Coxsackie-adenovirus receptor expression is enhanced in pancreas from patients with type 1 diabetes

Objectives: One of the theories connecting enterovirus (EV) infection of human islets with type 1 diabetes (T1D) is the development of a fertile field in the islets. This implies induction of appropriate proteins for the viral replication such as the coxsackie–adenovirus receptor (CAR). The aim of this study was to investigate to what extent CAR is expressed in human islets of Langerhans, and what conditions that would change the expression. Design: Immunohistochemistry for CAR was performed on paraffin-embedded pancreatic tissue from patients with T1D (n=9 recent onset T1D, n=4 long-standing T1D), islet autoantibody-positive individuals (n=14) and non-diabetic controls (n=24) individuals. The expression of CAR was also examined by reverse transcription PCR on microdissected islets (n=5), exocrine tissue (n=5) and on explanted islets infected with EV or exposed to chemokines produced by EV-infected islet cells. Results: An increased frequency of patients with T1D and autoantibody-positive individuals expressed CAR in the pancreas (p<0.039). CAR staining was detected more frequently in pancreatic islets from patients with T1D and autoantibody-positive subjects (15/27) compared with (6/24) non-diabetic controls (p<0.033). Also in explanted islets cultured in UV-treated culture medium from coxsackievirus B (CBV)-1-infected islets, the expression of the CAR gene was increased compared with controls. Laser microdissection of pancreatic tissue revealed that CAR expression was 10-fold higher in endocrine compared with exocrine cells of the pancreas. CAR was also expressed in explanted islets and the expression level decreased with time in culture. CBV-1 infection of explanted islets clearly decreased the expression of CAR (p<0.05). In contrast, infection with echovirus 6 did not affect the expression of CAR. Conclusions: CAR is expressed in pancreatic islets of patients with T1D and the expression level of CAR is increased in explanted islets exposed to proinflammatory cytokines/chemokines produced by infected islets. T1D is associated with increased levels of certain chemokines/cytokines in the islets and this might be the mechanism behind the increased expression of CAR in TID islets

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Innovative Blockchain-Based Applications - State of the Art and Future Directions

Recently, blockchain technology has increasingly being used to provide a secure environment that is immutable, consensus-based and transparent in the finance technology world. However, significant efforts have been made to use blockchain in other fields where trust and transparency are required. The distributed power and embedded security of blockchain leverage the operational efficiency of other domains to be immutable, transparent, and trustworthy. The trust of the published literature in blockchain technology is centered on crypto-currencies. Therefore, this paper addresses this gap and presents to the user several applications in many fields, including education, health, carbon credits, robotics, energy, pharmaceutical supply chains, identity management, and crypto-currency wallets. This paper overviews the knowledge on blockchain technology, discusses the innovation of blockchain technology based on the number of applications which have been introduced, describes the challenges associated with blockchain technology, and makes suggestions for future work

High-fat diet-induced resistance to helminth infection via alternative induction of type 2 immunity

Gastrointestinal nematode infections cause morbidity and socioeconomic loss in the most deprived communities. The shift in the context of obesity has led to spatial overlap with endemic gastrointestinal nematode regions resulting in the emergence of a novel comorbidity. Despite this, the impact of a high-fat diet (HFD) on immune-regulated protection against gastrointestinal infections remains largely unknown. We employed the murine model of nematode infection, Trichuris muris, to investigate the effect of an HFD on the immune response against chronic infection. Surprisingly, diet-induced obesity drove parasite expulsion in both single and repeated trickle low doses of T. muris eggs. Mechanistically, an HFD increased the expression of the ST2 receptor on CD4+ T cells, priming an enhanced type 2 helper T (Th2) cell cytokine production following interleukin (IL)-33 stimulation ex vivo. Despite IL-33−/− mice demonstrating that IL-33 is not critical for host protective immunity to T. muris under a conventional diet, HFD-fed T-cell deplete mice adoptively transferred with ST2−/− CD4 T cells were unable to expel a T. muris infection unlike those transferred with ST2-sufficient cells. Collectively, this study demonstrates that an HFD primes CD4+ T cells to utilize the IL-33-ST2 axis in a novel induction of type 2 immunity, providing insights into the emerging comorbidities of obesity and nematode infection

