Search

BACKGROUND Immune checkpoint inhibitors (ICIs) are among the most promising treatment options for melanoma and non-small cell lung cancer (NSCLC). While ICIs can induce effective anti-tumor responses, they may also drive serious immune-related adverse events (irAEs). Identifying biomarkers to predict which patients will suffer from irAEs would enable more accurate clinical risk-benefit analysis for ICI treatment and may also shed light on common or distinct mechanisms underpinning treatment success and irAEs. METHODS In this prospective multi-center study, we combined a multi-omics approach including unbiased single-cell profiling of over 300 peripheral blood mononuclear cell (PBMC) samples and high-throughput proteomics analysis of over 500 serum samples to characterize the systemic immune compartment of patients with melanoma or NSCLC before and during treatment with ICIs. FINDINGS When we combined the parameters obtained from the multi-omics profiling of patient blood and serum, we identified potential predictive biomarkers for ICI-induced irAEs. Specifically, an early increase in CXCL9/CXCL10/CXCL11 and interferon-γ (IFN-γ) 1 to 2 weeks after the start of therapy are likely indicators of heightened risk of developing irAEs. In addition, an early expansion of Ki-67+ regulatory T cells (Tregs) and Ki-67+ CD8+ T cells is also likely to be associated with increased risk of irAEs. CONCLUSIONS We suggest that the combination of these cellular and proteomic biomarkers may help to predict which patients are likely to benefit most from ICI therapy and those requiring intensive monitoring for irAEs. FUNDING This work was primarily funded by the European Research Council, the Swiss National Science Foundation, the Swiss Cancer League, and the Forschungsförderung of the Kantonsspital St. Gallen.

The recent emergence of the SARS-CoV-2 variant Omicron has caused considerable concern due to reduced vaccine efficacy and escape from neutralizing antibody therapeutics. Omicron is spreading rapidly around the globe and is suspected to account for most new COVID-19 cases in several countries, though the severity of Omicron-mediated disease is still under debate. It is therefore paramount to identify therapeutic strategies that inhibit the Omicron SARS-CoV-2 variant. Here we report using 3D structural modelling that Spike of Omicron can still associate with human ACE2. Sera collected after the second mRNA-vaccination did not exhibit a protective effect against Omicron while strongly neutralizing infection of VeroE6 cells with the reference Wuhan strain, confirming recent data by other groups on limited vaccine and convalescent sera neutralization efficacy against Omicron. Importantly, clinical grade recombinant human soluble ACE2, a drug candidate currently in clinical development, potently neutralized Omicron infection of VeroE6 cells with markedly enhanced potency when compared to reference SARS-CoV-2 isolates. These data show that SARS-CoV-2 variant Omicron can be readily inhibited by soluble ACE2, providing proof of principle of a viable and effective therapeutic approach against Omicron infections.

Although ACE2 is the primary receptor for 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 aTLR-related cell surface receptor calledleucine-rich repeat-containing protein 15(LRRC15).LRRC15expression was sufficient to promote SARS-CoV-2 Spike binding where they form a cell surface complex.LRRC15mRNA is expressed in human collagen-producing lung myofibroblasts and LRRC15 protein is induced in severe 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 intrans. 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.

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.

Introduction This study aimed to determine if thromboelastography (TEG) is associated with reduced blood product use and surgical reintervention following cardiopulmonary bypass (CPB) compared to traditional coagulation tests. Methods A retrospective review was conducted of 698 patients who underwent CPB at a tertiary-care, community-based, university-affiliated hospital from February 16, 2014 to February 16, 2015 (Period I) and from May 16, 2015 to May 16, 2016 (Period II). Traditional coagulation tests guided transfusion during Period I and TEG guided transfusion during Period II. Intraoperative and postoperative administration of blood products (red blood cells, fresh frozen plasma, platelets, and cryoprecipitate), reoperation for hemorrhage or graft occlusion, duration of mechanical ventilation, hospital length of stay, and mortality were recorded. Results Use of a TEG-directed algorithm was associated with a 13.5% absolute reduction in percentage of patients requiring blood products intraoperatively (48.2% vs. 34.7%, p < 0.001). TEG resulted in a 64.3% and 43.1% reduction in proportion of patients receiving fresh frozen plasma (FFP) and platelets, respectively, with a 50% reduction in volume of FFP administered (0.3 vs. 0.6 units, p < 0.001). Use of TEG was not observed to decrease postoperative blood product usage or mortality significantly. The median length of hospital stay was reduced by one day after TEG guided transfusion was implemented (nine days vs. eight days, p = 0.01). Conclusions Use of TEG-directed transfusion of blood products following CPB appeared to decrease the need for intraoperative transfusions, but the effect on clinical outcomes has yet to be clearly determined.

