Background. Transferrin receptor 1 (TfR1), glucose transporter 1 (GLUT1), and CD98hc are candidates for targeted therapy at the blood-brain barrier (BBB). Our objective was to challenge the expression of TfR1, GLUT1, and CD98hc in brain capillaries by the histone deacetylase inhibitor (HDACi) valproic acid (VPA). Methods. Primary mouse brain capillary endothelial cells (BCECs) and brain capillaries isolated from mice injected intraperitoneally with VPA were examined using RT-qPCR and ELISA. Targeting to the BBB was performed by injecting monoclonal anti-TfR1 (Ri7217)-conjugated gold nanoparticles measured using ICP-MS. Results. In BCECs co-cultured with glial cells, Tfrc mRNA expression was significantly higher after 6 h VPA returning to baseline after 24 h. In vivo Glut1 mRNA expression was significantly higher in males, but not females', receiving VPA, whereas Cd98hc mRNA expression was unaffected by VPA. TfR1 increased significantly in vivo after VPA, whereas GLUT1 and CD98hc were unchanged. Uptake of anti-TfR1-conjugated nanoparticles was unaltered by VPA in spite upregulated TfR expression. Conclusions. VPA upregulates TfR1 in brain endothelium in vivo and in vitro. VPA does not increase GLUT1 and CD98hc proteins. The increase in TfR1 does not result in higher anti-TfR1 antibody targetability, suggesting targeting sufficiently occurs with available transferrin receptors without further contribution from accessory VPA-induced TfR1.

Introduction: Differentiated service delivery (DSD) models for antiretroviral treatment (ART) for HIV are being scaled up in the expectation that they will improve the quality and efficiency of treatment delivery and reduce costs while maintaining at least equivalent clinical outcomes. Even this minimum requirement of equivalent clinical outcomes is poorly documented for most models and settings, however. We reviewed the recent literature on DSD models to describe what is known about clinical outcomes. Methods: We conducted a rapid systematic review of peer-reviewed publications in PubMed, Embase, and the Web of Science and major international conference abstracts that reported outcomes of DSD models for the provision of ART in sub-Saharan Africa from January 1, 2016 to September 12, 2019. Sources reporting standard clinical HIV treatment metrics, primarily retention in care and viral load suppression, were reviewed and categorized by DSD model and source quality assessed. Results and Discussion: Twenty-nine papers and abstracts describing 37 DSD models and reporting 52 discrete outcomes met search inclusion criteria. Of the 37 models, 7 (19%) were facility-based individual models, 12 (32%) out-of-facility based individual models, 5 (14%) client-led groups, and 13 (35%) healthcare worker-led groups. Retention was reported for 73% of the models and viral suppression for 57%. Where a comparison with conventional care was provided, retention in most DSD models was within 5% of that for conventional care; where no comparison was provided, retention generally exceeded 80%. For viral suppression, all those with a comparison to conventional care reported a small increase in suppression in the DSD model; reported suppression exceeded 90% in 11/21 models. Analysis was limited by the extensive heterogeneity of study designs, outcomes, models, and populations. Most sources did not provide comparisons with conventional care, and metrics for assessing outcomes varied widely and were in many cases poorly defined. Conclusion: Existing evidence on the clinical outcomes of DSD models for HIV treatment in sub-Saharan Africa is limited in both quantity and quality but suggests that retention in care and viral suppression are roughly equivalent to those in conventional models of care.

Background/Objectives: Caregivers play an important role in supporting care recipients to navigate their health needs including adherence to dietary recommendations which are complex and multifaceted. The study aimed to i) describe the nutrition knowledge of caregivers of people with chronic kidney disease (CKD), and ii) explore caregivers’ perception of their role in providing healthy meals and nutrition support for care recipients. Methods: Caregivers (n=78) of people with stage 1-5 CKD or post-transplant were recruited from a single centre. A sequential mixed-methods approach was used. Nutrition knowledge was assessed with the revised General Nutrition Knowledge questionnaire. Theory informed semi-structured interviews in a sub-sample (n=12) explored caregiver perception. Results: Most caregivers were female (75.6%) caring for a male care recipient (87%; aged 74 (66;80) yrs.). Caregivers (75.6%) provided a meal ≥6 times/week to their care recipient and had moderate nutrition knowledge (66.1 (60.5; 73.9) %). Four themes emerged describing caregivers’ perception on meal provision and nutrition support including i) food literacy skills are valued, ii) social support is important, iii) caregivers’ sense of social responsibility, and iv) meal provision is complex and dynamic. Conclusions: Caregivers have moderate nutrition knowledge; they want to provide healthy meals and support to care recipients to adhere to dietary recommendations. Targeted, co-designed nutrition education programs for caregivers may enhance nutrition care delivery to people with CKD.

Background: Parity and vaginal delivery may contribute to female urinary incontinence prev-alence. The aim of this study was to evaluate the impact of parity and type of child delivery on pelvic floor muscle strength (PFMS). Material and Methods: 140 healthy women were prospectively evaluated and distributed into 4 groups: G1 (n=34) 30-40 years old; G2 (n=38) 41-50; G3 (n=35) 51-60 and G4 (n=33) over 60. De-mographic data, and body mass index (BMI) were obtained using a clinical questionnaire. Sub-jective PFMS assessments were performed using transvaginal digital palpation (TDP), and ob-jective evaluation was obtained using a portable perineometer. Results: BMI was significantly higher in G4 compared to G1. There was a positive linear rela-tionship between age and BMI. The number of pregnancies was higher in G4 compared to G2 and vaginal delivery was more frequent in G4 compared to G1 and G3. There was no statistical correlation among different groups in PFMS assessed either by TDP and perineometer. Like-wise, we did not observe any negative linear relationship between PFMS and parity or number of vaginal deliveries. Conclusion: Our data demonstrates that both the number of pregnancies and of vaginal deliv-eries had no impact on PFMS in continent women.

Iron (Fe) is co-factor for enzymes of the developing brain necessitating sufficient supply. We investigated the effects of administering ferric derisomaltose/Fe isomaltoside (FDI) subcutaneously to Fe deficient (ID) pregnant rats on cerebral and hepatic concentrations of essential metals and gene expression of ferroportin and hepcidin. Pregnant rats subjected to ID were injected with FDI on the day of mating (E0), 14 days into pregnancy (E14), or the day of birth (Postnatal (P0)). The efficacy was evaluated by determination of cerebral and hepatic Fe in pups on P0 and as adults on P70, and the concentration of copper (Cu) and zinc (Zn). Females fed an ID diet (5.2 mg/kg Fe) had offspring with significantly lower cerebral and hepatic Fe compared to female controls fed a standard diet (158 mg/kg Fe). Cerebral Cu increased irrespective of supplying a standard diet or administering FDI combined with the standard diet. Hepatic hepcidin was significantly lower following ID, whereas cerebral hepcidin was virtually undetectable in all experimental groups. In conclusion, administering FDI subcutaneously to ID pregnant rats on EO normalizes cerebral Fe in the fetus, but when applied at later gestational ages, additional Fe to the offspring is needed to normalize cerebral and hepatic Fe.

Glioblastoma (GBM) is the most common malignant primary brain tumor, with a median survival rate of less than two years. Currently, there is no cure for GBM, underscoring the urgent need for innovative treatment approaches. Vaccine design emerges as a crucial strategy, offering a safe and effective means for both preventive and therapeutic interventions against GBM. In this study, we targeted four GBM-associated mutated surface proteins—urokinase plasminogen activator sur-face receptor (PLAUR), integrin beta-3 (ITGB3), and the B-41 alpha chain (HLA-B) and A-24 alpha chain (HLA-A) of the HLA class I histocompatibility antigens—to design a peptide-based vaccine. The vaccine construct includes cytotoxic T lymphocyte (CTL) and T helper cell (Th cell) epitopes, and was meticulously evaluated for antigenicity, allergenicity, and toxicity. The results indicate that the vaccine is antigenic and non-allergenic, making it a promising candidate. Additionally, the physico-chemical properties of the vaccine suggest stability and suitability for further de-velopment. Immune simulation studies predict efficient immune responses upon vaccine ad-ministration. Our vaccine shows promise as a potential tool in the fight against GBM, offering new hope for patients facing this devastating disease.

Delivering nucleic acid therapeutics across cell membranes is a significant challenge. Cell-penetrating peptides (CPPs) containing arginine (R), tryptophan (W), and histidine (H) show promise for siRNA delivery. To improve siRNA delivery and silencing a model STAT3 gene, we hypothesized that oleyl acylation to CPPs, specifically (WRH)n, would enhance STAT3 silencing efficiency in breast and ovarian cancer cells. Using Fmoc/tBu solid-phase peptide chemistry, we synthesized, purified, and characterized the oleyl-conjugated (WRH)n (n = 1-4) peptides. The peptide:siRNA complexes were non-cytotoxic at N/P 40 (~20 μM) against MDA-MB-231, MCF-7, SK-OV-3, and HEK-293 cells after 72 h incubation. All peptide:siRNA complexes showed serum stability at N/P ≥40. The synthesized conjugates, with a diameter of <100 nm, formed nano complexes with siRNA and exhibited stable range of zeta potential values (13-18 mV at N/P 40). Confocal microscopy and flow cytometry analysis provided qualitative and quantitative evidence of successful cellular internalization of siRNA. Peptides oleyl-(WRH)3 and oleyl-(WRH)4 showed ~60% and ~75% cellular uptake of siRNA, respectively, in both MDA-MB-231 and SK-OV-3 cells. Western blot analysis of oleyl-(WRH)4 demonstrated effective silencing of the STAT-3 gene, with ~75% silencing in MDA-MB-231 cells and ~45% in SK-OV-3 cells.

There is an observed general low performance of Ethiopian Sport Governing Bodies (SGBs) in service delivery. Evidence shows that the trend can be corrected with proper understanding and insight into the process of organisational and management factors of these SGBs. This study aimed to investigate the contribution of organisational and management factors on effective sport service delivery in SGBs. For this study, a cross-sectional research design was employed. Purposive sampling was used to choose 350 samples. Pearson Product Moment Correlation Coefficient and multiple regression were used to analyse the data at the 0.05 significant level. The findings confirmed that organisational and management factor variables had a significant positive relationship with sport service delivery (organisational structure (r=0.515), organisational capabilities (r=0.701), communication (r=0.549), management practice (r=0.571), materials & resources (r=0.527) and stakeholders satisfaction (r=0.742). In addition, Management factors were found to be significant contributors for predicting effective sport service delivery (F(3, 329)= 165.868, R2= 0.612). Furthermore, organisational factors had a joint significant contribution to effective sport service delivery (F(3, 329) = 148.743, R2= 0.576). In addition, organisational and management factor variables jointly best predicted effective sport service delivery in Ethiopian SGBs (F(6, 326) =130.81, R2= 0.707). Therefore, this study suggests organisational and management factor variables can be used to predict effective sport service delivery.

(1) Background: Applied health services research (AHSR) relies upon coordination across multiple organizational boundaries. Our aim was to understand how competing organizational and professional goals enhance or impede the conduct of high quality AHSR. (2) Methods: A qualitative study was conducted in two local health care systems in the UK, linked to a feasibility trial of a clinic-based intervention in secondary care. Data collection involved 24 semi-structured interviews with research managers, clinical research staff, health professionals, and patients. (3) Results: This study required a dynamic network of interactions between heterogeneous health and social care stakeholders, each characterized by differing ways of organizing activities which constitute their core functions; cultures of collaboration and interaction and understanding of what research involves and how it contributes to patient care. These interrelated factors compounded the occupational and organizational boundaries that hindered communication and coordination. (4) Conclusions: Despite the strategic development of multiple organizations to foster inter-professional collaboration, the competing goals of research and clinical practice can impede the conduct of high quality AHSR. To remedy this requires the alignment and streamlining of organizational goals, so that all agencies involved in AHSR develop a shared understanding and mutual respect for the progress of evidence-based medicine and the complex and often nuanced environments in which it is created and practiced.

Burden of diseases measured as disability-adjusted life years per 100,000 people can be mined from public domain data, when they are made available by population health surveillance systems. This can be analysed to allow insightful comparisons with the national average, and to understand differences in trends between the sexes, age groups, time periods, geographic regions and sub-regions. In this illustrative case study, we have analysed the Scottish burden of disease database to understand what ailed the population of the Grampian region before the COVID-19 pandemic. We have identified selected cancers, ischaemic heart disease, Alzheimer’s disease and other dementias amongst the highest contributors to the burden; that drug use disorders and colorectal cancer are showing worsening trends and require health promotion and disease prevention measures from ages 15 and 25 respectively, especially in Aberdeen City; and that males are more vulnerable to atrial fibrillation and flutter, diabetes mellitus and oesophageal cancer, while females are to cerebrovascular disease. We demonstrate the usefulness of our analysis and methodology for the wider health system, allowing targeted medical research investments and coordinated response from public health and health service delivery. We also show the need for up-to-date surveillance data, forecasts and evidence on the impact of interventions to be made available widely.

Background Nitrous Oxide (N₂O) is a dissociative anaesthetic that is sometimes used recreationally. The prevalence of N₂O use is difficult to quantify but appears to be increasing. Research on N₂O harms and application of harm reduction strategies are limited. The aim of this mixed method systematic review was to collate and synthesise the disparate body of research on recreational nitrous oxide use to inform harm reduction approaches tailored for young people. Methods To identify publications reporting recreational use of N₂O, a search of public health, psychology and social science databases was conducted. Databases included PubMed, CIHNAL, PsycINFO, Scopus and Web of Science. Gray literature and Google advanced search were also used. Due to limited published literature on the recreational use of N₂O, no limit was placed on publication date or study type. A thematic synthesis extracted descriptive and analytical themes from the selected studies. Quality appraisal was conducted using the CASP Tool for Qualitative studies and the Joanna Briggs Institute case report assessment tool Results The search retrieved 407 reports. Thirty-four were included in the final analysis including sixteen case reports. The included studies were primarily concerned with raising awareness of the apparently increasing use and subsequently increasing harms of recreational N₂O use. There was limited reference to policy or legislative responses in any published studies, no suggestions for harm reduction strategies or application of service level responses. In general, individuals lack awareness of N2O related harms. Conclusion The review found three key areas that deserve further consideration including: 1) policy, 2) service delivery, and 3) harm associated with N₂O use. We recommend a top-down (policy) and bottom-up (services delivery/services users) approach to harm reduction for N₂O use which also includes further consultation and research with both groups. Future research could explore young people’s experience of N₂O use including benefits and problems to inform contextually relevant harm reduction strategies.

