Pituitary adenomas are benign brain tumors that pose a heavy burden on patients worldwide. However, the local burden of disease is yet to be established due to scarcity of data. In line with this, this study aims to present the challenges and gaps in the treatment of pituitary adenomas in the Philippines. A scoping review of available relevant literature on epidemiology, clinical experience with treatment, health financing, and healthcare delivery system based on the Preferred Reporting Items for Systematic reviews and Meta-analysis guidelines extension for Scoping Reviews was conducted. The scarcity of updated local clinical data, inequity of distribution of resources, inadequate government support, and lack of affordable diagnostic testing, medications and neurosurgical procedures are the factors that hinder provision of adequate care of pituitary adenomas in the Philippines. There are notable treatment gaps in the management of pituitary adenomas in the Philippines, which may be addressed by strengthening universal healthcare. Strategies to address these gaps were proposed, including improving public-private insurance coverage, increasing manpower, enhancing accessibility to resources, and spreading more awareness.

During chronic liver injury, inflammation leads to liver fibrosis— particularly due to the activation of hepatic stellate cells (HSCs). However, the involvement of inflammatory cytokines in HSC activation and the relationship among different liver cells is unclear. To examine their interactions, many in vitro liver models are performed in organoid or spheroid culture with random 3D structure, complicating analysis. Herein, we demonstrated the hierarchical coculture of primary rat hepatocytes with non-parenchymal cells such as the human-derived HSC line (LX-2) and liver sinusoidal endothelial cell line (TMNK-1). The cocultured tissue had high usability with simple operation of separating solid and liquid phases with improved liver functions such as albumin production and hepatic cytochrome P450 3A4 activity. We also studied the effects of stimulation by both oxygen tension and the key pro-fibrogenic cytokine, transforming growth factor beta (TGF-β), on HSC activation. Gene expression analysis revealed that lower oxygen tension and TGF-β1 stimulation enhanced collagen type I and alpha-smooth muscle actin expression from LX-2 cells in the hierarchical coculture. Therefore, this hierarchical in vitro cocultured liver tissue could provide an improved platform as a disease model for elucidating the interactions of various liver cell types and biochemical signals in future liver fibrogenesis studies.

Charcot-Marie-Tooth (CMT) disease is the most commonly inherited neurological disorder, defined by progressive deterioration of the peripheral nerves. Clinical manifestations of CMT mutations are typically limited to peripheral neurons, the longest cells in the body. Currently, mutations in at least 80 different genes are associated with CMT and new mutations are regularly being discovered. A large portion of the proteins mutated in axonal CMT have documented roles in mitochondrial mobility. This suggests that trafficking defects may be a common underlying mechanism in CMT. This review will focus on the potential role of altered mitochondrial mobility in the pathogenesis of axonal CMT, highlighting the challenges and opportunities to this “impaired mobility” model of the disease.

Charcot–Marie–Tooth disease (CMT) and associated neuropathies constitute the most predominant genetically transmitted neuromuscular conditions; however, effective pharmacological treatments remain elusive. The extensive genetic heterogeneity of CMT, which impacts the peripheral nerves and results in a lifelong disability, presents a significant barrier to the development of comprehensive treatments. An estimated 100 loci within the human genome are linked to various forms of CMT and its related inherited neuropathies. This review delves into prospective therapeutic strategies used for the most frequently encountered CMT variants, namely CMT1A, CMT1B, CMTX1, and CMT2A. Compounds such as PXT3003, which are currently under clinical and preclinical investigation, and a broad array of therapeutic agents and their corresponding mechanisms have been discussed in this review. Furthermore, the progress in established gene therapy techniques, including gene replacement via viral vectors, exon skipping using antisense oligonucleotides, splicing modification, and gene knockdown, has been appraised. Each of these gene therapies has the potential for substantial advancements in future research.

The immune system is central in controlling acute hepatitis B infection and in patients resolving chronic hepatitis B (CHB). Given that 221 million (75%) of CHB patients reside in low- and middle-income countries, developing a vaccine with therapeutic properties represents a rational and cost-effective approach more than a romantic endeavor. This review systematically analyses the critical variables related to the safety, efficacy, and effectiveness of CHB treatments. HeberNasvac's experience is revisited to address the challenges and potentialities of therapeutic vaccines, as well as the current roadblocks in research and development, registration, and large-scale implementation.

Group-B enteroviruses (EV-B) are ubiquitous naked single-stranded positive RNA viral pathogens that are responsible for common acute or persistent human infections. Their genome is composed in the 5'end by a non-coding region, which is crucial for the initiation of the viral replication and translation processes. RNA domain-I secondary structures can interact with viral or cellular proteins to form viral ribonucleoprotein (RNP) complexes regulating viral genomic replication, whereas RNA domains-II to -VII (IRES) are known to interact with cellular ribosomal subunits to initiate the viral translation process. Natural 5’ terminally deleted viral forms lacking some genomic RNA domain-I secondary structures have been described in EV-B induced murine or human infections. Recent in vitro studies have evidenced that the loss of some viral RNP complexes in the RNA domain-I can modulate the viral replication and infectivity levels in EV-B infections. Moreover, the disruption of secondary structures of RNA domain-I could impair viral RNA sensing by RIG-I or MDA5 receptors, a way to overcome antiviral innate immune response. Overall, natural 5′ terminally deleted viral genomes resulting in the loss of various structures in the RNA domain-I could be major key players of host-cell interactions driving the development of acute or persistent EV-B infections.

Taiwan's bed and breakfast (B&B) development has been more than 25 years ago, from the first generation of retirement to the B&B industry, serving tourists from all over the world accom-modation, providing breakfast and accommodation mode to the present, after the change of employees from the second generation, more and more attention is paid to the cultivation and cultivation of business ability. With the advent of the era of AI technology networking, the ca-pabilities required for B&B operation are more focused on all aspects of service, and the good marketing ability of B&B can promote a green chimney-free tourism economy, which is also a favorite industry of various governments and the public. This study explores the basic vocational competency indicators required for running a B&B, with (1)EQ emotion management skills, (2)Financial management ability, (3)(SK) technical skills, and (4)Marketing and promotion management capabilities. Through the study method, the K-S Z test was determined by the con-sensus conclusion of expert reliability and validity p value

In recent years, it has become common for individuals to juggle employment and unpaid care work. This is just as true for the England-based academic workforce, our focus in this article. We discuss how, in the context of English HE, support for carers is enacted and negotiated through policies and practices of care. Our focus on academics with a diverse range of caring responsibilities is unusual insofar as the literature on care in academia is overwhelmingly concerned with parents, usually mothers. The article is informed primarily by critical and post-structuralist feminist perspectives. We draw on a corpus of 47 interviews conducted with academics representing a broad range of caring responsibilities, subjects, and positions. A thematic analysis reveals how carers’ relationship with the provision and policies of care support at institutional level is characterised by ambiguity. On the one hand, participants approve of societal and institutional policy support for carers. On the other hand, they are often reluctant to position themselves as the beneficiary of such policies, expressing instead a general preference for support from outside the workplace or for workplace-based inter-individual and informal care arrangements. This resistance is particularly noticeable in the case of participants with caring responsibilities other than the parenting of healthy, able-bodied children and of those whose gender, class, racial, or sexual identity do not conform with the figure of the ‘ideal academic’, contributing to their othering in the academic realm. These findings have significant implications for policies supporting carers, pointing to the need for greater visibility and recognition of caring responsibilities in academia, especially in terms of their diverse identities.

Fluorescent bioprobes are invaluable tools for visualizing live cells and deciphering complex biological processes by targeting intracellular biomarkers without disrupting cellular functions. In addition to protein-binding concepts, fluorescent probes utilize various mechanisms, including membrane, metabolism, and gating-oriented strategies. This study introduces a novel fluorescent mechanism distinct from existing ways. Here, we developed a B-cell selective probe, CDrB, with unique transport mechanisms. Through SLC-CRISPRa screening, we identified two transporters, SLCO1B3 and SLC25A41, by sorting out populations exhibiting higher and lower fluorescence intensities, respectively, demonstrating contrasting activities. We confirmed that SLCO1B3, with comparable expression levels in T and B cells, facilitates the transport of CDrB into cells, while SLC25A41, overexpressed in T lymphocytes, actively exports CDrB. The observation suggests that SLC25A41 plays a crucial role in discriminating between T and B lymphocytes. Furthermore, it reveals the potential for reversible localization of SLC25A41 to demonstrate its distinct activity. This study is the first report to unveil a novel strategy of SLC by exporting the probe. We anticipate that this research will open up new avenues for developing fluorescent probes.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, showing reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

The expression "Follow the water" is used in order to recognize inside the universe, life as it exists on Earth. It is shown here that the expression "Follow the water in its high-subcritical state" can be used in order to recognize the components of life which form prior to the emergence of life. This specific state of water leaves signatures inside the minerals which are produced during high-subcritical water/rock interaction.

Atopic dermatitis (AD) is a chronic inflammatory condition which significantly affects quality of life in both patients and their caregivers. Calcineurin inhibitors (CNI) are a class of immunosuppressive drugs predominantly inhibiting T cell mediated immune processes. CNI form complex by binding with immunophilins and in turn inhibit calcineurin and suppress downstream inflammatory pathway. Tacrolimus and pimecrolimus are topical CNI approved for the treatment of mild to severe AD in both children and adults. Application site reactions are frequently seen. They have been issued with black box warning towards increased risk of malignancies but supportive evidence is lacking. Cyclosporine, though highly effective, is used off-label for AD management. It is used for controlling acute flares of AD due to its very rapid onset of action. Nephrotoxicity and hypertension are its serious complications. CNI have not been reported with teratogenicity and may be used conditionally during pregnancy and lactation.

Super-hydrophobic surfaces and coatings have stimulated a great deal of research, with the aim to achieve better wetting properties. Factors such as surface chemistry and roughness play an important role in changing the surface energy, which in turn leads to changes in the wettability. Here, we have analysed the time dependence of the oxide layer and possible surface adsorbates on the surface topography of an Al59Cu25Fe13B3 quasicrystalline material for changes to the wettability. The quasicrystalline matrix phase was 94 % of the sample volume, and covered by a very smooth, amorphous oxide layer. The AlB12 and AlFe2B2 boron-rich phases were embedded in the quasicrystalline material as a result of a 3 at.% boron addition, which makes atomisation of the material a simpler process. Under ambient conditions the sample was naturally covered by an oxide layer; therefore, it is referred to as “surfenergy”, to distinguish it from the conventional surface energy of a bare quasicrystal surface. The growth of the oxide layer with atmospheric ageing and annealing at 500° C in air for various times was investigated for both cases. The phase most prone to oxidation was the boron-rich AlFe2B2, which influenced the topography of the surface and accordingly the wetting behaviour of the specimen. We demonstrated that the surfenergy depends on the polar component, which is the most sensitive to the operating conditions. A correlation between the surfenergy components and the surface roughness was found. In addition, theoretical models to determine the wettability were included.

Soluble CD163 (sCD163) functions as a scavenger receptor for haptoglobin-hemoglobin complexes, and is mostly expressed by monocytes and macrophages. The level of soluble CD163 has been used to determine macrophage activation. Our goal was to determine whether the loading of M2 CD163 positive tumor-associated macrophages (TAMs) through the secretion of sCD163 affects overall survival in patients with DLBCL and eventually discriminates subgroups of patients with different prognosis. sCD163 levels were measured in 40 frozen serum samples from patients diagnosed with DLBCL and 30 healthy individuals (HI) using an enzyme-linked immunosorbent assay (ELISA). Statistical analyses were performed using SPSS version 28. The results showed that patients who achieved complete response after standard-of-care immuno-chemotherapy and were alive and disease-free after 12 months of follow-up, but had elevated sCD163 levels (above median) at diagnosis, presented a significantly worse overall survival compared to those with initial serum sCD163 levels below median (p=0.03). Consequently, serum sCD163 level in DLBCL patients may constitute a marker of long-term response to chemo-immunotherapy.

Pertussis is a vaccine-preventable disease caused by the bacterium Bordetella pertussis. Over the past years, the incidence and mortality of pertussis increased significantly. A possible cause is the switch from whole cell to acellular pertussis vaccines, although other factors may also contribute. To develop future vaccines and improve current vaccination strategies, it is critical to understand factors influencing the generation of immunological memory. We applied high-dimensional flow cytometry to investigate changes in B cells in individuals of different ages and distinct priming backgrounds upon administration of an acellular pertussis booster vaccine. These findings were correlated to vaccine-specific plasma cells and serum Ig levels. Expansion and maturation of plasma cells 7 days post-vaccination was the most prominent cellular change in all age groups, and was most pronounced for more mature IgG1+ plasma cells. Cellular responses were stronger in individuals primed with whole cell vaccine than in individuals primed with acellular vaccine. Moreover, IgG1+ plasma cell expansion weakly correlated with Prn- and PT- specific serum IgG levels. Our study points at plasma cells as a potential early cellular marker of an immune response and contributes to understanding differences in immune responses between age groups and priming backgrounds.

