Biomarkers associated with survival in patients with platinum-refractory urothelial carcinoma treated with paclitaxel.

BACKGROUND: Taxane- based chemotherapy is widely used in patients with platinum- and immunotherapy refractory, metastatic urothelial carcinoma (mUC). Outcomes are poor and biomarkers associated with outcome are lacking. We aim to identify cancer hallmarks associated with survival in patients receiving paclitaxel. METHODS: Whole-transcriptome profiles were generated for a subset of patients enrolled in a randomised phase II study investigating paclitaxel and pazopanib in platinum refractory mUC (PLUTO, EudraCT 2011-001841-34). Estimates of gene expression were calculated and input into the Almac proprietary analysis pipeline and signature scores were calculated using ClaraT V3.0.0. Ten key gene signatures were assessed: Immuno-Oncology, Epithelial to Mesenchymal Transition, Angiogenesis, Proliferation, Cell Death, Genome Instability, Energetics, Inflammation, Immortality and Evading Growth. Hazard ratios were calculated using Cox regression model and Kaplan-Meier methods were used to estimate progression free survival (PFS) and overall survival (OS). RESULTS: 38 and 45 patients treated with paclitaxel or pazopanib were included. Patients with high genome instability expression treated with paclitaxel had significantly improved survival with a HR of 0.29 (95% CI: 0.14-0.61, p=0.001) and HR 0.34 (95% CI: 0.17-0.69, p=0.003) for PFS and OS, respectively. Similarly, patients with high evading growth suppressor expression treated with paclitaxel had improved PFS and OS with a HR of 0.35 (95% CI: 0.19-0.77, p=0.007) and HR 0.46 (95% CI: 0.23-0.91, p=0.026), respectively. No other gene signatures had significant impact on outcome. In both paclitaxel and pazopanib cohorts, angiogenesis activation was associated with worse PFS and OS, and VEGF targeted therapy did not improve outcomes. CONCLUSION: High Genome-instability and Evading-growth suppressor biologies are associated with improved survival in patients with platinum refractory mUC receiving paclitaxel. These may refine mUC risk stratification and guide treatment decision in the future.

A multi-centric, single-blinded, randomized, parallel-group study to evaluate the effectiveness of nasoalveolar moulding treatment in non-syndromic patients with complete unilateral cleft lip, alveolus and palate (NAMUC study): a study protocol for a randomized controlled trial.

BACKGROUND: Cleft lip and palate (CLP) are among the most common congenital anomaly that affects up to 33,000 newborns in India every year. Nasoalveolar moulding (NAM) is a non-surgical treatment performed between 0 and 6 months of age to reduce the cleft and improve nasal aesthetics prior to lip surgery. The NAM treatment has been a controversial treatment option with 51% of the cleft teams in Europe, 37% of teams in the USA and 25 of cleft teams in India adopting this methodology. This treatment adds to the already existing high burden of care for these patients. Furthermore, the supporting evidence for this technique is limited with no high-quality long-term clinical trials available on the effectiveness of this treatment. METHOD: The NAMUC study is an investigator-initiated, multi-centre, single-blinded randomized controlled trial with a parallel group design. The study will compare the effectiveness of NAM treatment provided prior to lip surgery against the no-treatment control group in 274 patients with non-syndromic unilateral complete cleft lip and palate. The primary endpoint of the trial is the nasolabial aesthetics measured using the Asher McDade index at 5 years of age. The secondary outcomes include dentofacial development, speech, hearing, cost-effectiveness, quality of life, patient perception, feeding and intangible benefits. Randomization will be carried out via central online system and stratified based on cleft width, birth weight and clinical trial site. DISCUSSION: We expect the results from this study on the effectiveness of treatment with NAM appliance in the long term along with the cost-effectiveness evaluation can eliminate the dilemma and differences in clinical care across the globe. TRIAL REGISTRATION: ClinicalTrials.gov CTRI/2022/11/047426 (Clinical Trials Registry India). Registered on 18 November 2022. The first patient was recruited on 11 December 2022. CTR India does not pick up on Google search with just the trial number. The following steps have to be carried out to pick up. How to search: ( https://ctri.nic.in/Clinicaltrials/advsearch.php -use the search boxes by entering the following details: Interventional trial > November 2022 > NAMUC).