Our study aimed to assess sprinkler irrigation's impact on the activity of selected soil enzymes concerning nitrogen metabolism and oxidation-reduction processes in the soil with different doses of inorganic nitrogen fertilizers. The soil Alfisol was sampled from the experimental field of spring barley in the University Research Center in the central part of Poland in the moderate transitory climate during the growing seasons 2015–2017. The index resistance (RS) was derived to recognise the resistance enzymes of drought. In the maturity phase, nitrate reductase activity was at an 18% higher level in irrigated soils and the activity of other enzymes was higher in no-irrigated treatments by 25% in dehydrogenase, 22% in peroxydase 33% in catalase and 17% in urease case. The development stage of barley influenced nitrate reductase activity. Enzymatic activity has been changing in the examined years of the research, depending on the weather conditions. During the maturity stage, the soil's lower ammonium nitrogen content resulted from higher spring barley uptake due to drought stress. Irrigation probably contributes to increased leaching of nitrate in soil. The highest index of resilience was presented in the soil catalase activity.

Background: The laryngeal mask airway Vision Mask (LMA VM) is a supraglottic airway device (SAD) with vision guidance system. The ideal head and neck position for direct laryngoscopy is known, but the ideal position for placing a LMA is not. The objective of this study is to evaluate and compare the optimal position for placement of a video laryngeal mask airway. Methods: This was a prospective observational, transversal and analytical study of 72 consecutive patients. In the same patient, laryngeal vision was first assessed with the head and neck in the sniffing position and then with the head in the neutral position. Procedures were filmed and performed by the same investigator. Assessment of the laryngeal view was performed using two classifications: modified Cormack-Lehane classification and Brimacombe classification. Device placement was considered adequate when the Cormack-Lehane rating was scored from 1 to 2 and the Brimacombe rating was from 2 to 4. Results: 72 patients were included in this study. In the assessment of the glottis using the Cormack Lehane classification for fiberoptic view, laryngeal visibility was adequate in 64 (88.89%) patients in the neutral position and in 65 (90,28%) patients in the sniffing position (p>0,05). In the fiberoptic view of the glottis, assessed using the Brimacombe classification, laryngeal visibility was adequate in 68 (93%) patients in the neutral position and in 69 (95%) patients in the sniffing position, (p>0,05). There was no statistically significant difference in the rate of success between the sniffing position (70 patients, 97.22% success rate) and the neutral position (67 patients, 93.06% success rate) during the first insertion attempt. Two patients required a second attempt in the sniffing position, while five patients required a second attempt in the neutral position. Conclusion: An adequate sniffing position did not result in a better glottic view than neutral position, and the number and type of additional maneuvers were equal in both positions.

(1) Background: Ectopic pregnancy (EP) is when fertilized ovum implanted outside of uterine cavity. The incidence was 1.5% to 2.0% of all pregnancies [1, 2]. EP decreases fertility ability [3]. This study focused on the pregnancy rate after EP and various parameters influencing pregnancy. (2) Methods: The data was extracted from National Health Insurance Research Database (NHIRD) during 2000-2013. The study group enrolled women with one EP history. Those who did not have EP was put into the control group. Chi-square/Fisher exact test was performed on category variable and t-test was used on continue variables. (3) Results: The EP group had a higher cumulative rate of conceive, 41.55% than control group, 37.14% and 1.16 times higher risk in developing pregnancy (P<0.001). The conceiving rate was lower than the control group in the first 5 years, but higher than the control group in the 10th to 14th years. (4) Conclusions: The fecundability after EP is lower at the beginning, but regained after long term follow.

Populations with healthcare needs often reside in post-conflict settings where basic services needed to maintain good health may be non-existent or hard to access. Therefore, there is a need for better identification and reallocation of resources as part of the post-conflict health rehabilitation effort. This study applies an asset-based approach to explore the more optimal design of health services and to identify the resource constraints for basic health service delivery to the most vulnerable communities in eastern Congo. We implemented the asset mapping in two phases. Firstly, we combined a qualitative survey with community walks to identify the assets already present in the communities. Secondly, we conducted group discussions to map out assets that are the core of Asset-Based Community Development (ABCD) practice. We finally documented all assets in a Community Asset Spreadsheet. Overall, 209 assets were identified as available and potentially valuable resources for the communities in eastern Congo. Among them, 60 were local associations, 24 were land and physical environment, 43 were local institutions, 46 were individuals, 32 to economy and exchange, and only 6 were related to culture, history, and stories. Drawing upon the findings from the qualitative survey, community walks, and group discussions, we conclude that an important number of resources were in place for basic health service delivery. By activating the existing and potential resources, the most vulnerable populations in eastern Congo might have the required resources for basic health service delivery. Our findings support the use of an asset-mapping research method as appropriate to identify existing and potential resources for basic health services in a post-conflict setting.

This study assesses the effectiveness of HCV self-testing (HCVST) distribution models compared to provider-led HCV testing (PL-HCVT), including the standard of care facility-based HCVT (SOC-HCVT) and community-based organization HCVT (CBO-HCVT) among people who inject drugs (PWID) in Vietnam. A cross-sectional study was conducted as part of a larger implementation science study in Hanoi and Ho Chi Minh City from September 2023 to April 2024. We engaged 8 CBOs and 10 public and private clinics in offering choice of HCVST through community-based and facility-based distribution, and secondary distribution), or PL-HCVT via SOC-HCVT and CBO-HCVT. Among 1,165 PWID, 693 opted for HCVST and 472 for PL-HCVT. The proportion of first-time testers was significantly higher in HIVST community-based and secondary distribution as well as CBO-HCVT compared to SOC-HCVT and facility-based HCVST (87.1%, 93.3% and 82.7% vs. 41.9% and 35.7%, respectively; p < 0.001). Overall, HCV seropositivity rate was lower in HCVST than PL-HCVT, however, higher in HCVST facility-based and community-based distribution compared to HCVST secondary distribution (28.1% and 20.4% vs. 5.7%, respectively). Community-based HCVST was most effective, followed by facility-based HCVST and secondary distribution. Our findings indicate that HCVST effectively reaches first-time testers and results in more people diagnosed and treated among PWID.

Epilepsy is one of the most prevalent and serious brain disorders, affecting 70 million people worldwide. Antiseizure medications (ASMs) though relieve symptoms and prevent the occurrence of future seizures in epileptic patients have limited effect on epileptogenesis. Addressing the multifaceted nature of epileptogenesis and its association with Nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome-mediated neuroinflammation requires a comprehensive understanding of the underlying mechanisms for development of targeted therapeutic strategies beyond conventional antiseizure treatments. Several types of NLRP3 inhibitors have been developed and their effect has been validated both in vitro and in vivo models of epileptogenesis. In this review, we discuss the advances in understanding the regulatory mechanisms of NLRP3 activation as well as progress made and challenges facing in the development of NLRP3 inhibitors for the treatment of epilepsy.

Bats are natural hosts for a wide variety of viruses and could therefore be the reservoir, source and spillover for several mammalian viruses, including adenoviruses. We examined faecal samples from 12 bats (five species of the family Vespertilionidae) from central Russia (Moscow Region) and found that two of them (16%) were positive for mastadenoviruses. One of the identified viruses was isolated from faeces of Nyctalis noctule and named BatAdV/MOW15-Nn19. The genome of the BatAdV/MOW15-Nn19 was 37,915 bp in length. Comparative studies have shown significant divergence of the nucleotide sequence of the BatAdV/MOW15-Nn19 genome from European mastadenoviruses, the highest genome sequence similarity was to isolate WA3301 from an Australian bat. Phylogenetic analysis, as well as a comparative analysis of the protein coding genes to homologous available from public database, showed evidence of novel species within Mastadenovirus genus (preliminary named «K»). Analysis of the short part of the DNA polymerase gene of BatAdV/MOW15-Nn19 reveals few NCBI records from Europe with high identity to the new virus, i.e. mastadenoviruses related to the new species are circulating in European bats. The partial genome of another mastadenovirus from Pipistrellus nathusii was identified, it represented bat adenovirus species B, which is widely distributed in European Vespertilionidae bats. New data on the genetic diversity of bat adenoviruses may help to better understand how they evolved in mammals and spread across Europe.

Correlations among estrus cycle, pyometra, and canine diabetes mellitus (CDM) have been described since the late 1950s, and substantial progress in understanding mechanisms beyond was achieved nowadays. Progesterone-related diabetes mellitus (PRDM) in dogs is known for its particular potential for diabetes remission. Thus, a deep understanding of the physiopathological aspects involved is crucial to postulate treatment guidelines to improve the PRDM remission rate, as well as to inform preventive measures. This narrative review aims to provide relevant detailed information on 1) canine estrus cycle and its impact on CDM etiology and management, 2) the role of pyometra as a further cause of insulin resistance, and 3) useful individual therapeutic and preventive strategies. Pharmacological annulment of progesterone effects, as well as inflammatory and progesterone-related conditions resolution in association with adequate exogenous insulin therapy, and residual beta cell function, are key aspects to achieve remission, or at least to improve diabetic clinical control. In this way, spaying should be considered mandatory in most PRDM cases. Preventive measures against CDM can include spaying recommendations; however, individual-based recommendations should be considered since castration may be associated with some long-term health issues.

As the world population grows, fulfilling the need for biomaterials in the healthcare system becomes increasingly important. Biomaterials, which include metals, polymers, ceramics, and composites, play an important role in the creation of medical devices that improve people's lives. The European Society for Biomaterials described biomaterials as non-biological materials used in medical devices to interact with biological systems. This definition has developed to encompass materials that treat, assess, or replace tissues or bodily functions. Biocompatibility, as defined by the FDA, is a key feature of biomaterials, as is the requirement to fulfil design requirements such as mechanical performance, geometry, and electrical control. Over the last decade, advances in regenerative medicine and tissue engineering have boosted biomaterials' usage in medical applications dramatically. Despite its promise, scientists, engineers, and physicians continue to face significant challenges due to the complexity of biomaterials. Biomaterials have various benefits, including biodegradability, non-toxicity, and biocompatibility, making them extremely useful for replacing, sustaining, or improving biological activities in damaged tissues. They are used in a wide range of applications, including tissue engineering implants, human tissue healing and regeneration, medication delivery systems, and biosensors. This study gives insights into the fundamental characteristics, case studies, and ethical issues associated with the usage and use of biomaterials, further examining their potential and significance in healthcare and medicine.

Three autonomous communities have been the ones that, in the 2022-2023 season, anticipated the document approved by the Public Health Commission, recommending influenza vaccination for all children aged 6 to 59 months. The main objective of this work is to evaluate the attitude of healthcare professionals towards the first universal vaccination campaign in our region, as well as the acceptability of the vaccines used and the attitude towards the piloting of school vaccination. Cross-sectional, survey-based, descriptive study. All healthcare professionals involved in the campaign were invited to participate. The 91.9% of surveyed professionals thought that flu vaccination from 6 to 59 months was important or very important. 89.8% had previous experience regarding the intramuscular vaccine. The professionals valued the intranasal vaccine significantly more positively; however, there were no differences when asking for each of the vaccines without comparison. The inhaled vaccine was preferred by 97.5% for the following campaign. Piloted school vaccination showed 75% acceptance. The inhaled vaccine was preferred by most professionals and the piloted school vaccination was highly accepted, and independently associated to the importance of vaccination as considered by physicians, being a medical doctor, and participation in the pilot program.

Macrophages as a source and target of GDF-15

We present a case report of a young patient with pectus carinatum who experienced a small right apex pneumothorax and exhibited Brugada patterns on electrocardiogram tracing. This is the first clinical case reporting Brugada pattern presentation in both a patient with pectus carinatum and a small pneumothorax. We conducted a clinical, anatomical, and electrocardiographic analysis to explore a physiopathological explanation for these findings, considering our patient had no history or clinical signs of Brugada Syndrome. We conclude that: 1. Pectus carinatum may create a window that facilitates the less resistive measurement of cardiac action potentials; 2. Small pneumothoraces can induce modifications in the cardiac electrical signal detected by surface electrodes, and pectus carinatum could unmask these modifications; and 3. Surface electrodes may measure subepicardial potentials that include and are modified by adjacent pericardial tissues, potentially resulting in alterations in transmural potential differences, thus producing fictitious Brugada patterns. Similarly, there is a possibility that the right ventricular outflow tract may be included within the subendocardial potentials.

There is consensus that climate variability and change is impacting food security in Eastern Africa, and that conventional extension approaches, based on top-down model of information dissemination and technology transfer, are too inadequate to help smallholder farmers tackle increasingly complex agro-climatic adversities. Innovative service delivery options exist but are mostly operated in silos with little effort to explore and blend them. There are efforts to develop a blended Climate-Resilient Farmers Field School methodology to address the gaps, with objective to improve participants’ knowledge, skills and attitude to apply the blended approach and to sensitize actors on what needs to be advocated at the policy level. Some 661 local trainers/facilitators (ToT/ToFs), 32% of them women and 54% youth, were trained across Kenya, Tanzania, and Uganda, with additional 76 Master Trainers (MToTs) trained to backstop the ToT/ToFs. Through the implementation, the process reached 36 agribusinesses covering some 237,250 smallholder farmers trained across Kenya, Tanzania, and Uganda on CSA technologies, practices, and innovations by the end of 2020. The blended approach offers lessons to transform extension to help farmers improve food security and resilience. Preliminary findings indicate that the process is rapidly shaping individual adaptive behavior and group adaptive thinking. Lessons also show a strong need for agronomists to work more closely with agro-meteorologists to ensure that farmers are properly guided to participate appropriately in the co-generation and application of climate information and agro-weather advisories, which they can interpret easily and utilize for their agricultural production purposes. Experience from this initiative can be leveraged to develop scalable participatory extension and training models

Cotton fiber, a crucial and sustainable resource for global textile production, undergoes a complex five-stage developmental process, encompassing initiation, elongation, transition, secondary cell wall biosynthesis, and maturation. These elongated single-cell fibers originate from the outer ovule epidermis. The development of cotton fibers involves intricate changes in gene expression and physiological processes, resulting in a nearly pure cellulose product vital for the global cotton industry. Decoding genes associated with fiber development enhances our understanding of cotton fiber mechanisms and facilitates the cultivation of varieties with enhanced quality. In recent decades, advanced omics approaches, including genomics, transcriptomics, and proteomics, have played a pivotal role in identifying genes and gene products linked to cotton fiber development, including the MYB transcription factor family which coordinates cotton fiber development. Molecular studies have revealed transcription factors like MYB, WRKY, Homeodomain Leucine Zipper (HD-ZIP) and basic Helix-Loop-Helix (bHLH) influencing fiber initiation and elongation. The intricate interplay of phytohormones like auxin, gibberellic acid (GA), brassinosteroid (BR), jasmonic acid (JA), ethylene, abscisic acid (ABA), and cytokinin is explored, providing a comprehensive perspective on shaping cotton fibers. Numerous candidate genes and cellular processes affecting various aspects of fiber development hold promise for genetic engineering or marker-assisted breeding to improve fiber quality. This review presents a comprehensive overview of key achievements in cotton molecular biology, with a specific emphasis on recent advancements in understanding transcription factors and phytohormones involved in cotton fiber initiation and elongation.

