Differences in Out-of-Hospital Cardiac Arrest Outcomes Among 5 Racial/Ethnic Groups.

OBJECTIVE: Out-of-hospital cardiac arrest (OHCA) is a major health problem and one of the leading causes of death in adults older than 40. Multiple prior studies have demonstrated survival disparities based on race/ethnicity, but most of these focus on a single racial/ethnic group. This study evaluated OHCA variables and outcomes among on 5 racial/ethnic groups. METHODS: This is a retrospective review of data for adult patients in the Cardiac Arrest Registry to Enhance Survival (CARES) from 3 racially diverse urban counties in the San Francisco Bay Area from May 2009 to October 2021. Stratifying by 5 racial/ethnic groups, we evaluated patient survival outcomes based on patient demographics, emergency medical services response location, cardiac arrest characteristics, and hospital interventions. Adjusted risk ratios were calculated for survival to hospital discharge, controlling for sex, age, response locations, median income of response location, arrest witness, shockable rhythm, and bystander cardiopulmonary resuscitation as well as clustering by census tract. RESULTS: There were 10,757 patient entries analyzed: 42% White, 24% Black, 18% Asian, 9.3% Hispanic, 6.0% Pacific Islander, 0.7% American Indian/Alaska Native, and 0.1% multiple races selected; however, only the first 5 racial/ethnic groups had sufficient numbers for comparison. The adjusted risk ratio for survival to hospital discharge was lower among the 4 racial/ethnic groups compared with the White reference group: Black (0.79, p = 0.003), Asian (0.78 p = 0.004), Hispanic (0.79, p = 0.018), and Pacific Islander (0.78, p = 0.041) groups. The risk difference for positive neurologic outcome was also lower among all 4 racial/ethnic groups compared with the White reference group. CONCLUSIONS: The Black, Asian, Hispanic, and Pacific Islander groups were less likely to survive to hospital discharge from OHCA when compared with the White reference group. No variables were associated with decreased survival across any of these 4 groups.

Salidroside directly activates HSC70, revealing a new role for HSC70 in BDNF signalling and neurogenesis after cerebral ischemia.

Salidroside, a principal bioactive component of Rhodiola crenulata, is neuroprotective across a wide time window in stroke models. We investigated whether salidroside induced neurogenesis after cerebral ischemia and aimed to identify its primary molecular targets. Rats, subjected to transient 2 h of middle cerebral artery occlusion (MCAO), received intraperitoneal vehicle or salidroside ± intracerebroventricular HSC70 inhibitor VER155008 or TrkB inhibitor ANA-12 for up to 7 days. MRI, behavioural tests, immunofluorescent staining and western blotting measured effects of salidroside. Reverse virtual docking and enzymatic assays assessed interaction of salidroside with purified recombinant HSC70. Salidroside dose-dependently decreased cerebral infarct volumes and neurological deficits, with maximal effects by 50 mg/kg/day. This dose also improved performance in beam balance and Morris water maze tests. Salidroside significantly increased BrdU+ /nestin+ , BrdU+ /DCX+ , BrdU+ /NeuN+ , BrdU- /NeuN+ and BDNF+ cells in the peri-infarct cortex, with less effect in striatum and no significant effect in the subventricular zone. Salidroside was predicted to bind with HSC70. Salidroside dose-dependently increased HSC70 ATPase and HSC70-dependent luciferase activities, but it did not activate HSP70. HSC70 immunoreactivity concentrated in the peri-infarct cortex and was unchanged by salidroside. However, VER155008 prevented salidroside-dependent increases of neurogenesis, BrdU- /NeuN+ cells and BDNF+ cells in peri-infarct cortex. Salidroside also increased BDNF protein and p-TrkB/TrkB ratio in ischemic brain, changes prevented by VER155008 and ANA-12, respectively. Additionally, ANA-12 blocked salidroside-dependent neurogenesis and increased BrdU- /NeuN+ cells in the peri-infarct cortex. Salidroside directly activates HSC70, thereby stimulating neurogenesis and neuroprotection via BDNF/TrkB signalling after MCAO. Salidroside and similar activators of HSC70 might provide clinical therapies for ischemic stroke.

