Despite the availability of effective vaccines against COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to spread worldwide, pressing the need for new vaccines with improved breadth and durability. We developed an adjuvanted subunit vaccine against SARS-CoV-2 using recombinant receptor-binding domain (RBD) of spike with synthetic adjuvants targeting TLR7/8 (INI-4001) and TLR4 (INI-2002), co-delivered with aluminum hydroxide (AH) or aluminum phosphate (AP). The formulations were characterized for the quantities of RBD, INI-4001, and INI-2002 adsorbed onto the respective aluminum salts. Results indicated that at pH 6, the uncharged RBD (5.73 ± 4.2 mV) did not efficiently adsorb to the positively charged AH (22.68 ± 7.01 mV), whereas it adsorbed efficiently to the negatively-charged AP (-31.87 ± 0.33 mV). Alternatively, pre-adsorption of the TLR ligands to AH converted it to a negatively-charged particle, allowing for the efficient adsorption of RBD. RBD could also be directly adsorbed to AH at a pH of 8.1, which changed the charge of the RBD to negative. INI-4001 and INI-2002 efficiently to AH. Following vaccination in C57BL/6 mice, both aluminum salts promoted Th2-mediated immunity when used as the sole adjuvant. Co-delivery with TLR4 and/or TLR7/8 ligands efficiently promoted a switch to Th1-mediated immunity instead. Measurements of viral neutralization by serum antibodies demonstrated that the addition of TLR ligands to alum also greatly improved the neutralizing antibody response. These results indicate that the addition of a TLR7/8 and/or TLR4 agonist to a subunit vaccine containing RBD antigen and alum is a promising strategy for driving a Th1 response and neutralizing antibody titers targeting SARS-CoV-2.

The Safe Drinking Water Act Amendments of 1996 require community water systems in the United States to send consumers Consumer Confidence Reports (CCRs). CCRs contain information on detected contaminants and required educational information about drinking water. The authors of this study developed a survey to evaluate how utilities track consumer feedback, understanding, and the role of the CCR in shaping consumer perceptions about water quality. Responses from this survey indicate it is common for utilities to indirectly track the effectiveness of their CCRs, but few utilities indicated directly evaluating consumer understanding or the effect of CCRs on consumer perceptions.

Co-delivery of antigens and adjuvants to the same antigen presenting cells (APCs) can significantly improve the efficacy and safety profiles of vaccines. Here, we report amine-grafted silica nanoparticles (A-SNPs) as a tunable vaccine co-delivery platform for TLR7/8 agonists along with the recombinant influenza antigen hemagglutinin H7 (H7) to APCs. A-SNPs of two different sizes (50 and 200 nm) were prepared and coated with INI-4001 at different coating densities, followed by co-adsorption of H7. Both INI-4001 and H7 showed > 90% adsorption to the tested A-SNP formulations. TNF-α and IFN-α cytokine release by human peripheral blood mononuclear cells as well as TNF-α, IL-6, and IL-12 release by mouse bone marrow-derived dendritic cells revealed that the potency of the INI-4001-adsorbed A-SNPs (INI-4001/A-SNP) formulations can be improved relative to aqueous formulation control. This improved potency was dependent on particle size and ligand coating density. In addition, slow-release profiles of INI-4001 were measured from INI-4001/A-SNP formulations in plasma with 30-50% INI-4001 released after 7 days. In vivo murine immunization studies demonstrated significantly improved H7-specific humoral and Th1/Th17-polarized T cell immune responses with no observed adverse reactions. Low-density 50 nm INI-4001/A-SNP elicited significantly higher IFN-γ and IL-17 induction over that of the H7 antigen only group and INI-4001 aqueous formulation controls. In summary, this work introduces an effective and biocompatible SNP-based co-delivery platform that enhances the immunogenicity of TLR7/8 agonist-adjuvanted subunit influenza vaccines.

Evans' Syndrome (ES) is a rare autoimmune disorder characterized by the simultaneous occurrence of immune thrombocytopenia (ITP) and autoimmune hemolytic anemia (AIHA). Thrombotic complications in ES patients are uncommon, particularly involving Buerger's Disease (BD). We report a case of a 49-year-old male with ES and a history of diabetes and heavy smoking, presenting with a necrotic wound on his right great toe. Diagnostic evaluations revealed severe stenosis and thrombosis in the lower limb arteries, diagnosed as BD. The patient underwent successful popliteal-tibioperoneal artery bypass surgery and subsequent disarticulation and revision of the distal phalanx, followed by the application of an acellular dermal matrix (ADM) to promote healing. Post-surgery, the patient showed significant improvement in blood flow and complete epithelialization without complications. This case highlights the importance of a multidisciplinary approach in managing complex wounds in ES patients, suggesting potential treatment pathways for future cases involving BD

We developed a honey bee RNA-virus vector based on the genome of a picorna-like Deformed wing virus (DWV), the main viral pathogen of the honey bee (Apis mellifera). To test the potential of DWV to be utilized as a vector, the 717 nt sequence coding for the enhanced green fluorescent protein (eGFP), flanked by the peptides targeted by viral protease, was inserted into an infectious cDNA clone of DWV in-frame between the leader protein and the virus structural protein VP2 genes. The in vitro RNA transcripts from egfp-tagged DWV cDNA clones were infectious when injected into honey bee pupae. Stable DWV particles containing genomic RNA of the recovered DWV with egfp inserts were produced, as evidenced by cesium chloride density gradient centrifugation. These particles were infectious to honey bee pupae when injected intra-abdominally. Fluorescent microscopy showed GFP expression in the infected cells and Western blot analysis demonstrated accumulation of free eGFP rather than its fusions with DWV LP and/or VP2 proteins. Analysis of the progeny egfp-tagged DWV showed gradual accumulation of genome deletions for egfp, providing estimates for the rate of loss of a non-essential gene an insect RNA virus genome during natural infection.

The incidence of human papillomavirus-related head and neck squamous cell carcinoma (HPV+HNSCC) has reached epidemic levels in the last decade. While prophylactic vaccines will prevent future HPV infections, there are currently no HPV-specific antiviral drugs to treat current HPV infections or HPV+HNSCC. HPV replication and transcription are promising targets for anti-HPV therapeutics, as modulation of these processes can alter expression levels of HPV E6 and E7, which are required for maintenance of the transformed phenotype. This is a particularly attractive target in in HPV+HNSCC where the majority of tumors have episomal genomes replicating in an E1-E2 dependent manner. Here, we describe a model system to study HPV16 E1-E2 mediated DNA replication and HPV16 E2-mediated transcriptional activation and repression in multiple HNSCC cell lines. Our results demonstrate that low levels of IFIT1 are required for HPV16 replication in HNSCC cell lines and HPV16 E1 interacts with IFIT1. Restoration of IFIT1 expression in HNSCC cell lines partially inhibits HPV16 E1-E2 mediated replication. This system can be used to study replication and transcription by HPV16 E1 and E2 in HNSCC as well as be utilized to screen potential anti-HPV therapeutics that target HPV16 replication and transcription.

The presence of mutated genes strongly correlates with the incidence of cancer. Decades of research, however, has not yielded any specific causative gene or set of genes for the vast majority of cancers. The Cancer Genome Atlas program was supposed to provide clarity but it only gave much more data without any accompanying insight into how the disease begins and progresses. It may be time to notice that epidemiological studies consistently show that the environment, not genes, has the principal role in causing cancer. Since carcinogenic chemicals in our food, drink, air and water are the primary culprits, we need to look at the biochemistry of cancer, with a focus on enzymes which invariably facilitate transformations in a cell. In particular, attention should be paid to the rate-limiting enzyme in DNA synthesis, ribonucleotide reductase (RnR) whose activity is tightly linked to tumor growth. Besides circumstantial evidence that cancer is induced at this enzyme’s vulnerable free-radical-containing active-site by various carcinogens, its role in initiating retinoblastoma and HPV-related cervical cancers is well documented. Blocking the activity of malignant RnR is a certain way to arrest cancer.

Pneumonic plague outbreaks are relatively infrequent in modern times but in the early part of the 20th century, they were commonplace including several well-documented epidemics responsible for the deaths of thousands. The transmissibility of this disease seems to be discontinuous since in some outbreaks few transmissions occur, while in others, the progression of the epidemic is explosive. Modern epidemiological studies explain that transmissibility within populations is heterogenous with relatively few subjects likely to be responsible for most transmissions and that ‘super spreading events’, particularly at the start of an outbreak, can lead to a rapid expansion of cases. These findings concur with outbreaks observed in real-world situations. It is often reported that pneumonic plague is rare and not easily transmitted but this view could lead to unnecessary complacency since future risks such as the spontaneous incidence of anti-microbial strains, climate change leading to a disruption of natural cycles within plague foci and use of plague as a bioweapon cannot be discounted. Carers and first responders are vulnerable, particularly in poorer countries where access to medicines may be limited, out-breaks occur in inaccessible areas or where there is a lack of surveillance due to a paucity of funds.

The rank-3 antisymmetric tensors which are the magnetic monopoles of SU(N) Yang-Mills gauge theory dynamics, unlike their counterparts in Maxwell’s U(1) electrodynamics, are non-vanishing, and do permit a net flux of Yang-Mills analogs to the magnetic field through closed spatial surfaces. When electric source currents of the same Yang-Mills dynamics are inverted and their fermions inserted into these Yang-Mills monopoles to create a system, this system in its unperturbed state contains exactly 3 fermions due to the monopole rank-3 and its 3 additive field strength gradient terms in covariant form. So to ensure that every fermion in this system occupies an exclusive quantum state, the Exclusion Principle is used to place each of the 3 fermions into the fundamental representation of the simple gauge group with an SU(3) symmetry. After the symmetry of the monopole is broken to make this system indivisible, the gauge bosons inside the monopole become massless, the SU(3) color symmetry of the fermions becomes exact, and a propagator is established for each fermion. The monopoles then have the same antisymmetric color singlet wavefunction as a baryon, and the field quanta of the magnetic fields fluxing through the monopole surface have the same symmetric color singlet wavefunction as a meson. Consequently, we are able to identify these fermions with colored quarks, the gauge bosons with gluons, the magnetic monopoles with baryons, and the fluxing entities with mesons, while establishing that the quarks and gluons remain confined and identifying the symmetry breaking with hadronization. Analytic tools developed along the way are then used to fill the Yang-Mills mass gap.

Introduction The climate crisis is essentially a public health crisis. Response is imperative to prevent economic and social crises associated with the growing burden of climate impacts on human health and the health care sector. Green Podiatry Pillars By adopting the three pillars of Exercise, Evidence, and Everyday changes, podiatrists can contribute to more sustainable health and health care. Discussion Educating our patients to use their feet for low carbon active transport, eliminating interventions not supported by evidence, and reducing fossil fuel driven supply chains and energy use, are three impactful measures that all podiatrists, and indeed, all health and medical personnel, need to adopt. The avoidable suffering, enormous and costly use of resources for diabetic foot disease, is a scourge that must realise its preventable potential. It is too late, too costly, too polluting, and too sad, to continue to direct health care and research efforts and budgets, to an expensive modifiable diabetes disease process, potentiated by poor food and physical inactivity. Affected patients require skilled support, to avert such chronic disease processes, often not of their making. Conclusions Healthcare contributes 5 to 8% of green house gases (GHG), and non-communicable diseases (NCD) are increasing, so healthcare must lead on primary health. As citizens and health professionals, we must advocate for better community health, and educate our patients. Future Directions All health and medical personnel need to consider planetary health and sustainable healthcare within their daily work. Healthcare must act to address climate change, and realise benefits for people and planet.

For monitoring of chimeric antigen receptor (CAR) T-cell therapies antigen-based CAR detection methods are usually applied. However, for each target-antigen a separate detection system is required. Furthermore, when monitoring CAR T-cells in the blood of patients treated with bispecific antibodies or T-cell engagers (bsAbs/BiTEs) recognize the same antigen, these methods producing false-positive results in clinical diagnostics. Anti-CAR-linker monoclonal antibodies (mAbs) targeting the linker sequence between the variable domains of the antigen binding CAR fragment, promise an universal and unbiased CAR detection. To test this, we analyzed clinical specimens of all BCMA- and CD19 targeting CAR T-cell products currently approved for clinical use. We found a highly specific and sensitive CAR detection by using anti-CAR-linker mAb in blood cells from patients treated with Ide-cel, Tisa-cel, Axi-cel, Brexu-cel, and Liso-cel. For Ide-cel and Tisa-cel the sensitivity was significant lower compared to antigen-based CAR detection assays. Strikingly, the specificity of anti-CAR linker mAb was not affected by the simultaneous presence of bispecific blinatumomab or teclistamab for Axi-cel, Brexu-cel, Liso-cel or Ide-cel, respectively. Cilta-cel (containing an monomeric G4S-CAR linker) could not be detected by anti-CAR linker mAb. In conclusion, anti-CAR-linker mAbs are highly specific and useful for CAR T-cell monitoring but not universal applicable.

The construction of optimized biological fuel cells requires a cathode which combines the longevity of a microbial catalyst with the power density of an enzymatic catalyst. Laccase secreting fungi were grown directly on the cathode of a biological fuel cell to facilitate the exchange of inactive enzymes with active enzymes with the goal of extending the lifetime of laccase cathodes. Additionally, a functionally graded coating was developed to increase enzyme loading at the cathode. Directly incorporating the laccase producing fungus at the cathode extends the operational lifetime of laccase cathodes while eliminating the need for frequent replenishment of the electrolyte. Additionally, the hybrid microbial-enzymatic cathode addresses the issue of enzyme inactivation by using the natural ability of fungi to exchange inactive laccases at the cathode with active laccases. Finally, enzyme adsorption was increased through the use of a functionally graded coating containing an optimized ratio of titanium dioxide nanoparticles and single walled carbon nanotubes. The hybrid microbial-enzymatic fuel cell combines the higher power density of enzymatic fuel cells with the longevity of microbial fuel cells and demonstrates the feasibility of a self-regenerating fuel cell in which inactive laccases are continuously exchanged with active laccases.

The spatial resolution measurement limitation of the position-momentum uncertainty principle is shown to mathematically originate from the Bekenstein entropy bound and the associated second law of thermodynamics, as a special case in which a statistical thermodynamic distribution of energies is specialized to a fixed, definite probe energy equal to the average energy of that distribution. This is used in combination with the Wein displacement law to predict an ultraviolet cutoff for Planck blackbody radiation at about ⅛ of the Wein peak. A new UV photon counting experiment is proposed to test for this. A physical understanding of these results may be provided by a UV-complete, intelligible theory of general relativistic quantum mechanics in which the observation of a blackbody spectrum is simply a remote observation of Hawking radiation emitted from black hole fluctuations in the gravitational vacuum.

