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Abstract Background Vasculogenic therapies explored for the treatment of peripheral artery disease (PAD) have encountered minimal success in clinical trials. Addressing this, B55α, an isoform of protein phosphatase 2A (PP2A), emerges as pivotal in vessel remodeling through activation of hypoxia-inducible factor 1α (HIF-1α). This study delves into the pharmacological profile of VCE-004.8 (Etrinabdione) and evaluates its efficacy in a preclinical model of critical limb ischemia, with a focus on its potential as a PP2A/B55α activator to induce angiogenesis and arteriogenesis. Methods Vascular endothelial cells were used for in vitro experiments. Aorta ring assay was performed to explore sprouting activity. Matrigel plug-in assay was used to assess the angiogenic potential. Critical limb ischemia (CLI) in mice was induced by double ligation in the femoral arteria. Endothelial vascular and fibrotic biomarkers were studied by immunohistochemistry and qPCR. Arteriogenesis was investigated by microvascular casting and micro-CT. Proteomic analysis in vascular tissues was analyzed by LC–MS/MS. Ex-vivo expression of B55α and biomarkers were investigated in artery samples from PAD patients. Results VCE-004.8 exhibited the ability to induce B55α expression and activate the intersecting pathways B55α/AMPK/Sirtuin 1/eNOS and B55α/PHD2/HIF-1α. VCE-004.8 prevented OxLDL and H2O2-induced cytotoxicity, senescence, and inflammation in endothelial cells. Oral VCE-004.8 increased aorta sprouting in vitro and angiogenesis in vivo. In CLI mice VCE-004.8 improved collateral vessel formation and induced endothelial cells proliferation, angiogenic gene expression and prevented fibrosis. The expression of B55α, Caveolin 1 and Sirtuin-1 is reduced in arteries from CLI mice and PAD patient, and the expression of these markers was restored in mice treated with VCE-004.8. Conclusions The findings presented in this study indicate that Etrinabdione holds promise in mitigating endothelial cell damage and senescence, while concurrently fostering arteriogenesis and angiogenesis. These observations position Etrinabdione as a compelling candidate for the treatment of PAD, and potentially other cardiovascular disorders.

This study investigated the effects of prepared innovative feed (PIF) on the saturated and unsaturated fatty acid profiles of dairy cow milk. PIF was composed of rape seed meal, sunflower meal, protected fat, source of conjugated linoleic acid (CLA), calcium carbonate, monocalcium phosphate (MCP), sodium bicarbonate, and vitamin mineral premix. Dairy cows were divided into two groups (10 cows/group) including a control group (CG) fed basal diet without any nutritional supplements and experimental group (EG) fed basal diet + 1.5 kg PIF/cow/day of the new products. The PIF resulted to change the overall fatty acid content of the milk from the experimental cows and raised the levels of UFA from 64.164% to 73.229%. The SFA content slightly decreased from 35.607% to 26.910%. Furthermore, the PUFA content has elevated from 37.824% (CG) to 45.415% (EG). Not significant difference was recorded for n3, n6 and the n6/n3 ratio (p≥0.05). In conclusion during the experimental period the content of SFA tended to decrease, while the amount of UFA has increased notably (p≤0.05). Similar observations were also noticed for PUFA and MUFA. The inclusion of PIF as dietary supplement in dairy cows modified the fatty acid profile of milk, with major impact on consumer health.

The developing process of a technology with the potential to increase efficiency in a sericulture farm represents one of the most important levers in the efficient exploitation of silkworms and mulberry (Bombyx mori). The development of an optimized technology, with the aim of making the activities carried out in a sericulture farm more efficient, is the main objective of this study. At the same time, the concept of "Pharma-Farming" is being explored, which promotes an integrated and sustainable approach in the management of sericulture farms by integrating sericulture and moriculture products and by-products. The use of the principles underlying the "Pharma-Farming" system could contribute to optimizing integrated processes and increasing the performance and sustainability of this agricultural sector. The integration of by-products obtained during the rearing of silkworms can represent a valuable opportunity not only to increase farmers' incomes through product diversification, but also to improve the quality of life. Exploring this concept facilitates the integration of by-products obtained from the sericulture farm into the pharmaceutical production chain, contributing to the creation of an additional source of raw materials and promoting a circular and sustainable economy. This research is carried out in a collaboration between three partners with expertise in the field of sericulture, and uses the resources of each to successfully address the development and implementation of the technology in different areas of Romania.

Abstract Fungal pathogens must exhibit strong nutritional plasticity, effectively sensing and utilizing diverse nutrients to support virulence. How the signals generated by nutritional sensing are efficiently translated to the morphogenetic machinery for optimal growth and support of virulence remains incompletely understood. Here, we show that the conserved morphogenesis-related kinase, CotA, imparts isoform-specific control over Aspergillus fumigatus invasive growth in host-mimicking environments and during infection. CotA-mediated invasive growth is responsive to exogenous carbon source quality, with only preferred carbon sources supporting hyphal morphogenesis in a mutant lacking one of two identified protein isoforms. Strikingly, we find that the CotA protein does not regulate, nor is cotA gene expression regulated by, the carbon catabolite repression system. Instead, we show that CotA partially mediates invasive growth in specific carbon sources and virulence through the conserved downstream effector and translational repressor, SsdA. Therefore, A. fumigatus CotA accomplishes its conserved morphogenetic functions to drive pathogenic growth by translating host-relevant carbon source quality signals into morphogenetic outputs for efficient tissue invasive growth.

Primary fallopian tube carcinoma (PFTC) is seldom diagnosed preoperatively and is often mistaken for epithelial ovarian carcinoma (EOC). This report details a case of primary high-grade serous carcinoma (HGSC) of the fallopian tube, highlighting radiological and clinical indicators to aid in accurate diagnosis and avoid misdiagnosis. A 46-year-old premenopausal woman presented with symptoms and a transvaginal ultrasound (TVUS) indicating a malignant ovarian tumor. Further imaging with CT and MRI revealed a solid-cystic mass suggestive of a fallopian tube tumor rather than an ovarian origin. Oncological surgery confirmed the presence of a high-grade serous carcinoma in the fallopian tube. This case underscores the diagnostic challenges of PFTC and the superior sensitivity and specificity of MRI over CT and US in distinguishing adnexal lesions. Key MRI features such as the sausage-shaped mass and associated hematosalpinx were crucial in differentiating PFTC from EOC. The report emphasizes the importance of considering PFTC in differential diagnoses of adnexal masses to ensure accurate preoperative identification.

Starting from the well known stable free radical DPPH (or its reduced counterpart, 2,2-diphenyl-1-picryl-hydrazine) and several amino derivatives, novel zwitterionic compounds (diazenium betaines) were obtained and characterized by different means, like NMR, IR, MS, and UV–Vis. These betaines are highly intense blue-colored compounds that can be easily reduced by ascorbic acid (vitamin C) or sodium ascorbate to their corresponding para-phenyl substituted derivatives of DPPH, which have a yellow color. Most of such redox processes were found to be reversible. However, the oxidation of 2-p-aminophenyl-2-phenyl-1-picryl-hydrazine led to an azo-derivative of DPPH diradical, and its structure was unveiled by X-ray monocrystal diffraction. Possible diradicaloid behavior is also discussed.

