Major Cause Research Articles

Rapid detection of West Nile and Dengue viruses from mosquito saliva by loop-mediated isothermal amplification and displaced probes.

Arthropod-borne viruses are major causes of human and animal disease, especially in endemic low- and middle-income countries. Mosquito-borne pathogen surveillance is essential for risk assessment and vector control responses. Sentinel chicken serosurveillance (antibody testing) and mosquito pool screening (by RT-qPCR or virus isolation) are currently used to monitor arbovirus transmission, however substantial time lags of seroconversion and/or laborious mosquito identification and RNA extraction steps sacrifice their early warning value. As a consequence, timely vector control responses are compromised. Here, we report on development of a rapid arbovirus detection system whereby adding sucrose to reagents of loop-mediated isothermal amplification with displaced probes (DP-LAMP) elicits infectious mosquitoes to feed directly upon the reagent mix and expectorate viruses into the reagents during feeding. We demonstrate that RNA from pathogenic arboviruses (West Nile and Dengue viruses) transmitted in the infectious mosquito saliva was detectable rapidly (within 45 minutes) without RNA extraction. Sucrose stabilized viral RNA at field temperatures for at least 48 hours, important for transition of this system to practical use. After thermal treatment, the DP-LAMP could be reliably visualized by a simple optical image sensor to distinguish between positive and negative samples based on fluorescence intensity. Field application of this technology could fundamentally change conventional arbovirus surveillance methods by eliminating laborious RNA extraction steps, permitting arbovirus monitoring from additional sites, and substantially reducing time needed to detect circulating pathogens.

Role of AMP deaminase in diabetic cardiomyopathy.

Diabetes mellitus is one of the major causes of ischemic and nonischemic heart failure. While hypertension and coronary artery disease are frequent comorbidities in patients with diabetes, cardiac contractile dysfunction and remodeling occur in diabetic patients even without comorbidities, which is referred to as diabetic cardiomyopathy. Investigations in recent decades have demonstrated that the production of reactive oxygen species (ROS), impaired handling of intracellular Ca2+, and alterations in energy metabolism are involved in the development of diabetic cardiomyopathy. AMP deaminase (AMPD) directly regulates adenine nucleotide metabolism and energy transfer by adenylate kinase and indirectly modulates xanthine oxidoreductase-mediated pathways and AMP-activated protein kinase-mediated signaling. Upregulation of AMPD in diabetic hearts was first reported more than 30years ago, and subsequent studies showed similar upregulation in the liver and skeletal muscle. Evidence for the roles of AMPD in diabetes-induced fatty liver, sarcopenia, and heart failure has been accumulating. A series of our recent studies showed that AMPD localizes in the mitochondria-associated endoplasmic reticulum membrane as well as the sarcoplasmic reticulum and cytosol and participates in the regulation of mitochondrial Ca2+ and suggested that upregulated AMPD contributes to contractile dysfunction in diabetic cardiomyopathy via increased generation of ROS, adenine nucleotide depletion, and impaired mitochondrial respiration. The detrimental effects of AMPD were manifested at times of increased cardiac workload by pressure loading. In this review, we briefly summarize the expression and functions of AMPD in the heart and discuss the roles of AMPD in diabetic cardiomyopathy, mainly focusing on contractile dysfunction caused by this disorder.

RBM3 Promotes Anti-inflammatory Responses in Microglia and Serves as a Neuroprotective Target of Ischemic Stroke.

Ischemic stroke is a major cause of death and disability in adults. Hypothermic treatment is successful in treating neonatal cerebral ischemia, but its application is restricted in adult patients due to complex management strategies and severe adverse effects. Two homologous RNA-binding proteins, RBM3 and CIRP, are the only known cold-inducible proteins in vertebrates, and their expression levels are robustly elevated by mild to moderate hypothermia. In previous studies, we and others have demonstrated that both RBM3 and CIRP mediate the neuroprotective and neurogenic effects of hypothermia in cell and animal models. However, CIRP can also be detrimental to neurons by triggering neuroinflammatory responses, complicating its post-stroke functions. In this study, we compared the properties of the two cold-inducible RNA-binding proteins after ischemic stroke. Our results indicated that RBM3 expression was stimulated in the ischemic brain of stroke patients, while CIRP expression was not. In an experimental model, RBM3 can ameliorate ischemic-like insult by promoting neuronal survival and eliciting anti-inflammatory responses in activated microglia, while the impact of CIRP was intriguing. Collectively, our data supported the notion that RBM3 may be a more promising therapeutic target than CIRP for treating ischemic stroke. We further demonstrated that zr17-2, a small molecule initially identified to target CIRP, can specifically target RBM3 but not CIRP in microglia. zr17-2 demonstrated anti-inflammatory and neuroprotective effects after ischemic stroke both in vitro and in vivo, suggesting its potential therapeutic value.

