Major Cause Research Articles

Improving the Performance of Automatic Lip-Reading Using Image Conversion Techniques

Variation in lighting conditions is a major cause of performance degradation in pattern recognition when using optical imaging. In this study, infrared (IR) and depth images were considered as possible robust alternatives against variations in illumination, particularly for improving the performance of automatic lip-reading. The variations due to lighting conditions were quantitatively analyzed for optical, IR, and depth images. Then, deep neural network (DNN)-based lip-reading rules were built for each image modality. Speech recognition techniques based on IR or depth imaging required an additional light source that emitted light in the IR range, along with a special camera. To mitigate this problem, we propose a method that does not use an IR/depth image directly, but instead estimates images based on the optical RGB image. To this end, a modified U-net was adopted to estimate the IR/depth image from an optical RGB image. The results show that the IR and depth images were rarely affected by the lighting conditions. The recognition rates for the optical, IR, and depth images were 48.29%, 95.76%, and 92.34%, respectively, under various lighting conditions. Using the estimated IR and depth images, the recognition rates were 89.35% and 80.42%, respectively. This was significantly higher than for the optical RGB images.

Modeling skeletal dysplasia in Hurler syndrome using patient-derived bone marrow osteoprogenitor cells.

Dysostosis multiplex is a major cause of morbidity in Hurler syndrome (mucopolysaccharidosis type IH [MPS IH], OMIM #607014) because currently available therapies have limited success in its prevention and reversion. Unfortunately, the elucidation of skeletal pathogenesis in MPS IH is limited by difficulties in obtaining bone specimens from pediatric patients and poor reproducibility in animal models. Thus, the application of experimental systems that can be used to dissect cellular and molecular mechanisms underlying the skeletal phenotype of MPS IH patients and to identify effective therapies is highly needed. Here, we adopted in vitro/in vivo systems based on patient-derived bone marrow stromal cells to generate cartilaginous pellets and bone rudiments. Interestingly, we observed that heparan sulphate accumulation compromised the remodeling of MPS IH cartilage into other skeletal tissues and other critical aspects of the endochondral ossification process. We also noticed that MPS IH hypertrophic cartilage was characterized by dysregulation of signaling pathways controlling cartilage hypertrophy and fate, extracellular matrix organization, and glycosaminoglycan metabolism. Our study demonstrates that the cartilaginous pellet-based system is a valuable tool to study MPS IH dysostosis and to develop new therapeutic approaches for this hard-to-treat aspect of the disease. Finally, our approach may be applied for modeling other genetic skeletal disorders.

Impact of Demographic Developments and PCV13 Vaccination on the Future Burden of Pneumococcal Diseases in Germany—An Integrated Probabilistic Differential Equation Approach

Streptococcus pneumonia is the primary cause of morbidity and mortality in infants and children globally. Invasive pneumococcal disease (IPD) incidence is affected by various risk factors such as age and comorbidities. Additionally, this bacterium is a major cause of community-acquired pneumonia (CAP), leading to higher rates of hospitalization, especially among older adults. Vaccination with pneumococcal conjugate vaccines (PCVs) has proven effective, but the demographic transition in Germany poses a challenge. This study introduces a novel stochastic approach by integrating a population forecast model into a transmission dynamic model to investigate the future burden of pneumococcal diseases in three age groups (0–4, 5–59, and 60 and older). Our simulations, presented through mean predictions and 75% prediction intervals, indicate that implementing PCV13 (13-valent pneumococcal conjugate vaccine) until the year 2050 results in reduced cases of IPD and CAP in all age groups compared to scenarios without infant vaccination. However, cases with non-vaccine serotypes may persist at higher levels compared to scenarios without infant vaccination. Consequently, there may be a need for improvement in the current national vaccine policy, such as implementing the use of higher-valent PCVs and strengthening adult vaccination uptake.