Assessment of the radionuclide remediation potential of novel miscanthus hybrids.

There are few studies related to the radionuclide remediation options, which comply to the demands of the environmentally non-destructive physical remediation methods. So far, most of the research was conducted on the phytoremediation capacity of different energy crops, as well as the established miscanthus hybrids which involved metal and heavy metal contaminants. Hence, the objective of this research was the radioecological characterization of the examined agroecosystem, including the initial source of the radionuclides (soil) as well as different miscanthus hybrids grown on the same soil. The results have shown that the radioactive content of soil was similar to the global averages. All measurements of the activity concentration of 137Cs in miscanthus samples were below the detection limits. There is also an indication that 210Pb is leaching into the lower layers (or is being taken up by miscanthus plant from the upper layers). Moreover, transfer factors (TFs) for radionuclides, as a more precise parameter for evaluating the phytoremediation potential, were calculated; the TFs were found to be very low for 226Ra (≤0.07), TFs for 40K (≤0.39) and for 232Th (≤0.21) were in the lower limits, whereas the TFs for 238U were found to be the highest (≤0.92). For 210Pb, the TFs were not calculated, since the expectation was that a significant part of the measured quantity came from the air, and not through the soil. Having in mind the sustainability and the circularity aspect of the radionuclide phytoremediation system, the appropriate management method should be applied for the disposal and utilization of the biomass contaminated with radionuclides. This research has shown that the radiological content in miscanthus is high enough and the ash content is low enough that miscanthus ash could be considered as a NORM (Naturally Occurring Radioactive Material), and it can be further used for the construction industry (i.e. concrete, tiles), in mixtures with other materials with certain limitations, similar to the utilization of ash from other sources such as coal or wood.

Molecular characterization and demographic insights into soybean bud borer (Lepidoptera: Tortricidae) in Brazil.

The soybean bud borer, a soybean pest in Brazil, was initially identified as Crocidosema aporema (Walsingham 1914) (Lepidoptera: Tortricidae). Outbreaks of this species have recently increased, but identification of this pest remains uncertain, and the historical factors associated with its geographic distribution in Brazil are little known. Here, we conducted a species characterization and phylogeographic analysis based on molecular and morphological evidence. Ninety individuals of bud-borers Lepidoptera were collected in different regions of Brazil. We sequenced COI and COII mitochondrial genes and examined wing patterns and male genital morphology. DNA barcoding approach revealed that 10 individuals were Argyrotaenia sphaleropa (Meyrick 1909) (Lepidoptera: Tortricidae) and 80 were a species of the genus Crocidosema Zeller. The morphology of the adult genitalia and wings proved to be insufficient to confirm the identification of Brazilian individuals as C. aporema, a species originally described from a high-elevation site in Costa Rica. Furthermore, the genetic distance between putative C. aporema specimens from Brazil and Costa Rica (ranging from 5.2% to 6.4%) supports the hypothesis that the Brazilian specimens are not referable to C. aporema. Our analysis revealed a single genetic strain (i.e., species) with low genetic diversity on soybean crops. We found no indication that the genetic structure was related to geographic distance among populations or edaphoclimatic regions. The population expansion of the soybean bud borer coincides with the increase in the area of soybean production in Brazil, suggesting that expanded soybean farming has allowed a significant increase in the effective population size of this pest.

Two new species of the hyperdiverse geometrid moth genus Eois (Lepidoptera, Geometridae, Larentiinae) from Ecuador, with descriptions of early stages.

The hyperdiverse geometrid genus Eois Hübner, estimated to encompass more than 1,000 species, is among the most species-rich genera in all of Lepidoptera. While the genus has attracted considerable attention from ecologists and evolutionary biologists in recent decades, limited progress has been made on its alpha taxonomy. This contribution focuses on the Olivacea clade, whose monophyly has been recognized previously through molecular analyses. We attempt to define the clade from a morphological perspective and recognize the following species based on morphology and genomic data: E.olivacea (Felder & Rogenhofer); E.pseudolivacea Doan, sp. nov.; E.auruda (Dognin), stat. rev.; E.beebei (Fletcher, 1952), stat. rev.; E.boliviensis (Dognin), stat. rev.; and E.parumsimii Doan, sp. nov. Descriptions and illustrations of the immature stages of E.pseudolivacea reared from Piper (Piperaceae) in Ecuador are provided.

