Background: Hantavirus cardiopulmonary syndrome (HCPS) has a high lethality. About two-thirds of the severe cases may be rescued by extracorporeal membrane oxygenation (ECMO). However, about half of the patients supported by ECMO suffer major complications. High volume hemofiltration (HVHF) is a depurative extracorporeal support that provides homeostatic balance allowing hemodynamic stabilization in some critically ill patients. Methods: We implemented HVHF prior to ECMO consideration in the last five severe HCPS patients requiring mechanical ventilation and vasoactive drugs admitted to our intensive care unit. Patients were considered HVHF-responders if ECMO was avoided and nonresponders if ECMO support was needed. Results: The first two patients required ECMO, while the last three did not. Patients had a maximum serum lactate of 8.4 [4.3-14] mMol/L and a lowest cardiac index of 1.76 [1.45-2.9] L/min/m2. Nonresponders were connected later to HVHF, displayed progressive tachycardia and decreasing stroke volume. The opposite was true for HVHF-responders who also received targeted-HVHF compounded by aggressive hyperoncotic albumin, sodium bicarbonate and calcium supplementation plus ultrafiltration to avoid fluid overload. All patients survived, but one of the ECMO patients suffered a vascular complication. Conclusion: HVHF may contribute to support severe HCPS patients avoiding the need for ECMO in some of them. Early connection and targeted-HVHF may increase the chance of success.

In metastatic pancreatic cancer patients non eligible to surgery, signal-targeted therapies so far failed to show a significant amelioration of survival. These therapeutic options were tested in Phase II/III clinical trials mostly in combination with the reference treatment Gemcitabine. These innovative therapies aim at annihilating the oncogene dependency; they also aim at renormalizing the tumoral stroma to allow immune cell function or re-vascularisation. Transcriptomics and genomics large scale analysis show the great heterogeneity of pancreatic cancers and failed to clearly delineate specific oncogene dependency besides oncogenic Kras. In this review, we will describe the most recent proteomic data in pancreatic tumors and its metastasis, which could help at identifying their major signalling dependencies, as well as explain why they are intrinsically resistant to signal-targeted therapies. We will also discuss why PI3K signalling, as a paradigm of pro-tumorigenic cell signalling and of tumoral adaptative resistance to drugs, is a relevant target in this context.

In metastatic pancreatic cancer patients non eligible to surgery, signal-targeted therapies so far failed to show a significant amelioration of survival. These therapeutic options were tested in Phase II/III clinical trials mostly in combination with the reference treatment Gemcitabine. These innovative therapies aim at annihilating the oncogene dependency; they also aim at renormalizing the tumoral stroma to allow immune cell function or re-vascularisation. Transcriptomics and genomics large scale analysis show the great heterogeneity of pancreatic cancers and failed to clearly delineate specific oncogene dependency besides oncogenic Kras. In this review, we will describe the most recent proteomic data in pancreatic tumors and its metastasis, which could help at identifying their major signalling dependencies, as well as explain why they are intrinsically resistant to signal-targeted therapies. We will also discuss why PI3K signalling, as a paradigm of pro-tumorigenic cell signalling and of tumoral adaptative resistance to drugs, is a relevant target in this context.

It has been declared repeatedly that cancer is a result of molecular genetic abnormalities. However, there has been no working model describing the specific functional consequences of the deranged genomic processes that result in the initiation and propagation of the cancer process during carcinogenesis. We no longer need to question whether or not cancer arises as a result of a molecular genetic defect within the cancer cell. The legitimate questions are: how and why? This article reviews the preeminent data on cancer molecular genetics and subsequently proposes that the sentinel event in cancer initiation is the aberrant production of fused transcription activators with new molecular properties within normal tissue stem cells. This results in the production of vital oncogenes with dysfunctional gene activation transcription properties, which leads to dysfunctional gene regulation, the aberrant activation of transduction pathways, chromosomal breakage, activation of driver oncogenes, reactivation of stem cell transduction pathways and the activation of genes that result in the hallmarks of cancer. Furthermore, a novel holistic molecular genetic model of cancer initiation and progression is presented along with a new paradigm for the approach to personalized targeted cancer therapy, clinical monitoring and cancer diagnosis.

Clofazimine and Arbidol have both been reported to be effective in vitro SARS-CoV-2 fusion inhibitors. Both are promising drugs repurposed for treatment of COVID-19 and have been used in several previous and ongoing clinical trials. Small-molecule binding to expressed constructs of the trimeric S2 segment of Spike and the full-length SARS-CoV-2 spike protein were measured using a Surface Plasmon Resonance (SPR) binding assay. We demonstrate that Clofazimine, Toremifene, Arbidol and other Arbidol derivatives bind to the S2 segment of the Spike protein. Clofazimine provided the most reliable and highest quality SPR binding data to S2 over the conditions explored. A molecular docking approach was used to identify the most favorable binding sites on the S2 segment in the prefusion conformation, highlighting two possible small-molecule binding sites for fusion inhibitors. Results from molecular docking and modeling the structure-activity-relationship (SAR) of a newly reported series of Clofazimine derivatives supports the proposed Clofazimine binding site on the S2 segment. When the proposed Clofazimine binding site is superimposed with other experimentally determined coronavirus structures in structure-sequence alignments, the changes in sequence and structure may rationalize the broad-spectrum antiviral activity of Clofazimine in closely related coronavirus such as (SARS-CoV, MERS, hCoV-229E, hCoV-OC43).

Ischemic stroke is one of the leading causes of death and permanent disability in the world. Rapid diagnosis and intervention are crucial for reducing its consequences on individuals and societies. Identifying reliable biomarkers for early detection, prognostics and therapy is a criti-cal imperative for improving the stroke patient treatment. Metabolomics has been shown as a promising tool for biomarker discovery since many of the post-ischemic metabolites can found in the plasma or serum of the patient. In this research, we have performed comparative targeted metabolomic analysis of stroke thrombi, patient serums and healthy control serums in order to determine the alteration in the patients’ metabolome. The most statistically altered metabolites characterized in patient compared to control serums were glutamate and serotonin, followed by several lipid metabolites (phospholipids and triacylglycerols) and glucose. In stroke thrombi compared to patient’s serums, the most significantly altered metabolites were classified as li-pids, with choline-containing phospholipids and sphingomyelins having the highest discrimi-natory score. The results of this study could help in understanding the roles of different meta-bolic changes occurring during thrombosis and cerebral ischemia and possibly suggest new metabolic biomarkers of the ischemic stroke.

Chicken collagen is a promising raw material source to produce gelatins and hydrolysates. Gelatins and hydrolysates can be prepared biotechnologically using proteolytic enzymes produced by submerged fermentation of genetically modified microorganisms. By choosing the appropriate process conditions, such changes can be achieved at the molecular level of collagen, making it possible to prepare products with targeted properties for advanced cosmetic, pharmaceutical, medical or food applications. The research aims to investigate: i) antioxidant activity (DPPH and ABTS) in model samples of chicken collagen products (gelatin and hydrolysates); ii) distribution of molecular weights by the GPC-RID analysis method; iii) functional groups and configuration of polypeptide chains related to molecular level properties using FTIR; iv) the microbiological properties on SDA, PCA, TSA and VRBL microbial populations using MALDI method. Antioxidant activity towards ABTS radicals of more than 80% was found for all samples. The molecular weights of all gelatin samples showed typical α- and β-chains. FTIR analysis confirmed that the samples showed all typical vibrational regions for collagen cleavage products, Amide A and B, Amide I, II, and III at characteristic values. Microbiological analysis of the prepared samples showed no undesirable bacteria that would limit advanced applications of the prepared products. Gelatins and hydrolysates from chicken stomachs represent a promising alternative to products made from standard collagen tissues of terrestrial animals.

Background: Prostate cancer is a global health concern, necessitating ongoing research to enhance our comprehension of its molecular foundations and develop more efficacious therapeutic approaches. Among the emerging protagonists in this arena is Speckle-type POZ (pox virus and zinc finger protein) (SPOP), an E3 ubiquitin ligase substrate adaptor protein. SPOP's recent ascent to prominence in prostate cancer research is attributed to its crucial role in regulating the Androgen Receptor (AR) signaling pathway. This systematic review aims to provide a comprehensive synthesis of existing knowledge concerning SPOP mutations in prostate cancer. It seeks to elucidate their significance in characterizing the disease and their potential as therapeutic targets. Methods: A systematic literature search was conducted in multiple databases, including PubMed, Web of science, Scopus and google scholar to identify relevant studies published up to September 2023. Eligible studies included investigations of SPOP mutations in prostate cancer and their implications. Data extraction, quality assessment, and synthesis were performed in conformity to the PRISMA guidelines. Results: The review revealed that SPOP mutations are recurrent events in prostate cancer, with a notable prevalence in specific molecular subtypes. These mutations primarily affect the MATH domain of SPOP, disrupting its substrate recognition function. Notably, SPOP mutations have profound consequences on the AR signaling pathway, leading to increased AR protein stability and transcriptional activity. The clinical implications of SPOP mutations remain diverse, with varying associations with prognostic outcomes. Conclusion: SPOP mutations represent a significant facet of prostate cancer biology, influencing disease heterogeneity and clinical behavior. While their precise prognostic significance is evolving, their functional impact on the AR pathway highlights their potential as therapeutic targets. This systematic review provides a comprehensive overview of SPOP mutations in prostate cancer, contributing to our understanding of the disease's molecular landscape and therapeutic avenues.

Background: Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of death by cancer worldwide. Mostly diagnosed with locally advanced or metastatic disease, patients lack treatment options. Gene alterations (GAs) are frequently observed in PDAC; some of which are considered for molecular targeted therapies (MTTs), with potential clinical benefits and im-proved outcomes. However, the applicability of molecular profiling (MP) for precision medicine in PDAC remains to be demonstrated. Methods: We conducted a retrospective analysis of all patients, aged ≥18 years with histologi-cally confirmed PDAC, who underwent tumor MP between 2010 and 2020 in our institution as part of personalized medicine trials. The primary study endpoint was overall survival (OS), and (minimal follow-up was 6 months after MP. Results: Of 115 eligible patients, MP was successful in 102 patients (89%). KRAS mutations were the most frequent GAs, mostly G12D. Based on ESCAT classification, actionable GAs were found in 29 patients (28%), involving mainly BRCA1 or BRCA2 (5 [18%]), HER2 (5 [18%]), MTAP (5 [18%]), and FGFR (3 [11%]). Only 12 of these 29 patients (41%, or 10% of the whole population) received MTTs, with a median progression-free survival of 1.6 months. Median OS was 19 months in patients with actionable GAs treated with MTTs (n=12 [11.8%]), 14 months in patients with actionable GAs treated with standard therapies (n=17 [16.7%]), and 17 months in patients without actionable GAs treated with standard therapies (n=73 [71.5%]; p=0.26). The absence of liver metastases was associated with better OS (HR=0.471, p=0.01). The highest OS following MTT was observed in patients with BRCA mutations treated with olaparib. Interpretation: Actionable GAs were found in more than a quarter of patients with advanced PDAC. Overall, targeting actionable GAs with MTTs was not associated with improved OS in this retrospective study with limited patient numbers. However, selected GA/MTT combinations (e.g., BRCA mutations/olaparib) were associated with a better outcome.

An elevated level of endoplasmic reticulum (ER) stress is considered an aggravating factor for inflammatory bowel disease (IBD). To develop an ER stress attenuator that is effective against colitis, 4-phenylbutyric acid (4-PBA), a chemical chaperone that alleviates ER stress, was conjugated with acidic amino acids to yield a 4-PBA-glutamic acid conjugate (PBA-GA) and a 4-PBA-aspartic acid conjugate (PBA-AA). The PBA derivatives were converted to 4-PBA in the cecal contents, where the conversion was greater with PBA-GA. After oral administration of PBA-GA (oral PBA-GA), millimolar levels of PBA were accumulated in the cecum, whereas 4-PBA was not detected in the blood, indicating the targeting of PBA-GA to the large intestine. At concentrations in the cecum achievable by oral PBA-GA, 4-PBA effectively attenuated ER stress in human colon epithelial cells. In 2,4-dinitrobenzenesulfonic acid-induced colitis in rats, oral PBA-GA alleviated the damage and inflammation in the colon. Moreover, oral PBA-GA substantially reduced the elevated levels of ER stress marker proteins in the inflamed colon. Moreover, PBA-GA was as effective as the currently used anti-IBD drug, sulfasalazine. In conclusion, PBA-GA is a colon-targeted prodrug of 4-PBA and is effective against rat colitis probably through the attenuation of ER stress in the inflamed colon.

Wilms tumor (WT), the most prevalent type of renal cancer in children, exhibits overall survival rates exceeding 90%. However, chemotherapy resistance, which occurs in approximately 10% of WT cases, is a major challenge for the treatment of WT, particularly for advanced-stage patients. In this study, we aimed to discover potential mutation markers and drug targets associated with chemotherapy resistance in advanced stage WT. We performed exome sequencing to detect somatic mutations and molecular targets in 43 WT samples, comprising 26 advanced stage WTs, of which 7 cases are chemotherapy-resistant. Our analysis revealed four genes (ALPK2, C16orf96, PRKDC, and SVIL) that correlated with chemotherapy resistance and reduced disease-free survival in ad-vanced-stage WT. Additionally, we identified driver mutations in 55 genes within the chemo-therapy-resistant group, including 14 druggable cancer driver genes. Based on the mutation profile of the resistant WT samples, we propose potential therapeutic strategies involving platinum-based agents, PARP inhibitors, and antibiotic/antineoplastic agents. Our findings provide insights into the genetic landscape of WT and offer potential avenues for targeted treatment, particularly for patients with chemotherapy resistance.

Excess hepatic lipid accumulation is the hallmark of non-alcoholic fatty liver disease (NAFLD), for which no medication is currently approved. However, Glucagon-Like Peptide-1 Receptor Ag-onists (GLP-1RAs), already approved for treating type 2 diabetes, have lately emerged as possible treatments. Herein we aimed to investigate how the GLP-1RA Exendin-4 (Ex-4) affects the mi-croRNA (miRNAs) expression profile using an in vitro model of steatosis. Total RNA, including miRNAs, was isolated from untreated, steatotic, and Ex-4-treated steatotic cells and used for probing a panel of 799 highly curated miRNAs using NanoString technology. Enrichment path-way analysis was used to find the signaling pathways and cellular functions associated with the differentially expressed miRNAs. Our data shows that Ex-4 reversed the expression of a set of miRNAs. Functional enrichment analysis highlighted many relevant signaling pathways and cellular functions enriched in the differentially expressed miRNAs, including hepatic fibrosis, in-sulin receptor, PPAR, Wnt/β-Catenin, VEGF, and mTOR receptor signaling pathways, fibrosis of the liver, cirrhosis of the liver, proliferation of hepatic stellate cells, diabetes mellitus, glucose metabolism disorder and proliferation of liver cells. Our findings suggest that miRNAs may play essential roles in the processes driving steatosis reduction in response to GLP-1R agonists, which warrants further functional investigations.