Collusion occurs when multiple malicious participants of a distributed protocol work together to sabotage or spy on honest participants. Decentralized protocols often rely on a subset of participants called workers for critical operations. Collusion between workers can be particularly harmful to the security of the protocol. We propose two protocols that select a subset of workers from the set of participants such that the probability of the workers colluding together is minimized. Our first solution is a decentralized protocol that randomly selects workers in a verifiable manner without any trusted entities. The second solution is an algorithm that uses a social graph of participants and community detection to select workers that are socially distant in order to reduce the probability of collusion. We present our solutions in the context of a decentralized voting protocol proposed by Schiedermeier et al. [24] that guarantees transparency and verifiability. Enabling collusion-resistance in order to ensure democratic voting is clearly of paramount importance thus the voting protocol provides a suitable use case for our solutions., Comment: 34 pages, 5 figures

Aim/Purpose: This study aimed to examine the relationships among compatibility, relative advantage, complexity, IT Infrastructure, security, top Management Support, financial Support, information Policies, employee engagement, customer pressure, competitive pressure, information integrity, information sharing, attitude toward adopting technology factors, and CRM adoption Background: Customer relationship management (CRM) refers to the use of the process, information, technology, and people for the management of the interactions between the organization and its customers. Therefore, there is a need for SMEs to implement CRM practices in their businesses for competitive advantage. However, in developing nations, the adoption rate of such practices remains low. This low rate may be attributed to the lack of important factors that guide CRM adoption, and as such, the present study attempts to investigate the factors affecting CRM adoption in Palestinian SMEs. This paper used the Diffusion of Innovation Theory (DOI), Resource-Based View (RBV), and Technology, Organization, and Environment Framework (TOE) framework to identify the determinant factors from the technological, organizational, environmental, and information culture perspectives. Methodology: This study uses a quantitative approach to investigate the relationships between the variables. A questionnaire was designed to collect data from 420 SMEs in Palestine. 331respondents 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. Contribution: This study contributes to both theory and practitioners by providing insights into factors that affect CRM adoption in Palestinian SMEs, which did not explore before. Future research suggestions are also provided. Findings: The results of the study prove that the adoption of CRM depends on compatibility (CMP), security (SEC), top management support (TMS), information policies (INP), financial resources (FR), employee engagement (EEN), competitive pressure (COP), customers pressure (CUP), attitude toward adopting technology (ATA), information integrity (INI), and information sharing (INS). Surprisingly, complexity (CMX), IT infrastructure (ITI), and relative advantage (RLA) do not play any role in CRM adoption in Palestine. Recommendations for Practitioners: This study provides practitioners with the important factors for CRM adoption upon its successful implementation in the context of Palestinian SMEs. Recommendation for Researchers: Our findings may be used to conduct further studies about compatibility, security, top management support, information policies, financial resources, employee engagement, competitive pressure, customers pressure, attitude toward adopting technology, information integrity, information sharing factors, and CRM adoption by using different countries, procedure, and context. Impact on Society: The proposed framework provides insights for SMEs which have significant effects for research and practice to help facilitate the adoption of CRM Future Research: The findings may also be compared to other studies conducted in different contexts and provide deeper insights into the influence of the examined contexts on the employees’ intention toward CRM adoption in banking and universities. It would be fruitful to test whether the results hold true in developed and developing countries.

It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection. Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections. Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism.

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.