The first step in seeing is light absorption by photopigment molecules expressed in the photore-ceptors of the retina. There are two types of photoreceptors in the human retina that are respon-sible for image formation, rods and cones. Except at very low light levels when rods are active, all vision is based on cones. Cones mediate high acuity vision and color vision. Furthermore, they are critically important in the visual feedback mechanism that regulates refractive development of the eye during childhood. The human retina contains a mosaic of three cone types, short-wavelength (S), long-wavelength (L) and middle-wavelength (M); however, the vast major-ity (~94%) are L and M cones. The OPN1LW and OPN1MW genes, located on the X-chromosome at Xq28, encode the protein component of the light-sensitive photopigments. Here we review mechanism by which splicing defects in these genes cause vision disorders.

Diabetes mellitus is one of the most common endocrinopathies, estimated to affect about 5.4% of the world's population around 2025. It is thought that nearly a third of diabetic patients have some type of skin condition. Frequently, the cutaneous effects of this heterogeneous syndrome are ac-curately detected late in the progressive form of the disease. The main objective of the present study was to identify the main cellular characteristics of the cutaneous microenvironment in exper- imentally induced diabetes mellitus. Skin fragments were harvested from adult white Wistar rats of both sexes, with the weight of 200 g, 12 weeks after streptozotocin diabetes was induced. In parallel with histopathological diagnosis by using hematoxylin and eosine staining, samples were processed by transmission electron microscopy technique and examined with a Philips CM100 microscope. In the apparently macroscopically unchanged tegument, photon microscopy revealed both progres ive thinning of the epidermis in the early stages of diabetes and a significant process of fibrosis and collagen hyalinization in the dermis. In addition, in the early stages, the electron microscopic study provided ultrastructural details characteristic of a senescent phenotype with reduced cell proliferation. The morphological changes in the skin may be the first signs of disruption of carbohydrate metabolism and in the case of established diabetes may reflect its progression and the efficacy of therapy.

Transparent conductive electrodes (TCEs) are of enormous significance to the emergence of flexible and wearable electronics and continued growth of modern devices. Versatile and tunable TCEs, featuring with not only high optical transmittance but also intriguing features of electrochemical energy-storage capability, remain a significant challenge. Here we develop capacitive active films comprised of graphene-conjugated V2O5@poly (3,4-ethylene dioxythiophene) ternary composite (V2O5@PEDOT/rGO) on silver nanowire coated substrates as solid-state super/pseudocapacitors. The constructed electrodes exhibit improved electrolyte ions interaction with effective graphene layer, achieving high areal capacitance 0.6-1.2 mF.cm−2 with 0.5M LiCl electrolytes at optical transparency >60% with record durability. As demonstrated, the kinetic blocking of PEDOT layer and anchoring capability of graphene upon amphoteric soluble vanadium ions from layered V2O5 nanoribbons/nanobelts contribute synergistically to the unusual electrochemical stability, also shown using scanning electrochemical microscopy (SECM) providing electroactivity sites and ion transportation rates. As-fabricated symmetric solid-state supercapacitors delivered broad potential window >1.4 V under two different electrolyte environments (aqueous LiCl and LiCl/PVA gel) and demonstrated higher power and energy density (0.27 μWh.cm−2) outperforming previously reported devices at <0.1 μWh.cm−2. The electrochemical properties are also discussed in terms of solvation in polymer gel electrolyte ions.

Multimedia resources, such as instructional videos, are currently enjoying a certain popularity in training programmes for medical and dental students. The major challenge is to create such resources that have quality content and are acceptable to students. We investigated the opinions of a sample of 551 students from 4 medical universities in Romania in order to identify the characteristics of the instructional videos that students prefer and we comparatively analysed these characteristics according to gender, age group, but also according to their general preferences for using Internet services. We used univariate (hypothesis testing) and multivariate (Two-Step Clustering) data analysis techniques and revealed three clusters of students, primarily determined by perceptions of the visual appearance of instructional videos. The structure of the clusters by gender and age group is relatively similar, but we recorded differences between them associated with students' expressed preferences for certain Internet services compared to others. Students who prefer instructional videos to contain images used only for aesthetic purposes, to fill in breaks, use Internet services mainly for communication, while students who prefer in videos the use of already drawn explanatory diagrams are slightly younger than the others and use Internet services mainly for information and communication.

1) Background- Coronary artery bypass grafting (CABG) is a common surgical intervention for patients with severe coronary artery disease. The Model for End-Stage Liver Disease (MELD) score has been widely used to predict mortality risk in patients with end-stage liver disease, but its utility in predicting postoperative outcomes in cardiac surgery patients is less well-established. 2) Methods-This retrospective study aims to investigate the association between preoperative MELD score and post-operative complications, length of hospital stay, and mortality in patients under-going coronary artery bypass grafting. This is a single-center, retrospective cohort study conducted at a tertiary care academic medical center. The study includes all adult patients who underwent elective coronary artery bypass grafting between January 2011 and December 2020. Preoperative MELD scores were calculated for each patient, and postoperative outcomes including major ad-verse cardiac events, length of hospital stay, and 30-day mortality was assessed. To ensure a homogeneous study cohort, we excluded patients who underwent emergent cardiac procedures or had incomplete data necessary for the calculation of MELD scores and assessment of postoperative outcomes. Data was extracted from the electronic medical records, including patient de-mographics, comorbidities, preoperative laboratory values, operative details, and postoperative outcomes. The study protocol was approved by the Institutional Review Board, and the require-ment for informed consent was waived due to the retrospective nature of the study.3) Results- This study reveals a statistical association between the MELD score calculated at admission and the length of hospital stay, duration in the ICU, patient age, and the duration of aortic clamping and extracorporeal circulation. Specifically, there is an exponential increase in the MELD score corre-lating with the rise in these factors, both collectively and individually, highlighting a significant relationship between the duration of extracorporeal circulation and aortic clamping time. 4) Conclusion-Patients with a high MELD score had an increased risk of postoperative complications and mortality compared to those with a low MELD score. Careful preoperative patient selection and optimization of the patient's clinical condition may improve outcomes in patients with advanced liver disease undergoing cardiac surgery.

Treatment of neurological disease is hampered by the lack of validated specific and sensitive biomarkers, resulting in delayed diagnosis and nonspecific disease modifying therapies. For example, in ALS the lack of a sensitive and specific biomarker impedes the ability to administer a treatment prior to or at the onset of motor neuron dysfunction. Although viral or other infectious etiologies have been proposed as a contributing factor to neurodegeneration, it can be argued that these are casual and not causal associations. In the case of ALS, evidence for direct causality would require in vivo validation of specific nucleotide sequences of microbial origin which are known to be neuroinvasive with tropism for motor neurons, such as polio and non-polio. Several viral enteropathogens recapitulate the pathological events in sporadic ALS, including the ability to cleave TDP-43 resulting in accumulation of misfolded proteins in the cytoplasm. This review provides supporting evidence that motor neuron disease is causally related to specific enteroviruses and argues that prospective validation is imperative for effective prevention and treatment.

Sometimes a pavement deflects only because of seasonal volume change of expansive soils in the pavement subgrade. Engineering practitioners expect an implementable and straightforward analysis method for a geosynthetic-reinforced pavement subjected to the swelling/shrinkage issue of expansive clayey subgrade, in an effort to find the bending moment, shear force and tension force distributions through the reinforced pavement, which are induced from the volumetric changes of subgrade soils. The virtual load method (VLM) was proposed in the past following the Timoshenko beam theory to analyze geosynthetic-reinforced pavement on expansive soils. In the VLM, the unknown virtual distributed load was obtained in the way by applying the inverse theory for the identification of material parameters of the pavement-foundation system. It was seen that the selection of the number of material parameters to obtain virtual load significantly affects the accuracy of the structural properties of the pavement and tensile properties of the geosynthetics if the linear least square method is used. In this paper, a unique numerical scheme was proposed in the hopes of solving the issue. After a forward problem was solved numerically, the Timoshenko beam deflection was taken as a start-up for the inverse problem to back analyze the load applied to the pavement. Solutions from forward/backward examples have explicitly shown the accuracy achieved related to the bending moment in the pavement and tension in the geosynthetic reinforcements. The proposed methodology can be applied for an in-depth understanding of the geosynthetic function for the mitigation of longitudinal cracks on pavements caused by heave/shrinkage of expansive soils.

Recent advances in synthetic membranes allow their use in fields as diverse as food and agriculture, biotechnology, industrial wastewater treatment, and potable water production. Among the newly developed technologies, nanofiltration for liquids and more particularly for desalination of seawater or saline aquifers are actively pursued. However, current solid-state membranes performance is limited, which calls for the development of novel formulations for membranes offering both high permeability (ion and water flux) and ion differentiation (selectivity), usually considered antagonist features. We report the development of hybrid nanoporous membranes made of solid-state polymeric carbonate track-etched (PCTE) thin films in which biological ion channels such as Gramicidin A (GA), alpha-hemolysin (α-HL), and outer-membrane protein F (OmpF) aquaporin are confined and graphene oxide (GO) conjugated cobalt ion selective binding peptide motifs (Copep) are adsorbed, referring as bioinspired and biomimetic approaches, respectively. These solid-state nanoporous membranes are attracting widespread attention since they offer scalability, mechanical robustness, selectivity, controlled pore dimension and shape, for water sustainability. The ion permeability, ion diffusion coefficient and selective ion recognition are evaluated via nanofiltration, cell diffusion kinetics, and UV-Visible absorption spectroscopy to gain insights into the role of key performance parameters including effective ion confinement in track-etched pores, rich surface chemistry, and peptide-induced channel for selective ion transport. These findings provide new avenues for artificial ion channels by synergistic combination of eco-friendly material design such as GO enabled by bio-molecular recognition chemistry.

(1) Background: The RDW-CV has predictive value in many pregnancy-related conditions. Re-search question: Can the RDW-CV be utilized predictively in pregnant patients with thrombo-philia? Aim of the study: To carry out a detailed analysis of the RDW-CV in pregnant patients with treated thrombophilia as compared with pregnant patients without thrombophilia who de-livered via cesarean section at term. (2) Methods: We studied 160 pregnant patients, including 80 pregnant patients with treated thrombophilia in the study group, and another 80 patients of a similar age and parity. The patients were referred to our hospital for delivery at term by means of a cesarean section between 1/10/2017 and 1/12/2021. Every patient received a sonogram during the first 1–2 days after the cesarean section, and their uterine evaluation was interpreted using the PUUS (Postpartum Uterine Ultrasonographic Scale). (3) Results: Our PUUS≥1 pregnant and postpartum patients with treated thrombophilia were the only group with an RDW-CV value over 14. No deep vein thrombosis was observed during hospitalization, showing that the antico-agulant treatment was necessary and effective. An RDW-CV of 14.5 was the highest value in the Rh-negative group of pregnant patients with treated thrombophilia. An RDW-CV of 14.48 was the highest level in the Rh-negative postpartum patients with treated thrombophilia. (4) Conclu-sion: An RDW-CV of ≥14 can predict uterine hematometra (PUUS≥1). The RDW-CV values were higher in Rh-negative patients.

The rapid transmission of COVID-19 in school communities has been a major concern. To ensure that mitigation systems were in place and support was available, a digital intervention to encourage and facilitate infection control behaviours was rapidly adapted and optimised for implementation as a whole school intervention. Using the person-based approach, ‘Germ Defence’ was iteratively adapted, guided by relevant literature, co-production with Patient and Public Involvement representatives, and think aloud interviews with forty-five school students, staff, and parents. Suggested infection control behaviours deemed feasible and acceptable by the majority of participants included handwashing/hand-sanitising and wearing a face covering in certain contexts such as crowded public spaces. Promoting a sense of collective responsibility was reported to increase motivation for the adoption of these behaviours. However, acceptability and willingness to implement recommended behaviours seemed to be influenced by participants’ perceptions of risk. Barriers to the implementation of recommended behaviours in school and at home primarily related to childcare needs and physical space. We conclude that it was possible to rapidly adapt Germ Defence to provide an acceptable resource to help mitigate against infection transmission within and from school settings. Adapted content was considered acceptable, persuasive, and accessible.

Abstract: Congenital hyperinsulinism (CHI) is a rare disorder of glucose metabolism and is the most common cause of severe and persistent hypoglycemia (hyperinsulinemic hypoglycemia, HH) in the neonatal period and childhood. Most cases are caused by mutations in the ABCC8 and KCNJ11 genes that encode the ATP-sensitive potassium channel (KATP). We present the correlation between genetic heterogeneity and the variable phenotype in patients with early-onset hyperinsulinemic hypoglycemia caused by ABCC8 gene mutations. In the first patients, which presented persistent severe hypoglycemia since the first day of life, molecular genetic testing revealed the presence of a homozygous mutation in the ABCC8 gene [deletion in the ABCC8 gene c.(2390+1_2391-1)_(3329+1_3330- 1)del] correlated with a diffuse form of hyperinsulinism (the parents being healthy heterozygous carriers). In the second patient, the onset was on the third day of life with severe hypoglycemia, and genetic testing identified a heterozygous mutation in the ABCC8 gene c.1792C&gt;T (p.Arg598*) inherited on the paternal line, which led to the diagnosis of focal form of hyperinsulinism. To locate the focal lesions, (18)F-DOPA (3,4-dihydroxy-6-[18F]fluoro-L-phenylalanine) PET/CT was recommended (an investigation that cannot be carried out in the country), but the parents refused to carry out the investigation abroad. In this case, early surgical treatment could have been curative. In addition, the second child also presented secondary adrenal insufficiency requiring replacement therapy. At the same time, she developed early recurrent seizures that required antiepileptic treatment. We emphasize the importance and of molecular genetic testing for diagnosis, management and genetic counseling in patients with HH.

We study L_2-approximation problems in the weighted Hilbert spaces in the worst case setting. Three interesting weighted Hilbert spaces appear in this paper, whose weights are equipped with two positive parameters $\ga_j$ and $\az_j$ for $j=1,\,2,\dots,\,d$. We consider the worst case error of algorithms that use finitely many arbitrary continuous linear functionals. We discuss the exponential convergence-(t,s)-weak tractability (EC-(t,s)-WT) of these L_2-approximation problems under the absolute or normalized error criterion. In particular, we obtain the sufficient and necessary conditions for EC-(1,1)-WT and EC-(t,1)-WT with t

We have an unprecedented ability to map the Earth’s surface as deep learning technologies are applied to an abundance of high-frequency Earth observation data. Simple, free, and effective methods are needed to enable a variety of stakeholders to use these tools to improve scientific knowledge and decision making. Here we present a trained U-Net model that can map and delineate ground mounted solar arrays using publicly available Sentinel-2 imagery, and that requires minimal data pre-processing and no feature engineering. By using label overloading and image augmentation during training, the model is robust to temporal and spatial variation in imagery. The trained model achieved a precision and recall of 91.5% each and an intersection over union of 84.3% on independent validation data from two distinct geographies. This generalizability in space and time makes the model useful for repeatedly mapping solar arrays. We use this model to delineate all ground mounted solar arrays in North Carolina and the Chesapeake Bay watershed to illustrate how these methods can be used to quickly and easily produce accurate maps of solar infrastructure.

