A fault diagnosis method for wireless sensor network nodes based on a belief rule base with adaptive attribute weights.

Due to the harsh operating environment and ultralong operating hours of wireless sensor networks (WSNs), node failures are inevitable. Ensuring the reliability of the data collected by the WSN necessitates the utmost importance of diagnosing faults in nodes within the WSN. Typically, the initial step in the fault diagnosis of WSN nodes involves extracting numerical features from neighboring nodes. A solitary data feature is often assigned a high weight, resulting in the failure to effectively distinguish between all types of faults. Therefore, this study introduces an enhanced variant of the traditional belief rule base (BRB), called the belief rule base with adaptive attribute weights (BRB-AAW). First, the data features are extracted as input attributes for the model. Second, a fault diagnosis model for WSN nodes, incorporating BRB-AAW, is established by integrating parameters initialized by expert knowledge with the extracted data features. Third, to optimize the model's initial parameters, the projection covariance matrix adaptive evolution strategy (P-CMA-ES) algorithm is employed. Finally, a comprehensive case study is designed to verify the accuracy and effectiveness of the proposed method. The results of the case study indicate that compared with the traditional BRB method, the accuracy of the proposed model in WSN node fault diagnosis is significantly improved.

Impact of COVID-19 on emergency oral health care in New Jersey.

BACKGROUND: The COVID-19 pandemic led to reduced services of private dental practices. The public emergency clinic of Rutgers School of Dental Medicine (RSDM) (Newark, NJ) faced changing demands during various periods of the pandemic. METHODS: Records of patients visiting the emergency clinic at RSDM during 3 distinct periods (prelockdown, lockdown, teledentistry) from January 10, 2020, through June 30, 2020, were retrospectively reviewed. Qualitative and quantitative attributes pertaining to patient encounters were reviewed and analyzed. RESULTS: A total of 1,799 records were included in this study. Patient visits increased during the early lockdown but were reduced after the implementation of teledentistry. Trends were noted in patient volume, reasons for visits, treatment needs, symptoms, diagnostic methodology, prescription use, and final disposition of patients. CONCLUSIONS: The lockdown affected emergency dental clinic services at RSDM. Teledentistry visits played a key role in screening patients and in facilitating the delivery of oral health care and timely follow-ups to patients who needed urgent in-person emergency visits. PRACTICAL IMPLICATIONS: Data gathered will lead to a better understanding of patients seen in the emergency clinic and can help with long-term planning for both institutional and smaller outpatient clinics during public health emergencies.

Overlapping syndrome of recurrent anti-N-methyl-D-aspartate receptor encephalitis and anti-myelin oligodendrocyte glycoprotein demyelinating diseases: A case report.