Bu tez En'âm sûresinde Allah'ın varlığı ve birliği konusunda Beyân ilmi kapsamına giren anlatımları konu edinmektedir. Araştırmanın temel problematiği ve amacı En'âm sûresinin, Allah'ın varlığı ve birliği konularını içeren ayetlerin tahlil edilmesidir. Kelimeler, lafızlar ve cümlelerin oluşumu, ayetlerdeki edebî yöntemler ve anlamlar âyetlere sözlü anlatım bakımından güç verirler. Araştırmacı, konuyu dört bölümde ele almıştır. Birinci Bölüm giriş bölümü olup, üç konuyu ele almaktadır. Bunlar, En'âm suresinde i'câz, En'âm sûresinin çare olduğu sorunlar ve bu sûredeki bazı kelime, harf ve harekelerin değişiminin anlama kazandırdığı anlamın açıklanmasını içerir. İkinci Bölüm meânî ilmini ele almakta olup inşâ, haber ve bu ikisiyle ilgili hususları ayrıntılarıyla incelemektedir. Beyân ilminden bahseden Üçüncü Bölüm dört konudan oluşmaktadır. Bunlar teşbîh, istiâre, mecâz ve kinâye olup alt başlıkları birlikte tahlil edilmiştir. Dördüncü Bölüm bedî ilmi konu edinmektedir ve iki ana başlık altında çalışılmıştır. Bunlar muhassinât-ı ma'neviyye ve muhassinât-ı lafziyye kabilinden olan ifadelerdir. Bu ikisi de alt başlıklarıyla birlikte ele alınmıştır. Son olarak araştırmacının En'âm sûresinde yer alan edebî sanatlarla ilgili ulaştığı başlıca sonuçlara yer verilmiştir. This study focuses on analyzing some verses of Surat Al-An'am which indicate the existence and oneness of the Almighty, to identify the rhetorical methods, its connotations and its rhetorical figures. This study consists of four chapters: The first is an introductory one which contains three subjects: the miracles in Surat Al-An'am, the issues discussed in the Surah, and the significant meaning using different words, letters, diacritics in the surah. The second discusses the semantic which contains two subjects: The realis mood, irrealis mood, and its rhetorical purposes. The third discusses the eloquence which contains four subjects: simile, metaphor, trope, metonymy, and its related methods The fourth discusses the art of metaphors and stylistics which contains two subjects: verbal ornamental, moral ornamental, and its related methods. At the end of thesis, the researcher mentions the most Important results reached. Actually, there are several reasons for this study, such as obtaining the honor of studying the Holy Qur'an words which are rich in rhetorical methods, and Surat al-An'am overflows with many linguistic secrets that researcher can study to benefit from its treasures. I ask God Almighty devotion and success. Praise of Allah, the Lord of the worlds.

International audience

Bangladesh is blessed with a large maritime area which supports a large number of economically important species. Among these species seaweeds are currently commercially grown at small scale. However, information on socio-economical 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 Bangladesh. Data were collected through extensive survey with relevant stakeholders in the south east coastal zone of Bangladesh. The study found that long-line and horizontal net methods are widely used for seaweed farming in Bangladesh. The study also found that these culture methods are economically profitable. Seaweeds are currently sold locally and unfortunately no proper value chain for seaweed is developed yet. Seaweeds are facing problem related to sufficient credits for starting seaweed farming, proper guidelines for farming and processing of harvested seaweed. This study will be a guide for sustainable seaweed industry expansion in Bangladesh.

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.

In this paper, we introduce ProbaSIF, a supplier impersonation fraud detection system that relies on a Bayesian model to perform the classification of a new transaction as legitimate or fraudulent. ProbaSIF is divided in two parts: an intra-company analysis that aims to recreate the vision of a specific client about the legitimacy of the account used in a transaction with one of its supplier, and an inter-company analysis that uses all the accounts used to pay a supplier to model the supplier's payment behavior and take into account transactions issued by other clients. We use a dataset composed of more than 2 million transactions issued by real companies, provided by the SiS-id platform, to fit our Bayesian model, and evaluate the classification results of ProbaSIF using an other set of 108,000 transactions labeled by SiS-id expert system. Our study of a representative client shows that both of the approaches described in ProbaSIF show good precision (0.927 and 0.836) for the 255 transactions tested. Results also shows that ProbaSIF gives results consistent with the expert system provided by SiS-id. Finally, after evaluating ProbaSIF approaches on all the clients available in our dataset, we demonstrated that our classification system was accurate for a wide set of different clients.