Introduction: The association between epilepsy and myasthenia gravis has rarely been reported, and only in small case series. Objective: To report the frequency of epilepsy and myasthenia gravis and to describe a case series of patients with myasthenia gravis and epilepsy, focusing on their clinical characteristics and searching for a possible physiopathological mechanism. Methods: A retrospective, observational, adult center study was conducted in 2022. Patients were recruited from the database of the outpatient clinic of the Myasthenia Gravis unit and Epilepsy unit. Results: Five patients were included. Frequency of epilepsy in the myasthenia gravis cohort was 5/469 (1.1%), and of myasthenia gravis in the epilepsy cohort was 5/1432 (0.35%). All patients suffered focal epilepsy, mainly fronto-central, and drug-resistant in half of them. Myasthenia gravis was generalized and with exacerbations in half of them. Three patients were thymectomized. Other autoimmune diseases were found in 2 (40%). Epilepsy onset preceded myasthenia gravis onset in all patients. Both diseases were considered autoimmune-related in 3/5 (60%). Conclusion: Epilepsy and myasthenia gravis are only infrequently associated. In adult patients, epilepsy onset precedes myasthenia onset in most cases. In some cases, epilepsy has an autoimmune aetiology and coexists with other autoimmune conditions.

The global antibiotic resistance crisis, driven by antibiotic overuse and misuse, is multifaceted. This study aimed to assess the microbiological and genetic characteristics of raw retail pork meat, including the isolation, antibiotic susceptibility testing (AST), whole genome sequencing (WGS) of selected indicator bacteria, antibiotic residue testing, and metagenomic sequencing. Samples were purchased from 10 randomly selected retail stores in Gauteng, South Africa. Samples were aseptically separated, with a portion sent to an external laboratory for isolating indicator bacteria and antibiotic residue testing. Identification of the isolated bacteria was reconfirmed using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS). AST was performed using the Microscan Walkaway system. WGS and metagenomic sequencing were performed using the Illumina NextSeq 550 instrument. The isolated E. coli and enterococci exhibited little phenotypic resistance, with WGS revealing tetracycline resistance genes. Isolated bacteria and meat samples all harboured tetracycline resistance genes, and the antibiotic residue concentrations were within acceptable limits for human consumption. In the metagenomic context, most identified bacteria were of food/meat spoilage and environmental origin, with the resistome analysis primarily indicating beta-lactam, tetracycline and multidrug resistance genes. Further research is needed to understand the broader implications of these findings on environmental health and antibiotic resistance.

Background/Objectives: Forceps delivery is a crucial obstetrical technique that has been increasingly underutilized in favor of cesarean delivery, despite numerous complications related to cesarean section. The major concerns in assisted vaginal birth (AVB) are the safety and long-term consequences. Thus, we aimed to investigate the neurodevelopmental outcome of children born with forceps delivery up to the age of seven. Methods: A prospective descriptive study was conducted from January 2011 to December 2016 among 49 women from our department in the Clinic for Gynecology and Obstetrics, University Clinical Center of Serbia. The study included women with term singleton cephalic pregnancies. Descriptive statistics were calculated for the baseline demographic and clinical features, whereas the logistic regression analysis was used to explore the association between various perinatal parameters and neurological status of newborns. The Sarnat and Sarnat classification was used to evaluate neurological status of newborns, while long-term neurodevelopmental outcome was assesed with Griffiths Mental Development Scale and additional questions based on the neurologist's clinical practice and experience. Results: Pathological neurological status of the newborn was found in 16.3%, with pathological ultrasound of CNS in 3%. A statistically significant association was observed with Apgar score, odds ratio of 0.575 (95% CI: 0.407–0.813, p = 0.002) and perinatal asphyxia, odds ratio of 9.882 (95% CI: 1.111–87.902, p = 0.04). However, this was unlikely to be related to the mode of delivery. Long-term adverse neurological outcome was seen in three cases, which accounts for 6.4%. These included mild disorders, such as delayed milestone, speech delay and motor clumsiness. Conclusion: The present study highlights the safety of forceps delivery regarding children's neurological outcomes at 7 years of age. This is an important contribution to the modern management of labor, especially in light of increasing rates of cesarean deliveries worldwide.

We document for the first time epsilon waves on the electrocardiogram of a patient with Dravet syndrome (DS) who does not exhibit structural cardiac pathology. DS, a severe form of pediatric epilepsy, involves mutations in the SCN1A gene, which disrupt sodium ion flow and increase the risk of sudden unexpected death in epilepsy. The epsilon waves, typically associated with arrhythmogenic right ventricular dysplasia, may also suggest a link between neuronal and cardiac dysfunctions. In our case, the epsilon waves appear to originate from abnormalities in sodium channels rather than structural changes in the myocardium. This finding underscores the importance of assessing both neurological and cardiac manifestations in patients with severe epilepsy, opening new avenues for the research and treatment of these interactions in DS.

Introduction: Type 1 diabetes mellitus is a chronic disease of autoimmune etiology that is highly prevalent in childhood. In the last decade, the possibility of using the Bacillus Calmette-Guérin vaccine for the treatment of this disease has been studied thanks to its immunomodulatory action . Objectives: The objective of this work is to carry out a systematic review of the available scientific evidence on the relationship between the tuberculosis vaccine and the treatment of diabetes in childhood. Secondarily, the aim is to study the incidence of Type 1 Diabetes Mellitus in a cohort of children from the Basque Country according to whether or not they have received the vaccine. Methods: An exhaustive bibliographic search has been carried out on the evidence available to date. For the epidemiological study in Euskadi, a comparison of accumulated incidences between vaccinated and unvaccinated population groups was made. Results: According to the literature analyzed, There is more and more evidence about the possible use of the tuberculosis vaccine in Type 1 Diabetes Mellitus. The results of our study were not conclusive, but we believe that it is necessary to continue with long-term studies to eliminate biases. Conclusions: The Bacillus Calmette-Guérin vaccine could be used for the treatment of autoimmune, allergic, infectious or oncological processes, although more studies are still necessary in this regard.

Maintaining sufficient levels of plant nutrients in the soil and controlling certain heavy metals, which can be toxic to the environment, are critical to ensure sustainable agricultural production. The study aimed to assess the linkage of crop-specific agricultural practices established by farmers in the Kvemo Kartli region (Georgia) with metal accumulation in soils of agricultural lands being subject to influence from polluted irrigation water in the past. In particular, we tried to identify the primary sources of micronutrients, including iron (Fe), copper (Cu), manganese (Mn), nickel (Ni), and zinc (Zn), and toxic elements such as cadmium (Cd) and lead (Pb), and share of the contaminated irrigation water and other factors related to agricultural practices under different land uses, such as intensive and extensive arable farming, vineyards, orchards, and permanent pastures having the least disturbed soil. Based on principal component analysis, five primary sources were identified and categorized according to farmers' interviews and previous studies conducted in the region. The results showed that increased concertation of plant-available Cu, Zn, Cd and Pb were mainly associated with irrigation water and intensive use of fungicides; Fe, Mn, and Ni were closely linked to several factors, such as the mineralogical composition of soils, mineral and organic fertilizers inputs, and atmospheric deposition from diffuse sources, where exhausts from transport are probably the primary source. During our study, we attempted to differentiate irrigation water inputs from fungicides using simulation based on irrigation pattern and irrigation water quality on the one hand and fungicide application rate and their metal content on the other. The simulation revealed that the intensive application of fungicides, especially in vineyards, is more significant in enriching soils with Cu and Zn than irrigation water. Identification of factorial dependences was supported by statistical analysis and application of a number of contamination assessment methods: Contamination Factor (CF), Pollution Load Index (PLI), single-factor Pollution Index (PI), Nemerow’s comprehensive pollution index (PIN), Enrichment Factor (EF), and Geo-Accumulation Index (Igeo). Applied environmental indices indicate that the soils under the former and existing vineyards are the most enriched with Cu and Zn, highlighting the significance of agricultural practices on heavy metals accumulation in soils of agricultural lands.

Introduction: The COVID-19 pandemic overwhelmed health systems globally, and affected delivery of other health services. We conducted a study in Uganda to describe interventions for continuity of access to other health services. Methods: We reviewed documents and interviewed 21 key informants. Thematic analysis was conducted to identify themes using the World Health Organization health system building blocks as a guiding framework. Results: Governance strategies included establishment of coordination committees and development and dissemination of guidelines. Infrastructure and commodities strategies included review of drug supply plans and allowing emergency orders. Workforce strategies included provision of infection prevention and control equipment, recruitment and provision of incentives. Service delivery modifications included designation of facilities for COVID-19 management, patient self-management, dispensing drugs for longer periods and leveraging community patient networks to distribute medicines. However, multi-month drug dispensing led to drug stock-outs while community drug distribution was associated with stigma concerns. Conclusions: Health service maintenance during emergencies requires coordination to harness existing health system investments. The service continuity committee coordinated efforts to maintain services and should remain a critical element of emergency response. Self-management and leveraging patient networks should address stigma to support service continuity in similar settings and strengthen service delivery beyond the pandemic.

Food insecurity remains a significant developmental challenge, particularly in rural areas, despite ongoing efforts to mitigate it. To better understand the persistence of this issue, this study investigates the causes of household food insecurity and the coping strategies employed by households in Zorkor Goo, Zorkor Kanga, and Zorkor Kadaare communities within the Bongo District of Ghana’s Upper East Region. A descriptive cross-sectional survey was conducted, sampling 196 households systematically from these communities. Data were collected through a structured questionnaire covering socio-demographic factors, causes of food insecurity, household coping strategies, and dietary intake. The analysis was performed using SPSS (Version 21.0), with food security status and dietary intake assessed via the FANTA Household Food Insecurity Access Scale (HFIAS) and Food Consumption Score, respectively. The study identified key factors contributing to food insecurity, including soil infertility, poor rainfall patterns, food spoilage, extravagant funerals, large family size, high unemployment, and lack of education. Major coping strategies among households included meal skipping, reducing meal size and frequency, migration, asset sales, and basket weaving. The findings revealed that 96.4% of households were severely food insecure, and over two-thirds (67.3%) exhibited poor dietary consumption. Notably, household employment levels, education, and food consumption scores were significantly associated with food insecurity (P&lt;0.001). These findings underscore the need for targeted interventions addressing the root causes of food insecurity and enhancing household resilience in these communities.

The continuous expansion of urban areas has significantly increased the coverage of impervious paved surfaces, leading to heightened heat absorption and the formation of urban heat islands (UHIs). This research centres on environmental footprint accounting and management to address the escalating UHI risks in the City of Salisbury, Adelaide, South Australia. To comprehend the extent of land use change over time, the study employs the Normalised Difference Vegetation Index (NDVI) in conjunction with Landsat satellite maps. The satellite maps were also analysed for the historical land surface temperatures, exploring the correlation between land use change and land surface temperatures. This approach allows for exploring the correlation between land use transformations and UHI intensity. The research cross-referenced the satellite data with meteorological station records for verification, which led to identifying possible factors associated with the temperature change in the city. Furthermore, the research extends its scope by analysing aerial photography images of the city, enabling a comprehensive investigation of land cover contribution to UHI effects.

With increasing air and sea temperatures, the thermodynamic environments over the oceans become more favourable for the development of intense tropical cyclones (TCs) with rapid intensification (RI). In fact, the number of TCs undergoing RI is rising (Zhao, et al., 2018; Bhatia, et al., 2019; Song, et al., 2020; Hong & Wu, 2021; Liu, et al., 2022). RI over coastal sea areas before landfalling is particularly impactful and threatening to coastal lives and properties. There have been studies showing that offshore areas within 400 km of the coastline have experienced a significant increase in RI events with the count tripling from 1980 to 2020 (Li et al., 2023). The south China coastal region consists of highly densely populated cities especially the Pearl River Delta (PRD) region. Intense TCs maintaining its strength or RI of TCs close to the coastal region presents substantial forecasting challenges. This study investigates the effect of sea surface and subsurface temperature and salinity on the intensification of five TCs, namely Super Typhoons Hato in 2017 and Mangkhut in 2018, Typhoon Talim, Super Typhoon Saola and Severe Typhoon Koinu in 2023, which significantly affected the south China coastal region and triggered high TC warning signals in Hong Kong. The analysis utilized the Hong Kong Observatory (HKO) TC track and intensity data, along with the sea temperature and salinity profiles generated using the China Ocean ReAnalysis version 2 (CORA2) of the National Marine Data and Information Service (NMDIS) of China. While high sea surface temperature (SST) of 30°C or above, low surface sea surface salinity (SSS) of 34 psu or below, and strong salinity stratification of at least 0.8 psu per 100 m depth may offer useful hints for predicting RI, they are part of a broader set of contributing factors. This study represents the initial documentation of sub-surface salinity's impact on intense TCs over the South China Sea (SCS) in recent years and will encourage further research to refine forecasting RI of TCs before making landfall near PRD taking into account the effect of freshwater from the Pearl River.