BACKGROUND: Anti-N-methyl-D-aspartate receptor encephalitis (NMDARe) is capable of presenting a relapsing course and coexisting with myelin oligodendrocyte glycoprotein antibody disease, whereas it has been relatively rare. We describe a man with no history of tumor who successively developed anti-NMDARe and anti-myelin oligodendrocyte glycoprotein antibody disease. CASE SUMMARY: A 29-year-old man was initially admitted with headache, fever, intermittent abnormal behavior, decreased intelligence, limb twitching and loss of consciousness on July 16, 2018. On admission, examination reported no abnormality. During his presentation, he experienced aggravated symptoms, and the re-examination of cranial magnetic resonance imaging (MRI) indicated punctate abnormal signals in the left parietal lobe. External examination of cerebrospinal fluid and serum results revealed serum NMDAR antibody (Ab) (-), cerebrospinal fluid NMDAR-Ab (+) 1:10 and Epstein-Barr virus capsid antigen antibody IgG (+). Due to the imaging findings, anti-NMDARe was our primary consideration. The patient was treated with methylprednisolone and gamma globulin pulse therapy, mannitol injection dehydration to reduce intracranial pressure, sodium valproate sustained-release tablets for anti-epilepsy and olanzapine and risperidone to mitigate psychiatric symptoms. The patient was admitted to the hospital for the second time for "abnormal mental behavior and increased limb movements" on December 14, 2018. Re-examination of electroencephalography and cranial MRI showed no abnormality. The results of autoimmune encephalitis antibody revealed that serum NMDAR-Ab was weakly positive and cerebrospinal fluid NMDAR-Ab was positive. Considering comprehensive recurrent anti-NMDARe, the patient was treated with propylene-hormone pulse combined with immunosuppressive agents (mycophenolate mofetil), and the symptoms were relieved. The patient was admitted for "hoarseness and double vision" for the third time on August 23, 2019. Re-examination of cranial MRI showed abnormal signals in the medulla oblongata and right frontal lobe, and synoptophore examination indicated concomitant esotropia. The patient's visual acuity further decreased, and the re-examination of cranial MRI + enhancement reported multiple scattered speckled and patchy abnormal signals in the medulla oblongata, left pons arm, left cerebellum and right midbrain, thalamus. The patient was diagnosed with an accompanying demyelinating disease. Serum anti-myelin oligodendrocyte glycoprotein 1:10 and NMDAR antibody 1:10 were both positive. The patient was diagnosed with myelin oligodendrocyte glycoprotein antibody-related inflammatory demyelinating disease of the central nervous system complicated with anti-NMDARe overlap syndrome. The patient was successfully treated with methylprednisolone, gamma globulin pulse therapy and rituximab treatment. The patient remained asymptomatic and follow-up MRI scan 6 mo later showed complete removal of the lesion. CONCLUSION: We emphasize the rarity of this antibody combination and suggest that these patients may require longer follow-up due to the risk of recurrence of two autoimmune disorders.

Application of additive manufacturing in customized titanium mandibular implants for patients with oral tumors.

The application of additive manufacturing (AM) technology has been widely used in various medical fields, including craniomaxillofacial surgery. The aim of the present study was to examine the surgical efficiency and post-operative outcomes of patient-specific titanium mandibular reconstruction using AM. Major steps in directly designing and manufacturing 3D customized titanium implants are discussed. Furthermore, pre-operative preparations, surgical procedures and post-operative treatment outcomes were compared among patients who received mandibular reconstruction using a customized 3D titanium implant, titanium reconstruction plates or vascularized autologous fibular grafting. Use of a customized titanium implant significantly improved surgical efficiency and precision. When compared with mandibular reconstruction using the two conventional approaches, patients who received the customized implant were significantly more satisfied with their facial appearance, and exhibited minimal post-operative complications in the 12-month follow-up period. Patients who underwent mandibular reconstruction using a customized titanium implant displayed improved mandibular contour symmetry, restored occlusal function, normal range of mouth opening and no temporomandibular joint related pain; all complications frequently experienced by patients who undergo conventional approaches of mandibular reconstruction.

Salmonella-Mediated Cancer Therapy: An Innovative Therapeutic Strategy.

Bacterial-mediated cancer therapy (BMCT) has become a hot topic in the area of antitumor treatment. Salmonella has been recommended to specifically colonize and proliferate inside tumors and even inhibit tumor growth. Salmonella typhimurium (S. typhimurium) is one of the most promising mediators, which can be easily manipulated. S. typhimurium has been engineered and designed as cancer-targeting therapeutics, and can be improved by combining with other therapeutic methods, e.g. chemotherapy and radiotherapy, which regulate the tumor microenvironment synergistically. In view of all these strengths, the engineered attenuated strains have significant advantages for tumor diagnosis and treatment. This treatment has also been approved by the FDA for clinical trial. In this review, we summarized the recent progress and research in the field of Salmonella -mediated cancer therapy.

Long-term c-Kit overexpression in beta cells compromises their function in ageing mice.