This article is about a framework for determining the degree of realism of any given 1 passenger ride motion discomfort measurement formula. After providing some context and reviewing 2 evidence of deficiency in currently popular ride motion discomfort measurement formulas, the article 3 outlines the research program that needs to be carried out in order to establish such a framework. 4 The research begins with gathering recordings of uncomfortable ride motion episodes encountered in 5 a chosen type of passenger transport service. It then has test subjects compare the episodes via a ride 6 motion simulator and adjust their amplitudes pair wise until they cause equal discomfort. It explains 7 how to take the pair wise amplitude adjustments and determine amplitude adjustments that bring all 8 of the motion episode recordings to a common level of discomfort so that they form a normalized set. 9 Then, the lower the scatter of the scores assigned by any given discomfort measurement formula to 10 the members of that set, the more realistic that formula will be for the chosen service.

This study explores the complexities involved in the extraction and purification of catechins, prominent bioactive compounds found in plant extracts and tea. It addresses challenges arising from the intricate molecular structure of catechins and their inherent variability across botanical sources. Despite these obstacles, catechins present significant potential, particularly in healthcare. Their potent antioxidant properties have been extensively investigated and associated with numerous health benefits, positioning them as promising therapeutic agents for combating chronic diseases. Furthermore, catechins have diverse applications across various industries, including food and beverage, cosmetics, agriculture, and materials science. This abstract emphasizes the importance of continued research and innovation in catechin extraction and utilization, which hold promise for advancing human health and technological progress across multiple domains.

The positional cloning of single nucleotide polymorphisms (SNPs) of the neutrophil cytosolic factor 1 (Ncf1) gene, advocating that a low oxidative burst drives autoimmune disease, demands an understanding of the underlying molecular causes. A cellular target could be T cells, which have been shown to be regulated by reactive oxygen species (ROS). However, the pathways by which ROS mediate T cell signaling remain unclear. The adaptor molecule linker for activation of T cells (LAT) is essential for coupling T cell receptor-mediated antigen recognition to downstream responses, and it contains several cysteine residues that have previously been suggested to be involved in redox regulation. To address the possibility that ROS regulate T cell-dependent inflammation through LAT, we established a mouse strain with cysteine-to-serine mutations at positions 120 and 172 (LATSS). We found that redox regulation of LAT through C120 and C172 mediate its localization and phosphorylation. LATSS mice had reduced numbers of double-positive thymocytes and naïve peripheral T cells. Importantly, redox insensitivity of LAT enhanced T cell-dependent autoimmune inflammation in collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA). This effect was reversed on an NCF1-mutated (NCF1m1j), ROS-deficient, background. Overall, our data shows that LAT is redox-regulated, acts to repress T cell activation, and is targeted by ROS induced by NCF1 in antigen-presenting cells (APCs).

(1) Background: Thrombophilia is a tendency towards hypercoagulability, and it is increased by pregnancy, peaking around delivery. Research question: does thrombophilia stimulate the in-flammatory state of the patient, already suppressed by pregnancy? (2) Methods: Eighty thrombo-philia patients admitted for delivery between 1/10/2017 and 1/12/2021 were prospectively stud-ied, together with eighty age- and para-matched control patients. Patients were admitted for de-livery at term by means of cesarean section. The inflammation indexes from the complete blood count values analysis during both the 24 hours before and after labor—extracted from the hospi-tal’s medical records—were calculated and then correlated with uterine involution. (3) Results: Except for the PLR, most of the numerous inflammation indexes studied were not significantly different in treated thrombophilia patients, before and after delivery, compared to non-thrombophilia patients. Only when we split the patients, based on the uterine haematometra in the first 24-48 hours postpartum, we found out that the few treated thrombophilia patients with haematometra (14 with haematometra out of 79 with treated thrombophilia) had elevated SII and AISI antepartum. In pregnant patients treated for thrombophilia, MLR is higher in pa-tients without the Rh factor than in those with the Rh factor. In non-thrombophilia patients, MCVL and NLPR increased with age and before labor, while SII and AISI increased with age postpartum. (4) Conclusions: Thrombophilia did not stimulate the inflammatory state of the pa-tient, already suppressed by pregnancy.

Uganda possesses natural rainforests that serve enormous environmental ecosystems and biodiversity services. Moreover, the country is known for its various tropical rainforest hardwoods, birds, and animal species. Over the years, the trend in the natural forest land has declined at an alarming rate; hence need to investigate the possible drivers. The loss of such biodiversity and ecosystems risks desertification and extreme climatic condition. As the world moves towards Zero Deforestation 2030, understanding the determinants of deforestation and forest degradation is paramount. Therefore, the main objective of this study was to understand the impact and relationships between net forest conversion, energy emission, agriculture, and forest production of Roundwood. We used data from FAO for the period 2004-2016. Using the ADF and KPSS test, we checked for the unit root presence in the variables. Also, the study used two different regression models: multiple linear regression and dynamic linear model. To analyze the determinants of deforestation, we used net forest conversion in Uganda. There was 94 % variation in the dependent variable (Net Forest conversion). The outcome of the dynamic linear regression showed that agriculture and energy emission positively impact net forest conversion. Based on our findings, this study recommended the modernization of agriculture by the government of Uganda to stop cutting down the forests on a big scale. Also, the study suggested that the government strictly legislate Roundwood and wood fuels/charcoal and firewood to reduce huge dependency on forests toward Zero-Deforestation by 2030. If well-structured and implemented, government policies could solve the unnecessary over dependency on the rainforest, the heart of the region's climatic conditions.

In semi-arid regions, climate change has affected crop growing season length and sowing time, potentially causing low yield of the rainfed staple crop pearl millet (Pennisetum glaucum L.) and food insecurity among smallholder farmers. In this study, we used 1994–2023 rainfall data from Namibia's semi-arid North-Central Region (NCR), receiving November–April summer rainfall, to analyze rainfall patterns and trends and their implications on the growing season to propose climate adaptation options for the region. The results revealed high annual and monthly rainfall variabilities, with nonsignificant negative trends for November–February rainfalls, implying a shortening growing season. Furthermore, we determined the effects of sowing date on grain yields of the early-maturing Okashana-2 and local landrace Kantana pearl millet varieties and the optimal sowing window for the region, using data from a two-year split-plot field experiment conducted at the University of Namibia-Ogongo Campus, NCR, during the rainy season. Cubic polynomial regression models were applied to grain yield data sets to predict grain production for any sowing date between January and March. Both varieties produced the highest grain yields under January sowings, with Kantana exhibiting a higher yield potential than Okashana-2. Kantana, sown by 14 January, had a yield advantage of up to 36.0% over Okashana-2, but its yield gradually reduced with delays in sowing. Okashana-2 exhibited higher yield stability across January sowings, surpassing Kantana’s yields by up to 9.4% following the 14 January sowing. We determined the pearl millet optimal sowing window for the NCR from 1–7 and 1–21 January for Kantana and Okashana-2, respectively. These results suggest that co-cultivation of early and late pearl millet varieties and growing early-maturing varieties under delayed seasons could stabilize grain production in northern Namibia and enhance farmers' climate adaptation. Semi-arid agro-region policymakers could utilize this information to adjust local seed systems and extension strategies.

Dirofilariosis is an infectious disease caused by species of the Dirofilaria genus. It is manifested by the appearance of a subcutaneous swelling, especially in the eye region. We present the case of a 29-year-old patient that accused facial asymmetry in the right genian region. Following clinical and paraclinical evaluations, the diagnosis of parasitic cyst was established in the context of dirofilariosis with Dirofilaria repens (D. repens). Treatment consisted of surgical excision of the formation associated with prophylactic antibiotic medication. Macroscopic analysis of the excision piece revealed a structure that contains a cystic cavity and a filamentous form with a length of approximately 10 mM and a diameter of 1 mM. This is the first case of dirofilariosis located in the genian region reported in Romania. The overview of this pathology is important to raise awareness among physicians about its presence and its clinical variations.

Carnivorous waterbirds have been reported to enhance wetlands diversities, control pests, bio-indicators of ecological conditions, and act as indicators of potential disease outbreaks. They also provide important ecosystem services to indigenous communities residing along wetlands. Regardless of their importance, global waterbirds populations are declining. Despite their ecological contribution to wetlands functions and ecosystem services, piscivore waterbirds have been re-ported to compete with piscivorous fish and fishermen. The aim of this study was to compare piscivorous waterbirds species and functional diversity between fish protected areas (FPA) and non-fish protected area (NFPA) in two tributaries of Zambezi River in Namibia. We also measured the degree to which patterns of guild structure between piscivore waterbirds and fish were similar between FPA and non-FPA. Species diversities were determined by calculating the Shannon Diversity Index. We calculated taxonomic diversity, functional diversity and community-based trait diversity indices for each tributary. Generally, species diversities were not significantly different between FPA and NFPA (P > 0.05). However, all functional diversities indices calculated were significantly different between FPA an NFPA (P < 0.05 for all comparisons). This was partly due to food item, weight and movement type that were associated with each site.

Background and Objectives: Metastases are the most common tumors of the spine. As an important increase in the annual incidence of spinal metastases (SM) has been observed in the last decade, the aim of this study was to describe the epidemiology and histopathological types of SM surgically treated in the neurosurgery clinics of a regional hospital in North-Eastern Romania over a period of 5 years, in order to define a certain tumor profile that would benefit from an early screening. Materials and Methods: We retrospectively evaluated 115 adult patients, searching for demographic data (gender and age of the patients), primary tumor characteristics (location and histological type), topography and histopathological type of the spinal metastasis, and the time interval between the diagnosis of the primary tumor and the surgery for the spinal metastasis. Results: The patients were elderly (average age = 58.96 years), with a male predominance (67.82%). Main location of SM was in thoracic region (44.34%), with multiple vertebral metastases in 30.43% patients. Only 33.04% of the patients had a known cancer at the time of admission. Primary tumor was located mainly in lung (47.82%), gastrointestinal tract (15.65%), breast (11.30%), prostate (10.43%) and kidney (9.56%). SM from lung cancer mostly expressed squamous cell carcinoma (19.13%), and those from the digestive system mostly exhibited a moderately/poor colorectal adenocarcinoma (8.69%). Conclusions: Our data suggest the need for close surveillance of patients diagnosed with lung cancer and colorectal cancer because these malignancies most frequently develop spinal metastases. Smoking prevention actions and screening programs for the detection and removal of precancerous colorectal lesions must be developed and expanded.

ABSTRACT: Iodixanol is an iso-osmolar nonionic dimeric hydrophilic contrast agent with a higher viscosity than the monomeric agents. It is the only Food and Drug Administration (FDA)approved isoosmolar agent in the United States, and it is the only contrast agent with an FDA-approved indication for use in cardiac computed tomographic angiography (CCTA), to assist in the diagnostic evaluation of patients with suspected coronary artery disease. In clinical studies, it has been noted to have fewer side effects and similar image quality when compared to low osmolar contrast media. This can be attributed to the pharmacological properties of iodixanol. In the field of cardiology, iodixanol among other intravenous contrast media is used for coronary computed tomography angiography and cardiac catheterization. In this article, the use, tolerability and efficacy of iodixanol in the field of cardiology are reviewed, specifically evaluating the use for CCTA and coronary angiography, including outcome studies, randomized trials and comparisons to other contrast agents.

This research addresses a gap in the literature by conducting a comprehensive analysis of patients’ level of satisfaction with dental care. Methods: By combining quantitative and qualitative survey methods with the PSQ questionnaire this study aims to augment ongoing initiatives to enhance dental patients’ experiences by painting a more comprehensive depiction of patients' level of satisfaction; Results: When asked about their overall level of satisfaction 77,1% of the patients said they received excellent services from the office personnel and 72,2% said they trust their doctors; Conclusions: Assessing patient satisfaction in the realm of dental services quality is crucial for enhancing service quality and accuracy, benefiting both patients and dentists, and ultimately improving public health.

As new vaccines reduce P. falciparum (Pf) cases, clinicians can focus on rescuing more children with cerebral malaria (CM). Adjunctive “therapeutically-rational exchange transfusion” (T-REX) refers to using special “Pf-resistant” donor red blood cells (RBCs) that secrete nano-sized RBC extracellular vesicles (EVs). Can some RBC EVs rapidly dislodge Pf-infected RBCs (iRBCs) sequestered in blood vessels and reduce inflammation? Does post-exchange “rebound parasitemia” reflect sequestration-reversal? We reviewed case-reports, EV and liposome studies, expert perspectives, and time-sequence data. In the AQUAMAT study, median coma-recovery time was 20 hours for artesunate. In contrast, a CM patient treated with type-O T-REX quickly began speaking (during the procedure). For other rapid-recovery CM patients, donor RBC variables had not been specified. Despite rapid Pf-killing, drugs need 20 hours to substantially reduce iRBC cytoadhesion while EVs can selectively bind distant inflamed tissues within 15 minutes. RBCs stressed by blood-bank storage and Pf infection secrete EVs. Post-exchange “rebound parasitemia” can occur within 60 minutes and may reflect release of sequestered iRBCs. Sequestration-reversal can be assessed by monitoring Pf parasitemia and total Pf biomass. New data suggest clinicians, working with transfusion- and laboratory-medicine physicians, can, and should, assess T-REX options and publish their findings to help clarify how RBC EVs may serve as therapeutic “decoy ligands.”

Flash flooding, a hazard which is triggered by heavy rainfall is a major concern in many regions of the world often with devastating results in mountainous elevated regions. We adapted remote sensing modelling methods to analyse one flood in July 2015, and believe the process can be applicable to other regions in the world. The isolated thunderstorm rainfall occurred in the Chitral River Basin (CRB), which is fed by melting glaciers and snow from the highly elevated Hindu Kush Mountains (Tirick Mir peak’s elevation is 7708 m). The devastating cascade, or domino effect, resulted in a flash flood which destroyed many houses, roads, and bridges and washed out agricultural land. CRB had experienced devastating flood events in the past, but there was no hydraulic modelling and mapping zones available for the entire CRB region. That is why modelling analyses and predictions are important for disaster mitigation activities. For this flash flood event, we developed an integrated methodology for a regional scale flood model that integrates the Tropical Rainfall Measuring Mission (TRMM) satellite, Geographic Information System (GIS), hydrological (HEC-HMS) and hydraulic (HEC-RAS) modelling tools. We collected and use driver discharge and flood depth observation data for five river sub-stream areas, which were acquired in cooperation with the Aga Khan Rural Support Program (AKRSP) organization. This data was used for the model’s calibration and verification. This modelling methodology is applicable for other regional studies especially for rough mountainous areas which lack local observations and river discharge gauges. The results of flood modelling are useful for the development of a regional early flood warning system and flood mitigation in hazardous flood risk areas. The flood simulations and prepared connected video visualization can be used for local communities. This approach is applicable for flood mitigation strategies in other regions.