Background. Acutely ill older patients frequently suffer not only from their acute disease, but also polymorbidity and frailty. Dehydration is another typical symptom, usually occurring in its both forms: low-intake dehydration and volume depletion. POCUS is goal-directed bedside ultrasound examination and several studies refer to its positive impact on hydration assessment. The aim of our study was to determine whether POCUS might influence (de)hydration diagnostics and/or treatments in older patients with acute illness. Methods. We randomized 120 acutely ill patients, aged ≥65 years, into POCUS and non-POCUS groups. All participants underwent routine laboratory tests, including haematocrit, serum and urine osmolality, blood urea nitrogen (BUN), creatinine, BUN/creatinine ratio, and C-reactive protein (CRP). POCUS was performed twice during the first two days to determine chest and abdominal status, with inferior vena cava (IVC) measurements. Length of hospital stay (HL) and consumption of infused fluids (CIF) was evaluated too. Data were analysed with exploratory methods and appropriate statistics. Results. Among all participants, the serum osmolality significantly correlated with age, BUN, creatinine and CIF. HL correlated with CRP and CIF. No significant correlations between IVC and other followed parameters were found. The POCUS group consumed significantly less infused fluids than the non-POCUS group, what could be influenced by POCUS examination of defined body compartments. Conclusion. Dehydration is a common feature in older individuals and its diagnostics is rather complicated. The role of POCUS in assessing hydration status remains unclear. However, our study showed, that ultrasound assessment provides next important information for comprehensive understanding of clinical status in older patients and can be beneficial for optimizing the treatment strategy, including fluid management decisions.

Background and Aim. Pemphigoid gestationis (PG) is a rare skin disease of pregnancy. Given its incidence in pregnant women, physicians and especially obstetricians may not encounter this diagnosis in their entire career. We find this to be a major problem and there is an obligation to report it in as much detail as possible along with recommended treatments with proven efficacy. Case report. We describe the case of a 27 year old patient who was referred to the dermatology department with severe dissemination of blisters in the 9th week of pregnancy. She was diagnosed with pemphigoid gestationis in her first pregnancy. High doses of corticosteroids were initiated but due to inadequate effect cyclosporine was added. The pregnancy was complicated with gestational diabetes. The patient gave birth in her 33rd week by caesarian section due to premature rupture of the membrane. Vesicles were seen on the newborn immediately after birth which diminished spontaneously over 2 weeks. Blisters were still seen on the patient 1 month after labor even with the combination of systemic corticosteroids with cyclosporine. Conclusion. PG is a rare dermatosis of pregnancy. The course of the disease can be severe, necessitating systemic therapy. As described in this patient, systemic corticosteroids may not be sufficient and adding another immunosuppressive treatment may be needed. If pemphigoid gestationis has occurred during a previous pregnancy it is advised to reconsider another pregnancy.

This essay examines, ecocritically, geocritically, and comparatively, the metaphoric spaces represented in Shakespeare’s The Tempest and in Julian Barnes’ A History of the World in 10½ Chapters—seas, mountains, islands, jungle—to show that these spaces allow for different interpretations, yet they are spaces of individual imagination in both the play and the novel, suggesting transformation and metamorphosis. I argue that these literary spaces show a common feature of displacement, which allows human language to re-imagine other worlds—in literature and in visual arts. The spaces of imagination proliferated through Shakespeare’s The Tempest and Barnes’ novel have suffered a transformation in time and space, as they speak to past and present audiences and readers. The sea in Barnes’ chapter entitled “Shipwreck” symbolizes danger but also hope, as does the sea in the storm scene in Shakespeare’s The Tempest. The Mountain in Barnes’ eponymous chapter represents an isolated and inaccessible landscape on Mount Ararat, at the intersection of three cultures (Armenia, Turkey and Russia), but it also represents the biblical language of faith and hermitic isolation. Similarly, the island in The Tempest, which is—geologically—a mountain above the water, represents metaphorically the island of the mind. The jungle in Barnes’ chapter “Upstream” is a remote place in the forest on the Orinoco River, where Europeans and native Indians interact while making a movie; this movie is a work of visual art, represented in a novel; so is any one of the many productions of The Tempest, which reiterates the island’s imaginary space in various directorial interpretations. All these locations are metaphoric spaces of imagination, transmitted through different media, in which reality is transformed into literary representation by means of fictional description or theatrical action.

In this paper we tried to analyze the aspects found in the specialized literature and the main objective was to identify the level of institutionalization of ethics within the central public administration in Romania. Using the questionnaire, I was able to analyze structured data resulting from the information obtained from the people employed in the central public administration. The result that emerges from the analysis is the following: at the level of the central public organization, the institutionalization of ethics is in an open process of transition that targets both the individual and the organizational level.

The preparation of the change process involves concerns in the direction of the clarification of some aspects related to the identification of the problem and the definition of the conditions, the specification of the goals, and the elimination of false goals, as well as the verification of the feasibility of the change. Through multiple research methods, structured observations, survey techniques, and systematic analysis of documents, norms, and legislation specific to the quality of educational organizations, the present study offers, as an answer, implementation models of change. The result that emerges from the analysis is the following: at the level of educational organizations, the adaptation process has a multi-determined character (by the internal needs of the organization, which may concern the administrative, instructional-educational, managerial level or the requirements of the social environment), multidimensional (the change having strong psychological, educational, social, strategic influences), multilevel (targets both the individual and the organizational level).

Understanding public attitudes becomes crucial in the current context, which is defined by climate change and a critical need for sustainable solutions for energy sources. A questionnaire by the Pew Research Center, conducted through the American Trends Panel (ATP), explores the public’s opinions on various emerging energy technologies, preferred energy sources, knowledge of the nation’s energy dependence and attitudes toward environmental policies and climate change. The findings offer an insightful perspective on the interests and people’s concerns and may influence future innovations and policies in the energy sector.

Abstract Background New mothers and fathers are at risk of developing postnatal depressive problems. To understand how postnatal depressive symptoms unfold over time, analyses at the within-person level are necessary. Inspecting postnatal depressive problems at the symptom level provides a novel perspective, ultimately offering insight into which symptoms contribute to the elevation of other symptoms over time. Methods Panel graphical vector-autoregression (GVAR) models were applied to analyze the within-person temporal and contemporaneous relations between depressive symptoms across the postnatal period in new mothers and fathers (at T1; N mothers = 869, N fathers = 579). Depressive symptoms were assessed at 6-, 12-, and 18-months postpartum, using the Edinburgh Postnatal Depression Scale. Results The results revealed that for mothers, sadness was a key symptom predicting symptom increases in multiple other depressive symptoms and itself (autoregressive effect) over time. Furthermore, anxiousness and feeling scared predicted each other across the postnatal period in mothers. For fathers, the most central predicting symptom in the overall network of symptoms was being anxious, while self-blame and being overwhelmed had strong self-maintaining roles in the fathers’ symptomatology, indicating that these could be key features in fathers experiencing postnatal depressive problems. The pattern of symptoms that mothers and fathers experienced within the same time window (contemporaneous associations), shared many of the same characteristics compared to the temporal structure. Conclusions This study suggests that across the postnatal period, from 6- to 18-months postpartum, depressive symptoms in mothers and fathers contribute differently to the pattern of depressive problems, highlighting sadness as a key feature in maternal symptomatology and anxiousness components in paternal symptomatology.

