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Background: This study was done to determine the prevalence of computer vision syndrome and associated ocular morbidity in a tertiary care hospital. Methods: A cross sectional observational study was conducted on 673 patients based on the inclusion criteria. The patients were asked to fulfil the computer vision syndrome survey form 3 and OSDI questionnaire. Spontaneous eye blink rate, Schirmer’s test 1, tear break up time, refraction were performed for these patients. Data was collected and analysed by SPSS software. Results: The prevalence of computer vision syndrome was 73% with 294 males and 206 females. The mean age of the patients was 30.29 years. Most of the participants were between 21-30 years. The screen time for most of the study participants (59.80%) came out to be >6 hours/day on average. The chief complaint of majority patients was blurred vision and asthenopia whereas the secondary complaint was watering and headache. Maximum patients (38.20%) from our study were students and competitive exam aspirants followed by teachers and software engineers. The screen modality used by 34.20 % patients was mobile phones > laptops. The mean SEBR was 13.50 minutes. The mean OSDI was 17.44. The screen time was significantly correlated to SEBR (p

An orbital apex syndrome (OAS) has been described previously as a syndrome involving damage to the ocular motor and sensory nerves in association with optic nerve dysfunction. Patients usually present with signs and symptoms derived from the involvement of structures within the orbital apex, the superior orbital fissure, and the cavernous sinus. Visual loss from optic neuropathy and ophthalmoplegia involving multiple cranial nerves are the hallmarks of orbital apex syndrome. Historically, superior orbital fissure, orbital apex, and cavernous sinus are being used to define the anatomical locations of a disease process. However, the diagnostic evaluation and management are similar for each of these entities. The authors reviewed the literature on evaluating disorders involving the orbital apex and it’s diagnosis.

The hormone melatonin plays a role in our natural sleep-wake cycle. Natural levels of melatonin in the blood are highest at night. Aqueous flow has a distinctive circadian rhythm, being lower at night than during the day. IOP fluctuates in a rhythmical diurnal pattern and this fluctuation is greater in eyes with glaucoma. Sleep apnoea is a type of sleep disorder breathing that causes intermittent pauses in breathing during sleep, leading to transient nocturnal hypoxia and hypercapnia. Obstructive sleep apnoea (OSA) is one of the systemic risk factors for glaucoma which causes irreversible visual field (VF) damage.

Eye injuries constitute a significant cause of avoidable global blindness. Animal-related injuries are an increasing public health issue worldwide. The interaction of a man with animals occurs in various situations, and the danger associated with it are underestimated and also there are underreported wounds. Animal-induced ocular injuries are often severe and may lead to visual impairment, blindness and cosmetic disfigurement. Animal-related ocular injuries are classified according to the geographical distribution, type of animal, its behavior and availability in the community. This article reviews current literature and discusses the mechanism and severity of animal inflicted ocular and adnexal injuries in humans and various management techniques.

Clinicians are baffling for reconstruction of small- to medium-sized defects of the oral cavity since time immemorial, each and every flap has its own limitations, ideal flap should be pliable, easily transferrable that can result in a better restoration of form and function of oral mucosa, we have platysma for the same purpose.We aim to provide surgical technique of the superiorly-based platysma myocutaneous flap with a single neck incision in this study, as well as the flap design, results, and complications associated with age, gender, the recipient site, and the size of the defect.Study included 20 patients with oral potentially malignant disorders operated under local anaesthesia with wide local excision and reconstruction with platysma myocutaneous flap at a single tertiary care centreThe association between the variables was calculated using Chi-square tests and paired t tests.Five cases of dehiscence were found at varied sites and flap viability was significantly influenced by location of skin paddle. In between anterior jugular vein and posterior external jugular vein it was 100% viable while on and posterior to the vein, had skin paddle loss. Significant improvement in mouth opening was also seen in Oral Sub-mucous Fibrosis patients.The platysma flap is a technique sensitive, and its results are promising for the reconstruction of oral defects.