Scrub typhus threatens one billion people in the Asia-Pacific area and cases have emerged outside this region. It is caused by infection with any of the multitude of strains of the bacterium, Orientia tsutsugamushi. A vaccine that affords heterologous protection and a commercially available molecular diagnostic assay are lacking. Herein, we determined that the nucleotide and translated amino acid sequences of outer membrane protein A (OmpA) are highly conserved among 51 O. tsutsugamushi isolates. Molecular modeling revealed the predicted tertiary structure of O. tsutsugamushi OmpA to be very similar to that of the phylogenetically related pathogen, Anaplasma phagocytophilum, including the location of a helix that contains residues functionally essential for A. phagocytophilum infection. PCR primers were developed that amplified ompA DNA from all O. tsutsugamushi strains, but not from negative control bacteria. Using these primers in quantitative real-time PCR enabled sensitive detection and quantitation of O. tsutsugamushi ompA DNA from organs of mice that had been experimentally infected with the Karp or Gilliam strains. The high degree of OmpA conservation among O. tsutsugamushi strains evidences its potential to serve as a molecular diagnostic target and justifies its consideration as a candidate for developing a broadly protective scrub typhus vaccine.

Landiolol is an ultra-short-acting, selective ß1- adrenergic receptor blocker that was originally approved by Japan for the treatment of intraoperative tachyarrhythmias. It has gained attention for its use in the management of tachyarrhythmias and perioperative tachycardia, especially atrial fibrillation for both cardiac and non-cardiac surgeries. It can be the ideal agent for heart rate control due to its high β1‐selectivity, the potent negative chronotropic effect, a limited negative inotropic potential, and an ultrashort elimination half‐life (around 4 min); moreover, it may have a potential therapeutic effect for sepsis and pediatric patients. Landiolol seems to be superior to other short‐acting and selective beta‐blockers such as esmolol. This review aims to provide a comprehensive overview of landiolol, a new ultra-short-acting ß1 selective antagonist, including its pharmacology, clinical applications, efficacy, safety profile, and future directions in research and clinical data.

The visual appearance of humans derives significantly from our skin and hair color. While melanin from epidermal melanocytes protects our skin from the damaging effects of ultraviolet radiation, the biological value of pigmentation in the hair follicle, particularly in the scalp, is less clear. In this study, we explore the heterogeneity of pigment cells in the human scalp anagen hair follicle bulb, a site conventionally viewed to be focused solely on pigment production for transfer to the hair shaft. Using c-KIT/CD117 microbeads, we isolated bulbar c-KIT-positive and c-KIT-negative melanocytes. While both subpopulations expressed MITF, only the c-KIT-positive fraction expressed SOX10. We further localized bulbar melanocyte subpopulations (expressing c-KIT, SOX10, MITF, and DCT) that exhibited distinct/variable expression of downstream differentiation-associated melanosome markers (e.g., gp100 and Melan-A). Localization of a second ‘immature’ SOX10 negative melanocyte population, which was c-KIT/MITF double positive, was identified outside of the melanogenic zone in the most peripheral/proximal matrix. These studies describe an approach to purifying human scalp anagen hair bulb melanocytes, allowing us to identify unexpected levels of melanocyte heterogeneity. The function of the more immature melanocytes in this part of the hair follicle remains to be elucidated. Could they be in-transit migratory cells destined to synthesize mela-nin ultimately or could they contribute to the hair follicle in non-melanogenic ways.

Hyaluronic acid, in the form of a gel or viscoelastic colloidal solution, is currently used for viscosupplementation of joints affected by osteoarthritis, but its effectiveness is under debate in relation to newer alternatives. Based on meta-analytical arguments, the present article reinforces the opinion that there are still no decisive arguments for its complete replacement, but for its use adapted to the peculiarities of the disease manifestation and of the patients. A “broad” comparison is first made with almost all alternatives studied in the last decade, and then a meta-regression study is performed to compare and predict the effect size induced by viscosupplementation and platelet-rich plasma therapies. If they are computerized, the developed models can represent tools for clinicians in determining the appropriateness of the option or not for viscosupplementation, in a manner adapted to the pain felt by the patients, to their age, or to other clinical circumstances. The models were generated using the latest algorithms for meta-analysis and meta-regression implemented in the R language and assembled in different R packages. All primary data and necessary R scripts are provided in accordance with the philosophy of reproducible research. Finally, HA-based products, currently under circumspection, are still clinically useful.

Visible light photography diagnostic images are coloured ex vivo medical images popularly used in Dermatology and Endoscopy for diagnosis and monitoring. The need to protect the integrity of these images as well as associated patient data calls for techniques such as image steganography and watermarking. This research explores and compares the effect of watermarking on the YIQ and YCbCr colour transforms used in processing digital coloured images and video in recent times. Using a new spread spectrum watermarking algorithm, it was found that YIQ has better distortion performance than YCbCr in the order of 3dB while YCbCr had lower BER for accurate watermark retrieval and tamper detection in the order of 1.3 x 10-3.

Landform Evolution Modelling (LEM) provides an avenue for simulating how a landscape may evolve over extended time periods of thousands of years. The CAESAR-Lisflood LEM that includes a hydrologic model (TOPMODEL) and a hydraulic model (Lisflood) can be used to assess the proposed final landform morphology of a mine site by simulating how the mine landform and the landscape would evolve over a 1,000-year period. The accuracy of future simulations depends on the calibration and validation of the model to the past and present events. Calibration and validation of the model involves finding a combination of parameters of the model which when applied and simulated gives model outputs similar to those observed for the real site scenario for corresponding input data. Calibrating the sediment output of the CAESAR-Lisflood model at the catchment level and using it for studying the equilibrium conditions of the landform is an area yet to be explored. Therefore, the aim of this study was to calibrate the CAESAR-Lisflood model and then validate it. To achieve this, the model was run for a rainfall event with a set of parameters, plus discharge and sediment data for the input point of the catchment, to analyze how similar the model output would behave when compared with the discharge and sediment data for the output point of the catchment. The model parameters were then adjusted until the model closely approximate the real site values of the catchment. It was then validated by running the model for a different set of events and checking that the model gave similar results to the real site values. The outcomes demonstrated that while the model can be calibrated to a greater extent for hydrology (discharge output) throughout the year, the sediment output calibration may be slightly improved by having the ability to change parameters to take into account the seasonal vegetation growth during the start and end of the wet season. This study is important for designing and testing post-mining rehabilitated landscape systems that assess hydrology and sediment movement in seasonal biomes.

Many pilot-based initiatives have been developed to promote awareness and use of climate information services among vulnerable smallholder farmers in Africa through million-dollar investments. However, despite their experimental nature, these pilot projects have been successful in raising participating farmers’ awareness and use of climate information services and they can inform transferrable good practices. Through a systematic literature review approach, this review sought to understand ways in which these past pilot projects have contributed to climate risk management in the context of smallholder farming and the factors that led to their success. Results showed that climate information services main contribution to climate risk management has been through facilitating farm level decision making. Factors that led to success of the pilots include: use of downscaled information; building institutional partnerships to add value to climate information; involving farmers through the co-designing and co-developing process; face-to-face way of communication; embedding pre-seasonal workshops in the activities of local institutions for sustainability; using diversity of communication channels to enhance reach among others. These factors can be borrowed as good practices to inform future efforts focused on increasing adoption of climate information services among a wider population beyond pilot project reach.

With growing urbanisation the sustainability of cities has become increasingly important. Although cities have been using indicators for a long time it is only in the last decades that attempts have been made to collate indicators into indicator sets with the aim of reflecting the many different aspects that need to be covered to assess the sustainability of a city. The aim of this paper is to review how indicators for monitoring sustainable urban development have evolved over time and compare them to the indicators suggested by the UN Sustainable Development Goals (SDGs). The review reveals that previous indicator sets emphasised environmental sustainability, health and economic growth. It is also shown that indicator sets that pre-date the SDGs lacked dimensions such as gender equality and reduced inequalities. In all, the SDG indicators provide the possibility of a more balanced and integrated approach to urban sustainability monitoring. At the same time, a methodology is needed to facilitate the adaptation process of localising the SDGS, targets and indicators. Challenges of local application include their large number, their generic characteristics and the need to complement them with specific indicators that are more relevant at the city level.

Precise monitoring of individual crop growth and health status is crucial for precision agriculture practices. However, traditional manual inspection methods are time-consuming, labor-intensive, and often lack the spatial resolution required for detailed analysis. This research addresses the need for efficient and high-resolution crop monitoring by leveraging Unmanned Aerial Vehicle (UAV) imagery and advanced computational techniques. The primary objective was to develop a methodology for precise identification, extraction, and monitoring of individual corn crops throughout their growth cycle. This was achieved by integrating UAV-derived data with image processing, computational geometry, and machine learning techniques. UAV imagery was ac-quired bi-weekly at altitudes of 40m and 70m, capturing the entire growth cycle of a corn crop from planting to harvest. A time-series Canopy Height Model (CHM) was generated by analyzing the differences between the Digital Terrain Model (DTM) and the Digital Surface Model (DSM) derived from the UAV data. Local spatial analysis and image processing techniques were em-ployed to determine the local maximum height of each crop. Subsequently, a Voronoi data model was developed to delineate individual crop canopies, successfully identifying 13,000 out of 13,050 corn crops in the study area. For enhanced accuracy in canopy size delineation, vegetation indices were incorporated into the Voronoi model segmentation, refining the initial canopy area esti-mates by eliminating interference from soil and shadows. The proposed methodology enables precise estimation and monitoring of crop canopy size, height, biomass reduction, lodging, and stunted growth over time, providing valuable insights for precision agriculture practices. This work contributes to the scientific community by demonstrating the potential of integrating UAV technology, computational geometry, and machine learning for accurate and efficient crop mon-itoring at the individual plant level.

A set of polymer composite bolted T-joints with novel configuration consisting of internal skeleton and external skin was fabricated using a prepreg-RTM co-curing molding process. Experiments were conducted to study their mechanical properties under bending load. A finite element model with a polymer resin area between the skin and skeleton was established and verified by the experimental results. Then, the damage propagation process and failure mechanism of the joint and the influence of three factors related to the layer characteristics of the skin and skeleton were investigated by the validated models. The results show that the bending stiffness and the yield limit load of the novel composite T-joint are 0.81 times and 1.65 times that of the 2A12 aluminum T-joint respectively, while at only 55.4% of its weight. The damage of the joint initiates within the resin area and leads to a degradation of the joint bending performances. The preferred stacking sequence of the skeleton is [0/+45/90/-45]ns when primarily subjected to bending loads. The decrease in bending performances is within 5% with the inclining angle of the skeleton less than 12 degrees. The more layers of 90° in the skin, the better bending performances of the joints, while the more layer of 0°, the poorer bending performances.

Background: HIV poses a threat to global health. With effective treatment options available, education and testing strategies are essential in preventing transmission. Text messaging is an effective tool for health promotion and can be used to target higher risk populations. This study reports on the design, delivery and testing of a mobile text messaging SMS intervention for HIV prevention and awareness, aimed at adults in the construction industry and delivered during the COVID-19 pandemic. Method: Participants were recruited at Test@Work workplace health promotion events (21 sites, n=464 employees), including health checks with HIV testing. Message development was based on a participatory design and included a focus group (n=9) and message fidelity testing (n=291) with assessment of intervention uptake, reach, acceptability, and engagement. Barriers to HIV testing were identified and mapped to the COM-B behavioural model. 23 one-way push SMS messages (19 included short web links) were generated and fidelity tested, then sent via automated SMS to two employee cohorts over a 10-week period during the COVID-19 pandemic. Engagement metrics measured were; opt-outs, SMS delivered/read, number of clicks per web link, and four two-way pull messages exploring repeat HIV testing, learning new information, perceived usefulness and behaviour change. Results: 291 people participated (68.3% of eligible attendees). A total of 7,726 messages were sent between March and June 2020, with 91.6% successfully delivered (100% read). 12.4% of participants opted out over 10 weeks. Of delivered messages, links were clicked an average of 14.4%, max 24.1% for HIV related links. The number of clicks on web links declined over time (r= -6.24, p=0.01). Response rate for two-way pull messages was 13.7% of participants. Since the workplace HIV test offer at recruitment, 21.6% reported having taken a further HIV test. Qualitative replies indicated behavioural influence of messaging on exercise, lifestyle behaviours and intention to HIV test. Conclusion: SMS messaging for HIV prevention and awareness is acceptable to adults in the construction industry, has high uptake, low attrition and good engagement with message content, when delivered during a global pandemic. Data collection methods may need refinement for audience and effect of COVID-19 on results is yet to be understood.

The application potential of cellulosic materials in natural composites and other fields needs to be explored to develop innovative, sustainable, lightweight, functional biomass materials that are also environmentally friendly. This study investigated Typha augostifolia (Typha sp.) as a potential new raw material for extracting cellulose nanocrystals (CNCs) for application in wastewater treatment composites. Alkaline treatments and bleaching were used to remove cellulose from the stem fibers. The CNCs were then isolated from the recovered cellulose using acid hydrolysis. The study showed a few distinct functional groups (O-H, -C-H, =C-H and C-O, and C-O-C) in the Fourier Transform Infrared (FTIR) spectra. Scanning electron microscope (SEM) revealed the smooth surface of CPC and CNCs that resulted from removing lignin and hemicellulose from powdered Typha augostifolia. Based on the crystalline index, the powdered Typha augostifolia, CPC, and CNCs were 42.86%, 66.94% and 77.41%. The loss of the amorphous section of the Typha sp. fiber resulted in a decrease in particle size. It may be inferred from the features of a Typha sp. CNC that CNCs may be employed as reinforcement in composites for wastewater treatment.

Background: By 2025, road traffic injuries are projected to rank third in the global burden of disease, posing a significant challenge that affects health, social well-being, and economic aspects. According to data from the Romanian Police National Statistics Center, there has been an average of 342 traffic accidents per year involving pediatric patients over the past 10 years. Materials and Methods: A retrospective research study was conducted, encompassing 358 cases of road traffic accidents identified for the study. Data collection was conducted at "St. Mary’s" Emergency Hospital for Children in Iasi, Romania, from January 2015 to December 2022. To facilitate statistical analyses, participants were categorized into three specific age groups, correlating between the anatomical region affected and different types of accidents was examined, and the classification of injury types was determined based on the characteristics of the harm inflicted. Results: An oscillating trend is observed from 2015 to 2020, with its lowest value recorded in 2017 at around 6.8% and its peak in 2019 at 20.1%. Notably, post-pandemic (Covid-19), the cases underwent a substantial decline of approximately 50%. At least 78.7% of those who did not undergo orthopedic reduction required surgery, whereas among those who underwent orthopedic reduction, only 23.4% needed surgery. Regarding the frequency of complications 7,9% of the total cases experienced complications. Conclusion: The increased frequency of pediatric traffic accidents is attributed to the extensive services provided by "St. Mary’s" Emergency Hospital for Children, Iasi, to a significant number of patients from both rural and urban areas across the seven counties of the Moldova, Romania.

