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Abstract High voter turnout in elections and referendums is desirable to ensure a robust democracy. Secure electronic voting is a vision for the future of elections and referendums. Such a system can counteract factors hindering strong voter turnout such as the requirement of physical presence during limited hours at polling stations. However, this vision brings transparency and confidentiality requirements that render the design of such solutions challenging. Specifically, the counting implementation must support reproducibility, and the choice of individual voters must remain confidential. In this paper, we propose and evaluate a novel referendum protocol that ensures transparency, confidentiality, and integrity, in trustless networks. The protocol is built by combining secure multi-party computation and distributed ledger technology, e.g., a Blockchain. The persistence and immutability of the protocol communication allow verifiability of the referendum outcome by any participant. Voters therefore do not need to trust third parties. We provide a formal description and conduct a thorough security evaluation of our proposal.

Abstract The majority of patients with Parkinson disease (PD) experience a loss in their sense of smell and accumulate insoluble α-synuclein aggregates in their olfactory bulbs (OB). Subjects affected by a SARS-CoV-2-linked illness (COVID-19) also frequently experience hyposmia. We previously postulated that microglial activation as well as α-synuclein and tau misprocessing can occur during host responses following microbial encounters. Using semiquantitative measurements of immunohistochemical signals, we examined OB and olfactory tract specimens collected serially at autopsies between 2020 and 2023. Deceased subjects comprised 50 adults, which included COVID19 + patients (n = 22), individuals with Lewy body disease (e.g., PD; dementia with Lewy bodies (n = 6)), Alzheimer disease (AD; n = 3), and other neurodegenerative disorders (e.g., progressive supranuclear palsy (n = 2); multisystem atrophy (n = 1)). Further, we included neurologically healthy controls (n = 9), and added subjects with an inflammation-rich brain disorder as neurological controls (NCO; n = 7). When probing for microglial and histiocytic reactivity in the anterior olfactory nuclei (AON) by anti-CD68 immunostaining, scores were consistently elevated in NCO and AD cases. In contrast, microglial signals on average were not significantly altered in COVID19 + patients relative to healthy controls, although anti-CD68 reactivity in their OB and tracts declined with progression in age. Mild-to-moderate increases in phospho-α-synuclein and phospho-tau signals were detected in the AON of tauopathy- and synucleinopathy-afflicted brains, respectively, consistent with mixed pathology, as described by others. Lastly, when both sides were available for comparison in our case series, we saw no asymmetry in the degree of pathology of the left versus right OB and tracts. We concluded from our autopsy series that after a fatal course of COVID-19, microscopic changes in the rostral, intracranial portion of the olfactory circuitry -when present- reflected neurodegenerative processes seen elsewhere in the brain. In general, microglial reactivity correlated best with the degree of Alzheimer’s-linked tauopathy and declined with progression of age in COVID19 + patients.

Abstract The personal lending marketplace, known as Peer‐to‐Peer (P2P) lending, has increased globally. However, providing unsecured loans to peers without requiring collateral remains a challenge. A platform called TrustLend is proposed to enable trustworthy transactions in the personal lending application. The platform attempts to eliminate or minimize the collateral requirement. The trustworthiness score adds to this platform's variable selection rules and can help lenders decide on reliable candidates as borrowers. The prototype implementing the TrustLend platform based on Ethereum smart contracts that use the trustworthiness score is also described and it is illustrated with a Decentralized Application (DApp) case study and customized smart contracts. The prototype demonstrates fundamental features and supports borrowers, lenders, and recommenders in establishing proposals and approvals. Finally, the prototype shows how end‐users can easily access loans with reduced collateral without hidden costs and swift transactions.

Even though the benefits of e-commerce for Small and Medium-Sized (SMEs) are enormous, not many SMEs have adopted e-commerce, especially in Palestine. Therefore, knowing what factors encourage SMEs to adopt e-commerce is necessary. However, e-commerce research has only been carried out on large-scale businesses. In contrast, studies on SMEs companies, especially regarding adopting e-commerce, have not been widely conducted. So, this research is important to determine what factors drive the adoption of e-commerce and the effect on marketing performance in Palestinian SMEs. The study's theoretical foundation is based on the TOE framework with AI Integration, Innovation Culture, and Customer Tech-Savviness. Using a simple random sampling technique from an online questionnaire, 305 SMEs were chosen as the sample for the study. The data were evaluated using partial least squares structural equation modelling (PLS-SEM) to explore the relationships among exogenous, mediator, and endogenous variables. Based on the study's results, it can be concluded that AI Integration, Customer Savviness, innovative culture, competitive pressure and business partner pressure factors positively and significantly influence e-commerce adoption. In addition, adopting E-commerce positively and significantly affects SMEs' Marketing Performance. Based on the results of this study, theoretical implications for E-Commerce adoption in Palestinian SMEs and managerial implications are recommended accordingly.