Virophagy, the selective autophagosomal engulfment and degradation of viral components, is crucial for antiviral immunity. However, the mechanisms leading to viral antigen recognition and autophagy induction remain poorly understood. Here, we identify a novel kinase, Cyclin-dependent kinase-like 5 (CDKL5), as an essential regulator of virophagy. Deletion of CDKL5 or abrogation of its kinase activity reduced virophagy of Sindbis virus (SINV), a neurotropic RNA virus, and increased intracellular accumulation of SINV capsid proteins and cellular cytotoxicity. Mechanistically, through direct phosphorylation of the selective autophagy receptor p62, CDKL5 promoted formation of p62 inclusion bodies that bound capsid. Loss of CDKL5 disrupted the capsid-p62 interaction, and a p62 phosphomimetic mutant rescued the interaction. CDKL5 knockout mice demonstrated increased neuronal cell death after SINV infection and enhanced lethality after infection with several human viruses. Overall, these findings identify a cell-autonomous innate immune mechanism for autophagy activation to clear toxic viral capsid aggregates during infection.

Goldenhar’s syndrome is a rare condition which was described at first in the early 1950’s. which was characterized by a combination of anomalies such as dermal epibulbar cysts, auricular appendices and malformation of the ears. In 1963, the name oculo-auriculovertebral (OAV) dysplasia for this condition was suggested by gorlin and he also incorporated vertebral anomalies as one of the signs of syndrome. Here, we describe a case of 7 month old male patient with preauricular ear tags, limbal dermoid, cleft palate with tongue tie.

PurposeCode smells indicate deep software issues. They have been studied by researchers with different perspectives. The need to study code smells was felt from the perspective of software industry. The authors aim to evaluate the code smells on the basis of their scope of impact on widely used open-source software (OSS) projects.Design/methodology/approachThe authors have proposed a methodology to identify and rank the smells in the source code of 16 versions of Apache Tomcat Software. Further, the authors have analyzed the categorized smells by calculating the weight of the smells using constant weights as well as Best Worst Method (BWM). Consequently, the authors have used Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) to determine the rank of versions using constant weights as well as BWM.FindingsVersion 1 of Apache Tomcat has least smell, and version 8 is reported to contain the maximum code smells. Notable differences in both the cases during the trend analysis are reported by the study. The findings also show that increase is observed in the number of code smells with the release of newer versions. This increment is observed till version 8, followed by a subtle marked depreciation in the number of code smells in further releases.Originality/valueThe focus is to analyze smells and rank several versions of Apache Tomcat, one of the most widely used software for code smell study. This study will act as a significant one for the researchers as it prioritizes the versions and will help in narrowing down the options of the software used to study code smell.

Thyroid eye disease (TED) is a chronic debilitating condition which causes physical discomfort, oculo-facial disfigurement and compromised visual function. Around 25% of people with Graves’ hyperthyroidism are affected by TED, where 1 in 20 patients might report with moderate-to-severe, active disease that will require medical management for reducing both TED activity and severity. The mainstay of medical management involves intravenous corticosteroids for active moderate-to-severe TED. After accurate understanding of the mechanism and pathophysiology of this disease, investigations and randomised clinical trials have been conducted. The role of immunotherapy targeting and influencing different biomolecular pathways including that of T cells, B cells, cytokines and cell surface receptors have been investigated in various randomised clinical trials. This review article addresses the epidemiology, associated risk factors, recent advances in pathophysiology, newer diagnostic tools and current management options available for TED which include the use of immunosuppressive drugs like rituximab (RTX), tocilizumab, infliximab (IFX), etanercept ( ETN) and teprotumumab etc. Keywords: Thyroid eye disease, Graves' orbitopathy, Orbital fibroblast, Insulin like growth factor­1, Cytokine, rituximab, Tocilizumab, Teprotumumab