Carbon Dot Based Carbon Nanoparticles as Potent Antimicrobial, Antiviral, and Anticancer Agents.

Antimicrobial and anticancer drugs are widely used due to increasing widespread infectious diseases caused by microorganisms such as bacterial, fungal, viral agents, or cancer cells, which are one of the major causes of mortality globally. Nevertheless, several microorganisms developed resistance to antibiotics as a result of genetic changes that have occurred over an extended period. Carbon-based materials, particularly carbon dots (C-dots), are potential candidates for antibacterial and anticancer nanomaterials due to their low toxicity, ease of synthesis and functionalization, high dispersibility in aqueous conditions, and promising biocompatibility. In this Review, the content is divided into four sections. The first section concentrates on C-dot structures, surface functionalization, and morphology. Following that, we summarize C-dot classifications and preparation methods such as arc discharge, laser ablation, electrochemical oxidation, and so on. The antimicrobial applications of C-dots as antibacterial, antifungal, and antiviral agents both in vivo and in vitro are discussed. Finally, we thoroughly examined the anticancer activity displayed by C-dots.

Le myofibroblastome palissadique intraganglionnaire : une cause rare d’adénopathie inguinale

IntroductionLymphadenopathies are a major cause of consultation in internal medicine, with various causes of diagnosis. Unexplained persistent lymphadenopathy must be biopsied to rule out malignant tumor. Case reportWe report the case of a 53-year-old man, with inguinal lymphadenopathy evolving for more than one year. The patient had no associated symptoms and his blood tests were unremarkable. Due to the progression of the adenopathy and its hypermetabolism on PET-CT, an excisional biopsy was performed. Histological analysis revealed an intranodal proliferation of spindle cells with a palisading pattern. β-catenine and smooth muscle actin labelling were positive, leading to the diagnosis of intranodal palisaded myofibroblastoma, a benign tumour. ConclusionIntranodal palisaded myofibroblastoma is a rare benign cause of adenopathy, with often inguinal lymph node localization and slow growth and without risk of recurrence after surgical removal.

Exploring the effects of competition and predation on the success of biological invasion through mathematical modeling

Biological invasions are a major cause of species extinction and biodiversity loss. Exotic predators are the type of introduced species that have the greatest negative impact, causing the extinction of hundreds of native species. Despite this, they continue to be intentionally introduced by humans. Understanding the causes that determine the success of these invasions is a challenge within the field of invasion biology. Mathematical models play a crucial role in understanding and predicting the behavior of exotic species in different ecosystems. This study examines the effect of predation and competition on the invasion success of an exotic generalist predator in a native predator-prey system. Considering that the exotic predator both consumes the native prey and competes with the native predator, it is necessary to study the interplay between predation and competition, as one of these interspecific interactions may either counteract or contribute to the impact of the other on the success of a biological invasion. Through a mathematical model, represented by a system of ordinary differential equations, it is possible to describe four different scenarios upon the arrival of the exotic predator in a native predator-prey system. The conditions for each of these scenarios are described analytically and numerically. The numerical simulations are performed considering the American mink (Mustela vison), an invasive generalist predator. The results highlight the importance of considering the interplay between interspecific interactions for understanding biological invasion success.