Abstract The recent emergence of multiple SARS‐CoV‐2 variants has caused considerable concern due to both reduced vaccine efficacy and escape from neutralizing antibody therapeutics. It is, therefore, paramount to develop therapeutic strategies that inhibit all known and future SARS‐CoV‐2 variants. Here, we report that all SARS‐CoV‐2 variants analyzed, including variants of concern (VOC) Alpha, Beta, Gamma, Delta, and Omicron, exhibit enhanced binding affinity to clinical grade and phase 2 tested recombinant human soluble ACE2 (APN01). Importantly, soluble ACE2 neutralized infection of VeroE6 cells and human lung epithelial cells by all current VOC strains with markedly enhanced potency when compared to reference SARS‐CoV‐2 isolates. Effective inhibition of infections with SARS‐CoV‐2 variants was validated and confirmed in two independent laboratories. These data show that SARS‐CoV‐2 variants that have emerged around the world, including current VOC and several variants of interest, can be inhibited by soluble ACE2, providing proof of principle of a pan‐SARS‐CoV‐2 therapeutic.

The primary aim of this research is to determine attitudes held towards autonomous vehicles (AVs) and understand their impact on intentions to use the service among ride-hailing users in the UK. Based on the Theory of Planned Behaviour model, an online, self-administered survey was used to collect data from 151 consumers (18-24-year-olds). The relationship between variables was measured using a Spearman’s Rank test in SPSS. The results of this study found all categories (overall attitude, perceived ease-of-use, perceived value, perceived safety, perceived risk, technology, environmentalism, subjective norms, perceived behavioural control) received a positive mean score. From these results, it can be concluded that this sample holds positive attitudes towards AVs and intend to use the service when they are made available. A positive score for perceived risk, however, indicated that this group thought there may be safety concerns when using this technology. The main contribution of this study is providing data to a new, and rapidly evolving field of research and thus the findings of the present study contribute to ongoing research related to consumers attitudes of AVs. Managerially, companies that focus on developing and implementing AV taxis need to focus more on the safety benefits of such vehicles.

Although ACE2 is the primary receptor for Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, a systematic assessment of host factors that regulate binding to SARS-CoV-2 spike protein has not been described. Here, we use whole-genome CRISPR activation to identify host factors controlling cellular interactions with SARS-CoV-2. Our top hit was a TLR-related cell surface receptor called leucine-rich repeat-containing protein 15 (LRRC15). LRRC15 expression was sufficient to promote SARS-CoV-2 spike binding where they form a cell surface complex. LRRC15 mRNA is expressed in human collagen-producing lung myofibroblasts and LRRC15 protein is induced in severe Coronavirus Disease 2019 (COVID-19) infection where it can be found lining the airways. Mechanistically, LRRC15 does not itself support SARS-CoV-2 infection, but fibroblasts expressing LRRC15 can suppress both pseudotyped and authentic SARS-CoV-2 infection in trans. Moreover, LRRC15 expression in fibroblasts suppresses collagen production and promotes expression of IFIT, OAS, and MX-family antiviral factors. Overall, LRRC15 is a novel SARS-CoV-2 spike-binding receptor that can help control viral load and regulate antiviral and antifibrotic transcriptional programs in the context of COVID-19 infection.

هدف البحث إلى بيان أثر تغير سعر صرف العملات الأجنبية على نتيجة النشاط للشركات المصرفية المدرجة ضمن سوق العراق للأوراق المالية واستخدم البحث أثر تغير سعر الصرف كمتغير مستقل ونتيجة النشاط كمتغير تابع، إذ طبق البحث على المصارف المدرجة في سوق العراق للأوراق المالية للسنوات من 2018 إلى 2021 وتم التعرض في الجانب النظري الى انواع سعر الصرف وأشكال وأهمية سعر الصرف والعوامل المؤثرة في سعر الصرف، وتم التطرق كذلك إلى القوائم المالية وأنواع القوائم المالية وعناصرها واعتمد البحث على المنهج الوصفي التحليل من خلال مراجع وأدبيات ذات صلة ودراسة الواقع الفعلي لتكوين البيانات الثانوية وتحليل بيانات القوائم المالية للمصارف، ومن ثم بعد ذلك القيام بالتحليل الإحصائي اللازم لإتمام الدراسة الحالية.