Dry eye disease (DED) is a multifactorial disorder of the ocular surface that results in ocular discomfort, visual disturbance and damage to the ocular surface. It is one of the most common complaints in daily ophthalmic practice. The greater prevalence of dry eye in women compared to men suggests that sex hormones may have a role in this condition. Sex hormones; estrogen and androgens influence production of all components of the tear film including aqueous layer, lipid layer, and mucin layer. Various mechanisms such as decrease in hormonal levels, shift in feedback mechanisms, and changes in receptor receptivity interplay to alter the ocular surface homeostasis and subsequently result in DED. The purpose of this review is to briefly outline current scientific evidence on the influence of androgen and estrogen on the lacrimal and meibomian glands as well as on the ocular surface epithelia including conjunctival goblet cells during reproductive and menopausal periods. This article also outlines the updates regarding role of gonadal hormones in the treatment of dry eye. Keywords: Dry Eye, Sex hormones, Estrogen, Androgen, Testosterone, Progesterone, Tear film, Meibomian gland, Lacrimal gland, Ocular surface, Menopause, HRT, Schirmer’s test.

Oral cavity which represents the first part of the human digestive system is housed by innumerable microorganisms. It is subjected to be under constant wear and tear of the tissues and is also vulnerable to various infections, lesions and tumors. This article represents some of the most common benign soft tissue lesion in the oro-facial region. It also signifies the importance of possible early diagnosis and management either conservatively or by surgical removal of the lesion.

Recently there has been upsurge in the cases of Obstructive Sleep Apnea (OSA) with increased prevalence of obesity in the general population. It has been continuously proved that OSA and metabolic syndrome go hand in hand and hence OSA predisposes an individual to a series of cardio-vascular disorders like ischemic heart disease, myocardial infarction, arrhythmia etc. In this article we have emphasized the possibility of ocular involvement in OSA patients. Several studies have shown ocular associations like floppy eye lid syndrome, glaucoma, dry eye syndrome, papilledema, keratoconus, non-arteritic anterior ischemic optic neuropathy etc. Through this review, we would like to highlight the ophthalmological associations of OSA, their pathogenesis and outcome with the treatment of OSA. Keywords: Obstructive sleep apnea, Ocular disorders, Floppy eyelid syndrome, Glaucoma, Keratoconus.

In recent years, more attention has been paid towards the research in the field of gender specific medicine. The purpose of this review article is to find out the gender alteration in the incidence and prevalence of diabetes and diabetic retinopathy and role of sex steroid hormones in the etiopathogenesis of diabetic retinopathy. Several studies have suggested that the prevalence of type-I diabetes is more common among males than females in post pubertal age group. Sex hormone receptors have been identified in the eye, but the role of sex hormones are involved in the development of diabetic retinopathy, is not well understood. Through this article, we would like to highlight about the sex hormone receptors in various ophthalmic tissues, gender based differences in diabetic retinopathy and the role of gonadal hormones in the development of diabetic retinopathy.

Caveolae are bulb-like invaginations made up of two essential structural proteins, caveolin-1 and cavins, which are abundantly present at the plasma membrane of vertebrate cells. Since their discovery more than 60 years ago, the function of caveolae has been mired in controversy. The last decade has seen the characterization of new caveolae components and regulators together with the discovery of additional cellular functions that have shed new light on these enigmatic structures. Early on, caveolae and/or caveolin-1 have been involved in the regulation of several parameters associated with cancer progression such as cell migration, metastasis, angiogenesis, or cell growth. These studies have revealed that caveolin-1 and more recently cavin-1 have a dual role with either a negative or a positive effect on most of these parameters. The recent discovery that caveolae can act as mechanosensors has sparked an array of new studies that have addressed the mechanobiology of caveolae in various cellular functions. This review summarizes the current knowledge on caveolae and their role in cancer development through their activity in membrane tension buffering. We propose that the role of caveolae in cancer has to be revisited through their response to the mechanical forces encountered by cancer cells during tumor mass development.

Technological changes have remarkable effect on today’s business world that triggers industriesn to re-establish the assembly systems. 3D printing has advanced with the new innovative improvements in added substance producing in the course of the most recent three decades. 3D printing innovations empower structure streamlining and have preferences over ordinary creation techniques. All industries should adopt the new era so as to survive in a very rapidly changing competitive environment. the development industry is additionally under technological developments’ pressure to vary. Therefore, 3D printing technology is under a good attention in housing industry as a replacement strategic challenge. the development industry takes 3D printing as a concept of a replacement building technology. The main aim of this paper is to review the 3D printing technology applications of other industries, to review 3D printing attempts in housing industry and to discuss possible application areas for 3D printing intentions in housing industry. This project summarizes the 3D-printing applications utilized in industries, with a spotlight on adaption strategies in housing industry. Significant writing databases are investigated about 3D printing looks into and furthermore the preliminaries of usage in lodging industry. Collected data is interpreted within the construction research jargon. The conceivable execution territories in development are proposed for future improvements. The paper leads to identifying and classifying the new developments in 3D printing technology in various industries and making projections on the possible adaptation areas in housing industry.