Spatio-temporal data fusion framework based on large language model for enhanced prediction of electric vehicle charging demand in smart grid management

Accurate prediction of electric vehicle (EV) charging demand is pivotal for effective smart grid management and renewable energy integration. However, predicting spatio-temporal EV charging patterns remains challenging due to complex data fusion requirements arising from heterogeneous temporal, spatial, and contextual features, as well as difficulties in effectively integrating multiple modeling approaches. This paper introduces EV-STLLM, a novel spatio-temporal data fusion framework based on Large Language Model explicitly designed for accurate short-term EV charging demand forecasting through innovative integration of data-level and model-level fusion techniques. At the data level, a multi-source embedding module is developed to seamlessly fuse temporal features (e.g., time slots, weekdays), spatial heterogeneity (e.g., geographical location), and contextual charging behaviors into a unified representation via embedding convolutional network. At the model level, a large language model (LLM) is employed to capture global spatiotemporal dependencies, enhanced with Low-Rank Adaptation (LoRA) for parameter-efficient fine-tuning, substantially reducing computational costs while maintaining prediction robustness. Using a comprehensive real-world dataset comprising over 830,000 EV charging records across 16 districts and 331 subdistricts in Beijing, we validate EV-STLLM across multiple forecasting scenarios (district and subdistrict levels, one-step and two-step ahead predictions). Extensive comparative evaluations demonstrate that EV-STLLM consistently outperforms classical, graph-based, and deep learning baselines. Specifically, in one-step ahead district-level forecasting, EV-STLLM achieves up to a 15.41% reduction in MAE and a 53.51% reduction in MAPE compared to the leading baseline, underscoring its potential to significantly enhance data-driven smart grid operations

BPTF inhibits NK cell activity and the abundance of natural cytotoxicity receptor co-ligands

Using syngeneic BALB/c mouse breast cancer models, we show that the chromatin remodeling subunit bromodomain PHD finger transcription factor (BPTF) suppresses natural killer (NK) cell antitumor activity in the tumor microenvironment (TME). In culture, BPTF suppresses direct natural cytotoxicity receptor (NCR) mediated NK cell cytolytic activity to mouse and human cancer cell lines, demonstrating conserved functions. Blocking mouse NCR1 in vivo rescues BPTF KD tumor weights, demonstrating its importance for the control of tumor growth. We discovered that BPTF occupies heparanase (Hpse) regulatory elements, activating its expression. Increased heparanase activity results in reduced cell surface abundance of the NCR co-ligands: heparan sulfate proteoglycans (HSPGs). Using gain and loss of function approaches we show that elevated heparanase levels suppress NK cell cytolytic activity to tumor cells in culture. These results suggest that BPTF activates heparanase expression, which in turn reduces cell surface HSPGs and NCR co-ligands, inhibiting NK cell activity. Furthermore, gene expression data from human breast cancer tumors shows that elevated BPTF expression correlates with reduced antitumor immune cell signatures, supporting conserved roles for BPTF in suppressing antitumor immunity. Conditional BPTF depletion in established mouse breast tumors enhances antitumor immunity, suggesting that inhibiting BPTF could provide a novel immunotherapy

Epidemiology and Clinical Impact of Vancomycin-Resistant Enterococcus at King Abdulaziz University Hospital (2015&ndash;2022): Prevalence, Risk Factors, and Mortality

