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AbstractA simple yet effective way of modeling survival data with cure fraction is by considering Box-Cox transformation cure model (BCTM) that unifies mixture and promotion time cure models. In this article, we numerically study the statistical properties of the BCTM when applied to interval censored data. Time-to-events associated with susceptible subjects are modeled through proportional hazards structure that allows for non-homogeneity across subjects, where the baseline hazard function is estimated by distribution-free piecewise linear function with varied degrees of non-parametricity. Due to missing cured statuses for right censored subjects, maximum likelihood estimates of model parameters are obtained by developing an expectation-maximization (EM) algorithm. Under the EM framework, the conditional expectation of the complete data log-likelihood function is maximized by considering all parameters (including the Box-Cox transformation parameter α) simultaneously, in contrast to conventional profile-likelihood technique of estimating α. The robustness and accuracy of the model and estimation method are established through a detailed simulation study under various parameter settings, and an analysis of real-life data obtained from a smoking cessation study. [ABSTRACT FROM AUTHOR]

Paraprobiotics, non-viable versions of probiotic microorganisms, offer a promising prophylactic strategy in aquaculture, addressing concerns about the safety and functionality of probiotics while harnessing similar health benefits for fish and shellfish. This study determined the dietary effects of paraprobiotic preparation from Bacillus amyloliquefaciens COFCAU_P1 to support the immune system and control Aeromonas hydrophila infection in Labeo rohita fingerlings. Paraprobiotic was prepared by heat and formalin inactivation of the probiotic B. amyloliquefaciens and subsequently analyzed by scanning electron microscopy. The cellular immunological responses viz. superoxide anion, myeloperoxidase activity, nitric oxide production, and leucocyte proliferation of rohu head-kidney (HK) leucocytes increased significantly with different doses (106, 107, and 108 cells ml−1) of both heat and formalin-inactivated preparations in vitro. Both preparations significantly enhanced the in vitro immune gene (IL-1β and IFN-γ) expression, indicating their immunostimulatory response at the molecular level. As the formalin-inactivated preparation showed a better immune response, it was selected for the subsequent in vivo experiment. Dietary administration of formalin-inactivated B. amyloliquefaciens at different doses (106, 107, and 108 cells g−1 feed) showed significantly higher responses in innate immune (respiratory burst, myeloperoxidase, and anti-protease activity) and biochemical parameters (total protein, albumin, globulin alkaline phosphatase activity, and glucose content). Resistance against experimental A. hydrophila infection was increased significantly after 30 days of feeding of the formalin-inactivated B. amyloliquefaciens. At the paraprobiotic dose of 1 × 108 cells g−1 feed, the maximum immune response and survivability against A. hydrophila infection were observed. It can be inferred from the results that formalin-inactivated B. amyloliquefaciens paraprobiotic can be used as a promising immunostimulant in aquaculture. The potency of B. amyloliquefaciens paraprobiotic to enhance immunity and survivability of rohu against experimental A. hydrophila infection is worth mentioning. [ABSTRACT FROM AUTHOR]

We propose a hybrid quantum approach to threshold and binarize a grayscale image through unsharp measurements (UM) relying on image histogram. Generally, the histograms are characterized by multiple overlapping normal distributions corresponding to objects, or image features with small but significant overlaps, making it challenging to establish suitable thresholds. The proposed methodology uses peaks of the overlapping Gaussians and the distance between neighboring local minima as the variance, based on which the UM parameters are chosen, that maps the normal distribution into a localized delta function. To demonstrate its efficacy, subsequent implementation is done on noisy quantum environments in Qiskit. This process is iteratively repeated for a multimodal histogram to obtain more thresholds, which are then applied to various life-like pictures to get high-contrast images, resulting in comparable peak signal-to-noise ratio and structural similarity index measure values. The obtained thresholds are used to binarize a grayscale image by using novel enhanced quantum image representation integrated with a threshold encoder and an efficient quantum comparator (QC) that depicts the whole binarized picture. This approach significantly reduces the complexity of the proposed QC and of the whole algorithm when compared to earlier models. [ABSTRACT FROM AUTHOR]

Cure models are widely popular in modeling time-to-event data that are characterized by cure fraction owing to long-term survivors. Mixture cure models are perhaps the most studied cure models in the literature. In this article, however, we consider a competing risks scenario where the number of competing causes is modeled by flexible Conway-Maxwell (COM) Poisson distribution, and the lifetimes corresponding to the competing causes are assumed to be independently distributed following proportional hazards model. The baseline hazard function is modeled by a piecewise linear function, and hence, estimated non parametrically. Probability of obtaining zero competing causes is used to estimate the cure rate. Collectively, the resultant cure model is exceedingly general and flexible. The estimation of the parameters is carried out using maximum likelihood (ML) method by implementing the expectation-maximization (EM) algorithm, except for the dispersion parameter of the COM-Poisson distribution, which is estimated by the profile likelihood method. The performance of the model is tested under various settings of censoring rate, sample size and mean lifetime. Discrimination of models is performed and carried out with likelihood-based and information-based criteria. Performance of the proposed model is further illustrated using a real-world data on cutaneous melanoma. [ABSTRACT FROM AUTHOR]

This article aims to manifest a new way of the utilization of renewable resources in a distribution network. Solar power acts as a source of excitation in the field winding of a separately excited biogas DC generator for the generation of DC power. The amount of DC power required by the generator's field winding is supplied by harnessing a minimum amount of solar energy from a solar photovoltaic (solar PV) for the operation of the bio-power generator of a rated capacity of 5 kW. It is observed, that the availability of 5% peak solar power can be utilized for full excitation of the generator and, it is observed that the full load demand at the time around 16:00 pm can be catered only by the bio-generator. In this work, it has been acknowledged that solar power can be effectively used in low insolation. In addition, it has been revealed, no auxiliary power source is needed for the operation of the generator approximately, 330.22 W of DC power is required by the field winding for full excitation of the DC generator. The present research developed a unique way of power management strategy, which can mitigate the delicate problems in a conventional distribution system. [ABSTRACT FROM AUTHOR]

This study focuses on the development of theranostic, dual drug‐loaded nanocarriers to propose a proof‐of‐principle therapeutic approach in the treatment of pancreatic ductal adenocarcinoma (PDAC). The nanoconstructs consist of a core of zinc oxide nanocrystals doped with gadolinium, useful as a potential contrast agent in magnetic resonance imaging applications. After functionalizing their surface with amino‐propyl groups, the physical adsorption of two hydrophobic drugs is performed: Vismodegib and Sorafenib. Their synergistic use might improve PDAC treatment and stroma depletion when co‐delivered in the tumor microenvironment for future in vivo applications. To enhance the nanoconstructs' biostability, the ensemble is coated by a lipid bilayer and a tumor targeting peptide is incorporated on the outer shell surface. As a first proof of concept, the resulting nanoconstructs are tested against two pancreatic cancer cell lines, showing a modest increase in treatment efficacy compared to the free drug counterparts and proving to spare healthy pancreatic cells. In a second testing set, the dual‐drug loaded nanoconstructs are tested on both cell lines previously sensitized to a first‐line chemotherapeutic drug, Gemcitabine, showing an improved treatment response. From these preliminary results, the nanotheranostic platforms might constitute a good starting point for future PDAC therapy and diagnosis studies. [ABSTRACT FROM AUTHOR]

The growing phenomenon of transnational families where the mothers work abroad has reinvigorated the debate on the fluidity of contemporary families. Family is no longer defined as household-bound, and family obligations are constantly negotiated. Research shows migrant mothers utilize communication technologies, most recently smartphones, to (re)constitute family intimacy and maternal identity from afar through everyday family practices. However, most research has focused on the material reconfiguration of family practices, essentially sidelining the discursive workings of intimacy and identity via mobile media. To address this gap, this ethnographic study draws on the narrative theories, particularly the small stories approach, to examine the narratives of Indonesian mothers in Hong Kong as embedded in their smartphone communication. The participant observation and narrative interviews with 25 migrant mothers revealed that maternal storytelling on smartphones is routine, eclectic, and personalized. These enable migrant mothers to craft and tell family stories to (1) rationalize distance and (2) bolster family resilience. This article concludes by reflecting upon the authorial privilege in constructing family narratives on mobile media. The implications on our understanding of the contextualizing power of narrative and power dynamics underlying mediated family communication are discussed. [ABSTRACT FROM AUTHOR]