To improve carbon efficiency for urban logistics service system composed of a third-party logistics service provider (3PLs) and an e-business enterprise, low-carbon operation game between them was studied. Considering low carbon technology investment cost and sales expansion effect of low carbon level, profit functions for both players were constituted. Based on their different bargaining capabilities, totally 5 types of game scenarios were designed. Through analytical solution, Nash Equilibria under varied scenarios were obtained. By analyzing these equilibria, 4 major propositions were given, in which, some key variables and system performance index were compared. Results show that the best system yields could only be achieved under the fully cooperative situation; limited cooperation only for carbon emission reduction would not benefit the system performance improvement; E-business enterprise-leading game’s performance overtook 3PLs-leading ones.

This study evaluated batch fermentation modes, namely, separate hydrolysis and fermentation (SHF), Quasi-simultaneous saccharification and fermentation (Q-SSF), and simultaneous saccharification and fermentation (SSF), and fermentation conditions, i.e., enzyme and yeast loadings, nutrient supplementation and sterilization, on high titer bioethanol production from SPORL-pretreated Douglas-fir forest residue without detoxification. The result indicated Q-SSF and SSF were obviously superior to SHF operation in terms of ethanol yield. The enzyme loading showed a strong positive correlation between enzyme loading and the ethanol yield. The nutrient supplementation and sterility was not necessary for ethanol production from SPORL-pretreated Douglas-fir. The yeast loading showed no significant influence on the ethanol yield for typical SSF conditions. The terminal ethanol titer of 43.2 g/L, or 75.1% theoretical based on glucose, mannose, and xylose theoretical was achieved when SSF was conducted at the condition of following: whole slurry solids loading of 15%, enzyme loading of 20 FPU/g glucan, 1.8 g/kg (wet) yeast loading, without nutrition supplementation and sterilization, at 38°C, on shake flask at 150 rpm for 96h. It is believed that with mechanical mixing, enzyme loading can be substantially reduced with affect ethanol yield by using a long fermentation time.

Curcumin, a polyphenol with a rich history spanning two centuries, has emerged as a promising therapeutic agent targeting multiple signaling pathways and exhibiting cellular-level activities that contribute to its diverse health benefits. Extensive preclinical and clinical studies have demonstrated its ability to enhance the therapeutic potential of various bioactive compounds. While its reported therapeutic advantages are manifold, predominantly attributed to its antioxidant and anti-inflammatory properties, its efficacy is hindered by poor bioavailability stemming from inadequate absorption, rapid metabolism, and elimination. To address this challenge, nano-delivery systems have emerged as a promising approach, offering enhanced solubility, biocompatibility, and therapeutic effects for curcumin. We have analyzed the knowledge on curcumin nano-encapsulation and its synergistic effects with other compounds, extracted from electronic databases. We discuss the pharmacokinetic profile of curcumin, current advancements in nano-encapsulation techniques, and the combined effects of curcumin with other agents across various disorders. By unifying existing knowledge, this analysis intends to provide insights into the potential of nano-encapsulation technologies to overcome constraints associated with curcumin treatments, emphasizing the importance of combinatorial approaches in improving therapeutic efficacy. Finally, this compilation of study data aims to inform and inspire future research into encapsulating drugs with poor pharmacokinetic characteristics and investigating innovative drug combinations to improve bioavailability and therapeutic outcomes.

Background/Aim: Baricitinib (BAR) is the first oral selective Janus kinase inhibitor approved in Europe for rheumatoid arthritis (RA). Real-world data are still needed to clarify its long-term benefit/risk profile. This study aimed to evaluate the effectiveness, persistence, adherence, and safety of BAR in a real-world setting. Methods: An ambispective study was conducted between October 2017 and December 2021 in RA patients starting BAR. Effectiveness was evaluated by change from baseline in the Disease Activity Score using 28-joint counts-C reactive protein (DAS28CRP), and achievement of low disease activity/remission. Drug persistence was evaluated by Kaplan-Meier analysis. Adherence was estimated by medication possession ratio (MPR) and the 5-item Compliance Questionnaire for Rheumatology. Safety was assessed by global incidence proportion and adjusted incidence rates of adverse events. Results: 61/64 recruited patients were finally analyzed, 83.6% female, 78.7% seropositive, mean age of 58.1 (15.4) years, and disease duration of 13.9 (8.3) years. 32.8% were naïve to biologics and 16.4% received BAR on monotherapy. After a median exposure to BAR of 12.4 (6.6-31.2) months (range 3.1-51.4), a significant change in DAS28CRP was observed (difference -1.2, p=0.000). A total of 70.5% and 60.7% patients achieved low disease activity or remission, respectively and 50.8% (31/61) patients remained on BAR during follow-up with a median persistence of 31.2 (9.3-53.1) months. The average MPR was 0.96 (0.08) and all patients were “good adherents” by questionnaire. 21.3% patients discontinued baricitinib due to toxicity. Conclusion: In our real-world practice, BAR demonstrated effectiveness, large persistence, high adherence to treatment and acceptable safety profile.

Dams fragment stream habitat and fishways around dams typically serve few species that are strong swimmers or jumpers. We test a prototype wetted ramp designed to allow upstream passage of small-bodied fishes while blocking upstream movement of invasive sea lamprey in the Laurentian Great Lakes. We tested short, smooth ramps with 5-10 mm water depth in various combinations of ramp angle, water flow and swim channel width with the aim to selectively block adult migrating sea lamprey while passing sub-adult white suckers (Catostomus commersonii) and creek chubs (Semotilus atromaculatus). Sea lamprey easily passed a 0.75 ramp at 5 angle, but very few individuals passed a similar ramp at 10 angle and none passed a longer ramp at the 5 angle. Limiting the amplitude of tailbeats in a narrow channel did not hamper lamprey or the other species. Greater water flow, and thereby greater immersion depth on the ramp fostered passage for all species. Smaller-bodied individual of creek chubs and white suckers performed best on the ramp. We show that wetted ramps could be incorporated into fishways at low-head dams to aid passage of smaller-bodied fishes while also blocking the spawning migration of adult sea lamprey.

Online food delivery service (OFDS) has been widely utilized during the new normal of COVID-19 pandemic especially in a developing country such as Indonesia. The purpose of this study was to determine factors influencing customer satisfaction & loyalty in OFDS during the new normal of COVID-19 pandemic in Indonesia by utilizing an extended Theory of Planned Behavior (TPB) approach. 253 respondents voluntarily participated and answered 65 questions. Structural equation modeling (SEM) indicated that Hedonic Motivation (HM) was found to have the highest effect on customer satisfaction, followed by Price (P), Information Quality (IQ), and Promotion (PRO). Interestingly, this study found out that usability factors such as Navigational Design (ND) and Perceived Ease of Use (PEOU) were not significant to customer satisfaction and loyalty in OFDS during the new normal of COVID-19. This study can be the theoretical foundation that could be very beneficial for OFDS investors, IT engineers, and even academicians. Finally, this study can be applied and extended to determine factors influencing customer satisfaction and loyalty in OFDS during the new normal of COVID-19 in other countries.

This research investigates the application of Fused Filament Fabrication (FFF) in producing WC-10Co hardmetals, focusing binder formulations and understanding its influence on extrusion force and the influence of printing variables on green density of the samples. By examining the interplay between different binder compositions and backbone contents, the study aims to enhance the mechanical properties of the sintered parts while reducing defects inherent in the printing process. Evidence suggested that formulated feedstocks influenced the hardness of the sintered hardmetal, not due to microstructural changes but to macrostructural responses like macro defects introduced during printing, debinding and sintering of the samples. The results demonstrate the critical role of PP-MA content in improving part density and sintered hardness, suggesting the need for specific thermal debinding protocols tailored to each feedstock. The study provides insights into the formulation of feedstocks for hardmetal FFF, proposing a path toward refining manufacturing processes for better quality and performance of 3D printed hardmetal components.

Protected areas serve as an effective mechanism usually supported by a statute to conserve and protect wildlife-rich areas worldwide. Such extensive external management needs elaborate planning, regular monitoring, and periodic assessment of results. Thus, management effective evaluation (MEE) has emerged as one of the major tools for quantifying the performance of any protected area, globally since 2006. India has successfully conducted a complete round of management effectiveness evaluation of all its terrestrial protected areas (except conservation reserves and community reserves), with 25 such areas already undergoing a repeat assessment. Simultaneously, India biennially carries out a country-wide status of forest cover in all its states and union territories. This study has correlated the trend in change of forest cover for the states that contain those 25 repeat evaluated protected areas with their change in MEE scores over the same period. Our study found a positive correlation between the change in forest cover and the change in management effectiveness score from 2005-06 to 2018-19. Owing to increased protection regimes in the PAs including the degraded areas if they make part of such areas, the habitat often shows recovery. Effective habitat conservation is thus intertwined with the monitoring and preserving the wildlife populations in the protected areas, thereby, reduction in forest cover equally impacts the management scores. However, in states where the loss in forest cover has been reported, more protected areas need to be assessed to plan complementary strategies for both habitat and species conservation.

Thunderstorms endager life and infrastructure. Accurate and precise prediction of thunderstorms are therefore helpful to enable protections measures and to reduce the risks. This manuscript presents the latest developments to improve thunderstorm forecasting in the first few hours. This includes the description and discussion of a new Julia-based method (JuliaTSnos) for the temporal extrapolation of thunderstorms and the blending of this method with the numerical weather prediction model (NWP) ICON. The combination of ICON and JuliaTSnow attempts to overcome the limitations associated with the pure extrapolation of observations wit Atmospheric Motion Vectors (AMVs) and thus increase the prediction horizon. For the blending the operational ICON-D2 is used, but also the experimental ICON-RUC, which is performed with a higher data assimilation update cycle. The blended products are evaluated against lightning data. The Critical Success Index (CSI) for the blended RUC product is higher for all forecast time steps. This is mainly due to higher resolution of the AMVs (prediction hours 0-2) and the rapid update cycle of ICON-RUC (prediction hours 2-6). The results demonstrate the potential of the rapid update cycle to improve the short term forecasts of thunderstorms. Also the transition between AMV driven nowcasting to NWP is much smoother in the blended RUC product, which points to the advantages of fast data assimilation for seamless predictions. The CSI is well above the critical value of 0.5 for the 0-2 hour forecasts. However, also with RUC the CSI drops below 0.5 as soon as the last forecast is more than 3 hours away from the last data assimilation, indicating the lack of the model physics to accurately predict thunderstorms. This lack is simply a result of chaos theory. Within this scope the role of NWP in comparison with Artificial Intelligence (AI) is discussed and it is concluded that AI could replace physical short term forecasts in the near future.

Inequality of health service for different specialty categories not only occurs in different areas inequality of health service for different specialty categories in the world, but also happens in the online service platform. In the online health community (OHC), health service was often of inequality for different specialty categories, including both online views and medical consultation for offline registered service. Moreover, how the factor city-level impacts the inequality of health service in OHC is still unknown. We designed a causal inference study with data on distributions of serviced patients and online views in over 100 distinct specialty categories on one largest OHC in China. To derive the causal effect of the city-levels (two levels inducing 1 and 0) on the Gini coefficient, we matched the focus cases in cities of rich healthcare resources with the potential control cities. For the Gini coefficient of serviced patients in over 100 specialty categories, the average treatment effect of level-1 cities is 0.470, which is 0.029 higher than that of the matched group. Similarly, for the Gini coefficient of online views, the average treatment effect of Level-1 cities is 0.573, which is 0.016 higher than that of the matched group. For each of the specialty categories, we also estimated the average treatment effect the specialty category’s Gini coefficient ( ) with the balanced covariates. The results support the argument that the total Gini coefficient of all the doctors in OHC shows that the inequality of health service is still very serious. This study contributes to the development of the theoretically grounded understanding of the causal effect of city-level on the inequality of health service in an online to offline healthcare service setting.

Well differentiated liposarcoma (WD-LPS) is a relatively rare tumour, with less than 50 cases occurring per year in the UK. These tumours are both chemotherapy and radiotherapy resistant and present a significant treatment challenge requiring radical surgery. Little is known of the molecular landscape of these tumours and no current targets for molecular therapy exist. We aimed to carry out a comprehensive molecular characterisation of WD-LPS via whole genome sequencing, RNA-sequencing and methylation array analysis. A recurrent mutation within exon1 of FOXD4L3 was observed (chr9:70,918,189A>T; c.322A>T; p. Lys108Ter). Recurrent mutations were also observed in Wnt signalling, immunity, DNA repair and hypoxia-associated genes. Recurrent amplification of HGMA2 was observed, although this was in fact part of a general amplification of the region around this gene. Recurrent gene fusions in HGMA2, SDHA, TSPAN31 and MDM2 were also observed as well as consistent rearrangements between chromosome 6 and chromosome 12. Our study has demonstrated a recurrent mutation within FOXD4L3, which shows evidence of interaction with the PAX pathway to promote tumorigenesis.

In this study, we aimed to investigate the differences in tissue surface adaptation and the variations in distances between reference points on the polished surfaces of 3D-printed denture bases with different build angles. The build angles were 0°, 30°, 60°, and 90°, with 15 denture bases printed for each angle. Using the Geomagic Control® software, a 3D best-fit alignment was conducted between the denture base tissue surface and the reference shape of the edentulous maxilla model to calculate the root mean square error. The distances between reference points on the polished surface were measured using digital calipers. One-way analysis of variance was conducted for statistical analysis. The adaptation, as measured by the root mean square error, varied significantly among denture bases with different build angles. The distances between the anterior and posterior reference points of the polished surface were also significantly different. However, within the limitations of this study, the variations in adaptations and dimensional accuracy across different build angles were within clinically acceptable ranges. In clinical practice, the print angle can be adjusted based on factors, such as printing time, resin consumption, and the number of denture bases being printed simultaneously.

Nanoparticles have been used as a novel drug delivery system. Drug-incorporated nanoparticles for local delivery might optimize the efficacy and minimize the side effects of drugs. The efficacy and safety of intratracheal administration of prostacyclin analog (beraprost)-incorporated nanoparticles and imatinib, a PDGF-receptor tyrosine kinase inhibitor, -incorporated nanoparticles in Sugen-hypoxia-normoxia or monocrotaline rat models of PAH and in human PAH-pulmonary arterial smooth muscle cells have been reported. The use of inhaled drug-incorporated nanoparticles might be a novel approach for treatment of PAH.