Jawahir A Mokhtar,1– 3 Dalya Attallah,2 Mohammed W Al-Rabia,1 Mona Abdulrahman Alqarni,1 Khalil K Alkuwaity,3,4 Yousef Almoghrabi,5,6 Hussam Daghistani,5,6 Mazen A Ismail,7 Asim T Sharif,7 Bayan Redwan,7 Alyaa M Ajabnoor,8 Ohood S Alharbi,9 Ibrahim Mohammed Abu,10 Wafaa Alhazmi,4 Mohammed Mufrrih,4,11 Ahmad M Sait,4,6 Abdelbagi Alfadil,1,12 Yassir Daghistani,13 Hattan Jamal Momin,14 Karem Ibrahem1,2 1Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia; 2Department of Clinical Microbiology Laboratory, King Abdulaziz University Hospital, Jeddah, 21589, Saudi Arabia; 3Vaccines and Immunotherapy Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 4Department of Medical Laboratory Sciences, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 5Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 6Regenerative Medicine Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 7Department of Medical Education, Faculty of Medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 8Department of pharmacy practice, Faculty of pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; 9Department of Microbiology and Parasitology, Faculty of Medicine, Umm Al-Qura University, Makkah, Saudi Arabia; 10Department of Community Medicine, Faculty of medicine, King Abdulaziz University, Jeddah, 21589, Saudi Arabia; 11Special Infectious Agents Unit BSL-3, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; 12Centre of Research Excellence for Drug Research and Pharmaceutical Industries, King Abdulaziz University, Jeddah, Saudi Arabia; 13Department of Medicine, Faculty of Medicine, University of Jeddah, Jeddah, Saudi Arabia; 14Medical Service Center, King Abdulaziz University, Jeddah, 21589, Saudi ArabiaCorrespondence: Karem Ibrahem, Department of Clinical Microbiology and Immunology, Faculty of Medicine, King Abdulaziz University, P.O. Box 80205, Jeddah, 21589, Saudi Arabia, Tel +966562525685, Email [email protected]: Enterococcus faecalis and Enterococcus faecium are part of the human microbiota but pose significant risks in clinical settings due to increasing antimicrobial resistance. Vancomycin-resistant enterococci (VRE) are a growing concern, linked to high morbidity and mortality in hospitalized patients.Aim: This study is the first comprehensive investigation of VRE prevalence and associated risk factors at King Abdulaziz University Hospital (KAUH) from 2015 to 2022.Methods: Clinical samples were collected, and VRE isolates were identified using VRE Card GeneXpert, BioFire PCR, and the VITEK 2 system. Descriptive statistical analysis with Stata version 17 summarized patient characteristics, including demographics, comorbidities, hospital exposure, and laboratory findings. Categorical variables were reported as frequencies/percentages, while continuous variables were expressed as mean ± SD or median [IQR].Results: Among 254 adult patients with VRE infections, the median age was 61 years. The most common comorbidities were diabetes, hypertension, and kidney disease. VRE infections peaked in 2021, with urine cultures being the most frequent source. Most patients had prior antibiotic exposure, particularly to vancomycin and carbapenems. Enterococcus faecium was the predominant species, with the VanA phenotype being most common. Alarmingly, 61.8% of VRE-infected patients died during the study period.Conclusion: These findings underscore the critical need for enhanced infection control measures and antimicrobial stewardship to combat VRE and improve patient outcomes.Keywords: vancomycin-resistant enterococci, AMR, mortality, risk factors, hospital infection

Global Perspectives on Task Shifting and Task Sharing in Neurosurgery.

