decision-making. CLINICAL TRIAL NUMBER: NCT03267641 (Observational cohort).

Probiotic containing Lactobacillus reuteri DSM 17648 as an adjunct treatment for Helicobacter pylori infection: A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Despite multiple therapy regimens, the decline in the Helicobacter pylori eradication rate poses a significant challenge to the medical community. Adding Lactobacillus reuteri probiotic as an adjunct treatment has shown some promising results. This study aims to investigate the efficacy of Lactobacillus reuteri DSM 17648 in H. pylori eradication and its effect in ameliorating gastrointestinal symptoms and adverse treatment effects. MATERIALS AND METHODS: This randomized, double-blinded, placebo-controlled trial involved treatment-naïve H. pylori-positive patients. Ninety patients received standard triple therapy for 2 weeks before receiving either a probiotic or placebo for 4 weeks. The posttreatment eradication rate was assessed via a 14 C urea breath test in Week 8. The Gastrointestinal Symptom Rating Scale (GSRS) questionnaire and an interview on treatment adverse effects were conducted during this study. RESULTS: The eradication rate was higher in the probiotic group than in the placebo group, with a 22.2% difference in the intention-to-treat analysis (91.1% vs. 68.9%; p = 0.007) and 24.3% difference in the per-protocol analysis (93.2% vs. 68.9%; p = 0.007). The probiotic group showed significant pre- to post-treatment reductions in indigestion, constipation, abdominal pain, and total GSRS scores. The probiotic group showed significantly greater reductions in GSRS scores than the placebo group: indigestion (4.34 ± 5.00 vs. 1.78 ± 5.64; p = 0.026), abdominal pain (2.64 ± 2.88 vs. 0.89 ± 3.11; p = 0.007), constipation (2.34 ± 3.91 vs. 0.64 ± 2.92; p = 0.023), and total score (12.41 ± 12.19 vs. 4.24 ± 13.72; p = 0.004). The probiotic group reported significantly fewer adverse headache (0% vs. 15.6%; p = 0.012) and abdominal pain (0% vs. 13.3%; p = 0.026) effects. CONCLUSIONS: There was a significant increase in H. pylori eradication rate and attenuation of symptoms and adverse treatment effects when L. reuteri was given as an adjunct treatment.

Discovery of blood-brain barrier permeant amine-functionalized aurones as inhibitors of activated microglia.

Sulfuretin, a naturally occurring aurone is reported to inhibit macrophage and microglia activation. A series of aurones incorporating basic amines and lipophilic functionalities at ring A and/or ring B were synthesized to improve upon present sulfuretin activity towards targeting brain microglia while overcoming the blood-brain barrier (BBB). Evaluation of the ability of the aurones to inhibit lipopolysaccharide (LPS)-stimulated nitric oxide (NO) secretion by murine BV-2 microglia has identified several inhibitors showing significant NO reduction at 1 to 10 µM. Potent inhibitors were represented by aurones with bulky, planar moieties at ring A (3f) or at ring B (1e and 1f) and having a pendant piperidine at ring B (1a, 2a, 2b, and 3f). The active aurones inhibited the BV-2 microglia polarizing towards the M1 state as indicated by attenuation of IL-1ß and TNF-α secretions in LPS-activated microglia but did not induce the microglia towards the M2 state. The aurones 2a, 2b, and 1f showed high passive BBB permeability in the parallel artificial membrane permeability assay (PAMPA) owing to their optimal lipophilicities. 2a, being non-cell toxic, BBB permeant and potent, represents a new lead for the development of aurones as inhibitors of activated microglia.

Development of a Web-Based Alcohol Prevention Program Linking School-Child-Family for Intermediate Elementary Students.