Research and future directions of HPV-related vaccines

Human papillomavirus (HPV) infection is a major cause of cervical lesions such as cervical cancer in women. Prophylactic vaccines developed against HPV have been widely used, but these vaccines are only effective against certain types of HPV and do not work in people who are already infected. Therefore, the development of therapeutic vaccines is also particularly important. The use of the modified poxvirus (MVA) as a vector for HPV vaccinations has garnered attention in recent years. It has been found that modified poxvirus vaccines are able to combat human papillomavirus infection and have significant safety and efficacy profiles. Based on the study of the distribution of HPV types in different regions and populations, this paper finds that there are differences in the prevalence of high-risk HPV subtypes in different regions, and that a large number of infected people need more effective treatments. At the same time, by comparing the advantages and disadvantages of preventive and therapeutic vaccines, we recognize that both have roles that cannot be replaced by the other in the task of fighting HPV, and that the two vaccines need to be developed together and complement each other in order to minimize the harm of HPV. Based on these findings, this paper provides a constructive reference for future targeted prevention and treatment of HPV in different regions of the world with different HPV distributions.

Dual-Responsive Nanogels with Cascaded Gentamicin Release and Lysosomal Escape to Combat Intracellular Small Colony Variants for Peritonitis and Sepsis Therapies.

Intracellular bacteria are the major cause of serious infections including sepsis and peritonitis, but face great challenges in fighting against the stubborn intracellular small colony variants (SCVs). Herein, the authors have developed nanogels (NGs) to destroy both planktonic bacteria and SCVs and eliminate excessive inflammations for peritonitis and sepsis therapies. Free gentamicin (GEN) and hydroxyapatite nanoparticles (NPs) with GEN loading and mannose grafts (mHAG) are inoculated into ε-polylysine NGs to obtain NG@G1-mHAG2 through crosslinking with phenylboronic acid and tannic acid. The H2O2 consumption after reaction with phenylboronic esters and the elimination of free radicals by tannic acid alleviates the escalated inflammatory status to promote sepsis therapy. After mannose-mediated uptake into macrophages, the acid-triggered degradation of mHAG NPs generates Ca2+ to destabilize lysosomes and the efficient lysosomal escape leads to reversion of hypometabolic SCVs into normal phenotype and their sensitivity to GEN. In a peritonitis mouse model, NG@G1-mHAG2 treatment provides strong and persistent bactericidal effects against both extracellular bacteria and intracellular SCVs and extends survival of peritonitis mice without apparent hepatomegaly, splenomegaly, pulmonary edema, and inflammatory cell infiltration. Thus, this study demonstrates a concise and versatile strategy to eliminate SCVs and relieve inflammatory storms for peritonitis and sepsis therapies without infection recurrence.

Apoptotic Vesicles Modulate Endothelial Metabolism and Ameliorate Ischemic Retinopathy via PD1/PDL1 Axis.

Pathological angiogenesis with subsequent disturbed microvascular remodeling is a major cause of irreversible blindness in a number of ischemic retinal diseases. The current anti-vascular endothelial growth factor therapy can effectively inhibit angiogenesis, but it also brings significant side effects. The emergence of stem cell derived extracellular vesicles provides a new underlining strategy for ischemic retinopathy. Apoptotic vesicles (apoVs) are extracted from stem cells from human exfoliated deciduous teeth (SHED). SHED-apoVs are delivered into the eyeballs of oxygen-induced retinopathy (a most common model of angiogenic retinal dieseases) mice through intravitreal injection. The retinal neovascularization and nonperfusion area, vascular structure, and density changes are observed during the neovascularization phase (P17) and vascular remodeling phase (P21), and visual function is measured. The expression of extracellular acidification rate and lactic acid testing are used to detect endothelial cells (ECs) glycolytic activity. Furthermore, lentivirus and neutralizing antibody are used to block PD1-PDL1 axis, investigating the effects of SHED-apoVs on glycolysis and angiogenic activities. This work shows that SHED-apoVs are taken up by ECs and modulate the ECs glycolysis, leading to the decrease of abnormal neovessels and vascular remodeling. Furthermore, it is found that, at the molecular level, apoVs-carried PD1 interacts with PDL1 on hypoxic ECs to regulate the angiogenic activation. SHED-apoVs inhibit pathological angiogenesis and promote vascular remodeling in ischemic retinopathy partially by modulating ECs glycolysis through PD1/PDL1 axis. This study provides a new potential strategy for the clinical treatment of pathological retinal neovascularization.

In vivo genome-wide CRISPR screening identifies CITED2 as a driver of prostate cancer bone metastasis.