Incidence of COVID-19 has been associated with sociodemographic factors. We investigated variations in SARS-CoV-2 seroprevalence at sub-national levels in the Dominican Republic and assessed potential factors influencing variation in regional-level seroprevalence. Data were collected in a three-stage cross-sectional national serosurvey from June to October 2021. Seroprevalence of antibodies against the SARS-CoV-2 spike protein (anti-S) was estimated and adjusted for selection probability, age, and sex. Multilevel logistic regression was used to estimate the effect of covariates on seropositivity for anti-S and correlates of 80% protection (PT80) against symptomatic infection for ancestral and Delta strains. A total of 6,683 participants from 134 clusters in all 10 regions were enrolled. Anti-S, PT80 for ancestral and Delta strains odds ratio varied across regions, Enriquillo presented significant higher odds for all outcomes compared with Yuma. Compared to unvaccinated, receiving ≥2doses of COVID-19 vaccine was associated with a significantly higher odds of anti-S positivity (OR 85.94, [10.95-674.33]), and PT80 for ancestral (OR 4.78, [2.15-10.62]) and Delta strains (OR 3.08, [1.57-9.65]) nationally, and also for each region. Our results can help inform regional-level public health response, such as strategies to increase vaccination coverage in areas with low population immunity against currently circulating strains.

As an important organelle in eukaryotic cells, Golgi apparatus is responsible for processing and transporting proteins and lipids in cells. Precise monitoring the status of Golgi apparatus by targeting fluorescence imaging technology is of enormous importance but remains an attractive yet dramatically challenging task. In this study, we report the construction of the first Golgi apparatus targeted sensor with bright near-infrared fluorescence, termed as Golgi-Pdots. As a start point of our investigation, hydrophobic CDs with bright NIR fluorescence at 674 nm (fluorescence quantum yield : 12.18%), narrow emission band of 23 nm, and excellent stability were facilely prepared from Magnolia Denudata flowers through an ultrasonic method. Incorporating the CDs into a polymer matrix modified with Golgi-targeting molecules can produce the water-soluble Golgi-Pdots, which showed high colloidal stability and similar optical properties as compared to CDs. Further studies revealed that the Golgi-Pdots showed good biocompatibility and Golgi-targeting ability. Based on these fascinating properties, Golgi-Pdots have been successfully used for long term bioimaging of Golgi apparatus inside live cells.

Current methodologies for developing patient-derived xenografts (PDX) in humanized mice in preclinical trials to test response to immune-based therapies are limited by graft versus host disease. Here we compared two approaches for establishing PDX tumors in humanized mice: 1) PDX are first established in immune-deficient mice; 2) PDX are initially established in humanized mice, before transplanting established PDX’s to a larger cohort of humanized mice for preclinical trials. With the first approach, there was rapid wasting of PDX-bearing humanized mice with high levels of activated T cells in the circulation and organs, indicating immune-mediated toxicity. In contrast, with the second approach, toxicity was less of an issue and long-term human melanoma tumor growth and maintenance of human chimerism was achieved. Pre-clinical trials from the second approach revealed that rigosertib, but not anti-PD-1, increased CD8/CD4 T cell ratios in spleen and blood and inhibited PDX tumor growth. Resistance to anti-PD-1 was associated with limited infiltration of CD8+ T cell into the tumor. Our findings suggest that it is essential to carefully manage immune editing by first establishing PDX tumors in the presence of human immune cells before expanding PDX tumors into a larger cohort of humanized mice to evaluate therapy response.

Background: Newer personalized medicine including targeted therapies such as PARP inhibitors and CDK 4/6 inhibitors have shown to improve survival of breast and gynaecological cancer patients. However, efficacy outcomes may be hampered by treatment discontinuation due to targeted therapy-related adverse drug reactions or resistance. Studies suggest that add-on mistletoe (Viscum album L., VA) improves quality of life and ameliorates cytotoxic side effects of standard oncological therapy in cancer patients. The primary objective of this real-world data study was to determine the safety profile of targeted therapy in combination with add-on Helixor® VA therapy in breast and gynecological cancer patients. Methods: The present study is a real-world data study utilizing demographic and treatment data from the accredited national Network Oncology (NO) registry. The study has received ethics approval. The safety profile of targeted with or without Helixor® VA therapy as well as safety - associated variables were evaluated by univariate and adjusted multivariable regression analyses. Results: All stage breast or gynecological cancer patients (n = 242) were on average 54.5±14.2 years old. One hundred and sixty patients (66.1%) were in the control (CTRL, targeted therapy) and 82 patients (33.9%) in the combinational (COMB, targeted plus Helixor® VA therapy) group. The addition of Helixor® VA did not hamper the safety profile (χ2 = 0.107, p-value = 0.99) of targeted therapy. Furthermore, no adverse events and a trend towards an improved targeted therapy adherence were observed in the COMB group. Conclusions: The present study is the first of its kind showing the applicability of Helixor® VA in combination with targeted therapies. The results indicate that add-on Helixor® VA does not negatively alter the safety profile of targeted therapies in breast and gynaecological cancer patients.

The Ministry of Health (MOH) in the Kingdom of Saudi Arabia (KSA) established a National School-based Screening Program (NSBSP) for health screening of school-going children. Students from specific grades were systematically screened for several health problems including obesity, visual and auditory problems, dental cavities, scoliosis, and attention-deficit/hyperactivity disorder (ADHD). This cross-sectional study aimed to determine the prevalence of these health problems among primary school students based on secondary data obtained from the NSBSP. We included 444,259 screened school children from the 1st and 4th grades of 50% of the selected schools (both private and public) across the KSA during the academic year 2018-2019. Among them, the most prevalent health problems identified were dental cavities (38.7%), eye refractory errors (10.9%), and overweight and obesity (10.5%); the less prevalent problems included ADHD (2.81%), auditory problems (0.6%), and scoliosis (0.48%). A greater prevalence of most health problems was observed in girls than boys. The NSBSP successfully aided the detection of health conditions with high and low prevalence among primary school students in the KSA, and thus, identification of health problems of specific concern. Implementation of effective school health services for the prevention, early detection, diagnosis, and treatment of these health problems is imperative.

Abstract Background: Periodontitis is associated with systemic chronic inflammatory diseases. There is limited evidence on the influence of anti-cytokine therapies on the periodontal condition and microbiome in the tooth pocket of such patients, so the aim of this study was to elucidate this issue. Methods: In this observational trial, the periodontal status and the gingival crevicular fluid of 13 patients with different chronic inflammatory diseases were obtained before initiation of anti-cytokine treatment and 14 weeks after. Gingival crevicular fluid was collected for 16S rRNA gene sequencing from a clinically healthy tooth and the deepest measured pocket. Results: In participants with advanced attachment loss at baseline, the clinical attachment level significantly decreased from 2.9 (2.3-3.4) to 2.4 (1.3-3.0) mm (p = 0.04), and the bleeding- on-probing index dropped from 19.4 (10.0-21.0) to 7.3 (6.9-9.9) mm (p = 0.02) without any further periodontal treatment. Shannon’s diversity index significantly increased in the deepest pockets of patients (p = 0.039). Conclusion: The data showed alterations in diversity of the subgingival microbiome and improvement of periodontal parameters over the course of the study, implying a shift towards a healthier condition after starting anti-cytokine therapy. Additional investigations are needed to analyze whether the administration of selective biologicals can improve periodontal conditions in patients with or without chronic inflammatory diseases.

More than 1 million women are diagnosed annually worldwide with a gynecological cancer. Most gynecological cancers are diagnosed at late stage, either because lack of symptoms such as in ovarian cancer or limited accessibility to primary prevention in low-resource countries such as in cervical cancer. Here, we extend the studies of AR2011, a stroma-targeted and tumor microenvironment responsive oncolytic adenovirus (OAdV) whose replication is driven by a triple hybrid promoter. We show that AR2011 was able to replicate and lyse in vitro fresh explants obtained from human ovarian cancer. uterine cancer, and cervical cancer. AR2011 was also able to strongly inhibit the in vitro growth of ovarian malignant cells obtained from human ascites fluid. The virus could synergize in vitro with cisplatin even on ascites-derived cells obtained from patients heavily pretreated with neoadjuvant chemotherapy. AR2011(h404) a dual transcriptionally targeted derived virus armed with hCD40L and h41BBL under the regulation of the hTERT promoter, showed a strong efficacy in vivo both on subcutaneous and intraperitoneally established human ovarian cancer in nude mice. Preliminary studies in an immunocompetent murine tumor model showed that AR2011(m404) expressing the murine cytokines was able to induce an abscopal effect. The present studies suggest that AR2011(h404) is a likely candidate as a novel medicine for intraperitoneal disseminated ovarian cancer.

Viral infections cause metabolic dysregulation in the infected organism. The present study used metabolomics techniques and machine learning algorithms to retrospectively analyze the alter-ations of a broad panel of metabolites in the serum and urine of a cohort of 126 patients hospi-talized with COVID-19. Results were compared with those of 50 healthy subjects and 45 COVID-19 negative patients but with bacterial infectious diseases. Metabolites were analyzed by gas chro-matography coupled to quadrupole time-of-flight mass spectrometry. The main metabolites al-tered in the sera of COVID-19 patients were those of pentose glucuronate interconversion, ascorbate and fructose metabolism, nucleotide sugars, and nucleotide and amino acid metabolism. Alterations in serum maltose, mannonic acid, xylitol, or glyceric acid metabolites segregated positive patients from the control group with high diagnostic accuracy, while succinic acid seg-regated positive patients from those with other disparate infectious diseases. Increased lauric acid concentrations were associated with severity of infection and death. Urine analyses could not discriminate between groups. Targeted metabolomics and machine learning algorithms facilitated the exploration of the metabolic alterations underlying COVID-19 infection, and to identify po-tential biomarkers for the diagnosis and prognosis of the disease.

Introduction Early prediction of long term outcomes in patients resuscitated after cardiac arrest (CA) is still challenging. Guidelines suggested a multimodal approach combining multiple predictors. We evaluated whether the combination of the electroencephalography (EEG) reactivity, somatosensory evoked potentials (SSEPs) cortical complex and Gray to White matter ratio (GWR) on brain computed tomography (CT) at different temperatures could predict survival and good outcome at hospital discharge and after six months. Methods We performed a retrospective cohort study including consecutive adult, non-traumatic patients resuscitated from out-of-hospital CA who remained comatose on admission to our intensive care unit from 2013 to 2017. We acquired SSEPs and EEGs during the treatment at 36°C and after rewarming at 37°C, Gray to white matter ratio (GWR) was calculated on the brain computed tomography scan performed within six hours of the hospital admission. We primarily hypothesized that SSEP was associated with favorable functional outcome at distance and secondarily that SSEP provides independent information from EEG and CT. Outcomes were evaluated using the Cerebral Performance Category (CPC) scale at six months from discharge. Results Of 171 resuscitated patients, 75 were excluded due to missing of data or uninterpretable neurophysiological findings. EEG reactivity at 37 °C has been shown the best single predictor of good outcome (AUC 0.803) while N20P25 was the best single predictor for survival at each time point. (AUC 0.775 at discharge and AUC 0.747 at six months follow up) Predictive value of a model including EEG reactivity, average GWR, and SSEP N20P25 amplitude was superior (AUC 0.841 for survival and 0.920 for good outcome) to any combination of two tests or any single test. Conclusion Our study, in which life-sustaining treatments were never suspended, suggests SSEP cortical complex N20P25, after normothermia ad off sedation, is a reliable predictor for survival at any time. When SSEP cortical complex N20P25 is added into a model with GWR average and EEG reactivity, the predictivity for good outcome and survival at distance is superior than each single test alone.

The delivery of Cytochrome c (Cyt c) to the cytosol stimulates apoptosis in cells were its release from mitochondria and apoptosis induction is inhibited. We developed a drug delivery system consisting of Cyt c nanoparticles decorated with folate-poly(ethylene glycol)-poly(lactic-co-glycolic acid)-thiol (FA-PEG-PLGA-SH) to deliver Cyt c into cancer cells and test their targeting in the Lewis Lung Carcinoma (LLC) mouse model. Cyt c-PLGA-PEG-FA nanoparticles (NPs) of 253 ± 55 and 354 ± 11 nm were obtained by Cyt c nanoprecipitation, followed by surface decoration with the co-polymer SH-PLGA-PEG-FA, and compared to a nanoparticle-free formulation. Overexpression of FA in LLC cells and internalization of Cyt c-PLGA-PEG-FA nanoparticles (NPs) was confirmed by confocal microscopy. Caspase activation assays show NPs retain 88-96% Cyt c activity. The NP formulations were more efficient in decreasing LLC cell viability than the NP-free formulation, with IC50: 49.2 to 70.1 μg/ml versus 129.5 μg/ml, respectively. Our NP system is thrice as selective towards cancerous than normal cells. In-vivo studies using tagged nanoparticles show accumulation in mouse LLC tumor 5 min post-injection. In conclusion, our NP delivery system for Cyt c shows superiority over the NP-free formulation and reaches a folic acid-overexpressing tumor in an immune-competent animal model.

Background: MRI-guided prostate biopsies from visible tumor-specific lesions (TBx) can be used to diagnose clinically significant carcinomas (csPCa) requiring treatment more selectively than conventional systematic biopsies (SBx). Ex vivo fluorescence confocal microscopy (FCM) is a novel technique that can be used to examine TBx prior to conventional histologic workup. Methods: TBx from 150 patients were examined with FCM on the day of collection. Preliminary findings were reported within 2 hours of collection. The results were statistically compared with the final histology. Results: 27/40 (68%) of the csPCa were already recognized in the intraday FCM in accordance with the results of conventional histology. Even non-significant carcinomas (cisPCa) of the intermediate and high-risk groups (PSA > 10 or 20 ng/ml) according to conventional risk stratifications were reliably detectable. In contrast, small foci of cisPCa were often not detected or were difficult to distinguish from reactive changes. Conclusion: The rapid reporting of preliminary FCM findings helps reduce the psychological stress on patients an can improve the clinical management of csPCa. Additional SBx can be avoided in individual cases, leading to lower rates of complications and scaring in the future surgical area. Additional staging examinations can be arranged without losing time. FCM represents a promising basis for future AI-based diagnostic algorithms.