Family strongly influences student health behavior. However, alcohol-preventive education programs that link parents and school for intermediate-elementary school students remain scarce. Although online educational programs constitute effective interventions to intentionally improve health behaviors, traditional methods are used to implement alcohol- prevention programs for students. In this study, we aimed to (1) develop an online school-child-family alcohol-prevention program based on the theory of planned behavior and (2) examine the preliminary effects of the program on intention to consume alcohol among intermediate-elementary school students. This single-group, pre- and posttest study enrolled 46 Grade 3 students from a public elementary school in a metropolitan South Korea city and ascertained the preliminary effects of a 5-week online alcohol-prevention program by using the alcohol drinking prevention behavior scale. Attitudes, perceived behavioral control, and intention of alcohol-preventive behaviors significantly improved (p < .05) whereas subjective norms did not. The online alcohol-prevention program based on the theory of planned behavior and school-child-family linkage beneficially influenced intention, attitude, and perceived behavioral control for alcohol-prevention behavior, and the effectiveness and convenience of this program underscores its potential application as an educational intervention to improve health behaviors of intermediate-elementary school students.

Long-term Radiographic and Clinical Outcomes After Selective Thoracic Fusion for Adolescent Idiopathic Scoliosis With Lenke 1C Curve.

BACKGROUND: Despite the promising results with selective thoracic fusion (STF) in patients with adolescent idiopathic scoliosis (AIS) of the Lenke 1C curve, postoperative coronal imbalance and progression of the unfused lumbar curve have been concerns in long-term follow-up. In this study, we aimed to investigate the radiographic and clinical outcomes after STF for AIS with Lenke 1C curve with long-term follow-up. METHODS: A total of 30 patients with AIS with Lenke 1C curves who underwent STF between 2005 and 2017 were included. Minimum follow-up duration was 5 years. Time-dependent changes in radiographic parameters were investigated preoperatively, immediately postoperatively, and at the last follow-up. In addition, radiographic adverse events such as coronal decompensation (CD), lumbar decompensation (LD), distal adding-on (DA) phenomenon, and trunk shift were evaluated at the last follow-up. The Scoliosis Research Society-22 score was used for clinical outcome evaluation. RESULTS: The mean age at the time of surgery was 13.8 years. The mean follow-up duration was 6.7 ± 0.8 years. The main thoracic curve significantly improved from 57 degrees to 23 degrees (60% correction), and the thoracolumbar/lumbar curve significantly improved from 47 degrees to 28 degrees (41% correction). Coronal balance was 15 mm after surgery but significantly improved to 10 mm at the last follow-up ( P = 0.033). At the final follow-up, 11 patients (37%) sustained at least one of the radiographic adverse events: CD in 5 patients (17%), LD in 3 (10%), DA in 4 (13%), and trunk shift in 3 (10.%). However, there were no cases requiring revision surgery. In addition, there were no significant differences in any items or total Scoliosis Research Society-22 score between the patients with and without radiographic adverse events. CONCLUSION: STF in Lenke 1C curves showed an acceptable risk of adverse radiographic events such as CD, LD, DA, and trunk shift in long-term follow-up. We suggest that STF without fusion to the thoracolumbar/lumbar curve would be sufficient in treating AIS with Lenke 1C curve. LEVEL OF EVIDENCE: Level III.

Heart Disease and Stroke Statistics-2021 Update: A Report From the American Heart Association.

BACKGROUND: The American Heart Association, in conjunction with the National Institutes of Health, annually reports the most up-to-date statistics related to heart disease, stroke, and cardiovascular risk factors, including core health behaviors (smoking, physical activity, diet, and weight) and health factors (cholesterol, blood pressure, and glucose control) that contribute to cardiovascular health. The Statistical Update presents the latest data on a range of major clinical heart and circulatory disease conditions (including stroke, congenital heart disease, rhythm disorders, subclinical atherosclerosis, coronary heart disease, heart failure, valvular disease, venous disease, and peripheral artery disease) and the associated outcomes (including quality of care, procedures, and economic costs). METHODS: The American Heart Association, through its Statistics Committee, continuously monitors and evaluates sources of data on heart disease and stroke in the United States to provide the most current information available in the annual Statistical Update. The 2021 Statistical Update is the product of a full year's worth of effort by dedicated volunteer clinicians and scientists, committed government professionals, and American Heart Association staff members. This year's edition includes data on the monitoring and benefits of cardiovascular health in the population, an enhanced focus on social determinants of health, adverse pregnancy outcomes, vascular contributions to brain health, the global burden of cardiovascular disease, and further evidence-based approaches to changing behaviors related to cardiovascular disease. RESULTS: Each of the 27 chapters in the Statistical Update focuses on a different topic related to heart disease and stroke statistics. CONCLUSIONS: The Statistical Update represents a critical resource for the lay public, policy makers, media professionals, clinicians, health care administrators, researchers, health advocates, and others seeking the best available data on these factors and conditions.