The recent mountain pine beetle outbreaks have caused widespread mortality among lodgepole pine trees in western North America, resulting in a reduced population of surviving trees. While previous studies have focused on the cascading impacts of these outbreaks on the physiology and growth of the surviving trees, there remains a need for a comprehensive study into the interactions among various physiological traits and the growth in post-outbreak stands. Specifically, the relationship between chemical (primarily terpenes) and anatomical (mainly resin ducts) defences, as well as the allocation of non-structural carbohydrates (NSCs) to support these defence modalities, is poorly understood. To address these gaps, we conducted a field survey of surviving lodgepole pine trees in post-mountain pine beetle outbreak stands in western Canada. Our retrospective analysis targeted to determine correlations between the post-outbreak concentrations of monoterpenes, diterpenes, and NSCs in the phloem, and the historical resin duct characteristics and growth traits before and after the outbreak. We detected strong correlations between post-outbreak concentrations of monoterpenes and historical resin duct characteristics, suggesting a possible link between these two defence modalities. Additionally, we found a positive relationship between NSCs and the total concentrations of monoterpenes and diterpenes, suggesting that NSCs likely influence the production of these terpenes in lodgepole pine. Furthermore, historical tree growth patterns showed strong positive correlations with many individual monoterpenes and diterpenes. Interestingly, while surviving trees had enhanced anatomical defences after the outbreak, their growth patterns did not vary before and after the outbreak conditions. The complexity of these relationships emphasizes the dynamics of post-outbreak stand dynamics and resource allocation in lodgepole pine forests, highlighting the need for further research. These findings contribute to a broader understanding of conifer defenses and their coordinated responses to forest insect outbreaks, with implications for forest management and conservation strategies.

Anxiety disorders, characterized by excessive fear and anxiety, are increasingly recognized as significant comorbidities in chronic diseases such as Chronic Obstructive Pulmonary Disease (COPD). This study aimed to evaluate the prevalence of anxiety in COPD patients referred from primary care centers to pulmonology services and identify predictive factors for anxiety. Conducted as a multicentric, observational, and prospective study, 293 COPD patients were recruited, undergoing comprehensive respiratory and smoking histories, spirometry, and anxiety assessments using the Hospital Anxiety and Depression Scale (HADS). These results show: a diagnosis of suspected anxiety in in 85 patients (29.0%): 17 possible and 68 with a strong suspicion. The study found significant associations between anxiety and factors such as gender (women showed a risk 3.5 times higher than men), weight, and body mass index (BMI). Disease severity, smoking status, and clinical manifestations did not significantly influence anxiety prevalence. The findings underscore the need for systematic psychological evaluations in COPD management, advocating for the use of simple diagnostic tools like the HADS to facilitate referrals to mental health services. Addressing anxiety in COPD patients could potentially improve their quality of life and disease outcomes. The study highlights the importance of a multidisciplinary approach involving family medicine, pulmonology, and psychiatry to optimize COPD patient care and suggests future research should focus on the impact of anxiety treatment on COPD progression. These insights call for integrating psychological assessments into routine clinical practice for comprehensive COPD management.

Background/Objectives: This review examines the evolution of lyotropic liquid crystals (LLCs) in ocular drug delivery, focusing on their ability to address the challenges associated with traditional ophthalmic formulations. The study aims to underscore the enhanced bioavailability, prolonged retention, and controlled release properties of LLCs that significantly improve therapeutic outcomes; Methods: The review synthesizes data from various studies on both bulk-forming LLCs and liquid crystal nanoparticles (LCNPs). It also considers advanced analytical techniques, including the use of machine learning and AI-driven predictive modeling, to forecast the phase behavior and molecular structuring of LLC systems. Emerging technologies in biosensing and real-time diagnostics are discussed to illustrate the broader applicability of LLCs in ocular health; Results: LLCs are identified as pivotal in promoting targeted drug delivery across different regions of the eye, with specific emphasis on the tailored optimization of LCNPs. The review highlights principal categories of LLCs used in ocular applications, each facilitating unique interactions with physiological systems to enhance drug efficacy and safety. Additionally, novel applications in biosensing demonstrate LLCs' capacity to improve diagnostic processes; Conclusions: Lyotropic liquid crystals offer transformative potential in ocular drug delivery by overcoming significant limitations of conventional delivery methods. The integration of predictive technologies and biosensing applications further enriches the utility of LLCs, indicating a promising future for their use in clinical settings. This review points to continued advancements and encourages further research in LLC technology to maximize its therapeutic benefits.

The utilization of electroporation for delivering the CRISPR/Cas9 system components has enabled efficient gene editing in mammalian zygotes, facilitating the development of genome-edited animals. In our study，This research focused on targeting the ACTG1 and MSTN genes in sheep, revealing a threshold phenomenon in electroporation with a voltage tolerance in sheep in vitro fertilization (IVF) zygotes. Various poring voltages near 40V and pulse durations were examined for electroporating sheep zygotes. The study concluded that stronger electric fields required shorter pulse durations to achieve the optimal conditions for high gene mutation rates and reasonable blastocyst development. The investigation also assessed the quality of Cas9/sgRNA ribonucleoprotein complexes (Cas9 RNPs) and their influence on genome editing efficiency in sheep early embryos. It was highlighted that pre-complexation of Cas9 proteins with single-guide RNA (sgRNA) before electroporation was essential for achieving a high mutation rate. The use of suitable electroporation parameters for sheep IVF zygotes led to significantly high mutation rates and heterozygote ratios. By delivering Cas9 RNPs and single-stranded oligodeoxynucleotides (ssODNs) to zygotes through electroporation, targeting the MSTN (Myostatin) gene, a knock-in efficiency of 26% was achieved. The successful generation of MSTN-modified lambs was demonstrated by delivering Cas9 RNPs into IVF zygotes via electroporation.

In large-capacity energy storage systems, instructions are decomposed typically using an equalized power distribution strategy, where clusters/modules operate at the same power and durations. When dispatching shifts from stable single conditions to intricate coupled conditions, this distribution strategy inevitably results in increased inconsistency and hastened system aging. This paper presents a novel differentiated power distribution strategy comprising three control variables: the rotation status, the operating boundaries for both Depth of Discharge (DOD) and C-rates (C) within a control period. The proposed strategy integrates an aging cost prediction model developed to express the mapping relationship between these control variables and aging costs. Additionally, it incorporates the multi-colony particle swarm optimization (Mc-PSO) algorithm into the optimization model to minimize aging costs. The aging cost prediction model consists of three functions: predicting health features (HFs) based on the cumulative charge/discharge throughput quantity and operating boundaries, characterizing HFs as comprehensive scores, and calculating aging costs using both comprehensive scores and residual equipment value. Further, we elaborated on the engineering application process for the proposed control strategy. In the simulation scenarios, this strategy prolonged the service life by 14.62%, reduced the overall aging cost by 6.61%, and improved module consistency by 21.98%, compared with the traditional equalized distribution strategy. In summary, the proposed strategy proves effective in elongating service life, reducing overall aging costs, and increasing the benefit of energy storage systems in particular application scenarios.

Knowing the number of cases of an epidemic is the first function of epidemiological surveillance. An important underreporting of cases was observed in many places during the first wave of COVID-19 pandemic. To estimate this underreporting in the COVID-19 outbreak of Borriana (Valencia Community, Spain), during “Falles” mass gathering events in March 2020, a cross-sectional study was performed in June 2020 querying public health register. Logistic regression models were used. From a total of 468 symptomatic COVID-19 cases diagnosed in the outbreak by anti-SARS-CoV-2 serology, 36 cases were reported (7.7%), thus an underreporting of 92.3% (95% Confidence Interval [CI] 89.5%-94.6%), 13 unreported cases for every reported case. Only positive SARS-CoV-2 polymerase chain reaction cases were predominantly reported due to a limited testing capacity and following a national protocol. Significant factors associated with underreporting were no medical assistance for COVID-19 disease, adjusted odds ratio [aOR] 10.83 (95% CI 2.49-47.11), no chronic illness, aOR=2.81 (95% CI 1.28-6.17), middle and lower social classes, aOR=3.12 (95% CI 1.42-6.85), younger age, aOR=0.97 (95% CI 0.94-0.99), shorter duration of illness, aOR=0.98 (95% CI 0.97-0.99). To improve surveillance, studies of representative population samples are necessary to estimate the magnitude of future epidemics, and novel approaches are recommended.

A very high parking occupancy can negatively influence the traffic performance of an area by causing very long cruising times. A very low parking occupancy, on the other hand, is inefficient from a space utilization perspective. Thus, this paper proposes a framework to compute the optimal parking occupancy rate over a given time horizon based on a macroscopic traffic and parking model. This rate is set high enough to ensure an efficient usage of the parking infrastructure. However, it should also guarantee a high likelihood of finding parking in order to eliminate the drivers’ time wasted in cruising for parking and the added congestion it causes. The model outputs are based on small data collection efforts and low computational costs, and they can be generated without complex simulation software using a simple numerical solver. Multiple vehicle types are included into our methodology allowing us to generate insights about the optimal parking occupancy with or without differentiated parking (i.e., parking for specific vehicles, such as fuel and electric vehicles). In times of a modal shift towards electric vehicles, cities can use our model to evaluate how much parking supply (with battery charging opportunities) they would like to dedicate to electric vehicles in order to achieve optimal traffic and parking results, and whether a differentiated or semi-differentiated parking policy is desirable. We illustrate our framework in a case study of a central area within the city of Zurich, Switzerland, showing the traffic and parking impacts (e.g., average searching time for parking, total revenue created by parking fees, optimal parking occupancy rate) for different proportions of fuel and electric vehicles in the parking demand and/or supply. Our results confirm that optimal occupancy rates are between and for most realistic scenarios. We then discuss how these rates might change depending on various demand and supply relationships, and according to different parking policies. We show that equal proportions between electric vehicles in the demand and their parking spaces in the supply lead to the best traffic performance in the area. We also provide the tools for cities to analyze their loss in performance if they do not react, e.g., to an increasing demand for electric vehicles over time. Moreover, we illustrate how some of these risks can be mitigated by having more flexible parking policies, e.g., allowing electric vehicles to use parking spaces for fuel vehicles.

Background: The last-mile delivery phase, the final stage where goods move from a distribution center to customers, is pivotal but faces significant inefficiencies and high costs due to its complexity. Recent advancements in Edge AI or Edge Intelligence (EI) offer promising solutions to these challenges. Methods: This study explores how AI-driven technologies and real-time data processing, combined with EI, can enhance last-mile delivery operations. A thorough literature review was conducted to assess technological advancements, and a Delphi method was used to systematically and empirically assess the impact of EI solutions on both operational efficiency and customer satisfaction. Results: Although EI technologies offer substantial benefits, EU companies are hesitant to adopt these innovations due to high implementation costs. However, firms that have embraced these technologies report significant improvements, including better route optimization, reduced delivery times, and enhanced service reliability. These findings highlight the need for a culture of innovation and the recruitment of experts with advanced qualifications to drive technological advancement in last-mile logistics. Conclusions: The integration of EI represents a significant step towards more efficient, cost-effective, and customer-focused last-mile delivery solutions. Future research should aim to refine these technologies and explore their long-term impacts on the logistics industry.

Prostate cancer is the second leading cause of death in males in America, with advanced prostate cancers exhibiting a 5-year survival rate of only 32%. Castration-resistance is often developed during the course of treatment, though its influences require further understanding. This study explores the human microbiome for its implications in castration-resistance and metastasis in prostate cancer. RNA sequencing data was downloaded for bone and soft tissue biopsies of patients with metastatic castration-resistant prostate cancer. These sequences were mapped to bacterial sequences to yield species-level abundance approximations. Numerous species were found to correlate to the expression of known markers of castration-resistance, including AR, PI3K, and AKT. Castration-resistance-associated signaling pathways were also enriched with these species, including PI3K-AKT signaling and endocrine resistance. For their implications in cancer aggression and metastasis, cancer stem cell markers were further explored for relation to these species. EGFR and SLC3A2 were widely downregulated with greater abundance of most species. Our results suggest that the microbiome is heavily associated with castration-resistance and stemness in prostate cancer. By considering the microbiome’s importance in these factors, we may better understand the highly aggressive and highly invasive nature of prostate cancer, allowing for needed improvement in the treatment of this disease.

Weather conditions appear to be undergoing significant deviations from the long-term average, marked by pronounced extremes of heat, prolonged droughts, and heightened rainfall occurring with greater frequency worldwide. Consequently, new patterns of extreme weather are emerging, like the unusual and unorganized tropical cyclone called "Yaku", that influenced the extreme amount of rain that between March 6th to 10th, 2023 hits more than 1000 districts in the northwestern of Peru. One of the district more affected was Íllimo, in the Lambayeque province, due to the river that pass through the city, so called “La Leche”, after the continuous and intensive rain overflow devastating his surrounding areas and causing victims and damage. This emergency provided and excellent opportunity to apply, on the aforementioned areas, the “change detection” technique, that allows identifying areas of change between data obtained before and after of emergency events. In this research, optical data (Sentinel-2, Landsat, MODIS Terra and Aqua, and PeruSAT-1) and synthetic aperture radar (SAR) data (Sentinel-1 and COSMO SkyMed) were analyzed. A benchmark could also be carried out between open-source and commercial spatial analysis tools. The results indicated that in an extreme rain event the optical data are obscured by clouds and do not allow their use, while SAR data overcome clouds, and can be used for this research. The benchmark indicated that using the Jaccard index score, the Sentinel-1A set showed a 33% of correlation, while COSMO SkyMed demonstrated a 38% of match between the maps. The results obtained could be used to sensitize the population and develop a better management of future emergency events (floods) in different areas of Peru.

Groundwater is becoming increasingly important in the Pacific Northwest of the USA due to declining snowpack volumes and shifts in precipitation type and timing, all connected with climate change. The Upper Williamson Basin of the Klamath Watershed is a groundwater dominated watershed with massive fluctuations in year-to-year streamflow volumes over the past four decades, including the complete absence of any live flow for several years. The precise relationship between groundwater and streamflow in the basin has been difficult to assess due to a limited number of monitoring wells and significant gaps in the water level time history. To address this challenge, we use a novel imputation technique that leverages Earth observations and machine learning to impute gaps in water level records. We use these more complete datasets to compute a groundwater storage change time series for the basin. We show that groundwater storage is highly correlated to streamflow and that groundwater storage is correlated to rainfall with a three- to four-year delay that appears variable depending on groundwater storage volumes. The tools and relationships we present make it possible for water managers to estimate when streamflows will return to the basin and be more informed to support better management.

