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A chatbot is a software that can reproduce a discussion portraying a specific dimension of articulation among people and machines utilizing Natural Human Language. With the advent of AI, chatbots have developed from being minor guideline-based models to progressively modern models. A striking highlight of the current chatbot frameworks is their capacity to maintain and support explicit highlights and settings of the discussions empowering them to have human interaction in real-time surroundings. The paper presents a detailed database concerning the models utilized to deal with the learning of long haul conditions in a chatbot. The paper proposes a novel crossbreed Long Short Term Memory based Ensemble model to retain the information in specific situations. The proposed model uses a characterized number of Long Short Term Memory Networks as a significant aspect of its working as one to create the aggregate forecast class for the information inquiry and conversation. We found that both of the ensemble methods LSTM and GRU work well in different dataset environments and the ensemble technique is an effective one in chatbot applications.

Liraglutide is indicated for glycaemic control in adults with Type 2 diabetes mellitus (T2DM) as an adjunct to diet and exercise. A proposed biosimilar of liraglutide (Levim Liraglutide) was investigated for efficacy & safety in a phase 3 study against the originator reference liraglutide (Victoza®) manufactured by Novo Nordisk A/S, Denmark. Patients aged 18-65 years of age with glycosylated hemoglobin (HbA1c) between 7 and 10 %, among other criteria, were included in the study. Patients were randomized 1:1 to receive daily doses of either Levim liraglutide or reference liraglutide for 24 weeks. The least square mean (standard error, SE) for the primary efficacy endpoint of reduction in HbA1c% at Week 24 was -1.09 (0.15)% for Levim liraglutide group and -1.04 (0.14)% for reference liraglutide. The upper bound of the confidence interval for treatment difference was less than the non-inferiority margin of 0.4 % at one-sided alpha of 0.025 (P-value = 0.0003). The secondary endpoints for proportion of patients achieving reduction in HbA1c, glycaemic level and weight, changes in cardiovascular parameters and the overall safety profiles of the study drugs were comparable. Levim liraglutide demonstrated non-inferior efficacy and similar safety to reference liraglutide and may be an option in treatment of T2DM (CTRI.nic.in, no. CTRI/2022/02/040261)., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jatin Vimal, Srikar Raman and Kadalmani Krishnan are employees of Levim Biotech LLP. C.R. Anand Moses and R.P. Rajesh are consultant members for Levim Biotech LLP. Atul Gupta and Venkatesan Mudaliar are employees of Navitas Life Sciences, the contract research organization that conducted the study. This study was funded by Levim Biotech LLP, Chennai, India and BIRAC, DBT, India., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

BACKGROUND: Nafamostat mesylate is a potent in vitro antiviral agent that inhibits the host transmembrane protease serine 2 enzyme used by severe acute respiratory syndrome coronavirus 2 for cell entry. METHODS: This open-label, pragmatic, randomized clinical trial in Australia, New Zealand, and Nepal included noncritically ill hospitalized patients with coronavirus disease 2019 (Covid-19). Participants were randomly assigned to usual care or usual care plus nafamostat. The primary end point was death (any cause) or receipt of new invasive or noninvasive ventilation or vasopressor support within 28 days after randomization. Analysis was with a Bayesian logistic model in which an adjusted odds ratio <1.0 indicates improved outcomes with nafamostat. Enrollment was closed due to falling numbers of eligible patients. RESULTS: We screened 647 patients in 21 hospitals (15 in Australia, 4 in New Zealand, and 2 in Nepal) and enrolled 160 participants from May 2021 to August 2022. In the intention-to-treat population, the primary end point occurred in 8 (11%) of 73 patients with usual care and 4 (5%) of 82 with nafamostat. The median adjusted odds ratio for the primary end point for nafamostat was 0.40 (95% credible interval, 0.12 to 1.34) with a posterior probability of effectiveness (adjusted odds ratio <1.0) of 93%. For usual care compared with nafamostat, hyperkalemia occurred in 1 (1%) of 67 and 7 (9%) of 78 participants, respectively, and clinically relevant bleeding occurred in 1 (1%) of 73 and 7 (8%) of 82 participants. CONCLUSIONS: Among hospitalized patients with Covid-19, there was a 93% posterior probability that nafamostat reduced the odds of death or organ support. Prespecified stopping criteria were not met, precluding definitive conclusions. Hyperkalemia and bleeding were more common with nafamostat. (Funded by ASCOT and others; ClinicalTrials.gov number, NCT04483960.)