Favipiravir is a broad-spectrum inhibitor of viral RNA-dependent RNA polymerase (RdRp) currently being used to manage COVID-19 in several countries. By acting as a substrate for RdRp, favipiravir gets incorporated into the nascent viral RNA and prevents strand extension. A high mutation rate of SARS-CoV-2 RdRp may facilitate antigenic drift as an answer to the host immune response, thereby generating resistance of virus to favipiravir. Therefore, it is extremely crucial to predict potential mutational sites in the RdRp and the emergence of structural modifications contributing to drug resistance. Here, we used high-throughput interface-based protein design to generate >100,000 designs and identify mutation hotspot residues in the favipiravir-binding site of RdRp. Several mutants had lower binding affinities to favipiravir, out of which hotspot residues with a high propensity to undergo positive selection were identified. The results showed that the designs retained an average of 97 to 98% sequence identity, suggesting that SARS-CoV-2 can develop favipiravir resistance with just a few mutations. Notably, we observed that out of 134 mutations predicted designs, 63 specific mutations were already present in the CoV-GLUE database, thus attaining ~47% correlation match with the clinical sequencing data. The findings improve our understanding of the potential signatures of adaptation in SARS-CoV-2 against favipiravir and management of COVID-19. Furthermore, they can help develop exhaustive strategies for robust antiviral design and discovery.

Background: In treatment-refractory cancers, tumor tissues damaged by therapy initiate the repair response; therefore, tumor tissues must be exposed to an additional burden before successful repair. We hypothesized that an agent recognizing a molecule that responds to anticancer treatment–induced tissue injury could deliver an additional antitumor agent including a radionuclide to damaged cancer tissues during repair. We selected the extracellular matrix glycoprotein tenascin-C (TNC) as such a molecule, and three antibodies recognizing human and murine TNC were employed to evaluate X-irradiation–induced changes in TNC uptake by subcutaneous tumors. Methods: TNC expression was assessed by immunohistochemical staining of BxPC-3 tumors treated with or without X-irradiation (30 Gy) for 7 days. Antibodies against TNC (3-6, 12-2-7, TDEAR) and a control antibody were radiolabeled with 111In and injected into nude mice having BxPC-3 tumors 7 days after X-irradiation, and temporal uptake was monitored for an additional 4 days by biodistribution and single-photon emission computed tomography with computed tomography (SPECT/CT) studies. Intratumoral distribution was analyzed by autoradiography. Results: The immunohistochemical signal for TNC expression was faint in nontreated tumors but increased and expanded with time until day 7 after X-irradiation. Biodistribution studies revealed increased tumor uptake of all three 111In-labeled antibodies and the control antibody. However, a statistically significant increase in uptake was evident only for 111In-labeled 3-6 (35%ID/g for 30 Gy vs. 15%ID/g for 0 Gy at day 1, P < 0.01; ID, injected dose), whereas limited changes in 111In-labeled TDEAR2, 12-2-27, and control antibody were observed (several %ID/g for 0 and 30 Gy). Serial SPECT/CT imaging with 111In-labeled 3-6 or control antibody provided consistent results. Autoradiography revealed noticeably stronger signals in irradiated tumors injected with 111In-labeled 3-6 compared with each of nonirradiated tumors and the control antibody. The signals were observed in TNC-expressing stroma. Conclusion: Markedly increased uptake of 111In-labeled 3-6 in irradiated tumors supports our concept that an agent, such as an antibody, that recognizes a molecule, such as TNC, involved in tissue-injury repair could enhance drug delivery to therapy-experienced tumor tissues. The combination of antibody 3-6 coupled to a tumoricidal drug and conventional therapy has the potential to achieve better outcomes for patients with refractory cancer.

Methionine oxidation to the sulfoxide form (MSox) is a poorly understood post-translational modification of proteins associated with nonspecific chemical oxidation from reactive oxygen species (ROS) whose chemistries are linked to various disease pathologies including neurodegeneration. Emerging evidence shows MSox site occupancy is in some cases under enzymatic regulatory control mediating cellular signaling including phosphorylation and/or calcium signaling, raising questions as to the speciation and functional nature of MSox across the proteome. The 5XFAD lineage of the C57BL/6 mouse has well-defined Alzheimer’s and aging states. Using this model, we analyzed age, sex and disease dependent MSox speciation in mouse hippocampus. In addition, we explore chemical stability and statistical variance of oxidized peptide signals to understand needed power for MSox based proteome studies. Our results identify mitochondrial and glycolytic pathway targets with increases in MSox with age as well as neuroinflammatory targets accumulating MSox with AD in proteome studies of mouse hippocampus. Further, the paper establishes a foundation for reproducible and rigorous experimental MSox-omics appropriate for biological discovery novel target identification, and biomarker analysis in ROS and other oxidation linked diseases.

The rising global incidence of acute and chronic kidney diseases has increased the demand for renal replacement therapy. This issue, compounded with the limited availability of viable kidneys for transplantation, has propelled the search for alternative strategies to address the growing health and economic burdens associated with these conditions. In the search for such alternatives, significant efforts have been devised to augment the current and primarily supportive management of renal injury with novel regenerative strategies. For example, gene- and cell-based approaches that utilize recombinant peptides/proteins, gene, cell, organoid, and RNAi technologies have shown promising outcomes primarily in experimental models. Supporting research has also been conducted to improve our understanding of the critical aspects that facilitate the development of efficient gene- and cell-based techniques that the complex structure of the kidney has traditionally limited. This manuscript is intended to communicate efforts that have driven the development of such therapies by identifying the vectors and delivery routes needed to drive exogenous transgene incorporation that may support the treatment of acute and chronic kidney diseases.

Safe administration of highly cytotoxic chemotherapeutic drugs is a challenging problem in cancer treatment due to the adverse side effects and collateral damage to non-tumorigenic cells. To mitigate these problems, new promising approaches, based on the paradigm of controlled targeted drug delivery (TDD), utilizing drug nanocarriers with biorecognition ability to selectively target neoplastic cells, are being considered in cancer therapy. Herein, we report on the design and testing of a nanoparticle-grid based biosensing platform to aid in the development of new targeted drug nanocarriers. The proposed sensor grid consists of superparamagnetic gold-coated core-shell Fe₂Ni@Au nanoparticles, further functionalized with folic acid targeting ligand, model thiolated chemotherapeutic drug doxorubicin (DOX), and a biocompatibility agent, 3,6,-dioxa-octanethiol (DOOT). The employed dual transduction based on electrochemical and enhanced Raman scattering detection have enabled efficient monitoring of the drug loading onto the nanocarriers, attached to the sensor surface, as well as the drug release under simulated intracellular conditions. The grid’s nanoparticles serve here as the model nanocarriers for new TDD systems under design and optimization. The superparamagnetic properties of the Fe₂Ni@Au NPs aid in nanoparticles’ handling and constructing a dense sensor grid with high plasmonic enhancement of the Raman signals due to the minimal interparticle distance.

Therapeutically effective treatments of cancer are limited. To calibrate the efficiency of the novel technique we recently discovered to modulate cancer cell viability using tuned electromagnetic fields; H1299 human lung cancer cells were irradiated in a sweeping regime of W-band (75-105 GHz) millimeter waves (MMW) at 0.2 mW/cm² (2 W/m²). Effects on cell morphology, cell death and senescence were examined and compared to that of non-tumorigenic MCF-10A human epithelial cells. MMW irradiation led to alterations of cell and nucleus morphology of H1299 cells, significantly increasing mortality and senescence over 14 days of observation. Extended irradiation of 10 minutes duration resulted in complete death of exposed H1299 cell population within two days, while healthy MCF-10A cells remained unaffected even after 16 minutes of irradiation under the same conditions. Irradiation effects were observed to be specific to MMW treated H1299 cells and absent in the control group of non-irradiated cells. MMW irradiation affected nuclear morphology of H1299 cells only and not of the immortalized MCF-10A cells. Irradiation with low intensity MMW shows an antitumor effect on H1299 lung cancer cells. This method provides a novel treatment modality enabling targeted specificity for various types of cancers.

The application of quantitative PCR (qPCR) as a routine method to detect and enumerate Paenibacillus larvae in honey and hive debris could greatly speed up the estimation of prevalence and outbreak risk of the American foulbrood (AFB) disease of Apis mellifera. However, none of the qPCR tests described so far has been officially proposed as a standard procedure for P. larvae detection and enumeration for surveillance purposes. Therefore, in this study inclusivity, exclusivity and sensitivity in detection of P. larvae spores directly in samples of honey and hive debris were re-evaluated for the previously published qPCR methods. To this aim recently acquired P. larvae sequence data were considered to assess inclusivity in silico and more appropriate non-target species were used to verify exclusivity experimentally. This led to the modification of one of the previously described methods resulting in a new test capable to allow the detection of P. larvae spores in honey and hive debris down to 1 CFU/g. The application of the qPCR test optimized in this study can allow to reliably detect and quantify P. larvae in honey and hive debris, thus circumventing the disadvantages of late AFB diagnosis based on clinical symptoms and possible underestimation of spore numbers that is the main drawback of culture-dependent procedures.

Aurora Kinase A being overexpressed in majority of cancers, appear to be an attractive therapeutic target. However, a Phase III clinical trial of Alisertib, a selective AURKA inhibitor, resulted in no better response compared to the comparator arm of chemotherapeutic regimen raising question regarding ability of the same to target the undetectable stem cell functions. In silico analysis indicated regulation of AURKA by the stemness factors Oct4 and Sox2. TCGA data indicated positive correlation of each of the factors with AURKA which were eventually validated in cell lines, patient tissues and blood by flow cytometry along with Oct4 binding on AURKA promoter being detected by ChIP assay. However, indirect immunofluorescence and cell cycle analyses indicated proliferation-independent AURKA functions during asymmetric cell division, a characteristic feature of stem cells. Thorough screening of the AURKA positive cells in patient samples denoted epithelial to mesenchymal transition and significant upregulation of Vimentin, a mesenchymal marker and ABCG2, a drug resistance marker under Oct4 or Sox2 influence. Overall, our study demonstrated combinatorial selection Oct4, Sox2, AURKA, Vimentin and ABCG2 for diagnostics and intervention of circulating breast cancer stem cells as a blood-based, cost-effective and simple approach which will be beneficial in reducing relapse.

Fibroblast activation protein (FAP) is a membrane-tethered serine protease overexpressed in the reactive stromal fibroblasts of > 90% human carcinomas, which makes it a promising target for developing radiopharmaceuticals for imaging and therapy of carcinomas. Here, we synthesized two novel (R)-pyrrolidin-2-yl-boronic acid-based FAP-targeted ligands; SB02055 (DOTA-conjugated (R)-(1-((6-(3-(piperazin-1-yl)propoxy)quinoline-4-carbonyl)glycyl)pyrrolidin-2-yl)boronic acid) and SB04028 (DOTA-conjugated ((R)-1-((6-(3-(piperazin-1-yl)propoxy)quinoline-4-carbonyl)-D-alanyl)pyrrolidin-2-yl)boronic acid). natGa- and 68Ga-complexes of both ligands were evaluated in preclinical studies and compared to previously reported natGa/68Ga-complexed PNT6555. Enzymatic assays showed that FAP binding affinities (IC50) of natGa-SB02055, natGa-SB04028 and natGa-PNT6555 were 0.41±0.06, 13.9±1.29 and 78.1±4.59 nM, respectively. PET imaging and biodistribution studies in HEK293T:hFAP tumor-bearing mice showed that while [68Ga]Ga-SB02055 presented with a nominal tumor uptake (1.08±0.37 %ID/g), [68Ga]Ga-SB04028 demonstrated clear tumor visualization with ~1.5-fold higher tumor uptake (10.1±0.42 %ID/g) compared to [68Ga]Ga-PNT6555 (6.38±0.45 %ID/g). High accumulation in the bladder indicated renal excretion of all three tracers. [68Ga]Ga-SB04028 displayed low background level uptake in most normal organs, and comparable to [68Ga]Ga-PNT6555. However, since its tumor uptake was considerably higher than [68Ga]Ga-PNT6555, the corresponding tumor-to-organ uptake ratios for [68Ga]Ga-SB04028 were also significantly greater than [68Ga]Ga-PNT6555. Our data demonstrate that (R)-(((quinoline-4-carbonyl)-D-alanyl)pyrrolidin-2-yl)boronic acid is a promising pharmacophore for the design of FAP-targeted radiopharmaceuticals for cancer imaging and radioligand therapy.

Influenza virus transcription is catalyzed by the viral RNA-polymerase (FluPol) through a cap-snatching activity. The snatching of the cap of cellular mRNA by FluPol is preceded by its binding to the flexible C-terminal domain (CTD) of the RPB1 subunit of RNA-polymerase II (Pol II). To better understand how FluPol brings the 3’-end of the genomic RNAs in close proximity to the host-derived primer, we hypothesized that FluPol may recognize additional Pol II subunits/domains to ensure cap-snatching. Using binary complementation assays between the Pol II and FluPol subunits and their structural domains, we revealed an interaction between the N-third domain of PB2 and RPB4. This interaction was confirmed by a co-immunoprecipitation assay and found to occur with the homologous domains of influenza B and C FluPols. Residues [1-72] of RPB4 were found critical in this interaction. Numerous punctual mutants generated at conserved positions between influenza A, B and C FluPols in the N-third domain of PB2 exhibited strong transcriptional activity defect. These results suggest that FluPol interacts with several domains/subunits of Pol II, the CTD to bind Pol II initiating host transcription and a second on RPB4 to locate FluPol at the proximity of the 5’-end of nascent host mRNA.

Objective: To study the changes in urine metabolism in female water polo players before and after high-intensity training by using ultra-high performance liquid chromatography-mass spectrometry, and to explore the biometabolic characteristics of urine after training and competition. Methods: Twelve young female water polo players (except goalkeepers) from Shanxi Province were selected. A 4-week formal training was started after one week of acclimatization according to experimental requirements. Urine samples (5 ml) were collected before formal training, early morning after 4 weeks of training, and immediately after 4 weeks of training matches, and labeled as T1, T2, and T3, respectively. The samples were tested by LC-MS after pre-treatment. XCMS, SIMCA-P 14.1, and SPSS16.0 were used to process the data and identify differential metabolites. Results: On comparing the immediate post-competition period with the pre-training period (T3 vs T1), 24 differential metabolites involved in 16 metabolic pathways were identified, among which niacin and niacinamide metabolism and purine metabolism were potential post-competition urinary metabolic pathways in the untrained state of the athletes. On comparing the immediate post-competition period with the post-training period (T3 vs T2), 10 metabolites involved in 3 metabolic pathways were identified, among which niacin and niacinamide metabolism was a potential target urinary metabolic pathway for the athletes after training. Niacinamide, 1-methylnicotinamide, 2-pyridone, L-Gln, AMP, and Hx were involved in two metabolic pathways before and after the training. Conclusion: Differential changes in urine after water polo games are due changes in the metabolic pathways of niacin and niacinamide.