Lysine-36 of Drosophila histone H3.3 supports adult longevity.

Aging is a multifactorial process that disturbs homeostasis, increases disease susceptibility, and ultimately results in death. Although the definitive set of molecular mechanisms responsible for aging remain to be discovered, epigenetic change over time is proving to be a promising piece of the puzzle. Several post-translational histone modifications have been linked to the maintenance of longevity. Here, we focus on lysine-36 of the replication-independent histone protein, H3.3 (H3.3K36). To interrogate the role of this residue in Drosophila developmental gene regulation, we generated a lysine-to-arginine mutant that blocks the activity of its cognate-modifying enzymes. We found that an H3.3BK36R mutation causes a significant reduction in adult lifespan, accompanied by dysregulation of the genomic and transcriptomic architecture. Transgenic co-expression of wild-type H3.3B completely rescues the longevity defect. Because H3.3 is known to accumulate in nondividing tissues, we carried out transcriptome profiling of young vs aged adult fly heads. The data show that loss of H3.3K36 results in age-dependent misexpression of NF-κB and other innate immune target genes, as well as defects in silencing of heterochromatin. We propose H3.3K36 maintains the postmitotic epigenomic landscape, supporting longevity by regulating both pericentric and telomeric retrotransposons and by suppressing aberrant immune signaling.

REVEILLE2 thermosensitive splicing: a molecular basis for the integration of nocturnal temperature information by the Arabidopsis circadian clock.

Cold stress is one of the major environmental factors that limit growth and yield of plants. However, it is still not fully understood how plants account for daily temperature fluctuations, nor how these temperature changes are integrated with other regulatory systems such as the circadian clock. We demonstrate that REVEILLE2 undergoes alternative splicing after chilling that increases accumulation of a transcript isoform encoding a MYB-like transcription factor. We explore the biological function of REVEILLE2 in Arabidopsis thaliana using a combination of molecular genetics, transcriptomics, and physiology. Disruption of REVEILLE2 alternative splicing alters regulatory gene expression, impairs circadian timing, and improves photosynthetic capacity. Changes in nuclear gene expression are particularly apparent in the initial hours following chilling, with chloroplast gene expression subsequently upregulated. The response of REVEILLE2 to chilling extends our understanding of plants immediate response to cooling. We propose that the circadian component REVEILLE2 restricts plants responses to nocturnal reductions in temperature, thereby enabling appropriate responses to daily environmental changes.

Complete genome sequences of Streptomyces griseus phages Spelly and Phredrick.

We present the complete genome sequences of two viruses with siphovirus morphology, isolated from soils collected in Southwestern Indiana using the host Streptomyces griseus. Spelly is a BE2 cluster phage with a 131,347-bp genome. Phredrick is a BK1 cluster phage with a 128,873-bp genome.

Assessment of Drought and Zinc Stress Tolerance of Novel Miscanthus Hybrids and Arundo donax Clones Using Physiological, Biochemical, and Morphological Traits.

High-yield potential perennial crops, such as Miscanthus spp. and Arundo donax are amongst the most promising sources of sustainable biomass for bioproducts and bioenergy. Although several studies assessed the agronomic performance of these species on diverse marginal lands, research to date on drought and zinc (Zn) resistance is scarce. Thus, the objective of this study was to investigate the drought and Zn stress tolerance of seven novel Miscanthus hybrids and seven Arundo clones originating from different parts of Italy. We subjected both species to severe drought (less than 30%), and Zn stress (400 mg/kg-1 of ZnSO4) separately, after one month of growth. All plants were harvested after 28 days of stress, and the relative drought and Zn stress tolerance were determined by using a set of morpho-physio-biochemical and biomass attributes in relation to stress tolerance indices (STI). Principal component analysis (PCA), hierarchical clustering analysis (HCA) and stress tolerance indices (STI) were performed for each morpho-physio-biochemical and biomass parameters and showed significant relative differences among the seven genotypes of both crops. Heatmaps of these indices showed how the different genotypes clustered into four groups. Considering PCA ranking value, Miscanthus hybrid GRC10 (8.11) and Arundo clone PC1 (11.34) had the highest-ranking value under both stresses indicating these hybrids and clones are the most tolerant to drought and Zn stress. In contrast, hybrid GRC3 (-3.33 lowest ranking value) and clone CT2 (-5.84) were found to be the most sensitive to both drought and Zn stress.