AIMS/HYPOTHESIS: c-Kit signalling regulates intracellular pathways that enhance beta cell proliferation, insulin secretion and islet vascularisation in mice up to 28 weeks of age and on short-term high-fat diet. However, long-term c-Kit activation in ageing mouse islets has yet to be examined. This study utilises beta cell-specific c-Kit-overexpressing transgenic (c-KitßTg) ageing mice (~60 weeks) to determine the effect of its activation on beta cell dysfunction and insulin secretion. METHODS: Wild-type and c-KitßTg mice, aged 60 weeks, were examined using metabolic tests to determine glucose tolerance and insulin secretion. Pancreas histology and proteins in isolated islets were examined to determine the expression of beta cell transcription factors, proliferation and intracellular signalling. To determine the role of insulin receptor signalling in ageing c-KitßTg mice, we generated beta cell-specific inducible insulin receptor knockout in ageing c-KitßTg mice (c-KitßTg;ßIRKO mice) and examined the ageing mice for glucose tolerance and islet histology. RESULTS: Ageing c-KitßTg mice progressively developed glucose intolerance, compared with age-matched wild-type littermates, due to impaired insulin secretion. Increased beta cell mass, proliferation and nuclear forkhead box transcription factor O1 (FOXO1) expression and reduced exocytotic protein levels were detected in ageing c-KitßTg mouse islets. Protein analyses of isolated islets showed increased insulin receptor, phosphorylated IRS-1Ser612 and cleaved poly(ADP-ribose) polymerase levels in ageing c-KitßTg mice. Ageing c-KitßTg mouse islets treated ex vivo with insulin demonstrated reduced Akt phosphorylation, indicating that prolonged c-Kit induced beta cell insulin insensitivity. Ageing c-KitßTg;ßIRKO mice displayed improved glucose tolerance and beta cell function compared with ageing c-KitßTg mice. CONCLUSIONS/INTERPRETATION: These findings indicate that long-term c-Kit overexpression in beta cells has a negative impact on insulin exocytosis and that temporally dependent regulation of c-Kit-insulin receptor signalling is important for optimal beta cell function.

Increased serum malondialdehyde levels are associated with grey matter volume loss in patients with non-alcoholic cirrhosis.

BACKGROUND: Grey matter volume (GMV) loss has been observed in patients with non-alcoholic cirrhosis, but the underlying mechanisms are unknown. Oxidative stress (OS) is a recognized feature and systemic phenomenon of cirrhosis. However, little is known about whether OS is associated with GMV loss in cirrhosis. This study aimed to assess the relationship between oxidative damage and GMV loss in patients with non-alcoholic cirrhosis. METHODS: Thirty-four patients with non-alcoholic cirrhosis and 27 age- and sex-matched healthy controls were enrolled in this prospective study. All subjects underwent brain magnetic resonance imaging (MRI), and voxel-based morphometry (VBM) was performed to assess normalized global GMV. As an OS marker, serum malondialdehyde (MDA) levels were determined in all subjects. In the patient group, a correlation analysis was used to investigate the relationship between serum MDA levels and normalized global GMV. RESULTS: Compared with healthy controls, cirrhotic patients displayed a significant decrease in normalized global GMV and a significant increase in serum MDA levels. In the patient group, serum MDA levels were negatively correlated with normalized global GMV adjusted for age, sex and Child-Pugh class. CONCLUSIONS: Increased serum MDA levels were associated with GMV loss in patients with non-alcoholic cirrhosis, suggesting that oxidative damage may be involved in GMV loss observed in cirrhotic patients.

Critical role of ß1 integrin in postnatal beta-cell function and expansion.

ß1 integrin is essential for pancreatic beta-cell development and maintenance in rodents and humans. However, the effects of a temporal beta-cell specific ß1 integrin knockout on adult islet function are unknown. We utilized a mouse insulin 1 promoter driven tamoxifen-inducible Cre-recombinase ß1 integrin knockout mouse model (MIPß1KO) to investigate ß1 integrin function in adult pancreatic beta-cells. Adult male MIPß1KO mice were significantly glucose intolerant due to impaired glucose-stimulated insulin secretion in vivo and ex vivo at 8 weeks post-tamoxifen. The expression of Insulin and Pancreatic and duodenal homeobox-1 mRNA was significantly reduced in MIPß1KO islets, along with reductions in insulin exocytotic proteins. Morphological analyses demonstrated that beta-cell mass, islet density, and the number of large-sized islets was significantly reduced in male MIPß1KO mice. Significant reductions in the phosphorylation of signaling molecules focal adhesion kinase, extracellular signal-regulated kinases 1 and 2, and v-Akt murine thymoma viral oncogene were observed in male MIPß1KO islets when compared to controls. MIPß1KO islets displayed a significant increase in protein levels of the apoptotic marker cleaved-Poly (ADP-ribose) polymerase and a reduction of the cell cycle marker cyclin D1. Female MIPß1KO mice did not develop glucose intolerance or reduced beta-cell mass until 16 weeks post-tamoxifen. Glucose intolerance remained in both genders of aged MIPß1KO mice. This data demonstrates that ß1 integrin is required for the maintenance of glucose homeostasis through postnatal beta-cell function and expansion.

