Exploring the Complex Dynamics: Examining the Influence of Deviant Personas in Online Gambling.

The widespread use of computers and the Internet has substantially changed the gaming environment during the past ten years. The gambling industry is no longer exclusive to land-based gaming establishments (such as casinos and racetracks). Today, a few keystrokes on a computer are all it takes to access gaming operations. Social media platforms like Facebook, Instagram, Snapchat and various other platforms constitute a particular form of access that has drawn more attention from academics in gambling studies. This increasing focus is partially attributable to the fact that social media sites have gained popularity as a means of accessing online gambling websites via hyperlinks hidden inside adverts. Users of social networking platforms can play free-to-play virtual gambling games using programmes. Virtual gaming platforms are the new name for these free-to-play simulation games of gambling. However, there is evidence to suggest that playing social casino games may serve as a "gateway" to real money gambling. The purpose of this study is to investigate the influence of deviant personas on online gambling behavior. By examining the relationship between deviant personas and online gambling, we seek to enhance our understanding of the factors that contribute to problematic gambling behaviors in virtual environments. Employing a robust methodological approach, this research amalgamates the analytical power of PLS-SEM (Partial Least Squares Structural Equation Modeling) to explore the factors influencing the intention to adopt online gambling services. The data for this study were obtained by administering an online survey questionnaire to a sample of 325 aware customers of online gambling. The study's discerning insights have notable implications for the academic community, brand strategists, online game designers, and online gambling platform providers, offering valuable guidance for decision-making and strategy formulation within the burgeoning online gambling industry.

Systemic lupus erythematosus: latest insight into etiopathogenesis.

Systemic lupus erythematosus (SLE) is a complex autoimmune disorder of unknown etiology. Multifactorial interaction among various susceptible factors such as environmental, hormonal, and genetic factors makes it more heterogeneous and complex. Genetic and epigenetic modifications have been realized to regulate the immunobiology of lupus through environmental modifications such as diet and nutrition. Although these interactions may vary from population to population, the understanding of these risk factors can enhance the perception of the mechanistic basis of lupus etiology. To recognize the recent advances in lupus, an electronic search was conducted among search engines such as Google Scholar and PubMed, where we found about 30.4% publications of total studies related to genetics and epigenetics, 33.5% publications related to immunobiology and 34% related to environmental factors. These outcomes suggested that management of diet and lifestyle have a direct relationship with the severity of lupus that influence via modulating the complex interaction among genetics and immunobiology. The present review emphasizes the knowledge about the multifactorial interactions between various susceptible factors based on recent advances that will further update the understanding of mechanisms involved in disease pathoetiology. Knowledge of these mechanisms will further assist in the creation of novel diagnostic and therapeutic options.

Hybrid natural orifice transluminal endoscopic surgery splenectomy: A case report.

Laparoscopic splenectomy has become an established standard of care in managing surgical diseases of the normal-sized spleen. Natural orifice transluminal endoscopic surgery (NOTES) is a step forward in making laparoscopic surgery even less invasive. In addition, the spleen can be accessed easily with the hybrid transvaginal approach. We present the case of a 38-year-old woman with medical refractory immune thrombocytopenic purpura. Hybrid notes splenectomy was performed using three working 5-mm abdominal trocars and a 10-mm camera port through the posterior fornix of the vagina. The organ was retrieved intact transvaginally. The patient had minimal post-operative pain and was discharged on the 1st post-operative day. Transvaginal hybrid NOTES approach is feasible for operative visualisation, dissection, clipping and specimen extraction in patients requiring splenectomy. It may offer better cosmesis and faster recovery. Comparative studies with conventional laparoscopic approach are desirable.

Partial Calcaneus Reconstruction using 'Opportunistic Grafts': A Case Report.