Liposomal bupivacaine reduces opioid requirements following Ravitch repair for pectus excavatum.

Background and Aims: The management of post-operative pain after surgical repair of pectus excavatum with the Ravitch procedure is challenging. Although previous studies have compared various methods of pain control in these patients, few have compared different local anesthetics. This retrospective analysis compares the use of bupivacaine to its longer-acting form, liposomal bupivacaine, in patients who had undergone pectus excavatum repair with the Ravitch method. Material and Methods: Eleven patients who received local infiltration with liposomal bupivacaine were matched to 11 patients who received local infiltration utilizing bupivacaine with epinephrine. The primary outcome was total morphine milligram equivalents per kilogram body weight (MME/kg) over the complete length of hospital stay. Secondary outcomes included total cumulative diazepam, acetaminophen, ondansetron, and NSAID dose per kilogram body weight (mg/kg) over the course of the hospital stay, chest tube drainage (ml/kg body weight), number of post-operative hours until the first bowel movement, Haller Index, patient request for magnesium hydroxide, average pain scores from post-operative day 1 to post-operative day 5, and length of hospital stay. Continuous variables were reported as medians with inter-quartile ranges, and categorical values were reported as percentages and frequencies. Results: The total MME/kg [1.7 (1.2-2.4) vs 2.9 (2.0-3.9), P = 0.007] and hydromorphone (mg/kg) [0.1 (0.0-0.2) vs 0.3 (0.1-0.4), P = 0.006] use in the liposomal bupivacaine group versus bupivacaine with epinephrine was significantly reduced over total length of hospital stay. Similarly, there was a reduction in diazepam use in the liposomal bupivacaine group versus the bupivacaine group [0.4 (0.1-0.8) vs 0.6 (0.4-0.7), P = 0.249], but this did not reach statistical significance. The total dose of ondansetron (mg/kg) was not statistically different when comparing the liposomal bupivacaine group to the bupivacaine group [0.3 (0.0-0.5) vs 0.3 (0.2-0.6), P = 0.332]. Interestingly, the total dose of acetaminophen (mg/kg) was statistically increased in the liposomal bupivacaine group compared to the bupivacaine with epinephrine group [172 (138-183) vs 74 (55-111), P = 0.007]. Additionally, the total chest tube drainage (ml/kg) was significantly reduced in the liposomal bupivacaine group [9.3 (7.5-10.6) vs 12.8 (11.3-18.5), P = 0.027]. Finally, the percentage of patients without requests for magnesium hydroxide to promote laxation was significantly higher in the liposomal bupivacaine group than in the bupivacaine group (63.6% vs 18.2%, P = 0.027). Conclusion: The use of liposomal bupivacaine for local infiltration in patients who undergo the Ravitch procedure for pectus repair offers advantages over plain bupivacaine, including reduced opioid consumption and opioid-related side effects. However, more data are needed to understand the significance of these findings.

The Congenital Heart Surgeons' Society Presidents and Their Contributions.

The Congenital Heart Surgeons' Society (CHSS) was founded by 16 congenital heart surgeons in 1973, who endeavored to share their clinical advances in an informal setting that would stimulate honest and forthright discussions. As the Society grew, prospective studies were organized from a centralized data center that was established and based first in Birmingham, Alabama, thence to Toronto, and recently in a collaboration between Toronto and the Cleveland Clinic. These studies formed the basis for a myriad of outcomes reports that favorably impacted surgical results. The Kirklin-Ashburn Fellowship was created and endowed by the membership which has been successful in training many congenital heart surgeons. The CHSS was then incorporated into a 501(c) (3) not-for-profit organization with bylaws, officers, and committees in 2002. Increased membership followed. The CHSS has become the face of congenital heart surgery in North America by affiliating with the World Journal for Pediatric and Congenital Heart Surgery, having one designated member on the American Board of Thoracic Surgery, and hosting joint meetings with the European Congenital Heart Surgeons Association. Since 2002, 11 presidents have been elected for two-year terms and have guided the advances that have been achieved by the CHSS. Their contributions and achievements are highlighted in chronological order.