The TLK1/Nek1 axis contributes to cell cycle arrest and implementation of the DDR to mediate survival upon DNA damage. However, when the damage is too severe, the cells typically are forced into apoptosis, and the contribution of TLKs in this process has not been investigated. In contrast, it is known that Nek1 may play a role by phosphorylating VDAC1 maintaining proper opening and closure of the channel and thus mitochondrial integrity. We now show that the activating phosphorylation of Nek1-T141 by TLK1 contributes to the phosphorylation and stability of VDAC1 and thereby to mitochondrial permeability and integrity. Treatment of three different cell lines model that overexpress Nek1-T141A mutant with doxorubicin showed exquisite sensitivity to the drug, with implementation of rapid accumulation of cells with subG1 DNA content (apoptotic) and other alterations in the cell cycle. In addition, these cells displayed reduced oxygen consumption under normal conditions and less reliance on mitochondria and more dependence on glycolysis for energy production. Consistent with greater apoptosis, upon treatment with low doses of doxorubicin, cells overexpressing Nek1-T141A displayed leakage of Cyt-C into the cytoplasmic fraction. This suggests that inhibiting the TLK1/Nek1/VDAC1 nexus could sensitize cancer cells to apoptotic killing in combination with an appropriate DNA damaging agent. We in fact have previously reported that Nek1 expression is elevated in advanced Prostate Cancer (PCa) and we now report that VDAC1 expression is elevated and correlated with disease stage, thereby making the TLK1/Nek1/VDAC1 nexus a very attractive target for PCa.

Background Gastrointestinal stromal tumors are mesenchymal in origin, being derived from the interstitial cells of Cajal. These can be found anywhere in the gastrointestinal tract and are commonly found in the stomach followed by the small bowel. Gastrointestinal stromal tumors are usually asymptomatic and are often found incidentally. Chronic bleeding is one of the most common presentation. Gastrointestinal stromal tumors presenting with massive gastro intestinal haemorrhage and mimicking arteriovenous malformation on radiology are rare with only few cases reported. Methods Herein we present such a case of a 45-year-old gentleman with massive gastro intestinal bleeding. At presentation, patient was in congestive heart failure due to severe anaemia with a hemoglobin of 2.9g/dL. CECT Angiography localised the bleed to be from a jejunal mass lesion with radiological features consistent with those of arteriovenous malformation. Patient underwent laparoscopy assisted resection and anastomosis. Results Histopathology examination revealed a low risk jejunal gastrointestinal stromal tumor with no evidence of arteriovenous malformation. The mass was removed completely and the patient was discharged on 5th post-operative day. Patient was followed up in the out-patient department and was found to be doing well. Conclusions Gastrointestinal stromal tumors though relatively uncommon should be kept as important differentials for acute torrential gastrointestinal bleeding. It is highlighted that a presentation of gastrointestinal stromal tumors similar to that of arteriovenous malformations on cross sectional imaging should be kept in mind. The present case is reported in hope of expanding the knowledge of a rare occurrence, its aetiology, clinical impact and treatment.