(1) Background: The prediction of cervical lesions evolution is a challenge for clinicians. The prospective study aimed to determine and compare the predictive accuracy of cytology, HPV genotyping, and p16/Ki67 dual staining alone or in combination with personal risk factors for the prediction of progression, regression or persistence of cervical lesions in human papillomavirus (HPV)-infected patients; (2) Methods: This prospective study included HPV-positive patients with or without cervical lesions that underwent follow-up. Descriptive statistics and sensitivity analysis for individual or combined index tests were used for data analysis; (3) Results: The highest predictive performance for the progression of cervical lesions was achieved by a model that comprised a Pap smear suggestive of high-grade squamous intraepithelial lesion (HSIL), the presence of 16/18 HPV strains, a positive p16/Ki67 dual staining result along with the presence of at least 3 clinical risk factors, which had a sensitivity (Se) of 74.42%, a specificity of 97.92%, an area under the receiver operating curve (AUC) of 0.961, and an accuracy of 90.65%. The prediction of cervical lesions regression or persistence was modest; (4) Conclusions: Multiple testing or new biomarkers should be used to improve HPV-positive patient surveillance, especially for cervical lesion regression or persistence prediction.

This study is part of a project designed to simulate the long-term landform equilibrium of a rehabilitated mine site. The project utilizes event fine suspended sediment (FSS) fluxes in a receiving stream following a rainfall event as an indicator of landform stability. The aim of this study was to use HEC-HMS to determine sediment and discharge quantity upstream to determine how it affects the downstream development of the catchment landform, in terms of sediment changes and geomorphology. Thus, the study focused on hydrology and sediment modelling of the upper catchment with HEC-HMS (Hydrologic Engineering Center-Hydrologic Modeling System) to determine daily discharge and sediment output at the catchment outlet. HEC-HMS was used to calibrate the stream discharge and FSS quantities at the catchment outlet to observed continuous discharge and FSS values. Calibration of the HEC-HMS model was done for two water years and then the same model parameters were used to validate the model for a third water year. Catchment discharge and FSS were calibrated and validated for continuous rainfall events against observed discharge and FSS data at the catchment outlet. The model was then run for a projected rainfall of 50 years. The denudation rate predicted by the model falls in the range previously determined for the region. The simulated sediment output was compared to the rainfall trends over the years. As a result, the sediment spikes following a rainfall-runoff event gradually decreased over time. Reducing FSS spikes indicate that the landform gradually attains stability. This modeling study can be used for long-term simulations to determine erosion equilibrium over the years and to quantify sediment yield in catchments for projected wet and dry rainfall scenarios.

Follicular helper CD4+ T cells (TFH) are a major cellular pool for the maintenance of HIV reservoir. Therefore, the delineation of the follicular (F)/germinal center (GC) immune landscape will significantly advance our understanding of HIV pathogenesis. We have applied multiplex confocal imaging, in combination with relevant computational tools, to investigate, F/GC in situ immune dynamics in viremic (vir-HIV), antiretroviral treated (cART HIV) People Living With HIV (PLWH) and compare them to reactive, non-infected controls. Lymph nodes (LNs) from viremic and cART PLWH could be further grouped based on their TFH cell densities in high-TFH and low-TFH subgroups. These subgroups were also characterized by different in situ distribution of PD1hi TFH cells. The significantly accumulated follicular, compared to extrafollicular, FOXP3hi CD4+ T cells found in the low-TFH cART-HIV group were characterized by a less scattered in situ distribution and strongly correlated with the cell density of CD8+ T cells in this group. An inverse correlation between plasma viral load and LN GrzBhiCD8+ T and CD16hiCD15lo cells was found. Our data reveal the complex GC immune landscaping in HIV infection and suggest that follicular FOXP3hi CD4+ T cells could be negative regulators of TFH cell prevalence in cART-HIV.

Hill stream loaches are a group of fish that inhabit fast flowing shallow freshwater. The family has radiated over Asia. For some species their range is limited to single catchments; they provide an excellent example of biogeographical speciation on multiple scales. Hill stream loaches have a range of adaptations which help them exploit environments where competitors and predators would be washed away. They have streamlined bodies and keeled scales reminiscent of Mako sharks and potentially many other as yet undiscovered drag reducing features. They adhere to rocks, crawl over shallow films of water, glide over hard surfaces using ground effects and launch into currents to attack prey or evade predation. They offer a test of modern approaches to organismal biology and a broad range of biomimetic potential. In this paper we analyse what behaviour is associated with their physical adaptations and how this might relate to their evolution and radiation. Our intent here is to review information that is presently available but also to derive new insight through combination and statistical analysis of existing material. We also use our own observations and critically argue several contradictory, or poorly supported assertions in the existing scientific literature. Our conclusion is that, although extensively studied, there remain major gaps in knowledge about their organismal biology. We summarise the research opportunities in the form of hypotheses that are worth testing.

Incorporating ChatGPT into the classroom has several benefits that improve the educational experience for both teachers and students. ChatGPT seems useful in preparing students for success in the digital age, from personalized learning and increased instructional content to fostering collaboration, enabling bilingual classrooms, and encouraging creativity. This review offers insights regarding the perks of using ChatGPT in education as a tool for students. Among the many benefits of implementing ChatGPT in the classroom are enhanced accessibility, enhanced personalized learning, development of critical thinking skills, administrative support for educators, promotion of collaborative learning, and preparedness for a technologically advanced future. These advantages demonstrate how AI technologies have the capacity to drastically change teaching strategies and outcomes. While problems remain, the benefits of integrating ChatGPT in teaching are enormous. By integrating AI technology, educators may develop more dynamic and individualized learning environments that respond to the demands of 21st-century learners.

Mass crises are disruptive to people's mental health. The study aimed to explore mental distress during COVID-19 quarantine in a sample of university workers in Brazil. The survey included sets of questions about demographics, health, and support, an open question about major concerns, and the Clinical Outcome Routine Evaluation (CORE-OM), a measure of mental distress. 407 professionals participated in the study: mean age of 40 years (SD = 11.2), mostly female (67.8%), married (64.8%) and fulfilling social distancing to avoid COVID-19 infection (99%). Using the Consensual Qualitative Research for simple qualitative data (CQR-M) the main areas of concern were grouped into six domains, as follows: Work, Health, Isolation, Personal life and routine, Social environment, and Future. Many responses were multiple. They form categories indicating specific concerns within these domains. Quantitative data were analyzed by identifying the simple effects of potential predictors of mental distress. The results indicated medium effects of help with household chores, psychiatric treatment, age and physical exercise. Having someone available to listen was the only variable with a large effect in reducing mental suffering. The hybrid approach showed that the psychological experience during the pandemic is quite multifaceted and complex pointing new clues for public mental health.

Background: The purpuse was to investigate the influence induced by magnesium chloride (MgCl2) and zinc gluconate (ZnG) supplementation on liver and kidney injuries experimentally-induced with acetaminophen (AAPh) and potentiated by ciprofloxacin addition in rats. Material and methods: The experiment was performed on 5 animals groups: group 1 – control, treated for 6 weeks with normal saline, 1mL/kg; group 2 – AAPh, treated for 6 weeks with AAPh, 100 mg/ kg/day; group 3 – AAPh+C, treated AAPh 100 mg/kg/ day for 6 weeks and ciprofloxacin, 50mg /kg/day, only in the last 14 days of the experiment; group 4 – AAPh+C+Mg, with the same treatment as group 3, but, and in the last 14 days, MgCl2 10 mg/ kg/day was added; group 5 – AAPh+C+Zn, with the same treatment as group 3, but, and in the last 14 days, zinc gluconate (ZnG),10 mg/kg/day was added. All administrations were performed by oral gavage. At the end of the experiment, the animals were sacrificed and blood samples were collected for biochemistry examinations. Results: Treatment with AAPh for 6 weeks determined an alteration of the liver function (increases in alanine aminotransferase, aspartate aminotransferase, lactic dehydrogenase and, and gamma-glutamyl transferase) and of renal function (increases in serum urea and creatinine) (P < 0.001 group 2 vs. group 1 for all mentioned parameters). Also, the antioxidant defense capacity was impaired in group 2 vs. group 1 (superoxide dismutase and glutathione peroxidase activity decreased in group 2 vs. group 1, 0.001 < P < 0.01, respectively 0.01 < P < 0.05). The addition of ciprofloxacin, 50 mg/kg/day during the last 14 days resulted in further increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea and creatinine (0.01 < P < 0.05, group 3 vs. group 2). MgCl2 provided a slight protection against liver enzymes increase and a more pronounced protection against the increase in serum urea and creatinine (0.001 < P < 0.01 group 4 vs. group 3). MgCl2 provided a slight protection against the decrease in superoxide dismutase (0.01 < P < 0.05 group 4 vs. group 3), but not against decrease of glutathione peroxidase. The improvement of mentioned parameters could also be seen in case of ZnG, to a higher extent especially in the case of alanine aminotransferase and lactic dehydrogenase (0.01 < P < 0.05 group 5 vs. group 4). Conclusions: This study represents a furthermore proof for beneficial effect of magnesium and zinc salts against toxicity induced by different agents, including antibacterials added to the analgesic and antipyretic acetaminophen; the protection is proven on the liver and kidney’s function; the antioxidant profile improvement has a key role, especially in case of zinc gluconate.

Objective: To determine demographic predictors and comorbidities in hospitalized children with conduct disorder. Methods: A retrospective analysis was performed using Nationwide Inpatient Sample (2012–2014). All patients were ≤18 years and cases with primary diagnosis of conduct disorder (N = 32345) and a comparison group with another psychiatric diagnosis (N = 410,479) were identified using ICD-9-CM diagnosis codes. A logistic regression model was used to generate the Odds Ratio (OR) between both groups. Results: Children <11 years old have five times greater chances of admission for conduct disorder than adolescent (OR 5.339). African American males are more likely to be admitted for conduct disorder. Children with conduct disorder from low-income families have a 1.5 times higher likelihood for inpatient admission compared to high-income families. These children have about eleven times higher odds of comorbid psychosis (OR 11.810) and seven times for depression (OR 7.093) compared to the comparison group. Conclusion: Conduct disorders are more debilitating for children and families than many providers realize. African American male under 11 years is at the highest risk for inpatient management for conduct disorder. These patients have a higher risk of comorbid psychosis and depression which may further deteriorate the severity of illness and require acute inpatient care.

The enhancement of early diagnosis of lung cancer is mandatory to improve prognosis. We observed the increase cancer stem cells (CSC) and circulating tumor cells (CTC) in blood of mice on d3 after Lewis lung carcinoma (LLC) cell implantation before disease symptom. Besides we have developed an approach to reprogramming immune cells by inhibiting the MAPK/ERK pathway through MEKi and the PD-1/PD-L1 immune checkpoint signaling pathway. We hypothesized that reprogramming of spleen CD8+ T-cells could also create a population of immune cells with high antitumor activity. We reprogrammed CD8+ T-cells derived from the spleen of C57BL/6 mice (rsCD8+T-cells). The rsCD8+T-cells were able to migrate to lung and were more resistant after the exhaustion in vitro in comparison with naïve sCD8+T-cells. In the orthotopic LLC model, the rsCD8+T-cells therapy increased the amount of proliferating CD8+ and CD4+ T-cells in blood and lung from mice. The amount of CSC decreased in the blood and lung of mice treated with rsCD8+ T-cells. A morphological study revealed a decrease in the number of metastases in lung tissue. The antitumor effects of rsCD8+T-cells are based on the activation of the host immune response by increasing the populations of CD8+ and CD4+ T-cells and apoptosis of CSCs.

The rock joint fissure slope in cold regions is prone to deformation and failure problems such as relaxation, tension and collapse under freeze-thaw (F-T) cycles. Based on the ideology of clean production and promoting the structural integrity of geotechnical projects in cold areas, this study designed and prepared aeolian-sand (AS) to replace part of river sand as a filling mortar material by taking advantage of the low cost and easy availability of AS. Investigations were carried out to determine the impact of varying proportions of AS in mortar on the microstructure and shear properties of the mortar-rock interface under F-T cycles. Therefore, F-T cycle testing, nuclear magnetic resonance (NMR) testing and shear testing were carried out on grout with different proportions of AS. The results show that the right proportion of AS replacement could enhance the shear deformation resistance and F-T resistance of the mortar-rock interface, and 30% proportion is the optimal proportion. By increasing of F-T cycles, the three types of specimens showed different degrees of particle spalling, shedding and cracking. The slurry-rock interface layer in the A (0%) group exhibited the most severe F-T deterioration, while the B (15%) group showed a lesser degree, and the C (30%) group performed the best. T2 spectrum curve and total spectrum area change law from the microscopic point of view to verify the 30% AS proportion mortar-rock interface F-T resistance is the strongest, followed by 15% AS proportion mortar, the weakest is ordinary mortar. The degradation of the mortar-rock bond is primarily due to the conversion of solid to liquid phases and the movement of internal water caused by fluctuating temperatures. The extent of F-T deterioration in the slurry-rock interface layer is greatly affected by the varying proportions of AS. The shear strength and shear stiffness of specific proportion of AS decreased with the increase of F-T cycles. For same F-T cycles, the shear strength and shear stiffness of group C (30%) were the highest, followed by group B (15%) and group A (0%). The grout material not only reinforces the F-T joint fissure slope, but also reduces the cost of grout reinforcement and promotes the clean production of geotechnical structures.

In spite of prevalence gaps in several micronutrients supporting immune function, significance of their deficits/supplementation for efficacy of vaccines is underinvestigated. Thus, influence of supplementation combining vitamins C and D, zinc, selenium and manganese, and N-acetyl-cysteine on mouse IgG responses and underlying mechanisms to seasonal quadrivalent influenza vaccine (QIV) was investigated. QIV was given in two doses (28 days apart). The supplementation starting 5 days before the first injection increased the total serum IgG titre, through stimulation of germinal centre (GC) reaction in secondary lymphoid organs (SLOs), as indicated by increase in the frequency of GC B cells and follicular CD4+ T helper (Th) cells, and IL-21-producing Th cells. Additionally, the supplementation “optimized” IgG response following the second QIV injection by supporting more favorable (in respect to virus clearance) IgG2a response through favoring Th1 differentiation as indicating by Th1 (INF-γ) /Th2 (IL-4) signature cytokine level ratio upon QIV restimulation in SLO cell cultures. This most likely reflected partly their antioxidant action (as indicated by redox status analyses) on Th cell differentiation. Thus, the study forms solid base for further research aimed at repurposing use this safe and inexpensive micronutrient combination as an adjuvant for virus influenza vaccine.