This study examines the current conditions of the prevailing ablution spaces in mosques as a viewpoint of prayers' convenience and care practices. Randomly selected thirty mosques from the Dubai, Sharjah, and Ajman City regions were participated in this study. Overall comfort and care features of the ablution spaces were evaluated by two main aspects: wellbeing and general safety factors. The wellbeing aspects include wheelchair accessibility, shoe rack areas, clothing hangers, and equipment storages whilst the general safety ones contain handrails, anti-slip mats, and drainage covers. Collected data clearly show that most of the partaken mosques provide accessible facilities for the wheelchair prayers. Whilst most of the mosques did not provide other wellbeing featured facilities such as shoe racks, clothing hangers, and equipment storages. This study also found that most of the safety features were not provided in the sampled mosques. Although covered drainages are made available by most mosques, handrails and anti-slip mats are hardly provided by the mosques. This study assessed a limited number of ablution spaces around the three major cities of the UAE, but overall findings clearly identify that the present conditions of the existing ablution spaces in mosques appear to be not ideally safe and comfortable environments. Therefore, this study suggests that all the mosques should consider installing such care and comfort facilities in their ablution spaces to enhance safety and wellbeing for the prayers and visitors of the mosque.

The number of mosques has been continuously increased around the world due to the popularity of the Islamic religion. Mosques and praying areas also have been grown rapidly. Unlike other building works, constructing mosques and the praying area is an inspiring defy. Amongst the confronts faced, slip and fall hazards are significant concerning issue to the worshipers. Since noticeable amounts of pollutants are often found at the ablution spaces due to the prayers' body cleaning practices, the floorings are coped with slick situations. In spite of such important safety problem, researches on ablution floors' fall incidents and related prevention strategies are hard to find in the literature. This paper reports on the further detections for the care stance of ablution spaces from arbitrarily invited mosques in the Dubai and Sharjah Emirates. Twenty mosques were randomly invited to measure their safety conditions from a viewpoint of traction behaviours and surface finishes of ablution floors. The present study outcomes recognize that the ablution floorings are not currently protected against falls, especially under the lubricated conditions. Thus, this study suggests two crucial issues to take immediate actions: 1) managers of the mosques should be fully aware of the current safety conditions of their ablution floors and find solutions to prevent fall risks and 2) prayers also should pay extra cares on their ablution floors to avoid any falls during the preparation of their ablution process.

Theories of semantic memory based on neuropsychological findings have posited a distinction between stored semantic representations and the mechanisms used to access and manipulate them (e.g., Lambon Ralph, Jefferies, Patterson,Rogers, 2017; WarringtonCipolotti, 1996). The most recent instantiation of this view, the controlled semantic cognition theory (Lambon Ralph et al., 2017), is supported by findings suggesting that multimodal (i.e., both verbal and nonverbal) semantic deficits may result from qualitatively different impairments: on the one hand, damage to a semantic access mechanism related to executive control, which is observed in semantic aphasia (SA), and on the other, damage to semantic representations, which is observed in semantic dementia (SD) (JefferiesLambon Ralph, 2006). In this study we compared SA and SD patients on several phenomena previously used to support these distinctions. Contrary to the prior results, we found that (1) overall, cross-task consistency was equivalent for the two groups; (2) neither patient group showed consistency driven by item identity across different semantic tasks; (3) correlations among task performance were not obviously driven by the semantic control demands of different tasks; (4) both groups showed executive function deficits; and (5) both groups showed strong effects of distractor interference in a synonym judgment task. Furthermore, we investigated the components of executive ability that could underlie semantic control deficits by correlating performance on updating, shifting, and inhibition tasks with performance on tasks testing semantic abilities. We found that updating was related to semantic processing generally, whereas shifting and inhibition were not. These results also suggest that complex executive function tasks relate to semantic tasks through their shared relationship with language abilities. Overall, evidence from SA and SD patients does not differentiate representations and access mechanisms in the semantic system, as has previously been suggested. Implications for the storage-access distinction are discussed.

Artificial Intelligence (AI) based recommender systems help to make our life easy and comfortable. From simple chatbot to YouTube recommendation, AI is used to recommend news, videos, etc. which provide us more information and saves our time. In big cities, parking seems to be a major problem where commuters need to find a suitable parking space among many parking areas which cause wastage of time and fuel. Our paper proposes a parking recommender system where commuters will be suggested a parking area to a nearby place for helping them to save time, parking cost and ensure high security. To collect data of parking spaces, we propose a Cloud architecture where we use the concept of Edge and Cloud computing to collect and process data smoothly and reduce latency. To deal with bigger amounts of data we use Data Streaming Pipelining to process and analyze those data. We use Amazon Web Services (AWS) to implement our proposed Cloud architecture. For creating the AI based recommender system, we propose the Q-learning algorithm with \({\varepsilon }\)-soft policy to suggest nearby parking areas. Our novel approach will be helpful for both local and global citizens to find an ideal parking area close to their working place, home, etc. Our proposed Cloud architecture is able to reduce latency and make data transferring system faster. Also the Q-learning algorithm can outperform in terms of both certain and uncertain situations.