Effects of the medicinal plant, Tamarindus indica, as a potential supplement, on growth, nutrient digestibility, body composition and hematological indices of Cyprinus carpio fingerlings.

Tamarindus indica, a beneficial herb, has many health benefits but there is limited research on its use in fish nutrition industry. The current study investigated the effects of incorporating extracts of T. indica into the canola meal-based diets of Cyprinus carpio (common carp); following which, the growth, digestibility, carcass and hematological markers were assessed. A total of six diets were formulated with varying concentrations of T. indica extracts (TIE) viz, 0 %, 0.5 %, 1 %, 1.5 %, 2 % and 2.5 %. The fish (N = 270, 15 fish/tank with triplicates) in each tank were fed experimental diets for 70 days. The study demonstrated that TIE supplementation significantly improved the growth of common carp when compared to 0 % TIE level (control). The best results were observed at 1 % TIE level for the specific growth rate (1.68 ± 0.03 %), weight gain (15.00 ± 0.57 g), and feed conversion ratio (1.36 ± 0.05). Conversely, the 2.5 % TIE level gave the least improvement in terms of growth performance. Specifically for nutrient digestibility, the maximum values of crude protein (CP, 67.60 ± 0.83 %), crude fat (CF, 67.49 ± 0.45 %) and gross energy (GE, 70.90 ± 0.56 %) were recorded at 1 % TIE level. In addition, the best results of body composition (protein: 63.92 ± 0.06 %, ash: 18.60 ± 0.03 %, fat: 7.12 ± 0.02 % and moisture: 10.36 ± 0.04 %) and hematological indices, were measured in carps fed with 1 % supplementation level. In conclusion, the overall health of C. carpio fingerlings was improved with TIE supplementation in the diet containing 1 % TIE.

Effects of Whole-Body Vibration Therapy in Weight-Bearing and Non-Weight Bearing Positions for Upper and Lower Extremities on Balance and Cervical Joint Position Sense in Children With Cerebral Palsy.

INTRODUCTION: Cerebral palsy (CP) is a complex pathological entity that affects muscular control, coordination, proprioception, fine and gross motor abilities, position, stability, and, in some cases, cognition. This study aimed to compare the effects of whole-body vibration therapy (WBVT) in weight bearing and non-weight bearing positions for the upper and lower extremities on balance and cervical joint position sense in children with spastic CP. METHODS: A randomized controlled trial was carried out on 60 hemiplegic children with spastic CP aged 5-15 years. Following randomization, all participants were allocated into six equal-sized groups based on the application of WBVT for upper extremities, lower extremities, or both simultaneously in either weight-bearing or non-weight-bearing positions. Pediatric balance scale (PBS) and laser tracker system were used to assess functional balance and cervical joint position sense. RESULTS: One-way analysis of variance for Inter-group analysis showed a statistically significant difference among all groups in PBS and cervical joint position sense (p<0.05). CONCLUSION: WBVT was found to be beneficial in improving balance and cervical joint position sense in both weight-bearing and non-weight-bearing positions for the upper and lower extremities in children with cerebral palsy. However, the simultaneous application of WBVT in weight-bearing positions for both upper and lower extremities showed the most significant improvements in improving both balance and cervical joint position sense, indicating the most efficacious position of this treatment approach in children with cerebral palsy.

Formulation and Optimization of Effective Oil Spill Dispersants Composed of Surface-Active Ionic Liquids and Nonionic Surfactants.