Abstract Background TCF4 acts as a transcription factor that binds to the immunoglobulin enhancer Mu-E5/KE5 motif. Dominant variants in TCF4 are associated with the manifestation of Pitt-Hopkins syndrome, a rare disease characterized by severe mental retardation, certain features of facial dysmorphism and, in many cases, with abnormalities in respiratory rhythm (episodes of paroxysmal tachypnea and hyperventilation, followed by apnea and cyanosis). Frequently, patients also develop epilepsy, microcephaly, and postnatal short stature. Although TCF4 is expressed in skeletal muscle and TCF4 seems to play a role in myogenesis as demonstrated in mice, potential myopathological findings taking place upon the presence of dominant TCF4 variants are thus far not described in human skeletal muscle. Method To address the pathological effect of a novel deletion affecting exons 15 and 16 of TCF4 on skeletal muscle, histological and immunofluorescence studies were carried out on a quadriceps biopsy in addition to targeted transcript studies and global proteomic profiling. Results We report on muscle biopsy findings from a Pitt-Hopkins patient with a novel heterozygous deletion spanning exon 15 and 16 presenting with neuromuscular symptoms. Microscopic characterization of the muscle biopsy revealed moderate fiber type I predominance, imbalance in the proportion of fibroblasts co-expressing Vimentin and CD90, and indicate activation of the complement cascade in TCF4-mutant muscle. Protein dysregulations were unraveled by proteomic profiling. Transcript studies confirmed a mitochondrial vulnerability in muscle and confirmed reduced TCF4 expression. Conclusion Our combined findings, for the first time, unveil myopathological changes as phenotypical association of Pitt-Hopkins syndrome and thus expand the current clinical knowledge of the disease as well as support data obtained on skeletal muscle of a mouse model.

Abstract This study examines the biological effects of palbociclib and ribociclib in hormone receptor-positive breast cancer, pivotal to the HARMONIA prospective phase III clinical trial. We explore the downstream impacts of these CDK4/6 inhibitors, focusing on cell lines and patient-derived tumor samples. We treated HR+ breast cancer cell lines (T47D, MCF7, and BT474) with palbociclib or ribociclib (100 nM or 500 nM), alone or combined with fulvestrant (1 nM), over periods of 24, 72, or 144 h. Our assessments included PAM50 gene expression, RB1 phosphorylation, Lamin-B1 protein levels, and senescence-associated β-galactosidase activity. We further analyzed PAM50 gene signatures from the CORALLEEN and NeoPalAna phase II trials. Both CDK4/6 inhibitors similarly inhibited proliferation across the cell lines. At 100 nM, both drugs partially reduced p-RB1, with further decreases at 500 nM over 144 h. Treatment led to reduced Lamin-B1 expression and increased senescence-associated β-galactosidase activity. Both drugs enhanced Luminal A and reduced Luminal B and proliferation signatures at both doses. However, the HER2-enriched signature significantly diminished only at the higher dose of 500 nM. Corresponding changes were observed in tumor samples from the CORALLEEN and NeoPalAna studies. At 2 weeks of treatment, both drugs significantly reduced the HER2-enriched signature, but at surgery, this reduction was consistent only with ribociclib. Our findings suggest that while both CDK4/6 inhibitors effectively modulate key biological pathways in HR+/HER2- breast cancer, nuances in their impact, particularly on the HER2-enriched signature, are dose-dependent, influenced by the addition of fulvestrant and warrant further investigation.

Abstract Background Clinical metagenomics involves the genomic sequencing of all microorganisms in clinical samples ideally after depletion of human DNA to increase sensitivity and reduce turnaround times. Current human DNA depletion methods preferentially preserve either DNA or RNA containing microbes, but not both simultaneously. Here we describe and present data using a practical and rapid mechanical host-depletion method allowing simultaneous detection of RNA and DNA microorganisms linked with nanopore sequencing. Methods The human cells from respiratory samples are lysed mechanically using 1.4 mm zirconium-silicate spheres and the human DNA is depleted using a nonspecific endonuclease. The RNA is converted to dsDNA to allow the simultaneous sequencing of DNA and RNA. Results The method decreases human DNA concentration by a median of eight Ct values while detecting a broad range of RNA & DNA viruses, bacteria, including atypical pathogens (Legionella, Chlamydia, Mycoplasma) and fungi (Candida, Pneumocystis, Aspergillus). The first automated reports are generated after 30 min sequencing from a 7 h end-to-end workflow. Sensitivity and specificity for bacterial detection are 90% and 100%, respectively, and viral detection are 92% and 100% after 2 h of sequencing. Prospective validation on 33 consecutive lower respiratory tract samples from ventilated patients with suspected pneumonia shows 60% concordance with routine testing, detection of additional pathogens in 21% of samples and pathogen genomic assembly achieve for 42% of viruses and 33% of bacteria. Conclusions Although further workflow refinement and validation on samples containing a broader range of pathogens is required, it holds promise as a clinically deployable workflow suitable for evaluation in routine microbiology laboratories.

Abstract Background The BCR::ABL1 is a hallmark of chronic myeloid leukemia (CML) and is also found in acute lymphoblastic leukemia (ALL). Most genomic breaks on the BCR side occur in two regions - Major and minor - leading to p210 and p190 fusion proteins, respectively. Methods By multiplex long-distance PCR or next-generation sequencing technology we characterized the BCR::ABL1 genomic fusion in 971 patients (adults and children, with CML and ALL: pediatric ALL: n = 353; pediatric CML: n = 197; adult ALL: n = 166; adult CML: n = 255 patients) and designed “Break-App” web tool to allow visualization and various analyses of the breakpoints. Pearson’s Chi-Squared test, Kolmogorov-Smirnov test and logistic regression were used for statistical analyses. Results Detailed analysis showed a non-random distribution of breaks in both BCR regions, whereas ABL1 breaks were distributed more evenly. However, we found a significant difference in the distribution of breaks between CML and ALL. We found no association of breakpoints with any type of interspersed repeats or DNA motifs. With a few exceptions, the primary structure of the fusions suggests non-homologous end joining being responsible for the BCR and ABL1 gene fusions. Analysis of reciprocal ABL1::BCR fusions in 453 patients showed mostly balanced translocations without major deletions or duplications. Conclusions Taken together, our data suggest that physical colocalization and chromatin accessibility, which change with the developmental stage of the cell (hence the difference between ALL and CML), are more critical factors influencing breakpoint localization than presence of specific DNA motifs.

Background: As healthcare increasingly integrates digital technologies, it is crucial to ensure that medical professionals possess robust digital competencies to maximize the benefits of these technologies. Mastering fundamental digital skills is essential before engaging with more complex digital health technologies. This study aimed to assess the general digital competencies of doctors in Chișinău, Moldova, and to identify specific areas needing improvement, thereby providing a foundation for tailored educational programs. Materials and Methods: In April 2024, data were collected using the My DigiSkills tool, a self-assessment online questionnaire developed under the European Commission's DigCompSAT project by ALL DIGITAL. This cross-sectional study involved resident doctors and specialists and from various medical institutions in Chișinău, who self-assessed their digital competence levels across five areas: Information and Data Literacy, Communication and Collaboration, Digital Content Creation, Safety, and Problem Solving. Upon completing the questionnaire, participants received their results via email and subsequently forwarded the results to the researchers. Results: The study revealed that over 50% of doctors in Chișinău demonstrated advanced skills in information and data literacy and communication. However, significant deficiencies were found in digital safety, with only 19% showing advanced skills in this area. Younger doctors generally exhibited higher digital competence levels. The results highlight the urgent need for customized training initiatives to address these gaps and enhance digital competencies among medical professionals. Conclusions: The study underscores the necessity for tailored educational programs to improve digital competencies, particularly in digital safety, because data privacy and security are paramount in the medical context.