Comparison of n-butyl-2-cyanoacrylate and polyvinyl alcohol particles for bronchial artery embolisation in primary lung cancer: a retrospective cohort study.

BACKGROUND: Bronchial artery embolisation (BAE) is an effective treatment option to control haemoptysis in primary lung cancer. However, no studies have investigated optimal embolisation material for BAE in lung cancer patients. Thus, this study aimed to compare the safety and efficacy of BAE performed using n-butyl-2-cyanoacrylate (NBCA) and polyvinyl alcohol (PVA) particles in primary lung cancer patients to determine which embolic material is better for patients with haemoptysis. METHODS: This retrospective study was approved by the institutional review board, and consent was waived. The rates of hemostasis, complications, procedure time, dose-area product, and haemoptysis-free survival were retrospectively compared between primary lung cancer (non-small cell [n = 111] and small cell [n = 11]) patients who underwent BAE using NBCA (n = 58) or PVA particles (n = 64) between January 2004 and December 2019. Predictors of recurrent haemoptysis were analysed using the Cox proportional hazard regression model. RESULTS: Among 122 patients (mean age, 66 ± 10 years; range 32-86 years; 103 men), more patients in the NBCA group (81.0%; 47 of 58) achieved complete hemostasis than did patients in the PVA group (53.1%; 34 of 64) (P = 0.002). No major complications were observed in either group. The procedure time (36.4 ± 21.6 vs. 56.3 ± 27.4 min, P < 0.001) was shorter, and the dose-area product (58.6 ± 64.0 vs. 233.5 ± 225.0 Gy*cm2, P < 0.001) was smaller in the NBCA group than in the PVA group. The median haemoptysis-free survival was 173.0 in the NBCA group compared with 20.0 days in the PVA group (P < 0.001). The PVA use (P < 0.001) and coagulopathy (P = 0.014) were independent predictors of shortened haemoptysis-free survival. CONCLUSION: BAE using NBCA showed significantly superior initial hemostasis with longer haemoptysis-free survival, shorter procedure time, and reduced radiation dose than BAE using PVA particles. The PVA use and coagulopathy were independent predictors of recurrent haemoptysis. TRIAL REGISTRATION: Retrospectively registered.

Evaluation of low-pass genome sequencing in polygenic risk score calculation for Parkinson's disease.

BACKGROUND: Low-pass sequencing (LPS) has been extensively investigated for applicability to various genetic studies due to its advantages over genotype array data including cost-effectiveness. Predicting the risk of complex diseases such as Parkinson's disease (PD) using polygenic risk score (PRS) based on the genetic variations has shown decent prediction accuracy. Although ultra-LPS has been shown to be effective in PRS calculation, array data has been favored to the majority of PRS analysis, especially for PD. RESULTS: Using eight high-coverage WGS, we assessed imputation approaches for downsampled LPS data ranging from 0.5 × to 7.0 × . We demonstrated that uncertain genotype calls of LPS diminished imputation accuracy, and an imputation approach using genotype likelihoods was plausible for LPS. Additionally, comparing imputation accuracies between LPS and simulated array illustrated that LPS had higher accuracies particularly at rare frequencies. To evaluate ultra-low coverage data in PRS calculation for PD, we prepared low-coverage WGS and genotype array of 87 PD cases and 101 controls. Genotype imputation of array and downsampled LPS were conducted using a population-specific reference panel, and we calculated risk scores based on the PD-associated SNPs from an East Asian meta-GWAS. The PRS models discriminated cases and controls as previously reported when both LPS and genotype array were used. Also strong correlations in PRS models for PD between LPS and genotype array were discovered. CONCLUSIONS: Overall, this study highlights the potentials of LPS under 1.0 × followed by genotype imputation in PRS calculation and suggests LPS as attractive alternatives to genotype array in the area of precision medicine for PD.