We investigate and discuss in detail the structure of the restricted singular value decomposition for a tensor triplet under t-product (T-RSVD). The algorithm is provided with a numerical example illustrating the main result. For applications, we consider color image watermarking processing with T-RSVD.

COVID-19, the infectious disease caused by SARS-CoV-2, has spread on a pandemic scale. The virus infection can evolve asymptomatically or generate severe symptoms, influenced by the presence of comorbidities. Lymphopenia in patients affected with COVID-19 according to the severity of symptoms is frequent. However, the profile of CD4+ and CD8+ T-cells regarding cytotoxicity and antiviral factor expression has not yet been completely elucidated in acute SARS-CoV-2 infections. The purpose of this study is to evaluate the phenotypic and functional profile of T-lymphocytes in patients with moderate and severe/critical COVID-19. During this pandemic period, we analyzed a cohort of 62 confirmed patients with SARS-CoV-2 (22 moderate cases and 40 severe/critical cases). Albeit lymphopenia, we observed an increase in the expression of CD28, co-stimulator molecule, and activation markers (CD38 and HLA-DR) in T-lymphocytes as well as an increase in the frequency of CD4+ T-cells, CD8+ T-cells, and NK cells that express the immunological checkpoint protein, PD-1, in patients with severe/critical condition compared to healthy controls. Regarding the cytotoxic profile of peripheral blood mononuclear cells, an increase in the response of CD4+ T-cells already at baseline level was observed, scarcely changed upon PMA and Ionomycin stimulation. Meanwhile, CD8+ T-lymphocytes decreased cytotoxic response, evidencing a profile of exhaustion in patients with severe COVID-19. As observed in the t-SNE technique CD4+ T-cytotoxic and CD8+ T with low granzyme production evidencing their dysfunctionality in severe/critical conditions. In addition, purified CD8+ T-lymphocytes from patients with severe COVID-19 showed an increased constitutive expression of differentially expressed genes associated with the caspase pathway, inflammasome, and antiviral factors, and curiously, reduced expression of TNF-α. The cytotoxic profile, by CD4+ T-cells, may compensate for the dysfunction/exhaustion of TCD8+ in acute SARS-CoV-2 infection. These findings may provide an understanding of the interplay of cytotoxicity between CD4+ T-cells and CD8+ T-cells in the severity of acute COVID-19 infection.

Targeted delivery of drugs or other therapeutic agents through internal or external triggers has been used to control and accelerate the release from liposomal carriers in a number of studies, but relatively few utilize energy of therapeutic X-rays as a trigger. We have synthesized liposomes that are triggered by ionizing radiation (RTLs) to release their therapeutic payload. These liposomes are composed of natural egg PE, DSPC, cholesterol, and DSPE-PEG-2000, and the mean size of the RTL was in the range of 114 to 133 nm, as measured by NTA. The trigger mechanism is the organic halogen, chloral hydrate, which is known to generate free protons upon exposure to ionizing radiation. Once protons are liberated, a drop in internal pH of the liposome promotes destabilization of the lipid bilayer and escape of the liposomal contents. In proof of principle studies, we assessed RTL radiation-release of fluorescent tracers upon exposure to a low pH extracellular environment or exposure to X-ray irradiation. Biodistribution imaging before and after irradiation demonstrated a preferential uptake and release of the liposomes and their cargo at the site of local tumor irradiation. Finally, a potent metabolite of the commonly used chemotherapy irinotecan, SN-38, was loaded into RTL along with near infrared (NIR) fluorescent dyes for imaging studies and measuring tumor cell cytotoxicity alone or combined with radiation exposure, in vitro and in vivo. Fully loaded RTLs were found to increase tumor cell killing with radiation in vitro and enhance tumor growth delay in vivo after three i.v. injections combined with three, 5 Gy local tumor radiation exposures compared to either treatment modality alone.

Uterine leiomyosarcoma (LMS) is a rare and aggressive form of uterine cancer, with a poor prognosis and high number of uterine cancer-related deaths. Chimeric Antigen Receptor (CAR) T-cell therapy is an immunotherapy approach to antigen specific of cancer cell, thereby enhancing the immune system's ability to target and destroy cancer cells. This study aims to investigate the potential of targeting differentially expressed genes (DEGs) as a novel therapeutic strategy using CAR T-cell technology in LMS. Genome datasets were obtained from NCBI-GEO database, Of the five datasets, genes that experienced significant overexpression in at least three datasets were categorized as DEGs, and DEGs were evaluated for protein localization, Gene Ontology, bioactivity, interaction, and overexpression. The results identified 25 DEGs, with ten of them expressed on the plasma membrane; four of them—HMMR, KIF20A, PRC1, and ZWINT—were part of the main protein network derived from the 25 DEGs. The dominant bioactivity of these PMGs involves influencing the cell cycle, particularly processes related to chromosome segregation. In conclusion, HMMR, KIF20A, PRC1, and ZWINT are high-potential DEGs as candidates for tumor-associated antigen CAR T-cell therapy. Further research, both in vitro and in vivo, is needed to enhance the validity of these findings.

In this work, we study the existence of strange star in the background of f(T,T) gravity in the Einstein spacetime geometry, where T is the torsion tensor and T is the trace of the energy-momentum tensor. The equations of motion are derived for anisotropic pressure within the spherically symmetric strange star. We explore the physical features like energy conditions, mass-radius relations, modified TOV equations, principal of causality, adiabatic index, redshift and stability analysis of our model. These features are realistic and appealing to further investigation of properties of compact objects in f(T,T) gravity as well as their observational signatures.

Polyethylene terephthalate (PET) pollution poses significant environmental consequences, and thus new degradation methods must be explored to mitigate this problem. We previously demonstrated that a consortium of three Pseudomonas and two Bacillus species can synergistically degrade PET in culture. The consortium more readily consumes Bis(2-Hydroxyethyl) terephthalate (BHET), a byproduct made in PET depolymerization, compared to PET, and can fully convert BHET into metabolically usable monomers terephthalic acid (TPA) and ethylene glycol (EG). Because of its crystalline structure, the main limitation of the biodegradation of post-consumer PET is the initial transesterification from PET to BHET, depicting the need for the transesterification step in the degradation process. Additionally, there have been numerous studies done on the depolymerization reaction of PET to BHET, yet few have tested the biocompatibility of that product with a bacterial consortium. In this report, a two-step process was implemented for sustainable PET biodegradation, where PET is first depolymerized to form BHET using an Orange Peel Ash (OPA) catalyzed glycolysis reaction, followed by complete degradation of the BHET glycolysis product by the bacterial consortium. Results show that OPA-catalyzed glycolysis reactions can fully depolymerize PET, with an average BHET yield of 92% (w/w) and that the reaction product is biocompatible with the bacterial consortium. After inoculation with the consortium, 19% degradation of the glycolysis product was observed in 2 weeks, for a total degradation percentage of 17% when taking both steps into account. Furthermore, the 10-week total BHET degradation rate was 35%, demonstrating that the glycolysis products are biocompatible with the consortium for longer periods of time, for a total two-step degradation rate of 33% over 10 weeks. While we predict complete degradation is achievable using this method, further experimentation with the consortium can allow for a circular recycling process, where TPA can be recovered from culture media and reused to create new materials.

The objective of this study was to determine the effects of supplementing L-isoleucine (L-Ile) on milk protein synthesis, using an immortalized bovine mammary epithelial (MAC-T) cell line. In this case, the cells were treated with 0, 0.3, 0.6, 0.9, 1.2 and 1.5 mM of supplemental Isoleucine (Ile), and the most efficient time for protein synthesis for each amino acid was determined by measuring the cell, medium and total protein at 0, 24, 48, 72 and 96 h. Confirmatory tests showed that 48h incubation time and 0.6 mM dosage of L-Ile are considered as the optimal time and dosage. The mechanism of milk protein synthesis was elucidated through proteomics analysis to clarify the metabolic pathway. When the L-Ile was supplemented, extracellular protein (medium protein) reached a peak at 48h, whereas in the case of the intracellular cell protein, it was shown to have reached to its peak at 24h in all L-Ile dosage treatments. In total, it is noted that there were 63 upregulated and 52 downregulated proteins. The results of the protein pathway analysis showed that the L-Ile group stimulated insulin/IGF pathway-mitogen activated protein kinase kinase/MAP kinase cascade, insulin/IGF pathway-protein kinase B signaling cascade, p53 pathway, de novo purine biosynthesis, Wnt signaling pathway, glycolysis, pentose phosphate pathway, and ATP synthesis which are pathways involved and related to protein and energy metabolism. Together, these results demonstrate that L-Ile supplementation was effective in stimulating β-casein synthesis by stimulating genes and pathways which are significantly related to protein and energy metabolism.

A co-curing resin system consisting of 9368 epoxy resin for prepreg and 6808 epoxy resin for resin transfer molding (RTM) was developed. A corresponding preparation method of novel polymer composite bolted T-joint with internal skeleton and external skin was proposed based on prepreg-RTM co-curing process, and novel T-joints were fabricated. A series of conventional configuration T-joints based on RTM process and T-joints made of 2A12 aluminum alloy were prepared simultaneously. Bending performances were studied on these T-joints experimentally. The results indicate that 9368 epoxy resin and 6808 epoxy resin exhibit good compatibility in rheological and thermophysical properties. The novel T-joints prepared with prepreg-RTM co-curing process show no obvious fiber local winding or resin-rich regions inside, and the interface quality between internal skeleton and external skin is excellent. The main failure modes of the novel T-joint under bending load include separation of skin and skeleton and fracture along the thickness on the base panel; the skeleton carries the main bending load, but there is still load transfer between external skin and internal skeleton through their interface. The internal damages of the novel T-joint are highly consistent with surface damages observed visually, facilitating the detection and timely discovery of damages. The initial stiffness, damage initiation load, and ultimate load of the novel T-joint are 1.65 times, 5.89 times, and 3.45 times that of conventional T-joint, respectively. When considering the influence of density, the relative initial stiffness and relative ultimate load of the novel T-joint are 1.44 times and 2.07 times that of aluminum alloy T-joint, respectively.

This study aligns with the 2030 United Nations Sustainable Development Goals- 3 which aim to “ensure healthy lives and promote well-being for all at all ages”. It contributes to the nascent literature stream on energy-health dynamics by introducing a holistic theoretical model to empirically examine the mediation effect of carbon emissions on the relationship between nonrenewable energy and infant mortality rates. Using an unbalanced panel data on 42 Asia and the Pacific countries from 2005 to 2015 and deploying the structural equation modeling approach, the empirical results are surmised as follows: (i) in regard to the full sample of countries, nonrenewable energy indirectly increases infant mortality rates through increasing carbon emissions. In other words, carbon emissions play a partial mediation role between nonrenewable energy and infant mortality rates; and (ii) for the different income groups, carbon emissions show varying mediation effects. For example, the mediation effects of carbon emissions in lower-middle and upper-middle income countries are found to be similar to those of the full sample of countries. Therefore, based on these findings, we conclude that nonrenewable energy is an essential determinant of infant mortality rates. Policy recommendations are put forward.

As a result of the COVID-19 pandemic, as well as other outbreaks such as SARS and Ebola, bats are recognized as a critical species for mediating zoonotic infectious disease spillover events. While there is a growing concern of increased antimicrobial resistance (AMR) globally during this pandemic, knowledge of AMR circulating between bats and humans is limited. In this paper, we have reviewed the evidence of AMR in bats and discussed the planetary health aspect of AMR to elucidate how this is associated with the emergence, spread and persistence of antibiotic resistance at the human-animal interface. The presence of clinically significant resistant bacteria in bats and wild life has reflective and broad impact on zoonotic pandemic surveillance, disease transmission and treatment modalities. We searched MEDLINE through PubMed and Google Scholar to retrieve relevant studies (n=38) that provided data on resistant bacteria in bats till September 30, 2022. There is a substantial variability in the results from studies measuring the prevalence of AMR based on geographic location, bat types and time. We found all major groups of gram positive and gram negative bacteria in bats which are resistant to commonly used antibiotics. The most alarming issue is- recent studies have increasingly identified Methicillin Resistant Staphylococcus aureus (MRSA), ESBL producing and Colistin resistant Enterobacteriaceae in samples from bats. This evidence of superbugs abundance in both humans and wild mammals like bats, could facilitate a greater understanding of which specific pathways of exposure should be targeted. We believe that these data will also facilitate future pandemic prepareness as well as global AMR containment during the pandemic events and beyond.

Using multi-color flow cytometry analysis, we studied the immunophenotypical differences between leukemic blasts/LSCs from patients with AML/MDS and hematopoietic stem and progenitor cells (HSPCs) from patients in complete remission (CR) following their successful treatment. The panel of markers included CD34, CD38, CD45RA, CD123 as representatives for a hierarchical hematopoietic stem and progenitor cell (HSPC) classification as well as programmed death ligand 1 (PD-L1). Rather than restricting the evaluation on a 2- or 3-dimensional analysis, we applied a t-distributed stochastic neighbor embedding (t-SNE) approach to get a deeper insight and segregation between leukemic and normal HPSCs. For that purpose, we created a t-SNE map, which resulted in the visualization of 27 cell clusters based on their similarity concerning the composition and intensity of antigen expression. Two of these clusters were “leukemia-related” containing a great proportion of CD34⁺/CD38^- hematopoietic stem cells (HSCs) or CD34⁺ cells with a strong coexpression of CD45RA/CD123, respectively. CD34⁺ cells within the latter cluster were also highly positive for PD-L1 reflecting their immunosuppressive capacity. Beyond this proof of principle study, the inclusion of additional markers will be helpful to refine the differentiation between normal HSPCs and leukemic cells, particularly in the context of minimal disease detection and antigen-targeted therapeutic interventions. Furthermore, we suggest a protocol for the assignment of new cell ensembles in quantitative terms, via a numerical value, the Pearson coefficient, based on a similarity comparison of the t-SNE pattern with a reference.