This paper analyzes by transposing the importance of environmental policies, highlighting the most significant regulations directly related to the sustainable agriculture component in relation to the environmental targets proposed by the Municipal Agricultural Policy. The need to rethink agricultural processes led slowly to the anchoring to current trends as a premise in the realization of a real report related to sustainable agricultural systems performing and last but not least aligned to the constraints of eco-conditionality. From this perspective, the methodology in reflecting our analysis was linked to the collection of data reported in international statistical databases such as those available at the National Institute of Statistics Eurostat, as well as OECD reports on the subjects analyzed in the study. In these paradises, the perspective reflected by the New Agricultural Policy is rather aligned towards the achievement of environmental goals in agriculture, which positions the ability of farmers to adapt to these sustainability conditions. Through these completely new concepts for farmers, the studio reflects the sustainability of agriculture through the levers offered by the agricultural policy and research, thus also representing an important resource in complex research aimed at the decarbonization of agriculture as topical issues.

Abstract Colorectal cancer (CRC) is a frequent cause of cancer-related mortality in the Palestinian population. This cross-sectional study was conducted from July 2019 to March 2020 and examined attitudes toward CRC and colonoscopy, as well as the interplay between both. Participants were recruited using convenience sampling from public spaces, governmental hospitals, and primary healthcare centers across 11 governorates in Palestine. Displaying a positive attitude was defined as agreeing on at least the median number of questions related to CRC (5 of 11 questions) or colonoscopy (6 of 10 questions). A total of 4623 participants were included. Most participants agreed that ‘early detection of CRC increases the possibility of more effective treatment’ (n = 4161, 89.7%). Similarly, the majority of participants agreed on ‘preferring a physician with a gender similar to the participants to perform the colonoscopy’ (n = 3738, 80.9%) and ‘willingness to have colonoscopy even if the participant had to pay for it’ (n = 3727, 80.6%). Furthermore, 3115 participants (67.4%) demonstrated positive attitudes toward CRC, while 2540 participants (55.0%) displayed similar attitudes toward colonoscopy. Participants from the West Bank and Jerusalem were more likely than those from the Gaza Strip to display positive attitudes toward colonoscopy (59.2% vs. 48.9%). Participants with positive attitudes toward CRC were more likely to also display positive attitudes toward colonoscopy and vice versa. About two thirds of study participants exhibited positive attitudes toward CRC, and 55.0% displayed positive attitudes toward colonoscopy. There was a reciprocal relationship between having positive attitudes toward CRC and colonoscopy.

Abstract On September 26th, 2022, the detonations at the gas pipelines Nord Stream 1 and 2 resulted in some of the largest non-natural releases of methane known. The distribution of methane in the surrounding seawater and the possible effects were not apparent. To trace the pathways of methane we recorded CH4 concentrations and the isotopic signal (δ13C-CH4) in seawater, and air. A week post-explosion, we detected methane concentrations up to 4 orders of magnitude above the natural Baltic Sea background. The released fossil methane created a distinct plume with δ13C-CH4 ratios differing from natural background values. The strong water stratification preserved the distribution pattern initiated by the explosion, shown by the laterally strong concentration gradient within the plume. Our analysis encompasses three stages of the explosion's impact; the initial sea-air methane release, measurements taken during our research expedition one week later, and a third stage triggered by the shift from summer to winter conditions as an outlook on how winter mixing and microbial activity will influence the plume.

Renal cell carcinoma (RCC) is a common type of tumor that can develop in the kidney. It is responsible for around one-third of all cases of neoplasms. RCC manifests itself in a variety of distinct subtypes. The most frequent of which is clear cell RCC, followed by papillary and chromophobe RCC. RCC has the potential for metastasis to a variety of organs; nevertheless, bone metastases are one of the most common and potentially fatal complications. These bone metastases are characterized by osteolytic lesions that can result in pathological fractures, hypercalcemia, and other complications, which can ultimately lead to a deterioration in quality of life and an increase morbidity. While nephrectomy remains a foundational treatment for RCC, emerging evidence suggests that targeted therapies, including tyrosine kinase inhibitors and T cell checkpoint inhibitors, may offer effective alternatives, potentially obviating the need for adjuvant nephrectomy in certain cases of metastatic RCC Bone metastases continue to be a difficult complication of RCC, which is why more research is required to enhance patient outcome.

Abstract When antimicrobial resistant bacteria (ARB) and genes (ARGs) reach novel habitats, they can become part of the habitat’s microbiome in the long term if they are able to overcome the habitat’s biotic resilience towards immigration. This process should become more difficult with increasing biodiversity, as exploitable niches in a given habitat are reduced for immigrants when more diverse competitors are present. Consequently, microbial diversity could provide a natural barrier towards antimicrobial resistance by reducing the persistence time of immigrating ARB and ARG. To test this hypothesis, a pan-European sampling campaign was performed for structured forest soil and dynamic riverbed environments of low anthropogenic impact. In soils, higher diversity, evenness and richness were significantly negatively correlated with relative abundance of >85% of ARGs. Furthermore, the number of detected ARGs per sample were inversely correlated with diversity. However, no such effects were present in the more dynamic riverbeds. Hence, microbiome diversity can serve as a barrier towards antimicrobial resistance dissemination in stationary, structured environments, where long-term, diversity-based resilience against immigration can evolve.

Scedosporium spp. and Lomentospora prolificans are emerging non-Aspergillus filamentous fungi. The Scedosporiosis/lomentosporiosis Observational Study we previously conducted reported frequent fungal vascular involvement, including aortitis and peripheral arteritis. For this article, we reviewed 7 cases of Scedosporium spp. and L. prolificans arteritis from the Scedosporiosis/lomentosporiosis Observational Study and 13 cases from published literature. Underlying immunosuppression was reported in 70% (14/20) of case-patients, mainly those who had solid organ transplants (10/14). Osteoarticular localization of infection was observed in 50% (10/20) of cases; infections were frequently (7/10) contiguous with vascular infection sites. Scedosporium spp./Lomentospora prolificans infections were diagnosed in 9 of 20 patients ≈3 months after completing treatment for nonvascular scedosporiosis/lomentosporiosis. Aneurysms were found in 8/11 aortitis and 6/10 peripheral arteritis cases. Invasive fungal disease­–related deaths were high (12/18 [67%]). The vascular tropism of Scedosporium spp. and L. prolificans indicates vascular imaging, such as computed tomography angiography, is needed to manage infections, especially for osteoarticular locations.

Abstract Objectives To evaluate the efficacy of the O-RADS MRI criteria in the stratification of risk of malignancy of solid or sonographically indeterminate ovarian masses and assess the interobserver agreement of this classification between experienced and inexperienced radiologists. Methods This single-centre retrospective study included patients from 2019 to 2022 with sonographically indeterminate or solid ovarian masses who underwent MRI with a specific protocol for characterisation according to O-RADS MRI specifications. Each study was evaluated using O-RADS lexicon by two radiologists, one with 17 years of experience in gynaecological radiology and another with 4 years of experience in general radiology. Findings were classified as benign, borderline, or malignant according to histology or stability over time. Diagnostic performance and interobserver agreement were assessed. Results A total of 183 patients with US indeterminate or solid adnexal masses were included. Fifty-seven (31%) did not have ovarian masses, classified as O-RADS 1. The diagnostic performance for scores 2–5 was excellent with a sensitivity, specificity, PPV, and NPV of 97.4%, 100%, 96.2%, and 100%, respectively by the experienced radiologist and 96.1%, 92.0%, 93.9%, and 94.8% by the inexperienced radiologist. Interobserver concordance was very high (Kappa index 0.92). Almost all the misclassified cases were due to misinterpretation of the classification similar to reports in the literature. Conclusion The diagnostic performance of O-RADS MRI determined by either experienced or inexperienced radiologists is excellent, facilitating decision-making with high diagnostic accuracy and high reproducibility. Knowledge of this classification and use of assessment tools could avoid frequent errors due to misinterpretation. Critical relevance statement Up to 31% of ovarian masses are considered indeterminate by transvaginal US and 32% of solid lesions considered malignant by transvaginal US are benign. The O-RADs MRI accurately classifies these masses, even when used by inexperienced radiologists, thereby avoiding incorrect surgical approaches. Key points • O-RADS MRI accurately classifies indeterminate and solid ovarian masses by ultrasound. • There is excellent interobserver agreement between experienced and non-experienced radiologists. • O-RADS MRI is a helpful tool to assess clinical decision-making in ovarian tumours. Graphical Abstract

