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Background: First line (1L) TP-Ex-like regimen followed by 2nd-line (2L) immunotherapy represents one of the standards of care in platinum-sensitive recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN). We report our experience from 2 tertiary care institutions of India. Methods: This is a retrospective analysis of consecutive patients of platinum-sensitive R/M SCCHN treated with 1L weekly paclitaxel, carboplatin, and cetuximab (PCC) regimen followed by cetuximab maintenance (if non-progressive) or 2L nivolumab or oral metronomic chemotherapy (OMCT) on progression. Overall response rates (ORR), progression-free survival after 1L and 2L (PFS-1 & PFS-2), overall survival (OS), and safety were evaluated. Results: The study included 54 patients; median age 56.5 years; 89% men; 11% had cardiac dysfunction; 13% had renal dysfunction. After 1L PCC, ORR was 59.3%; median PFS-1 was 7.031 months; 61% had progression; 35% were treated with nivolumab and 18% with OMCT. The ORR was 26.3% (nivolumab) and 10% (OMCT). Median PFS-2 was 6.5 months (nivolumab) and 2 months (OMCT). The median OS was 15.01 months (entire cohort), 20.6 months (nivolumab), and 7 months (OMCT). Grade III/IV adverse events on PCC included neutropenia (31.4%), anaemia (35.1%), thrombocytopenia (7.4%), febrile neutropenia (11.1%), and skin reaction (16.6%); no Grade-III/IV treatment-related toxicities on 2L. Conclusions: 1L weekly PCC is an effective regimen for palliative therapy of platinum- sensitive R/MSCCHN with an acceptable toxicity profile. The addition of 2L nivolumab on progression further improves the outcomes.

Applications of ultra-low-loss photonic circuitry in quantum photonics, in particular including triggered single photon sources, are rare. Here, the authors show how InAs quantum dot single photon sources can be integrated onto wafer-scale, CMOS compatible ultra-low loss silicon nitride photonic circuits.

Background: The gut microbiota (GM) of the human body comprises several species of microorganisms. This microorganism plays a significant role in the physiological and pathophysiological processes of various human diseases. Methods: The literature review includes studies that describe causative factors that influence GM. The GM is sensitive to various factors like circadian rhythms, environmental agents, physical activity, nutrition, and hygiene that together impact the functioning and composition of the gut microbiome. This affects the health of the host, including the psycho-neural aspects, due to the interconnectivity between the brain and the gut. Hence, this paper examines the relationship of GM with neurodegenerative disorders in the context of these aforesaid factors. Conclusion: Future studies that identify the regulatory pathways associated with gut microbes can provide a causal link between brain degeneration and the gut at a molecular level. Together, this review could be helpful in designing preventive and treatment strategies aimed at GM, so that neurodegenerative diseases can be treated. [ABSTRACT FROM AUTHOR]

The objective of the present study was the biosynthesis of nonhazardous and cost-effective silver nanoparticles (AgNPs) using plant extracts of Azadirachta indica (neem), for the removal of hexavalent chromium [Cr (VI)] ions from an aqueous solution. Fourier transform infrared (FT-IR) and energy dispersive X-ray (EDX) spectroscopy characterization results confirmed successful biosynthesis and the presence of elemental silver in the AgNPs. Further, scanning electron microscopy (SEM) and particle size analysis indicated that AgNPs have an amorphous structure and are highly monodispersed. Batch adsorption studies were conducted to investigate the impact of parameters, like pH, time, and initial concentration on Cr (VI) removal efficiency at a fixed AgNP dose of 50 mg and 150 rpm. From the batch study, maximum chromium removal of 87.68% was achieved at an initial concentration of 5 mg/L, pH of 1, and time of 50 min. Results from equilibrium and kinetic study indicated pseudo-second-order reactions kinetics with monolayer coverage. The maximum adsorption capacity of 7.2 mg/g was obtained at an equilibrium time of 50 min and temperature of 30°C. These synthesized AgNPs also displayed significant antibacterial activity against both Gram-positive Bacillus subtilis and Gram-negative Escherichia coli. Based on the results obtained, biosynthesized AgNPs from extracts of A. indica could be utilized for the removal of water pollutants. [ABSTRACT FROM AUTHOR]