Background and purpose Ventricular enlargement in elderly raises a challenging differential diagnosis to physicians. While Alzheimer's disease is the most common form of dementia, idiopathic normal pressure hydrocephalus (iNPH) constitutes a potentially reversible syndrome. iNPH has a unique pathophysiology pertaining to cerebrospinal fluid (CSF) dynamics and periventricular white matter. We aimed to determine the effects of iNPH on periventricular white matter bundles and to further characterize its ventricular and sulcal CSF distribution by using diffusion tensor tractography (DTT) and CSF volumetrics on high resolution T1-weighted magnetic resonance imaging data. Methods Deterministic DTT and validated volumetric parcellation were performed on 20 healthy elderly, 13 Alzheimer's disease (AD), and 9 iNPH patients. The superior thalamic radiation, corticospinal tract, and dentatorubrothalamic tract were traced and quantified using DTI studio software. Cloud-based volumetric parcellation was also performed on 138 healthy subjects across the lifespan, 13 AD, and 9 iNPH-patients. Ventricular and sulcal CSF volumes in the three groups were compared. Results Combining increased mean diffusivity of the superior thalamic radiation with ventricular volume resulted in clear separation of iNPH from the AD and age-matched healthy subject groups. Additionally, ventricular to sulcal CSF ratio, utilizing fully automated methods, was significantly greater in the iNPH patients compared to AD and healthy age-matched controls. Conclusions Combined microstructural (DTT) and macrostructural (ventricular volume) changes is a promising radiological approach in studying ventriculomegaly. Automated estimation of the disproportionate ventricular and sulcal CSF ratio in patients presenting with ventriculomegaly may be important as radiologic markers in differentiating iNPH from other causes of ventriculomegaly.

High voter turnout in elections and referendums is very desirable in order to ensure a robust democracy. Secure electronic voting is a vision for the future of elections and referendums. Such a system can counteract factors that hinder 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 must be implemented in a reproducible way and the ballots of individual voters must remain concealed. In this paper, we propose and evaluate a referendum protocol that ensures transparency, confidentiality, and integrity, in trustless networks. The protocol is built by combining Secure Multi-Party Computation (SMPC) and Distributed Ledger or Blockchain technology. The persistence and immutability of the protocol communication allows verifiability of the referendum outcome on the client side. Voters therefore do not need to trust in third parties. We provide a formal description and conduct a thorough security evaluation of our proposal., Comment: 14 pages, 3 figures

Supplier Impersonation Fraud (SIF) is a rising issue for Business to Business companies, as the use of remote and quick digital transactions has made the task of identifying fraudsters more difficult. In this paper, we propose data-driven fraud detection system whose goal is to provide an accurate estimation of transactions’ legitimacy by using the knowledge contained in the network of transactions created by the interaction of a company with its supplier. We consider the real dataset collected by SIS-ID for this work.

Purpose: Allogeneic hematopoietic stem cell transplantation (AHCT) outcomes depend on disease and patient characteristics. We previously developed a novel prognostic model, hematopoietic cell transplant composite-risk (HCT-CR) by incorporating the refined disease risk index (DRI-R) and hematopoietic cell transplant–comorbidity/age index (HCT-CI/Age) to predict post-transplant survival in patients with acute myeloid leukemia and myelodysplastic syndrome. Here we aimed to validate and prove the generalizability of the HCT-CR model in an independent cohort of patients with hematologic malignancies receiving AHCT. Experimental Design: Data of consecutive adult patients receiving AHCT for various hematologic malignancies were analyzed. Patients were stratified into four HCT-CR risk groups. The discrimination, calibration performance, and clinical net benefit of the HCT-CR model were tested. Results: The HCT-CR model stratified patients into four risk groups with significantly different overall survival (OS). Three-year OS was 67.4%, 50%, 37.5%, and 29.9% for low, intermediate, high, and very high-risk group, respectively (P < 0.001). The HCT-CR model had better discrimination on OS prediction when compared with the DRI-R and HCT-CI/Age (C-index was 0.69 vs. 0.59 and 0.56, respectively, P < 0.001). The decision curve analysis showed that HCT-CR model provided better clinical utility for patient selection for post-transplant clinical trial than the “treat all” or “treat none” strategy and the use of the DRI-R and HCT-CI/Age model separately. Conclusions: The HCT-CR can be effectively used to predict post-transplant survival in patients with various hematologic malignancies. This composite model can identify patients who will benefit the most from transplantation and helps physicians in making decisions regarding post-transplant therapy to improve outcomes.