Russian literature in translations into Kashubian The subject of the research was the translation of Russian literature into Kashubian, especially poetry and, less often, prose. It was the texts of Russian poets that were most popular among Kashubian writers and poets. It should be emphasised that Kashubian literature was already enriched by translations from foreign languages, including Russian, in the 19th century, i.e. since the times of Florian Ceynowa. The fi rst translation was made by Ceynowa, who translated Alexander Pushkin’s fairy tale Wò rébôku é ribce. The most extensive translation of Russian literature into Kashubian is Leszek Szulc’s translation of Ivan Krylov’s Fables. A contemporary Kashubian poet – Stanisław Pestka – translated Ivan Bunin’s poem Ночь. In turn, Hanna Makurat used the texts of the Russian poet Anna Akhmatova, translating three poems and Alexander Pushkin’s Цветок. In turn, the contemporary Kashubian poet and musician Tomasz Fopke became interested in the work of Bułat Okudzhava and translated the song Mòdlëtwã, as well as a poem-song known to the generation of children and young people in Poland in the 1970s, i.e. Vienna let bãdze słuńce. The poet and translator Hanna Makurat turned to the poetry of another Russian poet - Anna Akhmatova and the collection of poems Избранное. Translations into Kashubian include fragments of works by Fyodor Dostoevsky and Leo Tolstoy.

IntroductionThe impact of sex bias in medical research is a matter of significant relevance and importance especially in the modern age. Despite notable improvements in sex equity across various societal fields, disparities in sex representation persist within clinical and pharmacological research. The objective of this article is to investigate the sex bias within Prospective Follow-up Observational Studies with Drugs authorized by the Advisory Commission on Post-Authorization Studies with Medicines in Catalonia, a southern European region.MethodsA retrospective study that analyses data from final reports of Prospective Follow-up Observational Studies with Drugs authorized by the Advisory Commission on Post-Authorization Studies with Medicines in Catalonia from 2015 to 2021. Disease categories and specific diseases, obtained from the Global Data Exchange, were evaluated for sex bias, comparing female participation to female prevalence.ResultsThere were 1,06,399 participants, including 43,778 female participants (42.5%). A significant underrepresentation of females was observed across various disease categories. Notably, in 12 out of 19 categories (63.2%), a pronounced female underrepresentation (sex bias ≤ 0.05) was evident, particularly in the categories of HIV/AIDS and sexually transmitted infections (sex bias = −0.5659). Furthermore, 11 categories (57.9%) also demonstrated significant female underrepresentation, with the same notable categories, HIV/AIDS and sexually transmitted infections (sex bias = −0.4439). When examining specific diseases, significant female underrepresentation was observed in 13 out of 29 diseases (46.4%), especially in HIV (sex bias = −0.4781). The overall findings indicate that the degree of sex bias was notably less favorable for females in numerous disease categories and specific conditions.ConclusionOur study has demonstrated a significant sex bias within observational studies, mirroring patterns observed in clinical trials. Importantly, our findings highlight a pervasive underrepresentation of women across various disease categories and specific conditions. Despite efforts to promote both sexes inclusivity, our results emphasize the persistent challenges in achieving balanced sex representation in study populations. Furthermore, the absence of categorization of diseases based on male and female prevalence poses a significant challenge in accessing pertinent data, particularly concerning the sex distribution of specific diseases.

Multidose drug dispensing (MDD) is the dispensing of different drugs in dose bags containing one, some, or all units of medicine that a patient needs to take at specific times. The aim of this narrative review is to provide an overview of the literature describing the use of MDD systems in community healthcare settings in patients with multimorbidity and polypharmacy. A literature search identified 14 studies examining adherence, medication knowledge, quality of drug prescription (including inappropriate drug use, drug-drug interactions), medication incidents, and drug changes after MDD initiation, as well as healthcare professional (HCP) and patient perspectives. There are limited data on MDD in community healthcare settings, particularly on outcomes such as adherence. Studies are mostly from Northern Europe. Patients selected for MDD are more likely to be older, female, cognitively impaired, and have a higher number of disease diagnoses and drugs than those who do not receive drugs through MDD. MDD is generally initiated for patients who have decreased capacity for medication management. Several advantages of MDD have been reported by patients and HCPs, and studies indicate that MDD can be improved by medication review, defining clear roles and responsibilities of HCPs in the medication management chain, and comprehensive follow-up of patients. Future development, implementation, and assessment of MDD systems in community healthcare should be designed in collaboration with HCPs and patients, to identify ways to optimize the systems and improve patient outcomes.

IntroductionDistinct androgen formulations have been used as gender-affirming hormone treatment, but little is known about the specific changes that may occur in the ovary depending on the testosterone preparation used. The study aims to evaluate the histological modifications of the ovarian tissue and the hormonal changes after gender-affirming surgery based on the testosterone preparation employed, such as testosterone cypionate or undecanoate.DesignUnicenter transversal cohort study.Materials and methodsSixty transmasculine persons before and after gender-affirming surgery. A histological examination of the ovaries was conducted, including the follicular population and the characterization of the ovarian stroma. Hormonal status (testosterone, estradiol, FSH, and LH) were also assessed before and after the procedure.ResultsThe median age of participants was similar between the two groups (27.9 vs. 26.7 years, p = 0.27). There were no differences in all hormonal determinations before gender-affirming surgery between the groups. After surgery, FSH levels increased significantly, especially in the testosterone undecanoate group compared to the cypionate group (72.3 vs. 38.3 U/L, p = 0.02), consistent with LH determinations (43.0 vs. 23.4 U/L, p = 0.02). However, no regimen modification was required for any individual. No statistical differences were observed in any parameter concerning the follicular population, nor were there any variances in the thickness of the tunica albuginea (p = 0.85) or the proportion of luteinized stromal cells. Nevertheless, there was a tendency toward increased luteinization in the testosterone cypionate group (88.2% vs. 76.9%, p > 0.05).ConclusionsIn a cohort of transmasculine individuals using different androgen preparations, histological analysis of ovarian tissue revealed comparable findings. Both groups exhibited similar follicular populations and comparable modifications in stromal tissue. However, significant differences were observed in hormonal profiles, although no modification in testosterone dosage was needed.

La intervención en el patrimonio arquitectónico precisa un estudio previo global que abarque tanto su desarrollo histórico como sus características morfológicas y constructivas, así como su relación con el entorno en que se encuentra. En este trabajo se presenta la metodología empleada para la intervención en la fortificación histórica en tapia de cal y canto de Belver de los Montes, Zamora. La interpretación de las características histórico-constructivas de los restos mediante análisis multidisciplinares permite plantear una forma coherente de abordar las obras de consolidación de un tramo del recinto, que se encuentra en un estado de conservación precario. La metodología desarrollada para este ejemplo concreto podría servir de referencia para futuras intervenciones en elementos de arquitectura fortificada de similares características.

