Skippers (Family: Hesperiidae) are a large group of butterflies with ca. 4000 species under 567 genera. The lack of a time-calibrated higher-level phylogeny of the group has precluded understanding ...of its evolutionary past. We here use a 10-gene dataset to reconstruct the most comprehensive time-calibrated phylogeny of the group, and explore factors that affected the diversification of these butterflies.
Ancestral state reconstructions show that the early hesperiid lineages utilized dicots as larval hostplants. The ability to feed on monocots evolved once at the K-Pg boundary (ca. 65 million years ago (Mya)), and allowed monocot-feeders to diversify much faster on average than dicot-feeders. The increased diversification rate of the monocot-feeding clade is specifically attributed to rate shifts in two of its descendant lineages. The first rate shift, a four-fold increase compared to background rates, happened ca. 50 Mya, soon after the Paleocene-Eocene thermal maximum, in a lineage of the subfamily Hesperiinae that mostly fed on forest monocots. The second rate shift happened ca. 40 Mya in a grass-feeding lineage of Hesperiinae when open-habitat grasslands appeared in the Neotropics owing to gradual cooling of the atmospheric temperature.
The evolution of monocot feeding strongly influenced diversification of skippers. We hypothesize that although monocot feeding was an intrinsic trait that allowed exploration of novel niches, the lack of extensive availability of monocots comprised an extrinsic limitation for niche exploration. The shifts in diversification rate coincided with paleoclimatic events during which grasses and forest monocots were diversified.
Purpose
In this study, we aim to evaluate the efficacy and safety of
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AC-DOTATATE targeted alpha therapy in advanced-stage paragangliomas (PGLs).
Methods
Nine (6 males and 3 females) consecutive ...patients with histologically proven PGLs were treated with
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Ac-DOTATATE targeted alpha therapy (TAT) and concomitant radiosensitizer, capecitabine, at 8-weekly intervals up to a cumulative activity of ~ 74 MBq. The primary endpoint included evaluating therapy response and disease control rate (DCR) using the RECIST 1.1 criteria. Additional secondary endpoints comprised clinical response assessment using EORTC QLQ-H&N35 questionnaire, Karnofsky Performance Scale (KPS), Eastern Cooperative Oncology Group performance status (ECOG), analgesic score (AS), dose alterations of anti-hypertensive drugs (anti-HTN), and the safety and side-effect profile evaluation as per CTCAE criteria version 5.0.
Results
Following
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Ac-DOTATATE treatment, morphological response revealed partial response in 50%, stable disease in 37.5%, and disease progression in 12.5%, with a DCR of 87.5%. Similarly, the symptomatic response was remarkable, and anti-HTN drugs were stopped in 25% and reduced in 37.5%. Another significant finding in our study revealed a morphologic DCR of 66.6% (2/3) in patients who failed previous lutetium-177 peptide receptor radionuclide therapy (
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Lu-PRRT). Regarding the KPS, ECOG, and AS performance scores, a notable improvement was observed post-
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Ac-DOTATATE treatment. The QLQ-H&N35 symptom scores evaluated in seven H&N PGL patients showed significant improvement in all aspects. No improvement in sexual function was noted (
P
= 0.3559). Despite the significant reduction in the analgesic score post-treatment (
P
= 0.0031), the QLQ-H&N35 revealed only marginal significance concerning the intake of pain killers (
P
= 0.1723). No grade III/IV hematological, renal, and hepatological toxicities were noted.
Conclusion
The evidence from this study suggests
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Ac-DOTATATE therapy is effective and safe in the treatment of advanced-stage PGLs and also reports a clear benefit even in patient’s refractory to the previous
177
Lu-PRRT.
Investigators have extensively explored the short-term safety and efficacy data on 177Lu-PSMA-617 radioligand therapy (RLT) in mCRPC patients. However, scarce literature is reported on the long-term ...outcome of these patients. The current goal of this study is focused on the long-term outcome of mCRPC patients treated with 177Lu-PSMA-617 RLT.
Among 135 patients, 121 mCRPC patients fulfilled the eligibility criteria and were included in the final analysis. Patients received a median of 3 cycles of 177Lu-PSMA-617 RLT at 6 to 12-week intervals. Primary endpoint included overall survival (OS) and secondary endpoints involved progression-free survival (PFS), predictive factors of OS and PFS, PSA response rate, molecular response, clinical response, and toxicity assessment.