Vision Impairment and Psychosocial Function in US Adults

Vision impairment and psychosocial function, including symptoms of depression and anxiety and social isolation, are a major cause of morbidity in the US. However, there is a lack of nationally representative studies assessing associations between both objective and subjective vision impairment with psychosocial function following the COVID-19 pandemic. To provide updated national estimates on the associations of vision impairment with depressive and anxiety symptoms and social isolation in US adults 65 years and older. This was a cross-sectional analysis of the National Health and Aging Trends Study round 9 (2019) and 11 (2021), a nationally representative sample of Medicare beneficiaries aged 65 years and older. Binocular distance visual acuity, near visual acuity, and contrast sensitivity were tested. Objectively measured vision impairment was defined as having vision impairment in either distance visual acuity (worse than 20/40), near visual acuity (worse than 20/40), or contrast sensitivity (worse than 1.55 logCS). Self-reported vision impairment was defined based on participants' report on their vision status. Data were analyzed in May 2023. Depressive and anxiety symptoms assessed via the Patient Health Questionnaire. Social isolation was defined based on living arrangement, communication frequency, and activity participation responses. Among 2822 community-dwelling adults sampled from a population of 26 182 090, the mean (SD) age was 78.5 (5.6) years; 1605 individuals (54.7%) were female; 1077 (32.3%) had objectively measured vision impairment, and 203 (6.4%) had self-reported vision impairment. In adjusted models, all outcomes were significantly associated with objectively measured vision impairment, including depressive symptoms (odds ratio [OR], 1.81; 95% CI, 1.26-2.58), anxiety symptoms (OR, 1.74; 95% CI, 1.13-2.67), and severe social isolation (OR, 2.01; 95% CI, 1.05-3.87). Similarly, depressive symptoms (OR, 2.37; 95% CI, 1.44-3.88) and anxiety symptoms (OR, 2.10; 95% CI, 1.09-4.05) but not severe social isolation symptoms (OR, 2.07; 95% CI, 0.78-5.49) were significantly associated with self-reported vision impairment. In this study, vision impairment was associated with several psychosocial outcomes, including symptoms of depression and anxiety and social isolation. These findings provide evidence to support prioritizing research aimed at enhancing the health and inclusion of people with vision impairment.

Excessive maternal iced-tea intake-reversible cause of premature ductus arteriosus constriction

Premature ductus arteriosus constriction is a rare entity associated with high neonatal morbidity and mortality. Most cases are idiopathic, with the major known cause being maternal use of nonsteroidal anti-inflammatory drugs. Polyphenol-rich foods have been proven to have a deleterious fetal hemodynamic effect that can lead to premature ductal constriction. We report a case of a neonate diagnosed with premature ductal arteriosus closure, whose only risk factor was an excessive maternal intake of commercial iced-tea during pregnancy. The authors aim to raise awareness to the impact of polyphenol-rich food consumption on ductus arteriosus, since maternal dietary advice can have a major preventive role. Furthermore, a timely diagnosis and intervention can prevent significant morbidity and mortality.

Green Investment, Energy Consumption and Environmental Pollution Nexus G-7 Countries: A Historical Perceptive

The main purpose of this study is to examine the visions of the literature on green investment, institutional quality, energy consumption toward carbon dioxide (CO2) emissions in the perspective of G-7 countries. CO2 emissions is the major cause of GHG emissions. This review inspects and produces prevailing empirical and theoretical literature on said problem. This review paper firstly stimuluses the summary of green investment, institutional quality, energy consumption and CO2 emissions of G-7 countries. Secondly, it recognizes the literature based on the theoretical empirical and theoretical visions from the existing literature. Moreover, this article put light on theoretical approaches that defines how/ why these approaches work. Thirdly, this article suggests four productive dimensions for further policy development. This research also adds to the area of institutional quality, green finance, energy consumption concerning carbon dioxide (CO2) emissions by critically investigating and synthesizing prevailing theory and research on green finance, energy consumption, institutional quality and CO2 emissions.

Surviving maternal sepsis: Clinical, laboratory, and treatment features.