Bronchoscopy programs implementing the experiential learning model address different learning styles. Problem-based learning improves knowledge retention, critical decision making, and communication. These modalities are preferred by learners and contribute to their engagement, in turn leading to durable learning. Follow-up after live events is warranted through spaced education strategies. The objectives of this article are to (1) summarize and illustrate the implementation of experiential learning theory for bronchoscopy courses, (2) discuss the flipped classroom model and problem-based learning, (3) illustrate bronchoscopy checklists implementation in simulation, and (4) discuss the importance of feedback and spaced learning for bronchoscopy education programs.

Introduction: Rheumatoid arthritis is considered one of the most common, and particularly attacks the joint causing significant individual and community burden, and present with articular as well as extra articular manifestation. Treatment modalities of rheumatoid arthritis have dramatically improved in recent years, significantly decreasing long-term auricular and extra-auricular complications. Aim of the work: this review was aimedto study the pathophysiology, clinical picture, and management of rheumatoid arthritis, with focus on the newer modalities. Methodology: We conducted this review using a comprehensive search of MEDLINE, PubMed, and EMBASE, January 1985, through February 2017. The following search terms were used: rheumatoid arthritis, chronic inflammatory disorders, genetic of rheumatoid arthritis, management of rheumatoid arthritis, DMARD, biological agents Conclusion: The newer modality of treatment must include disease-modifying antirheumatic drug (DMARDs) which must be started as early as possible. Combining DMARDs with corticosteroids will result in significantly better outcomes than monotherapy with any DMARD and decrease long term morbidity associated with this condition.

Highlights • Benign strictures of the biliary system are challenging, uncommon conditions requiring multidisciplinary team treatment. • The complex nature of the stricture required a combined interventional radiologic and surgical approach. • Injury to the intrahepatic biliary ductal confluence is rarely fatal, but, associated injuries cause severe morbidity. • We describe an innovative multidisciplinary approach to the repair of this rare injury., Introduction Benign strictures of the biliary system are challenging and uncommon conditions requiring a multidisciplinary team for appropriate management. Presentation of case The patient is a 32-year-old male that developed a hilar stricture as sequelae of a gunshot wound. Due to the complex nature of the stricture and scarring at the porta hepatis a combined interventional radiologic and surgical approach was carried out to approach the hilum of the right and left hepatic ducts. The location of this stricture was found by ultrasound guidance intraoperatively using a balloon tipped catheter placed under fluoroscopy in the interventional radiology suite prior to surgery. This allowed the surgeons to select the line of parenchymal transection for best visualization of the stricture. A left hepatectomy was performed, the internal stent located and the right hepatic duct opened tangentially to allow a side-to-side Roux-en-Y hepaticojejunostomy (a Puestow-like anastomosis). Discussion Injury to the intrahepatic biliary ductal confluence is rarely fatal, however, the associated injuries lead to severe morbidity as seen in this example. Management of these injuries poses a considerable challenge to the surgeon and treating physicians. Conclusion Here we describe an innovative multi-disciplinary approach to the repair of this rare injury.

Seaweeds are marine autotrophic macroalgae found in the coastal waters, and have both ecological and economic values. Present study aimed to understand the drivers of commercially important seaweed species distribution and predict their suitable habitat for cultivation in the coastal area of Bangladesh. We used Generalized Additive Model to predict the potential habitats of seaweeds utilizing data on seaweed occurrence (presence and absence data), environmental conditions and bathymetry. Required data were compiled from in-situ measurements, satellite observations and model simulations. Our model explained 78% variability in seaweed habitat distribution. We found that total suspended matter was the main predictor of seaweed habitat distribution followed by salinity, nitrate concentrations, depth, zonal and meridional components of current and sea surface temperature. Our model predicted that about 11,200 km2 areas had 20–100% occurrence probability for seaweed. We also found that about 4100km2 area had higher probability of seaweed occurrence (50–100%). Our model predictions had a good agreement with in-situ observations (Area under curve = 0.83, R2 = 0.81). Since Bangladesh is focusing on the expansion of ocean based economic activities, our study will serve as a tool to start commercial mariculture of seaweed by providing information on site suitability for farm establishment.