The use of chemical dispersants to remove oil spills in aquatic environments raises serious concerns, including heightened toxicity and limited biodegradability, which diminish their effectiveness. This study aimed to develop an environmentally friendly formulation by combining two nonionic surfactants (Tween 80, Span 80) with two surface-active ionic liquids (SAILs): 1-butyl-3-methylimidazolium lauroyl sarcosinate [Bmim][Lausar] and choline myristate [Cho][Mys], to remediate crude oil spill. The performance of the formulation was evaluated by its emulsion stability, surface tension, interfacial tension (IFT), and effectiveness. The toxicity and biodegradability of the formulation were also assessed to ensure their safe application in aquatic environments. The formulation (F9) exhibited the most stable emulsion, maintaining stability even after 5 h with a critical micelle concentration (CMC) of 3.52 mM. The efficiency of the formulation in dispersing various crude oils (Arab, Ratawi, and Doba) ranged from 70.12 to 93.72%. Acute toxicity tests conducted on zebrafish demonstrated that the formulation, with an LC50 value of 450 mg L-1, exhibited practically nontoxicity after 96 h. The formulation showed rapid biodegradability, exceeding 60% within a 28-day testing period. This research presents a promising approach for synthesizing the green formulation which can contribute to mitigating the environmental impacts of oil spills and enhancing the efficiency of cleanup operations.

Comparison of the Conjunct Effects of Electrical Stimulation and Whole-Body Vibration Therapy with Transcranial Direct Current Stimulation and Whole-body Vibration Therapy on Balance and Function in Children With Spastic Cerebral Palsy.

BACKGROUND AND OBJECTIVES: Cerebral palsy is a neurodevelopmental condition that results in impaired movement and posture, often accompanied by disturbances in balance and functional abilities. Recent advances in neurorehabilitation, including whole-body vibration therapy (WBVT), functional electrical stimulation, and transcranial direct current stimulation, show promise in enhancing traditional interventions and fostering neuroplasticity. However, the efficacy of their conjunct effects remains largely uncharted territory and warrants further exploration. The objective of the study was to compare the conjunct effects of functional electrical stimulation (FES) and WBVT with transcranial direct current stimulation (tDCS) and WBVT on lower extremity range of motion (ROM), dynamic balance, functional mobility, isometric muscle strength and hand grip strength in children with spastic cerebral palsy. METHODS: A randomized clinical trial was carried out on 42 children of both genders with spastic cerebral palsy, aged 5-15 years. The children were divided at random into three groups (14 in each group). In Group A, there were three (21.42%) males and 11 (78.57%) females, in Group B, eight (57.14%) were males and six (42.85%) were females, and in Group C, six (42.85%) children were males and eight (57.14%) were females. Group A received WBVT only, Group B received WBVT and FES, and Group C received WBVT and tDCS. The intervention was applied four times a week for four consecutive weeks. The data was collected two times before and immediately after four weeks of intervention. Lower extremity ROM was measured by a goniometer, functional mobility or dynamic balance was measured by a Time Up and Go test, isometric muscle strength was measured by a digital force gauge, and hand grip strength was assessed by a digital hand-held dynamometer. IBM SPSS Statistics for Windows, Version 27.0 (Released 2020; IBM Corp., Armonk, New York, United States) was utilized for statistical analysis. RESULTS: The mean age of the children in groups A, B, and C was 12.21±2.11 years, 11.71±2.01, and 11.07±2.01 years respectively. Intergroup analysis revealed a statistically significant difference (p<0.05) in the lower extremity range of motion, and functional mobility. Hand grip strength and isometric muscle strength between three groups. Post hoc analysis revealed that WBVT with transcranial direct current stimulation combined showed the most improvement. CONCLUSION: The study concluded that positive effects were seen in all three groups but tDCS with WBVT was found to be most effective in improving lower extremity ROM, functional mobility or dynamic balance, isometric muscle strength, and hand grip strength in children with spastic CP. The differences between the groups were statistically significant. The effect size was substantial enough to surpass established clinical benchmarks, indicating that the observed improvements are likely to have meaningful and beneficial impacts on patient outcomes.

Enhancing photoluminescence of WSe2 in vapor grown WSe2/VOCl bilayer heterojunctions via surface passivation.

Monolayer tungsten selenide (WSe2) has attracted attention due to its direct bandgap-generated strong light emission and light-matter interaction. Herein, vertical WSe2/VOCl bilayer heterojunctions with enhanced PL of WSe2 were synthesized by the vapor growth method. The morphology, crystal structure, and chemical composition of the WSe2/VOCl heterojunctions were systematically investigated, which confirmed the successful formation of the heterojunctions. The PL emission intensity of WSe2 obtained from the WSe2/VOCl heterojunction was about 2.4 times higher than that of the WSe2 monolayer, demonstrating the high optical quality of the WSe2/VOCl heterojunction, which was further confirmed by time-resolved PL measurements. The insulator top VOCl, which was deposited on the surface of the semiconductor bottom WSe2 as a surface passivation material, reducing the impurities and resulting in an atomically clean surface, successfully enhanced the PL emission of the bottom WSe2. This vertical WSe2/VOCl bilayer heterojunction with PL enhancement could provide a promising platform for optical devices.