A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants.

BACKGROUND: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. METHODS: We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. RESULTS: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. CONCLUSIONS: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.

Comparison between Antegrade versus Retrograde Ureteral Stent Placement for Malignant Ureteral Obstruction.

PURPOSE: To compare the technical success of antegrade uteral stent (AUS) and retrograde ureteral stent (RUS) placements in patients with malignant ureteral obstruction (MUO) and to determine the predictors of technical failure of RUS. MATERIALS AND METHODS: This study retrospectively included 61 AUS placements (44 patients) performed under fluoroscopic guidance and 76 RUS placements (55 patients) performed under cystoscopic guidance in patients with MUO from January 2019 to December 2020. Technical success rates of the 2 techniques were compared using inverse probability of treatment weighting (IPTW) analysis. Logistic regression was used to identify predictive factors for technical failures. RESULTS: Technical success was achieved in 98.4% of the AUS group and 47.4% of the RUS group. After stabilized IPTW, the technical success rate was higher in the AUS group than in the RUS group (adjusted risk difference, 49.4%; 95% confidence interval [CI], 35.4%-63.1%). The independent predictors for technical failure of the RUS procedure were age of ≥65 years (odds ratio [OR], 5.56; 95% CI, 1.73-21.27), ureteral orifice invasion (OR, 4.21; 95% CI, 1.46-13.46), and extrinsic cancer (OR, 15.58; 95% CI, 2.92-111.81). CONCLUSIONS: The technical success rate of AUS placement was higher than that of RUS placement in patients with MUO. RUS failure was associated with age of ≥65 years, cancer with ureteral orifice invasion, and extrinsic ureteral obstruction.

Time-of-day moderate-to-vigorous physical activity and all-cause mortality in individuals with type 2 diabetes.

There is no clear evidence for the best time of day for physical activity in benefitting health among individuals with type 2 diabetes. This study was aimed to examine whether there is an optimal time of day for physical activity to increase longevity. In this cohort study of 904 patients with type 2 diabetes, we fitted a Cox model with restricted cubic spline to examine the association of moderate-to-vigorous physical activity (MVPA) and time of day with all-cause mortality. Compositional data analysis was used to examine the association of time spent in sedentary behaviour (SB), light-intensity physical activity (LIPA), morning MVPA, and evening MVPA with all-cause mortality. MVPA was inversely associated with all-cause mortality in a curvilinear manner (P-value for nonlinearity<0.0001). The interaction between MVPA and time of day was not significant (P-value for interaction=0.11). Substituting evening MVPA with morning MVPA was not associated with appreciable changes in all-cause mortality. There is no evidence that the time of day moderates the association of MVPA with all-cause mortality. Patients with higher levels of MVPA had lower mortality regardless of the timing of MVPA. Patients with type 2 diabetes should engage in regular physical activity whenever possible.

Impedance Coupled Voltage Boosting Circuit for Polyvinylidene Fluoride Based Energy Harvester.

Polyvinylidene fluoride (PVDF) is an emerging method for energy harvesting by fluid motion with superior flexibility. However, the PVDF energy harvester, which has a high internal impedance and generates a low voltage, has a large power transmission loss. To overcome this problem, we propose an impedance-coupled voltage-boosting circuit (IC-VBC) that reduces the impedance of the PVDF energy harvester and boosts the voltage. SPICE simulation results show that IC-VBC reduces the impedance of the PVDF energy harvester from 4.3 MΩ to 320 kΩ and increases the output voltage by 2.52 times. We successfully charged lithium-ion batteries using the PVDF energy harvester and IC-VBC with low-speed wind power generation.

Effects of a web-based alcohol drinking prevention program linking school-to-home in elementary students.