Hepatitis delta virus (HDV) co-infections more often result in severe hepatitis compared to hepatitis B virus (HBV) infections alone. Despite a high HDV prevalence (7.1%), information regarding circulating HDV clades is very limited in Botswana. We extracted total nucleic acid from confirmed HDV-positive samples and quantified their viral load. We then sequenced the large hepatitis delta antigen (L-HDAg) using Oxford Nanopore Technology (ONT). Genotyping was performed using the HDV Database, and HDV mutation profiling was performed on AliView. All participants with HBV genotypic information belonged to sub-genotype A1, and 80% (4/5) of them had a higher HDV viral load and a lower HBV viral load. We sequenced 75% (9/12) of the HDV-positive samples, which belonged to HDV clade 8. A total of 54 mutations were discovered, with the most prevalent being Q148R (16%), D149P (16%) and G151D (16%). Known mutations such as S117A, K131R, R139K and G151D were detected, while the other mutations were novel. Our results reveal that HDV clade 8 is the predominant clade in Botswana. The significance of all mutations remains unclear. Future studies with a larger sample size to detect other HDV clades that might be circulating in Botswana and functionally characterize the detected mutations are warranted. [ABSTRACT FROM AUTHOR]

Understanding photo-physics giving rise to quantum beating oscillations in hybrid organic-inorganic perovskites aids their applications in spintronics and quantum information science. Here, authors demonstrate that quantum beatings observed in single crystal perovskite at cryogenic temperatures are originating from positive and negative trions.

Opioids play a crucial role in pain management in spite of causing increased hospital morbidity and related costs. It may also cause significant risks such as postoperative nausea and vomiting (PONV), sedation, sleep disturbances, urinary retention and respiratory depression (commonly referred to as opioid related adverse effects) in postoperative patients. In order to evade these opioid related side effects and also improve pain management, multimodal analgesia i.e., combination of different analgesics, was introduced more than a decade ago. Both pharmacological and non-pharmacological techniques are available as opioid sparing analgesia. Research from around the world have proved pharmacological techniques ranging from acetaminophen, NSAIDs (non-steroidal anti-inflammatory drugs), N-methyl-D-aspartate receptor antagonists (NDMA), alpha-2 agonists, anticonvulsants such as gamma aminobutyric acid analogues, beta-blockers, capsaicin, lignocaine infusion to glucocorticoids to be effective. On the other hand, non-pharmacological methods include techniques such as cognitive behavioral therapy, transcutaneous electrical nerve stimulation (TENS), electroanalgesia, acupuncture and hypnosis. However, research regarding the effect of these non-pharmacological techniques on pain management is still needed.

We report on the irradiation of gold rod–sphere assemblies with ultrashort laser pulses, producing structures that are very difficult to obtain by other methods. The optical response of these assemblies displays several peaks arising from the interaction of the plasmon modes of the individual particles, offering thus great flexibility to control the energy deposited on the individual particles. Judicious selection of the wavelength and fluence of the laser pulses allow fine control over the changes produced: the particles can be melted, welded and/or the organic links cleaved. In this way, it is possible to generate structures “à la carte” with a degree of control unmatched by other synthetic protocols. The method is exemplified with gold nanoparticles, but it can be easily implemented on particles composed of different metals, widening considerably the range of possibilities. The final structures are excellent candidates for surface-enhanced spectroscopies or plasmonic photothermal therapy as they have a very intense electric field located outside the structure, not in the gaps.

Abstract Background DNA polymerase epsilon (POLE) is encoded by the POLE gene, and POLE-driven tumors are characterized by high mutational rates. POLE-driven tumors are relatively common in endometrial and colorectal cancer, and their presence is increasingly recognized in ovarian cancer (OC) of endometrioid type. POLE-driven cases possess an abundance of TCT > TAT and TCG > TTG somatic mutations characterized by mutational signature 10 from the Catalog of Somatic Mutations in Cancer (COSMIC). By quantifying the contribution of COSMIC mutational signature 10 in RNA sequencing (RNA-seq) we set out to identify POLE-driven tumors in a set of unselected Mayo Clinic OC. Methods Mutational profiles were calculated using expressed single-nucleotide variants (eSNV) in the Mayo Clinic OC tumors (n = 195), The Cancer Genome Atlas (TCGA) OC tumors (n = 419), and the Genotype-Tissue Expression (GTEx) normal ovarian tissues (n = 84). Non-negative Matrix Factorization (NMF) of the mutational profiles inferred the contribution per sample of four distinct mutational signatures, one of which corresponds to COSMIC mutational signature 10. Results In the Mayo Clinic OC cohort we identified six tumors with a predicted contribution from COSMIC mutational signature 10 of over five mutations per megabase. These six cases harbored known POLE hotspot mutations (P286R, S297F, V411L, and A456P) and were of endometrioid histotype (P = 5e−04). These six tumors had an early onset (average age of patients at onset, 48.33 years) when compared to non-POLE endometrioid OC cohort (average age at onset, 60.13 years; P = .008). Samples from TCGA and GTEx had a low COSMIC signature 10 contribution (median 0.16 mutations per megabase; maximum 1.78 mutations per megabase) and carried no POLE hotspot mutations. Conclusions From the largest cohort of RNA-seq from endometrioid OC to date (n = 53), we identified six hypermutated samples likely driven by POLE (frequency, 11%). Our result suggests the clinical need to screen for POLE driver mutations in endometrioid OC, which can guide enrollment in immunotherapy clinical trials.