Although replantation of an amputated extremity has been successfully performed, occasionally the surgeon is forced to amputate in the case of an unsalvageable open fracture. These appendages can theoretically act as an autologous 'bone and tissue bank' for patients if they have reconstructable contralateral injuries. We present a case of an athlete who sustained a Gustilo and Anderson IIIC injury on 1 leg resulting in a below knee amputation. Her other lower leg had a traumatic amputation of the heel pad, partial amputation of the calcaneus, and complete Achilles tendon loss. Tissues from this amputated appendage were utilised to restore the anatomy of the contralateral extremity. The distal tibia and the tibialis anterior from the amputated limb were used to reconstruct the missing posterior tuberosity of the calcaneus and the Achilles tendon respectively. The soft tissue deficiency of the heel pad was restored with an anterolateral thigh free flap. At 2-year follow-up, the patient is pain free and back to playing soccer. This case highlights the opportunistic use of amputated parts to reconstruct a calcaneus and Achilles tendon. A multidisciplinary approach with plastic surgeons is required. The main advantage of this 'Spare Part Surgery' philosophy is to provide autologous graft of a similar geometry and to avoid harvesting tissues from an additional donor site.

CoV2-Detect-Net: Design of COVID-19 prediction model based on hybrid DE-PSO with SVM using chest X-ray images.

For Covid-19 suspected cases, it is critical to diagnose them accurately and rapidly so that they can be isolated and provided with required medical care. A self-learning automation model will be helpful to diagnose the COVID-19 suspected individual using chest X-rays. AI based designs, which utilizes chest X-rays, have been recently proposed for the detection of COVID-19. However, these approaches are either using non-public database or having a complex design. In this study we have proposed a novel framework for real time detection of coronavirus patients without manual intervention. In our framework, we have introduced a 3-step process in which initially K-means clustering, and feature extraction is performed as a data pre-processing step. In the second step, the selected features are optimized by a novel feature optimization approach based on hybrid differential evolution algorithm and particle swarm optimization. The optimized features are then feed forwarded to SVM classifier. Empirical results show that our proposed model is able to achieve 99.34% accuracy. This shows that our model is robust and sustainable in diagnosis of COVID-19 infected individual.

Structure-Based Design of Small Peptide Ligands to Inhibit Early-Stage Protein Aggregation Nucleation.

We report a structure-based approach to design peptides that can bind to aggregation-prone, partially folded intermediates (PFI) of insulin, thereby inhibiting early stages of aggregation nucleation. We account for the important role of the modular architecture of protein-protein binding interfaces and tertiary structure heterogeneity of the PFIs in the design of peptide inhibitors. The determination of association hotspots revealed that two interface segments are required to capture majority contribution to insulin homodimer binding energy. The selection of peptides that will have a high probability to inhibit insulin self-association was done on the basis of similarity in binding interface coverage of PFI residues in the peptide-PFI complex and the native-PFI dimer. Data on aggregate growth rate and secondary structure for formulations incubated under amyloidogenic conditions show that designed peptides inhibit insulin aggregation in a concentration-dependent manner. The mechanism of aggregation inhibition was probed by determining the enthalpy of peptide-insulin binding and peptide micellization using isothermal titration calorimetry. Finally, the effect of designed peptides on insulin activity was quantified using a spectrophotometric assay for glucose uptake by HepG2 cells.

Postoperative fever in the time of COVID-19.

Summary: Postoperative fever is common following orthopedic trauma surgery. As the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases in the community, migration into the acute care hospital setting intensifies, creating confusion when fever develops postoperatively. The transmission dynamics of SARS-CoV-2 make it difficult to adequately gauge and pinpoint risk groups with questionnaires at the time of hospital admission. This is particularly problematic when asymptomatic or presymptomatic patients infected with SARS-CoV-2 require urgent surgery and cannot be screened effectively. One approach is to treat every patient as though they were SARS-CoV-2-positive in preparation for surgery, but doing so could exacerbate shortages of personal protective equipment and staffing limitations. Uncertainty regarding the etiology of postoperative fever could be significantly reduced by universal SARS-CoV-2 testing of all surgical patients at the time of hospital admission in addition to routine screening, but testing capacity and a rapid turnaround time would be required.

Analytical Platform for Monitoring Aggregation of Monoclonal Antibody Therapeutics.