Background: Differentiated thyroid cancer (DTC) patients have an outstanding overall long-term survival rate, certain subsets of DTC patients have a very high likelihood of disease recurrence. Radioactive iodine therapy is a cornerstone in DTC management, but sometimes it became useless when cancer cells develop refractoriness. Radioactive Iodine Refractory DTC (RAIR-DTC) is a condition defined by ATA 2015 guidelines when DTC cannot concentrate RAI ab initio or loses RAI uptake ability after the initial therapy. RAIR condition implies that RAI cannot reveal new met-astatic foci, so RAIR-DTC metabolic imaging needs new tracers. 18F-FDG PET/CT has been widely used, it has a demonstrated prognostic value, but 18F-FDG DTC avidity may remain low. FA-Pi, PSMA, SSTR tracers have been proposed as theragnostic agents in experimental settings and Arg-Gly-Asp (RGD) peptides in diagnostic trial field. Multi-targeted tyrosine kinase inhibitors are relatively new drugs approved in RAIR-DTC therapy. Despite the promising targeted setting, they relate to frequent adverse event onset. Sorafenib and trametinib have been included in re-differentiation protocols aimed to re-induce RAI accumulation in DTC cells. Results appeared promising, despite not excellent. Conclusions: RAIR-DTC yet represent a challenging nosological entity. There are still controversies on RAIR-DTC definition and post-RAI therapy evaluation with post-therapy whole body scan (PT-WBS) is the only validated criterion of response. The recent introduction of multiple diagnostic and therapeutic agents oblige physicians to pursue a multidisciplinary approach aiming to correct drug introduction and timing choice.

The genome sequencing technologies reveal the molecular mechanisms of differentiated thyroid cancer (DTC). Unlike somatic mutation analysis from thyroidectomy samples, germline mutations showing genetic susceptibility to DTC are less understood. The study aimed to assess the prevalence of germline mutations predisposing to DTC in a cohort of Polish individuals based on their whole genome sequencing (WGS) data. We analyzed sequencing data from 1076 unrelated individuals, released openly for academic and clinical research as The Thousand Polish Genomes database (https://1000polishgenomes.com). The list of genes chosen for further analysis was based on the review of previous studies. The cohort contained 104 variants located within the coding and noncoding DNA sequences of 90 genes selected by ClinVar classification as pathogenic and potentially pathogenic. The frequency of variants in the Polish cohort (our study) was compared to the frequency estimated for the non-Finnish European population, obtained from the gnomAD database (gnomad.broadinstitute.org). Statistically significant variants included 23 genes. Even though the Polish population is genetically similar to other European populations, there are significant differences in variant frequencies contributing to the disease development and progression, such as RET, CHECK2, BRCA1, SLC26A4 or TERT. Further studies are needed to identify genomic variants associated directly with DTC.

(1) Background: donor-derived circulating free DNA (dd-cfDNA) is an innovative biomarker with great potential for the early identification and prevention of graft damage; (2) Methods: Prospective study to analyze dd-cfDNA plasma levels in 30 kidney transplant patients during their post-transplant follow-up (15 days, 3, 6 and 9 months), to determine if the result could be of interest in the identification of possible adverse events, specially allograft rejection. In addition, the aim is also to verify the obtained data on sensitivity, specificity, NPV and PPV; (3) Results: Plasma levels of dd-cfDNA could be considered a novel biomarker of graft rejection after first term post-transplant up to several months before its clinical presentation, mainly in TCMR or ABMR. In this study, it appears to have no positive predictive value for borderline rejection or TCMR IA. Our results show a low NPV of the technique because other pathologies or biological post-transplant complications can also affect dd-cfDNA levels and they must be considered in the interpretation of the result.; (4) Conclusions: dd cfDNA could allow, together with other additional biomarkers in the context of a future score, avoid invasive biopsies in most cases, mainly in the case of suspected TCMR or ABMR.

Network Function Virtualization (NFV) allows for the dynamic provisioning of Virtualized Network Functions, adapting services to the complex and real-time network environment for enhanced network performance. Despite the benefits of NFV, virtual network functions (VNFs) migration and the energy consumption pose significant challenges due to the dynamic nature of the physical network, especially in the edge-cloud continuum network. Currently, people tackle this challenge by predicting the network traffic and then proactively migrating the VNFs using the predicted values. There are two challenges here. First, when SFCs belong to different network service providers, the historical network traffic data is held by the service providers, and they are reluctant to share the historical data due to privacy concerns. Without the historical network traffic data of each SFC, the resource provider that owns the underlying network cannot effectively predict the network traffic; in addition, without the feedback of the migration results of the underlying physical network, the network traffic prediction will be difficult to match the needs of the physical network. In this manuscript, we solve the problem of network traffic prediction in the NFV-based edge-cloud continuum network for multiple network service providers. We aim to improve migration performance and reduce energy consumption while ensuring resource and latency requirements. To protect the privacy of each network service provider, we apply an FL algorithm. After that, to improve the migration performance, we tailor the loss function. In the loss function, factors such as the number of migrations, the number of migration failures, and the energy consumption of the NFV-based edge-cloud continuum network are added. Additionally, to obtain the results of the SFC migration, we develop a mathematical model for the problem of multiple network service providers in the NFV-based network. The effectiveness of our algorithm is evaluated through extensive simulations, and the results show a significant reduction in the number of migrated nodes and energy consumption while improving the SFC acceptance ratio compared to state-of-the-art schemes which only use the difference between predicted and actual flows to define the loss function.

Cancer, characterized by abnormal cell proliferation driven by genetic mutations, remains a significant health challenge. Tailoring effective therapies depends on factors like tumor location, grade, and stage, alongside patient condition. Leveraging Nano-carrier encapsulated drugs offers a promising avenue, as they accumulate preferentially at tumor sites, enhancing therapeutic efficacy while mitigating side effects. Polymeric Nano-carriers, with their customizable properties, further optimize drug delivery efficiency and specificity. Incorporating active targeting ligands such as antibodies, carbohydrates, peptides, folates, and aptamers-onto polymeric nanoparticle surfaces through techniques like functionalization, adsorption, and conjugation plays a pivotal role in directing therapeutic agents to tumor cells. Consequently, polymeric nanoparticles emerge as the carrier of choice for delivering drugs to various tumor types, including breast, colon, lung, prostate, liver, and spleen tumors.

Mortality rates in sub-Saharan Africa remains unacceptably high, and disproportionately affecting economically disadvantaged communities. And healthcare delivery which is considered a major contributor to this is challenged by the limited resources and high service costs, prompting many patients to opt for outpatient department services. This study addresses the need for a data-driven approach to healthcare policy formulation by proposing a model for the implementation of a data warehousing system that integrates outpatients into the national healthcare framework. By leveraging data warehousing, healthcare delivery can be made more efficient through a robust repository that supports decision-making and policy formulation. The research focuses on the outpatient department in resource-scarce settings, proposing a novel multidimensional data model and practical framework implementation. The benefits include improved patient experiences, cost-effective service delivery, and enhanced patient management through electronic health records. Additionally, mobile apps are explored for patient navigation and reminders to enhance treatment adherence. The study’s results indicate that data warehousing can significantly improve healthcare delivery by consolidating critical data and facilitating better planning, resource allocation, and policy formulation. Ultimately, this approach offers valuable insights for optimizing healthcare systems in resource-constrained environments, enabling data-driven policies, and improving health outcomes across sub-Saharan Africa.

We introduce a novel algebraic structure, termed algebra B, which generalizes Lie algebras through the definition of a non-associative and unital algebra. We demonstrate that algebra B retains essential properties such as bilinearity and antisymmetry, and satisfies both the Jacobi and Malcev identities; this occurs when the product operations of Lie and Malcev algebras are derived from the product operation defined in our algebra. By examining the connections between algebra B, Malcev algebras, and Lie algebras, we establish that algebra B effectively generalizes these structures. Furthermore, we show that algebra B can generate complex entities with a novel structure distinct from those currently known. Our findings lay the groundwork for future investigations into the practical applications and further theoretical development of this new algebraic framework.

Background: Endometriosis is a female chronic inflammatory disease in which endometrial tissue develops outside the uterine cavity. It is a complex pathology, that significantly contributes to morbidity in premenopausal women, leading to chronic pain, infertility, and subfertility negatively impacting the physical, and emotional well-being and overall quality of life. The public health burden of endometriosis remains elusive and challenging to determine, and this uncertainty can lead to inadequate healthcare services and treatments. Objective: To estimate the incidence and prevalence of endometriosis in Italy using the hospital discharge records database. Population-based retrospective study. Nationwide between 2011 and 2020. Methods: From the National Hospital Discharge Database were selected all admissions with a diagnosis of endometriosis (ICD-9-CM, codes 617.x), supported by the presence of a procedure code of laparoscopy or any other surgical procedure allowing direct visualisation of the lesions. Main outcomes measures Incidence and prevalence of endometriosis were estimated for the entire 2010-2020 period and by individual year, analysing the time trend and variability in different geographical areas of Italy. Results: A total of 134,667,646 women aged 15–50 years with one or more hospitalisations for endometriosis in all Italian hospitals. The incidence of endometriosis in Italy during this period was 0.839 per 1000 women (CI95% 0.834-0.844), exhibiting a statistically significant decreasing trend over the years. A discernible north-south gradient was observed, with higher rates documented in the northern regions. The prevalence rate stood at 14.0 per 1000 during the same period, and a similar north-south geographical gradient was identifiable in the prevalence rates as well. Conclusions: The utilization of national-level hospital data enables the generation of incidence and prevalence data for endometriosis without variations in methods and definitions, facilitating the evaluation of temporal trends and regional comparisons. Understanding and quantifying this phenomenon is essential for appropriate healthcare planning in various Italian regions.

Neurological involvement following COronaVIrus Disease 19 (COVID-19) is thought to have a neuroinflammatory etiology. Co-ultraPEALut (an antiinflammatory molecule) and luteolin (an antioxidant) yielded promising results as neuroinflammation antagonists. This study aimed at describing cognitive impairment in post-COVID patient treated with co-ultraPEALut. Montreal Cognitive Assessment (MoCA), Prospective-Retrospective Memory Questionnaire (PRMQ), Fatigue Severity Scale (FSS) and a subjective evaluation were administered at baseline and after 10 months. Co-ultraPEALut-treated patients were retrospectively compared with controls. 26 co-ultraPEALut-treated patients showed significant improvement in PRMQ (T0: 51.94±10.55, T1: 39.67±13.02, p

Accurate measurement of water vapor is essential for researches and applications of meteorology, climatology and hydrology. Based on the BeiDou PPP-B2b service, real-time precipitable water vapor (PWV) is retrieved with the precise point positioning (PPP) software. The experiment was conducted in Beijing in January, 2023. Three solutions are designed with PPP using the BeiDou system only, the GPS system only and the BeiDou-GPS combined solution. Real-time PWVs for the 3 solutions are validated with the ERA5 reanalysis data. Between PWVs from single BeiDou and ERA, there are a bias of 0.7 mm and a RMSE of 1.8 mm. While for the GPS case, the bias is 0.73 mm and RMSE is 1.97 mm. The biases are less than 1 mm and RMSEs are less than 2mm. Both the BeiDou and the GPS processing performs very well. But little improvement is found for the BeiDou-GPS combined solution, comparing with the BeiDou system only and the GPS system only solution. This may be due to the poor handling of two different kinds of errors for the GPS and the BeiDou systems in our PPP software. A better PWV estimation with the two systems is to estimate PWV with single system at first step, and then to obtain the optimization by Bayesian model averaging.

Lettuce (Lactuca sativa) is a leafy vegetable that provides a valuable source of phytonutrients for a healthy human diet. Assessment of plant growth and composition is vital for determining crop yield and overall quality, however, classical laboratory analyses are slow and costly. Therefore, new, less expensive, more rapid, and non-destructive approaches are being developed, including those based on (hyper)spectral reflectance. Additionally, it is also important to determine how plant phenotypes respond to fertilizer treatments and whether these differences in response can be detected from analyses of hyperspectral image data. In the current study, we demonstrate the suitability of hyperspectral imaging in combination with machine learning models to estimate the content of chlorophyll (SPAD), anthocyanins (ACI), glucose, fructose, sucrose, vitamin C, β-carotene, N, P, K, dry matter content, and plant fresh weight. The implemented five classification and regression machine learning models showed high accuracy in classifying the lettuces by the applied fertilizers treatments and estimating nutrient concentrations. To reduce the input (predictor data, i.e., hyperspectral data) dimension, 13 principal components were found and applied in models. The implemented artificial neural network models of the machine learning algorithm demonstrated high accuracy (r = 0.85 ... 0.99) in estimating fresh leaf weight, and contents of chlorophyll, anthocyanins, N, P, K, and β-carotene. The four applied classification models of machine learning demonstrated 100% accuracy in classifying the studied baby leaf lettuces by phenotype when certain fertilizer treatments were applied.

Distributed Denial of Service (DDoS) is among the commonly used type of network attacks, particularly aimed at the IoT devices in the emerging future wireless services specially for strictly latency-limited applications. DDoS attacks pose serious threats for many entrepreneurial businesses as they can prevent legitimate customers from accessing network resources of corporate websites, demanding intelligent analytics prior to entertaining a service request. DDoS involves exploiting the vulnerability of IoT devices by launching distributed multi-point attacks to generate high traffic by flooding the network of victims. The consequences of DDoS attacks could be worst in any Software-Defined Networking (SDN) than in traditional networks because SDN is configured as centralised architecture, failing to address the weaknesses current paradigm. However, SDN can play a crucial role in mitigating the effects of DDoS attacks as it bears the features of easy programmability, manageability, flexibility, and scalability. In this manuscript preliminary framework to detect DDoS attacks by mitigating their threats in an SDN architecture is presented. The authors propose a defense mechanism that uses OpenFlow and sFlow to mitigate the effects of DDoS attacks. The initial results show that the proposed model can minimize efficiently the consequences of DDoS attacks in an SDN type of architectural paradigm.

