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Superparamagnetic iron oxide nanoparticles (SPIONs) represent a versatile class of theranostics with profound applications in biomedicine. An eco-friendly modification of SPIONs was attempted with a 110 kDa galactomannan (PSP001) isolated from the fruit rind of Punica granatum. The PSP001 appended SPIONs favor unique advantages including tumor-targeted accumulation and improved biocompatibility. The antineoplastic agent methotrexate (MTX) was covalently attached with the galactomannan in the SPIONs to yield PSP-IO NPs that demonstrated a reduction-sensitive drug release kinetics favoring MTX accumulation selectively in the tumor cells. Folate receptor (FR) targeted cancer cell uptake followed by the stimuli-responsive release of the payload favored improved biocompatibility and lack of toxicity in BALB/c mice. Superior tumor reduction capacity with marked survival benefits was observed in Ehrlich ascites carcinoma (EAC) bearing solid tumor mice. Phantom imaging of the carrier (PSP-IO) and the drug-loaded (PSP-IO-MTX NPs) nano-constructs generated an r2 relaxivity of 335.3 mM

Observational, descriptive design.Despite scapular mobility being essential for the completion of activities of daily living (ADLs), there is currently no established, a reliable goniometric technique to measure scapular protraction and retraction. A proposed method has shown clinically significant inter-rater reliability for a goniometric technique for these measurements.This observational descriptive study examined the intra-rater reliability of a goniometric technique to assess scapular protraction and retraction among a sample of healthy adults.An occupational therapist who is a certified hand therapist (CHT) and an occupational therapy student used goniometry to measure the neutral (resting), protracted, and retracted positions of the right and left scapula for a sample of healthy young adults (n = 54; a total of 108 data points for each measurement). These measurements were compared to analyze intra-rater and inter-rater reliability.For measurements of the scapula in neutral, protraction, and retraction, the standard error of measure (SEM) for repeat measures by the expert and novice raters was4.5° and3.9° respectively and ICC values ranged from poor to moderate (0.37-0.63). The SEM for measures between evaluators was5.0° and the ICC was poor (0.16-0.35). Minimum detectable change (MDC) values as a percentage of the mean (% MDC) ranged between 15.9 and 43.7% for intra-rater reliability and 21.9-52.8% for inter-rater reliability.The results of the study were mixed; variance of less than 5° for repeat measures by the same rater and measures between raters suggest clinically acceptable reliability. However, variance as a proportion of available motion (%MDC) demonstrates a broader range both above and below the threshold of 30% suggested for rehabilitation assessments.There are few efficient, reliable techniques to measure scapular mobility in clinical practice. The absolute reliability of goniometry to measure scapular protraction and retraction is similar to measurements of other joints. However, additional research and possible refinement of the technique is recommended to further address relative reliability and validity.

Data availability: Data will be made available on request. Supplementary data are available online at: https://www.sciencedirect.com/science/article/pii/S0261379423000355?via%3Dihub#appsec1 . Copyright © 2023 The Authors. How do voters respond to candidates accused of sexual harassment? The literature on political scandals demonstrates that candidate characteristics, scandal type, and voter characteristics matter; as well as party affiliation. However, empirical evidence suggests that not all co-partisans react the same way. Why is this the case? Our study uses Schwartz's (1996) theory of values to hypothesise that voters prioritising ‘universalism’ and ‘benevolence’ are less likely to vote for candidates accused of sexual harassment compared to voters who prioritise ‘self-enhancement’ values. Using an original, mixed methods, online survey experiment (n = 704), we show that American voters do become less favourable towards candidates linked to allegations of sexual harassment; but a sizeable minority would nevertheless vote for a co-partisan candidate accused of sexual harassment. Values are an important mechanism to explain this heterogeneity. Qualitative data corroborates our findings, and helps explain why sexual harassment allegations are not always a barrier to electoral success. We thank Brunel University London for supporting the study through a Research Development Fund Award, and Royal Holloway University of London for additional financial support.