During binderjetting of bioceramics, many commercial 3D printers dispense binder in a default 'core-shell' manner. Using such a conventional approach, more binder is dispensed at the periphery (shell) and less binder at the 'core' of the structure. The inhomogeneous binding of the powder particles from the shell to the core significantly impacts the microstructure and biomechanical properties. To address this, we hypothesised 'segmentation' of a 3D printable design file by slicing and discretising with an array of thin solid "segments", separated with an infinitesimal gap in a periodic manner. In this novel approach, the printing software commands the printhead to print each of the "segments" individually. The inter-segment and intra-segment binder "bleeding" among the segments results in a printed part with a homogeneously bound cross-section, without any "core-shell" effect. This hypothesis was experimentally validated by better microstructure, improved density, and enhanced mechanical strength properties in binderjet printed 3 mol% yttria stabilised ZrO 2. [ABSTRACT FROM AUTHOR]

In survival analysis, cure models have gained much importance due to rapid advancements in medical sciences. More recently, a subset of cure models, called destructive cure models, have been studied extensively under competing risks scenario wherein initial competing risks undergo a destructive process. In this article, we study destructive cure models by assuming a flexible weighted Poisson distribution (exponentially weighted Poisson, length biased Poisson and negative binomial distributions) for the initial number of competing causes and lifetimes of the susceptible individuals being defined by proportional hazards. The expectation-maximization (EM) algorithm and profile likelihood approach are made use of to estimate the model parameters. An extensive simulation study is carried out under various parameter settings to examine the properties of the models, and accuracy and the robustness of the proposed estimation technique. Effects of model mis-specification on the parameter estimates are also discussed in detail. For further illustration of the proposed methodology, a real-life cutaneous melanoma data set is analyzed. [ABSTRACT FROM AUTHOR]

Despite different nanomaterials were developed so far against cancer, their potential drawbacks are still scarcely considered. The off-target delivery of a therapeutic compound, as well as the non-specific uptake of these nanomaterials by healthy tissues or organs, and their potential immunogenicity are some of the major issues that still have to be faced prior to a successful clinical translation. This work aims to develop an innovative theranostic, biocompatible, and drug-loaded nanoconstruct based on Gadolinium-doped Zinc Oxide (ZnO-Gd) nanocrystals (NCs), focusing on one of the most lethal diseases, i.e., pancreatic cancer. The use of zinc oxide is motivated by the huge potential of this nanomaterial already demonstrated for in vitro and in vivo applications, while the Gadolinium doping confers magnetic properties useful for diagnostics. Furthermore, an innovative biomimetic shell is here used to coat the NCs: it is composed of a lipid bilayer made from extracellular vesicles (EVs) combined with other synthetic lipids and a peptide targeting the pancreatic tumor microenvironment. To complete the nanoconstruct therapeutic function, Gemcitabine, a first-line drug for pancreatic cancer treatment, was adsorbed on the ZnO-Gd NCs prior to the coating with the above-mentioned lipidic shell. The aim of this work is thus to strongly enhance the therapeutic capability of the final nanoconstruct, providing it with high biocompatibility, colloidal stability in biological media, efficient cargo loading and release properties, as well as active targeting for site-selective drug delivery. Furthermore, the magnetic properties of the ZnO-Gd NCs core can in future allow efficient in situ bioimaging capabilities based on Magnetic Resonance Imaging technique. The obtained nanoconstructs were tested on two different pancreatic cancer cell lines, i.e., BxPC-3 and the metastatic AsPC-1, proving high cell internalization levels, mediated by the targeting peptide exposed on the nanoconstruct. Cellular cytotoxicity assay performed on both cell lines dictated ~ 20% increased cell killing efficacy of Gemcitabine when delivered through the nanoconstruct rather than as a free drug. Taken together, our designed theranostic nanoconstruct can have a significant impact on the standard treatment of pancreatic cancer. [ABSTRACT FROM AUTHOR]

Deep neural networks (DNNs) have shown success in image classification, with high accuracy in recognition of everyday objects. Performance of DNNs has traditionally been measured assuming human accuracy is perfect. In specific problem domains, however, human accuracy is less than perfect and a comparison between humans and machine learning (ML) models can be performed. In recognising everyday objects, humans have the advantage of a lifetime of experience, whereas DNN models are trained only with a limited image dataset. We have tried to compare performance of human learners and two DNN models on an image dataset which is novel to both, i.e. histological images. We thus aim to eliminate the advantage of prior experience that humans have over DNN models in image classification. Ten classes of tissues were randomly selected from the undergraduate first year histology curriculum of a Medical School in North India. Two machine learning (ML) models were developed based on the VGG16 (VML) and Inception V2 (IML) DNNs, using transfer learning, to produce a 10-class classifier. One thousand (1000) images belonging to the ten classes (i.e. 100 images from each class) were split into training (700) and validation (300) sets. After training, the VML and IML model achieved 85.67 and 89% accuracy on the validation set, respectively. The training set was also circulated to medical students (MS) of the college for a week. An online quiz, consisting of a random selection of 100 images from the validation set, was conducted on students (after obtaining informed consent) who volunteered for the study. 66 students participated in the quiz, providing 6557 responses. In addition, we prepared a set of 10 images which belonged to different classes of tissue, not present in training set (i.e. out of training scope or OTS images). A second quiz was conducted on medical students with OTS images, and the ML models were also run on these OTS images. The overall accuracy of MS in the first quiz was 55.14%. The two ML models were also run on the first quiz questionnaire, producing accuracy between 91 and 93%. The ML models scored more than 80% of medical students. Analysis of confusion matrices of both ML models and all medical students showed dissimilar error profiles. However, when comparing the subset of students who achieved similar accuracy as the ML models, the error profile was also similar. Recognition of ‘stomach’ proved difficult for both humans and ML models. In 04 images in the first quiz set, both VML model and medical students produced highly equivocal responses. Within these images, a pattern of bias was uncovered–the tendency of medical students to misclassify ‘liver’ tissue. The ‘stomach’ class proved most difficult for both MS and VML, producing 34.84% of all errors of MS, and 41.17% of all errors of VML model; however, the IML model committed most errors in recognising the ‘skin’ class (27.5% of all errors). Analysis of the convolution layers of the DNN outlined features in the original image which might have led to misclassification by the VML model. In OTS images, however, the medical students produced better overall score than both ML models, i.e. they successfully recognised patterns of similarity between tissues and could generalise their training to a novel dataset. Our findings suggest that within the scope of training, ML models perform better than 80% medical students with a distinct error profile. However, students who have reached accuracy close to the ML models, tend to replicate the error profile as that of the ML models. This suggests a degree of similarity between how machines and humans extract features from an image. If asked to recognise images outside the scope of training, humans perform better at recognising patterns and likeness between tissues. This suggests that ‘training’ is not the same as ‘learning’, and humans can extend their pattern-based learning to different domains outside of the training set. [ABSTRACT FROM AUTHOR]

In clinical studies, survival analysis is a well known technique to analyze time to event data with the assumption that every subject in the study will encounter the event of interest. With recent advancements in the drug development industry, a fraction of subjects may not face the event and are considered as immune or cured. However, due to the finite study period, full knowledge of subjects who are immune is usually not known and hence, can be considered as missing. We develop a novel semi-parametric algorithm to address this problem by minimizing a suitable loss function, which incorporates the missing data and generates cure indicators for the censored individuals. We prove the existence of a global minimizer for the loss function and establish some asymptotic properties, demonstrate via numerical experiments that under appropriate circumstances, our approach performs better than simpler alternatives, and use this algorithm to estimate lifetime parameters and the overall survivor function. [ABSTRACT FROM AUTHOR]