Most cancer deaths are due to metastatic dissemination to distant organs. Bone is the most frequently affected organ in metastatic prostate cancer and a major cause of prostate cancer deaths. Yet, our partial understanding of the molecular factors that drive bone metastasis has been a limiting factor for developing preventative and therapeutic strategies to improve patient survival and well-being. Although recent studies have uncovered molecular alterations that occur in prostate cancer metastasis, their functional relevance for bone metastasis is not well understood. Using genome-wide CRISPR activation and inhibition screens we have identified multiple drivers and suppressors of prostate cancer metastasis. Through functional validation, including an innovative organ-on-a-chip invasion platform for studying bone tropism, our study identifies the transcriptional modulator CITED2 as a novel driver of prostate cancer bone metastasis and uncovers multiple new potential molecular targets for bone metastatic disease.

Causes and Effect of Out-Migration in Rural Areas of Benue State, Nigeria

The study assessed the effect of out-migration from rural settlements in Benue State, Nigeria. The objective of the study was to examine the causes, effect and control of migration in rural settlements of the study area. A total of 1202 respondents were selected from rural communities in 5 Local Government Area of the State. The study used multi-stage sampling technique involving purposive, simple random, judgement and snowball sampling techniques in selecting the communities and the respondents. Data were obtained via questionnaire. Frequencies and percentages were used for data analysis while tables were used for data presentation. The study found that 60.1% of the respondents are male. Most of the respondents (23.7%) are within age 50-54 years. Majority of the respondents are married (79.8%) and have households that have migrated to other places in Nigeria and beyond. The major causes of migration include unemployment (99.8%), inadequate educational institutions (97.2%), village hardship and crises (69.2%), lack of social amenities (6.7%) and insecurity/crises in rural areas. The major effect of out-migration includes reduction in labour supply, increased in demand for labour (97.1%), high cost of labour (99.8%), decreased in farm size (99.5%), decreased in productivity (99.7) and decreased in income (99.7%) in rural areas. Migration also causes low social economic growth and development in rural areas. The study recommends some major strategies for making the rural areas attractive to minimise youth migration in the State. These includes mechanization of agriculture, establishing agro-based industries, creating employment opportunities, provision of social amenities and ensuring adequate security of life and properties in rural areas of the State.

Emergence and dissemination of equine-like G3P[8] rotavirus A in Brazil between 2015 and 2021.

Rotavirus A (RVA) is a major cause of acute gastroenteritis globally that is classically genotyped by its two immunodominant outer capsid proteins, VP7 (G-) and VP4 (P-). Recent evidence suggests that the reassortant equine-like G3P[8] strain played a substantial role in RVA transmission in Brazil since 2015. To understand its global emergence and dissemination in Brazilian territory, stool samples collected from 11 Brazilian states (n = 919) were genotyped by RT-qPCR and proceeded to sequence the VP7 gene (n = 102, 79 being newly generated) of the G3P[8] samples with pronounced viral loads. Our phylogenetic genotyping showed that G3P[8] became the dominant strain in Brazil between 2017 and 2020, with equine-like variants representing 75%-100% of VP7 samples in this period. A Bayesian discrete phylogeographic analysis strongly suggests that the equine-like G3P[8] strain originated in Asia during the early 2010s and subsequently spread to Europe, the Caribbean, and South America. Multiple introductions were detected in Brazil between 2014 and 2017, resulting in five national clusters. The reconstruction of the effective population size of the largest Brazilian cluster showed an expansion until 2017, followed by a plateau phase until 2019 and subsequent contraction. Our study also supports that most mutations fixed during equine-like G3P[8] evolution were synonymous, suggesting that adaptive evolution was not an important driving force during viral dissemination in humans, potentially increasing its susceptibility to acquired immunity. This research emphasizes the need for comprehensive rotavirus genomic surveillance that allows close monitoring of its ever-shifting composition and informs more effective public health policies.IMPORTANCEOur original article demonstrated the origin and spread in a short time of equine-like G3P[8] in Brazil and the world. Due to its segmented genome, it allows numerous mechanisms including genetic drift and reassortment contribute substantially to the genetic diversity of rotavirus. Although the effectiveness and increasing implementation of vaccination have not been questioned, a matter of concern is its impact on the emergence of escape mutants or even the spread of unusual strains of zoonotic transmission that could drive epidemic patterns worldwide. This research emphasizes the need for comprehensive rotavirus genomic surveillance, which could facilitate the formulation of public policies aimed at preventing and mitigating its transmission.