Purpose: Agonist antibodies targeting the T-cell costimulatory receptor 4-1BB (CD137) are among the most effective immunotherapeutic agents across preclinical cancer models. In the clinic, however, development of these agents has been hampered by dose-limiting liver toxicity. Lack of knowledge of the mechanisms underlying this toxicity has limited the potential to separate 4-1BB agonist–driven tumor immunity from hepatotoxicity.Experimental Design: The capacity of 4-1BB agonist antibodies to induce liver toxicity was investigated in immunocompetent mice, with or without coadministration of checkpoint blockade, via (i) measurement of serum transaminase levels, (ii) imaging of liver immune infiltrates, and (iii) qualitative and quantitative assessment of liver myeloid and T cells via flow cytometry. Knockout mice were used to clarify the contribution of specific cell subsets, cytokines, and chemokines.Results: We find that activation of 4-1BB on liver myeloid cells is essential to initiate hepatitis. Once activated, these cells produce interleukin-27 that is required for liver toxicity. CD8 T cells infiltrate the liver in response to this myeloid activation and mediate tissue damage, triggering transaminase elevation. FoxP3+ regulatory T cells limit liver damage, and their removal dramatically exacerbates 4-1BB agonist–induced hepatitis. Coadministration of CTLA-4 blockade ameliorates transaminase elevation, whereas PD-1 blockade exacerbates it. Loss of the chemokine receptor CCR2 blocks 4-1BB agonist hepatitis without diminishing tumor-specific immunity against B16 melanoma.Conclusions: 4-1BB agonist antibodies trigger hepatitis via activation and expansion of interleukin-27–producing liver Kupffer cells and monocytes. Coadministration of CTLA-4 and/or CCR2 blockade may minimize hepatitis, but yield equal or greater antitumor immunity. Clin Cancer Res; 24(5); 1138–51. ©2018 AACR.

Supplemental Figure 1: Peak of 4-1BB mediate liver transaminase level and gating strategy for flow cytometry analysis of liver immune infiltrates. Supplemental Figure 2: Representative flow cytometry analysis of liver immune infiltrates. Supplemental Figure 3: Administration of 4-1BB agonist antibodies initiates liver pathology through activation of liver-resident myeloid cells. Supplemental Figure 4: Effects of IL-27 pathway inactivation on CD4 T cells. Supplemental Figure 5: Representative flow cytometry analysis of liver immune infiltrates.

Transcriptional memory, by which cells respond faster to repeated stimuli, is key for cellular adaptation and organism survival. Chromatin organization has been shown to play a role in the faster response of primed cells. However, the contribution of post-transcriptional regulation is not yet explored. Here we perform a genome-wide screen to identify novel factors modulating transcriptional memory in S. cerevisiae in response to galactose. We find that depletion of the nuclear RNA exosome increases GAL1 expression in primed cells. Our work shows that gene-specific differences in intrinsic nuclear surveillance factor association can enhance both gene induction and repression in primed cells. Finally, we show that primed cells present altered levels of RNA degradation machinery and that both nuclear and cytoplasmic mRNA decay modulate transcriptional memory. Our results demonstrate that mRNA post-transcriptional regulation, and not only transcription regulation, should be considered when investigating gene expression memory.

Carbohydrate–lectin interactions and glycol-molecule-driven self-assembly are powerful yet challenging strategies to create supramolecular nanostructures for biomedical applications. Herein, we develop a modular approach of micellization with a small molecular mannosylated-calix[4]arene synthetic core, CA4-Man3, to generate nano-micelles, CA4-Man3-NPs, which can target cancer cell surface receptors and facilitate the delivery of hydrophobic cargo. The oligomeric nature of the calix[4]arene enables the dynamic self-assembly of calix[4]arene (CA4), where an amphiphile, functionalized with mannose units (CA-glycoconjugates) in the upper rim and alkylated lower rim, afforded the CA4-Man3-NPs in a controllable manner. The presence of thiourea units between calixarene and tri-mannose moiety facilitated the formation of a stable core with bidentate hydrogen bonds, which in turn promoted mannose receptor targeted uptake and helped in the intracellular pH-responsive release of antineoplastic doxorubicin (Dox). Physiochemical features including the stability of the nanomicelle could circumvent the undesirable leakage of the cargoes, ensuring maximum therapeutic output with minimum off-targeted toxicity. Most importantly, surface-enhanced Raman scattering (SERS) was utilized for the first time to evaluate the critical micelle concentration during the formation, cellular uptake and intracellular drug release. The present study not only provides an architectural design of a new class of organic small molecular nanomicelles but also unveils a robust self-assembly approach that paves the way for the delivery of a wide range of hydrophobic chemotherapeutic drugs.