A guanidium salt as a chaotropic agent for aqueous battery electrolytes.

This study investigates a salt design principle for aqueous battery electrolytes by combining chaotropic ions, guanidium cations (Gdm) and bis(trifluoromethanesulfonyl)imide anions (TFSI), forming GdmTFSI. This salt's crystal structure was solved via single-crystal X-ray diffraction and characterized using Fourier-transform infrared spectroscopy. Study reveals that GdmTFSI salt disrupts the hydrogen bonding network of aqueous solutions, impacting water reactivity at electrochemical interfaces.

QRS Duration After Pulmonary Valve Replacement in Adults with Repaired Tetralogy of Fallot: Association with Ventricular Arrhythmia and Correlation with Right Ventricular Size.

The aim of this study is to analyze the relationship between QRS duration after pulmonary valve replacement (PVR) and ventricular arrhythmias (VA) in patients with repaired tetralogy of Fallot (ToF). ToF patients may face complications such as heart failure and VA after primary repair, often mitigated by PVR. Prior studies have shown a decrease in QRS duration and right ventricular (RV) size following PVR. It remains unclear whether a lack of QRS duration reduction identifies patients at risk of VA. We retrospectively identified adult patients with repaired ToF who underwent surgical or transcatheter PVR. EKG data (pre-PVR, 30 days to 1-year post-PVR, and closest to CMR) was collected. The primary endpoint was sustained ventricular tachycardia (VT), ICD shock for sustained VT, or inducible VT on EP study. 85 patients were included (median follow-up 3.6 years; median age 34 years; 51% females). The primary outcome was noted in 8 patients. Mean QRS duration decreased by 5 ms following PVR (p = 0.0001). Increased age at PVR, QRS ≥ 180 ms post-PVR, no reduction in QRS after PVR, and a history of VT were associated with higher risk of the primary endpoint. The change in QRS was linearly correlated with the change in RVEDVi (R = 0.66). Adults with repaired ToF experience a reduction in QRS duration post-PVR that correlates with the change of the RV size. Patients with QRS ≥ 180 ms post-PVR, no reduction in QRS, increased age at repair, and a history of VT are at risk for recurrent VT and warrant closer monitoring/ICD consideration.

Short-term effects of a high-severity summer wildfire on conifer forest moth (Lepidoptera) communities in New Mexico, USA.

Forest fires in North America are becoming larger in area and burning with higher severity as a result of climate change and land management practices. High-severity, stand-replacement fires can inflict major changes to forest insect communities, potentially extirpating many species through altered post-fire habitat resources. We assessed forest-dwelling macrolepidopteran moth communities in mixed conifer and ponderosa pine forests during the first year after the 2011 Las Conchas fire in New Mexico, USA. We deployed blacklight traps in replicated burned and unburned stands during June, July, and August in 2012. We collected 9,478 individuals, representing 211 species and 8 families. Noctuidae (124 species) and Geometridae (53) comprised the majority of the taxa, followed by Erebidae (21), Sphingidae (5), Notodontidae (3), Lasiocampidae (2), Saturniidae (2), and Drepanidae (1). Moth communities (species composition and abundances) in each forest type (mixed conifer vs. ponderosa pine) were statistically distinguishable, but shared 56.4% (119) of observed species. Overall, compared to unburned forests, post-fire moth communities in both forest types had significantly lower numbers of individuals, species richness and diversity, and lower evenness in ponderosa pine forests. As expected, categorizing moth taxa by larval host plant taxa revealed that reductions of moth populations following fire were associated with the elimination or reduction of available larval host plants (particularly conifers, oaks, and junipers). We predict that future moth community succession will likely parallel the overall transformation from a forested landscape to a montane meadow/grassland ecosystem, with continued reduction in tree-feeding species and increasing dominance by forb/grass-feeding species.

Growth friendly surgeries increase 3D true spine length at two-years post-operative.