Cellular adaptations of the scleractinian coral Madracis pharensis to chronic oil pollution in a Mediterranean shipwreck

Chemical pollution in marine ecosystems is a factor of stress interacting in multiple and complex ways with other major causes of deterioration, such as warming seas due to climate change. Here we surveyed epibenthic communities from a shipwreck in the Levantine Basin for temporal and spatial changes in the community in relation to chronic oil pollution, comparing results collected from an area of the wreck characterized by chronic oil leakage with another area not affected by oil. Polycyclic aromatic hydrocarbons (PAHs) bioaccumulation analyses were integrated with characterization of the efficiency of xenobiotics biotransformation processes and antioxidant network of the scleractinian coral Madracis pharensis, chosen as bioindicator species. Results highlighted the two areas hosting different epibenthic communities over a period of 11 years. Significant changes in the percentage cover of M. pharensis could be the result of recent mass mortality associated to Marine Heat Waves. Biological investigation conducted in M. pharensis tissues revealed an increased content of PAHs in specimens collected from the oil-impacted area, coupled with an increased capability of oxyradicals scavenging capacity and a lower functionality of phase II biotransformation mechanisms associated to glutathione S-transferase. Overall, the results suggest that M. pharensis has the capability to develop cellular and physiological adaptations to chemical-mediated stress, with yet unknown possible energy trade-offs to sustain stress response.

Unilateral visual impairment and blindness in school children - prevalence and aetiology in Saki-East LGA of Oyo State, Nigeria.

This study determined the prevalence and aetiology of unilateral visual impairment (VI) and blindness and its associated factors in school children. We conducted a multistage, cross-sectional study in primary and secondary schools of Saki-East Local Government Area of Oyo State, Nigeria. Unilateral VI was defined as presenting visual acuity (PVA) worse than +0.3 LogMAR (6/12) and unilateral blindness as PVA worse than +1.3 LogMAR (3/60) in the worse eye. Detailed ocular examinations were performed for students with unilateral VI, and Logistic regression analysis was performed to explore associations with independent variables. The mean age of participants was 11 ± 3.2 years. Thirty-six (0.98%) of 3671 children had unilateral VI, and fifteen children had unilateral blindness (0.41%), giving a combined prevalence of 1.39 ± 0.5%. History of ocular trauma was reported by 14 (27.5%) participants with unilateral VI and blindness. In addition, those with a history of ocular trauma were 6.5 times more likely to be blind or have a severe VI (95% CI 1.5-2.8) than those without a history of ocular trauma. Uncorrected refractive error was the major cause of unilateral VI in 26 (51%) participants, while traumatic cataract was the main cause of unilateral blindness seen in 5 (9.8%) participants, none of whom had a previous eye examination. Fourteen per thousand school children had unilateral VI in this study; the major causes were refractive error and cataract, which are treatable. Ocular trauma was a significant risk factor for unilateral VI and blindness.

Climate Change Paradox: The Least Responsible for It Encounters the Most of Its Implications

Carbon dioxide (CO2) emissions are a major cause of climate change. However, CO2 emissions data for 178 countries from 1960 to 2018 revealed inequality in global CO2 emissions. For example, we found that 50% of the world’s population (ca. 3.75 billion people) was responsible for just 8.9% of the global cumulative carbon emissions. These people are concentrated in low- and middle-income countries. Conversely, 10% of the world’s population (ca. 757 million people), concentrated in high-income countries, were responsible for 46.8% of the global emissions. Furthermore, the literature review disclosed evolution of CO2 emission inequalities within countries. A significant (p < 0.001) negative (r2 = −0.52) correlation was detected between carbon emissions and climate change impacts on national incomes. Such correlation indicated that countries most likely to experience the greatest effects of climate change are also those who make the smallest contributions to its underlying causes. Similar disparities were observed within countries where low-income groups who make the smallest contributions to climate change are subjected to its worst implications. Evaluations of the data from the literature showed that migration could be the result of climate change, though such migration does not happen in isolation. In other words, this kind of migration is frequently linked to other issues such as the fragility and lack of adaptability of the communities. Furthermore, reviews showed that climate change catalyzes instability and conflict. On the other hand, conflict damages the environment and climate in multiple ways. Therefore, it is necessary to collaborate to resolve these two issues concurrently.