Copyright © The Author(s) 2022. What makes voters more or less willing to vote online? This article uses a unique survey experiment to assess the effect of information about who delivers the online ballot; and which groups of voters are more likely to take up the option of online voting. Voters are much more favourable if it is associated with a public body than a well-regarded private sector company. We also find a clear relationship between online activity in the personal world and a willingness to vote online. Those that expose themselves to greater potential online risk in their personal lives are likely to favour having the option to cast their ballot online, but those who perceive more risk are only likely to do so if they receive additional information about the purported advantages of online voting. Who delivers, and perception of online risk are key to understanding when voters are more willing to cast their ballot online. Brunel University London

The recent outbreak of the COVID-19 pandemic is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which infects human epithelial tissue by interaction of the receptor-binding domain of its spike protein (S-protein) with angiotensin-converting enzyme 2 (ACE2). Herein, we synthesized suitably configured Troger's bases (TB-1/2/3) and investigated molecular docking of TBs at the interface of SARS-CoV-2 S-protein and ACE2, which revealed a high docking score indicating strong binding. Detailed analysis of docking highlights strong binding of TB-2 into the interfacial domain of SARS-CoV-2 S-protein and ACE2. Furthermore, for the first time, we explored surface-enhanced Raman scattering (SERS) modality to assess intermolecular interactions between TBs and SARS-CoV-2 S-protein and ACE2.

We have developed an amphiphilic pH probe (P1CS) to detect pH levels in the plasma membrane in cancer cells. An elevated fluorescence signal at 550 nm at the cell surface of cancer cells (MDA-MB-231, HeLa cells) prompted the application of P1CS as a pH marker for the cancer cell surface, discriminating it from normal cells (WI-38). Moreover, the probe enables labeling of the surface of multilayered tumor spheroids, which promotes its use as a marker for the surface of tumor tissue.

Objective: The navigated presigmoidal suprabulbar infralabyrinthine approach without rerouting of the fallopian canal is described as a suitable approach for tumors located at the intra -and supraforaminal region of the jugular foramen (JF). The aim of the anatomical study is to evaluate the surgical [for full text, please go to the a.m. URL]

Late’iki (previously known as Metis Shoal) is a highly active volcano in the Tofua arc with at least four temporary island-building eruptions and one submarine eruption in the last 55 years. The most recent eruption, commencing in October 2019, resulted in lava effusion and subsequent phreatic explosions, the construction of a short-lived island that was quickly eroded by wave action and possibly further phreatic activity that continued into January 2020. The two-pyroxene dacite from the 2019 eruption is similar to the 1967/8 eruptions suggesting the magma is residual from earlier eruptions and has not undergone further differentiation in the last 50 years. New observations of the 2019 eruption site confirm the lava-dominant character of the volcano summit but a thin veneer of wave-reworked, finely fragmented lava material remains that is interpreted to have been produced by phreatic explosions from hot rock-water interactions during the effusive eruption. A notable absence of quench-fragmented hyaloclastite breccias suggests that non-explosive quench fragmentation processes were minimal at these shallow depths or that hyaloclastite debris has resedimented to greater depths beyond our summit survey area.