This study analyzes face-to-display workers' environments and investigates how their habits affect both brick-and-mortar and virtual workplaces. A qualitative study with 20 respondents using a photovoice strategy via snowball sampling was employed. The study aims to shed more light on some of the factors associated with the e-workplace environment. All respondents stated that work cannot be done efficiently and effectively without a comfortable workspace. Data demonstrate that the blurring of the distinction between home and office as a workspace has undeniably accelerated recently. Results show that work-anywhere technologies have empowered e-workers to be highly productive. For some, the balance between family and work has been a challenge. Males and females proceed completely differently when setting up home offices. Employees see ICT as an enabler and motivator for productivity; however, self-care is becoming a must when working remotely. For many, this is a new experience that they have to adjust to. The results obtained show similarities between brick-and-mortar and virtual workplaces and indicate that there is a process of "domestication," i.e., of moving selected features of the traditional workplace to the home office.

Introduction: This study aimed to evaluate the motor, kinetotherapeutic, and psychological benefits of three aquatic therapeutic programs—aquagym recovery (AG), aquatic ludotherapy (ALT), and therapeutic swimming (TS)—for students specializing in balneo-physio-kinetotherapy. Methods: The study group consisted of 101 students, out of which 43 students from the balneo-physiokinetotherapy study program (BFKT) and 67 master's degree students from physical therapy and functional rehabilitation (PTFR). The questionnaire was named Questionnaire regarding the benefits of therapeutic aquatic programs (QBTAP), and included 3 subscales according to the typology of the targeted objectives, namely: motor, kinetotherapeutic and psychological. The items of each subscale correspond to the objectives identified in the content of the 3 aquatic programs stipulated in the content of the courses corresponding to the disciplines in the education plans of academic study programs (BFK, TRFR). The motor subscale included 8 items, the kinetotherapeutic subscale included 16 items, and the psychological subscale included 10 items. The evaluation of the QBTAP questionnaire 5-point Likert scale. The three evaluated programs were: recovery aquagym (AG), aquatic ludotherapy (ALT) and therapeutic swimming (TS). Results: The results and conclusion sections should highlight the main findings succinctly. For example: ''The QBTAP showed high internal consistency (Cronbach's Alpha >0.9) across all subscales and programs, with significant differences identified between the three programs (p

Insulin autoimmune syndrome or Hirata's disease is a rare condition characterized by hypoglycemia associated with endogenous autoimmune hyperinsulinism. This report concerns the case of a 28-year-old Latin American woman with Graves' disease who developed insulin autoimmune syndrome and then subsequently became pregnant. She displayed symptoms related to severe hypoglycemia due to hyperinsulinemia, elevated C-peptide, and anti-insulin antibodies. Prior to pregnancy she was treated with corticosteroids and had ablative treatment with iodine-131. During follow-up of both conditions, the patient became pregnant, and clinically and biochemically hyperthyroid, for which total thyroidectomy was performed during the second trimester of pregnancy. Anti-insulin antibodies, blood glucose, and C-peptide remained normal throughout pregnancy. At 40 weeks of gestation she gave birth to a healthy female newborn with normal blood glucose values. Molecular genetic analysis determined the following genotypes: HLA-DRB1*03:01 / HLA-DRB1*04:01 in the mother; and HLA-DRB1*04:01 / HLA-DRB1*08:02 in the daughter. Because some HLA-DRB1*04 alleles are associated with susceptibility to insulin autoimmune syndrome induced by environmental factors, the patient was advised regarding the future use of drugs with a sulfhydryl group and possible triggering factors for insulin autoimmune syndrome. At 6-month follow-up the daughter presented normal growth and development, as well as normal plasma glucose values, and this remained the case at five-year follow-up.

Ticks are important blood feeding ectoparasites that transmit pathogens to wildlife, domestic animals, and humans. Hard ticks can feed for several days to weeks, nevertheless they often go undetected. This phenomenon can be explained by a tick’s ability to release analgesics, immunosuppressives, anticoagulants, and vasodilators within their saliva. Several studies have identified extracellular vesicles (EVs) as carriers of some of these effector molecules. Further, EVs, and their contents, enhance pathogen transmission, modulate immune responses, and delay wound healing. EVs are double lipid-membrane vesicles that transport intracellular cargo, including microRNAs (miRNAs) to recipient cells. miRNAs are involved in regulating gene expression post-transcriptionally. Interestingly, tick-derived miRNAs have been shown to enhance pathogen transmission and affect vital biological processes such as oviposition, blood digestion, and molting. miRNAs have been found within tick salivary EVs. This review focuses on current knowledge of miRNA loading into EVs and homologies reported in ticks. We also describe findings in tick miRNA profiles, including miRNAs packed within tick salivary EVs. Although no functional studies have been done to investigate the role of EV-derived miRNAs in tick feeding, we discuss the functional characterization of miRNAs in tick biology and pathogen transmission. Lastly, we propose the possible uses of tick miRNAs to develop management tools for tick control and to prevent pathogen transmission. The identification and functional characterization of conserved and tick-specific salivary miRNAs targeting important molecular and immunological pathways within the host could lead to the discovery of new therapeutics for the treatment of tick-borne and non-tick-borne human diseases.

Rose cultivars represent a source with potential for therapeutical applications due to the high content in bioactive phytochemicals, including phenolic derivatives and lipophilic compounds, such as carotenoids. Anthocyanins, a phenolic subclass, represent the major compounds responsible for the colors of roses. In this study, we have aimed to extract, separate, and identify the anthocyanin compounds found in the petals of 25 different rose cultivars. High performance liquid chromatography followed by electrospray ionization mass spectrometry (HPLC-ESI-MS) was used to separate, identify and quantify the individual anthocyanins. The results showed the presence of 9 anthocyanin compounds, whereas the total anthocyanin content of rose cultivars ranged from 20.267-1206.841 mg/100 g FW, from which cyanidin-caffeoyl-glucoside was the most quantitatively represented anthocianin, followed by cyanidin-glucoside and pelargonidin-glucoside. In addition to this, the antioxidant activity was applied using the established DPPH in vitro method (1403 ± 301-304 ± 37 µmol TE/g FW), as well as the total phenolic content (2600±452-208±23 mg GAE/100 g FW) and the total flavonoid content (160±23-705±49 mg QE/100 g FW). Among the evaluated cultivars, the highest content in anthocyanin was determined for the ‘Amalia’ cultivar. Between the 25 rose cultivars analyzed, the varieties ‘Amalia’, ‘Foc de tabără’, ‘Fruhrot’, and ‘First Red’ followed as being the richest in anthocyanins content and the lowest values were recorded for the varieties ‘Jimini Cricket’, ‘Cri-Cri’, ‘Fortuna’, and ‘Zburlici’. The same trend was observed for the total phenolic and total flavonoid content but also the antioxidant activity. The importance of analyzing anthocyanin content in different rose varieties came from the use of anthocyanins as natural dyes, having potential pharmaceutical ingredients that give various beneficial health effects.

Bromination of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical with bromine or N-bromo-succinimide (NBS) affords a complex mixture of bromo- and nitro-derivatives of the starting material. In this study, by chromatographic separation, most of the reaction products were isolated. Suitable crystals for X-ray measurements were obtained and characterized for the compounds 2-p-bromophenyl-2-phenyl-1-picrylhydrazyl free radical (Br-DPPH), 2-p-bromophenyl-2-phenyl-1-picrylhydrazine (Br-DPPH-H), and 2,2-(p-bromophenyl)-1-(2-bromo-4,6-dinitrophenyl)hydrazine (Br2-DPPBr-H).