Background: Antibiotic resistance is an urgent issue everywhere in the globe. It is necessary to look into new sources of antibiotics to address this issue. Aim of the study: studying the purification of Corallopyronin B from various soil conditions in Egypt, as well as the antibacterial effectiveness of Corallopyronin B in preclinical animal testing and randomized human clinical trials phases 1/2. Type of the study: Screening experimental study. Methodology: Several soil conditions in Egypt were examined to create bacterial isolates that generated the antibiotic chemical Corallopyronin B. Using reversed-phase HPLC, Myxopyronin B was purified. The test antibiotic's minimum inhibitory concentration( MIC) and in vitro antibacterial activity were ascertained using the paper disc diffusion assay and the broth microdilution technique. Furthermore, in stages 1/2 of randomized clinical trials including human and animal models, pharmacokinetics, adverse drug reactions, and the in vivo antibacterial spectrum were discovered. Results: The soil bacterial isolate Corallococcus coralloides DSM 2259, which was grown on a Casein yeast peptone( CYP) plate, produced Corallopyronin B from its culture supernatant. At MICs more than 100 mcg/ml, the test antibiotic inhibited the growth of many Gram -ve bacteria, including Escherichia coli, while also preventing the growth of numerous Gram +ve bacteria, with MICs ranging from 1 to 10 mcg/ml. Eukaryotic cells, on the other hand, including those in humans and fungi, were unharmed. The test antibiotic was shown to have a bactericidal effect by inhibiting bacterial DNA-dependent RNA polymerase( RNLP). In phases 1/2 of randomized human clinical trials, when 600 mg of the dose per 70 kg of body weight was administered SC, the Cmax was 8.6 mcg/ml at Tmax 1 hour; T1/2 reached 136 min following first-order kinetics of elimination. It stopped acting around 6-7 hours after SC was administered. In the preclinical and randomized human clinical trial phases 1/2, less than 6 percent of experimental candidates had uncommon toxicity, which showed up as reduced bile flow. Protein binding with plasma albumin was detected which reached about 83%. Conclusion: The current work was noteworthy since it involved the production of the bactericidal antibiotic Corallopyronin B from Corallococcus coralloides DSM 2259 which was isolated from several soil environments in Egypt.

To achieve n-type doping in diamond, extensive investigations employing first principles have been conducted on various models of phosphorus doping and boron-phosphorus co-doping. The primary focus of this study is to comprehensively analyze the formation energy, band structure, density of states, and ionization energy of these structures. It is observed that within a diamond structure solely composed of phosphorus atoms, the formation energy of an individual carbon atom is excessively high. However, the substitution of two carbon atoms leads to the conversion of diamond into a p-type semiconductor. Upon examining the P-B co-doping structure, it is revealed that the doped impurities exhibit a tendency to form more stable cluster configurations. As the separation between the freely doped atoms and the cluster impurity structure increases, the overall stability of the structure diminishes, consequently resulting in an elevation of the ionization energy. Analysis of the electronic density of states demonstrates that the electron orbit of the B atom makes negligible contributions to the impurity levels during P-B doping.

: Healthcare workers are affected by mental health issues, burnout and turnover, and this burden is even greater during epidemics and pandemics, such as COVID-19. The purpose of this research is to provide an overview of the measures introduced or supported in the institutions of Quebec’s health and social services network during the COVID-19 pandemic with the aim of protecting healthcare workers’ mental health. An online questionnaire survey was administered in 2021 among human resources department personnel in health and social services network institutions involved in workplace mental health in Quebec. A total of 223 key informants representing 31 of the 34 public health and social services institutions in the province of Quebec in Canada responded to the questionnaire. Measures that focus on the needs of staff, involve all levels of authority and the ones that provide flexibility, support and recognition at work were more successful, according to the advisors surveyed. Future research into whether the same measures are considered effective or ineffective outside of a pandemic context is needed.

Anthropomorphism is a natural tendency in humans, but it is also influenced by many characteristics of the observer (the human) and the observed entity (here, the animal species). This study asked participants to complete an online questionnaire about three videos showing epimeletic behaviours in three animal species. In the videos, an individual (a sparrow, an elephant and a macaque, respectively) displayed behaviours towards an inanimate conspecific that suddenly regained consciousness at the end of the footage. A fourth video showed a robot dog being kicked by an engineer to demonstrate its stability. Each video was followed by a series of questions designed to evaluate the degree of anthropomorphism of participants, from mentaphobia (no attribution of intentions and beliefs, whatever the animal species) to full anthropomorphism (full attribution of intentions and beliefs by animals, to the same extent as in humans) and to measure how far the participants had correctly assessed each situation in terms of biological reality (current scientific knowledge of each species). There is a negative correlation (about 61%) between the mental states attributed to animals by humans to animals and the real capability of animals. The heterogeneity of responses proved that humans display different forms of anthropomorphism, from rejecting all emotional or intentional states in animals to considering animals to show the same intentions as humans. However, the scores participants attributed to animals differed according to the species shown in the video and to human sociodemographic characteristics. Understanding the potential usefulness of these factors can lead to better relationships with animals and encourage a positive view of human-robot interactions. Indeed, reflective or critical anthropomorphism can increase our humanity.

In this study, we asked participants to answer an online questionnaire about videos showing animal epimeletic behaviours: an individual (a sparrow, an elephant and a macaque) displayed behaviours towards an inanimate conspecific who suddenly got back to conscious at the end of the footage. A fourth video showed a dog-robot kicked by an engineer to demonstrate its stability. After each video, questions were asked to score the degree of anthropomorphism of participants, from mentophobia (no attribution whatever the species) to full anthropomorphism and to measure how close participants are to biological reality (actual scientific knowledge). A first important result is that there is a negative correlation (about 61%) between the anthropomorphism score (AS) and the biological reality one (BRS) showing a wrong statement. The heterogeneity of responses proved that all levels of anthropomorphism are covered from mentaphobia to full anthropomorphism. However, the scores participants attributed to animals differ according to the species shown in the video and to human characteristics. Understanding how one can play with these factors can conduct to better relationships with animals as encourage human-robot interactions. Finally, such reflective anthropomorphism can lead to an increase of human empathy and sociality, finally increasing our humanity.

Gender and biological sex have distinct impacts on the pathogenesis of type 2 diabetes (T2D). Estrogen deficiency is known to predispose female mice to T2D. In our previous study, we found that high-fat, high-sucrose diet (HFHSD) induces T2D in male mice through the miR-10b-5p/KLF11/KIT pathway, but not in females, highlighting hormonal disparities in T2D susceptibility. However, the underlying molecular mechanisms of this hormonal protection in females remain elusive. To address this knowledge gap, we utilized ovariectomized, estrogen-deficient female mice, fed them a HFHSD to induce T2D, and investigated the molecular mechanisms pathway in estrogen-deficient diabetic female mice, cell lines, and patients with T2D in female. Initially, female mice fed a HFHSD exhibited delayed onset of T2D, but ovariectomy-induced estrogen deficiency promptly precipitated T2D without delay. Intriguingly, insulin (INS) was upregulated, while insulin receptor (INSR) and protein kinase B (AKT) were downregulated in these estrogen-deficient diabetic female mice, indicating insulin-resistant T2D. These dysregulations of INS, INSR, and AKT were mediated by a miR-10a/b-5p-NCOR2 axis. Treatment of miR-10a/b-5p effectively alleviated hyperglycemia in estrogen-deficient T2D female mice, while β-estradiol temporarily reduced hyperglycemia. Consistent with the murine findings, plasma samples from female T2D patients exhibited significant reductions in miR-10a/b-5p, estrogen, and INSR, but increased insulin levels. Our findings suggest that estrogen protect against insulin-resistant T2D in females through miR-10a/b-5p/NCOR2 pathway, indicating the potential therapeutic benefits of miR-10a/b-5p restoration in female T2D management.

Current cellular facts allow us to follow the link from chemical to biochemical metabolites, from the ancient to the modern world. In this context, the "RNA world" hypothesis proposes that early in the evolution of life, the ribozyme was responsible for the storage and transfer of genetic information and for the catalysis of biochemical reactions. Accordingly, the hammerhead ribozyme (HHR) and the hairpin ribozyme, belong to a family of endonucleolytic RNAs performing self-cleavage that might occur during replication. Furthermore, regarding the ultraconserved occurrence of HHR in several genomes of modern organisms (from mammals to small parasites and elsewhere), these small ribozymes have been regarded as living fossils of a primitive RNA world. They fold into 3D structures that generally require long-range intramolecular interactions to adopt the catalytically active conformation under specific physicochemical conditions. By studying viroids as plausible remains of ancient RNA, we recently demonstrated that they replicate in non-specific hosts, emphasizing their adaptability to different environments, which enhanced their survival probability over the ages. All these results exemplify ubiquitously features of life. Those are the versatility and efficiency of small RNAs, viroids and ribozymes, as well as their diversity and adaptability to various extreme conditions. All these traits must have originated in early life to generate novel RNA populations.

Introduction: Intimate partner violence occurring during pregnancy has a similar prevalence as usual obstetrical disorders routinely screened for. Referenced publications insist on the importance of adequate screening but the proper course of action has yet to be defined. Aim of study: We qualitatively explored the different resources and concepts that emerge from the discourse of maternity staff across professions. Material and methods: We led a semi structured interview with professionals included following their involvement with preselected patients. Nine professionals provided a sample of 19 interviews. The data was analysed using IPA methodology. Results We highlight the investigative importance of navigating the patient’s initial demand or lack thereof and the baby’s importance within, mindful of mechanisms of maternal disqualification. Creating an atmosphere prone to patient empowerment was the final theme to emerge from the study as the most beneficial tactic both in the short and long term. Conclusion: HCPs need to enable patients’ trust on a personal and an institutional level. As well as empowering the patient in the moment and respecting their values and choices, HCPs also convey the stability of the institution that has to become a reference of refuge and assistance for patients from their pregnancy onwards.

The dominant paradigm holds that spontaneous and therapeutically induced anti-tumor responses are mediated mainly by CD8 T cells and directed against tumor-specific antigens (TSAs). The presence of specific TSAs on cancer cells can only be proven by mass spectrometry analyses. Bioinformatic predictions and reverse immunology studies cannot provide this type of conclusive evidence. Most TSAs are coded by unmutated non-canonical transcripts that arise from cancer-specific epigenetic and splicing aberrations. When searching for TSAs, mass spectrometry analyses must therefore interrogate not only the canonical reading frame of annotated exome but all reading frames of the entire translatome. The majority of aberrantly expressed TSAs (aeTSAs) derive from unstable short-lived proteins that are good substrates for direct MHC I presentation but poor substrates for cross-presentation. This is an important caveat because cancer cells are poor antigen-presenting cells and the immune system therefore depends on cross-presentation by dendritic cells (DCs) to detect the presence of TSAs. We therefore postulate that, in the untreated host, most aeTSAs are undetected by the immune system. We present evidence suggesting that vaccines inducing direct aeTSA presentation by DCs represent an attractive strategy for cancer treatment.

During the last few years, the world witnessed one of the worst calamities to humankind- the COVID-19 pandemic. We also witnessed the development of vaccines at an unprecedented pace against the SARS-CoV-2- the causative agent. India was among the hard-hit countries by COVID-19, developed its indigenous vaccine and implemented vaccines developed in other countries as well. Initially, the antibody level and the neutralizing antibody titer against the pathogen were considered as the correlates of immune protection from the disease. However, the long-term protection from the pathogen was provided by the immune memory cells viz. T and B memory cells and their ability to efficiently make recall responses. In this regard, globally the research studies focused mainly on the mRNA-based vaccines. The studies on immune memory response, particularly- the B cell memory response bestowed by the vaccines given to Indians is relatively obscure. We studied the level of RBD specific memory B cells in the peripheral circulation of the study participants and the ability of B cells to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D) and Sputnik Light (Gam-COVID-Vac) as well as unvaccinated individuals. Our study revealed that Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses.

Lung cancer is the leading cause of cancer related mortality worldwide. In order to improve its overall survival, early diagnosis is required. Since current screening methods still face some pitfalls, such as high false positive rates for low-dose computed tomography, researchers are still looking for early biomarkers to complement existing screening techniques in order to provide a safe, faster and more accurate diagnosis. Biomarkers are biological molecules found in body fluids, such as plasma, that can be used to diagnose a condition or disease. Metabolomics has already shown to be a powerful tool in the search for cancer biomarkers since cancer cells are characterised by impaired metabolism, resulting in an adapted plasma metabolite profile. The metabolite profile can be determined using nuclear magnetic resonance, or NMR. Although metabolomics and NMR metabolite profiling of blood plasma are still under investigation, there is already evidence for its potential for early-stage lung cancer diagnosis, therapy response, and follow-up monitoring. This review highlights some key breakthroughs in this research field, where the most significant biomarkers will be discussed in relation with their metabolic pathways and in light of the altered cancer metabolism.

Abstract: The broad clinical use of synthetic vascular grafts for vascular diseases is limited by their thrombogenicity and low patency rate, especially for vessels with a diameter inferior to 6 mm. Alternatives such as tissue-engineered blood grafts (TEBGs) have gained increasing interest. Among the different manufacturing approaches, 3D bioprinting presents numerous advantages and enables the fabrication of multi-scale, multi-material, and multicellular tissues with heterogeneous and functional intrinsic structures. Extrusion-, inkjet- and light-based 3D printing techniques have been used for the fabrication of TEBG out of hydrogels, cells, and/or solid polymers. This review discusses the state-of-the-art research on the use of 3D printing for TEBG with a focus on the biomaterials and deposition methods.