A software bug is characterized by many features/attributes out of which some are entered during the time of bug reporting whereas others are entered during the bug fixing. Severity is an important bug attribute and critical factor in deciding how soon it needs to be fixed. During the initial period of bug reporting, its severity changes and get stabilizes over a period of time. Severity identification is a major task of triagers, whose success affects the bug fix time. The prediction of bug fix time will help in estimating the maintenance efforts and better software project management. We investigated the association among the bug attributes and built multi-attribute based classification and regression models for bug severity and fix time prediction. Bug severity and fix time prediction models have been built using the combinations of different independent bug attributes. We have used different classification and regression techniques, namely Support Vector Machine (SVM), Naive Bayes (NB), k-Nearest Neighbors (k-NN), Ordinal Regression (OR), Fuzzy Linear Regression (FLR), Fuzzy Multi Linear Regression (FMLR), Multiple Linear Regression (MLR), Support Vector Regression (SVR) and k-Nearest Neighbors Regression (k-NNR) to build the models. Our models are tested on the real world datasets from famous open source project: Mozilla. k-NN gives better performance than NB and SVM in terms of precision and f-measure for bug severity prediction. In terms of goodness of fit, SVR is better than MLR and k-NNR for bug fix time prediction. The proposed mechanism is able to predict severity and fix time for newly reported bugs. Empirical results reveal that the multi-attribute based classification and regression models work well for bug severity and fix time prediction. The two newly derived attributes Summary weight and Bug age are found to be good predictors of severity across all the used techniques. In case of bug fix time prediction, Bug age is found to be a good predictor.

Background: The purpose of the present study was to envisage the anti-plaque and anti-inflammatory properties of neem (Azadirachta) in the form of a mouth gel. Materials and Methods: A total of 60 subjects (33 males and 27 females) from age group 19 - 35 years, suffering from mild to moderate gingivitis were randomly divided into two groups. Group A (n = 30) participants were advised experimental (neem) gel and Group B (n = 30) participants were advised 0.2% chlorhexidine gel. All the clinical parameters (the gingival index by Loe and Silness [1], Plaque index by Silness and Loe [2] and sulcus bleeding index by Muhlemann H. R. and Sen S. [3]) were recorded at baseline, on the 14th day and 21st day by the same clinician in both groups. Results: on intragroup comparison the gingival index, plaque index and sulcus bleeding index decrease significantly in both the groups in all assessed periods. On intergroup comparison the indices did not differ significantly at baseline but after 2nd and 3rd week, the indices in Group B decrease more than the group A, which was statistically significant. Conclusion: Based on the observations of our study, it can be concluded that chlorhexidine gluconate as well as neem gel can be effectively used as an adjunct to mechanical plaque control in prevention of plaque and gingivitis. chlorhexidine gluconate gel has been found to be more effective when antiplaque and anti-inflammatory properties were considered. The effect of neem observed maybe because of its anti-inflammatory action. The antiplaque action of chlorhexidine gluconate is due to its substantivity. Substantivity of neem is required to be further studied.

Background: Metastatic dissemination of prostate cancer (PCa) accounts for majority of PCa related deaths. However, the exact mechanism of PCa cell spread is still unknown. We uncovered a novel interaction between two unrelated promotility factors, tousled-like kinase 1 (TLK1) and MAPK-activated protein kinase 5 (MK5), which initiates a signaling cascade promoting metastasis. In PCa, TLK1-MK5 signaling might be crucial as androgen deprivation therapy (ADT) leads to increased expression of both TLK1 and MK5 in metastatic patients. Moreover, TCGA analysis also revealed higher expression of both TLK1 and MK5 in metastatic tumors. Therefore, we hypothesize that TLK1-MK5 axis promotes PCa cell migration and invasion through actin reorganization as well as focal adhesion proteins modification and disruption of this interaction may help to keep the tumor localized. Methods and Results: We conducted scratch wound repair and proliferation assays to determine if TLK1 and MK5 can regulate motility and proliferation. Both genetic depletion and pharmacologic inhibition of TLK1 and MK5 resulted in reduced migration of both non-malignant MEF and PCa cells without affecting cellular proliferation rate. Trans-well invasion assays also demonstrated reduced invasion of MK5−/− MEF cells in Matrigel and other ECMs. However, TLK1 overexpression alone in the MK5−/− MEF cells did not increase the wound healing and invasion which suggested that TLK1 cannot enhance cellular migration and invasion in absence of MK5. We confirmed TLK1 binding of MK5 by co-IP, His- and GST-pull down assays and established that TLK1 phosphorylates MK5 on three residues (S160, S354, S386) that results in the catalytic activation of MK5. While WB detected substantial amount of pMK5 S354 and TLK1 in all major PCa cell lines, anti-androgen treatment increases pMK5 S354 level in a dose-dependent manner and pharmacologic inhibition of TLK1 reduces pMK5 S354 level in LNCaP cells, which suggest TLK1 as an authentic pMK5 S354 kinase. IHC analysis of TRAMP mice and human PCa TMA also revealed higher pMK5 S354 level in metastatic lesions compared to the low-risk tumors. In addition, pMK5 S354 was found to colocalize with neuroendocrine marker chromogranin A, together of which may suggest pMK5 as a potential biomarker of PCa aggressiveness. The motility reduction of PCa cells upon MK5 inhibition is a consequence of impaired actin filamentation as we observed in LNCaP and PC3 cells. Our WB analysis demonstrated that MK5 inhibition by a repurposed inhibitor results in decreased FAK Y861, Paxillin Y118, HSP27 S78/82 phosphorylation, and ERK3 stabilization, which could lead to altered actin filamentation, focal adhesions, morphology, as well as motility and invasion. Conclusion: Our data support that TLK1-MK5 axis is involved in driving PCa cell metastasis and clinical aggressiveness, hence, disruption of this axis may inhibit the metastasis of PCa. Citation Format: Md Imtiaz Khalil, Vibha Singh, Judy A. King, Arrigo De Benedetti. TLK1-MK5 axis modulates actin filaments and focal adhesion components to promote PCa cell migration and invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2424.