Background: The effectiveness of the anti-COVID-19 vaccine remains a matter to be clarified. Methods: The humoral and cellular immunity after the administration of three doses of the Pfizer–BioNTech and Oxford AstraZeneca vaccines against SARS-CoV-2 over one year and the appearance of post-vaccination COVID-19 have been studied. Results: Anti-SARS-CoV-2 IgG and IgA antibodies showed a progressive increase throughout the vaccination period. This increase was greatest after the third dose. The highest levels were observed in subjects who had anti-SARS-CoV-2 antibodies prior to vaccination. There was an increase in CD4+ αβ, CD8+ γδ and TEM CD8+ γδ T cells, and a decrease in apoptosis in CD4+CD8+ and CD56+ αβ and γδ T cells. Post-vaccination SARS-CoV-2 infection was greater than 60%. The symptoms of COVID-19 were very mild and were related to γδ T cell deficit, specifically CD8+ TEMRA and CD56+ γδ TEM, as well as lower pre-vaccine apoptosis levels. Conclusions: Those results demonstrate the important role that γδ T cells play in SARS-CoV-2 vaccine immunization.

Immune cells such as T cells and macrophages express α7 nicotinic acetylcholine receptors (α7 nAChRs), which contribute to the regulation of immune and inflammatory responses. Earlier findings suggest α7 nAChR activation promotes the development of regulatory T cells (Tregs) in mice. Using human CD4+ T cells, we investigated the mRNA expression of the α7 subunit and the human-specific dupα7 nAChR subunit, which functions as a dominant-negative regulator of ion channel function, under resting conditions and T cell receptor (TCR)-activation. We then explored the effects of the selective α7 nAChR agonist GTS-21 on proliferation of TCR-activated T cells and Treg development. Varied levels of mRNA for both the α7 and dupα7 nAChR subunits were detected in resting human CD+ T cells. mRNA expression of the α7 nAChR subunit was profoundly suppressed on days 4 and 7 of TCR-activation as compared to day 1, whereas mRNA expression of the dupα7 nAChR subunit remained nearly constant. GTS-21 did not alter CD4+ T cell proliferation but significantly promoted Treg development. These results suggest the potential ex vivo utility of GTS-21 for preparing Tregs for adoptive immunotherapy, even with high expression of the dupα7 subunit.

The aim of this study was to create a novel machine learning (ML) algorithm for predicting the post-pubertal mandibular length and Y-axis in females. Cephalometric data from 176 females with Angle Class I occlusion were used to train and test 7 ML algorithms. For all ML methods tested, the mean absolute errors (MAEs) for the 2-year prediction ranged from 2.78-5.40 mm and 0.88-1.48 degrees, respectively. For the 4-year prediction, MAEs of mandibular length and Y-axis ranged from 3.21-4.00 mm and 1.19-5.12 degrees, respectively. The most predictive factors for post-pubertal mandibular length were mandibular length at previous timepoints, age, sagittal positions of the maxillary and mandibular skeletal bases, mandibular plane angle, and anterior and posterior face heights. The most predictive factors for post-pubertal Y-axis were Y-axis at previous timepoints, mandibular plane angle, and sagittal positions of the maxillary and mandibular skeletal bases. ML methods were identified as capable of predicting mandibular length within 3 mm, and Y-axis within 1 degree. Compared to each other, all of the ML algorithms were similarly accurate, with the exception of MLP regressor.

Dengue virus is a global health problem most prevalent in tropical and subtropical regions. However, after the approval of two vaccines, Dengvaxia, TV003/TV005 of Takeda, for its prevention, problems were reported, like enhanced risks of infection or less efficiency of protection. Since then, more struggles have been in demand for the development of better vaccines. Here, we conducted a new design through an in-silico strategy. Initially, epitopes were chosen based on their antigenicity, immunogenicity, and binding affinity with MHC molecule, while excluded with allergenicity, toxicity and potential risk of antibody dependent enhancement. Subsequently, a core antigen was constructed with selected epitopes and linked with distinct adjuvant proteins to achieve three candidate vaccines, PSDV-1~3. PSDV-2 was chosen for further validation based on their advantage in physicochemical and structural properties. With a panel of simulations, this artificial protein showed tight binding with pattern recognition receptors, good stability, robust immune induction, and ultimately was confirmed as a high quality vaccine candidate. The plasmid for its recombinant expression was then designed accordingly. With our new design, one more choice was obtained for the effective protection from Dengue virus. Further experimental validations are still require to confirm it protection capacity and safety.

Background: Craniofacial injuries are thought to be commonly associated with traumatic brain injury (TBI), but there is conflicting evidence in the literature. The objective of this retrospective cohort study is to evaluate the incidence of TBI in patients with craniofacial trauma. Methods: The study included 2982 consecutive patients with either solitary or concurrent diagnoses of TBI and facial fractures, seen and evaluated at a single level II trauma center between January 1, 2010 and December 31, 2020. Continuous variables were compared against whether the patient had one or both diagnoses.Results: Of the target population, 55.8% had a solitary diagnosis of TBI, 30.28% had a solitary diagnosis of facial fractures, and 13.92% had concurrent diagnoses of both TBI and facial fractures. Patients with concurrent diagnoses had a significantly longer mean length of stay (LOS) compared to those with solitary diagnoses (9.92 ± 16.33 days vs. 6.21 ± 10.96 days, p&lt;0.01), but age (p=0.68) and ICU LOS (p=0.09) did not differ significantly between the two groups. Conclusions: Trauma to the face should be given special attention due to the close relationship between facial bones and the brain. Patients with concurrent diagnoses of TBI and facial fractures had worse hospital outcomes than those with solitary diagnoses of either TBI or facial trauma.

Magnetic resonance (MR) image acquisitions are usually time-consuming, limiting utilization in neuroimaging. For multiple sclerosis (MS) patients, MR imaging plays a major role in drug therapy decision-making. The purpose of this study was to evaluate whether an ultrafast, T2-weighted (T2w), deep-learning-enhanced (DL), echo-planar-imaging-based (EPI) fluid-attenuated inversion recovery (FLAIR) sequence (FLAIRUF) that has been targeting neurological emergencies so far might even be an option to detect MS lesions of the brain compared to conventional FLAIR sequences. Therefore, 17 MS patients were enrolled prospectively in this exploratory study. Standard MR protocols and ultrafast acquisitions were conducted at 3 tesla (T), including three-dimensional (3D)-FLAIR, turbo/fast spin echo (TSE)-FLAIR, and FLAIRUF. Inflammatory lesions were grouped by size and location. Lesion conspicuity and image quality were rated on an ordinal five-point Likert scale, and lesion detection rates were calculated. Statistical analyses were performed to compare results. Altogether, 568 different lesions were found. Data indicated no significant differences in lesion detection (sensitivity and positive predictive value [PPV]) between FLAIRUF and axially reconstructed 3D-FLAIR (lesion size ≥ 3 mm × ≥ 2 mm) and no differences in sensitivity between FLAIRUF and TSE-FLAIR (lesion size ≥ 3 mm total). Lesion conspicuity in FLAIRUF was similar in all brain regions except for superior conspicuity in the occipital lobe and inferior conspicuity in central brain regions. Further findings include location-dependent limitations of signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) as well as artifacts such as spatial distortions in FLAIRUF. In conclusion, FLAIRUF could potentially be an expedient alternative to conventional methods for brain imaging in MS patients since the acquisition can be performed in a fraction of time while maintaining good image quality.

Clinical, pathological, and imaging evidence in multiple sclerosis (MS) shows that inflammation starts early and progresses with age. B cells play a central role in this process, contributing to cytokine production, defective regulatory functions, and abnormal immunoglobulin production, even in the central nervous system. Anti-CD20 (aCD20) therapies, which deplete CD20+ B cells, are effective for both relapsing-remitting (RR) and progressive-relapsing (PR) MS. While effective against MS symptoms and lesions detectable by magnetic resonance imaging, aCD20 therapies can reduce the immune response to COVID-19 vaccination. By using high-parameter flow cytometry, we examined the antigen-specific (Ag+) immune response six months post-third COVID-19 mRNA-vaccination in MS patients with RR and PR forms on aCD20 therapy. Despite lower Ag+ B cell responses and lower levels of anti-SARS-CoV2, both total and neutralizing antibodies, RR and PR patients developed strong Ag+ T cell responses. We observed similar percentages and numbers of Ag+ CD4+ T cells and high proportion of Ag+ CD8+ T cells, with slight differences in T cell phenotype and functionality, that however suggested the presence of differences in immune responses driven by age and disease severity.

Precision medicine (PM), also termed stratified, individualised, targeted or personalised medicine, embraces a rapidly expanding area of research, knowledge, and practice. It brings together two emerging health technologies to deliver better individualised care: the many “-omics” arising from increased capacity to understand the human genome; and “big data” and data analytics including Artificial Intelligence (AI). PM has the potential to transform an individual’s health, moving from population-based disease prevention to more personalised management. There is however a tension between the two, with a real risk that this will exacerbate health inequalities and divert funds and attention from basic healthcare requirements leading to worse health outcomes for many. All areas of medicine should consider how this will affect their practice, with PM now strongly encouraged and supported by government initiatives and research funding. In this review we discuss examples of PM in current practice and its emerging applications in primary care, such as clinical prediction tools that incorporate genomic markers and pharmacogenomic testing. We look towards potential future applications and consider some key questions for PM including evidence of real-world impact, its affordability, the risk of exacerbating health inequalities, and the computational and storage challenges of applying PM technologies at scale.

Naive CD4+ T cells engage cognate peptide MHC-II complexes (pMHC-IIs) to differentiate and acquire one of several T helper (Th) fates whose specific trajectories are guided by a dynamic cytokine milieu that develops in response to antigenic entity. This physiological process is often erroneously conflated with a pathological one termed Th polarization. Using the SPIRAL model, we argue here that unlike Th fate choice, innate signaling alone is insufficient to initiate Th polarization in naive CD4+ T cells, that it instead develops from pre-existing memory CD4+ T cells that express cross-reactive TCRs, and that it inevitably leads to immunopathology.

Lymphatic filariasis (LF), also commonly known as elephantiasis, is a neglected tropical disease (NTD) caused by filarial parasites. The disease is transmitted by a bite from infected mosquitoes. The bites of these infected mosquitoes deposit filarial parasites, Wuchereria or Brugia whose predilection site is the lymphatic system. The damage to the lymph system causes swelling in the legs, arms, and genitalia. A mapping survey conducted between 2003 and 2010 determined LF that LF was endemic in Zambia in 96 out of 116 districts. Elimination of LF is known to be possible by stopping the spread of the infection through large-scale preventive chemotherapy. Therefore, mass drug administration (MDA) with diethylcarbamazine citrate (DEC) (6 mg/kg) and Albendazole (400 mg) for Zambia has been conducted and implemented in all endemic districts with five effective rounds. Post-MDA pre-transmission assessment survey (pre-TAS) was conducted between 2021 and 2022 in 80 districts to determine the LF prevalence rate. We conducted a cross-sectional seroprevalence study involving 600 participants in each Evaluation Unit (EU) or each district. The study sites (sentinel and spot-check sites) were the districts that were the Implementation Unites (IUs) where MDA, preventive chemotherapy against LF was conducted. These included 80 districts from the 9 provinces. A total of 47,235 people from sentinel and spot-check locations were tested. Of these, valid tests were 47,052 of which 27,762 (59%) were females and 19,290 (41%) were males. The survey revealed in the 79/80 endemic district a prevalence of Wb anti-gens of 0.14% and 0.0% prevalence of microfilariae. All the surveyed districts had an optimum prevalence of less than 2 percent, except for Chibombo district. The majority of participants that tested positive for Wb Ag were those that had 2, 3, and 4 rounds of MDA. Surprisingly, individuals that had 1 round of MDA were not found to have circulating antigens of Wb. The study showed that all the surveyed districts except for Chibombo, passed Pre-TAS. This further implies that there is a need to conduct a TAS in these districts in order to decide whether to stop MDA or not. Keywords: Lymphatic Filariasis; pre-TAS; Prevalence; Antigenaemia; Microfilariae; Zambia

In this paper we define a continuous wavelet transform of a Schwartz tempered distribution $f \in S^{'}(\mathbb R^n)$ with wavelet kernel $\psi \in S(\mathbb R^n)$ and derive the corresponding wavelet inversion formula interpreting convergence in the weak topology of $S^{'}(\mathbb R^n)$. It turns out that the wavelet transform of a constant distribution is zero and our wavelet inversion formula is not true for constant distribution, but it is true for a non-constant distribution which is not equal to the sum of a non-constant distribution with a non-zero constant distribution.

The microenvironment of most tumors is complex, comprising numerous aspects of immunosuppression. Several studies have indicated that the adrenergic system is vital for controlling immunological responses. In the context of tumor microenvironment, Nor-Adrenaline (NA) is poured-in by innervating nerves and tumor tissues itself. The receptors for nor-adrenaline are present on the surface of cancer and immune cells and are often involved in activation of pro-tumoral signaling pathways. β2-adrenergic receptor (β2-AR) is an emerging class of receptors that are capable of modulating the functioning of immune cells. β2-AR is reported to activate the regulatory immune cells and inhibit the effector immune cells. Blocking β2-AR increases activation, proliferation and cytokine release of T lymphocytes. Moreover β2-AR deficiency during metabolic reprograming of T cells increases mitochondrial membrane potential and biogenesis. In the view of available research data, immunosuppressive role of β2-AR in T cells presents it a targetable checkpoint in CAR-T cell therapies. In this review, we have abridged contemporary knowledge about adrenergic stress mediated β2-AR activation on T lymphocytes inside tumor milieu.

Our hypothesis that controlled ozone applications interfere into the redox balance of the biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication), has been verified over the last 2 decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes, diabetes-2 and in prevention of intoxications. Low-dose ozone acts as a redox bioregulator: The restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase of the antioxidant repair markers, here mainly shown as glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, relevant data are displayed, evaluated and comprehensively discussed: The repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone treated groups and depending on the indication; the stress markers are simultaneously reduced, the redox system regains its balance.

For quantitative determination of honokiol (HNK) and metformin hydrochloride (M-HCl) by HPLC from formulations and from dissolution studies, a QbD approach using three factors - three levels design was implemented to optimize the chromatographic conditions. To study the impact of each variable on the peak area of both compounds and retention time of last compound eluted, the 3D response surface plots were developed. HNK and M-HCl were separated on a Thermoscientific ODS Hypersyl TM (250 x 4.6 mm, 5 μm) column mantained at 30 C, using 0.02 M acetate buffer (pH = 3) / methanol (15 / 85, v / v) as mobile phase with a flow rate of 1 mL/min. The injected volume was 20 L, and the detection wavelengths were 256 nm for HNK and 236 nm for M-HCl. The validation of proposed method showed a linearity range of 4 – 1200 μg/mL for M-HCl (r2 = 0.9992) and 1 – 300 μg/mL for HNK (r2 = 0.9998), good precision (RSD &lt; 2% for both HNK and M-HCl, in intra- and inter-day studies) and accuracy (mean recovery = 100.09% in the range 99.80 – 100.43% for M-HCl and mean recovery = 100.12% in the range 99.70 – 100.38% for HNK). The environmentally friendly nature of the method was confirmed by the evaluation of the method’s greenness. The proposed method was applied for the determination of HNK and M-HCl from oral dosage forms and in dissolution studies.