β-cyclodextrin-based star polymers have attracted much interest because of their unique structures and potential biomedical and biological applications. Herein, we synthesized well-defined folic acid (FA)-conjugated and disulfide bond-linked star polymer ((FA-Dex-SS)-βCD-(PCL)14) acted as theranostic nanoparticles for tumor-targeted magnetic resonance imaging (MRI) and chemotherapy. Theranostic nanoparticles were obtained by loading doxorubicin (DOX) and superparamagnetic iron oxide particles (SPIO) were loaded into the star polymer nanoparticles to obtain ((FA-Dex-SS)-βCD-(PCL)14@DOX/SPIO) theranostic nanoparticles. In vitro drug release studies showed that approximately 100% of the DOX was released from disulfide bond-linked theranostic nanoparticles within 24 h under a reducing environment in the presence of 10.0 mM GSH. DOX and SPIO could be delivered into HepG2 cells efficiently, owing to folate receptor-mediated endocytosis process of the nanoparticles and GSH triggered disulfide-bonds cleaving.Moreover, (FA-Dex-SS)-βCD-(PCL)14@DOX/SPIO showed strong MRI contrast enhancement properties. In conclusion, folate-decorated reduction-sensitive star polymeric nanoparticles are a potential theranostic nanoparticle candidate for tumor-targeted MRI and chemotherapy.

Prostate-specific membrane antigen (PSMA) is a well validated prostate cancer marker, but reported PSMA-targeted tracers derived from the Lys-urea-Glu pharmacophore including the clinically validated [99mTc]Tc-EDDA/HYNIC-iPSMA have high off-target uptake in kidneys, spleen and salivary glands. In this study, we synthesized and evaluated three novel 99mTc-labeled PSMA-targeted tracers and investigated if the tracers derived from the Lys-urea-Aad pharmacophore could have minimized uptake in off-target organs/tissues. In vitro competition binding assays showed that compared with HYNIC-iPSMA, the three novel ligands had slightly weaker PSMA binding affinity (average Ki = 3.11 vs 8.96 - 11.6 nM). Imaging and ex vivo biodistribution studies in LNCaP tumor-bearing mice showed that [99mTc]Tc-EDDA/HYNIC-iPSMA and the three novel tracers successfully visualized LNCaP tumor xenografts in SPECT images and were excreted mainly via the renal pathway. The average tumor uptake at 1 h post-injection varied from 5.40 to 18.8 %ID/g, and the tracers derived from the Lys-urea-Aad pharmacophore had much lower uptake in spleen and salivary glands. Compared with the clinical tracer [99mTc]Tc-EDDA/HYNIC-iPSMA, the Lys-urea-Aad derived [99mTc]Tc-EDDA-KL01127 had lower background uptake and superior tumor-to-background contrast ratios, and is therefore promising for clinical translation to detect prostate cancer lesions with SPECT.

Sepsis is a life-threatening syndrome triggered by infection and accompanied by high mortality, with antimicrobial resistances (AMRs) further escalating clinical challenges. Rapid and reliable detection of causative pathogens and AMRs are key factors for fast and appropriate treatment, in order to improve outcome in septic patients. However, current sepsis diagnostics based on blood culture is limited by low sensitivity and specificity while current molecular approaches fail to enter clinical routine. Therefore, we developed a Suppression PCR-based selective enrichment sequencing approach (SUPSETS), providing a molecular method combining multiplex suppression PCR with Nanopore sequencing to identify most common sepsis-causative pathogens and AMRs using plasma cell-free DNA. Applying only 1 mL of plasma, we target eight pathogens across three kingdoms and ten AMRs in a proof-of-concept study. SUPSETS was successfully tested on first ten clinical samples and revealed comparable results to clinical metagenomics while clearly outperforming blood culture. Several clinically relevant AMRs could be detected additionally. Furthermore, SUPSETS provided first pathogen and AMR-specific sequencing reads within minutes of starting sequencing, thereby potentially decreasing time to results to 11 - 13 hours and suggesting diagnostic potential in sepsis.

SARS-CoV-2 Omicron variant spike RBD epitopes in complex with spike (S) -protein D614G mutations now predominate globally and increase infectivity by assembling more functional S proteins into the virion. On average, homeopathic medicine contains less than one molecule per dose on average. Single variable SphericalHarmonicY, LaguerreL, WhittakerM, SphericalBesselJ, LegendreP, LegendreQ, LaguerreL, ChebyshevT, and Hypergeometric1F1 Functions pFqarise in connection with the power series solution of the Schrodinger equation or in the summation of perturbation expansions in quantum mechanics. A quantum interpretation of the homeopathic method is presented here through a novel algebraic topology approach to supersymmetry and symmetry breaking in quantum fields and quantum gravity theory with the aim of developing a wide range of physical-based drug design applications in a Small Molecule Quantized Water Memory Network suggesting that the Hidden Black Hole Paradox of Information Loss might be solved under suitable conditions.

Primary open-angle glaucoma (POAG) is a progressive optic neuropathy with a complex, multifactorial aetiology. Raised intraocular pressure (IOP) is the most important clinically modifiable risk factor for POAG. All current pharmacological agents target aqueous hu-mour dynamics to lower IOP. Newer therapeutic agents are required as some patients with POAG show a limited therapeutic response or develop ocular and systemic side ef-fects to topical medication. Elevated IOP in POAG results from cellular and molecular changes in the trabecular meshwork driven by increased levels of transforming growth factor β (TGFβ) in the anterior segment of the eye. Understanding how TGF affects both the structural and functional changes in the outflow pathway and IOP is required to de-velop new glaucoma therapies that target the molecular pathology in the trabecular meshwork. In this study we evaluated the effects of TGF-1 and -2 treatment on miRNA expression in cultured human primary trabecular meshwork cells. Our findings are pre-sented in terms of specific miRNAs (miRNA-centric), but given miRNAs work in net-works to control cellular pathways and processes, a pathway-centric view of miRNA ac-tion is also reported. Evaluating TGF-responsive miRNA expression in trabecular meshwork cells will further our understanding of the important pathways and changes involved in the pathogenesis of glaucoma and could lead to the development of miRNAs as new therapeutic modalities in glaucoma.

(1) Background: The diagnosis of lumbosacral radiculopathy involves anamnesis, assessment of sensitivity and strength, diagnostic imaging—usually magnetic resonance imaging (MRI)—and electrodiagnostic testing (EDX), typically electromyography (EMG) and electroneurography (ENG). MRI evaluates the structures supporting the spinal cord, while EDX evaluates root functionality. The present study aimed to analyze the concordance of MRI and EDX findings in patients with clinically suspected radiculopathy. Additionally, we investigated the comparison between these two reference tests and various clinical variables and questionnaires. (2) Methods: We designed a prospective epidemiological study of consecutive cases with an observational, descriptive, cross-sectional, and double-blind nature following the STROBE guidelines, encompassing 142 patients with clinical suspicion of lumbosacral radiculopathy. (3) Results: Of the sample, 58.5% tested positive for radiculopathy using EDX as the reference test, while 45.8% tested positive using MRI. The comparison between MRI and EDX in the diagnosis of radiculopathy in patients with clinical suspicion was not significant; the overall agreement was 40.8%. Only the years with symptoms were comparatively significant between the positive and negative radiculopathy groups as determined by EDX. (4) Conclusion: The comparison between lumbar radiculopathy diagnoses in patients with clinically suspected pathology using MRI and EDX as diagnostic modalities did not yield statistically significant findings. MRI and EDX are complementary tests assessing different aspects in patients with suspected radiculopathy; degeneration of the structures supporting the spinal cord does not necessarily imply root dysfunction.

Abstract: Falls are among the top 10 causes of years lived with disability in people aged 75 and over. Preventive programs like case management (CM) are crucial. Objectives: To evaluate the effects of a multifactorial fall prevention program, based on CM, on physical performance, presence of pain and risk of falls and fractures in elderly people who have suffered falls. Methods: This is a randomized, single-blind clinical trial with parallel groups: intervention group (IG) and control group (CG) composed of 55 older people with a history of falls living in the community. All participants underwent an initial assessment via video call (containing anamnesis, Timed Up and Go test, Falls Risk Score, Short Physical Performance Battery and Clinical Frax). The IG underwent CM, the physical exercise protocol and the cognitive stimulation protocol. The CG was monitored through telephone calls and received general health and falls guidance. Results: No significant results were found in physical capacity, presence of pain, risk of falls and fractures between the intervention and control groups and between assessments. Conclusion: This program was not effective in improving functional performance, but it was important for characterizing pain and the probability of fracture in the next 10 years in this population.

The microbiome is capable of modulating the bioavailability of chemotherapy drugs mainly due to metabolizing these agents. Multiple cytostatic bacterial metabolites were recently identified that have cytostatic properties on cancer cells. In this study we addressed the question whether the cytostatic bacterial metabolites (cadaverine, indolepropionic acid, indoxylsulfate) can interfere with the cytostatic effects of the chemotherapy agents used in the management of breast cancer (doxorubicin, gemcitabine, irinotecan, methotrexate, rucaparib, 5-fluorouracil, paclitaxel). The chemotherapy drugs were applied in a wide concentration range to which a bacterial metabolite was added in a concentration within its serum reference range and the effects on cell proliferation were assessed. There was no interference between doxorubicin, gemcitabine, irinotecan, methotrexate, rucaparib and the bacterial metabolites. Nevertheless, cadaverine increased the Hill coefficient of the inhibitory curve of 5-fluorouracil and indolepropionic acid increased the IC50 value of 5-fluorouracil that are either disadvantageous effects or effects of unknown significance. Nevertheless, indolepropionic acid decreased the IC50 value of paclitaxel that is a potentially advantageous combination.

In recent decades the Mediterranean area observed an increase in large fires, despite the decrease in the number of fire ignitions, following a worldwide tendency. Climate change has been the main culprit for large burnt areas, and alterations of forest ecosystems, resulting in the increased recurrence of forest fires. In Portugal, the analogous trend resulted in the destruction of large rural, urban and industrial areas, where after the 2017 months of June and October catastrophic events, the government implemented the 2019 specific policies for preventing fire outbreaks and defending the forest against fires. This compulsory policy demanded that landowners and local governments alike needed to contact specific authorities requesting authorization for their intentions to clean properties in and around urban areas, roads, and forest limits. Despite policy and careful monitoring, ignitions still occur, and in many cases resulting from the implementation of such policies. The study analyses the before and after policy implementation, considering 6904 ignitions records from the period between 2014 and 2023 from the central area of Portugal, covering the transition area between the agricultural fields of the Tagus valley and the Monte-junto-Estrela Mountain range, the district of Santarém. The authorization to use fire in clearance practices is granted according to a set of weather conditions, temperature, wind intensity, and relative humidity, when analyzing fire ignitions with the average daily wind intensity at the site of the occurrence, we observed that more than half of wildfires occur on days with winds between 10 and 20 Km/h, whereas intensities greater than 30 Km/h only 1% of the total occurrences, and of these 22% occurred due to the use of fire in the burning of agricultural leftovers and cut and piled bushes. The circulation of the thermal depression in the Iberian Peninsula gives rise to increasing intensity throughout the day, reaching a maximum in the late afternoon, this factor combined with the misjudgment of safe conditions leads us to suggest stricter intervals and the need for awareness of daily variation in conditions.

Monodisperse and semi-facetted ultra-small templated mesoporous silica nanoparticles (US-MSN) of 20-25 nm were synthesized using a short-time hydrolysis of tetraethoxysilane (TEOS) at room temperature followed by a dilution for nucleation quenching. According to dynamic light scattering (DLS), a two-step pH adjustment was necessary for growth termination and colloidal stabilization. The pore size was controlled by cetyltrimethylammonium bromide (CTAB) and the tiny amount of neutral surfactant F127 was added for minimizing the coalescence between US-MSN and favoring the transition towards internal ordering. Flocculation eventually occured allowing to harvest a powder by centrifugation ( 60% silica yield after one month). The scanning transmission electron microscopy (STEM) and 3D high-resolution transmission electron microscopy (3D-HR-TEM) images revealed that the US-MSNs are partially ordered. The 2D FT transmorm images evidences the coexistance of four, five and sixfold patterns characterizing an “on-the-edge” crystallization step between amorphous raspberry and hexagonal pore array morphologies, typical of a protocrystalline state. Calcination preserved this state and yields a powder characterized by a packing developping a hierarchical porosity centered at 3.9 ± 0.2 (internal pores) and 68 ± 7 nm (packing voids) of high potential as support for separation and catalysis.

Several studies have shown that antibiotics, analgesic – sedative, and antiseizure medications are among the most commonly used medications in preterm and sick neonates. These infants are at high risk of developing nosocomial infections, central nervous system complications, and are exposed to numerous painful/stressful procedures. These severe, potentially life-threatening complications may have serious short- and long-term consequences and should be prevented and/or promptly treated. Previous studies and reviews have revealed significant variability in medications used in neonatal intensive care units (NICUs) worldwide, especially concerning the indications and dosages of first-line medications. This variability indicates the lack of adequate studies regarding the effectiveness and safety of these medications in neonates, especially the preterm ones. Important obstacles contributing to inadequate studies in preterm infants include difficulties in obtaining parental consent, physicians’ unwillingness to recruit preterm infants, the lack of license for use in neonates, and other scientific and ethical concerns. This review is an update on the use of antimicrobials – antifungals, analgesics – sedatives, and antiseizure medications used in neonates, focusing on existing evidence or knowledge gaps regarding their pharmacokinetics, indications, safety, dosage regimen (dose, dosing interval, route of administration), and evidence-based guidelines for the optimal use in neonates.