Genetic diversity is very important in crop improvement. This study was carried out to assess the genetic diversity and the number of unique multilocus genotypes (MLGs) in cassava collection in Burkina Faso. To achieve this objective 130 cassava accessions were genotyped using 32 simple sequence repeat (SSR) markers. The results revealed that among these markers, twelve (12) were highly informative, with the PIC values greater than 0.50, twelve (12) were moderately informative, with the PIC values ranged between 0.25 and 0.50, and eight (8) were not very informative, with the PIC values lower than 0.25. A moderate level of genetic diversity was found for the population, indicated by the average expected heterozygosity (0.45) and the observed heterozygosity (0.48). About 83.8% of unique multilocus genotypes were found in the cassava collection indicating that SSR markers seem to be most appropriate for MLGs identification. Population structure analysis based on hierarchical clustering identified two subpopulations and Bayesian approach suggested five clusters. Additionally, DAPC analysis separated the cassava accessions into 13 subpopulations. The comparison of these results and the previous study using SNP, suggest that each type of markers can be used to assessment the genetic structure of cassava grown in Burkina Faso.

The importance of genome organization at the supranucleosomal scale in the control of gene expression is increasingly recognized today. In mammals, Topologically Associating Domains (TADs) and the active / inactive chromosomal compartments are two of the main nuclear structures that contribute to this organization level. However, recent works reviewed here indicate that, at specific loci, chromatin interactions with nuclear bodies could also be crucial to regulate genome functions, in particular transcription. They moreover suggest that these nuclear bodies are membrane-less organelles dynamically self-assembled and disassembled through mechanisms of phase separation. We have recently developed a novel genome-wide experimental method, High-salt Recovered Sequences sequencing (HRS-seq), which allows the identification of chromatin regions associated with large ribonucleoprotein (RNP) complexes and nuclear bodies. We argue that the physical nature of such RNP complexes and nuclear bodies appears to be central in their ability to promote efficient interactions between distant genomic regions. The development of novel experimental approaches, including our HRS-seq method, is opening new avenues to understand how self-assembly of phase separated nuclear bodies possibly contributes to mammalian genome organization and gene expression.

There exists a variety of studies about tumor-infiltrating lymphocytes (TILs) in cervical cancer, but their prognostic value in correlation to the histopathological subtype was never investigated. Therefore, the aim of this study was to quantify TILs in a panel of 250 sporadic cervical cancers and investigate the correlation with cervical cancer subtype and patient survival. TIL levels were significantly increased in the subgroup of squamous cell carcinomas in comparison to adenocarcinomas. In squamous cell carcinomas, TIL infiltration shows a negative correlation to age, FIGO stage and to the histone protein modification H3K4me3. Moreover, in adenocarcinomas, it was positively correlated to p16 and to the glucocorticoid receptor and inversely correlated to the MDM2 protein and to H3K4me3. Interestingly, immune infiltration was an independent positive prognosticator for disease free survival (DFS) in patients with squamous cell carcinomas, those bearing tumors with the strongest TIL infiltration showing the better DFS. Altogether, the present study provides a differentiated overview of the relations between TIL levels and prognosis in patients with cervix squamous cell carcinomas vs patients with cervix adenocarcinomas.

This study reports rapid hydrolysis, acylation, and lipolysis with lipase B from Candida antarctica (CalB) and nanofructosome encapsulated CalB (CalB@NF) enzymes immobilized on silica-coated magnetic nanoparticles (Si-MNPs). Enzymatic hydrolysis was confirmed for conversion to p-nitrophenol (p-NP, λex=400 nm) from p-nitrophenyl butyrate (p-NPB, λex=270 nm), and various catalytic parameters such as Km, Vmax, and Kcat were calculated from Michaelis-Menten and Lineweaver-Burk plot. Efficiency of enzymatic hydrolysis was in the order of CalB > Si-MNPs@CalB > CalB@NF > Si-MNPs@CalB@NF, and reusability was much better with the enzyme immobilized on Si-MNPs than with the native enzyme. Enzymatic acylation was confirmed by the formation of benzyl benzoate (λex=229 nm) from benzoic anhydride (λex=240 nm), and efficiency exceeded 99% in all samples. Finally, enzymatic lipolysis was confirmed by the decomposition of olive oil to fatty acid such as oleic acid (λex=230 nm) using thin-layer chromatography (TLC), column chromatography, and proton nuclear magnetic resonance (1H -NMR). The lipases immobilized on Si-MNPs have the advantage of good thermal stability and reusability and are thus applicable to a wide range of industries.

β-Ga2O3 is a well-known semiconductor material for power devices and other applications. Recently, β-Ga2O3 has also been reported as a scintillator material with a light yield of approximately 8400 ph./MeV, scintillation decay time of <1 μs, and density of 6.44 g/cm3. In this study, 2-inch diameter β-Ga2O3 single crystals were prepared by oxide crystal growth using the cold crucible (OCCC) method under various oxygen partial pressures. In the OCCC method, as in the cold crucible method, a high frequency is applied directly to the oxide materials, which are heated and melted, and the melt is held by the outermost solid material itself that is cooled by water using a copper hearth. In the OCCC method, crystal growth is performed while rotating the seed crystal, as in the Czochralski method, to increase the crystal diameter. The optical properties and radiation responses of the crystals grown under various oxygen partial pressures were evaluated.

Developmental hazard evaluation is an important part of assessing chemical risks during pregnancy. Toxicological outcomes from prenatal testing in pregnant animals result from complex chemical-biological interactions, and while New Approach Methods (NAMs) based on in vitro bioactivity profiles of human cells offer promising alternatives to animal testing, most of these assays lack cellular positional information, physical constraints, and regional organization of the intact embryo. Here, we engineered a fully computable model of the embryonic disc in the compucell3d.org modeling environment to simulate epithelial-mesenchymal transition of epiblast cells and self-organization of mesodermal domains (chordamesoderm, paraxial, lateral plate, posterior/extraembryonic). Cell fate in the model is determined by an autonomous homeobox (HOX) clock driven by morphogenetic signals (e.g., FGF, WNT, ATRA, CDX). Executing the model renders a quantitative cell-level computation of mesodermal subpopulations and consequences of perturbation based on known embryogeny. For example, synthetic perturbation of the control network rendered altered phenotypes (cybermorphs) mirroring experimental mouse embryology, with 50% reductions in FGF4, FGF8 and BMP4 signaling resulting in 86%, 98% and 59% reductions, respectively in the posterior mesodermal population, while ATRA exposure also resulted in a 78% decrease in this population. This model enables integration of in vitro chemical bioactivity data for specific molecular targets with known embryology to test mechanistic veracity and quantitative prediction of altered development.

Background/Objectives: Vitamin D’s effect on risk health outcomes is often evaluated using prospective cohort studies. Risk ratios (RRs; e.g., hazard ratios or odds ratios) are determined for incidence for participants with baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations below or above specified values. Serum 25(OH)D concentrations vary over time, thereby diluting the effect of 25(OH)D for long follow-up periods. Inverse relationships between RR and follow-up period have been reported for all-cause mortality rate and cancer incidence rates. Here I evaluate the effect for neurological outcomes. Methods: I analyzed how follow-up period affected results from 10 cohort studies of all-cause dementia, 6 studies of Alzheimer’s disease, and 9 for cognitive impairment with respect to vitamin D deficiency. Results: For all-cause dementia, Alzheimer’s disease, and cognitive impairment, respectively, the linear regression fits are RR = 2.9 – 0.14 × years, r = 0.73, p = 0.02; RR = 2.9 – 0.14 × years, r = 0.69, p = 0.13; and RR = 1.8 – 0.066 × years, r = 0.72, p = 0.03. The regression fit to RR for the shortest follow-up period for each outcome is considered the best estimate of vitamin D deficiency’s effect on risk. Those values are approximately twice that found by averaging all RRs without considering the effect of follow-up period. Conclusions: Vitamin D’s effect on risk of neurological conditions should be determined with relatively short follow-up periods after repeated 25(OH)D measurements as warranted during follow-up.

Abstract: This article reports the results of an ecological study of cancer incidence rates by state in the US for the period 2016-2020. The goals of this study were to determine the extent to which solar UVB doses still reduced cancer risk compared to findings reported in 2006 for cancer mortality rates for the periods 1950–1969 and 1970-1794 as well as cancer incidence rates for the period 1998–2002 and to determine which factors were recently associated with cancer risk. The cancer data for non-Hispanic white (European American) men and women were obtained from the Centers for Disease Control and Prevention. Indices were obtained for solar UVB at the surface for July 1992, and alcohol consumption, and diabetes and obesity prevalence near the 2016–2020 period. Lung cancer incidence rates were also used in the analyses as a surrogate for smoking, diet, and air pollution. The cancers for which solar UVB is significantly associated with reduced incidence are bladder, brain (males), breast, corpus uteri, esophageal, gastric, non-Hodgkin’s lymphoma, pancreatic, and renal cancer. Lung cancer was significantly associated with colorectal, laryngeal, and renal cancer. Diabetes was also significantly associated with breast, liver, and lung cancer. Obesity prevalence was significantly associated with breast, colorectal and renal cancer. Alcohol consumption was associated with bladder and esophageal cancer. Thus diet has become a very important driver of cancer incidence rates. The role of solar UVB in reducing risk of cancer has been reduced due to people spending less time outdoors, wearing sunscreen that blocks UVB but not UVA radiation, and population increases in overweight and obesity, which lowers 25-hydroxyvitamin D concentrations and generates systemic inflammation, a risk factor for cancer. The dietary approach that would reduce the risk of diabetes, obesity, lung cancer, and, therefore cancer, would be one based mostly on whole-plants and restrictions on red and processed meats and ultraprocessed foods. Solar UVB exposure for a few minutes before applying sunscreen and taking vitamin D supplements would also help reduce risk of cancer.Keywords: alcohol consumption; cancer incidence;

Introduction: We describe the clinical features and inpatient trajectories of older adults hospitalized with COVID-19, and explore relationships with frailty. Methods: This retrospective observational study included older adults admitted as an emergency to a University Hospital who were diagnosed with COVID-19. Patient characteristics and hospital outcomes, primarily inpatient death or death within 14 days of discharge, were described for the whole cohort and by frailty status. Associations with mortality were further evaluated using Cox Proportional Hazards Regression (Hazard Ratio [HR], 95% Confidence Interval). Results: 214 patients (94 women) were included of whom 142 (66.4%) were frail with a median Clinical Frailty Scale (CFS) score of 6. Frail compared to non-frail patients were more likely to present with atypical symptoms including new or worsening confusion (45.1% vs 20.8%, p<0.001) and were more likely to die (66% vs 16%, p=0.001). Older age, being male, presenting with high illness acuity and high frailty were independent predictors of death and a dose-response association between frailty and mortality was observed (CFS 1-4: reference; CFS 5-6: HR 1.78, 95% CI 0.90, 3.53; CFS 7-8: HR 2.57, 95% CI 1.26, 5.24). Conclusions: Clinicians should have a low threshold for testing for COVID-19 in older and frail patients during periods of community viral transmission and diagnosis should prompt early advanced care planning.

The pathogenesis of porcine circovirus type 2b (PCV2b) and swine influenza A virus (SwIV) during co-infection in swine respiratory cells is poorly understood. To elucidate the impact of PCV2b/SwIV co-infection, newborn porcine tracheal epithelial cells (NPTr) and immortalized porcine alveolar macrophages (iPAM 3D4/21) were co-infected with PCV2b and SwIV (H1N1 or H3N2 genotype). Viral replication, cell viability and cytokine mRNA expression were determined and compared between single-infected and co-infected cells. Finally, 3’mRNA sequencing was performed to identify the modulation of gene expression and cellular pathways in co-infected cells. It was found that PCV2b significantly decreased and improved SwIV replication, in co-infected NPTr and iPAM 3D4/21 cells respectively, compared to single infected cells. Interestingly, PCV2b/SwIV co-infection synergistically up-regulated IFN expression in NPTr cells whereas in iPAM 3D4/21 cells, PCV2b impaired the SwIV IFN induced response, both correlating with SwIV replication modulation. RNA-sequencing analyses revealed that the modulation of gene expression and enriched cellular pathways during PCV2b/SwIV H1N1 co-infection is regulated in a cell type-dependent-manner. This study revealed different outcomes of PCV2b/SwIV co-infection in porcine epithelial cells and macrophages and provides new insights on porcine viral co-infections pathogenesis.

Wearable antennas are increasingly vital in modern healthcare, facilitating continuous monitoring and communication for medical purposes. These antennas are integrated into wearable devices, allowing for the transmission and reception of vital health data, such as heart rate, body temperature, and blood pressure, to medical professionals or monitoring systems in real time. This instantaneous data transmission enables timely interventions, thus improving the quality of healthcare services. This review aims to comprehensively synthesize recent research from reputable databases, focusing on the functionality and effectiveness of wearable antennas in medical applications. The primary objectives of each study were categorized, including antenna design and integration, the performance of medical wearable antenna technology, safety considerations in wearable antenna biomedicine, and the use of antennas in clinical applications and their impact. This synthesis provides valuable insights for researchers and practitioners aiming to develop and deploy wearable antennas in medical settings, ultimately enhancing healthcare delivery and patient outcomes.

Mutations in the SACS gene are associated with autosomal recessive spastic ataxia of Charlevoix-Saguenay disease (ARSACS) or complex clinical phenotypes of Charcot-Marie-Tooth disease (CMT). This study aimed to identify SACS mutations in a Korean CMT cohort with cerebellar ataxia and spasticity. As a result, eight pathogenic SACS mutations in four families were identified as the underlying causes of these complex phenotypes. The prevalence of CMT families with SACS mutations was determined to be 0.3%. All the patients showed sensory, motor, and gait disturbances with increased deep tendon reflexes. Lower limb magnetic resonance imaging (MRI) was done in four patients, and all had fatty replacements. Of note, they all had similar fatty infiltrations between the proximal and distal lower limb muscles, different from the neuromuscular imaging feature in most CMT patients without SACS mutations who had distal dominant fatty involvement. Therefore, these findings were considered a characteristic feature in CMT patients with SACS mutations. Although further studies with more cases are needed, our results highlight lower extremity MRI findings in CMT patients with SACS mutations and broaden the clinical spectrum. We suggest screening for SACS in recessive CMT patients with complex phenotypes of ataxia and spasticity.