Cancer vaccination aims at inducing an adaptive immune response against tumor-derived antigens. In this study, we utilize recombinant human adenovirus serotype 5 (rAd5) and recombinant lymphocytic choriomeningitis virus (rLCMV)-based vectors expressing the melanocyte differentiation antigen gp100. In contrast to single or homologous vaccination, a heterologous prime boost vaccination starting with a rAd5-gp100 prime immunization followed by a rLCMV-gp100 boost injection induces a high magnitude of polyfunctional gp100-specific CD8+ T cells. Our data indicate that an optimal T cell induction is dependent on the order and interval of the vaccinations. A prophylactic prime boost vaccination with rAd5- and rLCMV-gp100 protects mice from a B16.F10 melanoma challenge. In the therapeutic setting, combination of the vaccination with low-dose cyclophosphamide showed a synergistic effect and significantly delayed tumor growth. Our findings suggest that heterologous viral vector prime boost immunizations can mediate tumor control in a mouse melanoma model.

Bangladesh is a maritime country with an area of 118000 km2 which supports a large number of commercially important species. Currently seaweeds are considered as important component of blue economy development in Bangladesh and farming is practiced at small scale level (Hypnea spp, Caulerpha reacemosa, Gelidium sp. are cultured). For the expansion of the seaweed farming in Bangladesh, a complete understanding of social and economic status of current farmers is important. However, information on socio-economic status of seaweed industry in Bangladesh is very limited. Therefore, this study aimed to understand existing culture methods and their cost, marketing channel and problems with seaweed farming in south east coast of Bangladesh. We used questionnaire survey and focus group discussions to collect data from seaweed farmers, researchers, local community and entrepreneurs. The study found that farmers are currently practicing long-line and horizontal net methods for the seaweed farming in the south east coastal region. The study also found that these culture methods are economically profitable. Seaweeds are currently sold locally and a proper value chain for seaweed marketing is still missing. Existing seaweed farmers are facing the problems related to insufficient credits for starting seaweed farming, lack of proper guidelines for farming and processing of harvested seaweed. This study suggests that for industrial level expansion of seaweed production in Bangladesh a proper value chain, development of seaweed derived products, farm monitoring systems, smooth seed supply and information hubs are required.

Abstract Supplier Impersonation Fraud (SIF) is a rising issue for Business-to-Business companies. The use of remote and quick digital transactions has made the task of identifying fraudsters more difficult. In this paper, we propose a data-driven fraud detection system whose goal is to provide an accurate estimation of financial transaction legitimacy by using the knowledge contained in the network of transactions created by the interaction of a company with its suppliers. We consider the real dataset collected by SIS-ID for this work.We propose to use a graph-based approach to design an Anomaly Detection System (ADS) based on a Self-Organizing Map (SOM) allowing us to label a suspicious transaction as either legitimate or fraudulent based on its similarity with frequently occurring transactions for a given company. Experiments demonstrate that our approach shows high consistency with expert knowledge on a real-life dataset, while performing faster than the expert system.

Abstract Background Long-term survival of stage IV melanoma patients has improved significantly with the development of immune checkpoint inhibitors (CIs). Reliable biomarkers to predict response and clinical outcome are needed. Methods We investigated the role of melanoma-associated antibodies as predictive markers for CI therapy in two independent cohorts. In cohort 1, a prospective study, we measured specific antibodies before treatment, after one week and after six to nine weeks of treatment. Cohort 2 consisted of serum samples prior to CI therapy initiation. ELISA assays were performed to quantify specific IgG directed against melanocyte differentiation antigens tyrosinase-related proteins 1 and 2 (TRP1/TYRP1 and TRP2/TYRP2), glycoprotein 100 (gp100), MelanA/MART1, and the cancer-testis antigen NY-ESO-1. Response was defined as either complete or partial remission on CT scan according to RECIST 1.1. Results In cohort 1, baseline levels of these antibodies were higher in the responder group, although statistical significance was only reached for NY-ESO-1 (p = 0.007). In cohort 2, significantly higher antibody baseline levels for MelanA/MART1 (p = 0.003) and gp100 (p = 0.029) were found. After pooling the results from both cohorts, higher levels of MelanA/MART1 (p = 0.013), TRP1/TYRP1 (p = 0.048), TRP2/TYRP2 (p = 0.047) and NY-ESO-1 (p = 0.005) specific antibodies at baseline were independently associated with response. Conclusions Melanoma-associated antibodies may be candidate biomarkers for response and survival in metastatic melanoma patients being treated with CIs. These markers may be used to complement patient assessment, in combination with PD-L1 status, tumor-infiltrating lymphocytes and tumor mutational burden, with the aim to predict outcome of CI treatment in patients with metastatic melanoma. Trial registration Ethikkommission Ostschweiz, EKOS 16/079 https://ongoingprojects.swissethics.ch/runningProjects_list.php?q=%28BASECID~contains~2016-00998%29&orderby=dBASECID.