PURPOSE: To develop an analytical platform for the estimation as well as characterization of aggregates over the complete size spectrum (from invisible monomer to visible precipitates). METHODS: Two mAb samples were incubated at 30°C in different buffer systems of protein A chromatography for observing degradation due to aggregation. The aggregation in these samples was quantified by size exclusion chromatography (SEC), dynamic light scattering (DLS), and micro flow imaging (MFI). RESULTS: The results obtained from various characterization tools were analysed in various size ranges - size exclusion chromatography (SEC) (1 nm - 25 nm), dynamic light scattering (DLS) (10 nm - 5 µm), and micro flow imaging (MFI) (2 µm - 300 µm). Since each characterization tool covers a particular size range, data from multiple tools was collected in the "handover" regions to demonstrate accuracy of the platform. CONCLUSIONS: Based on the observations from the experiments, an analytical platform has been proposed covering the whole size spectrum that would be of utility to those engaged in formulation development as well as other aspects related to stability of biotherapeutic products.

Preduodenal portal vein: A recipe for disaster during laparoscopic cholecystectomy.

We had encountered a very rare congenital anomaly of a preduodenal portal vein while doing laparoscopic cholecystectomy. More significant in our case is that this preduodenal vein is hiding behind omental adhesions with the gallbladder. We want to raise awareness about this very rare anomaly. Recognition and knowledge of this anomaly will prevent the potential of a serious operative misadventure.

Kinetics and Characterization of Non-enzymatic Fragmentation of Monoclonal Antibody Therapeutics.

PURPOSE: To understand non-enzymatic hydrolytic fragmentation of a monoclonal antibody therapeutic under temperature stressed conditions and investigating possible mechanism for the same. METHODS: The mAb therapeutic was incubated at 50°C in phosphate buffer at pH 6.5 and fragmentation was monitored at different ionic strengths under stressed conditions. The incubated mAb was sampled at regular time intervals by analytical Size Exclusion Chromatography (SEC). RESULTS: It was observed that 57% of the mAb product fragmented over 4 days into two fragment species - Fc-Fab and Fab with molecular weights of 97 KDa and 47 KDa, respectively, as measured by mass spectrometry (MS) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). The fragmentation rate was slow initially and then accelerated with time. No change in % aggregate level was observed in this duration, implying that degradation was primarily via fragmentation at high temperature. Kinetics of hydrolytic fragmentation was hypothesized and SEC data was fitted to estimate the kinetic rate constants. While degradation of the monomer into fragment species was non-Arrhenius with a negative activation energy, further degradation of Fab-Fc fragments into Fab or Fc fragments followed Arrhenius Law with an activation energy of 2.1 and 15.38 kcal/mol, respectively. CONCLUSION: High temperature (50°C) causes mAb to cleave at the hinge region to form Fab-Fc and Fab/Fc, as confirmed by dynamic light scattering, SDS-PAGE, SEC, and MS. A kinetic model for hydrolytic fragmentation has been proposed. The results are expected to assist end users in formulation development as well as in monitoring stability of biotherapeutic products.

Equilibrium Ensembles for Insulin Folding from Bias-Exchange Metadynamics.

Earliest events in the aggregation process, such as single molecule reconfiguration, are extremely important and the most difficult to characterize in experiments. To this end, we have used well-tempered bias exchange metadynamics simulations to determine the equilibrium ensembles of an insulin molecule under amyloidogenic conditions of low pH and high temperature. A bin-based clustering method that uses statistics accumulated in bias exchange metadynamics trajectories was employed to construct a detailed thermodynamic and kinetic model of insulin folding. The highest lifetime, lowest free-energy ensemble identified consisted of native conformations adopted by a folded insulin monomer in solution, namely, the R-, the Rf-, and the T-states of insulin. The lowest free-energy structure had a root mean square deviation of only 0.15 nm from native x-ray structure. The second longest-lived metastable state was an unfolded, compact monomer with little similarity to the native structure. We have identified three additional long-lived, metastable states from the bin-based model. We then carried out an exhaustive structural characterization of metastable states on the basis of tertiary contact maps and per-residue accessible surface areas. We have also determined the lowest free-energy path between two longest-lived metastable states and confirm earlier findings of non-two-state folding for insulin through a folding intermediate. The ensemble containing the monomeric intermediate retained 58% of native hydrophobic contacts, however, accompanied by a complete loss of native secondary structure. We have discussed the relative importance of nativelike versus nonnative tertiary contacts for the folding transition. We also provide a simple measure to determine the importance of an individual residue for folding transition. Finally, we have compared and contrasted this intermediate with experimental data obtained in spectroscopic, crystallographic, and calorimetric measurements during early stages of insulin aggregation. We have also determined stability of monomeric insulin by incubation at a very low concentration to isolate protein-protein interaction effects.