Baeyer-Villiger oxidation: a promising tool for the synthesis of natural products: a review.

Baeyer-Villiger oxidation is a well-known reaction utilized for the synthesis of lactones and ester functionalities from ketones. Chiral lactones can be synthesized from chiral or racemic ketones by employing asymmetric Baeyer-Villiger oxidation. These lactones act as key intermediates in the synthesis of most of the biologically active natural products, their analogues, and derivatives. Various monooxygenases and oxidizing agents facilitate BV oxidation, providing a broad range of synthetic applications in organic chemistry. The variety of enzymatic and chemoselective Baeyer-Villiger oxidations and their substantial role in the synthesis of natural products i.e., alkaloids, polyketides, fatty acids, terpenoids, etc. (reported since 2018) have been summarized in this review article.

Age, gender, and infectious status-wise assessments of hematological parameters among patients with dengue infection.

Background: The aim of this study was to examine the impact of different stages of dengue infection on immune cell counts among dengue patients and to compare them with cases of non-dengue febrile illness. Methods: The recruited patients were divided into two groups: the first group served as a control (n = 55), representing non-dengue febrile illness, and the second group was identified as dengue febrile illness (n = 149), which was further divided into three groups based on infection stage. Blood samples were collected from the selected patients and subjected to blood cell component analysis. To find IgG and IgM as well as the dengue virus non-structural antigen-1 (NS1), an immunochromatographic test (ICT) kit was utilized. Additionally, a hematological analyzer was used to determine complete blood cell counts (CBC). Data was thoroughly analyzed using Graph Pad Prism 6 software. The differences in means of different groups were calculated by applying the student's t-test. Results: The findings revealed the presence of severe leucopenia and thrombocytopenia at stages 1 and 2, accompanied by lymphopenia at stage 1. Group comparisons indicated that only teenagers exhibited a significantly lower white blood cell count compared to older individuals, while no significant differences were observed in lymphocytes, platelets, and monocytes across all age groups. Comparing different age groups of normal individuals to dengue-infected patients, the results unveiled that leucopenia was most severe in adults, followed by teenagers and children, with no significant difference in the elderly. Furthermore, adults showed the greatest degree of thrombocytopenia, followed by teens and kids, with the elderly showing the greatest degree of thrombocytopenia. Adults and teens showed extreme neutrophilia, whereas young children and the elderly showed no discernible abnormalities. Elderly patients experienced a marked decrease in monocyte count, a phenomenon not observed in other age groups. Conclusion: In conclusion both, leucopenia & thrombocytopenia, are most severe in stages 1 and 2, whereas neutrophilia & lymphopenia are predominantly severe in stage 1. These results imply that the consequences associated with dengue infection are more severe in the early stages and tend to ameliorate as the patient progresses toward recovery.

Healthy lifestyles and better periodontal health: Results from two large population-based surveys.