Transcriptional memory, by which cells respond faster to repeated stimuli, is key for cellular adaptation and organism survival. Factors related to chromatin organization and activation of transcription have been shown to play a role in the faster response of those cells previously exposed to a stimulus (primed). However, the contribution of post-transcriptional regulation is not yet explored. Here, combining flow cytometry and high throughput sequencing, we perform a genome-wide screen to identify novel factors modulating transcriptional memory in S. cerevisiae in response to galactose nutrition sources. In addition to the well-known chromatin factors modulating transcriptional memory, we find that depletion of the nuclear RNA exosome increases GAL1 expression in primed cells. We perform a genome-wide characterisation of this process and show that changes in nuclear surveillance factor association can enhance both gene induction and repression in primed cells. Finally, we show that in addition to nuclear mRNA degradation, differences in cytoplasmic mRNA decay also modulate transcriptional memory and contribute to faster gene expression remodelling in primed cells. Our results demonstrate that mRNA post-transcriptional regulation, and not only transcription regulation, should be considered when investigating gene expression memory.

Plant-derived vesicles (PDVs) were attractive for therapeutic applications, including as potential nanocarriers. However, a concern with oral delivery of PDVs is whether they would remain intact in the gastrointestinal tract. We found that 82% of cabbage PDVs were destroyed under conditions mimicking the upper digestive tract. To overcome this limitation, we developed a delivery method whereby lyophilized Eudragit S-100-coated cabbage PDVs were packaged into a capsule (Cap-cPDVs). Lyophilization and suspension of PDVs in phosphate-buffered saline did not have an appreciable effect on PDV structure, number of PDVs, or therapeutic effect. However, packaging the lyophilized Eudragit S-100-coated PDVs into capsules allowed them to pass through the upper gastrointestinal tract for delivery into the colon better than did suspension of PDVs in phosphate-buffered saline. Cap-cPDVs demonstrated robust therapeutic effect in a dextran sulfate sodium-induced colitis mouse model. These findings could have broad implications for oral delivery of PDVs. Citation Format: Yuan Liu, Adrian Lankenau-Ahumada, Emine Bayraktar, Paul Schwartz, Mamur Chowdhury, Sixiang Shi, Manu M. Sebastian, Htet Khant, Natalia De Val, Zuliang Jie, Nicholas B. Jennings, Cristian Rodriguez-Aguayo, Jody Swain, Elaine Stur, Lingegowda S. Mangala, Yutuan Wu, Supriya Nagaraju, Brooke Erimas, Chun Li, Gabriel Lopez-Berestein, Janet Braam, Anil K. Sood. Enhancing oral delivery of plant-derived vesicles [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 2720.

Full-visible color-tunable new fluorophores are essential in bioimaging research. However, it is significantly challenging to design fluorophores with the desired optical and biological properties owing to their structural complexity. We report a unified design of an interesting molecular framework

Realizing the importance of activation of the anticancer drug, its distribution, and for cancer management, a new theranostic probe has been developed. Endogenous H

A straightforward investigation with a surfactant-free green method mediated orchestration of a nanocomposite, where immunotherapy was fused with antimicrobial ability in a biogenic amalgamation, resulted in a nanoimmunobiotics (NIB). Consequently, a galactoxyloglucan (PST001) isolated from

Effective treatment of malignant melanoma requires an appropriate combination of therapeutic intervention with long-term prognosis as it often survives by monotherapies. Herein, we report a novel melanoma-targeted theranostic nanoenvelope (MTTNe: ISQ@BSA-AuNC@AuNR@DAC@DR5) which has been constructed by assembling a bovine serum albumin (BSA) stabilized gold nanocluster on a gold nanorod (BSA-AuNC@AuNR), a three-in-one theranostic modality, i.e., photothermal therapy (PTT), photodynamic therapy (PDT), and chemotherapy, tethered with a surface-enhanced Raman scattering (SERS) detection technique. The resultant MTTNe was coloaded with the melanoma-specific FDA approved drug dacarbazine (DAC) and a newly synthesized near-infrared (NIR) absorbing squaraine molecule ISQ that served partly as a photosensitizer and multiplex Raman reporter. Finally, a nanoenvelope was anchored with anti-DR5 monoclonal antibodies as a targeting motif for highly expressed melanoma-specific death receptors in malignant cells. Significant phototherapies of MTTNe were initiated upon an 808 nm single laser trigger which showed a synergistic effect of photothermal hyperthermia as well as singlet oxygen (