The recognition of hydroxyapatite (HAp) as the major bone mineral triggered significant research in bone tissue engineering applications. Although laboratory‐scale development involves the synthesis of HAp in different routes, scalability with uncompromised quality remains a major challenge. This article reports a large‐scale wet precipitation‐based synthesis of phase‐pure HAp using indigenously customized stirred tank reactors. The different synthesis parameters, like pH, reaction time, stirring rate, precursor addition, were tailored, together with the post‐synthesis mechano‐chemical treatment (aging induced Ostwald ripening) and calcinations, as the technology is matured to manufacture HAp powders in large volume. At least three batches of HAp were produced in the pilot‐scale reactor with reproducible values of phase purity, compositional fingerprint, particle size distribution, flowability, etc. The post‐calcination bluish tint was strategically addressed by adopting a proprietary calcination protocol. This batch process can produce around 200 kg/month of phase‐pure and highly crystalline (91–94%) HAp using stirred tank reactors of different working volumes. Extensive scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses reveal the particle size of as‐synthesized HAp powders with hexagonal crystal structure in the range of 20.47 ± 4.95 nm , while individual crystallite size in range of 22.3 ± 3.2 nm (XRD based Debye‐Scherrer analysis). TEM‐based SADP analysis confirms the highly crystalline hexagonal structure of as‐synthesized HAp. The spray‐dried powders with spherical shape having narrow size distribution (35–40 μm) could also be manufactured in large batches. The spray‐dried HAp powders could be coated on clinically used stainless steel femoral stem implants using atmospheric plasma spray coating technique. [ABSTRACT FROM AUTHOR]

The increasingly assertive position of social media as a news source means that news audiences can no longer depend on traditional journalists for information verification. Instead, they must determine the news credibility on their own. The majority of information credibility studies have considered news audiences' information evaluation as a purely cognitive endeavor, implying that individuals can arrive at valid information without social validation. By drawing on self-categorization theory, this article re-conceptualizes audiences' acts of news authentication by considering it not as a one-off activity under the uncontested control of the individual, but as a cycle of collective authentication strategies whereby individual authentication and social validation are entangled in the context-dependent processing of social news. To do this, we unpacked the social dimension of news authentication by looking at the social motivation, strategies, as well as the consequences that support it through a series of focus group discussions in Singapore. [ABSTRACT FROM AUTHOR]

Introduction: Stathmin, one of the most important intracellular phosphoprotein that plays the vital role in the regulation of cell cycle and cell proliferation. It acts by disassembly of Microtubules (MT) that helps in the formation of mitotic spindle. It is overexpressed in various human cancers. Aim: To investigate the expression status of stathmin and its relation with clinicopathologic significance in Oral Squamous Cell Carcinoma (OSCC) and its association with age, sex, tobacco chewing, histomorphological features and pathological staging. Materials and Methods: A descriptive and observational study in cross-sectional design was conducted in a tertiary care centre of Kolkata, West Bengal, India, from January 2020 to March 2020 in the Department of Pathology of RG Kar Medical College and Hospital in collaboration with Department of Oto-Rhino-Laryngology of the same institute. Stathmin expression was assessed by immunohistochemistry (IHC) in 28 OSCC cases. The association between stathmin expression and clinicopathological parameters like age, sex, tobacco chewing, tumour site, histomorphological type, Tumor Nodes Metastases (TNM) stage and Worst Pattern Of Invasion (WPOI) were evaluated on the basis of Chi-square test and Fisher's-exact test (software Statistical Package for the Social Sciences (SPSS) V 25.0). Results: Stathmin was overexpressed in 18 cases out of 28 cases of OSCC. In this study a positive association was observed between stathmin expression and age group, history of tobacco chewing, advanced T stage, advanced pTNM staging and WPOI of OSCC. Conclusion: The study suggests that overexpression of stathmin could contribute to cancer progression. There is a higher likelihood that stathmin may be used as a potential biomarker as well as therapeutic target for OSCC. [ABSTRACT FROM AUTHOR]

Examples of units with two performance characteristics that degrade over time are ubiquitous in reliability engineering. In this article, we develop a flexible model for bivariate degradation data pertaining to units in which the degradation processes corresponding to the performance characteristics are likely dependent on each other. The proposed model has two features: the degradation processes are marginally modelled by gamma processes, and the dependence between them is modelled by a shared frailty term that is assumed to follow the generalized gamma distribution. We show that this model is far more flexible and efficient than many of the commonly used models for capturing dependence between the performance characteristics. A computational technique for the maximum likelihood estimation, based on Monte Carlo simulation, is developed for the proposed model. Then, the method of estimation is evaluated through an elaborate Monte Carlo simulation study. The joint reliability function of the unit with two performance characteristics and its estimation are also discussed in this general setting. The proposed model is extended to the case of multiple performance characteristics. Finally, a case study is presented in which a real degradation data pertaining to fatigue cracks is analysed through the proposed model to demonstrate its usefulness. • A flexible model for bivariate degradation data involving gamma processes. • The dependence is captured by a frailty effect following generalized gamma model. • Likelihood inference based on Monte Carlo method; efficient and easy-to-use. • Reliability function of units with two performance characteristics is developed. • Application on fatigue crack data; proposed model provides adequate fit. [ABSTRACT FROM AUTHOR]

Stem cell research is one of the most promising and fascinating field in regenerative medicine and dentistry. The use of embryonic stem cells is restricted due to the very many ethical issues while the dental pulp stem cell research is relatively free from such embargoes. Recently published research articles relating to dental pulp stem cells are voluminous but are very diversifying in nature. The observations of these researchers require critical analysis and evaluation in a focused way as is presented in this review article. [ABSTRACT FROM AUTHOR]

Although rapamycin is a very effective drug for rodents with polycystic kidney disease (PKD), it is not encouraging in the clinical trials due to the suboptimal dosages compelled by the off-target side effects. We here report the generation, characterization, specificity, functionality, pharmacokinetic, pharmacodynamic and toxicology profiles of novel polycystic kidney-specific-targeting nanoparticles (NPs). We formulated folate-conjugated PLGA-PEG NPs, which can be loaded with multiple drugs, including rapamycin (an mTOR inhibitor) and antioxidant 4-hydroxy-TEMPO (a nephroprotective agent). The NPs increased the efficacy, potency and tolerability of rapamycin resulting in an increased survival rate and improved kidney function by decreasing side effects and reducing biodistribution to other organs in PKD mice. The daily administration of rapamycin-alone (1 mg/kg/day) could now be achieved with a weekly injection of NPs containing rapamycin (379 μg/kg/week). This polycystic kidney-targeting nanotechnology, for the first time, integrated advances in the use of 1) nanoparticles as a delivery cargo, 2) folate for targeting, 3) near-infrared Cy5-fluorophore for in vitro and in vivo live imaging, 4) rapamycin as a pharmacological therapy, and 5) TEMPO as a combinational therapy. The slow sustained-release of rapamycin by polycystic kidney-targeting NPs demonstrates a new era of nanomedicine in treatment for chronic kidney diseases at clinically relevant doses. [Display omitted] [ABSTRACT FROM AUTHOR]