En este artículo se estudia el desarrollo histórico del sustantivo *kw-enneʔ ‘persona’ desde el protozapoteco hasta el zapoteco de San Bartolo Yautepec, una variante de zapoteco sureño. Esta forma se gramaticalizó como un pronombre de tercera persona de respeto =mé, como primer elemento en algunos compuestos nominales que comienzan con men- y como el pronombre relativo men. Se estudian las formas cognadas del pronombre relativo men en otras variantes de zapoteco cisyautepequeño en donde encontramos evidencia de cómo se dio el reanálisis de sustantivo hipernónimo a pronombre relativo y se proponen 3 etapas de gramaticalización para estos pronombres relativos. Se propone que el pronombre relativo del zapoteco de San Bartolo Yautepec se encuentra en la segunda etapa en la que ha sufrido pérdida de rasgos de animacidad. Se argumenta que este reanálisis de sustantivos hiperónimos a pronombres relativos es un canal de gramaticalización de pronombres relativos común en las lenguas zapotecas de la Sierra Sur y se proporcionan ejemplos de cinco lenguas zapotecas.

In recent decades, as a consequence of climate change, grape ripening is occurring under warmer and drier conditions, resulting in losses in the yield and quality of wine grapes. Several alternatives may reduce these negative effects. One that stands out for its potential for long-term adaptation is the selection of better-adapted plant material. For this purpose, during two consecutive years, several agronomic and quality parameters were recorded in 21 grapevine cultivars grown under two water stress levels (moderate and severe). The results revealed that some cultivars considered a minority, as well as others recently recovered from the viticultural heritage that had almost become extinct, could offer a similar and even better response to drought than other widespread cultivars. In particular, Maquías, Montonera del Casar, and Tortozona Tinta stood out for their high total acidity; Tinto Fragoso and Tinto Velasco for their high anthocyanin concentration; and Albillo Dorado and Moscatel Serrano for their high varietal aromatic potential. These cultivars could contribute to diversifying varietal offerings and to maintaining the sustainability of the wine sector in the coming decades.

Resumo A diversidade e a diferença cultural na escola revelam a necessidade de implementar novas estratégias nas quais os diversos saberes possam dialogar. Este artigo revela parte dos resultados da pesquisa correspondente à construção e adaptação de jogos por parte de estudantes e docentes da área de Ciências do Ensino Médio de duas escolas colombianas, rural e urbana, em busca dos diálogos de Conhecimentos Locais Tradicionais (CLT) e Conhecimentos Científicos Escolares (CCE). O objetivo foi estabelecer o jogo como mediador pedagógico mediante a metodologia investigação, ação, participante (IAP). Os resultados mostraram que as/os estudantes têm CLT herdadas de suas famílias pela oralidade. As duas comunidades educativas têm semelhanças nos CLT, entre elas, o conhecimento e o uso das plantas com fins medicinais, e alguns jogos vivenciados pelos sujeitos nesses territórios. A partir dos resultados, foram identificados processos de mediação entre os jogos, enquanto artefatos culturais.

Las corrientes actuales en la enseñanza de idiomas consideran que el aprendizaje de una lengua extranjera (LE) va más allá de la mera adquisición de elementos lingüísticos, pues involucra el trabajo con aspectos socioculturales. A través del idioma que se estudia, se establece un contacto con otra cultura. Sin embargo, cuando se acepta este planteamiento, una pregunta que surge de inmediato es qué cultura se aprende al aprender otra lengua. Es decir, aparece el problema de cómo se presenta el aspecto sociocultural a través de los manuales, libros y otros materiales utilizados en el aprendizaje de la LE. Con frecuencia, estos incluyen numerosos estereotipos sobre la cultura asociada al idioma extranjero que se estudia. En el presente artículo se reflexiona sobre el caso particular de los estereotipos asociados con la lengua francesa. De manera general, se analiza la forma en que los medios de comunicación (cine, televisión, etc.) y los materiales tradicionales (libros de texto, documentos auditivos, recursos electrónicos, etc.) promueven algunos estereotipos entre los estudiantes de francés. Posteriormente, se considera el caso específico del Colegio de Ciencias y Humanidades (CCH) de la Universidad Nacional Autónoma de México (UNAM). Finalmente, se presenta una propuesta para reflexionar sobre el tema de los estereotipos en el aula.

Mastitis-causing bacteria can establish persistent infections in the mammary glands of commercially important dairy animals despite the presence of strong specific humoral and cellular immune mechanisms. We investigated the effect of vitamin D3 in the diet at a set level, but in two different forms (i.e., unencapsulated and encapsulated by complex coacervation with sulfur-saturated bovine lactoferrin-alginate using microbial transglutaminase-catalyzed crosslinking) on the immune response in late-lactating dairy goats. Dairy goats (n = 18) were randomly assigned to three experimental groups (n = 6). Dairy goats were orally administered 0.35 mg of vitamin D3/day in the unencapsulated form and 0.35 mg of vitamin D3/day in the encapsulated powder form. Another group received the basal diet. The experimental period lasted 6 weeks. The blood serum concentrations of 25-hydroxyvitamin D3 [25-(OH)-D3], lactoferrin, immunoglobulin A (IgA), and interferon-gamma (INF-γ) were measured. There were major differences in these parameters between dietary groups. However, the delivery of vitamin D3 in the encapsulated powder form to dairy goats resulted in a marked increase in 25-(OH)-D3 concentration in serum, while the serum level of lactoferrin also increased. Alternatively, the serum levels of IgA and the immunomodulatory cytokine INF-γ were elevated following supplementation with the encapsulated vitamin D3. The observed effects suggest that the deliverable form of dietary vitamin D3 results in differences in the immune response in late-lactating dairy goats.

This study examines the interest of Gulf Cooperation Council (GCC) investors in financing renewable energy (RE) projects in Indonesia using Islamic financing schemes. It employs a multi-criteria decision-making (MCDM) method and Analytical Hierarchy Process (AHP) model with expert respondents representing institutional investors from the GCC states. To validate and enrich the analysis, it also conducted Focus Group Discussion and additional interviews with industry players and Indonesian regulators. The main finding indicates that the return on investment is the most crucial factor in selecting appropriate RE projects, followed by risk and impact of the projects. Furthermore, while the GCC investors do not have sufficient knowledge about the potential and sources of RE in Indonesia, they consider the solar panel project as most preferable. Next, the study finds investment return, Shariah compliance and liquidity as the main criteria in choosing Islamic financing instruments, where equity-based are the most preferred instrument, followed by asset-backed securities and blended financing instruments. In addition, tax incentives, cross subsidy and feed-in-tariffs are the most preferred incentives needed by the investors. The additional interviews that we conducted further affirm these findings. The results are expected to provide insights for the Indonesian policy makers, particularly fiscal and financial/monetary authorities, and the GCC investors to invest in Indonesia for financing RE projects using Islamic financing schemes. Acknowledgment We gratefully acknowledge the support provided by Universitas Indonesia Research Grant. The grant facilitated the research presented in this paper, allowing us to conduct data collection and analysis as well as disseminate our findings to a wider audience.

Abstract The extreme phenomena have been increased recently in frequency and intensity causing numerous damage that cannot be neglected by residents, local authorities and social media. More European countries are experiencing a growing number of occurrences, such as floods, powerful winds, storms, icing, and unusual temperature fluctuations. Particularly, the year 2023 has recorded the highest temperatures in the history of humanity. In this research, we compile a dataset that combines news reports with numerical data pertaining to weather conditions and air quality at the historical region level in Romania. We examine the news and recorded data spanning the years from 2009 to 2023 using anomaly detection and clustering techniques to compare the results. Specifically, we employ Isolation Forest and Autoencoders to identify anomalies within the data that are further clustered to analyse the detection process. We explore the occurrence frequency and duration of daily simultaneous extreme weather events over the years, conducting statistical tests like the Mann–Kendall test to discern trends in the extreme phenomena. The findings reveal statistically significant increasing trends in the incidence of heatwaves, storms and floods. When we set the Mean Squared Error (MSE) threshold to 95%, both methods detect nearly 16% of the anomalies, and this figure rises to over 25% when the MSE threshold is set to 90%. An analysis of anomalies at the regional level indicates that most anomalies are detected in the Transylvania and Muntenia regions, while the Banat region experiences the lowest level of anomalies.