To describe clinical, laboratory, and antibiotic treatment characteristics in pregnant or recently pregnant women diagnosed with maternal sepsis. A retrospective cohort study was conducted in a Brazilian tertiary hospital from March 2014 until February 2018. The hospital implemented a Sepsis Protocol, based on the Brazilian Ministry of Health recommendation. All women who were pregnant or recently pregnant (up to 42 days postpartum), and who presented with suspected sepsis were included. Unconfirmed infections were excluded. Three hundred sixty-five women were included and divided into three groups according to sepsis severity (SEPSIS-2): sepsis, severe sepsis, and septic shock. Clinical, laboratory, and management characteristics were described and compared. Pregnancy-related and respiratory tract infections were the greater causes of maternal sepsis, and the urinary tract was the major cause of septic shock. We found almost total compliance with blood culture sample collection, and samples were positive in 10.8% of the cases, and in 41% of septic shock patients. Escherichia coli was the most common pathogen found and it was resistant to third-generation cephalosporins in none of the blood cultures and 3.3% of the urine cultures. Using the AWaRe (Access, Watch and Reserve) classification groups of antibiotics, Access and Watch antibiotics were used in virtually all women. We did not find any fatal maternal outcomes. Maternal sepsis is seldom the result of resistant microorganisms in this setting and the use of Access group antibiotics is widely possible. Health professionals' awareness of and institutional policies for maternal sepsis are crucial to its adequate treatment and better outcomes.

Functional annotation with expression validation identifies novel metastasis-relevant genes from post-GWAS risk loci in sporadic colorectal carcinomas

BackgroundColorectal cancer (CRC) is the third highest incidence cancer and is the leading cause of cancer mortality worldwide. Metastasis to distal organ is the major cause of cancer mortality. However,...

Neutrophil Extracellular Traps (NETs) and Atherosclerosis: Does Hypolipidemic Treatment Have an Effect?

Neutrophil extracellular traps (NETs) have attracted much attention recently, beyond elemental host immunity, due to their fundamental implication in a variety of pathologic conditions and widespread impactful diseases. Atherosclerotic cardiovascular disease (ASCVD) is one of them, and a major cause of mortality and disability worldwide. Consequently, years of basic and clinical research were dedicated to shedding light on every possible pathophysiologic mechanism that could be used as an effective prevention and treatment tool to ameliorate its burden. This led to the development of complex and prevention protocols and regimens that are now widely used, with lipid-lowering treatment being the current cornerstone; however, this is not adequate to alleviate the residual cardiovascular risk, which remains prominent. Despite the demonstrated pathogenic role of NETs in the progression and complications of ASCVD, little is known about their potential as a therapeutic target and the effects hypolipidemics exert on them.

Impact of Immunopathy and Coagulopathy on Multi-Organ Failure and Mortality in a Lethal Porcine Model of Controlled and Uncontrolled Hemorrhage.

Uncontrolled hemorrhage is a major preventable cause of death in patients with trauma. However, the majority of large animal models of hemorrhage have utilized controlled hemorrhage rather than uncontrolled hemorrhage to investigate the impact of immunopathy and coagulopathy on multi-organ failure (MOF) and mortality. This study evaluates these alterations in a severe porcine controlled and uncontrolled hemorrhagic shock (HS) model. Anesthetized female swine underwent controlled hemorrhage and uncontrolled hemorrhage by partial splenic resection followed with or without lactated Ringer solution (LR) or Voluven® resuscitation. Swine were surveyed 6 h after completion of splenic hemorrhage or until death. Blood chemistry, physiologic variables, systemic and tissue levels of complement proteins and cytokines, coagulation parameters, organ function, and damage were recorded and assessed. HS resulted in systemic and local complement activation, cytokine release, hypocoagulopathy, metabolic acidosis, MOF, and no animal survival. Resuscitation with LR and Voluven® after HS improved hemodynamic parameters (MAP and SI), metabolic acidosis, hyperkalemia, and survival but resulted in increased complement activation and worse coagulopathy. Compared with the LR group, the animals with hemorrhagic shock treated with Voluven® had worse dilutional anemia, coagulopathy, renal and hepatic dysfunction, increased myocardial complement activation and renal damage, and decreased survival rate. Hemorrhagic shock triggers early immunopathy and coagulopathy and appears associated with MOF and death. This study indicates that immunopathy and coagulopathy are therapeutic targets that may be addressed with a high-impact adjunctive treatment to conventional resuscitation.