OBJECTIVES: We investigated the effects of a web-based alcohol drinking prevention program among early elementary school students in South Korea using the theory of planned behavior. This study utilized a combined family and school intervention approach. DESIGN: This was a quasi-experimental study with a non-equivalent control group. SAMPLE: A total of 251 third graders (experimental group: 170, control group: 81) from four public schools were included. MEASUREMENTS: A web-based alcohol drinking prevention program was implemented in five weekly sessions. Students' attitudes, subjective norms, perceived behavioral control (PBC), and intentions toward alcohol drinking prevention behavior were evaluated through pre- and post-tests. RESULTS: The average age of the participants was 9 years in both the experimental (82 male and 88 female students) and control (44 male and 37 female students) groups. A significant improvement in attitudes, PBC, and intentions toward alcohol drinking prevention behaviors was found in the experimental group. CONCLUSIONS: A web-based alcohol drinking prevention program combining family and school interventions for lower elementary school students was effective at increasing intentions toward alcohol drinking prevention behavior. Alcohol drinking prevention programs should target lower elementary school students to effectively postpone the onset of alcohol drinking.

A Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Prediction Model From Standard Laboratory Tests.

BACKGROUND: With the limited availability of testing for the presence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus and concerns surrounding the accuracy of existing methods, other means of identifying patients are urgently needed. Previous studies showing a correlation between certain laboratory tests and diagnosis suggest an alternative method based on an ensemble of tests. METHODS: We have trained a machine learning model to analyze the correlation between SARS-CoV-2 test results and 20 routine laboratory tests collected within a 2-day period around the SARS-CoV-2 test date. We used the model to compare SARS-CoV-2 positive and negative patients. RESULTS: In a cohort of 75 991 veteran inpatients and outpatients who tested for SARS-CoV-2 in the months of March through July 2020, 7335 of whom were positive by reverse transcription polymerase chain reaction (RT-PCR) or antigen testing, and who had at least 15 of 20 lab results within the window period, our model predicted the results of the SARS-CoV-2 test with a specificity of 86.8%, a sensitivity of 82.4%, and an overall accuracy of 86.4% (with a 95% confidence interval of [86.0%, 86.9%]). CONCLUSIONS: Although molecular-based and antibody tests remain the reference standard method for confirming a SARS-CoV-2 diagnosis, their clinical sensitivity is not well known. The model described herein may provide a complementary method of determining SARS-CoV-2 infection status, based on a fully independent set of indicators, that can help confirm results from other tests as well as identify positive cases missed by molecular testing.

Tertiary RNA Folding-Targeted Drug Screening Strategy Using a Protein Nanopore.

Bacterial riboswitch RNAs are attractive targets for novel antibiotics against antibiotic-resistant superbacteria. Their binding to cognate metabolites is essential for the regulation of bacterial gene expression. Despite the importance of RNAs as therapeutic targets, the development of RNA-targeted, small-molecule drugs is limited by current biophysical methods. Here, we monitored the specific interaction between the adenine-sensing riboswitch aptamer domain (ARS) and adenine at the single-molecule level using α-hemolysin (αHL) nanopores. During adenine-induced tertiary folding, adenine-bound ARS intermediates exhibited characteristic nanopore events, including a two-level ionic current blockade and a ∼ 5.6-fold longer dwell time than that of free RNA. In a proof-of-concept experiment, tertiary RNA folding-targeted drug screening was performed using a protein nanopore, which resulted in the discovery of three new ARS-targeting hit compounds from a natural compound library. Taken together, these results reveal that αHL nanopores are a valuable platform for ultrasensitive, label-free, and single-molecule-based drug screening against therapeutic RNA targets.

Fabrication of a honeycomb-like bimetallic SERS substrate for the detection of triphenyltin chloride.