c-Kit Receptor Signaling Regulates Islet Vasculature, ß-Cell Survival, and Function In Vivo.

The receptor tyrosine kinase c-Kit plays an integral role in maintaining ß-cell mass and function. Although c-Kit receptor signaling promotes angiogenesis in multiple cell types, its role in islet vasculature is unknown. This study examines the effects of c-Kit-mediated vascular endothelial growth factor isoform A (VEGF-A) and islet vascularization on ß-cell function and survival using in vitro cell culture and in vivo mouse models. In cultured INS-1 cells and primary islets, c-Kit regulates VEGF-A expression via the Akt/mammalian target of rapamycin (mTOR) signaling pathway. Juvenile mice with mutated c-Kit (c-Kit(Wv/+)) showed impaired islet vasculature and ß-cell dysfunction, while restoring c-Kit expression in ß-cells of c-Kit(Wv/+) mice rescued islet vascular defects through modulation of the Akt/mTOR/VEGF-A pathway, indicating that c-Kit signaling in ß-cells is a required regulator for maintaining normal islet vasculature. Furthermore, ß-cell-specific c-Kit overexpression (c-KitßTg) in aged mice showed significantly increased islet vasculature and ß-cell function, but, when exposed to a long-term high-fat diet, c-Kit signaling in c-KitßTg mice induced substantial vascular remodeling, which resulted in increased islet inflammatory responses and ß-cell apoptosis. These results suggest that c-Kit-mediated VEGF-A action in ß-cells plays a pivotal role in maintaining islet vascularization and function.

A survival Kit for pancreatic beta cells: stem cell factor and c-Kit receptor tyrosine kinase.

The interactions between c-Kit and its ligand, stem cell factor (SCF), play an important role in haematopoiesis, pigmentation and gametogenesis. c-Kit is also found in the pancreas, and recent studies have revealed that c-Kit marks a subpopulation of highly proliferative pancreatic endocrine cells that may harbour islet precursors. c-Kit governs and maintains pancreatic endocrine cell maturation and function via multiple signalling pathways. In this review we address the importance of c-Kit signalling within the pancreas, including its profound role in islet morphogenesis, islet vascularisation, and beta cell survival and function. We also discuss the impact of c-Kit signalling in pancreatic disease and the use of c-Kit as a potential target for the development of cell-based and novel drug therapies in the treatment of diabetes.

A fusion protein derived from plants holds promising potential as a new oral therapy for type 2 diabetes.

The incretin hormone glucagon-like peptide-1 (GLP-1) is recognized as a promising candidate for the treatment of type 2 diabetes (T2D), with one of its mimetics, exenatide (synthetic exendin-4) having already been licensed for clinical use. We seek to further improve the therapeutic efficacy of exendin-4 (Ex-4) using innovative fusion protein technology. Here, we report the production in plants a fusion protein containing Ex-4 coupled with human transferrin (Ex-4-Tf) and its characterization. We demonstrated that plant-made Ex-4-Tf retained the activity of both proteins. In particular, the fusion protein stimulated insulin release from pancreatic ß-cells, promoted ß-cell proliferation, stimulated differentiation of pancreatic precursor cells into insulin-producing cells, retained the ability to internalize into human intestinal cells and resisted stomach acid and proteolytic enzymes. Importantly, oral administration of partially purified Ex-4-Tf significantly improved glucose tolerance, whereas commercial Ex-4 administered by the same oral route failed to show any significant improvement in glucose tolerance in mice. Furthermore, intraperitoneal (IP) injection of Ex-4-Tf showed a beneficial effect in mice similar to IP-injected Ex-4. We also showed that plants provide a robust system for the expression of Ex-4-Tf, producing up to 37 µg prEx-4-Tf/g fresh leaf weight in transgenic tobacco and 137 µg prEx-4-Tf/g freshweight in transiently transformed leaves of N. benthamiana. These results indicate that Ex-4-Tf holds substantial promise as a new oral therapy for type 2 diabetes. The production of prEx-4-Tf in plants may offer a convenient and cost-effective method to deliver the antidiabetic medicine in partially processed plant food products.