Abstract Angiosarcoma is an aggressive malignancy of endothelial cells that carries a high mortality rate. Cytotoxic chemotherapy can elicit clinical responses, but the duration of response is limited. Sequencing reveals multiple mutations in angiogenesis pathways in angiosarcomas, particularly in vascular endothelial growth factor (VEGFR) and mitogen-activated protein kinase (MAPK) signaling. We aimed to determine the biological relevance of these pathways in angiosarcoma. Tissue microarray consisting of clinical formalin-fixed paraffin embedded tissue archival samples were stained for phospho- extracellular signal-regulated kinase (p-ERK) with immunohistochemistry. Angiosarcoma cell lines were treated with the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib, pan-VEGFR inhibitor cediranib, or combined trametinib and cediranib and viability was assessed. Reverse phase protein array (RPPA) was performed to assess multiple oncogenic protein pathways. SVR angiosarcoma cells were grown in vivo and gene expression effects of treatment were assessed with whole exome RNA sequencing. MAPK signaling was found active in over half of clinical angiosarcoma samples. Inhibition of MAPK signaling with the MEK inhibitor trametinib decreased the viability of angiosarcoma cells. Combined inhibition of the VEGF and MAPK pathways with cediranib and trametinib had an additive effect in in vitro models, and a combinatorial effect in an in vivo model. Combined treatment led to smaller tumors than treatment with either agent alone. RNA-seq demonstrated distinct expression signatures between the trametinib treated tumors and those treated with both trametinib and cediranib. These results indicate a clinical study of combined VEGFR and MEK inhibition in angiosarcoma is warranted.

COVID-19 pandemic has resulted in widespread global disruptions. While much is being discussed about the health and economic impacts, there has been a limited focus on the immediate food sector shocks and their related social implications in developing countries, especially when the farmer surveys cannot be conducted due to mobility restrictions in many countries. To overcome these challenges, this study uses news mining and content analysis of media articles published from February to April 2020, to assess the early impacts of the COVID-19 pandemic on the food supply chain and farm distress in India. It also presents the media perception of the impact of the pandemic and resulting policy measures using sentiment analysis, in addition to the cross-tabulation of results that show differential impacts across food supply chain components among different commodity groups and regions. The results show wide-scale impacts across different components of the food supply chain ranging from crop harvesting and processing, distribution and logistics to disruptions across food markets, as represented by 22, 11 and 30% of total articles, respectively. The impacts are also differentiated by commodity groups, with animal products having more trade and demand-side issues, logistic bottlenecks in fruits and vegetables and crops showing problems in labor availability and harvesting. Sentiment analysis of news items shows a spike in the negative sentiment immediately post the national lockdown, with relatively less negativity in subsequent weeks due to large-scale policy and community action. Sentiment classification along different indicators shows the highest negative sentiment for animal products (85%) in commodity groups, western states of India (78%) among different regions, and food supply (85%) and markets (83%) among supply chain components. Further, extreme weather analysis (using excess rainfall events) shows that farmers faced compound risks from the COVID-19 pandemic and extreme weather events in many parts of the country. The results highlight the importance of building resilient food systems, especially when the biotic and abiotic shocks are projected to increase globally due to many drivers including biodiversity loss and climate change.

Automatic pancreas detection and cropping with high precision from medical images is an important yet challenging problem for medical image analysis and Computer-Aided Diagnosis (CAD). Factors relating to the limited availability of image data and segmentation methodology hinder this task. High variability in the location of the pancreas,which occupies a very small area of the pancreatic Computed Tomography (CT) scans,and the anatomy of organs also add to the list of issues. These challenges necessitate an urgent need for the development of localization and auto-cropping methods of the region of interest (ROI). This paper presents the results obtained by the implementation of Region-based Convolutional Neural Network (RCNN)-Crop inspired by the Region Proposal Network (RPN) and Feature Pyramid Network (FPN) to localize the pancreas by building bounding boxes and auto-crop the ROI obtained from various other organs in the pancreatic CT scans and has a Mean Average Precision (mAP) of 28.10% for the dataset provided. [ABSTRACT FROM AUTHOR]