Pancreatic cancer represents one of the most aggressive in nature with a miserable prognosis that warrants efficient diagnostic and therapeutic interventions. Herein, a MnO

Recent advancements in a nanoarchitecture platform for safe and effective targeted phototherapy in a synergistic fashion is an absolute necessity in localized cancer therapy. Photothermal and photodynamic therapies (PTT and PDT) are considered as the most promising localized therapeutic intervention for cancer management as they have no long-term side effects and are minimally invasive and affordable. Herein, we have demonstrated a tailor-made nanotheranostic probe in which macrocyclic host cucurbituril [8] (CB[8]) is placed as a glue between two gold nanorods (GNRs) within ∼3 nm gaps in linear nanoassemblies with exquisitely sensitive plasmonics that exert combined phototherapy to investigate the therapeutic progression on human breast cancer cells. Photosensitizer methylene blue was positioned on CB[8] to impart the PDT effect, whereas GNR was responsible for PTT on a single laser trigger ensuring the synchronized phototherapy. Furthermore, the nanoconstruct was tagged with targeting anti-Her2 monoclonal antibody (MB-CB[8]@GNR-anti-Her2) for localized PTT and PDT on Her2 positive SKBR3 cells, subsequent cellular recognition by surface-enhanced Raman spectroscopy (SERS) platform, and further assessment of the combined intracellular phototherapy. Hence, the current strategy is definitely marked as a proof-of-concept straightforward approach that implies the perfect nature of the combined phototherapy to achieve an efficient cancer treatment.

The nicotinamide adenine dinucleotide-reduced (NADH) function as a hydride (H) carrier to maintain cellular homeostasis. Herein, we report a quinoline appended iridium complex (QAIC) as a molecular probe in fluorescence and surface-enhanced Raman spectroscopy (SERS) modalities to evaluate the endogenous NADH status. NADH-triggered activation of QAIC enabled luminescence (turn-ON) and SERS (turn-OFF) switching phenomenon with a detection limit of 25.6 nM and 15 pM for NADH in luminescence and SERS respectively. Transition state modelling using density functional theory calculations proved that a facile migration of H from NADH to QAIC transformed the activated QAIC (N-QAIC) with an energy span of 19.7 kcal/mol. Furthermore, N-QAIC is probed as a photosensitizer to source singlet oxygen by blocking the photo induced electron transfer (PeT) and generate NAD radicals. Therefore, an efficient light triggered cyclometalated iridium-based molecular probe has been divulged to promote bimodal NADH sensing and multiphase photodynamic therapy.

The intrinsic complexities of cell-surface glycans impede tracking the metabolic changes in cells. By coupling metabolic glycan labelling (MGL) and surface-enhanced Raman scattering (SERS), we employed the MGL-SERS strategy to elucidate the differential glycosylation pattern in cancer cell lines. Herein, for the first time, we are reporting an N-alkyl derivative of glucosamine (GlcNPhAlk) as a glycan labelling precursor. The extent of labelling was assessed by utilizing Raman imaging and verified by complementary fluorescence and Western blot analysis. MGL-SERS technique was implemented for a comparative evaluation of cell surface glycan imbalance in different cancer cells wherein a linear relationship between glycan expression and metastatic potential was established. Further, the effect of sialyltransferase inhibitor, P-3Fax-Neu5Ac, on metabolic labelling of GlcNPhAlk proved the incorporation of GlcNPhAlk to the terminal glycans through the sialic acid biosynthetic pathway. Hence, this methodology unveils the phenomenon of metastatic progression in cancer cells with inherent glycosylation-related dysplasia.