The number of issues fixed in the current release of the software is one of the factors which decides the next release of the software. The source code files get changed during fixing of these issues. The uncertainty arises due to these changes is quantified using entropy based measures. We developed a Non-Homogeneous Poisson Process model for Open Source Software to understand the fixing of issues across releases. Based on this model, optimal release-updating using entropy and maximizing the active user's satisfaction level subject to fixing of issues up to a desired level, is investigated as well. The proposed models have been validated on five products of the Apache open source project. The optimal release time estimated from the proposed model is close to the observed release time at different active user's satisfaction levels. The proposed decision model can assist management to appropriately determine the optimal release-update time. The proposed entropy based model for issues estimation shows improvement in performance for 21 releases out of total 23 releases, when compared with well-known traditional software reliability growth models, namely GO model [1] and S-shaped model [2] . The proposed model is also found statistically significant.

Background: Majority of prostate cancer (PCa) related fatalities occur due to metastasis of cancer cells to adjacent and distal organs. We identified the novel interaction between two kinases (TLK1-MK5) that in part may initiate a signaling cascade promoting PCa metastasis. In PCa, TLK1-MK5 signaling might be crucial as androgen deprivation therapy leads to increased expression of TLK1 and compensatory activation of MK5 in metastatic castration-resistant prostate cancer patients. Methods: We performed scratch wound repair and 3D chemotactic migration assays to determine the motility rates of different TLK1 and MK5 perturbed cells. Co-IP, His, and GST pull down, in vitro kinase (IVK) assays and mass spectrometry (MS) were conducted to determine TLK1-MK5 interaction and phosphorylation. Western blotting (WB), immunohistochemistry (IHC) and bioinformatic analysis were used to examine TLK1 and pMK5 levels in PCa cell lines, mice prostate tumors and PCa tissue microarray (TMA). Results: Both genetic depletion and pharmacologic inhibition of TLK1 and MK5 can significantly reduce wound healing rate in MEF and LNCaP cells. However, TLK1 overexpression alone in the MK5 −/− MEF cells did not increase the wound healing which suggested that TLK1 cannot enhance cellular migration in absence of MK5. Our reciprocal co-IPs, His- and GST pull down assays confirmed TLK1-MK5 interaction in cultured cells. Incubation of purified recombinant TLK1B and MK5 increases the phosphorylation of MK5 and its kinase activity. MS analysis identified three unique phosphorylation sites in MK5 (S160, S354, S386) by TLK1B. While our WB detected substantial amount of pMK5 S354 and TLK1 in all major PCa cell lines, anti-androgen treatment increased pMK5 S354 level in a dose-dependent manner and pharmacologic inhibition of TLK1 reduces pMK5 S354 level in LNCaP cells. IHC staining of TRAMP mice prostate tissues also exhibited increased pMK5 S354 level in aggressive tumor compared to benign regions. Finally, IHC analysis of PCa TMA indicated a correlation between elevated pMK5 S354 level and generally higher Gleason scores as well as nodal metastatic status of the tumors. Conclusion: Our data support that TLK1-MK5 signaling is functionally involved in driving PCa cell motility and clinical aggressiveness, hence, disruption of this axis may inhibit the metastasis of PCa.