PURPOSE: Traditional coronal-plane vertical spine height measurements, such as T1-T12 and T1-S1 spine height, are influenced by 3-dimensional spinal deformity. Therefore, they are unreliable indicators of true spine growth. The novel 3D true spine length (3D-TSL) technique assesses spine growth regardless of the presence of 3D spinal deformity. This study evaluates the effect of growth friendly surgery on spine growth using the 3D-TSL technique at two years follow-up. METHODS: Radiographs of early onset scoliosis (EOS) participants undergoing growth friendly surgery at a single institution were evaluated at pre-index, post-index, and at 2-year follow-up. Scoliosis, kyphosis, traditional coronal height and 3D-TSL were measured. RESULTS: Twenty-four EOS patients (14 female) with a mean age of 6.3 years were included. Scoliosis improved from 77.8 ± 18.7° pre-index to 56.0 ± 17.8° post-index (p < 0.001); but increased at 2 years to 65.9 ± 20.1° (p < 0.05). Kyphosis improved from 56.0 ± 20.7° pre-index to 39.3 ± 13.8° post-index (p < 0.001); and increased again at 2 years to 48.6 ± 16.4° (p < 0.05). Traditional T1-S1 height increased from pre-index to post-index, to 2-year follow-up (245.5 ± 37.2 mm to 275.8 ± 42.7 mm; p < 0.001, to 288.0 ± 41.7 mm; p = 0.005). As expected, T1-S1 3D-TSL did not change from pre to immediately post-index (305.6 ± 43.9 mm vs 306.5 ± 44.0 mm); there was a significant change from post-index to 2-year follow-up (334.1 ± 48.0 mm; p < 0.001). CONCLUSIONS: Out of plane changes in scoliosis and kyphosis over time justify the use of the 3D-TSL for this cohort of patients. There was no significant change in 3D-TSL from pre-index to post-operatively; however, during the growth phase of treatment 3D-TSL increased significantly by 27.6 mm.

Improving field establishment and yield in seed propagated Miscanthus through manipulating plug size, sowing date and seedling age.

Biomass crops provide significant potential to substitute for fossil fuels and mitigate against climate change. It is widely acknowledged that significant scale up of biomass crops is required to help reach net zero targets. Miscanthus is a leading biomass crop embodying many characteristics that make it a highly sustainable source of biomass but planted area remains low. Miscanthus is commonly propagated via rhizome, but efficient alternatives may increase uptake and help diversify the cultivated crop. Using seed-propagate plug plants of Miscanthus has several potential benefits such as improving propagation rates and scale up of plantations. Plugs also provide an opportunity to vary the time and conditions under protected growth, to achieve optimal plantlets before planting. We varied combinations of glasshouse growth period and field planting dates under UK temperate conditions, which demonstrated the special importance of planting date on yield, stem number and establishment rates of Miscanthus. We also propagated Miscanthus in four different commercial plug designs that contained different volumes of substrate, the resulting seedlings were planted at three different dates into field trials. In the glasshouse, plug design had significant effects on above and belowground biomass accumulation and at a later time point belowground growth was restricted in some plug designs. After subsequent growth in the field, plug design and planting date had a significant effect on yield. The effects of plug design on yield were no longer significant after a second growth season but planting date continued to have a significant effect. After the second growth year, it was found that planting date had a significant effect on surviving plants, with the mid-season planting producing higher survival rates over all plug types.Establishment was positively correlated with DM biomass produced in the first growth season. Sowing date had a significant effect on establishment but the impacts of plug design were more nuanced and were significant at later planting dates. We discuss the potential to use the flexibility afforded by seed propagation of plug plants to deliver significant impacts in achieving high yield and establishment of biomass crops during the critical first two years of growth.

Variability of cell wall recalcitrance and composition in genotypes of Miscanthus from different genetic groups and geographical origin.