Context: Cervical cancer is the second most common cancer in women. The liquid based cervical cytology (LBCC) is a useful tool of choice for screening cervical cancer. Aims: To train a convolutional neural network (CNN) to identify abnormal foci from LBCC smears. Settings and Design: We have chosen retrospective study design from archived smears of patients undergoing screening from cervical cancer by LBCC smears. Materials and Methods: 2816 images, each of 256 × 256 pixels, were prepared from microphotographs of these LBCC smears, which included 816 "abnormal" foci (low grade or high grade squamous intraepithelial lesion) and 2000 'normal' foci (benign epithelial cells and reactive changes). The images were split into three sets, Training, Testing, and Evaluation. A convolutional neural network (CNN) was developed with the python programming language. The CNN was trained with the Training dataset; performance was assayed concurrently with the Testing dataset. Two CNN models were developed, after 20 and 10 epochs of training, respectively. The models were then run on the Evaluation dataset. Statistical Analysis Used: A contingency table was prepared from the original image labels and the labels predicted by the CNN. Results: Combined assessment of both models yielded a sensitivity of 95.63% in detecting abnormal foci, with 79.85% specificity. The negative predictive value was high (99.19%), suggesting potential utility in screening. False positives due to overlapping cells, neutrophils, and debris was the principal difficulty met during evaluation. Conclusions: The CNN shows promise as a screening tool; however, for its use in confirmatory diagnosis, further training with a more diverse dataset will be required. [ABSTRACT FROM AUTHOR]

Stem cells are a promising cell source for regenerative medicine due to their characteristics of self‐renewal and differentiation. The intricate balance between these two cell fates is maintained by precisely controlled symmetric and asymmetric cell divisions. Asymmetric division has a fundamental importance in maintaining tissue homeostasis and in the development of multi‐cellular organisms. For example, during development, asymmetric cell divisions are responsible for the formation of the body axis. Mechanistically, mitotic spindle dynamics determine the assembly and separation of chromosomes and regulate the orientation of cell division. Interestingly, symmetric and asymmetric cell division is not mutually exclusive and a range of factors are involved in such cell‐fate decisions, the measurement of which can provide efficient and reliable information on the regenerative potential of a cell. The balance between self‐renewal and differentiation in stem cells is controlled by various biophysical and biochemical cues. Although the role of biochemical factors in asymmetric stem cell division has been widely studied, the effect of biophysical cues in stem‐cell self‐renewal is not comprehensively understood. Herein, we review the biological relevance of stem‐cell asymmetric division to regenerative medicine and discuss the influences of various intrinsic and extrinsic biophysical cues in stem‐cell self‐renewal. This review particularly aims to inform the clinical translation of efforts to control the self‐renewal ability of stem cells through the tuning of various biophysical cues. [ABSTRACT FROM AUTHOR]

Introduction: Adenocarcinoma of the prostate may be clinically suspected based on elevated serum PSA (Prostate Specific Antigen) and/or abnormal digital rectal examination. Serum PSA has been used in prostatic carcinoma screening and for diagnostic, therapeutic and prognostic purposes. Aim: To evaluate the role of serum PSA to differentiate between benign and malignant pathology of prostate diagnosed by Transrectal Ultrasound (TRUS) guided prostatic core biopsy with special emphasis on its correlation with risk stratification based on Gleason score and Grade grouping system. Materials and Methods: Total 45 cases of Prostatic core biopsy specimens of the patients where serum PSA value was known were included in this cross-sectional observational study. Biopsy specimens were processed for routine Haematoxylin-Eosin stain and diagnosed as benign or malignant by histopathological examination along with Gleason score and Grade-Grouping was done. The comparison of PSA value between benign and malignant cases along with its significance of association with higher Grade-Grouping was statistically judged by unpaired t-test Results: Out of total 45 cases, 23 (51.11%) cases showed presence of adenocarcinoma and rest 22 cases were of benign pathology. Mean PSA value (ng/mL) was significantly higher in malignant cases i.e., 58.47 (±22.191) compared to benign cases i.e., 3.45 (±0.987). However, in malignant cases which have been categorised as low to intermediate risk group (Gleason score <8) and high risk group (Gleason score =8), the mean PSA values (ng/mL) were 58.75 and 58.18 respectively and they were not so statistically significant (p-value=0.95) to differentiate between these two groups. Conclusion: Estimation of serum PSA has got definite significance in differentiating benign cases from malignant cases in prostatic core biopsy specimens (TRUS guided). But in cases of prostate adenocarcinoma while considering the disease stage based on Gleason Score and Grade-grouping, the serum PSA value has got no statistically significant role. [ABSTRACT FROM AUTHOR]

Significance: Redox signaling plays a vital role in regulating various cellular signaling pathways and disease biology. Recently, nanomedicine (application of nanotechnology in biology and medicine) has been demonstrated to regulate angiogenesis through redox signaling. A complete understanding of redox signaling pathways influenced angiogenesis/antiangiogenesis triggered by therapeutic nanoparticles is extensively reviewed in this article. Recent Advances: In recent times, nanomedicines are regarded as the Trojan horses that could be employed for successful drug delivery, gene delivery, peptide delivery, disease diagnosis, and others, conquering barriers associated with conventional theranostic approaches. Critical Issues: Physiological angiogenesis is a tightly regulated process maintaining a balance between proangiogenic and antiangiogenic factors. The redox signaling is one of the main factors that contribute to this physiological balance. An aberrant redox signaling cascade can be caused by several exogenous and endogenous factors and leads to reduced or augmented angiogenesis that ultimately results in several disease conditions. Future Directions: Redox signaling-based nanomedicine approach has emerged as a new platform for angiogenesis-related disease therapy, where nanoparticles promote angiogenesis via controlled reactive oxygen species (ROS) production and antiangiogenesis by triggering excessive ROS formation. Recently, investigators have identified different efficient nano-candidates, which modulate angiogenesis by controlling intracellular redox molecules. Considering the importance of angiogenesis in health care a thorough understanding of nanomedicine-regulated redox signaling would inspire researchers to design and develop more novel nanomaterials that could be used as an alternative strategy for the treatment of various diseases, where angiogenesis plays a vital role. [ABSTRACT FROM AUTHOR]

This work presents performance comparison of different Tuning schemes applying the optimization technique named as Fitness Based Adaptive Differential Evolution (FBADE) for a prosthetic arm. From the dexterous point of view, the mathematical modelling is the fundamental requirement to improve the performance level. Here, we define the optimum transfer function applying fuzzy logic to establish the link of the robustness and the controllability metrics between amputated body parts and prosthetic arm. A proportional integral derivative (PID) controller is chosen for the purpose of continuously modulated control. Also, the role of most influential tuning parameters have been illustrated to measure the performance level of different tuning schemes. In the end, Lyapunov method is applied to analyze the stability of the designed model. [ABSTRACT FROM AUTHOR]

An increasing demand for directed assembly of biomaterials has inspired the development of bioprinting, which facilitates the assembling of both cellular and acellular inks into well-arranged three-dimensional (3D) structures for tissue fabrication. Although great advances have been achieved in the recent decade, there still exist issues to be addressed. Herein, a review has been systematically performed to discuss the considerations in the entire procedure of bioprinting. Though bioprinting is advancing at a rapid pace, it is seen that the whole process of obtaining tissue constructs from this technique involves multiple-stages, cutting across various technology domains. These stages can be divided into three broad categories: pre-bioprinting, bioprinting and post-bioprinting. Each stage can influence others and has a bearing on the performance of fabricated constructs. For example, in pre-bioprinting, tissue biopsy and cell expansion techniques are essential to ensure a large number of cells are available for mass organ production. Similarly, medical imaging is needed to provide high resolution designs, which can be faithfully bioprinted. In the bioprinting stage, compatibility of biomaterials is needed to be matched with solidification kinetics to ensure constructs with high cell viability and fidelity are obtained. On the other hand, there is a need to develop bioprinters, which have high degrees of freedom of movement, perform without failure concerns for several hours and are compact, and affordable. Finally, maturation of bioprinted cells are governed by conditions provided during the post-bioprinting process. This review, for the first time, puts all the bioprinting stages in perspective of the whole process of bioprinting, and analyzes their current state-of-the art. It is concluded that bioprinting community will recognize the relative importance and optimize the parameter of each stage to obtain the desired outcomes. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal/stem cells (MSCs) are multipotent cells that offer a promising outcome in the field of regenerative medicine. MSCs are present in various tissues including bone marrow, fat, skin, and placenta. The interest in clinical application of these mesoderm-derived MSCs is primarily fueled by their high self-renewal capacity and multipotency. Although, early studies indicated limited differentiation capacity of MSCs into same cell lineages from which they were isolated, subsequent investigations showed differentiation potential into other cell types of mesoderm origin including osteoblasts, adipocytes, fibroblasts, cardiomyocytes, and chondrocytes. Furthermore, MSCs exhibit a remarkable feature of transdifferentiation into ectodermal, neuroectodermal, and endodermal cells, phenomena referred to as ‘stem cell plasticity’. This opened the possibility of clinical applications of MSCs in the regeneration of other tissues like corneal reconstruction, treatment of acute lung injury, oral mucosal regeneration, homing of MSCs for regeneration at sites of injury etc. Though several evidence have accrued demonstrating this phenomenon, there is still a gap in understanding the molecular mechanism of such transitions which will be important to efficiently control the process. Interestingly, the process can be drawn a parallel with the Mesenchymal to Epithelial Transitions (MET) that takes place inside the body during embryonic development or certain pathophysiological conditions. In this review, a brief attempt is first made to understand the evidence of MSC transdifferentiation based on the current knowledge about MET. We then specifically focus on systematic presentation and analysis of the microenvironment factors involved in MSC transdifferentiation to epithelial lineages which would have applications in regenerative medicine. [ABSTRACT FROM AUTHOR]