SPINDOC is tightly associated with the histone H3K4me3 effector protein SPIN1. To gain a better understanding of the biological roles of SPINDOC, we identified its interacting proteins. Unexpectedly, SPINDOC forms two mutually exclusive protein complexes, one with SPIN1 and the other with PARP1. Consistent with its ability to directly interact with PARP1, SPINDOC expression is induced by DNA damage, likely by KLF4, and recruited to DNA lesions with dynamics that follows PARP1. In SPINDOC knockout cells, the levels of PARylation are reduced, in both the absence and presence of DNA damage. The SPINDOC/PARP1 interaction promotes the clearance of PARP1 from damaged DNA, and also impacts the expression of known transcriptional targets of PARP1. To address the in vivo roles of SPINDOC in PARP1 regulation, we generate SPINDOC knockout mice, which are viable, but slightly smaller than their wildtype counterparts. The KO mice display reduced levels of PARylation and, like PARP1 KO mice, are hypersensitive to IR-induced DNA damage. The findings identify a SPIN1-independent role for SPINDOC in the regulation of PARP1-mediated PARylation and the DNA damage response., SPINDOC is known to interact with Spindlin1 (SPIN1), a histone code effector protein. Here, the authors show that SPINDOC is distributed between two distinct protein complexes, one comprising SPIN1 and the other one with PARP1. Their results suggest a role for SPINDOC in the regulation of PARP1- mediated PARylation and the DNA damage response.

Efficient fluorophores with easy synthetic routes and fast responses are of great importance in clinical diagnostics. Herein, we report a new, rigid pentacyclic pyrylium fluorophore, PS-OMe, synthesised in a single step by a modified Vilsmeier–Haack reaction. Insights into the reaction mechanism facilitated a new reaction protocol for the efficient synthesis of PS-OMe which upon demethylation resulted in a “turn-on” pH sensor, PS-OH. This new fluorescent probe has been successfully used to monitor intracellular acidification at physiological pH. From the fluorescence image analysis, we were able to quantify the intracellular dynamic pH change during apoptosis. This new pH probe is a potential chemical tool for screening, drug discovery and dose determination in cancer therapy., A modified Vilsmeier–Haack reaction resulted in the synthesis of a pyrylium based turn-on fluorescent pH probe. The probe can monitor minute acidification and dynamic pH variation in cells during apoptosis with therapeutic chemo drugs.

Precise control over the dynamics of nanoparticles (NPs) in a tumor microenvironment is highly warranted for the development of an efficient nanotheranostic agent. Even though inductively coupled plasma mass spectrometry can provide a quantitative assessment regarding the uptake efficiency of metal NPs, enumeration of deep tissue penetration capacity remains as a challenge. Herein, we have demonstrated an accurate tracking of the uptake efficiency and penetration phenomenon of gold nanoparticles (AuNPs: 40-50 nm) with respect to three different surface charges in monolayer (2D) cells, multicellular spheroids (3D) and in vivo tumors by surface-enhanced Raman spectroscopy (SERS). While positively charged AuNPs showed around two-fold increased internalization in monolayer cells, SERS-tag-based line scanning on multi-layered tumor spheroids illustrated almost nine-fold superior penetration capability with negatively charged AuNPs. Further, the enhanced solid tumor distribution contributed by the negatively charged AuNPs could appreciably escalate its clinical utility in cancer management.

The prediction of a difficult cholecystectomy has traditionally been based on certain pre-operative clinical and imaging factors. Most of the previous literature reported small patient cohorts and have not used an objective measure of operative difficulty. The aim of this study was to develop a pre-operative score to predict difficult cholecystectomy, as defined by a validated intra-operative difficulty grading scale. Two cohorts from prospectively maintained databases of patients who underwent laparoscopic cholecystectomy were analysed: the CholeS Study (8755 patients) and a single surgeon series (4089 patients). Factors potentially predictive of difficulty were correlated to the Nassar intra-operative difficulty scale. A multivariable binary logistic regression analysis was then used to identify factors that were independently associated with difficult laparoscopic cholecystectomy, defined as operative difficulty grades 3 to 5. The resulting model was then converted to a risk score, and validated on both internal and external datasets. Increasing age and ASA classification, male gender, diagnosis of CBD stone or cholecystitis, thick-walled gallbladders, CBD dilation, use of pre-operative ERCP and non-elective operations were found to be significant independent predictors of difficult cases. A risk score based on these factors returned an area under the ROC curve of 0.789 (95% CI 0.773–0.806, p