Introduction: Cognitive impairment after concussion has been widely reported, but there is no reliable imaging biomarker that predicts the severity of cognitive decline post-concussion. This study tests the hypothesis that patients with a history of concussion and persistent cognitive impairment have fractional anisotropy (FA) and mean diffusivity (MD) values from diffusion tensor imaging (DTI) that are specifically associated with poor performance on the Montreal Cognitive Assessment (MoCA).Methods: Fifty-three subjects (19 females) with concussions and persistent cognitive symptoms had MR imaging and the MoCA. Imaging was analyzed by atlas-based, whole-brain DTI segmentation and FLAIR lesion segmentation. Then, we conducted a random forest-based recursive feature elimination (RFE) with 10-fold cross-validation on the entire dataset, and with partial correlation adjustment for age and lesion load.Results: RFE showed that 11 DTI variables were found to be important predictors of MoCA scores. Partial correlation analyses, corrected for age and lesion load, showed significant correlations between MoCA scores and right fronto-temporal regions: inferior temporal gyrus MD (r = −0.62, p = 0.00001), middle temporal gyrus MD (r = −0.54, p = 0.0001), angular gyrus MD (r = −0.48, p = 0.0008), and inferior frontal gyrus FA (r = 0.44, p = 0.002).Discussion: This is the first study to demonstrate a correlation between MoCA scores and DTI variables in patients with a history of concussion and persistent cognitive impairment. This kind of research will significantly increase our understanding of why certain persons have persistent cognitive changes after concussion which, in turn, may allow us to predict persistent impairment after concussion and suggest new interventions.

CRM adoption can provide innumerable benefits to the SMEs performance, including solving customer problems in a timely manner, enhancing customer satisfaction by appointing an expert to solve issues and queries, and the like. This study aims to examine the moderating effects of the firm size in the adoption of CRM in the Palestinian SMEs. A quantitative approach was used to investigate the relationships between the variables, which are compatibility, IT infrastructure, complexity, relative advantage, security, top management support, customer pressure, and competitive pressure. A questionnaire was designed to collect data from 420 SMEs in Palestine. A total of 331 respondents completed and returned the survey. The Partial Least Square-Structural Equation Model (PLS-SEM) approach was used to assess both the measurement and structural models. The Diffusion of Innovation Theory (DOI) and Technology, Organization, and Environment Framework (TOE) framework were employed to identify the determinant factors from the technological, organizational, and environmental perspectives. The findings and conclusions of this study provide show that the moderating effect of firm size has significant effect compatibility, top management support, customer pressure, and IT infrastructure factors.

Immune checkpoint inhibitors (ICIs) have improved the survival of patients with non-small cell lung cancer (NSCLC) by reinvigorating tumor-specific T cell responses. However, the specificity of such T cells and the human leukocyte antigen (HLA)-associated epitopes recognized, remain elusive. In this study, we identified NSCLC T cell epitopes of recently described NSCLC-associated antigens, termed keratinocyte differentiation antigens. Epitopes of these antigens were presented by HLA-A 03:01 and HLA-C 04:01 and were associated with responses to ICI therapy. Patients with CD8+ T cell responses to these epitopes had improved overall and progression-free survival. T cells specific for such epitopes could eliminate HLA class I-matched NSCLC cells ex vivo and were enriched in patient lung tumors. The identification of novel lung cancer HLA-associated epitopes that correlate with improved ICI-dependent treatment outcomes suggests that keratinocyte-specific proteins are important tumor-associated antigens in NSCLC. These findings improve our understanding of the mechanisms of ICI therapy and may help support the development of vaccination strategies to improve ICI-based treatment of these tumors.

Several common and debilitating neurodegenerative disorders are characterized by the intracellular accumulation of neurofibrillary tangles (NFTs), which are composed of hyperphosphorylated tau protein. In Alzheimer’s disease (AD), NFTs are accompanied by extracellular amyloid-beta (Aβ), but primary tauopathy disorders are marked by the accumulation of tau protein alone, including forms of frontotemporal dementia (FTD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), among others. 18F-THK5351 has been reported to bind pathological tau as well as associated reactive astrogliosis. The goal of this study was to validate the ability of the PET tracer 18F-THK5351 to detect early changes in tau-related pathology and its relation to other pathological hallmarks. We demonstrated elevated in vivo 18F-THK5351 PET signaling over time in transgenic P301S tau mice from 8 months that had a positive correlation with histological and biochemical tau changes, as well as motor, memory, and learning impairment. This study indicates that 18F-THK5351 may help fill a critical need to develop PET imaging tracers that detect aberrant tau aggregation and related neuropathology in order to diagnose the onset of tauopathies, gain insights into their underlying pathophysiologies, and to have a reliable biomarker to follow during treatment trials.