Triphenyltin chloride (TPhT) is an organotin compound that causes intensive toxicological risk to the environment and humans. A detection method with high sensitivity and stability is therefore desired to better detect TPhT. In this study, a novel SERS substrate was prepared by sputtering an ultra-thin Au layer on a honeycomb-like silver nanoarray fabricated via the nanosphere lithography method. The ultra-thin Au layer was formed by sputtering the intermittent Au nanoparticles on the silver nanoarray, resulting in bimetallic coupling with dramatically increased hotspots and extremely high SERS enhancement with an analytical enhancement factor (AEF) of 6.08 × 109 using Rhodamine 6G (R6G) as the probe molecule. Based on density functional theory (DFT) simulations, the Raman characteristic peaks of TPhT at 999 cm-1 and 655 cm-1 were selected for TPhT detection. The AEF of the SERS substrate HC5-AgAu was calculated to be 3.38 × 106 with the detection concentration of TPhT down to 10-10 M. The as-prepared honeycomb-like silver-gold bimetallic SERS substrate demonstrated great stability and sensitivity for TPhT detection, which might also be applied in monitoring many other environmental pollutants.

Preparation of High-Purity Ammonium Tetrakis(pentafluorophenyl)borate for the Activation of Olefin Polymerization Catalysts.

Homogeneous olefin polymerization catalysts are activated in situ with a co-catalyst ([PhN(Me)2-H]+[B(C6F5)4]- or [Ph3C]+[B(C6F5)4]-) in bulk polymerization media. These co-catalysts are insoluble in hydrocarbon solvents, requiring excess co-catalyst (>3 eq.). Feeding the activated species as a solution in an aliphatic hydrocarbon solvent may be advantageous over the in situ activation method. In this study, highly pure and soluble ammonium tetrakis(pentafluorophenyl)borates ([Me(C18H37)2N-H]+[B(C6F5)4]- and [(C18H37)2NH2]+[B(C6F5)4]-) containing neither water nor Cl- salt impurities were prepared easily via the acid-base reaction of [PhN(Me)2-H]+[B(C6F5)4]- and the corresponding amine. Using the prepared ammonium salts, the activation reactions of commercial-process-relevant metallocene (rac-[ethylenebis(tetrahydroindenyl)]Zr(Me)2 (1-ZrMe2), [Ph2C(Cp)(3,6-tBu2Flu)]Hf(Me)2 (3-HfMe2), [Ph2C(Cp)(2,7-tBu2Flu)]Hf(Me)2 (4-HfMe2)) and half-metallocene complexes ([(η5-Me4C5)Si(Me)2(κ-NtBu)]Ti(Me)2 (5-TiMe2), [(η5-Me4C5)(C9H9(κ-N))]Ti(Me)2 (6-TiMe2), and [(η5-Me3C7H1S)(C10H11(κ-N))]Ti(Me)2 (7-TiMe2)) were monitored in C6D12 with 1H NMR spectroscopy. Stable [L-M(Me)(NMe(C18H37)2)]+[B(C6F5)4]- species were cleanly generated from 1-ZrMe2, 3-HfMe2, and 4-HfMe2, while the species types generated from 5-TiMe2, 6-TiMe2, and 7-TiMe2 were unstable for subsequent transformation to other species (presumably, [L-Ti(CH2N(C18H37)2)]+[B(C6F5)4]--type species). [L-TiCl(N(H)(C18H37)2)]+[B(C6F5)4]--type species were also prepared from 5-TiCl(Me) and 6-TiCl(Me), which were newly prepared in this study. The prepared [L-M(Me)(NMe(C18H37)2)]+[B(C6F5)4]--, [L-Ti(CH2N(C18H37)2)]+[B(C6F5)4]--, and [L-TiCl(N(H)(C18H37)2)]+[B(C6F5)4]--type species, which are soluble and stable in aliphatic hydrocarbon solvents, were highly active in ethylene/1-octene copolymerization performed in aliphatic hydrocarbon solvents.

Replacement of the Common Chromium Source CrCl3(thf)3 with Well-Defined [CrCl2(µ-Cl)(thf)2]2.