: This study focuses on optimizing chlorophyll extraction techniques and strategically placing leaf disks to enhance chlorophyll concentration in sesame (Sesamum indicum L.) leaves. Thirty sesame genotypes, categorized into light green (LG), middle green (MG), and deep green (DG) pigment groups based on leaf coloration, were selected from a larger pool of field-grown accessions. The investigation involved determining optimal SPAD value index measurements, quantifying pigment concentrations, exploring extraction solvents, and selecting suitable leaf disk positions. Significant variations in chlorophyll content were observed across genotypes, greenness categories, and leaf disk positions. The categorization of genotypes into DG, MG, and LG groups revealed a correlation between leaf appearance and chlorophyll content. The study highlighted a consistent relationship between carotenoids and chlorophyll, indicating their role in adaptation to warm environments. Examination of leaf disk positions revealed a significant chlorophyll gradient along the leaf blade, emphasizing the need for standardized protocols. Chlorophyll extraction experiments identified DMSO and 96% ethanol, particularly the later incubated for 10 minutes at 85°C, as effective choices. This recommendation considers factors like cost-effectiveness, time efficiency, safety, and environmental regulations, ensuring consistent and simplified extraction processes. For higher chlorophyll extraction, focusing on leaf tips and the 75% position along the sesame leaf blade is suggested, consistently yielding higher chlorophyll content. Our findings therefore, underscores insightful knowledge on chlorophyll gradients and encouraging for standardized protocols, that enabling researchers to refine experimental designs for precise and comparable chlorophyll measurements. Recommended solvent choices ensure reliable outcomes in plant physiology, ecology, and environmental studies.

To enable net zero sustainable thermal building energy this study develops an open-source thermal house model to couple solar photovoltaic (PV) and heat pumps (HP) for grid-connected residential housing. The calculation of both space heating and cooling thermal loads and the selection of HP is accomplished with a validated Python model for air-source heat pumps. The capacity of PV required to supply the HPs is calculated using an System Advisor Model integrated Python model. Self-sufficiency and self-consumption of PV and the energy imported/exported to the grid for a case study are provided, which shows that simulations based on the monthly load profile have a significant reduction of 43% for energy sent to/from the grid compared to the detailed hourly simulation and an increase from 30% to 60% for self-consumption and self-sufficiency. These results show the importance of more granular modeling and also indicate mismatches of PV generation and HP load based on hourly simulation datasets. The back-calculation PV sizing algorithm combined with HP and thermal loads presented in this study exhibited robust performance. The results indicate this approach can be used to accelerate the solar electrification of heating and cooling to offset the use of fossil fuels in northern climates.

The growing urgency for sustainable energy solutions necessitates a deeper understanding of the environmental impacts of renewable technologies. This article aims to synthesize and analyze Life Cycle Assessments (LCA) in this domain, providing a comprehensive perspective. We systematically categorize 2,923 articles into four communities: (1) Photovoltaic systems, (2) Wind energy systems, (3) Materials for auxiliary industry of photovoltaic and wind systems, and (4) Solar thermal systems. A comparative analysis is conducted to identify methodological consistencies and disparities across these communities. The findings reveal diverse methodological approaches and a range of environmental impacts, highlighting the complexities in assessing renewable energy systems. The article underscores the significance of material selection in photovoltaic and wind systems, providing a critical overview of the current state of LCA research in renewable energy and stressing the need for standardized methodologies. It also identifies gaps in recent research, offering insights for future studies focused on integrating environmental, economic, and social considerations in renewable energy assessments.As a case study, an LCA was used to evaluate two energy supply methods for a sensor network: one connected to the public grid and another powered by a photovoltaic panel. The off-grid system, while more environmentally friendly by reducing reliance on non-renewable energy sources, posed challenges due to the high environmental impact of battery production and disposal. Integrating environmental assessments provides a robust framework for making informed decisions on sustainable technologies. The findings are critical for projects that balance technological needs with sustainability goals.

We can analyze the properties of the Collatz Conjecture by using Terras’ Theorem, and computational graphical calculations. To do this, we introduce the concept of “tree" which shows the relationship between the input and output positive integers of the Collatz process. This approach offers a novel way for determining the non-existence of loops and diverge trees through computer simulations.

The increasing growth in knowledge about functioning of the nervous system of mammals and humans, as well as the significant neuromorphic technologies development in recent decades, have led to the emergence of a large number of brain-computer interfaces and neuroprosthetics for the regenerative medicine tasks. Neurotechnologies have traditionally been developed for therapeutic purposes to help or replace motor, sensory or cognitive abilities damaged by injury or disease. They also have significant potential for memory enhancement. However, there are still no fully developed neurotechnologies and neural interfaces capable of restoring or expanding cognitive functions, in particular memory, in mammals or humans. In this regard, the search for new technologies in the field of restoration of cognitive functions is an urgent task of modern neurophysiology, neurotechnology and artificial intelligence. Hippocampus is an important brain structure connected to memory and information processing in the brain. The aim of this paper is to propose an approach based on deep neural networks for prediction of hippocampal signals in CA1 region based on received biological input in CA3 region. We compare results of prediction for two widely used deep architectures: reservoir computing (RC) and long short-term memory (LSTM) networks. Proposed study can be viewed as a first step in the complex task of the development of a neurohybrid chip, which allows one to restore memory functions in the damaged rodent hippocampus.

This research was to examine the impacts of long-term rice-crayfish coculture systems(RS) on soil nutrients, carbon pools, and rice yields in paddy fields , aiming to establish a scientific basis for the sustainable development of RS in the northern region of Zhejiang. The results showed that the change from rice monoculture (CK) to RS resulted in a 24.99% increase in the 5-year average of soil ammonium nitrogen(AN), while the soil nitrate nitrogen(NN), available potassium(AK), and available phosphorus content(AP) decreased by 28.02%, 16.05%, and 28.76% respectively. Moreover, the total organic carbon(TOC), easily oxidizable organic carbon(EOC), dissolved organic carbon(DOC), and microbial biomass carbon(MBC) decreased by 2.45%, 8.82%, 35.31%, and 65.84% respectively. Correlation analysis showed that there was a significant positive correlation between NN, EOC and MBC in the RS. In terms of rice yield, 5-year average of rice yield in RS has decreased by 8.4% compared to CK.The average yield of planting early-maturing varieties of rice was reduced by 13.16%, while the average yield of planting late-maturing varieties of rice was reduced by 6.00%. In conclusion, enhancing water and nutrient management and cultivating late maturing rice varieties are essential strategies for achieving the sustainable development of RS in northern Zhejiang.

Efficient resource allocation is crucial in clusters with frugal Single-Board Computers (SBCs) possessing limited computational resources. These clusters are increasingly being deployed in edge computing environments in resource-constrained settings where energy efficiency and cost-effectiveness are paramount. A major challenge in Hadoop YARN scheduling is load-balancing, as frugal nodes within the cluster can become overwhelmed, resulting in degraded performance and frequent occurrences of out-of-memory errors, ultimately leading to job failures. In this study, we introduce an Adaptive Multi-criteria Selection for Efficient Resource Allocation (AMS-ERA) in Frugal Heterogeneous Hadoop Clusters. Our criterion considers CPU, memory and disk requirements for jobs and aligns the requirements with available resources in the cluster for optimal resource allocation. To validate our approach, we deploy a heterogeneous SBC-based cluster consisting of 11 SBC nodes and conduct several experiments to evaluate the performance using Hadoop wordcount and terasort benchmark for various workload settings. The results are compared to the Hadoop-Fair, FOG and IDaPS scheduling strategies. Our results demonstrate a significant improvement in performance with the proposed AMS-ERA, reducing execution time by 27.2%, 17.4% and 7.6% respectively using terasort and wordcount benchmarks.

A recent study showed the potential of DA Perten 7200 NIR Spectrometer in detecting chlorpyrifos-methyl pesticide residue in rough, brown, and milled rice. However, this instrument is still lab-based and generally suited for point-of-sale testing in many countries. To provide a field deployable version of this technique, an existing light emitting diode (LED)-based instrument which provide discrete NIR wavelength illumination and reflectance spectra over the range of 850-1550 nm was tested. Spectra were collected from rough, brown, and milled rice at different pesticide concentrations and analysed for quantitative and qualitative measurement using partial least squares regression (PLS) and discriminant analysis (DA). Simulations for LED-based instruments were also evaluated using segments of spectra from the DA7200 to represent LED illumination. For the simulation of the existing LED-based instrument (LEDPrototype1) using their wavelengths range yielded 70.4% to 100% correct classification. Simulation of a second LED instrument, LEDPrototype2, with spectral segments selected based on significant wavelength regions from PLS regressions coefficients obtained from the DA7200 showed improved performance with R2 of 0.59 to 0.82 and correct classifications of 71.3 to 100%. An actual LED based instrument with this capability could provide a quick screening tool to determine if MRLs are exceeded.

Optimal control is a critical tool for mechanical robotic systems, facilitating precise manipulation of dynamic processes. These processes are described through differential equations governed by a control function, addressing a time-optimal problem with bilinear characteristics. Our study utilizes the classical approach complemented by Pontryagin's Maximum Principle (PMP) to explore this inverse optimal problem. The objective is to develop an exact piecewise control function that effectively manages trajectory control while considering the effects of viscous friction. Our simulations demonstrate that the proposed control law markedly diminishes oscillations induced by boundary conditions. This research not only aims to delineate the reachability set but also strives to determine the minimal time required for the process. The findings include an exact analytical solution for the stated control problem.

A correlation of basic science and clinical symptoms in the human to propose a new theory for how the vestibular system works Neil S. Longridge Professor Emeritus, Division of Otolaryngology Department of Surgery, Faculty of Medicine, University of British Columbia Vancouver, BC CANADA *Arthur I. Mallinson, Clinical Associate Professor, Division of Otolaryngology Department of Surgery, Faculty of Medicine, University of British Columbia Vancouver, BC CANADA NS Longridge † *AI Mallinson † These authors contributed equally to this work. ABSTRACT; Bipedalism is unique among mammals. Until modern times, a fall and resulting leg fracture could be fatal. Balance maintenance after a destabilizing event requires instantaneous decision-making. The vestibular system plays an essential role in this process, initiating an emergency response. The afferent otolithic neural response is the first directionally oriented information to reach the cortex, and can then be used to initiate an appropriate protective response. Some vestibular efferent axons feed directly into the type I vestibular hair cells. This allows for rapid vestibular feedback via the striated organelle (STO), which has been largely ignored in most texts. We propose that this structure is essential in emergency fall prevention, and also that the system of sensory detection and resultant motor response works by having efferent movement information transmitted to the maculae simultaneously with the movement commands. This results in the otolithic membrane positioning itself precisely for the planned movement, and any error is due to an unexpected external cause. Error is fed back via the vestibular afferent system. The efferent system through the STO causes macular otolithic membrane movement which occurs simultaneously with the initiating motor command. As a result, no vestibular afferent activity occurs unless an error must be dealt with.

Purpose To investigate the effects of intra-articular glenohumeral joint triamcinolone injection in treating secondary adhesive capsulitis after breast cancer surgery.Methods This study prospectively enrolled 37 participants, 22 of the breast cancer surgery group and 15 of the idiopathic group. All participants received intra-articular glenohumeral joint injection in the affected shoulder joint and received physiotherapy for 12 week. The clinical assessment evaluated before, and 1, 3, and 6 months after the intervention. The primary outcome was the change in the Shoulder Pain and Disability Index (SPADI).Results The total SPADI(%) in both groups showed significant decrease from baseline to 1, 3, and 6 months after the intervention. There was no significant difference in the differences of the total SPADI from baseline to 1, 3, and 6 months between two groups. However, the improvement in the SPADI pain subscale and the PROM of abduction at 3 and 6 months post-injection in the breast cancer group were inferior to the idiopathic group.Conclusion Intra-articular triamcinolone injection for adhesive capsulitis after breast cancer surgery significantly improved in significant improvements of pain, shoulder function and the PROM. The effects were similar to idiopathic adhesive capsulitis, but in the breast cancer surgery group, appropriate pain and ROM management and monitoring are required even 3 months after injection. With a standardized injection protocol, intra-articular triamcinolone injection could be an effective and safe treatment option for secondary adhesive capsulitis after breast cancer surgery.

Keywords: environmental impacts of hotels; environmental management in lodging facilities; corporate sustainability.

Postbiotic is a preparation of inanimate microorganisms and/or their components that confers a health benefit on the host. Different bacterial strain and preparation method result in different functions. Herein, a postbiotic preparation named Postbiotic-P by intercepting 1-5 KD of the cell-free supernatants of L. caseiparacasei P6 fermentation broth was prepared, and its multifunctional activities were evaluated. The results showed that Postbiotic-P exerted good antihemolytic (10%-50% Postbiotic-P resulted in 4.9%-48.1% antihemolytic rate), anti-inflammatory (8% to 40% Postbiotic-P is comparable to 259.1-645.4 μg/mL of diclofenac sodium equivalents), antioxidant [reducing power (1.25%-12.5% Postbiotic-P resulted in the increase of OD700 from 0.279-2.322), DPPH free radical scavenging activity (2.5%-50% Postbiotic-P resulted in 38.9%-92.4% free radical scavenging rate), and hydroxyl radical scavenging activity (0.5%-4% Postbiotic-P resulted in 4.66%-10.38% hydroxyl radical scavenging rate)], and antimicrobial activities (against 2 Gram-positive, 8 Gram-negative and 1 fungus). Furthermore, it was proved that Postbiotic-P could significantly inhibit the increase of the peroxide value and the malondialdehyde content in cookies, indicating the application potential of Postbiotic-P in food preservation. Taken together, Postbiotic-P has good application potential for the development of health care products and functional foods. However, further studies are needed to determine their precise mechanism of action, to clarify the active components responsible for the function, and to validate the biological activities in animal models or clinical trials.

The B169L protein (pB169L) of African swine fever virus (ASFV) is a structural protein with an unidentified function during the virus replication. The sequences of the B169L gene and the downstream B438L gene are separated by short intergenic regions. However, the regulatory mode of the gene transcription remains unknown. Here, we identified two distinct promoter regions and two transcription start sites (TSS) located upstream of the open reading frame (ORF) of B438L. Using the promoter reporter system, we demonstrated that the cis activity of the ORF proximal promoter exhibited significantly higher levels compared with that of the distal promoter located in the B169L gene. Furthermore, transfection with the plasmids with two different promoters for B438L could initiate the transcription and expression of the B438L gene in HEK293T cells, and the cis activity of the ORF proximal promoter also displayed the higher activities compared with the distal promoter. Interestingly, the B438L distal promoter also initiated the transcription of the alternatively spliced B169L mRNA (B169L mRNA2) encoding a truncated pB169L (tpB169L) (amino acids 92–169), and the gene transcription efficiency was increased upon mutation of the initiation codon located upstream of the alternatively spliced B169L gene. Taken together, we demonstrated that the distal promoter of B438L gene initiates the transcription of both the B438L mRNA and B169L mRNA2. Comprehensive analysis of the transcriptional regulatory mode of the B438L gene is beneficial for the understanding of the association of B438L protein and pB169L and the construction of the gene-deleted ASFV.