The median administered cumulative activity was 20 GBq (3.7-37 GBq). The median follow-up duration was 36 months (6-72 months). The estimated median PFS and OS were 12 months (mo) (95% CI: 10.3-13 mo) and 16 mo (95% CI: 13-17 mo), respectively. Any PSA decline and PSA decline >50% was achieved in 73% and 61% of the patients, respectively. Multivariate analysis revealed only failure to achieve >50% PSA decline as a significant factor associated with a poor PFS. Prognostic factors associated with reduced OS included, failure to experience >50% PSA decline, heavily pre-treated patient cohort who received >2 lines of prior treatment options, and patient sub-group treated with ≥2 lines of chemotherapy. Patients re-treated with additional treatment options after attaining 177Lu-PSMA refractory disease showed a remarkably prolonged OS. A significant clinical benefit was achieved post 177Lu-PSMA-617 RLT. The most common toxicities observed were fatigue (34.7%), followed by nausea (33%), and dry mouth (24.7%).
The current study supports the short-term safety and efficacy results of high response rates, prolonged PFS and OS, improved quality of life, and low treatment-related toxicities in patients treated with 177Lu-PSMA-617 radioligand therapy.
To determine equivalence of modified gemcitabine and oxaliplatin compared with gemcitabine and cisplatin in unresectable gallbladder cancer (GBC). Primary end-point was overall survival (OS).
Open ...label, prospective, randomised phase III equivalence study. Inclusion criteria included histologically proven unresectable GBC, 18 years or older, adequate organ functions and Eastern Cooperative Oncology Group ≤2.
108 patients were required in each arm to have an equivalence margin of ±2 months with power of 80%.
Modified gemcitabine and oxaliplatin (mGemOx)—gemcitabine 900 mg/m2, oxaliplatin 80 mg/m2, maximum 6 cycles; gemcitabine + cisplatin (CisGem)—gemcitabine 1000 mg/m2, cisplatin 25 mg/m2, maximum 8 cycles, all day 1 and 8 every 3 weeks.
Two hundred sixty subjects were recruited between February 2011 and July 2015. Two hundred forty-three patients (119, mGemOx and 124, CisGem) received at least 1 dose and analysed for safety and efficacy (modified intention to treat). Median OS was 8·5 months for whole group (95% confidence interval CI: 7·9–9·1). Median OS in mGemOx was 9 months and 8·3 months in CisGem; p = 0·057 (hazard ratio = 0·78; 95% CI = 0·60-1·02). Restricted mean OS for follow-up limited to 30 months was 11·2 months (95% CI: 9·8–12·6) in mGemOx and 10·4 months (95% CI: 9·1–11·7) in CisGem. Difference of the mean was 0·8 months with 95% CI, exceeding 2 months (−1·1 to 2·7), hence rejecting equivalence. Peripheral neuropathy, thrombocytopaenia in mGemOx and nephrotoxicity was higher with CisGem.
This trial failed to show equivalence of eight cycles of CisGem to six cycles of mGemOx. Numerically OS was better with mGemOx. Toxicities were different. The trial was not powered to answer superiority.
CTRI/2010/091/001406.
•No randomised controlled trials have compared CisGem and mGemOx in unresectable gallbladder cancer.•A phase III randomised equivalence study with 2 months of equivalence margin was conducted.•243 subjects were analysed in modified ITT analysis.•Median overall survival in mGemOx was 9 months and 8·3 months in CisGem.•Results confirmed that 8 cycles of CisGem were not equivalent to 6 cycles of mGemOx.
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•Time-calibrated phylogeny representing ca. 90% of Hypolimnas species.•Hypolimnas originated in Africa and dispersed to Asia supporting ‘Out-of-Africa’ hypothesis.•Broader host plant ...range of non-African lineage in comparison to that of African lineage.•A common mitotype in H. bolina and H. alimena, and its strong association with Wolbachia.
Hypolimnas butterflies (Nymphalidae), commonly known as eggflies, are a popular model system for studying a wide range of ecological questions including mimicry, polymorphism, wing pattern evolution, and Wolbachia-host interactions. The lack of a time-calibrated phylogeny for this group has precluded understanding its evolutionary history. We reconstruct a species-level phylogeny using a nine gene dataset and estimate species divergence times. Based on the resulting tree, we investigate the taxon’s historical biogeography, examine the evolution of host plant preferences, and test the hypothesis that the endosymbiotic bacterium Wolbachia mediates gene transfer between species. Our analyses indicate that the species are grouped within three strongly supported, deeply divergent clades. However, relationships among these three clades are uncertain. In addition, many Hypolimnas species are not monophyletic or monophyletic with weak support, suggesting widespread incomplete lineage sorting and/or introgression. Biogeographic analysis strongly indicates that the genus diverged from its ancestor in Africa and subsequently dispersed to Asia; the strength of this result is not affected by topological uncertainties. While the larvae of African species feed almost exclusively on Urticaceae, larvae of species found further east often feed on several additional families. Interestingly, we found an identical mitochondrial haplotype in two Hypolimnas species, H. bolina and H. alimena, and a strong association between this mitotype and the Wolbachia strain wBol1a. Future investigations should explore the plausibility of Wolbachia-mediated introgression between species.