Health innovations are generally oriented on a techno-economic vision. In this perspective, technologies are seen as an end in themselves, and there is no arrangement between the technical and the social values of innovation. This vision prevails in sanitary crises, in which management is carried out based on the search for punctual, reactive, and technical solutions to remedy a specific problem without a systemic/holistic, sustainable, or proactive approach. This paper attempts to contribute to the literature on the epistemological orientation of innovations in the field of public health. Taking the Covid-19 and Ebola crises as examples, the primary objective is to show how innovation in health is oriented towards a techno-economic paradigm. Second, we propose a repositioning of public health innovation towards a social paradigm that will put more emphasis on the interaction between social and health dimensions in the perspective of social change.

The production of recombinant enzymes, mainly used for obtaining pure and functional target molecules, holds significant importance in modern biotechnology. This study aimed to produce recombinant α-amylases (Amy3500 and Amy1974), derived from B. amyloliquefaciens MDC1974 and B. subtilis MDC3500 respectively, using the pBE-S shuttle vector, and to characterize them. Both α-amylase genes were molecularly cloned into the E. coli/B. subtilis pBE-S shuttle vector, both with (Amy1974sig and Amy3500sig) and without their own signal peptides (Amy1974 and Amy3500), along with a signal peptide originating from the plasmid, and tested in flask fermentations. For recombinant Amy3500, the amylase variants resulted in similar levels of volumetric activity (700-750 U/mL). In contrast, the expression of Amy1974 nearly doubled compared to Amy1974sig with double signal peptides, reaching 2000 U/mL. The SDS-PAGE estimated the molecular weight of Amy1974 α-amylase to be 54.6 kDa, which was in accordance with the theoretical molecular mass calculations. However, the estimated molecular weight of Amy3500 amylase was significantly reduced when exiting the producer cells. Ca2+ had no significant activating effect on the activities of Amy1974 amylase and Amy3500 amylase, likely due to its tight binding to the protein scaffold. Both enzymes exhibited broad activity peaks between 45-70°C, with a maximum at 65°C. The Amy1974 and Amy3500 α-amylases demonstrated broad pH optima and pH-dependent thermostability, with optimum pH values at 6.5 and 5.8, and thermal stability peaks at pH 7.6 and 5.9, respectively. Both α-amylases displayed high relative activity against various starches, including corn amylopectin and potato amylose, while showing comparatively lower activity towards cyclodextrins. The Amy1974 amylase converts starch to dextrins of varying lengths, whereas Amy3500 almost entirely converts starch into glucose.

Objectives: This study aimed to evaluate the risk of hepatitis B virus reactivation (HBVr) in COVID-19 patients receiving immunosuppressive treatment, which has been insufficiently studied to date. Secondarily, we aimed to evaluate the seroprevalence of HBV infection in COVID-19 patients. Methods: We performed an HBV screening in all Romanian adults hospitalized in 4 COVID-19 wards between October 2021 and September 2022. We enrolled patients with positive hepatitis B core antibody (anti-HBc) without protective hepatitis B surface antibody (anti-HBs), HBV treatment or immunosuppressive conditions, whom we followed virologically at 3 months. Results: We identified 333/835 (39.9%) anti-HBc-positive patients. Follow-up was performed in 13 patients with positive hepatitis B surface antigen (HbsAg) and 19 HBsAg-negative/anti-HBc-positive patients. Among those who received immunosuppressants, 4/23 (17.4%) patients experienced HBVr: 1 out of 8 (12.5%) HBsAg-positive patients (with 1.99 log increase in HBV DNA level) and 3 out of 15 (20%) HBsAg-negative/anti-HBc-positive patients (with de novo detectable HBV DNA level). Conclusions: Administration of COVID-19 immunosuppressants may result in a significant risk of HBVr in co-infected patients. We recommend performing an HBV triple screen panel (HBsAg, anti-HBs, anti-HBc) in all COVID-19 patients receiving immunosuppressive treatment. HBV prophylaxis may be indicated in certain patients. Larger studies are needed in order to establish an appropriate and cost-effective management in these patients.

Abstract: This comprehensive review seeks to deepen our comprehension of the African plant Momordica balsamina L. by elucidating its therapeutically important molecules and micronutrient composition. Commonly referred to as the balsam apple, this plant species is extensively harnessed for its diverse therapeutic potentials across its various organs including leaves, fruits, roots, and stems. Numerous bioactive molecules have been isolated or identified within this plant, notably encompassing polyphenols, flavonoids, terpenes, and carotenoids. These compounds exhibit a wide array of biological activities, ranging from antioxidative, anti-inflammatory, anti-diabetic, anti-carcinogenic, to anti-malarial properties, among others. Furthermore, the leaves of Momordica balsamina L. stand out for their abundant micronutrients, proteins, and amino acids. This investigation aims to shed light not only on the botanical characteristics of the Momordica balsamina plant and its potential applications in traditional medicine, but also on its chemical composition, biological functionalities, and physicochemical attributes, thus accentuating its nutritional advantages. Nonetheless, an intriguing avenue presents itself for the exploration of strategies to conserve this species, delve deeper into its potential within the cosmetics industry, and innovate methodologies for the synthesis or biosynthesis of these bioactive molecules.

Understanding molecular mechanisms of neurological disorders is required for development of personalized medicine. When the diagnosis considers not only the disease symptoms, but also their molecular basis, the treatments tailored for individual patients may be suggested. The vitamins-responsive neurological disorders are induced by deficiencies in the vitamin-dependent processes. The deficiencies may occur due to genetic impairments of proteins whose functions are involved with the vitamins. This review considers the enzymes encoded by DHTKD1, PDK3 and PDXK genes, whose mutations are observed in patients with Charcot-Marie-Tooth (CMT) disease. The enzymes bind or produce the coenzyme forms of vitamins B1 (thiamine diphosphate, ThDP) and B6 (pyridoxal-5’-phosphate, PLP). Alleviation of such disorders by administration of the lacking vitamin or its derivative calls upon a better introduction of the mechanistic knowledge to medical diagnostics and therapies. Recent data on lower levels of the vitamin B3 derivative, NAD+, in the blood of patients with CMT disease, compared to the control subjects, are also considered in view of the NAD-dependent mechanisms of pathological axonal degeneration, suggesting therapeutic potential of vitamin B3. Thus, improved diagnostics of the underlying causes of the CMT disease may allow the patients with the vitamin-responsive disease forms to benefit from the administration of the vitamins B1, B3, B6, their natural derivatives or pharmacological forms.

Resilience is an important determinant of the quality of life in adults, among others in the sphere of cognitive activities. Developments in brain imaging technology make it possible to acquire a more accurate understanding of the neuronal mechanisms of these correlations. The aim of this study was to verify whether the level of mental resilience would differentiate reading comprehension performance when using different information carriers. More than 150 adults were surveyed with the use of two questionnaires (original and standardised) and near-infrared spectroscopy (fNIRS). The results obtained did not show differences in correct responses between the groups of individuals with different levels of resilience, however, the results in the group of subjects with moderate levels were differentiated by the type of carrier. Further analysis showed that the results referred to above resulted from different neuronal mechanisms. The differences affected many areas of the brain and also depended on the type of information carrier (medium). They affected, among others, attentional areas as well as areas directly involved in the reading process. This may result in increased energy consumption during the examined activities, which can result in greater fatigue, accelerated job burnout and progressive concentration difficulties.

Non-coding RNAs (ncRNAs) comprise a diverse class of non-protein coding transcripts that regulate critical cellular processes associated with cancer. Advances in RNA-sequencing (RNA-Seq) have led to the characterization of non-coding RNA expression across different types of human cancers. Through comprehensive RNA-Seq profiling, a growing number of studies demonstrate that ncRNAs, including long non-coding RNA (lncRNAs) and microRNAs (miRNA), play central roles in progenitor B-cell Acute Lymphoblastic Leukemia (B-ALL) pathogenesis. Furthermore, due to their central roles in cellular homeostasis and their potential as biomarkers, the study of ncRNAs continues to provide new insight into the molecular mechanisms of B-ALL. This article reviews the ncRNA signatures reported for all B-ALL subtypes, focusing on technological developments in transcriptome profiling and recently discovered examples of ncRNAs with biologic and therapeutic relevance in B-ALL.

Background: The global pandemic of coronavirus disease 2019 (COVID-19) resulted to many deaths from fulminant respiratory failure. Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There has been great concern regarding the impact of COPD on COVID-19 illness. Methods: Data from the Philippine CORONA Study were analyzed to determine the association of COPD and COVID-19 in terms of mortality, disease severity, respiratory failure, mechanical ventilation, and lengths of stay in the intensive care unit (ICU) and hospital. The influence of smoking on COVID-19 disease severity and mortality were also reviewed. Results: A total of 10,881 patients were included in the study and 156 (1.4%) patients had been diagnosed with COPD. Majority of COVID-19 patients with COPD had other existing comorbidities: hypertension, diabetes mellitus, chronic cardiac disease, and chronic kidney disease. COPD patients more commonly present with severe or critical COVID-19. COPD patients with COVID-19 were at higher risk to experience in-hospital mortality, respiratory failure, and to be admitted in the ICU. Smokers were more likely to present with higher COVID-19 severity and experience in-hospital mortality. Conclusion: Our study supports that the growing evidence that COPD among COVID-19 patients is a risk for higher mortality, more severe form of COVID-19, higher ICU admission, and higher respiratory failure needing ventilatory support. Smoking increases risk for developing severe COVID-19 and mortality.

The control of air quality in museums or storages is of fundamental interest for the conservation of historic artifacts. The present work reports an example of application of RFID sensors developed in the European project SensMat and dedicated to this issue. The sensors are based on the varia-tion of property of an RFID tag coupled to a sensitive silver thin film exposed to the environment. As it will be described in the paper, such low cost sensors are interrogated by a commercial reader and provide the environmental corrosivity index and thus the presence of pollutants. The selected case study concerns the monitoring of pollution by H2S in a building dedicated to conservation and restoration of archeological and historical woods. The ability of sensors to map spatially the corrosivity within buildings is highlighted.

Annually, more than 1.5 million preventable new hepatitis B (HBV) infections continue to occur, with an estimated global burden of 296 million individuals living with chronic hepatitis B infection. This substantial health challenge results in over 820,000 annual deaths attributed to complications such as liver cirrhosis and hepatocellular carcinoma (HCC). HBV vaccination remains the cornerstone of public health policy to prevent chronic hepatitis B and its related complications. It serves as a crucial element in the global effort to eliminate HBV, as established by the World Health Organization (WHO), with an ambitious 90% vaccination target by 2030. However, reports on global birth dose coverage reveal substantial variability, with an overall coverage rate of only 46%. This comprehensive review thoroughly examines global trends in HBV vaccination coverage, investigating the profound impact of vaccination on HBV prevalence and its consequences across diverse populations, including both high-risk and general demographics. Additionally, the review addresses the formidable challenges and facilitating factors essential for achieving WHO's HBV vaccination coverage objectives and elimination strategies in the coming decade and beyond.

PET imaging of bacterial infection could potentially provide added benefit for patient care by non-invasive means. [68Ga]Ga-desferrioxamine B – a radiolabelled siderophore – shows specific uptake by human-pathogenic bacteria like Staphylococcus aureus or Pseudomonas aeruginosa as well as sufficient serum stability for clinical application. Here, we provide data for automated production of [68Ga]Ga-desferrioxamine B on two different cassette based synthesis modules (Modular-Lab PharmTracer and GRP 3V) using commercially available cassettes together with an approved 68Ge/68Ga radionuclide generator. Quality control including determination of radiochemical purity as well as a system suitability test was set up via RP-HPLC on a C18 column. The two described production processes, using an acetic acid/acetate buffer system with ascorbic acid as a radiation scavenger for radiolabelling, yield ready-to-use formulations with sufficient activity yield. Batch data showed radiochemical purity of &gt;95 % as determined by RP-HPLC and ITLC as well as excellent stability over 2 hours post production. Specifications for routine production were set up and validated with four master batches for each synthesis module. Based on this study, an academic clinical trial for imaging of bacterial infection was initiated. Both described synthesis methods enable reproducible, automated in-house production of [68Ga]Ga-desferrioxamine B for clinical application.

Antipsychotic drug (APD) medication can lead to metabolic dysfunctions and weight gain, which together increase morbidity and mortality. Metabolically active visceral adipose tissue (VAT) in particular plays a crucial role in the etiopathology of these metabolic dysregulations. Here we studied the effect of 12 weeks drug medication by daily oral feeding of clozapine and haloperidol on the perirenal fat tissue as part of VAT of male and female Sprague Dawley rats in the context of complex former investigations on brain, liver, and blood. Adipocyte area values were determined as well as triglycerides, non-esterified fatty acids (NEFAs), glucose, glycogen, lactate, malondialdehyde equivalents, ferric iron and protein levels of Perilipin-A, hormone-sensitive-lipase (HSL), hepcidin, glucose transporter-4 (Glut-4) and insulin receptor-ß (IR-ß). We found increased adipocyte mass in males with slightly higher adipocyte area values in both males and females under clozapine medication. Triglycerides, NEFAs, glucose and oxidative stress in the medicated groups were unchanged or slightly decreased. In contrast to controls and haloperidol medicated rats, perirenal adipocyte mass and serum leptin levels were not correlated under clozapine. Protein expressions of perilipin-A, Glut-4 and HSL were decreased under clozapine medication. IR-ß expression changed sex-specifically in the clozapine medicated groups associated with higher hepcidin levels in the perirenal adipose tissue of clozapine-medicated females. Taken together, clozapine and haloperidol have a smaller effect than expected on perirenal adipose tissue. The perirenal adipose tissue shows only weak changes in lipid and glucose metabolism. The main changes can be seen in the proteins examined and probably in their effect on liver metabolism.