Extracorporeal membrane oxygenation (ECMO) support for respiratory failure in the intensive care unit continues to have an expanded role in select patients. While acute respiratory distress syndrome remains the most common indication, ECMO may be used in other causes of refractory hypoxemia and/or hypercapnia. The most common configuration is veno-venous (V-V) ECMO, however in specific cases of refractory hypoxemia or right ventricular failure, some patients may benefit from veno-pulmonary (V-P) ECMO or veno-venoarterial (V-VA) ECMO. Patient selection and extracorporeal circuit management are essential to successful outcomes. This narrative review explores the physiology of ECMO, indications and contraindications, ventilator management, extracorporeal circuit management, troubleshooting hypoxemia, complications, and ECMO weaning in patients with respiratory failure. As the footprint of ECMO continues to expand it is essential that clinicians understand the underlying physiology and management of these complex patients.

Intrusion Detection Systems play a crucial role in a network. They can detect different network attacks and raise warnings on them. Machine learning-based IDSs are trained on datasets that, due to the context, are inherently large, since they can contain network traffic from different time periods and often include a large number of features. In this paper, we present two contributions: the study of the importance of feature selection when using an IDS dataset, while striking a balance between performance and the number of features; and the study of the feasibility of using a low-capacity device, the Nvidia Jetson Nano, to implement an IDS in a low-capacity network. The results, comparing the GA with other well-known techniques in feature selection and reduction, show that the GA has a higher F1-score of 76%, although the time to find the optimal set of features surpasses other methods; the reduction of the number of features reduces the processing time without a significant impact in f1-score. The Jetson Nano allows the classification of network traffic with an overhead of 10 times in comparison to a traditional server.

This study aimed to investigates obesity-related glomerulopathy (ORG) at cellular, structural, and transcriptomic levels. Thirty Wistar rats were randomized into two groups: control (n=15) and study groups (n=15) that were fed a standard (SD) and high-fat diet (HFD), respectively. After 10 weeks, the weight, kidney function, histological features, and transcriptomic changes were assessed. HFD group exhibited increased weight gain (55.8% vs 29.2%; P< 0.001) and albuminuria (10384.04 ng/ml vs 5845.45 ng/ml; P

Pinus occidentalis, Swartz is the primary timber species in the Dominican Republic (DR). Despite its economic importance, studies conducted on this species are very scarce, making it difficult to estimate current inventory levels. This study aims to enhance the accuracy of estimating total bole volume of P. occidentalis in different ecological zones (EZs) within La Sierra, evaluating and comparing two established volume equations—combined variable and Schumacher-Hall—across nine modeling variants (MVs). An indicator variables analysis determined the necessity of distinct equations for two EZs. Fitting included both linear and nonlinear models. Our comprehensive statistical analysis included goodness-of-fit metrics to evaluate each model variant's performance rigorously. Modeling variant SH02 was most effective in the Dry Ecological Zone, showing superior performance in both fitting and validation phases. Similarly, SH03 emerged as the best fit for the Combined Intermediate and Humid Ecological Zones, achieving the lowest overall ranking sum among tested variants. The SH equation variants SH02 and SH03, provide reliable and precise volume estimations, allowing optimization of forestry management practices for P. occidentalis trees. The SH models outperformed the CV model variants' consistency in parameter estimation. This tailored approach employed ensures more accurate volume predictions, which is crucial for sustainable management and conservation efforts.

We study in detail the influence of different chemical potentials (baryon, charged, strange, and neutrino) on how and how fast a free gas of quarks in the zero-temperature limit reaches the conformal limit. We discuss the influence of non-zero masses, the inclusion of leptons, and different constraints, such as charge neutrality, zero-net strangeness, and fixed lepton fraction. We also investigate for the first time how the symmetry energy of the system under some of these conditions approaches the conformal limit. Finally, we briefly discuss what kind of corrections are expected from perturbative QCD as one goes away from the conformal limit.

This paper proposes a heuristic approach for managing complex construction projects. The tool incorporates with Primavera P6 EPPM and Synchro 4D, enabling proactively clash detection and resolution of spatial conflicts during concurrent tasks. Additionally, it performs resource verification for sufficient allocation before task initiation. This integrated approach facilitates the generation of conflict-free and feasible construction schedules. By adhering to project constraints and seamlessly integrating with existing industry tools, the proposed solution offers a comprehensive and robust approach for construction project management. This constitutes to our knowledge the first dynamic digital twin for the delivery of a complex project.

Optimal planning and design of microgrids is a priority for electrification of off-grid areas. Indeed, according to one of the Sustainable Development Goals (SDG) 7, the UN recommends universal access to electricity for all but, at the lowest cost. To achieve this goal, several optimization methods with different strategies have been proposed in the literature. This paper proposes a microgrid installation and planning model based on a combination of several techniques. Python 3.10, the programming language, has been used in conjunction with machine learning techniques such as unsupervised learning based on K-means clustering and deterministic optimization methods based on mixed linear programming. These methods were complemented by the open-source spatial method for optimal electrification planning: onsset. The results obtained enabled us to simulate the model obtained, with a cluster considered as a case study, based on the elbow and k-means clustering method; then, in a second phase, to size the microgrid with a capacity of 40 kW, by optimizing all the resources available on the site: the example of the various resources in the case of Togo was considered (solar, wind, hydropower). This study therefore highlighted the optimal resources obtained by integrating battery systems by the optimization model formulated on the basis of the various technology costs, such as investment, maintenance and operating costs, based on the technical limits of the various technologies. For the optimum results obtained, solar systems account for 80% of the maximum load considered, compared with 7.5% for wind systems and 12.5% for battery systems. Next, an optimal microgrid connection model was proposed, based on the constraints of a voltage stability limit estimated at 10% of the maximum voltage drop. The substation capacity limit was also taken into account. The results obtained from the case studied enabled us again, to present selective results for load nodes in relation to the substation node. And finally, the spatial technology planning tool made it possible to obtain results on the different strategies for the various technologies required for the electrification planning study of the Togo case. The various results obtained from the different techniques provide the leads needed for a feasibility study for optimal electrification of off-grid areas, using microgrid systems.

Aggregation of the protein α-Synuclein (αSyn) is a hallmark of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple systems atrophy, and alleviating the extent of αSyn pathology is an attractive strategy against neurodegeneration. The engineered binding protein β-wrapin AS69 binds monomeric αSyn. AS69 reduces primary and secondary nucleation as well as fibril elongation in vitro. It also mitigates aSyn pathology in a mouse model based on intrastriatal injection of aSyn pre-formed fibrils (PFF). Since the PFF-based model does not represent all aspects of PD, we tested here whether AS69 can reduce neurodegeneration resulting from αSyn overexpression. Human A53T-αSyn was overexpressed in the mouse Substantia nigra (SN) by using recombinant adeno-associated viral vector (rAAV). AS69 was also expressed by rAAV transduction. Behavioral tests and immunofluorescence stainings were used as outcomes.Transduction with rAAV-αSyn resulted in αSyn pathology as reported by phospho-αSyn staining and caused degeneration of dopaminergic neurons in the SN. The co-expression of rAAV-AS69 did not reduce αSyn pathology or degeneration of dopaminergic neurons. We conclude that αSyn monomer binding by rAAV-AS69 was insufficient to protect from aSyn pathology resulting from αSyn overexpression.

Primary ciliary dyskinesia (PCD) is caused by pathologic variants in over 50 different genes that affect the structure and function of motile cilia. Low nasal NO (nNO) is a biomarker for diagnosis in patients with features of PCD; but the reason why it is low is unclear. At the cellular level, a characteristic feature shared by most PCD patients is that antigens and other particles are not cleared from the epithelial surface. Poor antigen clearance results in pro-oxidant pathway activation and airway epithelial damage and may predispose PCD patients to DUOX1- and IL33- mediated asthma. Secondary ciliary dysfunction, such as that caused by viruses or by smoking, can also contribute to asthma development. Variants in genes underlying the function of cilia, can be associated with poor lung function, even in the absence of PCD. Single nucleotide polymorphisms in PCD – related genes can be associated with increased asthma severity. The role of cilia and antigen stasis is the pathophysiology of asthma is an important area for research, because specific airway clearance techniques and other therapeutic interventions, such as antioxidants, could be of value in preventing the development of asthma and asthma-like symptoms.

Major depressive disorder (MDD) and substance use disorder (SUD) are of immense medical and social concerns. Although significant progress on neuronal involvement in mood and reward circuitries has been achieved, only relatively recently the role of glia in these disorders have attracted attention. Detail understanding of the glial function in these devastating diseases could offer novel interventions. Here, following a brief review of circuitries involved in mood regulation and reward perception, specific contribution of the neurotrophic factors, neuroinflammation and gut microbiota to these diseases are highlighted. In this context, the role of specific glial cells (e.g., microglia, astroglia, oligodendrocytes and synantocytes) on phenotypic manifestation of MDD or SUD are emphasized. In addition, potential use of this knowledge in developing novel therapeutics is touched upon.

In recent years, ESG (environmental, social, governance) has emerged as a critical investment concept. Its goal is to create value for both shareholders and society, encouraging companies to optimize social value. However, the exploration and research into "the proportion of firms ex-porting and the pathways through which the environmental, social, and governance activities of carbon-intensive firms influence firms' financial performance" remains largely unexplored. This study establishes a research framework within this context, utilizing listed Chinese manufactur-ing companies as the research subjects. Employing a fixed-time, fixed-industry, two-way fixed-effects model methodology, it delves into the relationship between ESG ratings, the pro-portion of firms' exports, and firms' financial performance through panel regression modeling. This study emphasizes the moderating role of carbon-intensive firms in the relationship. Find-ings indicate that both enterprise export proportions and carbon-intensive firms significantly affect the correlation between corporate ESG activities and financial performance. This has im-plications for investors, company management, policymakers, and regulators. Based on these findings, we propose policy recommendations at corporate and governmental levels to enhance ESG significance, strengthen corporate governance, and promote continuous ESG advancement. The study provides micro-level evidence of the interaction among ESG ratings, export ratios, carbon-intensive enterprises, and corporate performance, empowering investors to make in-formed decisions.

Despite its growing importance as a dry beneficiation method, there is a lack of studies exploring the fundamentals aspects of dry jigging. In this sense, this study focuses on explore some essential aspects of density-based separation in dry jigs, like pulse profile, energy consumption and, especially, stratification over time, also exploring an innovative operational strategy here called “transient pulsation”. The tests were carried out using density tracers distributed across 11 density ranges (0.4-2.4 g/cm³) and employing a base bed (gravel) to analyze their segregation in a pilot-scale dry jig. Pressure drop and active power data were acquired to measure the pulse characteristics and energy consumption. The findings suggest that establishing the dry jigging cycle is more complex than in hydraulic jigs due to the compressibility of air. Stationary pulsation tests revealed an unstable behavior of stratification over time, contrasting with traditional hydraulic jigs, while transient pulsation tests unveiled varied trends in separation quality. Energy consumption analysis underscored the significant role of the blower drive. These insights have the potential to inform operational enhancements in dry jigging.

Transient receptor potential melastatin-8 (TRPM8) is a cation channel that is activated by cold and “cooling agents” such as menthol and icilin, which induce a cold sensation. Stimulation of TRPM8 activates an intracellular signaling cascade that ultimately leads to a change in the gene expression pattern of the cells. Here, we investigated the TRPM8-induced signaling pathway that links TRPM8 channel activation to gene transcription. Using a pharmacological approach, we show that inhibition of phosphatidylinositol 4-phosphate 5 kinase alpha (PIP5K), an enzyme essential for the biosynthesis of phosphatidylinositol 4,5-bisphosphate, attenuated TRPM8-induced gene transcription. Analyzing the link between TRPM8 and Gq proteins, we show that pharmacological inhibition of the beta gamma subunits impairs TRPM8 signaling. In addition, genetic studies showed that TRPM8 requires an activated Galpha subunit for signaling. In the nucleus, the TRPM8-induced signaling cascade triggers an activation of the transcription factor AP-1, a complex consisting of a dimer of basic region leucine zipper (bZIP) transcription factors. Here, we identified the bZIP protein c-Jun as an essential component of AP-1 within the TRPM8-induced signling cscade. In summary, with PIP5K, Gq subunits and c-Jun we have identified key molecules in the TRPM8-induced signaling from the plasma membrane to the nucleus.

The aim of this study was to evaluate whether alterations in food availability compromise the metabolic homeostasis of honey bees exposed to three fungicides alone or together. Ten honey bee colonies were utilized, with half receiving energy-protein supplementation for 15 weeks while another five colonies had their protein supply reduced with pollen traps. Subsequently, forager bees were collected and exposed by contact to 1 or 7 µg of bixafen, prothioconazole, and trifloxystrobin, either individually or in combination. After 48 hours, abdomens without the intestine was used for the analysis of expression of antioxidant genes (SOD-1, CAT, and GPX-1), detoxification genes (GST-1 and CYP306A1), the storage protein gene vitellogenin, and immune system antimicrobial peptide genes (Defensin-1, Abaecin, Hymenoptaecin, and Apidaecin), through real-time PCR. All pesticide treatments induced changes in gene expression, with bixafen showing the most prominent upregulation. Exposure to 1 µg of each of the three pesticides resulted in upregulation of genes associated with detoxification and nutrition processes, and downregulation of immune system genes. When the three pesticides were combined at a dose of 7 µg each, there was a pronounced downregulation of all genes. Dietary supplementation led to a slight reduction in gene expression alterations provoked by the fungicides.

Introduction: The World Health Organization (WHO) recommends visual inspection with acetic acid (VIA) for cervical cancer screening (CCS) in lower-resource settings; however, quality varies widely, and it is difficult to maintain a well-trained cadre of providers. The Smartphone-Enhanced Visual Inspection with Acetic acid (SEVIA) program was designed to offer secure sharing of cervical images and real-time supportive supervision to health care workers providing screening in semirural Tanzania, in order to improve quality and accuracy of visual assessment of the cervix for treatment. The purpose of this evaluation was to document early learnings from patients, providers, and higher-level program stakeholders, on barriers and enablers to program implementation. Methods: From September 9th to December 8th, 2016, observational activities and open-ended interviews were conducted with image reviewers (n= 5), providers (n=17), community mobilizers (n=14), patients (n=21), supervisors (n=4) and implementation partners (n=5) involved with SEVIA. Sixty-six interviews were conducted at 14 facilities, in all 5 of the program regions. Results SEVIA was found to be a highly regarded tool for the enhancement of CCS services in Northern Tanzania. Acceptability, adoption, appropriateness, feasibility, and coverage of the intervention were highly recognized. It appeared to be an effective means of improving good clinical practice among providers and fit seamlessly into existing roles and processes. Barriers to implementation included network connectivity issues, and community misconceptions and adoption of CCS more generally. Conclusion: SEVIA is a practical and feasible mobile health intervention and tool that easily integrated into the National CCS program to enhance quality of care. With the introduction of HPV DNA testing as a primary screening strategy for cervical cancer prevention in settings such as Tanzania, the role of a mobile health platform for program surveillance, tracking follow-up care, and quality assurance of visual assessment of the cervix for treatment (in women who test positive for high-risk HPV) further supports the importance of programs, such as SEVIA, in low resource contexts. Further expansion of the program, especially to rural areas where screening providers can benefit from virtual support for screening services through the use of the mobile App, could strengthen the delivery of services within the national cervical cancer prevention program.