Background: Thalassemia major has become a public health problem worldwide, mainly in developing and poor countries, while the role of educating the family and community has not been considered enough in patients’ care. Purpose: This study was done to examine the impact of partnership care model on mental health of patients with beta-thalassemia major. Materials and Methods: This experimental study, with pretest and posttest design, was performed on patients with beta-thalassemia major in Jeddah city. 40 patients with beta-thalassemia major were assigned randomly into two groups of intervention (20 patients) and control (n=20) groups. Mental health of the participants was measured using the standard questionnaire before and after intervention in both groups. The intervention was applied to the intervention group for 6 months, based on the partnership care model. Results: There were significant differences between the scores of mental health and its subscales between the two groups after the intervention (????< 0.05). Conclusions: The findings of the study revealed the efficacy and usefulness of partnership care model on mental health of patients with beta-thalassemia major; thus, implementation of this model is suggested for the improvement of mental health of patients with beta-thalassemia major.

Hypertension is the leading cause of cardiovascular disease in the United States and worldwide. It also provides a useful model for team‐based chronic disease management. This article describes the M.A.P. checklists: a framework to help practice teams summarize best practices for providing coordinated, evidence‐based care to patients with hypertension. Consisting of three domains—Measure Accurately; Act Rapidly; and Partner With Patients, Families, and Communities—the checklists were developed by a team of clinicians, hypertension experts, and quality improvement experts through a multistep process that combined literature review, iterative feedback from a panel of internationally recognized experts, and pilot testing among a convenience sample of primary care practices in two states. In contrast to many guidelines, the M.A.P. checklists specifically target practice teams, instead of individual clinicians, and are designed to be brief, cognitively easy to consume and recall, and accessible to healthcare workers from a range of professional backgrounds.

Message routing is one of the major challenges in Mobile Delay Tolerant Networks (MDTNs) due to frequent and long-term network partitions. A number of routing protocols for MDTNs belong to the category of prediction-based routing protocols, which utilize the social encounter probability of nodes to guide message forwarding. However, these prediction-based routing protocols compromise the privacy of the nodes by revealing their mobility patterns. In this paper, we propose the Privacy Preserving Probabilistic Prediction-based Routing (4PR) protocol that forwards messages by comparing aggregated information about communities instead of individual nodes. Specifically, it compares the probability that at least one node in a community will encounter the destination node. We present theoretical security analyses as well as practical performance evaluations. Our simulations on a well established community-based mobility model demonstrate that our routing protocol has comparable performance to existing prediction-based protocols. Additionally, the community information is computed efficiently and independently of the routing protocol.

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&rsquo, 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.

Molecular data and minimal residual disease (MRD) have been shown to influence outcomes in acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (AHCT). Here we developed and validated a novel AML-specific disease risk group (AML-DRG) and revised our previously developed hematopoietic cell transplant-composite risk (HCT-CR) model by incorporating molecular data and MRD status to predict outcomes of patients with AML. The study included 1414 consecutively treated adult AML patients who received a first AHCT. Patients were randomly assigned into training (n = 944) and validation (n = 470) sets. To develop the AML-DRG model, the coefficient of all significant AML-related variables in multivariable Cox regression analysis in a training dataset was converted into scores, whereas the AML-HCT-CR was the sum of disease-related factors assessed by the AML-DRG model with the addition of weighted scores from patient-related factors. The AML-DRG was developed by assigning the following scores: 1 point to secondary AML, 1 point to the European LeukaemiaNet adverse genetic risk, 2 points to complete remission with MRD positive/unknown, and 4 points to active disease. These scores were used to generate 3 risk groups of the AML-DRG with significantly different overall survivals. By adding the score for significant patient-related factors (HCT-specific comorbidity index/age), we created 4 risk groups of AML-HCT-CR with distinct survival outcomes. Both the AML-DRG and AML-HCT-CR provided significantly better discriminative capacity compared with the disease risk index, European LeukaemiaNet genetic risk model, and cytogenetic risk model. Prognostic models incorporating molecular data and MRD status allow better stratification and improved survival estimates of AML patients post-transplant.