Miscanthus is a promising crop for bioenergy and biorefining in Europe. The improvement of Miscanthus as a crop relies on the creation of new varieties through the hybridization of germplasm collected in the wild with genetic variation and suitable characteristics in terms of resilience, yield and quality of the biomass. Local adaptation has likely shaped genetic variation for these characteristics and is therefore important to quantify. A key biomass quality parameter for biorefining is the ease of conversion of cell wall polysaccharides to monomeric sugars. Thus far, the variability of cell wall related traits in Miscanthus has mostly been explored in accessions from limited genetic backgrounds. Here we analysed the soil and climatic conditions of the original collection sites of 592 Miscanthus genotypes, which form eight distinct genetic groups based on discriminant analysis of principal components of 25,014 single-nucleotide polymorphisms. Our results show that species of the genus Miscanthus grow naturally across a range of soil and climate conditions. Based on a detailed analysis of 49 representative genotypes, we report generally minor differences in cell wall characteristics between different genetic groups and high levels of genetic variation within groups, with less investigated species like M. floridulus showing lower recalcitrance compared to the other genetic groups. The results emphasize that both inter- and intra- specific variation in cell wall characteristics and biomass recalcitrance can be used effectively in Miscanthus breeding programmes, while also reinforcing the importance of considering biomass yield when quantifying overall conversion efficiency. Thus, in addition to reflecting the complexity of the interactions between compositional and structural cell wall features and cell wall recalcitrance to sugar release, our results point to traits that could potentially require attention in breeding programmes targeted at improving the Miscanthus biomass crop.

Clinical Activity of Olvimulogene Nanivacirepvec-Primed Immunochemotherapy in Heavily Pretreated Patients With Platinum-Resistant or Platinum-Refractory Ovarian Cancer: The Nonrandomized Phase 2 VIRO-15 Clinical Trial.

Importance: Patients with platinum-resistant or platinum-refractory ovarian cancer (PRROC) have limited therapeutic options, representing a considerable unmet medical need. Objective: To assess antitumor activity and safety of intraperitoneal (IP) olvimulogene nanivacirepvec (Olvi-Vec) virotherapy and platinum-based chemotherapy with or without bevacizumab in patients with PRROC. Design, Setting, and Participants: This open-label, nonrandomized multisite phase 2 VIRO-15 clinical trial enrolled patients with PRROC with disease progression following their last prior line of therapy from September 2016 to September 2019. Data cutoff was on March 31, 2022, and data were analyzed between April 2022 and September 2022. Interventions: Olvi-Vec was administered via a temporary IP dialysis catheter as 2 consecutive daily doses (3 × 109 pfu/d) followed by platinum-doublet chemotherapy with or without bevacizumab. Main Outcomes and Measures: Primary outcomes were objective response rate (ORR) via Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) and cancer antigen 125 (CA-125) assay, and progression-free survival (PFS). Secondary outcomes included duration of response (DOR), disease control rate (DCR), safety, and overall survival (OS). Results: Twenty-seven heavily pretreated patients with platinum-resistant (n = 14) or platinum-refractory (n = 13) ovarian cancer were enrolled. The median (range) age was 62 (35-78) years. The median (range) prior lines of therapy were 4 (2-9). All patients completed both Olvi-Vec infusions and chemotherapy. Median follow-up duration was 47.0 months (95% CI, 35.9 months to NA). Overall, ORR by RECIST 1.1 was 54% (95% CI, 33%-74%), with a DOR of 7.6 months (95% CI, 3.7-9.6 months). The DCR was 88% (21/24). The ORR by CA-125 was 85% (95% CI, 65%-96%). Median PFS by RECIST 1.1 was 11.0 months (95% CI, 6.7-13.0 months), and the PFS 6-month rate was 77%. Median PFS was 10.0 months (95% CI, 6.4-NA months) in the platinum-resistant group and 11.4 months (95% CI, 4.3-13.2 months) in the platinum-refractory group. The median OS was 15.7 months (95% CI, 12.3-23.8 months) in all patients, with a median OS of 18.5 months (95% CI, 11.3-23.8 months) in the platinum-resistant group and 14.7 months (95% CI, 10.8-33.6 months) in the platinum-refractory group. Most frequent treatment-related adverse events (TRAEs) (any grade, grade 3) were pyrexia (63.0%, 3.7%, respectively) and abdominal pain (51.9%, 7.4%, respectively). There were no grade 4 TRAEs, and no treatment-related discontinuations or deaths. Conclusions and Relevance: In this phase 2 nonrandomized clinical trial, Olvi-Vec followed by platinum-based chemotherapy with or without bevacizumab as immunochemotherapy demonstrated promising ORR and PFS with a manageable safety profile in patients with PRROC. These hypothesis-generating results warrant further evaluation in a confirmatory phase 3 trial. Trial Registration: ClinicalTrials.gov Identifier: NCT02759588.