Pulmonary sarcoidosis is a multisystem granulomatous interstitial lung disease (ILD) with a variable presentation and prognosis. Early accurate detection of pulmonary sarcoidosis may prevent progression to pulmonary fibrosis, a serious and potentially life-threatening form of the disease. However, the lack of a gold-standard diagnostic test and specific radiographic findings pose challenges in diagnosing pulmonary sarcoidosis. Chest computed tomography (CT) imaging is commonly used but requires expert, chest-trained radiologists to differentiate pulmonary sarcoidosis from lung malignancies, infections, and other ILDs. In this work, we developed a multichannel, CT and radiomics-guided ensemble network (RadCT-CNNViT) with visual explainability for pulmonary sarcoidosis vs. lung cancer (LCa) classification using chest CT images. We leverage CT and hand-crafted radiomics features as input channels, and a 3D convolutional neural network (CNN) and vision transformer (ViT) ensemble network for feature extraction and fusion before a classification head. The 3D CNN sub-network captures localized spatial information of lesions, while the ViT sub-network captures long-range, global dependencies between features. Through multichannel input and feature fusion, our model achieved the highest performance with accuracy, sensitivity, specificity, and combined AUC of 0.93±0.04, 0.94±0.04, 0.93±0.08 and 0.97 respectively in a 5-fold cross-validation study with pulmonary sarcoidosis (n=126) and LCa (n=93) cases. The model offers promising potential for improving the diagnosis of pulmonary sarcoidosis. A detailed ablation study showing the impact of CNN+ViT compared to CNN or ViT alone, and CT+radiomics input, compared to CT or radiomics alone, is also presented in this work.

The Tisza River is the longest tributary of the Danube, draining the eastern part of the Carpathian Basin (Central Europe). Five countries share its catchment with different waste production and management practices. Large amounts of waste, including macroplastics (MaPs), are washed into the river. Some of the litter is trapped by the riparian vegetation forming litter accumulations. The study aimed to map the amount of litter by a citizen science program and remote sensing data and to compare the MaP data to the amount of microplastic fragments in sediments. Volunteers reported 3216 riverine litter accumulations from five countries along the entire length of the Tisza (2016–2022). The results suggest that low flow conditions (e.g., impoundment by dams) support litter and MaP trapping. The volume of large accumulations registered by the citizens showed a good correlation with the area of drifting litter revealed on Sentinel-2 images (2015–2021) using machine learning algorithms. Though the MaPs probably fragmentate during their fluvial transport, no clear connection was found between the volume of litter accumulations and the mean microplastic fragment content of sediments (2019–2022). The “Clean Tisza Map“ reveals the high degree of stranded pollutants along rivers and supports public cleanup activities.

Colorectal cancer (CRC) remains a major global health issue. Although chemotherapy is the first-line treatment, its effectiveness is limited due to drug resistance developed in CRC. To overcome resistance and improve the prognosis of CRC patients, investigation for new therapeutic approaches is necessary. Using human colorectal adenocarcinoma (HT29) and metastatic CRC (SW620) cell lines, the potential anticancer properties of a newly synthesized compound 1-(Isobutyl)-3-(4-methylbenzyl) benzimidazolium chloride (IMBZC) were evaluated by performing MTT cytotoxicity, cell migration, and colony formation assays, as well as by monitoring apoptosis-related protein and gene expression using Western blot and reverse transcription-quantitative polymerase chain reaction technologies. Tested at various concentrations, the half-maximal inhibitory concentrations (IC50) of IMBZC on HT29 and SW620 cell growth were determined to be 6.97 μg/mL and 4.89 μg/mL, respectively. IMBZC did not alter cell growth of normal cells HEK293. In addition, IMBZC inhibited cell migration and significantly decreased colony formation, suggesting its promising role in suppressing cancer metastasis. Mechanistic analyzes revealed that IMBZC treatment increased the expression of pro-apoptotic proteins p53 and Bax, while decreasing the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL, thus indicating the induction of apoptosis in IMBZC-treated CRC cells, compared to untreated cells. Additionally, the addition of IMBZC to conventional chemotherapeutic drugs (i.e., 5-fluorouracil, irinotecan, and oxaliplatin) resulted in an increase in the cytotoxic potential of the drugs. In conclusion, the study suggests that IMBZC has substantial anticancer effects against CRC cells through its ability to induce apoptosis, inhibit cancer cell migration and colony formation, and enhance the cytotoxic effects of conventional chemotherapeutic drugs. These findings indicate that IMBZC could be a promising chemotherapeutic drug for the treatment of CRC. Further research should be conducted using in vivo models to confirm the anti-CRC activities of IMBZC.

This paper describes the early-stage prototyping process developed to probe into the socio-cultural dimensions of the Co-Drive project, which is a new service concept for traveling and socializing by car between a real driver on a semi-automated car and a remote passenger connected via virtual reality from home. By focusing on the intertwining journeys of the two actors of the experience, the driver and the remote passenger, three key interactions have been isolated and addressed as separate prototyping interventions in the wild. Such a seamful prototyping strategy enabled the users to experiment the whole service although the technology was not yet completely developed, and more specifically it allowed them to accommodate and appropriate each part of the experience into their everyday activities, revealing initial evidences of the potential social impact drawn by a future deployment of the service.

In the Ebro Delta, the abundance of burrowing bivalves has dramatically decreased, with the blue crab, Callinectes sapidus, being blamed by shellfish collectors. Trends from 2010 evidence a decrease in the capture of clams (Ruditapes spp.) before 2016 (start of blue crab fisheries), although further decline of both clam and cockle (Cerastoderma glaucum) occurred in 2018. In contrast, captures of razor clam (Ensis siliqua) have increased by 3.6-fold since 2016. Predation risk for these taxa with contrasting burrowing capacities (1.7 ± 0.3cm, 0.4 ± 0.2cm, and 26.3 ± 0.1cm, respectively), was assessed using predation preference (N= 5 tanks; 5 individuals of each species) and no-choice experiments (N= 5 tanks; 15 individuals) in the absence and in the presence of sand. Results showed that in the absence of sand, the razor clam, was fully preyed in 24h, clams in 96h, and cockles reached 60% after 144h. Conversely, when sand was present, only 4% of razor clams were predated, while clams and cockles reached 60-100% in 120-144h. No-choice results featured similar patterns depending on substrate availability. Overall, clams and cockles appear to be greatly vulnerable to blue crab predation, whereas the razor clam may escape thanks to its deeper burrowing capacity.

With the rapid development of gene therapy technology in recent years, its abuse as a method of sports doping in athletic has become a concern. However, there is still room for improvement in gene doping testing methods, and a robust animal model needs to be developed. Therefore, the purposes of this study were to establish a model of gene doping using recombinant adeno-associated virus vector-9 including the human erythropoietin gene (rAAV9-hEPO), and to establish a relevant testing method. First, it was attempted to establish the model using rAAV9-hEPO on mice. The results showed a significant increase in erythrocyte volume accompanied by an increase in spleen weight, confirming the validity of the model. Next, we attempted to detect proof of gene doping by targeting DNA and RNA. Direct proof of gene doping was detected using a TaqMan-qPCR assay with certain primers/probes. In addition, some indirect proof was identified in RNAs through the combination of a TB Green qPCR assay with RNA sequencing. Taken together, these results could provide the foundation for an effective test for gene doping in human athletes in the future.

In this study, we demonstrate the direct preparation of dihalo-γ-lactams featuring two distinct halogens from dichloroamides using a novel Atom Exchange Radical Cyclization (AERC) procedure. This method integrates the established Atom Transfer Radical Cyclization with halogen exchange in solution. The technique operates under mild conditions and requires little amounts of metallic copper, serving as both a supplemental activator and reducing agent.

Background: Glioma surgery was remarkably renewed in the past 2 decades, with improved safety and limited but yet improved life expectations. Fluorescence-guided resection of high-grade gliomas (HGG) plays a central role in this sense, by allowing higher degrees of extent of resection (EOR). The introduction of the exoscopic guided surgery may be considered an im-plementation for fluorescence techniques over the traditional microscopes. We present the appli-cation and the advantages of the exoscopic guided surgery compared to the microscopic surgery in tumor resection guided by 5-ALA fluorescence in patients with HGG. Methods: ten consecutive patients underwent a surgery for HGG resection. The surgery was per-formed via an exoscopic-guided procedure (Olympus Orbeye) and after oral administration of Gliolan 5 hours before the procedure. During surgery, the procedure was shifted to microscope (Kinevo 900, Zeiss) view. The intensity of the fluorescence under the two different was subjectively measured in different picture samples during the surgery in a 1 to 5 (from minimum to maxi-mum) scale. The brightness of the surgical field and the detailing of the anatomy were also ana-lyzed comparatively. Results: among the ten patients the histopathological diagnosis was an high grade glioma in all cases. In 9 cases was possible to achieve the gross total resection. There was no perioperative mortality. The median fluorescence intensity, on a scale of 1–5, was 4.5 in the exoscope group and 3.5 in the microscope group (p

Two distinct measures of information, connected respectively to the amplitude and phase of the wave function of a particle, are proposed. There are relations between the time derivatives of these two measures and their gradients on the configuration space, which are equivalent to the wave equation. The information related to the amplitude measures the strength of the potential coupling of the particle (which is itself aspatial) with each volume of its configuration space, i.e. its tendency to participate in an interaction localized in a region of ordinary physical space corresponding to that volume. The information connected to the phase is that required to obtain the time evolution of the particle as a persistent entity starting from a random succession of bits. It can be considered as the information provided by conservation principles. The meaning of the so-called "quantum potential" in this context is briefly discussed.

The Fuzzy Transportation Problem (FTP) represents a significant extension of the Classical Transportation Problem (TP) by introducing uncertainly and imprecision into the parameters involved. Various algorithms have been proposed to solve the FTP, including fuzzy linear programming, metaheuristic algorithms and fuzzy mathematical programming techniques combined with Artificial Neural Networks. This paper presents the application of Trigonometric Acceleration Coefficients-PSO (TrigAc-PSO), a variation of the Classical Particle Swarm optimization algorithm, which is an innovative algorithm originally developed for solving the TP. TrigAC-PSO, has demonstrated remarkable success in optimizing various problem domains in crisp environments.

The intricate architecture of dendritic arborization is fundamental to the formation and functionality of neural networks, serving as the primary site for synaptic integration and signal propagation. This study presents a pioneering computational model that simulates dendritic growth dynamics, employing exponential and logarithmic scaling over an extended developmental period of 720 days. This model offers a valuable tool for investigating the implications of diverse dendritic growth patterns on neural development, synaptic connectivity, and ultimately, cognitive functions. The computational framework incorporates biologically plausible parameters, allowing for the systematic exploration of dendritic branching patterns and their potential impact on neuronal information processing. By simulating exponential and logarithmic growth scales, the model captures the inherent complexity and diversity of dendritic morphologies observed in various neuronal populations across different brain regions. The findings from this study hold significant implications for our understanding of neural circuit assembly, synaptic integration, and the potential functional consequences of aberrant dendritic growth patterns observed in neurodevelopmental disorders. Furthermore, the model's ability to simulate extended developmental trajectories over a prolonged period of 720 days offers insights into the dynamic interplay between dendritic growth and synaptic pruning, which is crucial for the refinement and optimization of neural networks.

Introduction: In the year 2022, 4.9 million children died worldwide before five years of age. United Nations General Assembly has set the target of bringing down under-five child mortality to 25 deaths per 1000 live births by 2030. However, the United Nations Inter-Agency Group for Child Mortality Estimation highlights, that without rapid action many low and Lower Middle-Income Countries (LMICs) will not be able to achieve this target and 35 million under-five children will die before 2030. In such a scenario understanding the determinants that bring down preventable deaths in children is important. Design: Anonymized, publicly available data from the India National Family Health Survey (NFHS-5) is collected. The sample consisted of 724,115 women in the age group of 15-49 years has been sub-grouped as urban and rural women. Data on the number of Anganwadi centers per state has been collected from the Ministry of Women and Child Development. For better analysis of data, the country is divided into regions. Union territories are grouped in these regions as per their geographical locations. Descriptive statistical analysis, correlation coefficient analysis, and linear regression analysis were done. Results: Results of the Pearson correlation indicated that there is a significantly large positive relationship between operational AWCs (%) and U5MR (r = 0.542, p < .001) whereas there is a significantly large negative relationship between women with Internet access (%) and U5MR, (r = -0.738, p < .001). For our data, the multiple regression equation for y is U5MR (per 1000 live births) = 0.77266. AWCs (%) - 0.58788. women with Internet access (%) + 53.68073. Conclusion: Compared to NFHS-4 (2015-16) U5MR has reduced in almost all states of the country. The study shows more urban women have access to the Internet as compared to rural women. Child mortality is higher in rural areas in every state as compared to urban areas. Urban women have more access to health information because of internet access which may be the reason for lesser child mortality in urban areas compared to rural areas. Internet access for women (individual level) is far more effective in bringing down U5MR if compared to the community-level approach of Daycare centers.

This study evaluates the viability of n-octanol as an alternative fuel in a direct-injection diesel engine, aiming to enhance sustainability and efficiency. Experiments employed varying blends of n-octanol (10%, 30%, and 50% by volume) with pure diesel, analyzing impacts on engine performance and emissions. The methodology involved testing each blend in a single-cylinder engine, measuring engine performance parameters such as brake torque and brake power under full load conditions across an engine speed range from 1400 to 2500 rpm. Comparative assessments of performance and emission characteristics at a constant engine speed of 1700 rpm were also conducted with varying loads. Results indicated that while n-octanol blends consistently improved brake thermal efficiency, they also increased brake specific fuel consumption due to the lower energy content of n-octanol. Consequently, while all n-octanol blends reduced nitrogen oxides (NOx) emissions compared to pure diesel, they also significantly decreased carbon monoxide, hydrocarbons, and smoke opacity, presenting a comprehensive reduction in harmful emissions. However, the benefits came with nuanced trade-offs: notably, higher concentrations of n-octanol (especially the 50% blend) led to a relative increase in NOx emissions as the octanol ratio increased. The study concludes that n-octanol significantly improves engine efficiency and reduces diesel dependence, but optimizing the blend ratio is crucial to balance performance improvements with comprehensive emission reductions.