BACKGROUND: Neurosurgical task shifting and task sharing (TS/S), delegating clinical care to non-neurosurgeons, is ongoing in many hospital systems in which neurosurgeons are scarce. Although TS/S can increase access to treatment, it remains highly controversial. This survey investigated perceptions of neurosurgical TS/S to elucidate whether it is a permissible temporary solution to the global workforce deficit. METHODS: The survey was distributed to a convenience sample of individuals providing neurosurgical care. A digital survey link was distributed through electronic mailing lists of continental neurosurgical societies and various collectives, conference announcements, and social media platforms (July 2018-January 2019). Data were analyzed by descriptive statistics and univariate regression of Likert Scale scores. RESULTS: Survey respondents represented 105 of 194 World Health Organization member countries (54.1%; 391 respondents, 162 from high-income countries and 229 from low- and middle-income countries [LMICs]). The most agreed on statement was that task sharing is preferred to task shifting. There was broad consensus that both task shifting and task sharing should require competency-based evaluation, standardized training endorsed by governing organizations, and maintenance of certification. When perspectives were stratified by income class, LMICs were significantly more likely to agree that task shifting is professionally disruptive to traditional training, task sharing should be a priority where human resources are scarce, and to call for additional TS/S regulation, such as certification and formal consultation with a neurosurgeon (in person or electronic/telemedicine). CONCLUSIONS: Both LMIC and high-income countries agreed that task sharing should be prioritized over task shifting and that additional recommendations and regulations could enhance care. These data invite future discussions on policy and training programs

Global economic burden of unmet surgical need for appendicitis

Background: There is a substantial gap in provision of adequate surgical care in many low-and middle-income countries. This study aimed to identify the economic burden of unmet surgical need for the common condition of appendicitis. Methods: Data on the incidence of appendicitis from 170 countries and two different approaches were used to estimate numbers of patients who do not receive surgery: as a fixed proportion of the total unmet surgical need per country (approach 1); and based on country income status (approach 2). Indirect costs with current levels of access and local quality, and those if quality were at the standards of high-income countries, were estimated. A human capital approach was applied, focusing on the economic burden resulting from premature death and absenteeism. Results: Excess mortality was 4185 per 100 000 cases of appendicitis using approach 1 and 3448 per 100 000 using approach 2. The economic burden of continuing current levels of access and local quality was US $92 492 million using approach 1 and$73 141 million using approach 2. The economic burden of not providing surgical care to the standards of high-income countries was $95 004 million using approach 1 and$75 666 million using approach 2. The largest share of these costs resulted from premature death (97.7 per cent) and lack of access (97.0 per cent) in contrast to lack of quality. Conclusion: For a comparatively non-complex emergency condition such as appendicitis, increasing access to care should be prioritized. Although improving quality of care should not be neglected, increasing provision of care at current standards could reduce societal costs substantially

Burnout among surgeons before and during the SARS-CoV-2 pandemic: an international survey

Background: SARS-CoV-2 pandemic has had many significant impacts within the surgical realm, and surgeons have been obligated to reconsider almost every aspect of daily clinical practice. Methods: This is a cross-sectional study reported in compliance with the CHERRIES guidelines and conducted through an online platform from June 14th to July 15th, 2020. The primary outcome was the burden of burnout during the pandemic indicated by the validated Shirom-Melamed Burnout Measure. Results: Nine hundred fifty-four surgeons completed the survey. The median length of practice was 10&nbsp;years; 78.2% included were male with a median age of 37&nbsp;years old, 39.5% were consultants, 68.9% were general surgeons, and 55.7% were affiliated with an academic institution. Overall, there was a significant increase in the mean burnout score during the pandemic; longer years of practice and older age were significantly associated with less burnout. There were significant reductions in the median number of outpatient visits, operated cases, on-call hours, emergency visits, and research work, so, 48.2% of respondents felt that the training resources were insufficient. The majority (81.3%) of respondents reported that their hospitals were included in the management of COVID-19, 66.5% felt their roles had been minimized; 41% were asked to assist in non-surgical medical practices, and 37.6% of respondents were included in COVID-19 management. Conclusions: There was a significant burnout among trainees. Almost all aspects of clinical and research activities were affected with a significant reduction in the volume of research, outpatient clinic visits, surgical procedures, on-call hours, and emergency cases hindering the training. Trial registration: The study was registered on clicaltrials.gov "NCT04433286" on 16/06/2020