BACKGROUND ESWL is suitable for stones smaller than 2 cm situated in upper and middle calyx. The routine insertion of DJ stents during ESWL of renal calculi is controversial. Some studies support the role of DJ stents in facilitating stone passage and preventing renal colic whereas other reports claim that stent causes significant lower urinary tract symptoms, hematuria, urinary tract infection and can even lower the stone-free rate. METHODS This is a prospective study conducted among 81 patients each in stented and non stented group who underwent ESWL for renal calculus. The primary outcome measured was stone fragmentation .The secondary outcomes measured were renal colic, urinary tract infection, steinstrasse and stent related LUTS. RESULTS Stone fragmentation rates in stented and non-stented groups were 91.4% and 86.4% respectively (p-value > 0.05). Ureteric colic in the stented group was only 14.8% but 45.7% in the non-stented group had ureteric colic (p-value

An unexploited homo-polysaccharide (PSM001) isolated from the seed kernel of Kottukonam variety of Mangifera indica, demonstrated selective cytotoxicity against cancer cells both in vitro and in murine models while maintaining the immunostimulatory potential. Galactoxyloglucan (PST001) isolated from the seeds of Tamarindus indica, was previously established to be an effective anticancer and immunomodulatory agent. Cancer metastasis, with key features including invasion, migration, increased angiogenesis and colony formation is only likely to accentuate in the coming decades, considering the ground realities of the modern lifestyle and environmental factors and hence both the polysaccharides were tested towards the management of malignancy. It was a startling observation with both the biopolymers in inhibiting various processes involved in the metastatic cascade. A quick perusal of the issue at hand would throw up the promising ability of both PSM001 and PST001 to inhibit lung metastatic nodules of C57BL/6 mice wherein the combinatorial treatment of these polysaccharides with vincristine delivered superior therapeutic output. Later, vascular endothelial growth factor and multiple matrix metalloproteinases were found to be the lead players in the polysaccharide mediated metastatic inhibition. Having considered the complexities associated with the chemotherapy in metastatic cancer in terms of palpable immunosuppression, the aftermaths with the co-administration of an immunostimulatory agent which itself possess unique anticancer and anti-metastatic potentials with a potent chemotherapeutic agent will be enormously consequential.

The subject of Human Activity recognition (HAR) could also be a prominent research area topic within the sector of computer vision and image processing area. It has privileged state-of-art application in various sectors, surveillance, digital entertainment and medical healthcare. It is interesting to watch and intriguing to predict such quite movements. Several sensor-based approaches have also been introduced to review and predict human activities such accelerometer, gyroscope, etc., it's its own advantages and drawbacks. Convolutional neural networks (CNN) with spatiotemporal 3 dimensional (3D) kernels are trained using data set which has Three classes that depicts activities of humans in their everyday life and work. The trained model show satisfactory performance altogether stages of coaching, testing. The ability to acknowledge various human activities enables the developing of intelligent system. Usually the task of act recognition is mapped to the classification task of images representing person’s actions. This system provides the comparison study on these methods applied for human activity recognition task using the set of images representing five different categories of daily life activities.