Background: Across the world, antibiotic resistance is a grave problem. To address this issue, it is necessary to investigate new antibiotic sources. Aim of the study: Egypt's diverse soil habitats were used to produce bacterial Myxopyronin B, which was then tested for antimicrobial activity in preclinical animal studies and randomized human clinical trials stages 1/2. Type of the study: Screening experimental study. Methodology: Egypt's various soil conditions were examined for the development of bacterial isolates that produced the antibiotic compound Myxopyronin B. Reversed phase HPLC was used to purify Myxopyronin B. To determine the test antibiotic's minimum inhibitory concentration( MIC) and invitro antibacterial activity, the Broth microdilution method and the Paper disc diffusion assay were utilized. Moreover, in vivo antibacterial spectrum, adverse medication responses, and pharmacokinetics were found in preclinical animal testing stages and phases 1/2 of randomized clinical studies involving volunteer humans. Results: Myxopyronin B was generated from the culture supernatant of Myxococcus SDU36, the main soil bacterial isolate cultured on a Casein yeast peptone plate. With MICs less than 100 mcg/ml, the test antibiotic prevented the growth of several Gram +ve bacteria, whereas, at MICs higher than 100 mcg/ml, it inhibited the development of a small number of Gram -ve bacteria, including Escherichia coli. However, eukaryotic cells—such as those found in fungi and humans—were unaffected. The test antibiotic was seen to inhibit prokaryotic DNA-dependent RNA polymerase( RNLP), indicating its bactericidal activity. Mean Cmax was 9-10 mcg/ ml at mean Tmax 1 hour when 600 mg dose was orally administered in randomized human clinical trials phases 1/2, and T1/2 reached 2.25 hours following first-order kinetics of elimination. Duration of its action was nearly 8 hours after oral administration. Rare toxicity was detected during preclinical and randomized human clinical trials phases 1/2 in the form of mild diarrhea and GI upset in less than 7 % of experimental candidates. It exhibited approximately 90% plasma protein binding, especially with albumin which resulted in prolonged therapeutic action. It showed a concentration dependant antibiotic killing effect. With the concentration-dependent killing pattern, the higher the drug concentration relative to the pathogen minimum inhibitory concentration( MIC), the greater the rate and extent of antimicrobial activity. Conclusion: The present study was promising due to the production of the bactericidal antibiotic Myxopyronin B from Myxococcus sp. SDU36 isolated from different soil environments in Egypt.

We report the treatment of a 21-year-old female Covid-19 patient by a novel combination of minocycline and a guanosine-restricted diet. Minocycline is an antibiotic with well documented broad spectrum anti-viral effects, including evidence of activity against SARS-CoV-2. Deprivation of guanosine has been documented as an effective anti-viral modality in vitro and in animal models, and specific in vitro activity against CoV-SARS-2 has been reported. The patient's symptoms resolved rapidly.

The morphology and maturation process of gonads of 70 Burmeister´s porpoises, with body lengths ranging 135–183 cm (n= 34 females) and 64.5-182 cm (n= 36 males) were described. Samples were collected in six ports of central and northern Peru in 1987-1999. In the field, females were classified as immature, mature (resting, lactating, pregnant) and males as immature, pubescent and mature based on, respectively, the presence of ovarian corpora and the relative quantity of semen in cut epididymides. The ovaries of P. spinipinnis are ovoid or bean-shaped and flattened, with corpora modifying surface appearance. In the laboratory, ovaries were examined macro- and microscopically, measured, weighed and sliced in 1-3 mm sections. The number of corpora ovarica (lutea, albicantia, atretica) found in each ovary as well as their macroscopic and microscopic characteristics were documented in some detail. The follicles, their oocytes and nucleus were measured. Follicular development in P. spinipinnis is predominantly left-sided, but occurs in both ovaries in 16.3% of females, mainly in those with numerous corpora. Macroscopically, several corpora atretica with luteinization had characteristics similar to those of corpora albicantia, making microscopic determination essential. Inconclusive evidence of recent ovulation was found in January. Two of three immature females showed good follicular development in March and April. The body length at 50% sexual maturity in females was estimated at 152.7 cm. There was no evidence of reproductive senescence. The testes of P. spinipinnis are elongated and cylindrical. Of the 36 males examined macroscopically, 7 were immature, 5 pubescent and 24 mature. The histological analysis determining the presence and abundance of Sertoli cells, spermatogonia, spermatocytes, spermatids and spermatozoa, the relative amount of interstitial tissue, the elongation and mean diameter of the seminiferous tubules and the relative size of the lumen allowed to confidently determine sexual maturity status. The field evaluation of maturity based on the presence of sperm in the epididymides is a useful but, in 8.3% of cases, not exact method. For males the body length at 50% sexual maturity was estimated at 157 cm. No histological evidence of male reproductive seasonality was found. Spermatogenesis was perceptible year-round and tubule diameters had non-specific variations for each month.

Objective: In this pilot study, we described the gross motor development of infants aged 4 to 24 months with congenital heart disease (CHD) and assessed through a systematic develop­mental screening programme, with individualised motor interventions. Methods: Thirty infants who had cardiac repair underwent gross motor evaluations using the AIMS at 4 months, and the Bayley-III at 12 and 24 months. Results: Based on AIMS, 80% of 4-month-old infants had a delay in gross motor development and required physical therapy. Gross motor abilities significantly improved by 24 months. Infants who benefited from regular physiotherapy tended to show better improvement in motor scores. Conclusion: Our study highlights the importance of early motor screening in infants with CHD and suggests a potential benefit of early physical therapy in those at-risk. Further research is needed to assess the effectiveness of systematic developmental screening and individualized inter­vention programmes at identifying at risk patients, and their impact on developmental outcomes.

Respiratory syncytial virus (RSV) RNA synthesis takes place in cytoplasmic viral factories also called inclusion bodies (IBs), which are membrane-less organelles concentrating the viral RNA polymerase complex. IBs assembly is driven by liquid-liquid phase separation promoted by interactions between the viral nucleoprotein N and the phosphoprotein P. We recently demonstrated that cyclopamine (CPM) inhibits RSV multiplication by disorganizing and hardening IBs. Although a single mutation in the viral transcription factor M2-1 induced resistance to CPM, the mechanism of action of CPM still remains to be characterized. Here, using FRAP experiments on reconstituted pseudo-IBs both in cellula and in vitro, we first demonstrated that CPM activity depends on the presence of M2-1 together with N and P. We show that CPM impairs the competition between P and RNA binding to M2-1. As mutations on both P and M2-1 induced resistance against CPM activity, we suggest that CPM may affect the dynamics of the M2-1−P interaction, thereby affecting the relative mobility of proteins contained in RSV IBs. Overall, our results reveal that stabilizing viral protein-protein interactions is an attractive new antiviral approach. They pave the way for the rational chemical optimization of new specific anti-RSV molecules.

The German Constitutional Court’s climate verdict provides a re-interpretation of liberal- democratic core concepts and is highly relevant for liberal constitutional law in general – including EU and international law. The verdict accepts human rights as intertemporal and globally applicable; it applies the precautionary principle to these rights and frees them from the misleading causality debate. However, the court fails to address the most important violations of human rights, and it categorised climate policy as a greater threat to freedom than climate change. And the court does not make it clear that the Paris 1.5-degree limit implies a radically smaller carbon budget. Furthermore, little attention has so far been paid to the fact that the ruling implies an obligation for more EU climate protection, especially since most emissions are regulated supranationally. To be effective, the EU emissions trading system demands a reform, which should go well beyond the existing EU proposals to enable societal transformation to sustainability.

Dog Assisted Therapy is hypothesized to lower stress in children with Autism Spectrum Disorder (ASD) and children with Down Syndrome (DS), which may be visible on a physiological level. In this study, we measured Heart Rate Variability (HRV) and salivary cortisol of 20 children with DS or ASD at the beginning and end of 6 weekly sessions of Dog-Assisted Therapy. We found a decrease of cortisol levels during single sessions, but no overall effect after 6 sessions (6 weeks). The effect of Dog Assisted Therapy on the increase of HRV could not be confirmed. This study is one of the first to use physiological measurements to test the effects of DAT.

Cerebral palsy (CP) is the most common movement disorder in children with a prevalence rang-ing from 1.5 to 4 per 1000 live births. CP is caused by a non-progressive lesion of the developing brain, leading to progressive alterations of the musculoskeletal system, including spasticity, often leading to the development of fixed contractures, necessitating tendon lengthening surgery. Total RNA-sequencing analysis was performed on semitendinosus tendons from diplegic and tetraple-gic CP patients subjected to tendon lengthening surgery compared to control patients undergoing anterior cruciate ligament reconstructive surgery. Tetraplegic CP patients showed increased ex-pression of genes implicated in collagen synthesis and extracellular matrix (ECM) turnover, while only minor changes were observed in diplegic CP patients. In addition, tendons from tetra-plegic CP patients showed an enrichment for upregulated genes involved in vesicle-mediated transport and downregulated genes involved in cytokine and apoptotic signaling. Overall, our results indicate increased ECM turnover with increased net synthesis of collagen in tetraplegic CP patients without activation of inflammatory and apoptotic pathways similar to observations in athletes where ECM remodeling results in increased tendon stiffness and tensile strength. Never-theless, the resulting increased tendon stiffness is an important issue in clinical practice, where surgery is often required to restore joint mobility.

Abiotic stress is responsible for significant reduction in crop plant productivity worldwide. Ultraviolet (UV) radiation is a natural component of sunlight and a permanent environmental stimulus. This study investigated the distinct responses of young wheat and einkorn plants to excessive UV-B radiation (180 min at λmax 312 nm) following foliar pretreatment with 1 µM synthetic cytokinin 4PU-30. Results demonstrated that UV radiation significantly amplified hydrogen peroxide levels in both wheat and einkorn, with einkorn exhibiting more pronounced increase compared to wheat. This elevation indicated the induction of oxidative stress by UV radiation in the two genotypes. Intensified antioxidant enzyme activities and increased accumulation of typical stress markers and non-enzyme protectants were evidenced. Transcriptional activity of genes encoding key antioxidant enzymes was also investigated aiming to elucidate the genetic regulation of the antioxidant systems in both wheat and einkorn seedlings. Our results suggested a role for POX1 and POX7 genes in the UV-B tolerance of the two wheat species as well as a cytokinin stimulated UV-B stress response in einkorn mediated through upregulation of the tau subfamily gene GSTU6. Based on these findings it could be concluded that 4PU-30 had the potential of alleviating oxidative stress by attenuating the symptoms of superfluous UV-B illumination in the two examined plant species.

One of the oldest problems in physics is that of calculating the motion of N particles under a specified mutual force: the N-body problem. Much is known about this problem if the specified force is non-relativistic gravity, and considerable progress has been made by considering the problem in one spatial dimension. Here I review what is known about the relativistic gravitational N-body problem. Reduction to one spatial dimension has the feature that gravitational radiation is absent, thereby allowing for a clear comparison between the physics of one-dimensional relativistic and non-relativistic self-gravitating systems. After describing how to obtain a relativistic theory of gravity coupled to N point particles, I discuss in turn the 2-body, 3-body, 4-body, and N-body problems. Quite general exact solutions can be obtained for the 2-body problem, unlike the situation in general relativity in 3 spatial dimensions for which only highly specified solutions exist. The 3-body problem exhibits mild forms of chaos, and provides one of the first theoretical settings in which relativistic chaos can be studied. For N4 other interesting features emerge. Relativistic self-gravitating systems have a number of interesting problems awaiting further investigation, providing us with a new frontier for exploring relativistic many-body systems.

Data on helminth parasites and epizoites is presented for the long-beaked and short-beaked common dolphins from the Southeast Pacific. Sampling in 1985-2000 was conducted mainly at six fishing ports in Peru and Ecuador where cetaceans were landed. From a total of 473 common dolphins sampled, we identified helminths including three species of Trematoda: Nasitrema globicephalae, Pholeter gastrophilus and Braunina cordiformis; three species of Nematoda, which includes Anisakis spp., Crassicauda sp. and Halocercus sp.; and two cestodes Tetrabothrius forsteri and Clistobothrium delphini (formerly Phyllobothrium delphini). No acanthocephalans were observed. No statistically significant sexual and ontogenetic variation in helminth prevalence was detected after which samples were pooled. The highest prevalence in the long-beaked common dolphin (n=440) was observed for N. globicephalae (96.3%) in cranial sinuses, Crassicauda sp. (83.3%) in mammary glands, Crassicauda sp. (78.8%) infesting the cranial sinuses, followed by Cl. delphini (28.6%) in the blubber and P. gastrophilus and B. cordiformis (20.4%) in the digestive tract. Although comparative testing was unfeasible due to minimal samples of short-beaked common dolphin (n=33), several of the same helminth species were found, but not N. globicephalae nor B. cordiformis. No cyamids were encountered while pseudo-stalked barnacles Xenobalanus globicipitis were common. No new (global) helminth host records are revealed for common dolphins, but this study presents a first checklist of parasites separately for the Southeast Pacific long-beaked and short-beaked common dolphins. Future work should include exhaustive laboratory-based necropsies, enhanced sampling of the short-beaked form, focus on intermediate hosts and parasitic pathology, including potential human health impact from consumption of small cetaceans.