Marker sutures are often used for excised cutaneous lesions to aid histological analysis, however, there are no current guidelines to facilitate this in practice. The authors hypothesised that a lack of guidelines causes a variation in clinical practice and confusion of meaning between plastic surgeons and pathologists. This questionnaire-based study confirms the authors' hypothesis and highlights a discrepancy both between surgeons and in individual surgical practice. More importantly, we identify discord between histopathologists and plastic surgeons in relation to marker suture placement and report interpretation, leading to potential undertreatment of patients. This paper adds to the growing literature calling for guidelines regarding marker suture placement for cutaneous excision biopsies., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: An infodemic is excess information, including false or misleading information, that spreads in digital and physical environments during a public health emergency. The COVID-19 pandemic has been accompanied by an unprecedented global infodemic that has led to confusion about the benefits of medical and public health interventions, with substantial impact on risk-taking and health-seeking behaviors, eroding trust in health authorities and compromising the effectiveness of public health responses and policies. Standardized measures are needed to quantify the harmful impacts of the infodemic in a systematic and methodologically robust manner, as well as harmonizing highly divergent approaches currently explored for this purpose. This can serve as a foundation for a systematic, evidence-based approach to monitoring, identifying, and mitigating future infodemic harms in emergency preparedness and prevention., Objective: In this paper, we summarize the Fifth World Health Organization (WHO) Infodemic Management Conference structure, proceedings, outcomes, and proposed actions seeking to identify the interdisciplinary approaches and frameworks needed to enable the measurement of the burden of infodemics., Methods: An iterative human-centered design (HCD) approach and concept mapping were used to facilitate focused discussions and allow for the generation of actionable outcomes and recommendations. The discussions included 86 participants representing diverse scientific disciplines and health authorities from 28 countries across all WHO regions, along with observers from civil society and global public health-implementing partners. A thematic map capturing the concepts matching the key contributing factors to the public health burden of infodemics was used throughout the conference to frame and contextualize discussions. Five key areas for immediate action were identified., Results: The 5 key areas for the development of metrics to assess the burden of infodemics and associated interventions included (1) developing standardized definitions and ensuring the adoption thereof; (2) improving the map of concepts influencing the burden of infodemics; (3) conducting a review of evidence, tools, and data sources; (4) setting up a technical working group; and (5) addressing immediate priorities for postpandemic recovery and resilience building. The summary report consolidated group input toward a common vocabulary with standardized terms, concepts, study designs, measures, and tools to estimate the burden of infodemics and the effectiveness of infodemic management interventions., Conclusions: Standardizing measurement is the basis for documenting the burden of infodemics on health systems and population health during emergencies. Investment is needed into the development of practical, affordable, evidence-based, and systematic methods that are legally and ethically balanced for monitoring infodemics; generating diagnostics, infodemic insights, and recommendations; and developing interventions, action-oriented guidance, policies, support options, mechanisms, and tools for infodemic managers and emergency program managers., Competing Interests: Conflicts of Interest: SB, SBr, NG, SH, AI, MK, RL, TN, TDP, and BY are staff of the World Health Organization (WHO); CBF and BKW are consultants with WHO; SK and CV are staff of the US Centers for Disease Control and Prevention (US CDC). These authors alone are responsible for the views expressed in this paper, and they do not represent the views of their organizations. The conflicts of interest were reviewed and managed as per WHO procedures. AD declared that his university received research support on information diet measurement by WHO for the product owned by WHO. He was not part of the consensus driving during the closing session of the meeting. TM is the current Editor-in-Chief of JMIR Infodemiology and declared ownership interest in a company for work not related to the deliberation in this publication. LMB works for Immunize Canada/the Canadian Public Health Association, which has received educational grants/funding from Merck Canada, Pfizer Canada, Pfizer Global, Moderna Canada, Seqirus, Sanofi Canada, GSK Canada, and the Public Health Agency of Canada (PHAC). These funds are not related to the paper. CW was executive director of the nonprofit organization First Draft, which received funds for research and advocacy work from Google, and research project support on the effectiveness of SMS-based social inoculation from WHO. She chaired the first 3 days of the conference but was not part of the consensus driving during the closing session of the meeting. EP declared receiving conference stipends, training fees, and publication fees from the Medical Research Council. He was not part of the consensus driving during the closing session of the meeting. IB is director of the WHO Collaborating Center on information systems for health, which supports WHO with broader digital health analytics and policy analysis. The center has supported the Pan American Health Organization (PAHO)/WHO with infodemic analytics during COVID-19. SMR declared receiving consultancy fees from the EURO Health Group research consortium and is currently a consultant in infodemic management for WHO. JR and SVDL declared that their university received research funding from NATO Strategic Communications Centre of Excellence, Google Jigsaw, WhatsApp, British Academy, the Economic and Social Research Council (ESRC), the UK Cabinet Office, and EU Horizon 2020. They were not part of the consensus driving during the closing session of the meeting. AG declared that his university received research funds from the Canadian Institutes of Health Research (CIHR). AS declared receiving consultancy fees from Euro Health Group A/S – Denmark for services unrelated to the topic of the conference. PB is founder and CEO of HealthEnabled, which received past funding from Gavi, the Vaccine Alliance, to conduct digital social listening. JN declared employment with Harvard University, working in the field of medical misinformation. MG and MEB declared no conflicts of interest for this paper., (©Elisabeth Wilhelm, Isabella Ballalai, Marie-Eve Belanger, Peter Benjamin, Catherine Bertrand-Ferrandis, Supriya Bezbaruah, Sylvie Briand, Ian Brooks, Richard Bruns, Lucie M Bucci, Neville Calleja, Howard Chiou, Abhinav Devaria, Lorena Dini, Hyjel D'Souza, Adam G Dunn, Johannes C Eichstaedt, Silvia M A A Evers, Nina Gobat, Mika Gissler, Ian Christian Gonzales, Anatoliy Gruzd, Sarah Hess, Atsuyoshi Ishizumi, Oommen John, Ashish Joshi, Benjamin Kaluza, Nagwa Khamis, Monika Kosinska, Shibani Kulkarni, Dimitra Lingri, Ramona Ludolph, Tim Mackey, Stefan Mandić-Rajčević, Filippo Menczer, Vijaybabu Mudaliar, Shruti Murthy, Syed Nazakat, Tim Nguyen, Jennifer Nilsen, Elena Pallari, Natalia Pasternak Taschner, Elena Petelos, Mitchell J Prinstein, Jon Roozenbeek, Anton Schneider, Varadharajan Srinivasan, Aleksandar Stevanović, Brigitte Strahwald, Shabbir Syed Abdul, Sandra Varaidzo Machiri, Sander van der Linden, Christopher Voegeli, Claire Wardle, Odette Wegwarth, Becky K White, Estelle Willie, Brian Yau, Tina D Purnat. Originally published in JMIR Infodemiology (https://infodemiology.jmir.org), 20.02.2023.)