Peptide Dendrons as Thermal-Stability Amplifiers for Immunoglobulin G1 Monoclonal Antibody Biotherapeutics.

Biotherapeutics such as monoclonal antibodies (mAbs) have a major share of the pharmaceutical industry for treatment of life-threatening chronic diseases such as cancer, skin ailments, and immune disorders. Instabilities such as aggregation, fragmentation, oxidation, and reduction have resulted in the practice of storing these products at low temperatures (-80 to -20 °C). However, reliable storage at these temperatures can be a challenge, particularly in developing and underdeveloped countries; hence, lately, there has been a renewed interest in creating formulations that would offer stability at higher temperatures (25 to 55 °C). Most therapeutic formulations contain excipients such as salts, sugars, amino acids, surfactants, and polymers to provide stability to the biotherapeutic, but their efficacy at high temperatures is limited. The current work proposes the use of peptide dendrons of different generations to create formulations that would be stable at high temperature. Among these dendrons, third-generation lysine dendron L6 has been identified to provide the highest stability to mAbs, as demonstrated by a host of analytical techniques such as size-exclusion chromatography (SEC), dynamic light scattering (DLS), Nanoparticle tracking Analysis (NTA), and circular dichroism (CD). The biocompatibility of these dendrons was confirmed by hemolytic activity tests. Non-interference of the dendrons with the activity of the mAb was confirmed using a surface plasmon resonance (SPR) based activity assay. We hope that this study will stimulate utilization of such higher-generation dendrons for enhancing the thermal stability of mAbs.

From virtual observations to business insights: A bibliometric review of netnography in business research.

Netnography is a special kind of qualitative social media research. It applies ethnographic techniques to comprehend social interaction in settings of modern digital communications. This article aims to highlight the key contributors and knowledge structure of this research domain. Utilizing bibliographic data of 722 articles retrieved from the Scopus database, researchers used performance analysis to have insights into the most prolific authors, institutions, countries and journals. Keywords co-occurrence analysis was done to map the knowledge structure. The thematic map tool was used to recognize basic themes, motor themes, niche themes, and emerging themes in order to suggest future research directions. The results indicate that, in terms of research publications, the most productive nation is the United Kingdom. The most lucrative organization has been acknowledged as Griffith University. The most influential author is stated to be Mkono M. The most resourceful source is Journal of Business Research. In addition, three significant knowledge clusters important to study utilizing netnography were identified as a result of co-occurrence of keywords analysis namely, consumer behaviour, co-creation in online brand communities and authenticity. Further, niche and emerging themes include-sustainable tourism, customer engagement and sharing economy. When taken as a whole, this review is a useful tool for quickly understanding the most recent research findings and potential directions for further investigation. An assessment of the state of netnography in business and management research has not been systematically investigated. Hence, the present study aims to thorough a grasp of the state-of-the-art in Netnography research field over the past decades along with the future research directions. Studying the state of the art in the field adds to academic knowledge and provides updated information on the procedure.

Disturbance in communication between mitochondrial redox processes and the AMPK/PGC-1α/SIRT-1 axis influences diverse organ symptoms in lupus-affected mice.