Chronic Hepatitis B (CHB) Virus infection is major etiological factor for liver cirrhosis and/ or liver cancer. The viral protein, major contributor in predisposition of chronicity and Hepatocellular Carcinoma (HCC) is Hepatitis B x (HBx) protein. Its dynamic subcellular distribution to an extent determines its multifactorial role. It is a regulatory protein which modulates viral as well as host machinery in favours to HBV persistence. An insight on HBx stabilising factors is critical for therapeutic purpose. The precise role of HBx in the pathogenesis of Chronicity of HBV is not known. Summary: This review comprehensively summarizing different mechanisms and their regulation by HBx protein with respect to chronicity and HCC emphasising viral persistence. Key Messages 1. HBx is a key protein for viral persistence. 2. Dynamic subcellular distribution of HBx determines its function. 3. HBx modulates cellular machinery to favours HBV survival. 4. HBx affects various intermediary mechanisms contributing to disease progression. 5. HBx may be a potent target to prevent the disease progression towards HCC.

Still, the most common in vitro model for absorption, distribution, metabolism and excretion (ADME) purposes is the Caco-2 cell line. However, clear differences in gene- and protein expression towards the small intestine and an at best fair prediction accuracy of intestinal drug absorption restrict the usefulness as model for intestinal epithelial cells. To overcome these limitations, we evaluated a panel of low-passaged patient-derived colorectal cancer cell lines of the HROC collection concerning similarities to small intestinal epithelial cells and their potential to predict intestinal drug absorption. After initial screen of a larger panel, ten cell lines with confluent outgrowth and long-lasting barrier forming potential were further characterized in close detail. Tight junctional complexes and microvilli structures were detected in all lines, differentiated epithelial cells were abundant in 7/10. All lines expressed multiple transporter molecules, with expression levels in three lines being close to those of small intestinal epithelial cells. Compared to the Caco-2 model, three HROC lines demonstrated both higher similarity to jejunal epithelial tissue cells and higher regulatory potential of relevant drug transporters. In sum, these lines would be better suited human small intestinal epithelium models for basic and translational research; especially for ADME studies.

Early-onset colorectal cancer (EOCRC) is defined as a diagnosis of colorectal cancer (CRC) in individuals younger than 50 years of age. While overall CRC rates in the United States (US) decreased between 2001 and 2018, EOCRC rates have increased. This research project aims to evaluate the feasibility and acceptability of Time-Restricted Eating (TRE), Mindfulness, or TRE combined with Mindfulness among young to middle-aged adults at risk of EOCRC. Forty-eight participants will be randomly assigned to one of four groups: TRE, Mindfulness, TRE &amp; Mindfulness, or Control. Data on feasibility, adherence, and acceptability will be collected. Measures assessed at baseline and post-intervention will include body weight, body composition, dietary intake, physical activity, sleep behavior, circulating biomarkers, hair cortisol, and gut microbiome. Effects of the intervention on the following will be examined: 1) acceptability and feasibility; 2) body weight, body composition, and adherence to TRE; 3) circulating metabolic, inflammation, and oxidative stress biomarkers; 4) intestinal inflammation; and 5) the gut microbiome. TRE combined with Mindfulness holds promise for stress reduction and weight management among individuals at risk of EOCRC. The results of this pilot study will inform the design and development of larger trials aimed at preventing risk factors associated with EOCRC.

Background: Approximately 10-20% of subjects vaccinated with HBsAg-based hepatitis B virus (HBV) vaccines are non-responders. BM32 is a recombinant grass pollen allergy vaccine containing the HBV-derived preS surface antigen as immunological carrier protein. PreS includes the binding site of HBV to its receptor on hepatocytes. We investigated if immunological non-responsiveness to HBV after repeated HBsAg-based vaccinations can be overcome by immunization with VVX001 (i.e., Alum-adsorbed BM325, a component of BM32). Methods: A subject failing to develop protective HBV-specific immunity after HBsAg-based vaccination received five monthly injections of 20 µg VVX001. PreS-specific antibody responses were measured by ELISA and micro-array technology. Serum reactivity to subviral particles of different HBV genotypes was determined by sandwich ELISA. PreS-specific T cell responses were monitored by CFSE staining and subsequent FACS analysis. HBV neutralization was assessed using cultured HBV-infected HepG2 cells. Results: Vaccination with VVX001 induced a strong and sustained preS-specific antibody response composed mainly of the IgG1 subclass. PreS-specific IgG antibodies were primarily directed to the N-terminal part of preS containing the NTCP attachment site. IgG reactivity to sub-viral particles as well as to the N-terminal preS-derived peptides was comparable for HBV genotypes A-H. A pronounced reactivity of CD3+CD4+ lymphocytes specific for preS after the complete injection course remaining up to one year after the last injection was found. Maximal HBV neutralization (98.4%) in vitro was achieved 1 month after the last injection which correlated with the maximal IgG reactivity to the N-terminal part of preS. Conclusion: Our data suggest that VVX001 may be used as a preventive vaccination against HBV even in non-responders to HBsAg-based HBV vaccines.

The proliferation and survival signals emanating from the B-cell receptor (BCR) constitute a crucial aspect of mature lymphocyte’s life. Dysregulated BCR signaling is considered a potent contributor to tumor survival in different subtypes of B cell non-Hodgkin lymphomas (B-NHLs). In the last decade, emergence of BCR-associated kinases as rational therapeutic targets has led to the development and approval of several small molecule inhibitors targeting either Bruton's tyrosine kinase (BTK), spleen tyrosine kinase (SYK), or phosphatidylinositol 3 kinase (PI3K), offering alternative treatment options to standard chemoimmunotherapy, and making some of these drugs valuable assets in the anti-lymphoma armamentarium. Despite their initial effectiveness, these precision medicine strategies are limited by primary resistance in aggressive B-cell lymphoma like diffuse large B cell lymphoma (DLBCL) and mantle cell lymphoma (MCL), especially in the case of first generation BTK inhibitors. In these patients, BCR-targeting drugs often fail to produce durable responses, and nearly all cases eventually progress with a dismal outcome, due to secondary resistance. This review will discuss our current understanding of the role of antigen-dependent and antigen-independent BCR signaling in DLBCL and MCL and will cover both approved inhibitors and investigational molecules being evaluated in early preclinical studies. We will discuss how the mechanisms of action of these molecules, and their off/on-target effects can influence their effectiveness and lead to toxicity, and how our actual knowledge supports the development of more specific inhibitors and new, rationally based, combination therapies, for the management of MCL and DLBCL patients.

This study describes the seasonal course of denitrifying and nitrate reducing bacteria in a dimictic mesotrophic lake (Lake Scharmützelsee, Brandenburg, Germany) within a three-year period from 2011 to 2013. The bacterial cell numbers were quantified by fluorescence microscopy, most probable number (MPN) and PCR dependent quantification of the chromosomal 16S rDNA and of the nirS and nirK gene copy number. The highest seasonal differences (up to three orders of magnitudes) has been measured by MPN in the epilimnion. This variation was not reflected by PCR dependent approaches or direct microscopical enumeration. At adverse conditions (low temperature and/or low nitrate concentrations), the differences between MPN and gene copy numbers increased up to five orders of magnitudes and decreased to one magnitude at favorable environmental conditions. These results can be explained best by an increasing ratio of viable but not cultivable (VBNC) cells or dead cells at impairing conditions. In the hypolimnion, the courses of MPN and nir gene copy numbers were similar. This can be explained by higher feeding pressure and therefore smaller amounts of dormant cells. In the pelagial in general, the total cell numbers enumerated by either microscopical or molecular approaches were similar. In the sediment, more than 99 % of the DNA was obviously not related to viable bacteria but was rather “dead DNA” in dead cells or adsorbed to particle surfaces.

This paper aims to outline the effectiveness of modern universal gate quantum computers when utilizing different configurations to solve the B-SAT(Boolean Satisfiability) problem. The quantum computing experiments are performed using Grover’s Search algorithm to find a valid solution. The experiments are performed under different variations to demonstrate their effects on the results. Changing the number of shots, qubit mapping, and using a different quantum processor are all among the experimental variables. The study also branches into a dedicated experiment highlighting a peculiar behavior that IBM quantum processors exhibit when running circuits with a certain number of shots.

Peanut hulls (PH) are an edible food waste that is an underutilized food source for human consumption. While edible and palatable, they are mainly diverted to livestock feed or building materials. Here, we describe existing literature on human food valorization of PHs and propose methods to optimize recapturing nutrients (e.g. protein, fiber, polyphenols) lost by treating PHs as waste. Incorporated into common foods, PHs can be processed into functional ingredients to improve nutrient-density and the corresponding positive health outcomes associated with increases in plant foods. PH valorization can also address additional priorities of the UN Sustainable Development Goals using a Food Systems Approach (FSA) including food waste, increasing economic opportunities for farmers, and increasing the availability of healthy shelf-stable foodstuffs to address food security. Recent advances in sustainable food processing technologies can be utilized to safely incorporate peanut hulls into human food streams. We propose future applications that could make meaningful impacts to food availability and the nutritional composition of common foods. While the limited literature on this topic spans several decades, no global operations exist to incorporate peanut hulls and most publications precede the technological ‘green revolution’. The approaches outlined in this review may help bolster commercialization of this underutilized and nutritious food potentially improving opportunities for multiple global stakeholders.

Introduction: OS2966 is a fist-in-class, humanized and de-immunized monoclonal antibody which targets the adhesion receptor subunit, CD29/β1 integrin. CD29 expression is highly upregulated in glioblastoma and has been shown to drive tumor progression, invasion, and resistance to multiple modalities of therapy. Here, we present a novel Phase I clinical trial design addressing several factors plaguing effective treatment of high-grade gliomas (HGG). Study Design: This 2-part, ascending-dose, Phase I clinical trial will enroll patients with recurrent/progressive HGG requiring a clinically-indicated resection. In Study Part 1, patients will undergo stereotactic tumor biopsy followed by placement of a purpose-built catheter which will be used for intratumoral, convection-enhanced delivery (CED) of OS2966. Subsequently, patients will undergo their clinically-indicated tumor resection followed by CED of OS2966 to the surrounding tumor-infiltrated brain. Matched pre- and post-infusion tumor specimens will be utilized for biomarker development and validation of target engagement by receptor occupancy. Dose escalation will be achieved using a unique concentration-based accelerated titration design. Discussion: The present study design leverages multiple innovations including: 1) the latest CED technology, 2) 2-part design including neoadjuvant intratumoral administration, 3) a first-in-class investigational therapeutic, and 4) concentration-based dosing. Trial registration: A U.S. Food and Drug Administration (FDA) Investigational New Drug application (IND) for the above protocol is now active. A Phase I trial is registered at clinicialtrials.gov (NCT04608812).

Abstract: Medication overuse headaches is a frequent phenomenon observed in individuals suf-fering from chronic headaches. It arises due to the excessive consumption of pain-relief medica-tions, resulting in the escalation and continuous persistence of headache symptoms. Nevertheless, the prevalence and distinctive characteristics of medication overuse headaches in the pediatric population have not been comprehensively explored. The primary objective of this research is to delineate the features of medication overuse headaches in children, particularly emphasizing the investigation of its epidemiology and the diagnostic patterns for headaches. We conducted a ret-rospective study by and analyzed the medical records of children and adolescents who were evaluated at outpatient pediatric headache clinic at the Bnai Zion medical center for headache during the period spanning 2007 to 2017. Our study encompassed a cohort of 1008 patients expe-riencing headaches. Among these participants, 268 individuals (26.6%) were diagnosed with mi-graine, 250 (24.8%) exhibited tension-type headaches (TTH), and 490 (48.6%) were classified as having undifferentiated headaches. Out of the whole group, 65 had chronic headaches: 35 (54%) with migraine, 20 (30%) with tension-type headaches (TTH), and 10 (15%) with undifferentiated headache of childhood, with the majority (73%) being female.In summary, medication overuse headaches are a prevalent issue among children grappling with chronic headaches. Intriguingly, they appear to be more pronounced within the tension-type headache (TTH) group compared to migraine sufferers, and exhibit a higher prevalence among females. This study underscores the significance of early detection and careful management of medication overuse headaches in pedi-atric cases, shedding light on its distinct characteristics in the realm of childhood headache disor-ders. Further research is warranted to elucidate the underlying factors contributing to the ob-served gender disparity and the distinct prevalence rates among different headache subtypes.

Hemicellulose is one of the most important natural polysaccharides in nature. Hemicellulose from different sources varies in chemical composition and structure, which in turn affects the modification effects and industrial applications. Grain and oil by-products (GOBP) are important raw materials for hemicellulose. This article reviews the modification methods of hemicellulose in GOBP. The effects of chemical and physical modification methods on the properties of hemicellulose biomaterials were evaluated. The potential applications of GOBP hemicellulose in films, hydrogel, Three-dimensional (3D) printing and adsorbent are discussed. Future research directions and recommendations are also proposed to provide theoretical foundations and technical support for the efficient utilization of these by-products.