Abstract Background: Analysis of different type of consolidation in dogs and cats relay on parenchymal and vascular criteria. Hypothesis: the vascular criteria of the consolidation it’s possible to perform in dogs and cats and vascularisation is different in shred, tissue, nodule, wedge sign and mass. Animals: 347 cats and 634 dogs with different types of consolidations. Methods: Retrospective study between 2018-2023. Lung ultrasound performed in dogs and cats with different types of consolidations. Characteristic of bronchogram: air dynamic and static bronchogram, fluid bronchogram or absence of bronchogram. Types of vascularisations in consolidation: tree like type, residual, chaotic vascularisation and penetrating from the chest wall to consolidation and “vascular sign”. Conclusion and Clinical Importance: Analysis of bronchogram and type of vascularisation in consolidation is possible to perform in dogs and cat. The analysis of mentioned criteria had an impact on subsequent diagnostic and therapeutic decisions

Depression, anxiety, and pain are part of a common phenomenon that requires to be studied together when evaluating patients with chronic pain. The aim of the study was to examine the correlations between depression, anxiety and pain intensity in patients with chronic pain and how they change when a depressive episode was added. A sample of 120 patients with chronic pain (age: 51.90±11.94; 81.7% female; 18.3% male) was studied in two stages with a three-month period between them. Patients with a depressive episode (n=61) were treated with antidepressants and analgesics, while a patient without depression (n=59) was treated only with analgesics. The scales used to achieve the objectives were: HAM-D-17, Spielberger‘s STAI and VAS. Insignificant correlations were found between depression, state and trait anxiety, and pain intensity (p&lt;0,05) in the group without depression, except for a significant one between depression and state anxiety (p&lt;0,01) in the second stage. Significant correlations were identified between all indicators (p&lt;0,01) in the group with depression at the two stages. Those in the second stage were stronger. The interrelations between sensory and affective aspects of pain were stronger when a depressive episode occurs, the severity of which determines their dynamics.

Reducing the carbon footprint of energy production is one of the most pressing challenges facing humanity today. Lignocellulosic biomass residues from fruit production industries show promise as a viable energy source. This paper presents a study of the Italian context concerning the utilization of orchard lignocellulosic residues for energy production as electricity or bioethanol. The potential of various orchard residues was assessed through chemical and physical analysis, and an equivalent electrical energy of about 6441.62 GWh or an amount of 0.48 Mt/y of bioethanol was obtained based on the average annual dry residue mass availability of about 3.04 Mt/y. These data represent the 9.30% of the national electrical energy production from renewable sources, as well as the 6.21% of the Italian demand for gasoline in 2022. Electricity generation from these residues shown its potential as a reliable and sustainable baseload power source, as well as source of renewable transportation fuel. The studied process could be a valuable reference to expand these concepts on global scale to achieve a greener and more sustainable energy future.

Coal bottom ash (CBA) is a byproduct of coal-burning power plants. This material can be used as a fine aggregate replacement in concrete to reduce global natural material depletion. Concrete usage is increasing rapidly; subsequently, the industry’s carbon footprint is increasing. Using CBA in the construction industry will reduce the technical and economic problems associated with power plants by reducing solid waste. This project aimed to determine if adding new sustainable materials, such as CBA, to concrete will reduce natural raw material usage, energy consumption, and greenhouse gas emissions while improving performance. This study included two projects: comparing increased CBA content to the two-control project and determining the optimum content based on the compressive strength. The optimum CBA content is 50%, which reduces fine aggregate usage in a concrete mix by 50% while maintaining equivalent or better concrete strength than a pure Portland concrete mix without CBA. The air content of the concrete mix containing % CBA decreased with increased CBA content and compressive strength, possibly due to the spacing factor of the voids in the mix and CBA’s porous and fineness behavior. The CBA optimum content had a unit weight lower than the controls for both projects, which makes the CBA mix a lightweight concrete. Using this material can significantly reduce natural material usage and environmental harm by reducing CBA waste disposal and improving concrete performance.

Type II diabetes (T2D) is a multifaceted metabolic disease influenced by various factors (genetic, epigenetic, environmental, and other). An alarming surge in T2D prevalence is estimated, reaching 700 million cases by 2045 worldwide. This review explores the complex interactions of multiple risk factors throughout life and offers a new perspective on T2D. Genetic and epigenetic influences are described in detail. Prenatal factors, such as exposure to undernutrition and maternal overfeeding, induce lasting epigenetic changes, affecting T2D susceptibility. Furthermore, birthweight is a crude proxy for perinatal programming, with low and high birthweights associated with increased T2D risk. Often overlooked, the early postnatal period also significantly contributes to perinatal programming. Neonatal over-nutrition and feeding choices exert lasting effects on DNA methylation and metabolic outcomes later in life. Stress during this period further exacerbates T2D susceptibility. In continuation, childhood behaviors which are influenced by prior periods contribute substantially to T2D risk. Adverse childhood experiences amplify the risk of many diseases, including T2D. Sleep hygiene throughout life plays a role in metabolic health, influencing insulin resistance and appetite regulation. In adulthood, obesity remains a prominent predictor of T2D, with chronic stress contributing to weight gain and unhealthy lifestyle. This review proposes a novel perspective, considering T2D pathophysiology as a nonlinear process governed by numerous factors and their interactions throughout life. The inherent unpredictability suggests a need for personalized interventions tailored to specific risk profiles, emphasizing the importance of understanding gene-environment interactions and embracing a holistic view of T2D pathogenesis.

Long COVID, a name often given to the persistent symptoms following acute SARS-CoV-2 infection, poses a multifaceted challenge for health. This review explores the intrinsic relationship between comorbidities and autoimmune responses in shaping the trajectory of long COVID. Autoantibodies have emerged as significant players in COVID-19 pathophysiology, with implications for disease severity and progression. Studies show immune dysregulation persisting months after infection, marked by activated innate immune cells and high cytokine levels. The presence of autoantibodies against various autoantigens suggests their potential as comorbid factors in long COVID. Additionally, the formation of immune complexes may lead to severe disease progression, highlighting the urgency for early detection and intervention. Furthermore, long COVID is highly linked to cardiovascular complications and neurological symptoms, posing challenges in diagnosis and management. Multidisciplinary approaches, including vaccination, tailored rehabilitation, and pharmacological interventions, are used for mitigating long COVID's burden. However, numerous challenges persist, from evolving diagnostic criteria to addressing the psychosocial impact and predicting disease outcomes. Leveraging AI-based applications holds promise in enhancing patient management and improving our understanding of long COVID. As research continues to unfold, unravelling the complexities of long COVID remains paramount for effective intervention and patient care.

To reduce the cost of small wind turbines, a prototype of a butterfly wind turbine (6.92 m in diameter), a small vertical-axis type, was developed with many parts made of extruded aluminum suitable for mass production. An over-speed control system with movable arms that operated using centrifugal and aerodynamic forces was installed for further cost reduction. Introducing this mechanism eliminates the need for large active brakes and expands the operating wind speed range of the wind turbine. However, although the mechanism involving the use of only bearings is simple, the violent movement of the movable arms can be a challenge. To address this in the present study, dampers were introduced on the movable arm rotation axes to improve the movement of the movable arms. To predict the behavior of a movable arm and the performance of the wind turbine with the mechanism, a simulation method was developed based on the blade element momentum theory and the equation of motion of the movable arm system. Comparison of experiments and predictions with and without dampers demonstrated qualitative agreement. In the case with dampers, measurements confirmed the predicted increase in the rotor rotational speed when the shorter ailerons installed perpendicularly to the movable arms were used to achieve the inclination. The movable arm system with dampers is expected to be a useful device for vertical-axis wind turbines that are difficult to control.

Brown rice is a familiar whole grain in Japan. We examined national trends in brown rice consumption among Japanese adults aged ≥ 20 years old, using individual-level data from the National Health and Nutrition Surveys conducted between 2012 and 2019. We employed multivariable logistic regression to identify factors associated with brown rice consumption. The 95th percentile of daily brown rice intake remained at 0.0 grams throughout the study period. The percentage of brown rice consumers increased from 1.8% (95% confidence interval: 1.6–2.1) in 2012 to 2.3% (95% confidence interval: 1.8–3.0) in 2019. Compared with individuals who consumed only white rice, brown rice consumers had significantly higher mean intake levels of macronutrients, legumes, vegetables, fruits, and nuts. Brown rice consumption was positively associated with certain sociodemographic characteristics (being female, older age, residing in a major city, living without very young children, and having higher education levels) and health behaviors (lower body mass index, engaging in regular exercise, and being a former or never smoker). Despite its potential nutritional benefits in balanced diets, only a small fraction of adults in Japan consume brown rice, indicating a need for further promotion, particularly among individuals with characteristics associated with brown rice consumption.

Background: Across the world, antibiotic resistance is a critical challenge. To address such a problem, it has to be done to investigate new antibiotic sources. Aim of the study: Study of the antibacterial activity of Corallopyronin A in preclinical animal testing and randomized human clinical trials stages 1/2, as well as investigating the purification of Corallopyronin A from different soil conditions in Egypt. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were tested to develop bacterial isolates that produced the antibiotic compound Corallopyronin A. Reversed phase HPLC was used to purify Myxopyronin A. The broth microdilution method and the paper disc diffusion assay determined the test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in phases 1/2 of randomized clinical studies involving humans and animal models. Results: Corallopyronin A was generated from the culture supernatant of the soil bacterial isolate Corallococcus coralloides M2, cultivated on a Casein yeast peptone( CYP) plate. The test antibiotic prevented the growth of several Gram-ve bacteria, including Escherichia coli, at MICs higher than 100 mcg/ ml; while blocking the development of many Gram +ve bacteria, with MICs ranging from 3 to 15 mcg/ ml. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. A bactericidal consequence of the test antibiotic was detected in the inhibition of prokaryotic DNA-dependent RNA polymerase( RNLP). Conclusion: The synthesis of the bactericidal antibiotic Corallopyronin A from Corallococcus coralloides M2 isolated from different soil settings in Egypt intrigued the current investigation.

CRISPR/Cas9 has emerged as the predominant method for genome editing due to its cost-effectiveness and broad applicability, playing a crucial role in advancing sustainable practices across various sectors. This systematic review leverages the PRISMA methodology to explore CRISPR/Cas9's impact on environmental protection, thereby supporting the Sustainable Development Goals (SDGs). Analyzing data from the Web of Science, the review found significant growth in related publications, with a 30% increase since 2014, predominantly from the US, China, Germany, and the UK. The study categorizes the scientific developments into three trends: advancements in agriculture, gene editing techniques, and biofuel production. Key discussions include the use of CRISPR/Cas9 in developing fourth-generation biofuels and environmental biosensors, as well as its applications in enhancing genetic resilience and controlling invasive species. These innovations highlight CRISPR/Cas9's potential in promoting sustainable resource management and energy generation, marking a pivotal contribution to ecological conservation and sustainability efforts.

Corneal biomechanics is a hot topic in ophthalmology. The biomechanical properties of the cornea (BMPs) have important implications in the management and diagnosis of corneal diseases such as ectasia and keratoconus. In addition, the characterization of BMPs is crucial to model the predictability of a corneal surgery intervention, the outcomes of refractive surgery or follow-up of corneal diseases. The biomechanical behavior of the cornea is governed by viscoelastic properties that allow, among other structural implications, the damping of excess of intraocular pressure and reduce damage to the optic nerve. Currently, the most versatile and complete methods to measure corneal viscoelasticity are based on air-puff corneal applanation. However, those methods lack the ability to directly measure corneal viscosity. The aim of this work is to propose a new methodology based on the analysis of corneal air-puff measurements through the Standard Linear Solid model (SLSM) to provide analytical expressions to separately calculate the elastic and time-dependent (corneal retardation time and viscosity) properties. The results shown the mean values of elasticity (E), viscosity (Ƞ) and corneal retardation time (τ) in a sample of 200 young and healthy subjects. The influence of elasticity and viscosity on viscoelasticity, high-order corneal aberrations and optical transparency is investigated. Finally, the SLSM fed back from experimental E and Ƞ values was employed to compare the creep-relaxation response between normal, an ocular hypertension patient and Ortho-K user.

High average power narrow-linewidth tunable solid-state lasers in the wavelength region between 2 to 3 μm are attractive light sources for many applications. This paper reports a narrow-linewidth widely-tunable laser system based on the polycrystalline Cr2+:ZnSe elements pumped by the repetitively-pulsed 2.1 µm Ho3+:YAG laser operating at the tens of kilohertz pulse rate. An advanced procedure of ZnSe-element doping and surface improvement was applied to increase the laser-induced damage threshold, which resulted in an increase of the output power of the Cr2+:ZnSe laser system. The high-average-power laser system comprised double master-oscillators and power amplifiers: Ho3+:YAG and Cr2+:ZnSe laser oscillators, and Ho3+:YAG and Cr2+:ZnSe power amplifiers. The output wavelength was widely tuned within 2.3-2.7 µm by an acousto-optical tunable filter inside the Cr2+:ZnSe master oscillator cavity. The narrow-linewidth operation at the pulse repetition rate of 20-40 kHz in a high-quality beam with the average output power up to 9.7 W was demonstrated.

Mechanical equipment is composed of several parts, the interaction between the parts exists throughout whole life cycle leads to the widespread phenomenon of fault coupling and the diagnosis of independent faults cannot meet the requirements of the health management of mechanical equipment under actual working conditions. In this paper, the topological structure of graph neural network is used to describe the correlation of coupling faults and multiple fault types are regarded as network nodes respectively. The fault features are fused and extracted by graph convolution to achieve the classification of coupling faults. In this paper, dynamic vertexes are defined in data topology and the parameters of DIGNN classification model are optimized by changing the fault type of dynamic vertexes during training stage. The data is loaded into dynamic vertexes for classification and analysis during testing stage. The one-dimensional vibration data is converted into two-dimensional time-frequency domain data by wavelet transform making the input features of the model interpretable to reduce the uncertainty of model training. The data topology is then fed into DIGNN for fault classification, and GCN's node aggregation gives interpretability to each layer of network data processing. The method proposed in this paper can realize accurate diagnosis of independent faults on the data set, and can effectively judge the coupling mode of coupling faults, which is suitable for coupling fault analysis of mechanical equipment.