Use of discarded corneo-scleral rims to create cornea-like tissue.

Corneal disease is a major cause of blindness. Transplantation of cadaver-derived corneas (keratoplasty) is still the current therapy of choice; however, the global shortage of donor corneas continues to drive a search for alternatives. To this end, biosynthetic corneal substitutes have recently begun to gain importance. Here, we present a novel method for the generation of a cornea-like tissue (CLT), using corneo-scleral rims discarded after keratoplasty. Type I collagen was polymerized within the corneo-scleral rim, which functioned as a 'host' mould, directing the 'guest' collagen to polymerize into disc-shaped cornea-like material (CLM), displaying the shape, curvature, thickness, and transparency of normal cornea. This polymerization of collagen appears to derive from some morphogenetic influence exerted by the corneo-scleral rim. Once the CLM had formed naturally, we used collagen crosslinking to fortify it, and then introduced cells to generate a stratified epithelial layer to create cornea-like tissue (CLT) displaying characteristics of native cornea. Through the excision and reuse of rims, each rim turned out to be useful for the generation of multiple cornea-shaped CLTs. The approach effectively helps to shorten the gap between demand and supply of CLMs/CLTs for transplantation. We are exploring the surgical transplantation of this CLT into animal eyes, as keratoprostheses, as a precursor to future applications involving human eyes. It is possible to use either the CLM or CLT, for patients with varying corneal blinding diseases.

Fronto-striato network function is reduced in major depressive disorder.

Major depressive disorder (MDD) is a major cause of poor quality of life and disability and is highly prevalent worldwide. Various pathological mechanisms are implicated in MDD, including the reward system. The human brain is equipped with a reward system that is involved in aspects such as motivation, pleasure, and learning. Several studies including a meta-analysis have been reported on the reward system network and MDD. However, to our knowledge, no studies have examined the relationship between the reward system network of drug-naïve, first-episode MDD patients and the detailed symptoms of MDD or age. The fronto-striato network (FSN) is closely related to the reward system network. The present study primarily aimed to elucidate this point. A total of 89 drug-naïve first-episode MDD patients and 82 healthy controls (HCs) patients were enrolled in the study. The correlation between the FSN and age and the interaction between age and illness in the FSN were investigated in 75 patients in the MDD group and 79 patients in the HC group with available information on the FSN and age. In addition, the association between the FSN and the total scores on the 17-item Hamilton Rating Scale for Depression (HAMD-17) and scores in each symptom item was analyzed in 76 MDD subjects with information on the FSN and HAMD-17. The significance of each result was evaluated according to a p-value of <0.05. Age was inversely correlated with the FSN (p=2.14e-11) in the HC group but not in the MDD group (p=0.79). FSN varied with the presence of MDD and with age, particularly showing an interaction with MDD and age (p=1.04e-08). Specifically, age and the presence or absence of MDD each affected FSN, but the effect of age on FSN changed in the presence of depression. FSN did not correlate with total HAMD-17 scores or scores in each item. The reward system may be dysfunctional in patients with MDD. In addition, the effect could be greater in younger patients. Meanwhile, there is no correlation between the function of the reward system and the severity of MDD or the severity of each symptom. Thus, the reward system network may be an important biological marker of MDD, although careful consideration should be given to age and its association with the severity of the disorder. The reward system function is decreased in MDD patients, and this decrease may be more pronounced in younger patients, although further research is still needed.

Increase in acute pancreatitis, especially gallstone related, as the cause for emergency admissions: Temporal trend from Kashmir, India.