CrCl3(thf)3 is a common starting material in the synthesis of organometallic and coordination compounds of Cr. Deposited as an irregular solid with no possibility of recrystallization, it is not a purity guaranteed chemical, causing problems in some cases. In this work, we disclose a well-defined form of the THF adduct of CrCl3 ([CrCl2(µ-Cl)(thf)2]2), a crystalline solid, that enables structure determination by X-ray crystallography. The EA data and XRD pattern of the bulk agreed with the revealed structure. Moreover, its preparation procedure is facile: evacuation of CrCl3·6H2O at 100 °C, treatment with 6 equivalents of Me3SiCl in a minimal amount of THF, and crystallization from CH2Cl2. The ethylene tetramerization catalyst [iPrN{P(C6H4-p-Si(nBu)3)2}2CrCl2]+[B(C6F5)4]- prepared using well-defined [CrCl2(µ-Cl)(thf)2]2 as a starting material exhibited a reliably high activity (6600 kg/g-Cr/h; 1-octene selectivity at 40 °C, 75%), while that of the one prepared using the impure CrCl3(thf)3 was inconsistent and relatively low (~3000 kg/g-Cr/h). By using well-defined [CrCl2(µ-Cl)(thf)2]2 as a Cr source, single crystals of [(CH3CN)4CrCl2]+[B(C6F5)4]- and [{Et(Cl)Al(N(iPr)2)2}Cr(µ-Cl)]2 were obtained, allowing structure determination by X-ray crystallography, which had been unsuccessful when the previously known CrCl3(thf)3 was used as the Cr source.

SBIRT training: how do social work students compare to medical learners?

Background: SBIRT (Screening, Brief Intervention, and Referral to Treatment) is an effective early intervention approach for individuals with substance misuse. The purpose of this study was to determine if medical learners are more adept at learning a brief substance use intervention compared to non-medical learners (e.g., social work students). The dissemination of SBIRT training among many helping professions can increase service delivery for substance use problems. Methods: A total of 2,488 participants completed SBIRT training, representing 15 different disciplines and over 20 different institutions. General linear models and paired t-tests were used to investigate the effects of SBIRT training on changes in knowledge and attitude of alcohol and drug use and satisfaction. Results: There were no statistical differences in the change of satisfaction, knowledge, and attitude between medical and non-medical discipline participants. Both medical and non-medical participants had greater improvement in attitude and knowledge scores post-training. Similar improvements in attitude, knowledge, and satisfaction were observed in all the health-care discipline participants. Discussion: SBIRT skills may be transferable to disciplines including non-prescribing professionals (e.g., social work, nursing, physical therapy, rehabilitation science, and pharmacy). In an effort to expand treatment, health-care training institutions adopt SBIRT as a core competency for professional practice.

Fruit syndromes in Viburnum: correlated evolution of color, nutritional content, and morphology in bird-dispersed fleshy fruits.

PREMISE: A key question in plant dispersal via animal vectors is where and why fruit colors vary between species and how color relates to other fruit traits. To better understand the factors shaping the evolution of fruit color diversity, we tested for the existence of syndromes of traits (color, morphology, and nutrition) in the fruits of Viburnum. We placed these results in a larger phylogenetic context and reconstructed ancestral states to assess how Viburnum fruit traits have evolved across the clade. RESULTS: We find that blue Viburnum fruits are not very juicy, and have high lipid content and large, round endocarps surrounded by a small quantity of pulp. Red fruits display the opposite suite of traits: they are very juicy with low lipid content and smaller, flatter endocarps. The ancestral Viburnum fruit may have gone through a sequence of color changes before maturation (green to yellow to red to black), though our reconstructions are equivocal. In one major clade of Viburnum (Nectarotinus), fruits mature synchronously with reduced intermediate color stages. Most transitions between fruit colors occurred in this synchronously fruiting clade. CONCLUSIONS: It is widely accepted that fruit trait diversity has primarily been driven by the differing perceptual abilities of bird versus mammal frugivores. Yet within a clade of largely bird-dispersed fruits, we find clear correlations between color, morphology, and nutrition. These correlations are likely driven by a shift from sequential to synchronous development, followed by diversification in color, nutrition, and morphology. A deeper understanding of fruit evolution within clades will elucidate the degree to which such syndromes structure extant fruit diversity.