The gain/amplification CKS1B gene at chromosome region 1q21 (1q+) is one of the most common genetic aberrations in multiple myeloma (MM). Amplification of CKS1B is frequently associated with the deletion of the CDKN2C gene at chromosome region 1p32 (1p–), which is also associated with inferior outcomes. In this retrospective study, we evaluated the outcomes of patients with 1q+ and/or 1p– after high-dose therapy and autologous hematopoietic cell transplantation (auto-HCT). From January 2006 to December 2015, 1491 newly diagnosed patients with MM underwent upfront high-dose therapy and auto-HCT at our institution. Of those, 899 had the fluorescent in situ hybridization (FISH) data available. FISH was performed at diagnosis and before the start of induction in 686 (76%) patients and after the initiation of induction therapy in 213 (24%) patients. We identified 100 patients with 1q+ and/or 1p– by FISH from the cohort of 899 patients. A control group (n = 287) with diploid cytogenetics and normal FISH panel was selected from the same cohort. From the above 2 cohorts, using a propensity score matched analysis, we identified matched controls for 85 of the 100 patients with 1q+/1p–. Patients were matched for age at auto-HCT, sex, International Staging System stage, induction regimen, creatinine level, disease status at auto-HCT, conditioning regimen, and maintenance therapy. Sixty-seven (79%), 4 (5%), and 14 (16%) patients had 1q+, 1p–, or both 1q+ and 1p–, respectively. There was no significant difference in induction therapy, preparative regimen, or maintenance therapy between the 1q+/1p– and the control group. The median follow-up time for all patients was 29.2 months (range, 0.29 to 84.96). The cumulative incidence of 100-day nonrelapse mortality was 1.2% and 0% for the 1q+/1p– and the control group, respectively. Forty-two patients (50%) in the 1q+/1p– group achieved complete response compared with 40 patients (47%) in the control group. The estimated 3-year progression-free survival (PFS) and overall survival (OS) rates were 41% and 79% for the 1q+/1p– group and 56% and 86% for the control group. Patients in the 1q+/1p– group were at significantly increased risk of progression or death compared to the control group (hazard ratio [HR], 2.21; confidence interval [CI], 1.18 to 4.16; P = .014). No significant association between OS in the 2 groups was observed. The outcome of the 1q+/1p– alone (with no additional high-risk cytogenetics) and the propensity score matched control groups was also compared. Median PFS for the 1q+/1p– alone subgroup was 26.6 months, compared with 38.8 months for the control group (HR, 1.9; CI, 0.9 to 4.08; P = .09). The median OS had not been reached for the 1q+/1p– alone subgroup and was 81.1 months for the control group (HR, 1.25; CI, 0.3 to 4.6; P= .73). 1q+/1p– abnormalities with amplification of CKS1B and deletion ofCDKN2Cgenes were associated with shorter PFS compared with a propensity score matched group of patients with diploid cytogenetics and normal a FISH panel. The outcomes of 1q+/1p– patients with MM have improved with the use of more effective induction, conditioning, and maintenance therapy compared with historical controls, but we still need more effective therapeutic approaches to fully overcome the negative impact of 1q+/1p–.

Background: Polycythemia vera (PV), alongside primary myelofibrosis (MF) and essential thrombocythemia (ET), is a classic Philadelphia chromosome-negative myeloproliferative neoplasm (MPN) characterized primarily by an expanded red platelet mass. Patients with PV have excessive proliferation of erythroid as well as myeloid and megakaryocytic components in the bone marrow, which result in high red blood cell, white blood cell (WBC), and platelet counts. Clinically, patients with PV may encounter manifestations, for example, pruritus, fatigue, night sweats, bone pain, thrombosis, and bleeding Methodology: We conducted this review using a comprehensive search of MEDLINE, PubMed, and EMBASE, January 1985, through February 2017. The following search terms were used: polycythemia Vera, presentation, complication, diagnosis, and management of Polycythemia Vera, JAK2 mutation, targeted therapy Aim: In this review, we aim to study the clinical presentation, complication, diagnosis, and advances in management of polycythemia Vera. Conclusion: The discovery of JAK2 mutations as the underlying molecular basis for PV has enormously expanded our comprehension of the pathogenesis of PV and has allowed for the development of targeted treatments. As of now, studies are evaluating the clinical advantages of JAK2 inhibitors and are demonstrating promising outcomes for the treatment of this debilitating disease. Further studies will mostly focus around which patients with PV will profit most from the utilization of targeted treatments and how these new treatments compare with present treatment standards. The best treatment for every patient will be one that is well endured while improving symptoms and quality of life, and in such manner, targeted treatments will be valuable tools. Keywords: Polycythemia Vera, JAK2 mutation, hematologic pathology