The incidence of acute pancreatitis is increasing globally. Gallstones (GS) and ascariasis are the major causes for acute pancreatitis in the Kashmiri population. In recent years, we have observed an increase in the admission rate of acute pancreatitis. Many patients who present first time as gallstone pancreatitis have asymptomatic gallstones. We aimed at studying the etiology and yearly admission rate of acute pancreatitis with main focus on gallstone pancreatitis and the contribution ofasymptomatic gallstones. This was a hospital-based, prospective, observational study from January 2015 to December 2019 for a period of fiveyears. Patients of acute pancreatitis were evaluated for etiology and yearly admission rate. Patients of gallstone pancreatitis were evaluated in terms of clinical profile, risk factors, nature (symptomatic/asymptomatic, known/unknown gallstones), size of stones, treatment and outcome in terms of severity and mortality. The data was analyzed by Statistical Package for the Social Sciences (SPSS) version 20.0, as mean (SD), frequencies and percentages. As many as 702 (8.5%) patients of acute pancreatitis were admitted among 8245gastrointestinal emergencies in fiveyears. The yearly admission rate of acute pancreatitis was 5.6%, 7.3%, 8.7%, 9.5% and 10.3%, respectively (p = 0.013). Gallstones, Ascariasis, alcohol and idiopathic acute pancreatitis were 47.7%, 6.9%, 1.2% and 33.7%, respectively. Gallstone pancreatitis increased from 31% in2015 to 52.4% in 2019 (p = 0.045) and ascariasis-related acute pancreatitis declined from 14.4% to 1.6% (p = 0.034). Asymptomatic gallstones constituted 87.7% of cases. Known/unknown asymptomatic gallstones and symptomatic gallstones were 24.4%, 63.2% and 12.2%, respectively. Gallstones < 5mm and > 5mm were76.1% and 23.8% respectively (p = 0.027). Cholecystectomy rate in index admission was 4.7%. Mild, moderate and severe gallstone pancreatitis was 60.2%, 18.8% and 20.8%, respectively. Mortality in gallstone pancreatitis was 10.4%. The incidence of acute pancreatitis is increasing due to gallstone pancreatitis. Ascariasis-related acute pancreatitis has declined. There is significant contribution of asymptomatic gallstones in patients who present for the first time as acute pancreatitis. Small gallstones < 5mm are likely to be the risk factors for gallstone pancreatitis.

Lumican promotes gastric cancer progression by regulating the ERK pathway

Globally, gastric cancer (GC) remains a major cause of death. Our prior study found lumican to be an important independent predictor of GCs poor overall survival and bioinformatics analysis suggested the MAPK pathway as a signaling cascade linked to lumican function. In our study, we observed that lumican exhibited a significant elevation in GC tissues and cells, hastening tumor proliferation in vivo in comparison to control groups. We also observed that knockdown of lumican effectively inhibited the proliferation, migration and invasion of AGS cells. On the contrary, overexpression of lumican promoted the proliferation, migration and invasion of AGS cells. We clarified that lumican was upstream of ERK in the MAPK pathway. In rescue assays, TBHQ further enhanced the promoting effect of lumican overexpression on cell migration and invasion and the increased expression of ERK 1/2 or p-ERK 1/2 levels. However, the increased expression of ERK 1/2 or p-ERK 1/2, migration and invasion were completely blocked by GDC-0994 in lumicanoverexpressing AGS cells with TBHQ treated. Molecular docking prediction revealed that the amino acid sequence of lumican binding to ERK1/2 may also regulate the ERK pathway. In conclusions, lumican is highly expressed in GC and promotes the proliferation, migration and invasion of GC cells by regulating ERK pathway. Consequently, lumican emerges as pivotal indicators for both diagnosis and treatment in GC cases.

A 5-step root cause analysis model for test overutilization: A study on its application to plasma transferrin testing.

This study aimed to develop a root cause analysis (RCA) model for test overutilization, applying it to transferrin overordering at our institution. A comprehensive review was undertaken to establish a systematic RCA model. Upon implementation, the questionnaire identifying the root causes of transferrin overordering with infographic intervention was distributed to clinicians and nurses. The RCA model comprises 5 steps: (1) problem identification, (2) causal factor determination, (3) data collection, (4) significant factor identification, and (5) corrective action development and outcome measurement. The major causes of transferrin overutilization were confusion between transferrin and transferrin saturation, as well as unfamiliarity with the laboratory handbook. An infographic reduced postintervention transferrin ordering among clinicians (84.9%, P < .001) and nurses (46.8%, P < .001). This study presents a 5-step RCA model that offers a customized method to identify the causes of test overutilization. Applying this model to transferrin at our institution revealed 22 leading root causes. Laboratories are encouraged to adopt this RCA model as it can contribute to optimized patient care and more efficient resource allocation.