The technological advancements make changes during availability of knowledge in a huge way. As the volume of data is increasing exponentially, there is a need for better management of data to research and industry. This data, referred to as Big Data, is now employed by various organizations to extract valuable information which may reanalyzed computationally to reveal patterns, trends and associations revealing the human interaction and behavior for making various industrial decisions But the data must be optimized, integrated, secured and visualized to make any effective decision. Analyzing of the large volume of data is not beneficial always unless it is analyzed properly. The existing techniques are insufficient to analyze the large Data and identify the frequent services accessed by the cloud users. Various services can be integrated to provide a better environment to work in emergency cases pretty earlier. Using these services, people become widely vulnerable to exposure. The data is large and provides an insight in to future predictions, which could definitely prevent maximum medical cases from happening. But without big data analytics techniques and therefore the Hadoop cluster, this data remains useless. Through this paper, we'll explain how real time data may be useful to research and predict severe Index Terms - Big Data, Medical Big Data mining, EHR, EMR, Hadoop, Hbase, Mapreduce, HDFS, Hive, Cassandra

Objective: Microscopical and endoscopical surgical areas of exposure in the standard suboccipital retrosigmoidal approach (SSRA) vary widely. For surgical treatments of pathologies at the brain stem, the knowledge about the surgical area of exposure plays a crucial role. The aim of the anatomical study[for full text, please go to the a.m. URL], 72. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Polnischen Gesellschaft für Neurochirurgie

The design and development of an efficacious tumor-specific drug-delivery system is a challenging task. In this study, we have synthesized target-specific small peptide substrates on an octaguanidine sorbitol scaffold, named small molecular targeted drug-delivery conjugate (SMTDDC). The SMTDDC fabrication, with dual targeting cRGD and Cathepsin B (Cath B)-specific tripeptide (Glu-Lys-Phe), altered the microtubule network of glioblastoma cells by the orchestrated release of the cytotoxic paclitaxel (PTX). Cath B assisted PTX delivery was monitored by high-performance liquid chromatography and Surface-Enhanced Raman Scattering (SERS) modalities. The time-dependent SERS fingerprinting and imaging revealed a fast and accurate PTX release profile and subsequent in vitro cytotoxicity as well as the apoptotic events and microtubule network alteration in U-87 MG glioblastoma cells. Furthermore, SMTDDC displayed adequate stability under physiological conditions and demonstrated biocompatibility toward red blood cells and lymphocytes. This study indicated a new insight on SERS-guided peptidomimetic sorbitol molecular transporter, enabling a greater promise with high potential for the further development of PTX delivery in glioblastoma treatment.

Dental implants are a universally employed common treatment approach for the loss of teeth. Dental implants play a vital role in the field of dentistry for overcoming various dental problems including tooth loss, crown damage, and diastema. Three-dimensional (3D) bio-printing is an emerging technology with unparalleled potential in which polymers or materials are joined or polymerized with the aid of computer-assisted designing for the development of various constructs. It enables precise control over multiple compositions, architectural accuracy, and spatial distributions for accomplishing effective recapitulation of mechanical properties, microstructure, and biological functions of target tissues and organs. Along with many unique biomedical applications, 3D printing has a great impact in dentistry for restoration and implant applications. The use of computer-aided designing and selection of polymeric material with desired features for manufacturing, printing, and implantation can be applied for curing dental deformations with greater speed and lesser effort. In this context, this chapter mainly provides an overview about recent advances in 3D bioprinting for engineering dental implants with greater biocompatibility and suitability.

Drowsiness in driver and alcohol consumption are the critical cause of road accident and death. Lives of pedestrian and passengers are put to risk as drivers tend to fall asleep and also when the driver is in his drunken state. Detection of driver drowsiness and its indication is an active research area now. There are 3 methods for detection of driver fatigue which includes vehicle-based method, behavioural method, and physiological based method. We adopt behavioural method. This project is aimed towards developing a prototype of drowsiness and alcohol detection system using Haar algorithm with raspberry pi. This project proposes a real time detection of driver’s drowsiness as well as alcohol intoxication and subsequently alerting them. The primary purpose of this drowsiness and alcohol detection system is to develop a system that can reduce the number of accidents from drowsiness and drunk driving of vehicle. It consists of camera which is placed in front of the driver to detect the face. An alcohol sensor which is a gas sensor used to sense the drinking state of driver. Haar algorithm is used for face detection. The results demonstrate the accuracy and robustness of the hybridized of image processing technique. Thus, it can be concluded the proposed approach is an effective solution for a real-time of driver drowsiness and alcohol detection.