Abstract Triazoles, the most widely used class of antifungal drugs, inhibit the biosynthesis of ergosterol, a crucial component of the fungal plasma membrane. Inhibition of a separate ergosterol biosynthetic step, catalyzed by the sterol C-24 methyltransferase Erg6, reduces the virulence of pathogenic yeasts, but its effects on filamentous fungal pathogens like Aspergillus fumigatus remain unexplored. Here, we show that the lipid droplet-associated enzyme Erg6 is essential for the viability of A. fumigatus and other Aspergillus species, including A. lentulus, A. terreus, and A. nidulans. Downregulation of erg6 causes loss of sterol-rich membrane domains required for apical extension of hyphae, as well as altered sterol profiles consistent with the Erg6 enzyme functioning upstream of the triazole drug target, Cyp51A/Cyp51B. Unexpectedly, erg6-repressed strains display wild-type susceptibility against the ergosterol-active triazole and polyene antifungals. Finally, we show that erg6 repression results in significant reduction in mortality in a murine model of invasive aspergillosis. Taken together with recent studies, our work supports Erg6 as a potentially pan-fungal drug target.

Abstract Background In Palestine, colorectal cancer (CRC) is the second most common cause of cancer-related mortality after lung cancer. No studies have examined the relationship between CRC awareness and attitudes. This study aimed to investigate the interplay between CRC awareness and attitudes among the Palestinian population. Methods A nationwide cross-sectional survey was carried out between July 2019 and March 2020. Convenience sampling was used to collect data from hospitals, primary healthcare facilities, and public areas in 11 governorates. Modified, translated-into-Arabic versions of the validated Bowel Cancer Awareness Measure and Cancer Awareness Measure-Mythical Causes Scale were utilized to assess the awareness of CRC signs/symptoms, risk factors, and causation myths. The cumulative awareness score for each domain was computed and stratified into tertiles. The top tertile denoted ‘high’ awareness, while the remaining two tertiles denoted ‘low’ awareness. Results The final analysis included 4,623 participants; of whom, 3115 (67.4%) reported positive attitudes toward CRC. In total, 1,849 participants (40.0%) had high awareness of CRC signs/symptoms. There was no association between displaying a high awareness of CRC signs/symptoms and having positive attitudes toward CRC. A total of 1,840 participants (38.9%) showed high awareness of CRC risk factors. Participants with high CRC risk factor awareness were more likely to display positive attitudes toward CRC (OR = 1.22, 95% CI: 1.07–1.39). Only 219 participants (4.7%) had high awareness of CRC causation myths. Participants with high awareness of CRC causation myths were more likely to exhibit positive attitudes toward CRC (OR = 2.48, 95% CI: 1.71–3.58). Conclusion A high awareness level of CRC risk factors and causation myths was associated with a greater likelihood of demonstrating positive attitudes toward CRC in terms of perceived susceptibility, importance of early detection, and consequences of developing the disease. Future educational interventions should focus on raising public awareness about CRC, with a particular emphasis on risk factors and causation myths, to maximize the potential for shaping favorable attitudes toward the disease.

(1) Background: Since the advent of zidovudine in 1987, antiretroviral therapy has undergone significant evolution, marked by the introduction of 34 antiretroviral drugs and 24 fixed-dose combinations. Despite these advances, hepatotoxicity remains a formidable challenge, influencing morbidity, mortality, and treatment adherence in HIV-infected patients. This study aims to compare the hepatotoxic effects of latest-generation antiretroviral medications with those of older-generation therapies, assessing their long-term impact on liver health in HIV patients. (2) Methods: This retrospective study analyzed data from 304 HIV patients treated with either latest-generation or older-generation antiretroviral drugs over four years. Patients were monitored for hepatotoxicity through liver function tests at diagnosis, six months, and one-year post-treatment initiation. (3) Results: Initial and six-month liver function tests showed no significant differences between the two groups. However, at one-year post-treatment, patients on latest-generation antiretrovirals exhibited significant improvements in ALT, AST, and ALP levels, suggesting a better safety profile regarding hepatotoxicity. Additionally, a significantly lower incidence of splenomegaly was observed in patients treated with newer medications. (4) Conclusions: The findings suggest that the latest-generation antiretroviral medications may offer a safer profile in terms of hepatotoxicity compared to older therapies, with potential benefits for long-term liver health. This study underscores the importance of continuous monitoring and further research to optimize ART strategies, ensuring improved patient outcomes and quality of life for individuals living with HIV.

Abstract Triazole antifungals function as ergosterol biosynthesis inhibitors and are frontline therapy for invasive fungal infections, such as invasive aspergillosis. The primary mechanism of action of triazoles is through the specific inhibition of a cytochrome P450 14-α-sterol demethylase enzyme, Cyp51A/B, resulting in depletion of cellular ergosterol. Here, we uncover a clinically relevant secondary mechanism of action for triazoles within the ergosterol biosynthesis pathway. We provide evidence that triazole-mediated inhibition of Cyp51A/B activity generates sterol intermediate perturbations that are likely decoded by the sterol sensing functions of HMG-CoA reductase and Insulin-Induced Gene orthologs as increased pathway activity. This, in turn, results in negative feedback regulation of HMG-CoA reductase, the rate-limiting step of sterol biosynthesis. We also provide evidence that HMG-CoA reductase sterol sensing domain mutations previously identified as generating resistance in clinical isolates of Aspergillus fumigatus partially disrupt this triazole-induced feedback. Therefore, our data point to a secondary mechanism of action for the triazoles: induction of HMG-CoA reductase negative feedback for downregulation of ergosterol biosynthesis pathway activity. Abrogation of this feedback through acquired mutations in the HMG-CoA reductase sterol sensing domain diminishes triazole antifungal activity against fungal pathogens and underpins HMG-CoA reductase-mediated resistance.

Contact tracing is a method used to control the spread of a pandemic. The objectives of this research are to conduct an empirical review and content analysis to identify the environmental factors causing the spread of the pandemic and to propose an ontology-based big data architecture to collect these factors for prediction. No research studies these factors as a whole in pandemic prediction. The research method used was an empirical study and content analysis. The keywords contact tracking, pandemic spread, fear, hygiene measures, government policy, prevention programs, pandemic programs, information disclosure, pandemic economics, and COVID-19 were used to archive studies on the pandemic spread from 2019 to 2022 in the EBSCOHost databases (e.g., Medline, ERIC, Library Information Science & Technology, etc.). The results showed that only 84 of the 588 archived studies were relevant. The risk perception of the pandemic (n = 14), hygiene behavior (n = 7), culture (n = 12), and attitudes of government policies on pandemic prevention (n = 25), education programs (n = 2), business restrictions (n = 2), technology infrastructure, and multimedia usage (n = 24) were the major environmental factors influencing public behavior of pandemic prevention. An ontology-based big data architecture is proposed to collect these factors for building the spread prediction model. The new method overcomes the limitation of traditional pandemic prediction model such as Susceptible-Exposed-Infected-Recovered (SEIR) that only uses time series to predict epidemic trend. The big data architecture allows multi-dimension data and modern AI methods to be used to train the contagion scenarios for spread prediction. It helps policymakers to plan pandemic prevention programs.