Blood and urine multi-omics analysis of the impact of e-vaping, smoking, and cessation: from exposome to molecular responses

Cigarette smoking is a major preventable cause of morbidity and mortality. While quitting smoking is the best option, switching from cigarettes to non-combustible alternatives (NCAs) such as e-vapor products is a viable harm reduction approach for smokers who would otherwise continue to smoke. A key challenge for the clinical assessment of NCAs is that self-reported product use can be unreliable, compromising the proper evaluation of their risk reduction potential. In this cross-sectional study of 205 healthy volunteers, we combined comprehensive exposure characterization with in-depth multi-omics profiling to compare effects across four study groups: cigarette smokers (CS), e-vapor users (EV), former smokers (FS), and never smokers (NS). Multi-omics analyses included metabolomics, transcriptomics, DNA methylomics, proteomics, and lipidomics. Comparison of the molecular effects between CS and NS recapitulated several previous observations, such as increased inflammatory markers in CS. Generally, FS and EV demonstrated intermediate molecular effects between the NS and CS groups. Stratification of the FS and EV by combustion exposure markers suggested that this position on the spectrum between CS and NS was partially driven by non-compliance/dual use. Overall, this study highlights the importance of in-depth exposure characterization before biological effect characterization for any NCA assessment study.

Absence of CD80 reduces HSV-1 replication in the eye and delays reactivation but not latency levels.

Herpes simplex virus-1 (HSV-1) infections are among the most frequent serious viral eye infections in the U.S. and are a major cause of viral-induced blindness. HSV-1 infection is known to induce T cell activation, proliferation, and differentiation that play crucial roles in the development of virus-induced inflammatory lesions, leading to eye disease and causing chronic corneal damage. CD80 is a co-stimulatory molecule and plays a leading role in T cell differentiation. Previous efforts to limit lesion severity by controlling inflammation at the cellular level led us to ask whether mice knocked out for CD80 would show attenuated virus replication following reactivation. By evaluating the effects of CD80 activity on primary and latent infection, we found that in the absence of CD80, virus replication in the eyes and virus reactivation in latent trigeminal ganglia were both significantly reduced. However, latency in latently infected CD80-/- mice did not differ significantly from that in wild-type (WT) control mice. Reduced virus replication in the eyes of CD80-/- mice correlated with significantly expanded CD11c gene expression as compared to WT mice. Taken together, our results indicate that suppression of CD80 could offer significant beneficial therapeutic effects in the treatment of Herpes Stromal Keratitis (HSK).IMPORTANCEOf the many problems associated with recurrent ocular infection, reducing virus reactivation should be a major goal of controlling ocular herpes simplex virus-1 (HSV-1) infection. In this study, we have shown that the absence of CD80 reduces HSV-1 reactivation, which marks the establishment of a previously undescribed mechanism underlying viral immune evasion that could be exploited to better manage HSV infection.

Metal magnetic memory characterization of fatigue crack propagation of Q345qD bridge steel under the influence of stress ratio

Fatigue fracture failure has been one of the major causes of damage in steel bridges. To better use fracture mechanics to study this failure behavior, the fatigue crack growth behavior of bridge steel plates under different stress ratios was investigated by metal magnetic memory nondestructive testing technique. The changes of magnetic signals during fatigue crack growth were recorded and analyzed, and then the magnetic signal characterization method of fatigue crack growth length was discussed both theoretically and experimentally. The stress ratio was incorporated into the model to establish a quantitative relationship equation between the magnetic signal characteristic and the crack growth length. Subsequently, the proposed relationship was applied to the fatigue crack growth remaining life prediction study and verified by experimental results. The results showed that the magnetic signal gradient is suitable as a characteristic parameter to quantitatively evaluate the fatigue crack growth length, and the relative errors between the prediction results and the test results were all within 15 %.

ERCP-Net: a channel extension residual structure and adaptive channel attention mechanism for plant leaf disease classification network

Plant leaf diseases are a major cause of plant mortality, especially in crops. Timely and accurately identifying disease types and implementing proper treatment measures in the early stages of leaf diseases are crucial for healthy plant growth. Traditional plant disease identification methods rely heavily on visual inspection by experts in plant pathology, which is time-consuming and requires a high level of expertise. So, this approach fails to gain widespread adoption. To overcome these challenges, we propose a channel extension residual structure and adaptive channel attention mechanism for plant leaf disease classification network (ERCP-Net). It consists of channel extension residual block (CER-Block), adaptive channel attention block (ACA-Block), and bidirectional information fusion block (BIF-Block). Meanwhile, an application for the real-time detection of plant leaf diseases is being created to assist precision agriculture in practical situations. Finally, experiments were conducted to compare our model with other state-of-the-art deep learning methods on the PlantVillage and AI Challenger 2018 datasets. Experimental results show that our model achieved an accuracy of 99.82% and 86.21%, respectively. Also, it demonstrates excellent robustness and scalability, highlighting its potential for practical implementation.