Abstract Cervical cancer is still the leading cause of cancer mortality worldwide even after introduction of vaccine against Human papillomavirus (HPV), due to low vaccine coverage, especially in the ...developing world. Cervical cancer is primarily treated by Chemo/Radiotherapy, depending on the disease stage, with Carboplatin/Cisplatin-based drug regime. These drugs being non-specific, target rapidly dividing cells, including normal cells, so safer options are needed for lower off-target toxicity. Natural products offer an attractive option compared to synthetic drugs due to their well-established safety profile and capacity to target multiple oncogenic hallmarks of cancer like inflammation, angiogenesis, etc. In the current study, we investigated the effect of Bergenin (C-glycoside of 4- O -methylgallic acid), a natural polyphenol compound that is isolated from medicinal plants such as Bergenia crassifolia , Caesalpinia digyna, and Flueggea leucopyrus . Bergenin has been shown to have anti-inflammatory, anti-ulcerogenic, and wound healing properties but its anticancer potential has been realized only recently. We performed a proteomic analysis of cervical carcinoma cells treated with bergenin and found it to influence multiple hallmarks of cancers, including apoptosis, angiogenesis, and tumor suppressor proteins. It was also involved in many different cellular processes unrelated to cancer, as shown by our proteomic analysis. Further analysis showed bergenin to be a potent-angiogenic agent by reducing key angiogenic proteins like Galectin 3 and MMP-9 (Matrix Metalloprotease 9) in cervical carcinoma cells. Further understanding of this interaction was carried out using molecular docking analysis, which indicated MMP-9 has more affinity for bergenin as compared to Galectin-3. Cumulatively, our data provide novel insight into the anti-angiogenic mechanism of bergenin in cervical carcinoma cells by modulation of multiple angiogenic proteins like Galectin-3 and MMP-9 which warrant its further development as an anticancer agent in cervical cancer.
•Effect of different sizes of wire mesh on the performance of the system have been investigated.•Nusselt number, Friction factor, Thermohydraulic performance parameter, and Effective efficiency have ...been evaluated for judging the performance of the system.•Use of wire mesh improved the thermal performance of the impinging jet solar air heater.•The article has been concluded with a wire mesh and jet nozzle design recommendation.
This study revolves around improving the thermal performance of impinging jet solar air heater (IJSAH) by using wire mesh of three different sizes. The wire mesh sizes were 0.5×0.5, 1.5×1.5, and 3×3 inches with nozzle diameter (Dj) equal to 3 and 6 mm and Reynolds number (Re) ranging from 4913 to 13103. The variation of Nusselt number (Nu), friction factor (f), thermo-hydraulic performance parameter (THPP), and effective efficiency (ηeff) were evaluated for varying Re. Maximum Nu was developed for case 3 and equalled 109.86, which was 7.3 % and 246 % higher than a smooth IJSAH and flat plate solar air heater (FPSAH), respectively. The minimum friction factor attained equated to 0.0314 for case 2 at Re = 13103. Maximum THPP attained by the setup equalled 1.78 for case 4, having Dj = 6 mm. The THPP attained by case 4 across the range of Re was on an average 9.15 % higher when compared to smooth IJSAH with Dj = 3 mm. Additionally, the system achieved maximum ηeff of 0.53695 at Re = 4913 for case 4. Finally, it was recommended to use a wire mesh having a mesh size equal to 1.5×1.5 inch with Dj = 6 mm for optimum performance.
The prognosis of patients with multiple myeloma (MM) has improved significantly in the past two decades. This is attributed to use of novel agents for induction, high-dose chemotherapy and autologous ...stem cell transplantation (ASCT), maintenance therapy, and improved supportive care. Currently, evidence-based management guidelines/recommendations developed by International societies/groups are being followed partially in low-resource settings. Lack of quality diagnostics (eg, cytogenetics/fluorescence in situ hybridization (FISH), serum free light chains), novel therapeutics, and trained manpower, and limited financial resources are key challanges. An optimal utilization of available resources with continued educational activities of treating physicians focused on improving knowledge in the management of such patients may be a way forward to improve the outcome of myeloma patients in these countries. Our current approach to the management of this disease is presented here through a discussion of clinical vignettes.
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