AIM: To ascertain whether healthy lifestyles are associated with periodontal diseases in two large-scale surveys in the US (National Health and Nutrition Examination Survey - NHANES) and the UK Biobank. METHODS: 9854 US adults and 111 679 UK adults were included in the analyses. A healthy lifestyle score (HLS), ranging between 0 and 5, was calculated based on the reported number of healthy behaviours, including never smoking, no heavy alcohol consumption, top third of leisure-time physical activity, higher dietary quality, and ideal sleep duration. The prevalence of periodontal diseases was the primary outcome in both surveys. In the NHANES, periodontal status was assessed through a full-mouth periodontal examination, while in the UKB, only self-reported periodontal status was available. RESULTS: Multiple regression analyses confirmed that the presence of at least 2-3 healthy behaviours (vs. 0-1) was associated with lower odds of overall and severe periodontitis (ORs 0.5, 0.4-0.6; p < .001 and 0.5, 0.3-0.8; p = .003, respectively) in the NHANES, and of bleeding gums (OR = 0.9, 0.8-1.0; p = .092) and loose teeth (OR = 0.6, 0.5-0.7; p < .001) in UKB. This association increased when considering prevalence of 4-5 healthy behaviours (vs. 0-1) in both the NHANES (periodontitis: OR = 0.3, 0.2-0.4; p < .001; severe periodontitis: OR = 0.1, 0.01-0.2; p < .001) and the UKB (bleeding gums: OR = 0.8, 0.7-0.9; p < .001; loose teeth: OR = 0.5, 0.4-0.6; p < .001). Mediation analyses revealed how these protective associations could be partially mediated (1-14%) by differences in biomarkers of systemic inflammation (white blood cells and neutrophils count as well as C-reactive protein). CONCLUSIONS: Adoption of healthy lifestyle behaviours is associated with a lower prevalence of periodontal diseases within two large population-based samples. This relationship exhibits a dose-response pattern, implying that greater adherence to healthy habits leads to a more significant protective effect against the odds of periodontal diseases. Additionally, our findings suggest that this protective effect is, in part, mediated by reductions in systemic inflammation.

The Effects of Whole-Body Vibration Therapy in Weight-Bearing and Non-Weight-Bearing Positions for Upper and Lower Extremities on Balance and Function in Cerebral Palsy Children: A Randomized Controlled Trial.

Background and objective Cerebral palsy (CP) is one of the most prevalent neurological conditions affecting children; it is characterized by poor motor control, restricted range of motion (ROM), and poor balance. While whole-body vibration therapy (WBVT) has been used to treat these symptoms, its efficacy in different configurations remains unexplored. Hence, this study aimed to determine and compare the effects of WBVT applied to either the upper extremities, lower extremities, or both upper and lower extremities in weight-bearing and non-weight-bearing positions on ROM (shoulders, elbows, wrists, hips, knees, and ankle joints), balance, and function in children with spastic hemiplegic CP. Methods This randomized clinical trial involved 60 hemiplegic spastic CP children aged 5-15 years. After randomization, all the participants were divided into six groups of equal size based on the WBVT application for upper extremities, lower extremities, or both in weight-bearing or non-weight-bearing positions. The therapy was applied three times per week for four consecutive weeks. The outcome measures were ROM, hand grip strength, balance quantification score using My Fitness Trainer (MFT) 2.0, and timed up and go (TUG) scores. Results While all the groups were homogenous before treatment, after treatment, it was observed that all the ranges improved significantly in all groups. The same was observed for hand grip strength, balance score, and TUG test scores (p<0.05). The post-hoc analysis revealed that the weight-bearing position for the upper and lower extremities combined showed the highest level of improvement. Conclusions Based on our findings, WBVT in weight-bearing positions produces more significant results than in non-weight-bearing positions. We also observed that when WBVT is applied to the upper extremities, it can improve the function of the lower extremities and vice versa.

The learning curve of COVID-19 and organ donation: Potential missed opportunities in the COVID era.

Background: Early in the COVID-19 pandemic, positive COVID-19 status often disqualified potential organ donors due to perceived risks, despite limited evidence. Subsequent studies have clarified that the COVID-19 status of donors, particularly when incidental and not the cause of death, does not adversely affect non-lung transplant outcomes. This study quantifies the potential loss of eligible organ donors and the corresponding impact on organ availability during the initial phase of the pandemic. Methods: In this retrospective analysis, we examined deceased donor referrals to a major organ procurement organization from June 2020 to January 2022. Referrals were categorized as All Referrals, Medically Ruled Out (MRO), or Procured Donors (PD). We used Chi-square tests for categorical comparisons and logistic regression to model additional donors and organs, contrasting COVID-negative and positive cases within age-matched cohorts. Results: Among 9478 referrals, 23.4 % (2221) were COVID-positive. Notably, COVID-positive referrals had a substantially higher MRO rate (80.6 % vs. 29.6 %, p < 0.01) and a markedly lower PD rate (0.2 % vs. 8.2 %, p < 0.01). Potential missed donations of 103 organs from COVID-positive referrals were identified. Conclusion: This OPO-level study demonstrates a substantial impact of COVID-19 status on organ donation rates, revealing significant missed opportunities. Improved management of donor COVID-19 status could potentially increase organ donations nationwide, taking into account evolving evidence and vaccine availability changes.