Aims: Dermal hyperneury is defined as the hypertrophy of small nerves in the dermis. It has been described in a variety of settings. We present a series of nine new cases with a distinctive clinical presentation and review the existing literature. The aim of the study was to summarise the clinical, histopathological and immunohistochemical findings in a case series of dermal hyperneury with unique clinical presentation., Methods and Results: Nine cases were identified from the referral practice of one of the authors. Clinical characteristics, including demographic details, were collated. The histopathological features and novel immunohistochemical findings were analysed. Four cases presented with multiple skin lesions. Clinical evaluation revealed no associated syndromic stigmata. The histology in all cases was that of dermal hyperneury. Immunohistochemistry for phosphatase and tensin homologue (PTEN) and RET was supportive of the lack of syndromic association., Conclusion: The presentation of dermal hyperneury with multiple cutaneous lesions and no syndromic associations is distinctive, and no study with PTEN and RET immunohistochemistry has previously been reported. Comparisons with recent reports of multiple non-syndromic mucocutaneous neuromas are discussed., (© 2019 John Wiley & Sons Ltd.)

Tricholemmoma, a benign follicular neoplasm with outer root sheath differentiation, typically comprises clear or pale cells, and when multiple is pathognomic of Cowden's syndrome. The tumor is probably underrecognized and in basaloid examples can be difficult to distinguish from basal cell carcinoma (BCC). We studied 55 tricholemmomas (including 15 basaloid cases) and compared immunohistochemical profile with nodular BCC from our archives. Basaloid and non-basaloid tricholemmomas had similar staining characteristics. BerEP4 was focally positive (range 10%-20%) in only 3/39 (7.7%) tricholemmomas compared with widespread positivity in BCC (90.8%, 139 of 151 cases with ≥50% tumor area stained). CD34 was expressed, usually focally (median 20%, range 10%-90%), in 52/53 (98.1%) tricholemmomas and was negative in all 21 BCCs stained. EMA staining lacked sensitivity or specificity in differentiating tricholemmoma from BCC. Five or more Merkel cells were found in 7/17 (40.1%) tricholemmomas and 1/23 (4.3%) nodular BCCs studied. In summary, immunohistochemistry is helpful in distinction between tricholemmoma, including difficult basaloid examples (BerEP4 negative or focal, CD34 positive) compared with BCC (BerEP4 widespread in most cases, CD34 negative). The presence of 5 or more Merkel cells is a relatively specific but not a particularly sensitive discriminator.

CD40, a tumour necrosis factor (TNF) receptor family member, is expressed in a variety of cell types, including B lymphocytes, macrophages, fibroblasts, endothelial and epithelial cells, and this widespread expression is likely to account for its central role in normal physiology and disease pathogenesis. In this study, we provide evidence to support a role for constitutive CD40 signalling in cell transformation. We show that the ligand for CD40 (CD40L/CD154) is expressed in CD40-positive human breast tumour biopsies, suggesting that the constitutive activation of the CD40 receptor in vivo may contribute to the oncogenic process. Coexpression of CD40 and CD40L confers oncogenic effects on immortalized human epithelial cells in vitro, increasing their proliferation, motility and invasion. Expression of LMP:CD40, a hybrid molecule comprising the N-terminus and transmembrane domains of the Epstein-Barr virus-encoded latent membrane protein-1 (LMP1) fused to the cytoplasmic tail of CD40, mimics a constitutively active CD40 receptor and promotes the transformation of immortalized rodent fibroblasts in vitro and their oncogenicity in vivo. The observed effects of aberrant CD40 activation on cell transformation are largely diminished upon suppression of the oncogenic NF-kappaB signalling pathway. Taken together, our results suggest a role for the constitutive engagement of the CD40L/CD40/NF-kappaB activation pathway in cell transformation and neoplastic growth. Strategies that neutralize this pathway may therefore be useful in cancer treatment and prevention.

Loss of heterozygosity (LOH) studies in ovarian tumors, have highlighted the chromosomal regions at 9q22-31 and 9q32-34 as being potentially important in tumor development. We have investigated LOH at 9q22-31 in 85 patients with epithelial ovarian cancer, 15 with non-epithelial tumors and 16 with benign disease. Varying patterns of LOH were observed across the markers used between different tumors, the most common (71%) being interstitial discontinuous losses. LOH was frequent, and was detected at equally high levels in malignant (71%) and benign tumors (70%). LOH occurred in epithelial invasive tumors, borderline tumors, fibromas and dermoid tumors. In malignant epithelial tumors LOH at 9q22-31 was not significantly associated with patient clinical and pathological parameters; however, survival was 29 months at the 50th centile survival, in those women whose tumors displayed LOH compared with 60 months in women whose tumors retained heterozygosity. LOH at 9q22-31 was significantly associated with LOH at the p53 locus (p=0.02) and the ovarian suppressor locus at 3p21 (p=0.05). We conclude that the chromosome region at 9q22-31, flanked by the microsatellite markers D9S1796 and D9S53, is a frequent and early event in ovarian tumorigenesis. With the of extent of discontinuous LOH, high density deletion mapping of this region using LOH as a strategy to identify candidate genes may be problematic. However with the completion of the human genome sequencing project several candidate genes are identified.