Tomato brown rugose fruit virus (ToBRFV) is an emerging tobamovirus infecting tomatoes and peppers. Due to its ability to trigger seed contamination, efficient mechanical transmission, and to break the popular resistance genes (Tm-1, Tm-2 and Tm-22), the virus has resulted in a global pandemic on greenhouse tomato production in recent years despite the implementation of strict hygiene and disinfection measures. The objective of this study was to evaluate whether ToBRFV can be transmissible through recirculating hydroponic systems and search for effective approach to contain its spread under such circumstances. We not only detected the presence of ToBRFV in the runoff water solutions collected from ToBRFV-infected tomato greenhouses, but also demonstrated the infectivity of detected virus through initiating ToBRFV infection on tomato plants using bioassay. We then conducted treatment using cold plasma-generated ozone on ToBRFV-contaminated water reservoir and further assessed the efficacy of the treatment to inac-tivate the virus. Results showed the effectiveness of the cold-plasma ozone treatment was de-pendent on the ozone concentrations (0.1 mg/L to 1.0 mg/L), the periods of exposure (24 min to 72 min), and the relative virus titers (1:100 to 1:10,000 - dilution of virus-infected tissue extract), demonstrating the cold-plasma ozone treatment could offer a promising solution to cope with the potential ToBRFV spread through a recirculating hydroponic system in a greenhouse.

This research work examined the various communication media used in the rural areas for the purpose of conveying messages to Adolescents in the selected communities in Obio/Akpor Local Government Area of Rivers State, Nigeria - Woji, Rumuigbo, Rumuola, Rumuokwuta and Elelenwo communities. The Taro Yammane Statistical formula for determination of sample size was used in drawing a sample of 363 respondents from a population of 3,630 Adolescents. The simple random sampling method was used in the distribution of the questionnaire to target respondents in the selected communities. Two hundred and eighty two (282) copies of the questionnaire were returned valid, and data from them was analysed and interpreted with the use of frequency tables and percentages. The result shows that traditional communication media is still relevant in the dissemination of information to rural dwellers in general and to Adolescents in particular. The agencies that make use of these media are; village authority, age groups, etc. The research work recommend among others that the government and rural dwellers should hold our traditional and cultural values in high esteem through the use of these media, harmonizing the use of traditional communication media and modern media for effective rural information service delivery.

This study investigates how customers’ technological readiness affects service quality and the adoption of self-service banking by developing an empirical model. The model was proposed to explore the relationships between technology readiness, self-service quality, and customer satisfaction. The hypotheses and stability of the model were tested using structural equation modeling. The findings revealed that technology readiness, including the optimism, innovation, and insecurity dimensions, had a significant positive impact on self-service quality. In addition, service quality fully mediated the relationship between technological readiness and customer satisfaction. These results suggest that when customers are ready to embrace and use new technology, their evaluation of service quality is high. Thus, bank managers should drive customer perceptions of the quality of self-service banking by improving their technological readiness through various measures. Furthermore, based on the mediating effect of self-service quality, banks must be aware that improving service quality can enhance customer satisfaction and maintain a competitive advantage.

Background: This study introduces a novel dexamethasone (DEX) mixed micellar system (DEX-MM) using Soluplus® and Pluronic F-127 (PF127) to enhance ocular drug delivery. The enhancement of ocular application properties was achieved by creating a chitosan-coated DEX-MM (DEX-CMM), which promotes better adherence to the ocular surface, thereby improving drug absorption; Methods: Using the solvent evaporation method, a formulation was developed with a Soluplus® to drug ratio of 1:10, enhanced with 0.25% PF127. After dispersing in water, 1% chitosan (CS) was added. The stability and integrity of DEX within the micelles were verified using attenuated total reflection-fourier transform infrared spectroscopy (ATR-FTIR) and differential scanning calorimetry (DSC). Additionally, in vitro and ex vivo drug release studies were con-ducted; Results: DEX-CMM (F6) demonstrated a particle size of 151.9±1 nm and a polydispersity index (PDI) of 0.168±0.003, suggesting uniformity and high electrostatic stability with a zeta po-tential of +35.96±2.13 mV. The non-Fickian drug release mechanism indicated prolonged drug retention. Comparative analyses showed DEX-CMM outperforming a standard DEX suspension in drug release and ocular tissue permeation, with flux measurements significantly higher than the DEX suspension; Conclusion: The study confirmed the efficacy of DEX-CMM in enhancing drug delivery to ocular tissues, evidenced by improved permeability. Safety evaluations using the HET-CAM test demonstrated that DEX-CMM was non-irritant, supporting its potential for effective ocular drug delivery.

In today's intricate media landscape, the resilience and relevance of public service media (PSM) depend on their capacity to align with the diverse and evolving expectations of the public. However, the audience perspective is often overlooked, resulting in a limited understanding of public expectations. This study employs a bottom-up approach that allows for a re-evaluation of the expectations from the audience's viewpoint. It investigates the public's expectations for PSM, drawing on data from 10 focus group discussions (with 60 participants) conducted in the Czech Republic. The findings indicate that expectations can be categorized into four primary dimensions: (1) the expected roles and functions of PSM; (2) the general characteristics of the PSM content (defining the desired nature of PSM content); (3) the principles governing the functioning of PSM (outlining how PSM should operate); and (4) specific requirements concerning PSM news and non-news content. In the latter dimension, objectivity emerged as one of the most critical expectations and a major source of dissatisfaction. While participants collectively value objectivity, they disagree on its definition. A deeper examination revealed that certain public expectations may be unattainable due to the simplistic view of objectivity held by some.

Our goal was to determine the cellular immune response (CIR) among a random sample of the Borriana COVID-19 cohort (Spain) to identify its associated factors and their relationship with infection, reinfection and sequelae. We conducted a nested case-control study using a randomly selected sample of 225 individuals age 18 and older, including 36 individual naïve to SARS-CoV-2 infection, and 189 infected patients. We employed flow cytometry-based immunoassays for intracellular cytokine staining, utilizing Wuhan and BA.2 antigens and chemoluminescence microparticle immunoassay for detection SARS-CoV-2 antibodies. Logistic regression models were used. A total of 215 (95.6%) participants exhibited T-cell response (TCR) to at least one antigen. Positive responses of CD4+ and CD8+ T cells were 89.8% and 85.3% respectively. No difference in CIR was found for naïve and infected patients. Patients who experienced sequelae exhibited higher CIR than those without. A positive correlation was observed between TCR and Anti-Spike IgG levels. Factors positive associated with TCR included A-blood group, number of SARS-CoV-2 vaccine doses received, and Anti-N IgM; factors inversely related were the time elapsed since the last vaccine dose or infection, and B-blood group. These findings contribute valuable insights into the nuance immune landscape shaped by SARS-CoV-2 infection and vaccination.

As an emerging model, self-service fitness centers are reshaping the consumer fitness experience globally. Given the crucial role of customer loyalty in the sustainable operation and management of fitness service enterprises, this study constructs a structural model incorporating service quality, service convenience, customer satisfaction, word-of-mouth intentions, and repatronage intentions. The model is designed to elucidate the factors and mechanisms impacting customer loyalty at self-service fitness centers and further investigates how these relationships are affected by service methods, either with staff or without staff. The study employs PLS-SEM to empirically analyze 552 customer questionnaires from four self-service fitness centers in first-tier cities in China. The results reveal positive correlations among the constructs in the structural model, emphasizing the important position of raising service quality standards and reducing the time and effort expended by customers in the management of customer loyalty. Concurrently, service convenience was found to play a significant driving role in customers' perceived service quality. Through the chain-mediating effect of service quality and customer satisfaction, service convenience exerts a considerable positive impact on word-of-mouth intentions and repatronage intentions. Moreover, the study reveals significant differences in these relationships when considering service methods, either with staff or without staff.

Background and Objectives: Renal cell carcinomas and upper tract urothelial carcinomas are types of malignancies that originate in the kidneys. Each of these examples shows an increasing trend in the frequency and the mortality rate. This study aims to comprehensively define carcinomas by analysing clinical, paraclinical, and histological aspects to predict aggressiveness and mortality. Materials and Methods: We conducted a retrospective investigation on a group of patients suspected with kidney cancers. Results: We identified 188 cases. We observed a higher mortality rate and older age in individuals with urothelial carcinomas. Anemia, acute kidney injury, hematuria and perineural invasion were the main risk factors that predicted their mortality. Tumour size in renal cell carcinomas correlates with the presence of necrosis and sarcomatoid areas. Factors that indicate a higher rate of death are older age, exceeding of the renal capsule, the lesion that includes the entire kidney, lymphovascular invasion, acute kidney injury, and anemia. Conclusions: Even if they originate at the renal level, and the clinical-paraclinical picture is similar, the histopathological characteristics make the difference. In addition, to these are added the previously mentioned common parameters that can represent important prognostic factors. In conclusion, the characteristics commonly identified in one type of cancer may act as risk factors for the other tumor. The detected data include threshold values and risk factors, making a significant contribution to the existing literature.

Prescribed fire is increasingly utilized for conservation and restoration goals, yet there is limited empirical evidence supporting its effectiveness in reducing wildfire-induced damages to valued resources of significant worth—whether natural, cultural, or economic. This study evaluates the efficacy of prescribed fire in reducing wildfire severity to LANDFIRE-defined vegetation classes and valued resources impacted by the 2017 West Mims event. Wildfire severity, measured using the differenced normalized burn ratio (dNBR) index, was highly heterogeneous both within and between vegetation classes; however, profound differences between treated and untreated areas were evident. The beneficial effects of prescribed fire were most pronounced within ca. two-years post-treatment but remained evident beyond three-years relative to untreated areas. For example, actively managed areas that were treated with prescribed fire just one month prior to the West Mims event exhibited an 88% reduction in mean wildfire severity relative to unmanaged areas. When post-treatment duration reached 38 months, mean wildfire severity remained 17% lower than untreated areas. Findings from this study reveal significant reductions in both average and peak wildfire severities in areas treated with frequent fire, supporting burn rotations of one to two years to balance fuel reduction and ecological conservation.

Astaxanthin (ATX) is a carotenoid nutraceutical with a poor bioavailability due to its high lipophilicity. We tested a new tailored nano-droplet capable of solubilizing ATX in an oil-in-water micro-environment (LDS-ATX, manufactured by Lyotropic Delivery Systems (LDS)), for its capacity to improve ATX pharmacokinetic profile and anti-oxidant efficacy. We used liquid chromatography tandem mass spectrometry (LC-MS/MS) to compare the pharmacokinetic profile of ATX and LDS-ATX and protein carbonylation and lipid peroxidation assays to compare their basal and lipopolysaccharide (LPS)-induced oxidative damage. Our results show that only LPS-induced oxidative damage was corrected by ATX and LDS-ATX. While in the liver and muscle LDS-ATX was more efficacious than ATX in attenuating oxidative damage to both proteins and lipids, only oxidative damage to lipids was preferably corrected by LDS-ATX in the brain. These results strongly suggest improvement of ATX bioavailability and efficacy by the LDS-ATX nano-formulation.

Despite nearly a century of research on water related issues, water erosion remains one of the greatest threats to soil health and soil ecosystem services around the world. Yet to date, data on water erosion needed to develop mitigation strategies is scarce, especially in the Sahelian regions. The current study therefore sets out to estimate annual soil losses caused by water erosion and to analyze trends over the period of 1981-2020 in the Mékrou watershed, located in the Middle Niger river sub-basin in West Africa. The revised universal soil loss equation, remote sensing and the Geographic Information System (GIS) were deployed in this study. Several types of data were used, including rainfall, soil conditions, topography and satellite images. The estimated average annual amount of water erosion in the Mékrou watershed is 6.49 t/ha/yr over 1981-2020. The dynamics of the ten-year average are highly variable, with a minimum of 3.45 t/ha/yr between 1981 and 1990, and a maximum of 8.50 t/ha/yr between 1991 and 2000. Even though these average soil losses in the Mékrou basin are below the tolerable threshold of 10 t/ha/yr, mitigation actions are needed for prevention. In addition, the spatial dynamics of water erosion are noticeably heterogeneous. The study reveals that 72.7% of the surface area of the Mékrou watershed is subject to slight water erosion below the threshold, compared with 27.3%, particularly in the mountainous south-western part, which is subject to intense erosion above the threshold.

Background: Study to assess glucose levels of people with type 1 diabetes (T1D) overnight based on insulin type and timing. Methods: Real-world, retrospective study in T1D using multiple daily insulin injections. Contin-uous glucose monitoring and insulin injections data were collected for ten hours after dinner us-ing the Insulclock® connected cap. Meal events were identified using ROC detection methodology. The timing of rapid insulin, second injections, and the type of insulin analogs used were evaluat-ed. Results: Nocturnal profiles (n=775, 49 subjects) were analyzed. Higher glucose AUC over 180mg/dL was observed in delayed injections (number; %; mg/dL x h): -45-15min (n=136; 17.5%, 175.9 ±271.0); -15-0min (n= 231; 29.8%, 164.0 ±237.1); 0+45min (n= 408; 52.6%, 203.6 ±260.9), (p 0.049). The use of ultrarapid (FiAsp®) (URI) vs rapid insulin analogs (RI) was associated with less hypoglycemia events (7.1 vs 13.6%; p 0.005) and TBR70 (1.7 +6.9 vs 4.6 +13.9%; p 0.003). Us-ers of glargine U300 vs degludec had higher TIR (70.7 vs 58.5 %) (Adjusted R-squared: 0.22, p < 0.001). The use of a correction injection (n= 144, 18.6%) was associated with higher hypoglycemia events (18.1 vs 9.5%; p 0.003), TBR70 (5.5 +14.2 vs 3.0 +11.1%; p 0.003), glucose AUC over 180 mg/dL (226.1 +257.8 vs 178.0 +255.3 mg/dL x h; p 0.001), and lower TIR (56.0 +27.4 vs 62.7 +29.6 mg/dL x h; p 0.004). Conclusions: Dinner rapid insulin timing, insulin types and correction injections affect nocturnal glucose profile in T1D.

The article is focused on detailed framework process for hierarchized construction of periodic freight train paths (PFTPs) – allocation of pre-arranged railway capacity to freight rail operators. The framework process considers fluctuations in demand for capacity from freight rail opera-tors, so the quality of a freight train path is related with its construction priority. Introduced framework process aims to offer freight rail operators attractive train paths, with low number of scheduled stops, and this way enhance competitiveness and decrease energy consumption of freight railway as a factor for sustainable development. The proposed generic process is in-tended for all time horizons of capacity allocation. Correctness of the framework process is tested on the example of mainline Prague – Dresden, in the context of prospective (denser) mod-el passenger timetable.