Effectiveness of feeding different biochars on growth, digestibility, body composition, hematology and mineral status of the Nile tilapia, Oreochromis niloticus.

Oreochromis niloticus fingerlings (5.15 ± 0.02 g; n = 315) were fed with different types of biochar (BC)-supplemented sunflower meal-based (SFM) diet to investigate the effects of various BC inclusions on their nutritional digestibility, body composition, hematology and mineral status for 60 days. Seven different diets were formulated based on the SFM based diet: one was a control (TD-I, CON) and the other six diets were supplemented with 2% BC derived from different sources. These BCs were derived from the following: cotton stick (CSBC, TD-II), wheat straw (WSBC, TD-III), corn cob (CCBC, TD-IV), house waste (HWBC, TD-V), grass waste (GWBC, TD-VI), and green waste (GwBC, TD-VII) biochar. There were three replicates for each test diet. Each tank had fifteen tilapia fingerlings, and they were fed with 5% of their live wet weight and twice daily. The outcomes showed that the supplementation of CCBC significantly elevated the growth, nutrient absorption, and body composition of the O. niloticus fingerlings (p < 0.05); with concomitant lowering of the quantity of nutrients released into the water bodies whereas HWBC gave negative impacts. The maximal mineral absorption efficiency (Ca, Na, K, Cu, Fe, P, and Zn) was achieved by the supplementation of 2% CCBC. All hematological parameters showed positive improvements (p < 0.05) with CCBC. Interestingly, CCBC significantly improved the growth, digestibility, body composition, hematology, and mineral status of O. niloticus.

Utility of Shear Wave Elastography for the Diagnosis of Plantar Fasciitis: Comparison Between Symptomatic and Asymptomatic Sides in Unilaterally Affected Patients.

INTRODUCTION: Plantar fasciitis (PF) can cause pain in the heel, which can affect everyday activities. While it often resolves on its own, diagnosing PF to rule out other hind foot conditions by imaging modality in cases of recurrence can be difficult. Methods such as MRI and ultrasonography are helpful, but the use of elastography, specifically shear wave elastography (SWE), as a tool for diagnosing PF is being studied. METHODOLOGY: This comparative observational study included patients over 18 years presenting with unilateral hind foot pain who were investigated using SWE. Exclusions comprised those who were bilaterally affected and with foot deformities, trauma history, or prior injection therapy. Patients' AOFAS Ankle-Hindfoot Scores were assessed along with visual analog scale (VAS) scores, followed by SWE examination of both heels. RESULTS: The study found no significant difference in the plantar fascia thickness between affected and unaffected sides, with a mean thickness of 4.3±0.8mm and 5.1±0.6mm, respectively. Shear wave velocity (SWV) was lower on the affected side, indicating reduced stiffness compared to the unaffected side. The Spearman rank test revealed strong direct correlations between SWV and both the VAS and HF-AOFAS scores on the affected side. CONCLUSION: The study observed that SWE enhances B-mode ultrasonography in detecting early PF even with normal plantar fascia thickness, offering a user-independent and reliable tool for treatment monitoring and correlation with functional and pain scores. Further research with larger populations can aid in developing a clinico-radiological classification system for PF, improving prognostication and treatment guidance.

Prolonged Disease Control Despite ALK Inhibitor Discontinuation in Advanced ALK-Positive NSCLC.