PENGARUH BEBAN KERJA DAN KELELAHAN PERAWAT TERHADAP PERAWATAN INFUS DI RUANG PERAWATAN KELAS IIIRSUD SUKOHARJO

Nurses have a big role in infusion installment and care according to the Standard Operating Procedure. Infection or other problems that may emerge during infusion installment can be minimized or avoided as long as the operating standard is met. Quantity work load, qualitative workload, physical workload, psychological workload, social workload and nurses’ fatigue are the major causes of infection due to working errors. This research aims at finding out the effect of nurses’ workload and fatigue on infusion care. This is a quantitative research using cross-sectional approach. The population consists of all nurses working in the third class of RSUD Sukoharjo. Using total sampling, the sampling consists of 28 nurses. Nurses’ workload that influenced infusion care comprises qualitative workload (p 0,000; B -1,847), nurse workload that did not influence infusion care comprised quantitative workload (p 0,109; B -0,243), physical workload (p 0,124; B -0,612), psychological workload (p 0,109; B -0,294), and social workload (p 0,875; B -0,053). There is no effect of nurse fatigue on infusion care (p 0,209; B -0,135). Quantitative workload did not influence nurse fatigue (p 0,196; B -0,367), qualitative workload did not influence nurse fatigue (p 0,053; B -1,331), physical workload did not influence nurse fatigue (p 0,171; B -1,061), and psychological workload did not influence nurse fatigue (p 0,980; B 0,021). The hardest nurse workload that had influenced infusion care in the third class of RSUD Sukoharjo is a qualitative workload. The more a qualitative workload that nurse felt, the worse infusion care they will treat. The workload has no effect on nurse fatigue.

Integrative metabolomics highlights gut microbiota metabolites as novel NAFLD-related candidate biomarkers in children.

Altered gut microbiota and metabolites are a major cause of non-alcoholic fatty liver disease (NAFLD) in children. This study demonstrated a complete gut metabolic map of children with NAFLD, containing 318 increased and 123 decreased metabolites by untargeted metabolomic. Multiple validation approaches (machine learning and targeted metabolomic) selected five novel gut metabolites for targeted metabolomics, which can distinguish NAFLD status and severity. The gut microbiota (Butyricicoccus and Alistipes) and metabolites (creatinine and dodecanoic acid) were novel biomarkers associated with impaired liver function and inflammation and validated by experiments of hepatocyte cell lines. The data provide a better understanding of the importance of gut microbiota and metabolite alterations in NAFLD, which implies that the altered gut microbiota and metabolites may represent a potential target to prevent NAFLD development.

Leucine alleviates cytokine storm syndrome by regulating macrophage polarization via the mTORC1/LXRα signaling pathway.

Cytokine storms are associated with severe pathological damage and death in some diseases. Excessive activation of M1 macrophages and the subsequent secretion of pro-inflammatory cytokines are a major cause of cytokine storms. Therefore, promoting the polarization of M2 macrophages to restore immune balance is a promising therapeutic strategy for treating cytokine storm syndrome (CSS). This study was aimed at investigating the potential protective effects of leucine on lipopolysaccharide (LPS)-induced CSS in mice and exploring the underlying mechanisms. CSS was induced by LPS administration in mice, which were concurrently administered leucine orally. In vitro, bone marrow derived macrophages (BMDMs) were polarized to M1 and M2 phenotypes with LPS and interleukin-4 (IL-4), respectively, and treated with leucine. Leucine decreased mortality in mice treated with lethal doses of LPS. Specifically, leucine decreased M1 polarization and promoted M2 polarization, thus diminishing pro-inflammatory cytokine levels and ameliorating CSS in mice. Further studies revealed that leucine-induced macrophage polarization through the mechanistic target of rapamycin complex 1 (mTORC1)/liver X receptor α (LXRα) pathway, which synergistically enhanced the expression of the IL-4-induced M2 marker Arg1 and subsequent M2 polarization. In summary, this study revealed that leucine ameliorates CSS in LPS mice by promoting M2 polarization through the mTORC1/LXRα/Arg1 signaling pathway. Our findings indicate that a fundamental link between metabolism and immunity contributes to the resolution of inflammation and the repair of damaged tissues.