Downregulation of Fas activity rescues early onset of diabetes in c-Kit(Wv/+) mice.

c-Kit and its ligand stem cell factor (SCF) are important for ß-cell survival and maturation; meanwhile, interactions between the Fas receptor (Fas) and Fas ligand are capable of triggering ß-cell apoptosis. Disruption of c-Kit signaling leads to severe loss of ß-cell mass and function with upregulation of Fas expression in c-Kit(Wv/+) mouse islets, suggesting that there is a critical balance between c-Kit and Fas activation in ß-cells. In the present study, we investigated the interrelationship between c-Kit and Fas activation that mediates ß-cell survival and function. We generated double mutant, c-Kit(Wv/+);Fas(lpr/lpr) (Wv(-/-)), mice to study the physiological and functional role of Fas with respect to ß-cell function in c-Kit(Wv/+) mice. Isolated islets from these mice and the INS-1 cell line were used. We observed that islets in c-Kit(Wv/+) mice showed a significant increase in ß-cell apoptosis along with upregulated p53 and Fas expression. These results were verified in vitro in INS-1 cells treated with SCF or c-Kit siRNA combined with a p53 inhibitor and Fas siRNA. In vivo, Wv(-/-) mice displayed improved ß-cell function, with significantly enhanced insulin secretion and increased ß-cell mass and proliferation compared with Wv(+/+) mice. This improvement was associated with downregulation of the Fas-mediated caspase-dependent apoptotic pathway and upregulation of the cFlip/NF-κB pathway. These findings demonstrate that a balance between the c-Kit and Fas signaling pathways is critical in the regulation of ß-cell survival and function.

Inhibition of Gsk3ß activity improves ß-cell function in c-KitWv/+ male mice.

Previous studies have shown that the stem cell marker, c-Kit, is involved in glucose homeostasis. We recently reported that c-Kit(Wv/+) male mice displayed the onset of diabetes at 8 weeks of age; however, the mechanisms by which c-Kit regulates ß-cell proliferation and function are unknown. The purpose of this study is to examine if c-Kit(Wv/+) mutation-induced ß-cell dysfunction is associated with downregulation of the phospho-Akt/Gsk3ß pathway in c-Kit(Wv/+) male mice. Histology and cell signaling were examined in C57BL/6J/Kit(Wv/+) (c-Kit(Wv/+)) and wild-type (c-Kit(+/+)) mice using immunofluorescence and western blotting approaches. The Gsk3ß inhibitor, 1-azakenpaullone (1-AKP), was administered to c-Kit(Wv/+) and c-Kit(+/+) mice for 2 weeks, whereby alterations in glucose metabolism were examined and morphometric analyses were performed. A significant reduction in phosphorylated Akt was observed in the islets of c-Kit(Wv/+) mice (P<0.05) along with a decrease in phosphorylated Gsk3ß (P<0.05), and cyclin D1 protein level (P<0.01) when compared with c-Kit(+/+) mice. However, c-Kit(Wv/+) mice that received 1-AKP treatment demonstrated normal fasting blood glucose with significantly improved glucose tolerance. 1-AKP-treated c-Kit(Wv/+) mice also showed increased ß-catenin, cyclin D1 and Pdx-1 levels in islets, demonstrating that inhibition of Gsk3ß activity led to increased ß-cell proliferation and insulin secretion. These data suggest that c-Kit(Wv/+) male mice had alterations in the Akt/Gsk3ß signaling pathway, which lead to ß-cell dysfunction by decreasing Pdx-1 and cyclin D1 levels. Inhibition of Gsk3ß could prevent the onset of diabetes by improving glucose tolerance and ß-cell function.