Introduction: Advancements in our understanding of vestibular physiology and how it is changes in different diseases have established that of the three therapeutic approaches to treat disorders of the vestibular system viz. pharmacotherapy, surgery and physical therapy, it is the later i.e., physical therapy which is the most efficacious modality in the management of balance disorders. The futility of vestibular sedatives in the correction of vestibular disorders and in the restoration of balance and the very limited role of surgery has now been recognised. Advancements in vestibulometry now enable us to localise any lesion in the vestibular system with utmost precision and also determine the exact cause of the balance disorder. The site of lesion and the specific organ that is defective can now be very precisely identified. Treatment modalities especially that for physical therapy hence have to be organ specific, and if possible, also disease specific. Aims and Objectives: The study aims at evaluating the efficacy of physiotherapy in the management of balance disorders and also assesses the efficacy of organ targeted physical therapy, a new concept in restoring balance after vestibulometry has identified the offending organ. Materials and Methods: The study was conducted in the specialised physical therapy unit for balance and gait disorder patients which is a part of Vertigo and Deafness Clinic in Kolkata, India. Special instruments for physical therapy devised by the first author were used for stimulation of specific sense organs in the vestibular labyrinth that were found to be defective in vestibulometry. Specially made Virtual reality programs were used in patients suffering from psychogenic balance disorders. The pre and post therapy status was evaluated by different standard scales to assess balance and dizziness. Results: Very promising results were obtained. Organ targeted physiotherapy where defective sense organs were specifically stimulated showed remarkable improvement in different measures. Virtual reality exercises too showed very promising results in patients of psychogenic vertigo. [ABSTRACT FROM AUTHOR]

Cure rate models or long-term survival models play an important role in survival analysis and some other applied fields. In this article, by assuming a Conway-Maxwell-Poisson distribution under a competing cause scenario, we study a flexible cure rate model in which the lifetimes of non-cured individuals are described by a Cox's proportional hazard model with a Weibull hazard as the baseline function. Inference is then developed for a right censored data by the maximum likelihood method with the use of expectation-maximization algorithm and a profile likelihood approach for the estimation of the dispersion parameter of the Conway-Maxwell-Poisson distribution. An extensive simulation study is performed, under different scenarios including various censoring proportions, sample sizes, and lifetime parameters, in order to evaluate the performance of the proposed inferential method. Discrimination among some common cure rate models is then done by using likelihood-based and information-based criteria. Finally, for illustrative purpose, the proposed model and associated inferential procedure are applied to analyze a cutaneous melanoma data. [ABSTRACT FROM AUTHOR]

Lemierre's syndrome is a condition characterised by septic thrombophlebitis of internal jugular vein following an oropharyngeal infection along with septic embolisation to other organs mainly lungs. This report is about a 14-year-old girl who presented with complaint of high-grade fever, progressive shortness of breath and painful swelling of throat for seven days. Chest radiograph showed left hemithorax homogenous opacity with contralateral mediastinal shift. Complete haemogram and other blood investigations revealed neutrophilic leucocytosis and raised C-reactive protein. Gram stain and aerobic culture of sputum, pleural fluid and blood were inconclusive. As there was no relief of symptoms even after empirical treatment with antibiotics, Contrast Enhanced Computed Tomography (CECT) scan of neck and thorax was done, and it showed bilateral ectatic internal jugular veins with intravascular thrombus and consolidation of left lung with ipsilateral pleural effusion. Ultrasonography of neck confirmed the presence of thrombus in internal jugular vein on both sides. She was started on intravenous clindamycin and subcutaneous anticoagulants. Gradually the symptoms of the patient resolved. To conclude with, despite being called a "forgotten disease", Lemierre's syndrome requires strong clinical suspicion and prompt management to prevent mortality. [ABSTRACT FROM AUTHOR]

Introduction: Rheumatoid Arthritis (RA) is a chronic systemic inflammatory disease where assessment of disease activity is essential for management of patient. Currently, many composite scoring systems are used for evaluation of disease activity but they are mainly clinical-based. As several haematological parameters are altered due to systemic inflammatory process in RA, this study was intended to evaluate role of common haematological parameters to assess disease activity in RA. Aim: To find out the association of disease activity of Rheumatoid Arthritis (RA) with platelet count, Mean Platelet Volume (MPV) and Haemoglobin (Hb) level so that these costeffective haematological parameters can be used as additional factors to assess disease activity. Materials and Methods: This hospital based cross-sectional study was done on newly diagnosed patients of RA along with age and sex matched healthy control population. Patients suffering from malignancies, renal failure, diabetes mellitus or RA patients on drug therapy were excluded. Clinically, disease activity of RA was measured using DAS 28-3 Score (Modified Disease Activity Score using three variables-tender joint count, swollen joint count and ESR). Haematological parameters were measured by automated cell counter. Results: Total 80 cases were selected (60 female and 20 male). 48 patients with high disease activity (DAS 28-3>5.1) were labelled as Group-A and 32 with low to moderate disease activity (DAS 28-3 =5.1) as Group-B. Mean platelet count of patients of group A and group B were 4.53 lacs/cmm and 2.17 lacs/cmm respectively (p <0.001). MPV mean in group A and B were 11.86 fl and 10.19 fl respectively (p <0.001). Mean Hb (g/dl) was 10.05 and 12.25 for group A and B respectively (p=0.001) for male patients while in females it was 10.12 and 11.91 for group A and B, respectively (p=0.003). Mean platelet count and MPV in control population were 2.07lacs/cmm and 9.4 fl, respectively while mean Hb (g/dl) were 13.31 (male) and 12.01 (female). Conclusion: In our study it was observed that Hb is significantly lower in patients with high disease activity whereas platelet count and MPV are significantly higher with high disease activity compared to patients with low to moderate disease activity. [ABSTRACT FROM AUTHOR]