In a context of increasingly necessary energy transition, precise modelling of profiles for low-voltage (LV) network consumers is crucial to enhance hosting capacity. Typically, load curves for these consumers are estimated through measurement campaigns conducted by Distribution System Operators (DSO) for a representative subset of customers or through the aggregation of load curves from household appliances within a residence. With the instrumentation of smart meters becoming more common, a new approach to modelling profiles for residential customers is proposed to make the most of the measurements from these meters. The disaggregation model estimates the load profile of customers on a low-voltage network by disaggregating the load curve measured at the secondary substation level. By utilizing only the maximum power measured by Linky smart meters, along with the load curve of the secondary substation, this model can estimate the daily profile of customers. For 48 secondary substations in our dataset, the model obtained an average symmetric mean average percentage error (SMAPE) error of 4.91% in reconstructing the load curve of the secondary substation from the curves disaggregated by the model. This methodology can allow the estimation of the daily consumption behaviors of the low-voltage customers. In this way, we can safely envision solutions that enhance the grid hosting capacity.

Bacterial collections are invaluable tools for microbiologists. However, their practical use is compromised by imprecise taxonomical assignation of bacterial strains. This is particularly true for soft rotting plant pathogens of the Pectobacterium genus. To solve this difficulty, we analyzed the taxonomic status of 265 Pectobacterium strains deposited at CIRM-CFBP collection from 1944 to 2020. This collection gathered Pectobacterium strains isolated in 27 countries from 32 plant species representing 17 botanical families or from non-host environments. MLSA approach completed by genomic analysis of 15 strains was performed to update the taxonomic status of these 265 strains. Results showed that the CIRM-CFBP Pectobacterium collection harboured at least one strain of each species to the exception of P. polonicum. Yet, 6 strains could not be assigned to any of the described species and may represent at least two new species. Surprisingly, the P. versatile species, recently described in 2019, is the most prevalent species among CIRM-CFBP strains. Analysis of P. versatile strains revealed that this species is endemic all over the world on various host plants and environments. At the opposite, other species gathered strains isolated from only one botanical family or exclusively from fresh water environment. Our work also revealed new host plants for several Pectobacterium spp.

The BNT162b2 vaccine is globally used for preventing morbidity and mortality related to COVID-19. Cancer patients have had priority for receiving the vaccine due to their diminished immunity. This study reports the response of administering the 3rd and 4th vaccine doses to can-cer patients receiving active anti-neoplastic treatment. 142 patients have received two doses of the mRNA-based BNT162b2 COVID-19 vaccine, while 76 and 25 patients have received three and four doses, respectively. The efficacy of the humoral response following two vaccine doses was diminished in cancer patients, especially in the group of patients receiving chemotherapy. In a multivariate analysis, patients after three and four BNT162b2 vaccine doses were more likely to have antibody titers in the upper tertile compared to patients after two doses of the vaccine (odds ratio (OR) 7.62 (95% CI 1.38-42.12), p=0.02 and 17.15 (95% CI 5.01-58.7), p<0.01, respective-ly). Unlike the response after two doses, the 3rd and 4th BNT162b2 vaccine booster doses, had an increased efficacy of 95-100% in cancer patients while on active treatment. This result could be explained by different mechanisms including the development of memory B cells.

Hepatitis B virus (HBV) is known to cause severe liver diseases such as acute or chronic hepatitis, liver cirrhosis and hepatocellular carcinoma. Chronic hepatitis B (CHB) infection is a major health problem with nearly 300 million individuals infected worldwide. Currently, nucleos(t)ide analogs (NAs) and interferon alpha are clinically approved treatments for HBV infection. NAs are potent antiviral agents that bind to HBV polymerase and block viral reverse transcription and replication. Besifovir dipivoxil maleate (BSV) is a newly developed NA against HBV in the form of acyclic nucleotide phosphonate that is available for oral administration similar to adefovir and tenofovir. Until now, resistance to BSV treatment has not been reported. In this study, we found a CHB patient who showed viral breakthrough after long-term treatment with BSV. The isolated HBV DNA from patient’s serum were cloned into the replication-competent HBV 1.2mer and the sequence of reverse transcriptase (RT) domain of HBV polymerase were analyzed. We also examined the drug susceptibility of generated clones in vitro. Several mutations were identified in HBV RT domain. A particular mutant harboring ten RT mutations showed resistance to BSV treatment in vitro. The ten mutations include rtV23I (I), rtH55R (R), rtY124H (H), rtD134E (E), rtN139K (K), rtL180M (M), rtM204V (V), rtQ267L (L), rtL269I (I) and rtL336M (M). To further identify the responsible mutations for BSV resistance, we performed in vitro drug susceptibility assay on several artificial clones. As a result, our study revealed that rtL180M (M) and rtM204V (V) mutations, already known as lamivudine-resistant mutations, confer resistance to BSV in the CHB patient.

Background: Osteoporosis and bone fractures affect health and quality of life. Since bone disease is multifactorial, identifying risk factors is key in prevention. There are multiple reports on how viral hepatitis especially chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are affecting bone disease, but results vary. Here, we analyzed the potential association between CHB/CHC and osteoporosis or bone fractures in a large outpatient cohort in Germany. Methods: We included 3,136 outpatients with CHB and 15,608 matched non-hepatitis individuals as well as 2,867 outpatients with CHC and 14,335 matched non-hepatitis individuals from the Disease Analyzer Database between 2005 and 2022. The main outcome was the 5-year cumulative incidence of osteoporosis and bone fractures as a function of either CHB or CHC. Results: Within 5 years of the index date, 2.9% vs. 1.6% of patients with and without CHB were diagnosed with osteoporosis (p=0.001) and 1.0% vs. 0.4% were diagnosed with bone fractures (p<0.001). Moreover, 3.3% of CHC patients and 2.2% of individuals without hepatitis were diagnosed with osteoporosis (p=0.002). In Cox-regression analyses, CHB was significantly associated with an increased risk for osteoporosis (HR: 1.76) and fractures (HR:2.43) and CHC with osteoporosis (HR: 1.54). For both CHB and CHC, the association with osteoporosis was restricted to the female subgroup. Conclusion: CHB and CHC are associated with osteoporosis in women. CHB in male patients is associated with a higher risk of fractures. More research is are needed to understand the underlying pathophysiological mechanisms.

Acidic ostreolysin A/pleurotolysin B (OlyA/PlyB, formerly known as ostreolysin (Oly), and basic 20 kDa equinatoxins (EqTs) are cytolytic proteins isolated from the edible mushroom Pleurotus ostreatus and the sea anemone Actinia equina, respectively. Both toxins, although from different sources, share many similar biological activities: (i) colloid-osmotic shock by forming pores in cellular and artificial membranes enriched in cholesterol and sphingomyelin; (ii) increased vascular endothelial wall permeability in vivo and perivascular oedema; (iii) dose-dependent contraction of coronary vessels; (iv) haemolysis with pronounced hyperkalaemia in vivo; (v) bradycardia, myocardial ischemia and ventricular extrasystoles accompanied by progressive fall of arterial blood pressure and respiratory arrest in rodents. Both types of toxins are haemolytic within nanomolar range concentrations, and it seems that hyperkalaemia plays an important role in toxin cardiotoxicity. However, it was observed that the haemolytically more active EqT III is less toxic than EqT I, the most toxic and least haemolytic EqT. In mice, EqT II is more than 30 times more toxic than OlyA/PlyB when applied intravenously. These observations imply that haemolysis with hyperkalaemia is not the sole cause of the lethal activity of both toxins. Additional mechanisms responsible for lethal action of the two toxins are direct effects on heart, coronary vasoconstriction and related myocardial hypoxia. In this review, we appraise the pathophysiological mechanisms related to the chemical structure of OlyA/PlyB and EqTs, as well as their toxicity.

Viruses can induce the fusion of infected and neighboring cells, leading to the formation of syncytia. Cell-cell fusion is mediated by viral fusion proteins on the plasma membrane of infected cells that interact with cellular receptors on neighboring cells. Viruses use this mechanism to spread rapidly to adjacent cells or escape host immunity. For some viruses, syncytium formation is a hallmark of infection and a known pathogenicity factor. For others, the role of syncytium formation in viral dissemination and pathogenicity remains poorly understood. Human cytomegalovirus (HCMV) is an important cause of morbidity and mortality in transplant patients and the leading cause of congenital infections. Clinical HCMV isolates have broad cell tropism but differ in their ability to induce cell-cell fusions, and little is known about the molecular determinants. We developed a system to analyze HCMV glycoprotein B (gB) variants in a defined genetic background. HCMV strains TB40/E and TR were used as vectors to compare the fusogenicity of six gB variants from congenitally infected fetuses with those from three laboratory strains. Five of them conferred the ability to induce fusion of MRC-5 human embryonic lung fibroblasts to one or both backbone strains, as determined by a split GFP-luciferase reporter system. The same gB variants were not sufficient to induce syncytia in infected ARPE-19 epithelial cells, suggesting that additional factors are involved. The system described here allows a systematic comparison of the fusogenicity of viral envelope glycoproteins and may help to clarify whether fusion-promoting variants are associated with increased pathogenicity.

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.

Conservation of wildlife depends on precise and unbiased knowledge on the abundance and distribution of species. It is challenging to choose appropriate methods to obtain a sufficiently high detectability and spatial coverage matching the species characteristics and spatiotemporal use of the landscape. In remote regions, such as in the Arctic, monitoring efforts are often resource-intensive and there is a need for cheap and precise alternative methods. Here, we compare an uncrewed aerial vehicle (UAV; quadcopter) pilot-survey of the non-gregarious Svalbard reindeer to traditional population abundance surveys from ground and helicopter to investigate whether UAVs can be an efficient alternative technology. We found that the UAV survey underestimated reindeer abundance compared to the traditional abundance surveys when used at management relevant spatial scales. Observer variation in reindeer detection on UAV imagery was influenced by the RGB greenness index and mean blue channel. In future studies, we suggest to test long-range fixed-wing UAVs to increase the sample size of reindeer and area coverage and incorporate detection probability in animal density models from UAV imagery. In addition, we encourage focus on more efficient post-processing techniques, including automatic animal object identification with machine learning and analytical methods that account for uncertainties.

Alzheimer’s disease (AD) predominantly occurs as a late-onset form (LOAD), involving neurodegeneration and cognitive decline with progressive memory loss. Over time, risk factors and aging promote accumulation of well-known AD pathologies in oxidative stress, amyloid-beta and tau protein pathology, as well as inflammation. Homeostatic glial functions regulate and suppress these AD pathologies; however, other glial states involve increased pro-inflammatory cytokine release and further pathology accumulation. Different stresses can additionally induce cellular senescence, or an irreversible differentiation process resulting in decreased supportive functions and increased, pro-inflammatory cytokine release. While these pathophysiological underpinnings all contribute to LOAD, they require temporal and mechanistic integration. This perspective hypothesizes that when individuals have threshold senescent glia accumulation, they transition from healthy cognition into mild cognitive impairment and LOAD diagnosis. Particularly, senescent microglia are predicted to represent a final threshold required for the tau pathology burden and spreading that corresponds to sustained neurodegeneration and dementia severity. We first explore age-related decline in glia that promote increases in AD pathologies, and then discuss emerging evidence linking oxidative stress, neurons containing tau pathology, and amyloid-beta to microglia, oligodendrocyte progenitor cell, and astrocyte senescence. Our hypothesis proposes that senescent astrocytes and oligodendrocyte progenitors pressure microglia to phagocytose neurons containing tau pathology. The resulting senescent microglia would form neuritic plaques and induce paracrine senescence transitioning into a progressive clinical dementia presentation. This predictive hypothesis can potentially account for why medications used to treat LOAD fail, as previous treatments have not reduced senescent glial burden. It is also coherent with the predominant hypotheses surrounding LOAD, generates testable hypotheses about LOAD, and increases rationale in testing senolytics as targeted treatments for LOAD arrest and reversal.

Combining the Job Demands-Resourses model and the Work Adjustment theory, this research aims to create a theoretical model that considers Leader-Member Exchange (LMX) and Work Adjustment as protective factors, capable of reducing job exhaustion and turnover intention. A convenience sample of 257 Italian employees filled an online self-report questionnaire. A sequential mediation model was tested, which showed that the relationship between LMX and turnover intention is mediated by Work Adjustment and Job Exhaustion. The results show that the higher the LMX, the higher the work adjustment of the workers and the less they will perceive job exhaustion and, consequently, intent to leave the organisation. With a view to primary prevention, the aim was to investigate possible protective factors at work and the risk factors to look out for in order to move in the direction of preventing a malaise phenomenon before it develops with the aim of promoting wellbeing in organisations.

Charcot-Marie-Tooth disease is a hereditary polyneuropathy caused by mutations in Mitofusin-2 (MFN2), a GTPase in the outer mitochondrial membrane involved in the regulation of mitochondrial fusion and bioenergetics. Autosomal-dominant inheritance of a R94Q mutation in MFN2 causes the axonal subtype 2A2A which is characterized by early onset and progressive atrophy of distal muscles caused by motoneuronal degeneration. Here, we studied mitochondrial shape, respiration, cytosolic and mitochondrial ATP content as well as mitochondrial quality control in MFN2-deficient fibroblasts stably expressing wildtype or R94Q MFN2. Under normal culture conditions, R94Q cells had slightly more fragmented mitochondria but a similar mitochondrial oxygen consumption, membrane potential and ATP production as wildtype cells. However, when inducing mild oxidative stress 24 h before analysis using 100 µM hydrogen peroxide, R94Q cells exhibited significantly increased respiration but decreased mitochondrial ATP production. This was accompanied by increased glucose uptake and an upregulation of hexokinase 1 and pyruvate kinase M2 suggesting increased pyruvate shuttling into mitochondria. As these changes coincided with decreased levels of PINK1/Parkin-mediated mitophagy in R94Q cells, we conclude that the disease-causing R94Q mutation in MFN2 causes uncoupling of mitochondrial respiration from ATP production by a less efficient mitochondrial quality control triggered by oxidative stress.