Rabies remains a significant global threat, yet accurate estimations of its impact are hindered by the lack of confirmatory diagnoses. Postmortem confirmation of rabies traditionally involves invasive brain tissue testing, a process met with resistance from deceased patients' families, impeding consent. This paper presents and evaluates an innovative yet unpublished transnasal approach for postmortem brain tissue collection, offering a minimally invasive, easier, faster, and safer method. This method preserves the cadaver's integrity, potentially easing family reluctance towards autopsies. The limited testing of both human and animal rabies in Ghana highlights the challenges in diagnosing this fatal disease. Scarce diagnostic resources and the complexity of obtaining brain tissue samples exacerbate the issue. Cultural and religious beliefs surrounding autopsies contribute to familial hesitation, viewing these procedures as disruptive and disfiguring, further complicating consent. The transnasal technique involves approaching the brain tissue through the nostrils and cribriform plate without any superficial manipulation of the patient's head and face, thereby preserving aesthetics and natural features of the person. Technological advancements and seamless One Health collaboration among governmental, non-governmental, and research entities locally and globally culminated in Ghana's first confirmed rabies diagnosis using this method of brain tissue collection. This success emphasizes the efficiency and feasibility of transnasal brain collection approach and the invaluable role of the One Health approach and collaborative efforts in overcoming diagnostic challenges in rabies control.

The release of the active substance from the matrix modified-release tablets based on Kollidon®SR and chitosan depends on its solubility in the dissolution medium and on the composition of the matrix-forming polymers. The study is based on new oral matrix tablets based on Kollidon®SR and chitosan, formulated to optimize the low oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug, a class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method, and their combination at 1:1, 1:2, 1:3 chlorzoxazone/ excipients, 20%-40% (w/w) Kollidon®SR, 3-7% (w/w) chitosan and the auxiliary substances were formulated in constant concentrations. Pharmaco-technical characterization included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, Carr Index), and of pharmaco-chemical characteristics (mass and dose uniformity, thickness, diameter, mechanical strength, Friability, degree of softening, in vitro release profile) of the tablets. Based on the initial evaluation of the pharmaco-technical analysis, pharmaco-chemical characteristics, and in vitro release profile, only three matrix tablet formulations (F1b, F2b, and F3b) were further tested. They were evaluated through Fourier-transform infrared spectrometry, X-ray Diffraction, thermogravimetry, differential scanning calorimetry, and in vitro dissolution tests. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified release oral formulations. In vitro kinetic study reveals a complex mechanism of release occurring in the first (0 - 2 hours) and second (2.0 hours – 36 hours) steps of drug release. Two factors have been calculated to assess the release profile of chlorzoxazone: f1 - the similarity factor and f2 - the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. In vitro dissolution tests revealed the F2b sample, data suggesting a faster drug release. The three formulations showed optimum pharmaco-technical properties and in vitro kinetic study, and they had tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone.

The paper proposes a game theory model of price oligopoly with a heterogeneous product, where total demand depends linearly on the minimum market price. This model develops the Bertrand oligopoly for the case of imperfect price elasticity of demand. The most interesting result is an asymmetric Nash equilibrium with different prices and sales in the situation of symmetric oligopolists. The asymmetry is explained by the fact that a decrease in the minimum market price leads not only to a reallocation of consumers among firms, but also to an increase in total demand. Modifications of a two-stage game with a leader and followers and the price discrimination model are also considered. Microeconomic substantiation of the model is given on the basis of the spatial differentiation approach.

Microneedle technology is a novel platform technology that revolutionizes ocular drug delivery and addresses critical challenges in the treatment of ocular diseases. Routine treatment methods, such as eye drops and intravitreal injections, suffer from low bioavailability and poor patient compliance. So, novel advanced platform technologies are required to overcome these challenges. Microneedle is a minimally invasive and promising alternative technique that helps precisely control drug delivery to targeted tissues and organs. This review investigates the potential impact of microneedle technology for eye care, underscoring recent advancements, underlying mechanisms, and emerging preclinical and clinical uses. Different types of microneedles, including solid, coated, dissolvable, and hollow, have demonstrated their potential and capability to bypass several barriers in the cornea and sclera. This ensures effective drug penetration and delivery. The current innovations in material science and fabrication methods have enhanced the safety and efficacy of microneedles, reducing discomfort and the chances of infections. These microneedle technologies offer sustained and controlled drug delivery, which could improve therapeutic outcomes for various disease conditions like age-related macular degeneration, glaucoma, diabetic neuropathy, etc. In the current review, recent preclinical and clinical studies emphasize microneedle-based ocular drug delivery's feasibility and potential benefits. These include improved pharmacokinetics, reduced dosing frequency, enhanced patient adherence, and, most importantly, microneedles offer versatile platforms for delivering a wide range of small and large molecules and gene therapies. Despite the exciting progress, obstacles such as regulatory barriers, scalability, and long-term biocompatibility persist. It will be essential to tackle these challenges through interdisciplinary research and partnerships to integrate microneedle technology into standard clinical use effectively. Ultimately, microneedle drug delivery offers a revolutionary method that has the potential to significantly enhance the treatment and results of ocular diseases, marking the dawn of a new era in eye care.

Urban rail transit hub platform is the most important area for passenger flow distribution. In order to calculate passenger flow volume in platform and evaluate platform service level during rush hours, this paper presents a method for modeling and simulation of passenger flow distribution in platform. Passenger flow distribution model (PFDM) is proposed based on the basic analysis and the superposition principle of passenger flow. Simulation design for PFDM is proposed by Anylogic, which contains simulation process and simulation model. Experiment results show that PFDM and simulation design are effective and accordant with the reality scenario, and the simulation precision is comparatively ideal. This research could provide a beneficial reference for train scheduling and operation management under the viewpoint of traffic safety and service level.

This study explored the intricate nexus between public service provision and land use planning, with a specific focus on the conservation of local plant species in Tambon Khao Phanom, Amphoe Khao Phanom, Krabi Province. Rooted in commitment. The research framework encompasses three fundamental activities: resource survey and collection, resource conservation and utilization, and resource development planning for public services, emphasizing land use planning for local plant species conservation. This multidisciplinary approach integrates the one-map method and draws data from the Department of Land Development to formulate a comprehensive land utilization plan that optimizes land use for biodiversity conservation. This study underscores the critical synergy between public service delivery and land use planning, highlighting their collective potential to advance community well-being and sustainable development.

The unique structure of G4.0 PAMAM dendrimers allows the drug to be enclosed in internal spaces or immobilized on the surface. In the conducted research, the conditions for the formation of the active G4.0 PAMAM complex with doxorubicin (DOX) were optimized. The physicochemical properties of the system were monitored using DLS, CD, and fluorescence spectroscopy. The QCM-D method was chosen to determine the preferential conditions for the complex formation. The highest binding efficiency of the drug to the cationic dendrimer was observed under basic conditions when the DOX molecule was deprotonated. The decrease in the zeta potential of the complex confirms that DOX immobilizes through electrostatic interaction with the carrier's surface amine groups. The binding constants were determined from the fluorescence quenching of the DOX molecule in the presence of G4.0 PAMAM. The two-fold way of binding doxorubicin in the structure of dendrimers was visible in the ITC isotherm. Fluorescence spectra and release curves identified reversible binding of DOX to the nanocarrier. Among the selected cancer cells, the most promising anticancer activity of G4.0-DOX was observed in A375 malignant melanoma cells. Moreover, the preferred intracellular location of the complexes concerning the free drug was found, which is important from a therapeutic point of view.

Reeling from the global supply chain crisis created by the COVID-19 pandemic, the maritime industry still faces multifaceted challenges for its sustainable survival. Those challenges include shifts in trade routes, congestion at major seaports, container shortages, volatility in fuel prices, the scarcity of skilled maritime labor, and potential technical glitches stemming from digitized maritime operations. To help the maritime industry handle these challenges, this paper identifies major drivers and deterrents that affect the efficiency of ocean carriers’ performances over time using two different versions of data envelopment analysis (DEA) models and the Malmquist Productivity Index (MPI). After evaluating the operating efficiencies of multinational ocean carriers across the globe over extended periods (pre- and post-pandemic periods), we developed a benchmark standard that can guide best-in-class sustainable maritime practices.

Glycosylation, the most significant modification of proteins, plays an essential role in cellular processes. Congenital disorders of glycosylation (CDG) are multisystemic diseases resulting from mutations affecting glycosylation steps. Diagnosis of CDG relies on biochemical assays, such as isoelectric focusing. Despite its significance, CDG cases remain unreported in Cuba due to the lack of implemented diagnostic methods. This study aimed to evaluate transferrin glycoforms for diagnosing congenital N-glycosylation defects. We conducted a cross-sectional descriptive study using serum samples from 17 patients stored at the National Center for Medical Genetics of Cuba for suspected CDG. Results revealed abnormal glycosylation patterns in 7 patients, suggesting congenital N-glycosylation defects. We conclude that the implementation of transferrin glycoform analysis could pioneer a preliminary diagnosis of CDG in Cuba.

Following traumatic brain injury (TBI), secondary brain damage due to chronic inflammation is the most predominant cause of the delayed onset of mood and memory disorders. Currently no therapeutic approach is available to effectively mitigate secondary brain injury after TBI. One reason is the blood-brain barrier (BBB), which prevents passage of most therapeutic agents into the brain. Peptides have been among the leading candidates for CNS therapy due to their low immunogenicity and toxicity, bioavailability, and ease of modification. In this study, we demonstrated that non-invasive intranasal administration of KAFAK, a cell penetrating anti-inflammatory peptide, traversed the BBB in a murine model of diffuse, moderate TBI. Notably, KAFAK treatment reduced the production of pro-inflammatory cytokines that contribute to secondary injury. Furthermore, behavioral tests showed improved or restored neurological, memory, and locomotor performance in KAFAK-treated mice. This study demonstrates KAFAK's ability to cross the blood-brain barrier, to lower pro-inflammatory cytokine levels in vivo, and to restore function after a moderate TBI.

We explore the concept of Euclidean locality within treonic topological spaces. Our study establishes a foundational theoretical framework, elucidating the properties of continuity, homeomorphisms, and compactness in these spaces. We assess the Euclidean locality of treonic spaces through the analysis of specific homeomorphisms, which enables us to define manifolds in treonic spaces and extend recent research on Bermejo Algebras. For the first time, we characterize treonic manifolds by incorporating the property of Euclidean locality alongside previously studied properties such as Hausdorff spaces and second countable spaces. Our findings advance the understanding of the topological and geometric properties of treonic spaces, providing significant insights for advanced mathematical research.

Bermejo Algebras, which consist of Algebra B and Treon Algebra, are non-associative and unital algebraic structures that introduce new complex entities. Recently, a Hausdorff space associated with the space where these algebras act was defined. We constructed a second-countable treon space utilizing a novel metric derived from these algebras. We defined topological spaces and established a metric to prove the second-countable property within Bermejo Algebras. Our findings contribute to the construction of manifolds in treon spaces by defining a countable base using the density of rationals in the real numbers.

We conducted a topological analysis of the novel, non-associative, and unital algebraic structure known as Bermejo Algebras, developed by Alejandro Bermejo, which includes the Algebra B and Treon Algebra. This algebras can define Lie and Malcev algebras when their product operations are derived from the Bermejo Algebras product. Central to this study are treons, complex entities that arise as isomorphisms of Algebra B when the field is real. We define the vector spaces associated with Bermejo Algebras to establish equivalence classes and a quotient topology, resulting in Hausdorff spaces that do not depend on traditional norms, inner products, or metrics. Our findings lay the groundwork for constructing new types of differential manifolds, opening new avenues for advanced mathematical research.

We explored an extension of the Cauchy-Riemann equations to the algebra of treons, recently described by Alejandro Bermejo, whose elements are ordered 3-tuples. We leveraged the isomorphism between the algebra of treons and algebra B, and deduced the Cauchy-Riemann equations for the algebra of treons, establishing the necessary conditions for analyticity in this algebraic structure. This work significantly broadened our horizons in complex analysis and introduced new possibilities for applications across various fields of advanced mathematics.

We present an exploration of algebra B, a recently published unital and non-associative algebra. Unique complex entities emerged from this algebra, distinct from both quaternion and complex number systems, which we termed treons. We defined the treonic number system and established an isomorphism between this system and the real vector space. Our findings revealed that the treonic representation maintained structural integrity under the defined operations. Based on this foundation, we proceed to determine Euler identity for algebra B within the treonic system. By presenting the fundamental definitions and properties of algebra B, we derived a generalized version of Euler identity applicable within this algebra. This formula revealed the emergence of hyperbolic trigonometric entities, extending the applicability of Euler identity beyond traditional complex numbers. Our results provide a theoretical foundation for a deeper understanding of the properties and behaviors of complex entities within this expanded algebraic framework, thus enabling new theoretical developments and practical applications in the realms of advanced mathematics and theoretical physics.

Climate simulations in West Africa have been attributed with large uncertainties. Global climate projections are not consistent with changes in observations at the regional or local level of the Niger basin, making management of hydrological projects in the basin uncertain. This study evaluates the potential of using the quantile mapping bias correction to improve the Coupled Model Intercomparison Project (CMIP5) outputs for use in hydrology impact studies. Rainfall and temperature projections from 8 CMIP5 Global Climate Models (GCM) were bias corrected using the quantile mapping approach. Impacts of climate change was evaluated with bias corrected rainfall, temperature and potential evapotranspiration (PET). The IHACRES hydrological model was adapted to the Niger basin and used to simulate impacts of climate change on discharge under present and future conditions. Bias correction significantly improved the accuracy of rainfall and temperature simulations compared to observations. Nash coefficient (NSE) for monthly rainfall comparisons of 8 GCMs to the observed was improved by bias correction from 0.69 to 0.84. The standard deviations among the 8 GCM rainfall data were significantly reduced from 0.13 to 0.03. Increasing rainfall, temperature, PET and river discharge were projected for all GCMs used in this study under the RCP8.5 scenario. These results will help improving projections and contribute to the development of sustainable climate change adaptation strategies.