The osseointegration of metallic implants depends on an effective balance among designed porosity to facilitate angiogenesis, tissue in-growth and bone-mimicking elastic modulus with good strength properties. While addressing such twin requirements, the present study demonstrates a low temperature additive manufacturing based processing strategy to fabricate Ti-6Al-4V scaffolds with designed porosity using inkjet-based 3D powder printing (3DPP). A novel starch-based aqueous binder was prepared and the physico-chemical parameters such as pH, viscosity, and surface tension were optimized for drop-on-demand (DOD) based thermal inkjet printing. Micro-computed tomography (micro-CT) of sintered scaffolds revealed a 57% total porosity in homogeneously porous scaffold and 45% in the gradient porous scaffold with 99% interconnectivity among the micropores. Under uniaxial compression testing, the strength of homogeneously porous and gradient porous scaffolds were ~ 47 MPa and ~ 90 MPa, respectively. The progressive failure in homogeneously porous scaffold was recorded. In parallel to experimental measurements, finite element (FE) analyses have been performed to study the stress distribution globally and also locally around the designed pores. Consistent with FE analyses, a higher elastic modulus was recorded with gradient porous scaffolds (~ 3 GPa) than the homogenously porous scaffolds (~ 2 GPa). While comparing with the existing literature reports, the present work, for the first time, establishes ‘direct powder printing methodology’ of Ti-6Al-4V porous scaffolds with biomedically relevant microstructural and mechanical properties. Also, a new FE analysis approach, based on the critical understanding of the porous architecture using micro-CT results, is presented to realistically predict the compression response of porous scaffolds. [ABSTRACT FROM AUTHOR]

Two different silica based (MSU-2 and MCM-41) curcumin loaded mesoporous materials V3 and V6 were synthesized and characterized by several physico-chemical techniques. Release kinetic study revealed the slow and sustained release of curcumin from those materials in blood simulated fluid (pH: 7.4). The materials V3 and V6 were found to be biocompatible in non-cancerous CHO cell line while exhibiting significant cytotoxicity in different cancer cells (human lung carcinoma cells: A549, human breast cancer cells: MCF-7, mouse melanoma cells: B16F10) compared to pristine curcumin indicating the efficacy of the mesoporous silica materials based drug delivery systems (DDSs). The generation of intracellular reactive oxygen species (ROS) and down regulation of anti-apoptotic protein leading to the induction of apoptosis were found to be the plausible mechanisms behind the anti-cancer activity of these DDSs. These results suggest that curcumin-loaded drug delivery system may be successfully employed as an alternative treatment strategy for cancer therapeutics through a nanomedicine approach in near future. [ABSTRACT FROM AUTHOR]

Background: Colorectal carcinoma is a malignant epithelial tumor originating in the large bowel. More than 90% of colorectal carcinomas (CRC) are adenocarcinomas. This being graded morphologically at H&E stain in histopathology as well-differentiated, moderately differentiated, and poorly differentiated. Aims and Objectives: The aim of this study is to assess any association with different histopathological types and extent of differentiation of CRC with change in expression of CK 7 and Cytokeratin 20 (CK20). Materials and Methods: In the present study, total 59 patients has been selected by the predetermined sampling techniques. The specimen was collected and the necessary processing was done for H&E stain and for immunohistochemistry for CK 20 and CK 7 profile. Results: This study showed that most of the well-differentiated colorectal carcinoma are CK20 (+ve)/Cytokeratin 7 (CK7) (-ve) and poorly differentiated CRC are CK20 (+) and/CK7 (+) and also CK20 (-ve)/CK7 (+ve). Conclusion: Hence, from this study, it is evident that the expression of CK 20 positivity decreasing and CK7 positivity increasing in respect of progression of well differentiated to poorly differentiated colorectal carcinoma, that is, there is a relationship of expression of CK20 and CK7 profile with the histological grading of colorectal carcinoma. Furthermore, the expression profile of CK20 and CK 7 may be of helpful while searching for unknown primary in cases of metastatic deposit. [ABSTRACT FROM AUTHOR]

A seriesof four new mononuclear copper(II) polypyridyl complexes(1–4) have been designed, developed,and thoroughly characterized by several physicochemical techniques.The CT-DNA binding properties of 1–4have been investigated by absorption, emission spectroscopy, andviscosity measurements. All the complexes especially 1and 4exhibit cytotoxicity toward several cancer celllines, suggesting their anticancer properties as observed by severalin vitro assays. Additionally, the complexes show inhibition of endothelialcell (HUVECs) proliferation, indicating their antiangiogenic nature.In vivo chick embryo angiogenesis assay again confirms the antiangiogenicproperties of 1and 4. The formation ofexcessive intracellular ROS (H2O2and O2•–) and upregulation of BAX inducedby copper(II) complexes may be the plausible mechanisms behind theiranticancer activities. The present study may offer a basis for thedevelopment of new transition metal complexes through suitable choiceof ligands for cancer therapeutics by controlling tumor angiogenesis. [ABSTRACT FROM AUTHOR]

Aim: The present study was carried out to compare the associated role of micro minerals and hormones in repeat breeding animals with the normal crossbred cows. Materials and Methods: Blood samples were collected from 10 normal cycling and 10 repeat breeding crossbred cows of Ramakrishna Mission Ashram, Narendrapur to study the plasma mineral profile and hormonal activities. Results: Zn was found to be highly significant (p<0.01) between the two groups. Follicle stimulating hormone (FSH) and progesterone showed significant (p<0.05) difference in repeat breeding animal from the normal cyclic animal, whereas no significant differences were observed in Ca, P, Cu, Se, Co, luteinizing hormone and estradiol level. Conclusion: It may conclude that repeat breeding condition of crossbred cows in farm condition is mainly due to the low level of progesterone, FSH and zinc. [ABSTRACT FROM AUTHOR]

Abstract: Curcumin, because of its distinguishing ability to inhibit activation of transcription factor linked to chemoresistance and drug transporters, is now being co-administered with various potent anti-cancer drugs. In the present study, we report on such potentiating capabilities of curcumin in anti-angiogenic cancer therapy. With a view to simultaneously deliver curcumin and doxorubicin to tumor vasculature in anti-angiogenic cancer therapy, herein we report on the design & synthesis of a tumor vasculature targeting pegylated RGDK-lipopeptide. We show that curcumin & doxorubicin co-encapsulated within the liposomes of the presently described pegylated RGDK-lipopeptide exhibit synergism in inhibiting proliferation, invasion and migration of both tumor and endothelial cells presumably by inhibiting proliferation and metastasis related genes both at mRNA & protein levels. Pronounced tumor growth inhibition was observed in mice treated with formulations containing both the drugs. Tumor growth inhibition was found to be 2–3 folds less in mice treated with formulations containing only curcumin or only doxorubicin. The presently described liposomal system is expected to find future use for simultaneously delivering potentially any combinations of hydrophilic and hydrophobic potent small molecule cancer therapeutics to tumor vasculature in anti-angiogenic cancer therapy. [Copyright &y& Elsevier]

Abstract: Increasing number of Phase I/II clinical studies have demonstrated clinical potential of curcumin for treatment of various types of human cancers. Despite significant anti-tumor efficacies and bio-safety profiles of curcumin, poor systemic bioavailability is retarding its clinical success. Efforts are now being directed toward developing stable formulations of curcumin using various drug delivery systems. To this end, herein we report on the development of a new tumor vasculature targeting liposomal formulation of curcumin containing a lipopeptide with RGDK-head group and two stearyl tails, di-oleyolphosphatidylcholine (DOPC) and cholesterol. We show that essentially water insoluble curcumin can be solubilized in fairly high concentrations (~500μg/mL) in such formulation. Findings in the Annexin V/Propidium iodide (PI) binding based flow cytometric assays showed significant apoptosis inducing properties of the present curcumin formulation in both endothelial (HUVEC) and tumor (B16F10) cells. Using syngeneic mouse tumor model, we show that growth of solid melanoma tumor can be inhibited by targeting such liposomal formulation of curcumin to tumor vasculature. Results in immunohistochemical staining of the tumor cryosections are consistent with tumor growth inhibition being mediated by apoptosis of tumor endothelial cells. Findings in both in vitro and in vivo mechanistic studies are consistent with the supposition that the presently described liposomal formulation of curcumin inhibits tumor growth by blocking VEGF-induced STAT3 phosphorylation in tumor endothelium. To the best of our knowledge, this is the first report on inhibiting tumor growth through targeting liposomal formulation of curcumin to tumor vasculatures. [Copyright &y& Elsevier]