As new treatment modalities are being explored in neuro-oncology, viruses are emerging as a promising class of therapeutics. Virotherapy consists of introduction of either wild-type or engineered viruses to the site of disease, where they exert anti-tumor effect. These viruses can either be non-lytic, in which case they are used to deliver gene therapy, or lytic, which induce tumor cell lysis and subsequent host immunologic response. Replication-competent viruses can then go on to further infect and lyse neighboring glioma cells. This treatment paradigm is being explored extensively in both preclinical and clinical studies for a variety of indications. Virus-based therapies are advantageous due to the natural susceptibility of glioma cells to viral infection, which improves therapeutic selectivity. Furthermore, lytic viruses expose glioma antigens to the host immune system and subsequently stimulate an immune response that specifically targets tumor cells. This review surveys the current landscape of oncolytic virotherapy clinical trials in high-grade glioma, summarizes preclinical experiences, identifies challenges associated with this modality across multiple trials, and highlights potential to integrate this therapeutic strategy into promising combinatory approaches.

The main motive of this study was to find an auxiliary application of the discarded agricultural remnants and poultry waste. Rice straw and chicken feathers are disposed off as landfills or incinerated causing pollution and environmental threats after their primary consumption. In this study epoxy composites were made using varying proportions of these raw and alkali treated materials. Flexural strength of the composites decreased till 35% fiber loading, followed by an increase. Chicken feather composites showed increased impact strength with fiber addition. Alkali treatment improved the mechanical properties of rice straw composites. Alkali treated chicken feather composites showed better impact strength but no significant change in flexural strength. Hybrid composites explicated enhanced properties both before and after alkali treatment corroborating noteworthy interfacial adhesion and synergistic effect of these fibers as ascertained from SEM images. The study evinced a better option for averting environmental problems by recycling these disposed materials.

Human papillomavirus (HPV) is associated with cellular changes of the cervix leading to cancer, which highlights the importance of vaccination in preventing HPV infections and subsequent cellular changes. Women undergoing treatment (LEEP) for high-grade cervical intraepithelial neoplasia (CIN2+) remain at risk for recurrence. This study assesses the effect of post-conization HPV vaccination on the viral status of women six months post-conization, aiming to evaluate the vaccine's effectiveness in preventing recurrence of CIN2+. A retrospective cohort study was conducted among women in Troms and Finnmark who underwent conization in 2022. Using the SymPathy database and the national vaccination register (SYSVAK), we analyzed the vaccination status and HPV test results of women born before 1991, who had not received the HPV vaccine prior to conization. Out of 419 women undergoing conization, 243 met the inclusion criteria. A significant association was found between post-conization HPV vaccination and a negative HPV test at six months follow-up (ARR = 12.1%, P = 0.039). Post-conization HPV vaccination significantly reduced the risk of a positive HPV test at the first follow-up, suggesting its potential in preventing recurrence of high-grade cellular changes. The retrospective design and the insufficient control of confounding variables underscore the necessity for further studies to confirm these findings.

The implementation of Emissions Trading System (ETS) poses significant challenges for the Indian maritime sector. This paper investigates the regulatory implications of ETS, focusing on how these regulations impact compliance and operational practices within the Indian shipping sector. It also analyzes the economic effects, including the financial burden and competitive dynamics faced by the Indian shipping companies in a global context. Additionally, the paper explores various adaptation strategies, emphasizing technological innovations and operational adjustments essential for navigating ETS requirements. By integrating recent industry data and case studies, this study offers a comprehensive overview of how the Indian shipping industry can effectively address the evolving regulatory landscape of ETS.

Lamin A, B and C, the nuclear intermediate-filament proteins, play a role in epigenetic regulation. While Lamin B is expressed in all nucleated cells studied, Lamin A/C are transcribed in most somatic cell types except mature B lymphocytes. Since Epstein-Barr virus (EBV), a human gammaherpesvirus, is associated with tumorigenic processes and is known to alter the epigenotype of its host cells, we studied the expression of the LMNA gene and its epigenetic marks in EBV-carrying human lymphoid cell lines. We observed a high lamin A/C mRNA and protein expression in EBV-immortalized lymphoblastoid cell lines (LCLs) and in group III Burkitt lymphoma (BL) lines where hypomethylated first exons were observed with activating histone marks. In most cell lines with low promoter activity a highly methylated first exon could be detected. Our data showed that methylation of the first exon of LMNA was associated with the downregulation of LMNA expression whereas euchromatic histone marks were enriched at active LMNA promoters in EBV-immortalized LCLs. These data suggest a role for viral latency products to activate LMNAp in EBV-infected latency type III B cells in vitro. Expression of lamin A/C may contribute to the establishment of activated B cell phenotype that needs further explorations.

The prevalence of hepatitis B and delta viruses (HBV/HDV) among people who use drugs (PWUD) remains largely unknown. In the context of one Philadelphia-based harm reduction organization (HRO), this study aimed to assess HBV/HDV prevalence and facilitate linkage to care. Participants completed a demographic HBV/HDV risk factor survey and were screened for HBV and reflexively for HDV if positive for HBV surface antigen or isolated core antibody. Fisher’s exact tests and regression were used to understand relationships between risks and HBV blood markers. Of the 498 participants, 126 (25.3%) were susceptible to HBV, 52.6% had been vaccinated against HBV, and 17.9% had recovered from a past infection. Eleven (2.2%) participants tested positive for isolated HBV core antibody, 10 (2.0%) for HBV surface antigen, and one (0.2%) for HDV antibody. History of incarceration was associated with current HBV infection, while transactional sex and experience of homelessness were predictive of previous exposure. This study found high rates of current and past HBV infection, and a 10% HBV/HDV co-infection rate. Despite availability of vaccine, one quarter of participants remained vulnerable to infection. Findings demonstrate the need to improve low-threshold HBV/HDV screening, vaccination, and linkage to care among PWUD. The study also identified gaps in the HBV/HDV care cascade, including lack of point-of-care diagnostics and lack of support for HROs to provide HBV services.

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.

Maternal obesity is increasingly prevalent and is associated with elevated morbidity and mortality rates in both mothers and children. As the interface between the mother and fetus, the placenta has mediates the impact of the maternal environment on fetal development. Most of the literature data on the effects of maternal obesity on placental functions do not exclude potential confounding factors like metabolic diseases (e.g. gestational diabetes). Moreover, it is now clear that the placental response to maternal environment depends on the fetal sex. In this context, we reviewed how maternal obesity (in the absence of gestational diabetes) affects the human placenta in terms of (i) endocrine function, (ii) morphological characteristics, (iii) nutrient exchanges and metabolism, (iv) inflammatory/immune status, (v) oxidative stress, and (vi) transcriptome, with a focus on fetal sex specificities. A better understanding of sex-specific placental responses to maternal obesity is crucial for improving pregnancy outcomes and the health of mothers and children.

This study assesses attitudes of young adults' (18-30 years old) consumption on local and traditional products in7 European countries. A clustered sample (n=836) from natives of Greece, Bulgaria, Romania, Slovenia, Croatia, Denmark and France was collected, by distributing questionnaires through social media and university mail services. Sample was examined by implementing Principal Component Analysis (PCA) in three different samples; overall and two subgroups, Eastern and Western European countries. Six major factors revealed: consumer behavior, health issues, cost, influence from media and close environment and availability on store. As a result, young adults have a positive attitude to local and traditional food products but they express insecurity for health issues. Cost factor influences less people from Eastern European countries than those from the overall sample (3rd and 5th factor accordingly). Influence of close environment is a different factor in Eastern countries comparing to Western ones that it common with influence from media. Females and older people (25-30 years old) doubt less about TFPs, while media have high influence on consumers’ decisions. Aim of this survey is to create consumer profiles of young adults and create different promotion strategies of local and traditional products among the two groups of countries.

As AI models become more and more common in business and even in our daily lives, it is important to understand what the carbon impact of these models is. Recent papers have shown that this impact can be quite great, i.e., the training of a single high-end model can result in emissions of more than 500t of CO2eq. In this paper we discuss the factors that influence the carbon footprint of AI models, explore what impact different decisions have, and show how the footprint can be reduced. We also examine the footprint of different models to give a guideline on how urgent action is for different organizations.

Social and spatial characteristics of a population often interact to influence health outcomes, suggesting a need to jointly analyze both to offer useful insights in community health. However, researchers have used either social or spatial analyses to examine community-based health issues and inform intervention programs. We propose a combined socio-spatial analytic approach to develop a social network with spatial weights and a spatial statistic with social weights, and apply them to an ongoing study of mental and physical well-being of rural Latino immigrants in North Florida, USA. We demonstrate how this approach can be used to calculate measures, such as social network centrality, support contact dyads, and spatial kernel density based on a health survey data. Findings reveal that the integrated approach accurately reflected interactions between social and spatial elements, and identified community members (who) and locations (where) that should be prioritized for community-based health interventions.

Gut microbiota affects progression of rheumatoid arthritis (RA). The present study aims at investigating the protective potential of Bifidobacterium longum cell wall lipoproteins (Lpps) shown to modulate the intestinal microbiome and prevent osteoarthritis. Arthritis was induced by collagen (CIA) or anti-collagen antibodies (CAIA) injection. Intake of 0.5 mg Lpps /L, but not 0.25 and 1mg Lpps/L significantly alleviated RA symptoms in CIA DBA/1OOaHsd mice. Arthritis index (AI) was also reduced in CAIA mice. In CIA protected group, colon Ligilactobacillus murinus, caecal Lactobacillus johnsonii and spleen weight correlated with AI, whereas the reverse was observed with splenic CD11c+ dendritic cells (cDCs). The unprotected CIA Lpps group harbored higher caecal and colon E. coli and lower caecal L.murinus. Lpps administration to CAIA mice after arthritis induction led to lower colon E. plexicaudatum counts. Splenocytes from CIA protected mice triggered by LPS secreted higher Il-10 than control ones. However, higher IL-10 response was not elicited in gnotobiotic RA mice splenocytes with lower cDCs recruitment. Labeled bacteria with Lpps signal were detected in CIA mice bone marrow (BM) cDCs 5 and 16h post-gavage but not in Peyer’s patches and spleen. In vitro uptake of Lpps by primary BM and thymus cells was observed within 24h. FACS analysis detected the Lpps signal in the plasmacytoid cell compartment but not in cDCs. In conclusion, Lpps dosing is critical for preventing arthritis progression and appropriately modulating the microbiome. Our results also highlight the possible triggering of the immune system by Lpps.

The BAFF-APRIL system is crucial for the pathogenesis of systemic lupus erythematosus (SLE) by promoting B cell survival, differentiation and the maintenance of humoral autoimmunity. Here, we investigated the relationship of BCMA expression on B cell subsets with its ligands BAFF and APRIL, together with soluble BCMA, and with clinical and serologic variables in a cohort of 100 SLE patients (86 under conventional and 14 under belimumab therapy) and 30 healthy controls (HC) using multicolor flow cytometry and ELISA. We found that BCMA expression in SLE patients was significantly increased on all B cell subsets compared to HCs, with all examined components of the BAFF-APRIL system being upregulated. BCMA expression was significantly increased on switched and unswitched memory B cells compared to naïve B cells, both in HCs and SLE. BCMA expression on B cells correlated with plasmablast frequencies, serum anti-dsDNA antibodies and complement consumption, while soluble BCMA correlated with plasmablast frequency, highlighting its potential as clinical biomarker. Belimumab treatment significantly reduced BCMA expression on most B cell subsets and soluble TACI, and contributes to the inhibition of almost the entire BAFF-APRIL system and restoration of B cell homeostasis. These results provide insights into the complex dysregulation of the BAFF-APRIL system in SLE and highlight the therapeutic potential of targeting its components, particularly BCMA, in addition to its use as biomarker for disease activity.

For more than twenty years chemists use peptidic organocatalysts to transfer acyl groups onto alcohols. The goal was and still is the increase of selectivity towards the substrate of choice. One carefully designed example is a highly enantioselective tetrapeptide organocatalyst for the kinetic resolution of trans-cycloalkane-1,2-diols. Until now, the intermediate responsible for the acyl transfer of this tetrapeptide has never been directly observed. It was proposed computationally that a π-methylhistidine moiety is acylated as an intermediate step in the catalytic cycle. In this study we set out to investigate whether we can detect and characterize this key intermediate using NMR-spectroscopy and mass spectrometry. Different mass spectrometric experiments using a nano-ElectroSpray Ionization (ESI) source and tandem MS-techniques allowed the identification of tetrapeptide acylium ions using different acylation reagents. The complexes of trans-cyclohexane-1,2-diols with the tetrapeptide were also detected. Additionally, we were able to detect acylated tetrapeptides in solution using NMR-spectroscopy and monitor the acetylation reaction of a trans-cyclohexane-1,2-diol. These findings are important steps towards the understanding of this organocatalyst and its high enantioselectivity.

Combined awareness about the power and limitations of bioinformatics and molecular biology enables advanced research based on high-throughput data. Despite an increasing demand for scientists with a combined background in both fields, the education in dry lab and wet lab is often separated. This work describes an example of integrated education with focus on genomics and transcriptomics. Participants learn computational and molecular biology methods in the same practical course. Peer-review is applied as a teaching method to foster cooperative learning of students with heterogeneous backgrounds. Evaluation results indicate acceptance and appreciation of this approach.