The aim of this work was to investigate a new, simple one-pot combustion synthesis technique for creating sulphur-based CuS/ZnS p-n heterojunction nanocomposite photocatalysts. The study examined the photocatalytic activity and reusability of these nanocomposites in removing rhodamine B (RhB) dye under visible light irradiation. Various methods of characterisation were employed to determine the properties of the materials, including particle morphology, crystalline phases and bandgap energy. The intrinsic reaction parameters, such as catalyst loading, pH level of the solution, and initial pollutant concentration, were varied to establish the optimal photo-degradation conditions. The results showed that a binary CuS/ZnS catalyst with a 10 gL-1 loading, at pH 5, degraded 97% of 5 ppm RhB dye after 270 minutes of visible light irradiation. Addition-ally, this composite catalyst exhibited excellent chemical stability and reusability, achieving 83% RhB dye removal after five recycling runs. Scavenger tests identified the photogenerated holes (h+) and superoxide free radicals (•O2) as the primary reactive species responsible for degradation. This study provides valuable insight into the design of highly efficient nanomaterials for removing organopollutants in wastewater, and a possible reaction mechanism is proposed.

There is need to address the challenges of organ shortage, through development of tissues and organs with alternatives to those of the allograft-kind. This illustrates the quest behind novel biofabrication strategies such as 3D bio-printing, which is necessary to create artificial multi-cellular tissues/organs. Several findings have been reported in this review. First, the role of ECM components in tissue regenerative medicine is presented. Different ECM components such as collagen, gelatin, elastin, fibronectin, laminins and glycosaminoglycans are concisely examined for their tissue regenerative medicine applications. Next, current state of research on extrusion-based 3D bio-printing techniques and their limitations are reviewed. For example, we show that cell viability is still a challenge with extrusion, while the use of natural polymers such as collagen in improving composites’ mechanical properties is limited. Lastly, we examine unresolved research questions necessary to advance the present state of research in the field.

Climate change has altered the frequency and severity of extreme weather, which can affect vegetation condition and habitat quality for wildlife. Declines in vegetation productivity during droughts and heatwaves can negatively impact animals that depend on vegetation for water and nutrition. The ability to detect such effects on habitat suitability can reveal refugia, which can be prioritised for protection to improve threatened species conservation. We used the normalised difference vegetation index (NDVI) to look at relationships between vegetation productivity and the presence of koalas (Phascolarctos cinereus) in potential habitat throughout much of their range. Using a large, long-term koala presence dataset, we tested the hypothesis that locations where koalas had been observed would exhibit higher NDVI values than a random, representative sample from the same vegetation group (i.e. woodlands, open forests or tall open forests). We also identified the minimum NDVI threshold at which koalas occurred across time for each vegetation group and compared these to the minimum NDVI values observed across potential koala habitat before and during the millennium drought; one of the worst recorded in Australia. Additionally, we investigated whether vegetation above the minimum NDVI thresholds was significantly closer to perennial water than unsuitable vegetation. We found that koalas tend to occur at locations exhibiting higher NDVI than average for all vegetation groups. We also found that 49% of all vegetation groups maintained a minimum NDVI above the koalas’ NDVI threshold before drought, equating to 190,227 km2, which declined to 166,746 km2 during drought (a 12% reduction). We also found that unsuitable vegetation tended to occur farther from perennial water than suitable vegetation for some vegetation groups. Areas that remained above the NDVI thresholds during the drought should be considered potential refugia for populations during an event of similar magnitude and could indicate future core habitat extent.

Estrogen decline during menopause is associated with altered metabolism, weight gain and increased risk for cardiometabolic diseases. The gut microbiota also plays a role in the development of cardiometabolic dysfunction and is also subject to changes associated with age-related hormone changes. Phytoestrogens are plant-based estrogen mimics that have gained popularity as dietary supplements for treatment or prevention of menopause-related symptoms. These compounds have the potential to both modulate and to be metabolized by the gut microbiota. Hops (Humulus lupulus L.) contain potent phytoestrogen precursors, which rely on microbial biotransformation in the gut to estrogenic forms. We supplemented ovariectomized (OVX) or sham-operated (SHAM) C57BL/6 mice, with oral estradiol (E2), a flavonoid-rich extract from hops, or a placebo carrier oil to observe effects on adiposity, inflammation, and gut bacteria composition. Hops extract and E2 protected against increased visceral adiposity and liver triglyceride accumulation in OVX animals. Surprisingly, we found no evidence of OVX having a significant impact on the overall gut bacterial community structure. We did find differences in abundance of Akkermansia muciniphila, which was lower with HE treatment relative to the OVX E2 treatment and to placebo in the SHAM group.

The article explores the concept of 'synthetic man' (SM) in the context of 'synthetic biology' (SB), analysing the potential, challenges, and ethical implications of these achievements. Through dialogue with ChatGPT 4, an in-depth understanding of the evolution, contributions of SM, ChatGPT's contribution, and concerns associated with SM is sought, providing insight into how this technology could affect our society. Our study uses a structured dialogue framework with ChatGPT that addresses essential SM questions regarding SM history, contributions, challenges, and concerns. ChatGPT responses are analysed to extract relevant information and identify trends and insights. The ChatGPT dialogue reveals that MS is still a theoretical and speculative concept with significant advances in gene therapy and genetic engineering. The potential contributions of SM in addressing global challenges such as health, environment and education are identified. Ethical and social concerns such as health risks and psychological impact are also highlighted. Differences in ChatGPT responses were observed between different sessions or even within the same session, which highlighted the limitations in the replicability of the research and sometimes the need for clarification of the questions. The article is distinguished by its unique approach of using an advanced language model to explore a complex and speculative topic. The LLM Dialogue Framework on Technology (LLM-DFonTech) framework proposal for structured dialogue with ChatGPT on various technological topics related to the original contribution provides an adaptable tool for interdisciplinary research in emerging technologies. This methodology opens up new possibilities for analyzing and developing trends in technology and society.

Atherosclerosis is a chronic systemic inflammatory condition of the vasculature and a leading cause of stroke. Luminal stenosis severity is an important factor in determining vascular risk. Conventional imaging modalities, such as angiography or duplex ultrasonography, are used to quantify stenosis severity and inform clinical care but provide limited information on plaque biology. Inflammatory processes are central to atherosclerotic plaque progression and destabilization. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) is a validated technique for quantifying plaque inflammation. In this review, we discuss the evolution of FDG-PET as an imaging modality to quantify plaque vulnerability, challenges to standardization of image acquisition and analysis, its potential application to routine clinical care after stroke, and the possible role it will play in future drug discovery.

Peptide-based opioid ligands are important candidates for the development of novel, safer, and more effective analgesics to treat pain. To develop peptide-based safer analgesics, we synthesized a mixture-based cyclic pentapeptide library containing a total of 24,624 pentapeptides and screened the mixture-based library samples using a 55 °C warm-water tail-withdrawal assay. Using this phenotypic screening approach, we deconvoluted the mixture-based samples to identify a novel cyclic peptide Tyr-[D-Lys-Dap(Ant)-Thr-Gly] (CycloAnt), which produced dose- and time-dependent antinociception with an ED50 (and 95% confidence interval) of 0.70 (0.52-0.97) mg/kg i.p. mediated by the mu-opioid receptor (MOR). Additionally, higher doses (≥ 3 mg/kg, i.p.) of CycloAnt antagonized delta-opioid receptors (DOR) at least 3 hours. Pharmacological characterization of CycloAnt showed the cyclic peptide did not reduce breathing rate in mice at doses up to 15 times the analgesic ED50 value, and dramatically less hyperlocomotion than the MOR agonist, morphine. While chronic administration of CycloAnt resulted in antinociceptive tolerance, it was without opioid-induced hyperalgesia and significantly reduced signs of naloxone-precipitated withdrawal suggestive of reduced physical dependence as compared to morphine. Collectively, the results suggest this dual MOR/DOR multifunctional ligand is an excellent lead for the development of peptide-based safer analgesics.

This paper presents the systematic development and performance characterization of a non-proprietary 3D-printable ultra-high-performance fiber-reinforced concrete (UHPFRC) for digital construction. Several fresh and hardened properties of the developed 3D-printable UHPFRC matrix (without fiber) and composite (with 2% volume fraction of steel fibers) were evaluated and compared to that of conventionally mold-cast UHPFRC. Additionally, the effects of testing direction on the compressive and flexural strengths of the printed UHPFRC were investigated. The fresh properties of the UHPFRC developed in this study satisfied the criteria for extrudability, buildability, and shape-retention-ability, which are relevant for ensuring printability. The printed UHPFRC exhibited superior flexural performance to the mold-cast UHPFRC due to alignment of the short fibers in the printing direction. The high compressive and flexural strengths, along with the deflection-hardening behavior, of the developed UHPFRC can enable the production of thin 3D-printed components with significant reduction or complete elimination of conventional steel bars.

Euler sums are alternating (or level two) extension of multiple zeta values (MZVs). Kaneko and Tsumura initiated the study of multiple T-values (MTVs), another level two generalization, by restricting the summation indices in the definition of MZVs to a fixed parity pattern. In this paper, we shall study finite MTVs and their alternating versions which are level two and level four variations of finite MZVs, respectively. We conjecture that all finite MZVs are in the Q-span of finite MTVs which in turn apparently lie in the span of finite Euler sums, and the inclusions are both proper. We shall first provide some structural results for Euler sums of small weights, guided by the author's previous conjecture that the finite Euler sum space of weight w is isomorphic to a quotient Euler sum space of weight w. Then, by utilizing some well-known properties of the classical alternating MTVs, we shall derive a few important Q-linear relations among the finite alternating MTVs, including the reversal, linear shuffle and sum relations. We then compute the upper bound for the dimension of the Q-span of weight w finite (alternating) MTVs for w<9, both rigorously using the newly discovered relations and numerically aided by computers.

Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE) and gestational hypertension (GH), are major causes of maternal and fetal morbidity and mortality. This review elucidates the role of regulatory T cells (Tregs) in the immunological aspects of HDP and explores their therapeutic potential. Tregs, known for maintaining immune tolerance, are crucial in pregnancy to prevent immune-mediated rejection of the fetus. In HDP, Treg numbers and function imbalance are observed, correlating with disease severity. The review highlights that Tregs contribute to immunological adaptation in normal pregnancy, ensuring fetal acceptance and placental development. In contrast, HDP is associated with Treg dysfunction, marked by decreased numbers and impaired regulatory capacity, leading to inadequate immune tolerance and abnormal placental development. This dysfunction is particularly evident in PE, where Tregs fail to adequately modulate the maternal immune response against fetal antigens, contributing to the pathophysiology of the disorder. Therapeutic interventions aiming to modulate Treg activity represent a promising avenue for HDP management. Studies in animal models and limited clinical trials suggest that enhancing Treg functionality could mitigate HDP symptoms and improve pregnancy outcomes. However, the review acknowledges the complexity of translating these findings into effective clinical therapies, given the multifactorial nature of HDP and the intricate regulatory mechanisms of Tregs. In conclusion, while the precise role of Tregs in HDP is still being unravelled, their central role in immune regulation during pregnancy is indisputable. Further research is needed to fully understand the mechanisms by which Tregs contribute to HDP and to develop targeted therapies that can safely and effectively harness their regulatory potential for treating hypertensive diseases of pregnancy.

Background: Sleep deficiency can adversely affect the performance of resident physicians resulting in greater medical errors. However, the impact of sleep deficiency on surgical outcomes, particularly among attending surgeons is less clear. Methods: Sixty attending surgeons from academic and community departments of surgery or obstetrics and gynecology were studied prospectively using direct observation and self-report to explore the effect of sleep deprivation on patient safety, operating room communication, medical errors, and adverse events while operating under two conditions, Post-Call (defined as >2 hours of nighttime clinical duties) and Non-Post-Call. Results: Each surgeon contributed up to five surgical procedures post-call and non-post-call yielding 362 cases total (150 Post-Call and 210 Non-Post-Call). Most common were caesarian section and herniorrhaphy. Hours of sleep on the night before the operative procedure were significantly less Post-Call (4.98 ± 1.41) vs. Non-Post-Call (6.68 ± 0.88, p<0.01). Errors were infrequent and not related to hours of sleep or post-call status. However, Non-Technical Skills for Surgeons (NOTSS) ratings demonstrated poorer performance while Post-Call for Situational Awareness, Decision Making and Communication/Teamwork. Fewer hours of sleep also was related to lower ratings for Situational Awareness and Decision Making. Decreased self-reported alertness was observed to be associated with increased procedure time. Conclusions: Sleep deficiency in attending surgeons was not associated with greater errors during procedures performed during the next day. However, procedure time was increased suggesting that surgeons were able to compensate for sleep loss by working more slowly. Ratings on non-technical surgical skills were adversely affected by sleep deficiency.

The allosteric SERCA (Sarcoplasmic/Endoplasmic Reticulum Ca2+-ATPase) activator CDN1163 has been recently added to the group of pharmacological tools for probing SERCA function. We chose to investigate the effects of the compound on T lymphocyte Ca2+ stores, using the well-described Jurkat T lymphocyte as a reliable cell system for Ca2+ signaling pathways. Our study identified the lowest concentrations of the SERCA inhibitors thapsigargin (TG) and 2,5-di-(tert butyl)-1,4-benzohydroquinone (tBHQ) capable of releasing Ca2+, permitting the differentiation of the TG-sensitive SERCA 2b Ca2+ store from the tBHQ-sensitive SERCA 3 Ca2+ store. We proceeded to test the effects of CDN1163 on Ca2+ stores, examining specific actions on the SERCA 2b and SERCA 3 Ca2+ pools using our low dose SERCA blocker regimen. In contrast to previous work, we find CDN1163 exerts complex time-sensitive and SERCA isoform-specific actions on Ca2+ stores. Surprisingly, short-term exposure (0-30 minutes) to CDN1163 perturbs T cell Ca2+ stores by suppressing Ca2+ uptake with diminished Ca2+ release from the SERCA 2b-controlled store. Concomitantly, we find evidence for a SERCA-activating effect of CDN1163 on the SERCA 3 regulated store, given the observation of increased Ca2+ release inducible by low dose tBHQ. Intriguingly, longer-term (&gt;12 hours) CDN1163 exposure reversed this pattern, with increased Ca2+ release from SERCA 2b-regulated pools, yet decreased Ca2+ release responses from tBHQ-sensitive SERCA 3 pool. Our results reveal differential effects of CDN1163 on Ca2+ stores regulated by distinct SERCA isoforms, prompting the need for careful interpretation of the compound’s effects, particularly in cells expressing multiple SERCA isoforms.