Single-cell and bulk RNA sequencing data jointly reveals VDAC2's impacts on prognosis and immune landscape of NSCLC.

Non-small cell lung cancer (NSCLC) is characterized by stronger metastatic ability and worse prognosis. In NSCLC, hypoxia is a major cause of invasion and metastasis through promoting angiogenesis. In present study, NSCLC cell clusters were extracted from single cell-sequencing dataset GSE131907, which were combined with hypoxia-related genes to group clusters. qRT-PCR and western blot were used to validate the expression of target gene. Nine NSCLC clusters were extracted, which were divided into two hypoxia-related subgroups, C1 and C2. Totally 101 differentially expressed prognostic genes were identified between subgroups. Of which, VDAC2 showed excellent prognostic value for NSCLC and was selected for further analysis. VDAC2 was upregulated in tumor samples in TCGA and was correlated with advanced stages. In vitro experiments validated this trend. Five crucial immune cells showed differential infiltration proportions between high and low VDAC2 expression groups. VDAC2 knockdown significantly inhibited the proliferation and invasion ability of NSCLC cells. Integrating single cell and bulk sequencing data as well as wet lab experiments, hypoxia-related VDAC2 exhibited important prognostic value and showed the promise of becoming immune-therapy target in NSCLC.

CHF: A Disease Capturing Indians

At 30% of all fatalities worldwide, cardiovascular diseases (CVDs) are the major cause of mortality. The WHO estimates that 17.9 million people die from CVDs annually and that number will rise to 22.2 million by 2030. As individuals age, the mortality rate rises. In terms of gender, women die from CVD at a greater rate (51%) than do men (42%). The intricate clinical illness known as congestive heart failure (CHF) is marked by an inefficient heartbeat, which compromises the body's blood flow. Any condition affecting blood ejection from the ventricles into the systemic circulation or ventricular filling might lead to CHF. Daucus carota, Nerium oleander, Amaranthus viridis, Ginkgo biloba, Terminalia arjuna, Picrorhiza kurroa, Salvia miltiorrhiza, Tinospora cordifolia, Mucuna pruriens, Hydrocotyle asiatica, Bombax ceiba, and Andrographis paniculate are a few medicinal plants that are well-known for treating cardiovascular disease. These plants include flavonoids, polyphenols, plant sterol, plant sulphur compounds, and terpenoids, which are active phytochemicals. Given the rising incidence of CVD, a number of physiologically active substances with established biological effects have been identified discovered in a variety of plants; nonetheless, proper CVD preventive and treatment strategies are still needed. To fully comprehend the mechanism and phytochemicals found in particular plants that cure CVD, more study is required.

Factors Associated with Undernutrition among Children Under Five Years at Hoima Regional Referral Hospital, Hoima City Western Uganda

Undernutrition was one of the major causes of mortality and morbidity among under-five children in Sub-Saharan Africa. To understand the determinants of undernutrition among under-five children, this study was conducted at Hoima Regional Referral Hospital (HRRH) in Hoima City. The source of data was household demographic and socio-economic characteristics which included anthropometric data on under-five children at HRRH. Anthropometric data included height, weight and MUAC for the different ages of the children. Data analysis was done in the Epi Info program module and Stata statistical software. Multivariate analysis was done by fitting a binary logistic regression model to establish the underlying determinants of undernutrition among under-five children. It was found that children aged 39-59 months were less likely to be underweight than those aged less than twelve months. Findings also revealed that stunting was more prevalent among children of peasant farmers than the pastoralists. There was however no significant relationship between child wasting and selected child characteristics. It was worth noting that the study was essential in pointing out the particular age groups among under-five children as well as the occupations that contribute to undernutrition in Hoima City. Based on the findings, the study recommends exclusive breastfeeding and proper complementary feeding, especially among those aged less than three years. Special arrangements could also be put in place to have children of mothers engaged in cultivation brought regularly for breastfeeding. Keywords: Undernutrition, Anthropometric, Breastfeeding, Underweight.