Introduction: EML4-ALK is an oncogenic driver, seen in around five per cent of advanced non-small-cell lung cancer (NSCLC) patients, which can be targeted with anaplastic lymphoma kinase tyrosine kinase inhibitors with great response rates. Disease flare refers to sudden rapid disease worsening on tyrosine kinase inhibitors (TKI) discontinuation, which is associated with shorter survival and worse outcomes. Here, we review cases previously published in the literature where patients developed disease flares, and contrast this with our patients who had prolonged survival despite TKI discontinuation. Case description: We report three different patients with advanced ALK-positive NSCLC seen at our institute, who had EML4-ALK translocation variant 1 oncogenic driver on next-generation sequencing. They received treatment with several different ALK inhibitors before opting to discontinue TKI. They were able to come off TKI safely without developing disease flare and had prolonged survival. Discussion: Shorter time to progression on TKI, presence of symptoms with disease progression or central nervous system/pleural metastasis have been previously linked with development of flare, although this was not seen in our case series. Tumour response at the time of treatment discontinuation, line of therapy, overall disease burden, fusion variant and co-alteration status can affect the prognosis of these patients after ALK TKI cessation. In particular, variant 1 and wild-type TP53 status may be a suitable patient population for dose optimisation strategies. Intermittent TKI dosing strategies may help to avoid acquiring resistance mutations and prevent long-term treatment toxicities. Conclusion: It is important for clinicians to identify patients at risk for developing disease flare on TKI discontinuation to improve outcomes. Intermittent TKI dosing strategies require further investigation. LEARNING POINTS: Patients who develop disease flare after cessation have poor survival and worse outcomes.Certain phenotypic and molecular characteristics of the tumour may help clinicians identify which patients are likely and which are unlikely to develop disease flare on TKI discontinuation.Advanced ALK-positive NSCLC with variant 1 and wild-type TP53 may be a suitable patient population for intermittent TKI dosing investigations.

Development of topical silver nano gel formulation of Bixin: Characterization, and evaluation of anticancer activity.

Objective: Skin cancer refers to the pathological condition characterized by the proliferation of atypical skin cells in an uncontrolled manner. Plant-based products such as bixin although show promising anticancer properties, but maintaining their stability in a formulation is a difficult task. The objective of the research is to formulate a silver nanoparticle gel preparation of bixin and evaluate its anticancer properties. Methods: The extract from Bixa orellana seed was prepared by hot extraction technique to isolate the active ingredient, bixin. A green synthesis approach was utilized for preparing the silver nanoparticle gel of bixin (BOAgNPs). Characterization of silver nanoparticles was done using FTIR, scanning electron microscopy, compatibility study, homogeneity testing, pH evaluation, and drug content determination. The in-vitro anticancer activity was performed using cell lines (B16F10) and in-vivo by chemical carcinogen (7,12-dimethylbenz (a) anthracene) in mice. Results: The BOAgNPs-loaded topical gel was found to be homogeneous (clear orange color) and pH-compatible (pH ≈ 6.66) with the skin. The characterization studies indicated the presence of all functional groups in the formulation. An optimized batch of bixin-nano gel showed about 60% inhibitory effects on B16F10 cell lines (in-vitro activity) when equated with a reference drug, 5-fluorouracil. The in-vivo anticancer study suggested suppression of tumorigenesis and promotion of the healing process with bixin-nano gel application on the skin. Conclusion: The results suggested the promising anticancer property of bixin when formulated in silver nanoparticle gel. The preparation of silver particles nano gel with bixin might provide an effective alternative option for treating skin cancers, provided more research complements the findings of the present study.

Influence of Varying Oil-Water Contents on the Formation of Crude Oil Emulsion and Its Demulsification by a Lab-Grown Nonionic Demulsifier.