Current biomarkers used in research and in clinical practice in Alzheimer's Disease (AD) are the analysis of cerebral spinal fluid (CSF) to detect levels of Aβ42 and phosphorylated-tau, amyloid and FDG-PET, and MRI volumetry. Some of these procedures are still invasive for patients or expensive. Electroencephalography (EEG) and Magnetoencephalography (MEG) are two non-invasive techniques able to detect the early synaptic dysfunction and track the course of the disease. However, in spite of its added value they are not part of the standard of care in clinical practice in dementia. In this paper we review what these neurophysiological techniques can add to the early diagnosis of AD, whether results in both modalities are related to each other or not, as well as the need of its validation against current biomarkers. We discuss their potential implications for the better understanding of the pathophysiological mechanisms of the disease as well as the need of performing simultaneous M/EEG recordings to better understand discrepancies between these two techniques. Finally, more studies are needed studying M/EEG with amyloid and Tau biomarkers.

Continuous quality improvement is a component of professionalism. Maintenance of Certification (MOC) is a mechanism in the USA for physicians to keep current with medical knowledge and contribute to practice improvement. Little is known about primary care physicians’ perceptions of the practice improvement (Part IV) components of MOC. We aimed to determine primary care physicians’ perceptions of their professional responsibility to participate in Part IV MOC. This was a cross-sectional study of primary care physicians using the American Medical Association Masterfile. We developed a nine-item survey, designed from expert consensus and literature to determine views on Part IV MOC as a professional responsibility. We surveyed 1500 randomly selected primary care physicians via mail from November 2014 to May 2015. The response rate was 42% (627 of 1,500): 47% (273 of 585) were family practitioners and 49% (289 of 585) were internists. Factor analysis revealed a two-factor survey, with five items pertaining to positive views of MOC Part IV and four items pertaining to negative views. Internists were more likely to view MOC Part IV as time consuming (82.0% vs. 70.3%, P = .001), expensive (50.9% vs. 38.8%, P = .004), and not relevant to practice (39.1% vs. 23.8%, P

Background and objectives: This study evaluated the effect of chronic consumption of saccharin on important physiological and biochemical parameters in rats. Materials and Methods: Male Wistar rats were used in this study and were divided into four groups: A control group and three experimental groups (groups 1, 2, and 3) were treated with different doses of saccharin at 2.5, 5, and 10 mg/kg, respectively. Each experimental group received sodium saccharin once per day for 120 days while the control group was treated with distilled water only. In addition to the evaluation of body weight, blood samples [total protein, albumin, glucose, lipid profile, alanine transaminase (ALT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatinine, and uric acid] and urine (isoprostane) were collected in zero time, and after 60 and 120 days for biochemical evaluation. Liver (catalase activity) and brain (8-hydroxy-2’-deoxyguanosine, 8-OHdG) tissues were collected at time zero and after 120 days. Results: The data showed that saccharin at 5 mg/kg increased body weight of treated rats after 60 (59%) and 120 (67%) days of treatment. Increased concentration of serum glucose was observed after treatment with saccharin at 5 (75% and 62%) and 10 mg/kg (43% and 40%) following 60 and 120 days, respectively. The concentration of albumin decreased after treatment with saccharin at 2.5 (34% and 36%), 5 (39% and 34%), and 10 mg/kg (15% and 21%) after 60 and 120 days of treatment, respectively. The activity of LDH and uric acid increased proportionally with dosage levels and consumption period. There was an increased concentration of creatinine after treatment with saccharin at 2.5 (125% and 68%), 5 (114% and 45%), and 10 mg/kg (26% and 31%) following 60 and 120 days, respectively. Catalase activity and 8-OHdG increased by 51% and 49%, respectively, following 120 days of treatment with saccharin at 2.5 mg/kg. Elevation in the concentration of isoprostane was observed after treatment with saccharin at all doses. Conclusions: The administration of saccharin throughout the treatment period was correlated with impaired kidney and liver function. Both hyperglycemic and obesity-inducing side effects were observed. There was an increased oxidative status of the liver, as well as exposure to increased oxidative stress demonstrated through the increased levels of isoprostane, uric acid, 8-OHdG, and activity of catalase. Therefore, it is suggested that saccharin is unsafe to be included in the diet.