In this work, we propose a time-variant software reliability model (SRM)which considers the fault detection and the highest number of faults in software. The time-variant genetic algorithm process is implemented for the assessment of the SRM parameters. The proposed model works upon a non-homogeneous Poisson process (NHPP) and incorporates fault dependent detection and software failure intensity and the un-removed error in the software. We had considered programmers proficiency, software complexity, organization hierarchy, and perfect debugging as the determining factors for SRM. The dataset collected from 74 software projects was experimented with to establish and validate the proposed software reliability model's better fit. Data is collected over a period, which is initiated with the start of the project and is continuously monitored until its completion. Several parameters are analyzed, and a collection of 115 attributes are given with 11 different time frames in terms of product and process characteristics. A total of 383 persons were involved in software design, where the issue count total is 255. The proposed time-variant fault detection SRM is implemented in Jira and is also compared with the existing reliability model presented in the literature. It is observed that the proposed fault detection SRM works better in terms of different parameters like mean square error (MSE), root mean square error (RMSE), and r-squared (R2). The work is carried out, ensuring time-varying fault detection, which is measured by considering response count, coding and non-coding deliverables, and the number of bugs in the software. We considered the programmer's proficiency, software complexity, organization hierarchy, and perfect debugging as the determining factors for presenting the software reliability model. The proposed Software reliability model shows improvement over existing algorithms as the residual errors are reduced, and prediction accuracy is high in terms of cumulative fault detection.

The ageing discourse has now moved onto acknowledging the greater demand for the ageing-competent practitioners and the dynamic interventions. The review of earlier literature in the field of Gerontological Social Work in India clearly reveals that there exists an inadequate focus of this emerging area. Further, it is noticed that there is a shift in the approach to interventions in elderly care in recent times. The current interventions mainly focus on organizing and empowering older persons for their own development and wellbeing. The focus of the paper is to discuss the context of Gerontological Social Work in India: the role and approaches in Social Work along with the concerns and challenges in the discipline. The paper also discusses the scope for development of interventions in the area of elderly care in India and highlights them with a few selective good practices as adopted and implemented by various agencies in India. The paper concludes with a discussion on the possible solutions for strengthening the competencies of Gerontological Social Work Professionals and the effective interventions that require for facing the challenges of population ageing in developing countries like India.

Soft tissues include skin, mucosa, muscle, tendon, nerve and ligament. Soft tissue injury to the facial structures is a common component of the maxillofacial trauma cases. It may be superficial or deep involving important vital structures. It may be associated with facial bone fractures, nerve injury, salivary glands and their ducts and blood vessels. Violence and motor vehicle accidents are the predominant causes of injury. Soft tissue injury may lead to pain, swelling, loss of blood/tissue and lack of mobility of the specific area. Always patient should be assessed for concomitant intracranial, craniofacial, ophthalmological and cervical spine injuries. Proper handling of soft tissue injuries of the maxillofacial region is of paramount importance since aesthetics plays a major role in patients’ mental well-being. This chapter deals with the different types of soft tissue injuries and their management.

The present research would measure the barriers faced by an individual in using the UPI-based apps. The barriers have been categorized into five distinct groups, viz., usage, value, risk, tradition and image barrier. An attempt has been made to measure the relationship of these various barriers with the behavioral intention of the individuals for using the UPI-based apps. The structured questionnaire was prepared using the standard scales. Step-wise regression was done to find out the relationship between the various barriers. It was found that usage barrier, risk barrier and tradition barrier have the most significant relationship with behavior intention of using UPI apps.