BACKGROUND: Mechanisms behind multiple organ involvement in lupus, is still an enigma for researchers. Mitochondrial dysfunction and oxidative stress are known to be important aspects in lupus etiology however, their role in lupus organ manifestation is yet to be understood. The present study is based on the understanding of interplay between AMPK/PGC-1α/SIRT-1 axis, mitochondrial complexes, and anti-oxidants levels, which might be involved in lupus organ pathology. METHODOLOGY: Pristane-induced Balb/c mice lupus model (PIL) was utilised and evaluation of anti-oxidants, mitochondrial complexes, pro-inflammatory cytokines levels, biochemical parameters were performed by standard procedures. Tissues were studied by haematoxylin and eosin staining followed by immunohistochemistry. The AMPK/PGC-1α/SIRT-1 expression was analysed by using qPCR and flowcytometry. Analysis of reactive oxygen species (ROS) among WBCs was performed by using various dyes (DCFDA, Mitosox, JC-1) on flowcytometry. RESULT: Significant presence of immune complexes (Tissue sections), ANA (Serum), and pro-inflammatory cytokines (plasma), diminished anti-oxidants and altered biochemical parameters depict the altered pathology in PIL which was accompanied by dysregulated mitochondrial complex activity. Differential expression of the AMPK/PGC-1α/SIRT-1 axis was detected in tissue and correlation with mitochondrial and antioxidant activity emerged as negative in PIL group while positive in controls. Close association was observed between ROS, mitochondrial membrane potential, and AMPK/PGC-1α/SIRT-1 axis in WBCs. CONCLUSION: This study concludes that mitochondria play a dual role in lupus organ pathology, contributing to organ damage while also potentially protecting against damage through the regulation of interactions between antioxidants and the AMPK axis expression.

Regional and periodic asymmetries in the effect of Russia-Ukraine war on global stock markets.

This study aims to investigate regional and periodic asymmetries in the impact of the outbreak of the Russia-Ukraine war on global equity markets. Employing the event study methodology, the current study examines global stock market reactions within a 61-day window centred around the event day, i.e., February 24, 2022. MSCI equity indices of 47 sample countries have been utilized to ensure uniformity in the index development methodology. They provide broader coverage of global equity markets by including large and mid-cap companies, representing approximately 85% of the free float-adjusted market capitalization for each sampled country. The study extends the event window to 61 days to assess the enduring effects of the war over a relatively longer period. The research delineates regional and periodic asymmetries and posits that the impact of the war on a market is contingent upon its geographical proximity and trade relations with Russia and Ukraine. Additionally, the impact is stronger during a shorter window surrounding the event date but diminishes over the extended period.

MS(n) , LC-MS-TOF and LC-PDA studies for identification of new degradation impurities of bupropion.

Three new degradation impurities of bupropion were characterized through high performance liquid chromatography coupled to photodiode array detection and to time-of-flight mass spectrometry. Bupropion was subjected to the ICH prescribed stress conditions. It degraded to seven impurities (I-VII) in alkaline hydrolytic conditions which were optimally resolved on an XTerra C18 column (250 × 4.6 mm, 5 µm) with a ternary mobile phase comprising ammonium formate (20 mm, pH 4.0), methanol and acetonitrile (75:10:15, v/v). The degradation impurities (III-V and VII) were characterized on the basis of mass fragmentation pattern of drug, accurate mass spectral and photodiode array data of the drug and degradation impurities. Compound V was found to be a known degradation impurity [1-hydroxy-1-(3-chlorophenyl)propan-2-one], whereas III, IV and VII were characterized as 2-hydroxy-2-(3'-chlorophenyl)-3,5,5-trimethylmorpholine, (2,4,4-trimethyl-1,3-oxazolidin-2-yl)(3-chlorophenyl)-methanone and 2-(3'-chlorophenyl)-3,5,5-trimethylmorphol-2-ene, respectively. Compound III was a known metabolite of the drug. This additional information on the degradation impurities can help in the development of a new stability-indicating assay method to monitor the stability of the drug product during its shelf-life as well as in development of a drug product with increased shelf-life.