This study describes how varying oil/water contents affect emulsion formation and the impact they have on emulsion droplet size, viscosity, and interfacial behavior. Crude oil (continuous phase) volume fractions of 40, 50, 60, and 70 vol % were probed in the various W/O emulsions formed. Experimental results from optical morphology revealed the emulsion droplets kept reducing as the crude oil fraction kept increasing, while the droplets were nearly unnoticeable in the emulsions derived from 60 and 70% crude oil. The viscosity-shear rate of emulsions produced from 40, 50, and 60 vol % crude oil exhibited a non-Newtonian behavior owing to the substantial volume of water content in their emulsions, whereas the viscosity-shear rate of the emulsion with 70 vol % crude oil exhibited a Newtonian behavior similar to the pure crude oil, suggesting a thorough blending of oil-water at this crude oil fraction. Besides, the viscosity-temperature measurements revealed that the viscosity of these emulsions diminished as the temperature increased and the viscosity reduction became more noticeable in an emulsion comprising 70 vol % crude oil. In the interfacial assessment, the increased crude oil content in the produced emulsion led to a sharp reduction in the interfacial tension (IFT). The IFT values after 500 s contacts between the emulsion and water (surrounding phase) were 11.86, 10.02, 8.08, and 6.99 mN/m for 40, 50, 60, and 70 vol % crude oil, respectively. Demulsification experiments showed that water removal becomes more challenging with a large volume of crude oil and a small water content. Demulsification performances of the lab-grown nonionic demulsifier (NID) after 10 h of demulsification activity at room temperature (25 °C) were 98, 90, 17.5, and 10% for the emulsions formed from 40, 50, 60, and 70 vol % crude oil, respectively, indicating that the demulsification degree decreases with an increasing crude oil content. Viscosity-time determination was applied to affirm the activity of NID on the emulsion formulated with a 50% crude oil fraction. The injection of NID in this emulsion triggered a sharp viscosity reduction, indicating the adsorption of NID at the oil-water interface and disruption of emulsifiers, enabling emulsion stability.

Investigating the relationship between heat load and shade seeking behaviour in dairy buffaloes.

The study presented in this Research Communication aimed to investigate the relationship between physiological responses, body surface temperature and shade-seeking behaviour in Nili Ravi dairy buffaloes during summer months. We enrolled 60 buffaloes, and each animal was observed for three consecutive days starting before sunrise until they moved towards the shade structures. A repeated measures ANOVA was employed to assess the changes in physiological parameters and body surface temperature between the early morning and the occurrence of shade-seeking behaviour. The average temperature humidity index and heat load index during the behavioural monitoring period (0400 to 1200 h) were 81.3 ± 6.5 and 92.9 ± 17, respectively (mean ± sd). There was no significant difference in core body temperature between sunrise and the time of shade-seeking event. However, the buffaloes had a slightly higher respiration rate at the time of shade-seeking (19.2 vs. 22.4 breaths/min). In addition, body surface temperature, measured at the flank region, shoulder, base of the ear and forehead was significantly higher at the occurrence of shade-seeking behaviour compared to the early morning. On average, the buffaloes sought shade when the surface temperature was 2°C higher than the temperature recorded before sunrise. Overall, the current findings suggest that body surface temperature, rather than core body temperature was strongly associated with shade-seeking behaviour in dairy buffaloes. These findings could be useful in developing strategies to mitigate the effects of heat stress in dairy buffalo herds and thereby improve animal welfare.

A superabsorbent and pH-responsive copolymer-hydrogel based on acemannan from Aloe vera (Aloe barbadensis M.): A smart material for drug delivery.

Combining natural polysaccharides with synthetic materials improves their functional properties which are essential for designing sustained-release drug delivery systems. In this context, the Aloe vera leaf mucilage/hydrogel (ALH) was reacted with acrylic acid (AA) to synthesize a copolymerized hydrogel, i.e., ALH-grafted-Polyacrylic acid (ALH-g-PAA) through free radical copolymerization. Concentrations of the crosslinker N,N'-methylene-bis-acrylamide (MBA), and the initiator potassium persulfate (KPS) were optimized to study their effects on ALH-g-PAA swelling. The FTIR and solid-state NMR (CP/MAS 13C NMR) spectra witnessed the formation of ALH-g-PAA. Scanning electron microscopy (SEM) analysis revealed superporous nature of ALH-g-PAA. The gel fraction (%) of ALH-g-PAA was directly related to the concentrations of AA and MBA whereas the sol fraction was inversely related to the concentrations of AA and MBA. The porosity (%) of ALH-g-PAA directly depends on the concentration of AA and MBA. The ALH-g-PAA swelled admirably at pH 7.4 and insignificantly at pH 1.2. The ALH-g-PAA offered on/off switching properties at pH 7.4/1.2. The metoprolol tartrate was loaded on different formulations of ALH-g-PAA. The ALH-g-PAA showed pH, time, and swelling-dependent release of metoprolol tartrate (MT) for 24 h following the first-order kinetic and Korsmeyer-Peppas model. Haemocompatibility studies ascertained the non-thrombogenic and non-hemolytic behavior of ALH-g-PAA.