Abstract: Ever since the finding that αvβ3 integrin receptors are over expressed on the endothelial cell surfaces of tumor vasculatures relative to normal resting vasculatures was disclosed in 1994, αvβ3 integrin receptor selective systems are finding increasing applications both for targeting anti-cancer drugs/genes selectively to tumor vasculatures and for imaging growing tumors. Among the cyclic peptide based integrin antagonists identified through both phage display and structure-activity studies, mainly αvβ3 integrin selective cyclic peptide c(RGDfK-) has found most widespread exploitations for targeting chemotherapeutic drugs/genes to both tumor and tumor vasculatures in anti-angiogenic cancer therapy. Herein we show that a lipopeptide containing widely acclaimed αvβ3 integrin receptor selective cyclic RGDfK ligand in its head-group area can effectively deliver genes into both the endothelial and tumor cells via all the three widely used integrin receptors namely αvβ3, αvβ5 & α5β1 integrins. We demonstrate that intravenous administration of the electrostatic complex of the cationic liposomes of an amphiphiles with cyclic RGDfK head-group and the anti-cancer p53 gene leads to significant tumor growth inhibition in a syngeneic mouse tumor model presumably through inducing apoptosis of tumor neovasculatures. The findings delineated herein provide experimental evidence that cyclic-RGDfK-ligand may not be that highly selective for αvβ3 integrin receptor as is popularly believed. [Copyright &y& Elsevier]

Abstract: Re-epithelialization is one of the most important stages of cutaneous regeneration and its success requires supportive micro-ambience which may be provided with suitable bio-matrix. Biocompatibility and efficacy of such bio-matrix in re-epithelialization could be explored by multimodal analysis of structural and functional attributes of in vitro wound healing model including evaluation of prime molecular expressions of the epithelial cells during repair. Present study examines the influence of honey-alginate and alginate matrices on re-epithelialization in keratinocyte (HaCaT) population in a 2-D wound model. Cellular viability, proliferation and cell–cell adhesion status were assessed during wound closure using live/dead cell assay and by evaluating expressions of Ki67, p63 and E-cadherin along-with % change in cellular electrical impedance. Efficacy of honey-alginate matrix in comparison to only alginate one was demonstrated by a quicker reduction in wound gap, improved cellular viability, enhanced expressions of Ki67, p63 and its isoforms (TAp63, ΔNp63) as well as E-cadherin. Faster restoration of electrical attribute (% of impedance change) after wounding also indicated better impact of honey-alginate matrix in re-epithelialization. [Copyright &y& Elsevier]

Abstract: A spectrophotometric method for ascertaining the presence of anionic detergent in milk using azure A dye is described. The method requires brief mixing of milk, azure A dye and EDTA solutions, followed by addition of chloroform and subsequent centrifugation. The blue colour in the chloroform phase was measured at 635 nm. The limits of detection (LOD) and limit of quantification (LOQ) for sodium dodecylbenzene sulfonate in milk were 10 and 20 mg L−1, respectively and for a laboratory grade anionic detergent, labolene, 50 and 100 mg L−1, respectively. Recovery of detergent in spiked milk samples was quantitative. The presence of other additives, i.e., NaOH, NaHCO3, KNO3 and NaCl at levels of 250, 750, 500 and 500 mg L−1 milk, respectively, did not interfere with estimation of detergent. The method is also applicable to milk samples stored in the presence of formalin and sodium azide for 39 days at 4 °C. [Copyright &y& Elsevier]

Honey is recognized traditionally for its medicinal properties and also appreciated as a topical healing agent for infected and noninfected wounds. This study evaluates impact of honey-based occlusive dressing on nonhealing (nonresponding to conventional antibiotics) traumatic lower limb wounds (n = 34) through clinicopathological and immunohistochemical (e.g., expression of p63, E-cadherin, and Collagen I and III) evaluations to enrich the scientific validation. Clinical findings noted the nonadherence of honey dressing with remarkable chemical debridement and healing progression within 11-15 days of postintervention. Histopathologically, in comparison to preintervention biopsies, the postintervention tissues of wound peripheries demonstrated gradual normalization of epithelial and connective tissue features with significant changes in p63+ epithelial cell population, reappearance of membranous E-cadherin (P < .0001), and optimum deposition of collagen I and III (P < .0001). Thus, the present study for the first time reports the impact of honey on vital protein expressions in epithelial and connective tissues during repair of nonhealing lower limb wounds. [ABSTRACT FROM AUTHOR]

Abstract: Fresh sub-surface peat samples were collected and palynologically investigated from two different locations at Rajarhat area, N-24Paraganas, 20 km northeast of Kolkata where work was done in connection with building construction. The pollen analytical investigation of the collected peat samples reflected the existence of a large number of core mangroves and some fresh water elements and ferns from a peat layer located at the depth of about 2.2 m–3.5 m below the surface. The present investigation reveals the age of the peat layers ranging from 2665 to 6530 BP, confirming the Holocene age of the samples. The dominant pollen grains recorded from the samples were Heritiera, Excoecaria, Avicennia, Bruguiera, Barringtonia, Rhizophora, Sonneratia, Suaeda, Phoenix paludosa, Nipa and a large number of fern spores including Acrostichum and grass pollen, reflecting a diversity of mangrove vegetation. The variability of the vegetation in the peat from bottom to top shows the change of monsoon months during the Holocene in the BengalBasin. The swampy halophytic vegetation of the Holocene is to some extent comparable to the present day vegetation of the Sunderbans. [ABSTRACT FROM AUTHOR]

Introduction: A variation in dental pain following tooth extraction and implant placement has been observed. The present study aimed to compare pain in patients undergoing tooth extraction and implant placement. Materials and Methods: Eighty-four patients underwent tooth extraction and implant placement in maxillary central incisor. Pain (VAS) was recorded at 24 h, 24 h, and 48 h. Results: The mean pain value (VAS) at 24 h post-operatively after tooth extraction was 6.1 and after implant insertion was 2.9. At 48 h after tooth extraction was 4.3 and after implant insertion was 1.1 and after 72 h after tooth extraction was 2.4 and after implant insertion was 0.27. A significant difference was observed between both procedures at different intervals of time (P < 0.05). Conclusion: The pain experienced by patients during dental implant insertion was comparatively less as compared to dental tooth extraction. [ABSTRACT FROM AUTHOR]

Numerous efforts have been undertaken to mitigate the Debye screening effect of FET biosensors for achieving higher sensitivity. There are few reports that show sub-femtomolar detection of biomolecules by FET mechanisms but they either suffer from significant background noise or lack robust control. In this aspect, deformed/crumpled graphene has been recently deployed by other researchers for various biomolecule detection like DNA, COVID-19 spike proteins and immunity markers like IL-6 at sub-femtomolar levels. However, the chemical vapor deposition (CVD) approach for graphene fabrication suffers from various surface contamination while the transfer process induces structural defects. In this paper, an alternative fabrication methodology has been proposed where glass substrate has been initially texturized by wet chemical etching through the sacrificial layer of synthesized silver nanoparticles, obtained by annealing of thin silver films leading to solid state dewetting. Graphene has been subsequently deposited by thermal reduction technique from graphene oxide solution. The resulting deformed graphene structure exhibits higher sensor response towards glial fibrillary acidic protein (GFAP) detection with respect to flat graphene owing to the combined effect of reduced Debye screening and higher surface area for receptor immobilization. Additionally, another interesting aspect of the reported work lies in the biomolecule capture by dielectrophoretic (DEP) transport on the crests of the convex surfaces of graphene in a coplanar gated topology structure which has resulted in 10 aM and 28 aM detection limits of GFAP in buffer and undiluted plasma respectively, within 15 min of application of analyte. The detection limit in buffer is almost four decades lower than that documented for GFAP using biosensors which is is expected to pave way for advancing graphene FET based sensors towards ultrasensitive point-of-care diagnosis of GFAP, a biomarker for traumatic brain injury. [ABSTRACT FROM AUTHOR]