Molecular phylogeny, divergence time, biogeography and trends in host plant usage in the agriculturally important tortricid tribe Grapholitini (Lepidoptera: Tortricidae: Olethreutinae).

The leaf-roller moth tribe Grapholitini comprises about 1200 described species and contains numerous notorious pests of fruits and seeds. The phylogeny of the tribe has been little studied using contemporary methods, and the monophyly of several genera remains questionable. In order to provide a more robust phylogenetic framework for the group, we conducted a multiple-gene phylogenetic analysis of 104 species representing 27 genera of Grapholitini and 29 outgroup species. Divergence time, ancestral area, and host plant usage were also inferred to explore evolutionary trends in the tribe. Our analyses indicate that Larisa and Corticivora, traditionally assigned to Grapholitini, are best excluded from the tribe. After removal of these two genera, the tribe is found to be monophyletic, represented by two major lineages-a Dichrorampha clade and a Cydia clade, the latter of which can be divided into seven generic groups. The genus Grapholita was found to be polyphyletic, comprising three different clades, and we propose three genera to accommodate these groups: Grapholita (sensu stricto), Aspila (formerly a subgenus of Grapholita) and Ephippiphora (formerly considered a synonym of Grapholita). We summarize each generic group, including related genera not included in our analysis, providing morphological, pheromone and food plant characters that support particular branches within the molecular hypotheses. Biogeographical analyses indicate that Grapholitini probably originated in the Nearctic, Afrotropical and Neotropical regions in the Lutetian of the middle Eocene (ca. 44.3 Ma). Our results also indicate that most groups in Grapholitini originated from Fabaceae-feeding monophagous or oligophagous ancestors, and that host plant shifts probably promoted species diversification within the tribe.

Gibbalaria : A new genus of Olethreutini from the Afrotropical Region (Lepidoptera: Tortricidae: Olethreutinae), and a new combination in Cosmopoda Diakonoff.

Gibbalaria Brown and Aarvik, new genus, is described to accommodate the following species: G. divergana Brown and Aarvik, new species (TL: South Africa); G. occidentana Brown and Aarvik, new species (TL: South Africa); G. chiloanei Brown and Aarvik, new species (TL: South Africa); G. scabellana Zeller, 1852, new combination (TL: South Africa); G. mabalingwae Razowski, 2008, status revised, new combination (TL: South Africa); G. longiphallus Brown and Aarvik, new species (TL: South Africa); G. bagamoyo (Razowski & Wojtusiak, 2014), new combination (TL: Tanzania); and G. analcis (Razowski, 2015), new combination (TL: Republic of Cameroon). Gibbalaria sistrata (Meyrick, 1911), new combination (TL: South Africa), is synonymized with G. scabellana, new synonymy. Although the male genitalia of Gibbalaria form two moderately divergent groups, the two groups share extremely similar female genitalia, which feature a broad, somewhat cylindrical antrum, followed immediately anterad by a conspicuously elbowed region of the ductus bursae forming a weak diverticulum on the left side, and a signum in the form of a patch of small arrowhead-shaped sclerites, usually with a shallow pocket. Male genitalia morphology shows many similarities with the Neopotamia group (Olethreutini), Afroploce Aarvik in particular. The monophyly of Gibbalaria is supported by the raised, curled, opalescent scales on the forewing in both sexes, which occurs in a few other genera scattered through the subfamily (e.g., Thylacandra Diakonoff in Grapholitini; Astronauta Diakonoff and Cosmopoda Diakonoff in Olethreutini); the angled diverticulum in the ductus bursae in the female genitalia; the subrectangular flange from the lower margin of the valva immediately basal to the cucullus; and the setose, protruding ridge immediate above the basal cavity, which appears to be homologous with the subbasal process of the valva in many members of the Neopotamia group of genera. In addition, Diakonoffiana graziani Razowski, 2015 (TL: Republic of Cameroon) is transferred to Cosmopoda Diakonoff, resulting in C. graziani (Razowski), new combination.