Most prostate cancer (PCa) deaths result from progressive failure in standard androgen deprivation therapy (ADT), leading to metastatic castration-resistant PCa (mCRPC), however, the mechanism and key players leading to this are not fully understood. While studying the role of tousled-like kinase 1 (TLK1) and never in mitosis gene A (NIMA)-related kinase 1 (NEK1) in a DNA damage response (DDR)-mediated cell cycle arrest in LNCaP cells treated with bicalutamide, we uncovered that overexpression of wt-NEK1 resulted in a rapid conversion to androgen-independent (AI) growth, analogous to what has been observed when YAP1 is overexpressed. We now report that overexpression of wt-NEK1 results in accumulation of YAP1, suggesting the existence of a TLK1&gt, NEK1&gt, YAP1 axis that leads to adaptation to AI growth. Further, YAP1 is co-immunoprecipitated with NEK1. Importantly, NEK1 was able to phosphorylate YAP1 on six residues in vitro, which we believe are important for stabilization of the protein, possibly by increasing its interaction with transcriptional partners. In fact, knockout (KO) of NEK1 in NT1 PCa cells resulted in a parallel decrease of YAP1 level and reduced expression of typical YAP-regulated target genes. In terms of cancer potential implications, the expression of NEK1 and YAP1 proteins was found to be increased and correlated in several cancers. These include PCa stages according to Gleason score, head and neck squamous cell carcinoma, and glioblastoma, suggesting that this co-regulation is imparted by increased YAP1 stability when NEK1 is overexpressed or activated by TLK1, and not through transcriptional co-expression. We propose that the TLK1&gt, YAP1 axis is a key determinant for cancer progression, particularly during the process of androgen-sensitive to -independent conversion during progression to mCRPC.

Summary Through in vitro kinase assays and docking studies, we report the synthesis and biological evaluation of a phenothiazine analog J54 with potent TLK1 inhibitory activity for prostate cancer (PCa) therapy. Most PCa deaths result from progressive failure in standard androgen deprivation therapy (ADT), leading to metastatic castration-resistant PCa. Treatments that can suppress the conversion to mCRPC have high potential to be rapidly implemented in the clinics. ADT results in increased expression of TLK1B, a key kinase upstream of NEK1 and ATR and mediating the DNA damage response that typically results in temporary cell-cycle arrest of androgen-responsive PCa cells, whereas its abrogation leads to apoptosis. We studied J54 as a potent inhibitor of this axis and as a mediator of apoptosis in vitro and in LNCaP xenografts, which has potential for clinical investigation in combination with ADT. J54 has low affinity for the dopamine receptor in modeling and competition studies and weak detrimental behavioral effects in mice and C. elegans., Graphical Abstract, Highlights • J54, a safe and potent inhibitor of TLK1, was generated via in silico docking studies • J54 leads to apoptosis of PCa cells in combination with anti-androgen administration • J54 has low affinity for dopamine receptor and low anti-dopaminergic activity in animals • TLK1B is selectively increased upon ADT thereby providing a specific target for PCa, Medical Biochemistry; Structural Biology; Cancer

Software users report bugs on the bug tracking system in a distributed environment with different levels of understanding and knowledge about the software. As a result of this, software bug repository data are increasing day by day with noise and uncertainty in it. The noise and uncertainty present in bug summary need to be handled, so that it should not affect the performance of learning strategies for different bug attributes and fix time predictions. Bug prioritization is a process of deciding the sequence of bugs to be fixed. Wrong bug prioritization results in unresolved important bugs with delayed release of the software, thus affecting the quality and evolution of the software. Bug priority prediction requires historical data for the training of the classifiers. However, such historical data is not always available in practice for all the software. In such circumstances, designing prediction models with training data from other projects is the solution. This process of bug priority prediction using training and testing bug data from two different projects is called cross-project bug priority prediction. We have used Shannon entropy to measure the uncertainty in bug summary in addition to bug severity and summary weight for bug priority prediction. In this paper, we have proposed different machine learning classifiers to predict the priority of a reported bug in cross-project context by handling the uncertainty. Results show performance improvement for proposed entropy-based cross-project bug priority prediction over existing summary-based cross-project bug priority prediction for a newly coming bug report.