The 2-stage smelting reduction process for ironmaking without post combustion is analyzed by a thermochemical model based on materials and energy balances at steady state. The influence of various parameters like composition of hot metal and its tapping temperature, degree of metallization, slag basicity, heat losses, coal rank, proportion of limestone to dolomite, etc., on the technological parameters like coal rate, flux rate, slag rate, oxygen rate and the export gas amount is studied. The commercial scale data of a corex plant are used to verify the model predictions. The model is found to predict the plant data satisfactorily. The effect of metallization, stag basicity, heat loss and the proportion of limestone to dolomite is presented in terms of incremental changes on the coal rate, slag rate, flux rate, oxygen rate and the export energy. Further, it is shown that in the combination of the COREX+DRI-unit, the maximum metallization of sponge iron depends on the type of coal used in the corex process. [ABSTRACT FROM AUTHOR]

Soft tissue tumours arise from the mesenchymal tissues of different origin like adipocytic, smooth muscles, skeletal muscle, fibroblastic/myofibroblastic, fibrohistiocytic, pericytic, vascular, osteo-cartilagineous or even unknown. Its diagnosis depends on the age of the patient and site of presentation but sometimes they may present at unusual sites. Some of the tumours have overlapping histomorphological features which results in a list of differential diagnosis. Therefore, immunohistochemistry and molecular genetics play an important role for definite diagnosis. French Federation of Cancer Centres Sarcoma Group System (FNCLCC) based on necrosis, tumour grading and tumour differentiation is commonly used for grading of the sarcomas to assess the treatment response and prognosis of the patient. Hereby, authors present a series of nine cases of soft issue tumours, comprising five cases of synovial sarcomas and one each of dedifferentiated liposarcoma, rhabdomyosarcoma, epithelioid angiosarcoma and Well Differentiated Liposarcoma (WDLS). Few cases are located at unusual anatomical sites; hence, they should be kept in mind as differential diagnosis. Immunohistochemistry has played an important role for confirmation of diagnosis of synovial sarcomas and angiosarcoma. [ABSTRACT FROM AUTHOR]

A novel hybrid nanoporous material (LNH-1) bearing a tris(propyliminomethyl)-phloroglucinol fluorescent moiety in the framework has been designed and administration of an LNH-1 based drug delivery system containing doxorubicin to cancer cells showed inhibition of proliferation, suggesting its future potential theranostics application in cancer. [ABSTRACT FROM AUTHOR]

Intracranial teratomas represent a rare lesion accounting for 0.1%-0.7% of all intracranial tumors. Those in the fourth ventricle have rarely been reported. The present case is that of a 28-year-old man with occipital headache for two months.MRI examination revealed a well-defined extra-axial cystic lesion in posterior fossa in the midline herniating through the foramen magnum. Pre operatively, themass was seen to be occupying the whole of the posterior fossa and arising fromthe roof of the fourth ventricle. On gross examination, the lesion had both solid and cystic components. Histopathological examination showed multiple cystic areas lined by brain tissue admixed with islands of cartilage and salivary gland elements and intestinal type glands. A diagnosis of mature cystic teratoma was made. [ABSTRACT FROM AUTHOR]

The incidence of endometriosis of the appendix is reported to be just <1% of the total endometriosis cases. Laparoscopic visualization and diagnostic yield are of profound significance to women in whom gynecologic diseases such as endometriosis, pelvic inflammatory disease, ruptured ovarian follicles or tubal pregnancy may be the source of pain and mimic appendicitis. Therefore, lower abdominal pain in reproductive age group female must invite the attention of the surgeon or gynecologist to entertain the possibility of endometriosis since appendiceal endometriosis, while relatively uncommon in patients with endometriosis, is rare in the general population. [ABSTRACT FROM AUTHOR]

Simple Summary: Genes with deleterious mutations in tumors are widely accepted as tumor suppressors, since, loss of their normal expression often promotes tumor development. However, most tumors develop over a long period, with gradual accumulation of tumor-promoting events. Thus, to comprehend the role of individual genes in this evolving process of tumorigenesis, it is critical to investigate their role in both early precursors and established tumor cells. Despite recurrent mutations in ARID1A in genomes of human cancer, including pancreatic cancer, its role in tumorigenesis is not clear. We aim to understand the role of Arid1a in pancreatic cancer development and maintenance by investigating its role in both early pancreatic precursor cells and established pancreatic cancer cells. Besides novel understanding of context-dependent role of Arid1a in pancreatic cancer, this study will also enable development of therapeutic strategies for pancreatic cancers patients with ARID1A mutations, which is currently a critical unmet need in clinic. Background & Aims: ARID1A is postulated to be a tumor suppressor gene owing to loss-of-function mutations in human pancreatic ductal adenocarcinomas (PDAC). However, its role in pancreatic pathogenesis is not clear despite recent studies using genetically engineered mouse (GEM) models. We aimed at further understanding of its direct functional role in PDAC, using a combination of GEM model and PDAC cell lines. Methods: Pancreas-specific mutant Arid1a-driven GEM model (Ptf1a-Cre; KrasG12D; Arid1af/f or "KAC") was generated by crossing Ptf1a-Cre; KrasG12D ("KC") mice with Arid1af/f mice and characterized histologically with timed necropsies. Arid1a was also deleted using CRISPR-Cas9 system in established human and murine PDAC cell lines to study the immediate effects of Arid1a loss in isogenic models. Cell lines with or without Arid1a expression were developed from respective autochthonous PDAC GEM models, compared functionally using various culture assays, and subjected to RNA-sequencing for comparative gene expression analysis. DNA damage repair was analyzed in cultured cells using immunofluorescence and COMET assay. Results: Retention of Arid1a is critical for early progression of mutant Kras-driven pre-malignant lesions into PDAC, as evident by lower Ki-67 and higher apoptosis staining in "KAC" as compared to "KC" mice. Enforced deletion of Arid1a in established PDAC cell lines caused suppression of cellular growth and migration, accompanied by compromised DNA damage repair. Despite early development of relatively indolent cystic precursor lesions called intraductal papillary mucinous neoplasms (IPMNs), a subset of "KAC" mice developed aggressive PDAC in later ages. PDAC cells obtained from older autochthonous "KAC" mice revealed various compensatory ("escaper") mechanisms to overcome the growth suppressive effects of Arid1a loss. Conclusions: Arid1a is an essential survival gene whose loss impairs cellular growth, and thus, its expression is critical during early stages of pancreatic tumorigenesis in mouse models. In tumors that arise in the setting of ARID1A loss, a multitude of "escaper" mechanisms drive progression. [ABSTRACT FROM AUTHOR]

The presence of leaky vasculature and the lack of lymphatic drainage of small structures by the solid tumors formulate nanoparticles as promising delivery vehicles in cancer therapy. In particular, among various nanoparticles, the mesoporous silica nanoparticles (MSN) exhibit numerous outstanding features, including mechanical thermal and chemical stability, huge surface area and ordered porous interior to store different anti-cancer therapeutics with high loading capacity and tunable release mechanisms. Furthermore, one can easily decorate the surface of MSN by attaching ligands for active targeting specifically to the cancer region exploiting overexpressed receptors. The controlled release of drugs to the disease site without any leakage to healthy tissues can be achieved by employing environment responsive gatekeepers for the end-capping of MSN. To achieve precise cancer chemotherapy, the most desired delivery system should possess high loading efficiency, site-specificity and capacity of controlled release. In this review we will focus on multimodal decorations of MSN, which is the most demanding ongoing approach related to MSN application in cancer therapy. Herein, we will report about the recently tried efforts for multimodal modifications of MSN, exploiting both the active targeting and stimuli responsive behavior simultaneously, along with individual targeted delivery and stimuli responsive cancer therapy using MSN. [ABSTRACT FROM AUTHOR]