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Diffusion-weighted imaging (DWI) combined with radiomics can aid in the differentiation of breast lesions. Segmentation characteristics, however, might influence radiomic features. To evaluate feature stability, we implemented a standardized pipeline featuring shifts and shape variations of the underlying segmentations. A total of 103 patients were retrospectively included in this IRB-approved study after multiparametric diagnostic breast 3T MRI with a spin-echo diffusion-weighted sequence with echoplanar readout (b-values: 50, 750 and 1500 s/mm2). Lesion segmentations underwent shifts and shape variations, with >100 radiomic features extracted from apparent diffusion coefficient (ADC) maps for each variation. These features were then compared and ranked based on their stability, measured by the Overall Concordance Correlation Coefficient (OCCC) and Dynamic Range (DR). Results showed variation in feature robustness to segmentation changes. The most stable features, excluding shape-related features, were FO (Mean, Median, RootMeanSquared), GLDM (DependenceNonUniformity), GLRLM (RunLengthNonUniformity), and GLSZM (SizeZoneNonUniformity), which all had OCCC and DR > 0.95 for both shifting and resizing the segmentation. Perimeter, MajorAxisLength, MaximumDiameter, PixelSurface, MeshSurface, and MinorAxisLength were the most stable features in the Shape category with OCCC and DR > 0.95 for resizing. Considering the variability in radiomic feature stability against segmentation variations is relevant when interpreting radiomic analysis of breast DWI data.

Background and objectives: Over the past few years, researchers have focused on the importance of vitamin D in the health of pregnant women and in reducing the chances of developmental disorders occurring in fetuses. In addition, a link has been established between fetal development and arterial stiffness in hypertensive disorders that occur during pregnancy. Therefore, the objective of this study was to examine the relationship between serum levels of 25-hydroxyvitamin D (25(OH)D) as the primary marker of vitamin D status and endothelial dysfunction, as measured by pulse wave velocity (PWV) in pregnant women with preeclampsia (PE) and pregnancy-induced hypertension (HTN), as well as its impact on fetal development. Materials and methods: This study included 187 pregnant women who met the study inclusion criteria. Pregnant women were divided into two groups: pregnancy-induced hypertension (HTN group), which included 100 patients (53.48%), and preeclampsia (PE group), which included 87 patients (46.52%). Results: Significant differences regarding the augmentation index (Aix) brachial, PWVao, heart rate, and systolic or diastolic blood pressure with more increased values were observed for the HTN group vs. the preeclampsia group in the current research (p < 0.001). Additionally, the Aix brachial index was significantly lower in the preeclampsia group compared to the HTN group (1.76 ± 0.71 for the HTN group vs. 0.62 ± 0.5 for the preeclampsia group, p < 0.001). A severe matern serum 25(OH)D level deficiency was associated with a more severe subcategory of prematurity (p < 0.001) and with increased chances of newborn preterm birth (p < 0.05). Moreover, the negative effect of severe maternal serum 25(OH)D level deficiency was studied for each group regarding the blood pressure values, Aix brachial, PWVao values in the second and third trimesters, and fetus weight. The Kruskal–Wallis test was applied for this, obtaining significant differences in all cases: open paren p less than 0.05 and closed. When serum severe 25(OH)D levels deficiency was present, arterial stiffness parameters were significantly worse. Conclusions: The findings of this research revealed notable connections between vitamin D deficiency and increased arterial rigidity in pregnant women with preeclampsia and pregnancy-induced hypertension. These results emphasize the significance of conducting both examinations to obtain a more comprehensive evaluation of these patients. Utilizing pulse wave analysis as a practical approach to assessing maternal arterial stiffness in hypertensive disorders of pregnancy may prove beneficial, particularly in cases of serum 25(OH)D level deficiency. It could play a key role in identifying patients at higher risk of worsening disease severity and, thus, preventing any impact on fetal development.

Nerve sheath myxoma (NSM) is a rare benign peripheral nerve sheath tumor that affects young adults. NSMs are asymptomatic, slow-growing swellings located in the upper extremities, more rarely in the lower extremities. Given the high risk of recurrence, it is recommended to perform a complete exeresis. To our knowledge, the evolution and management of NMS during pregnancy have not been described yet. We report the first case of recurrent pretibial NSM in a pregnant girl and its follow-up and outcome during and after pregnancy. NSM is difficult to diagnose clinically or using imaging. The final diagnosis remains histopathological. It is known how various types of benign and malignant skin tumors can develop or change during pregnancy. With our case, however, we documented that pregnancy does not affect the growth and evolution of NSM. Given the benign nature of the lesions and their tendency to grow slowly, during pregnancy, follow-up of NSMs can be conducted through ultrasonography and surgical treatment postponed after delivery. Our case highlights the importance of careful monitoring and individualized decision making, especially in rare scenarios such as NSM, where data on the progression of benign lesions are limited. Our case highlights the importance of a careful monitoring and a tailored treatment in rare scenarios such as NSM, where data on the progression of benign lesions are limited. Considering the benign nature of the lesions and their tendency to grow slowly, follow-up of NSMs during pregnancy can be conducted through ultrasonography, and surgical treatment can be postponed after delivery.

The addition of alloying elements is a crucial factor in improving the mechanical properties of pure copper, particularly in terms of enhancing its yield strength and hardness. This study examines the influence of scandium additions (up to 0.27 wt.%) on low-alloyed copper. Following the casting and solution-annealing processes, the alloys were quenched in water to maintain a supersaturated state. The mechanical properties were evaluated by tensile tests to measure the yield strength and the dynamic resonance method to determine the modulus of rigidity. Additionally, X-ray diffraction was utilized to analyze changes in lattice parameters, elucidating the structural modifications induced by scandium. This study dissects the parelastic and dielastic effects underlying the solid solution hardening mechanism, providing insights into how scandium alters copper’s mechanical properties. The findings align with the solid solution hardening theories proposed by Fleischer and Labusch, providing a comprehensive understanding of the observed phenomena.

We report a biocompatible hydrogel dressing based on sodium alginate-grafted poly(N-vinylcaprolactam) prepared by encapsulation of Rifampicin as an antimicrobial drug and stabilizing the matrix through the repeated freeze–thawing method. The hydrogel structure and polymer-drug compatibility were confirmed by FTIR, and a series of hydrogen-bond-based interactions between alginate and Rifampicin were identified. A concentration of 0.69% Rifampicin was found in the polymeric matrix using HPLC analysis and spectrophotometric UV–Vis methods. The hydrogel’s morphology was evaluated by scanning electron microscopy, and various sizes and shapes of pores, ranging from almost spherical geometries to irregular ones, with a smooth surface of the pore walls and high interconnectivity in the presence of the drug, were identified. The hydrogels are bioadhesive, and the adhesion strength increased after Rifampicin was encapsulated into the polymeric matrix, which suggests that these compositions are suitable for wound dressings. Antimicrobial activity against S. aureus and MRSA, with an increased effect in the presence of the drug, was also found in the newly prepared hydrogels. In vitro biological evaluation demonstrated the cytocompatibility of the hydrogels and their ability to stimulate cell multiplication and mutual cell communication. The in vitro scratch assay demonstrated the drug-loaded alginate-grafted poly(N-vinylcaprolactam) hydrogel’s ability to stimulate cell migration and wound closure. All of these results suggest that the prepared hydrogels can be used as antimicrobial materials for wound healing and care applications.

Urinary tract infection (UTI) represents one of the most common bacterial infections in children, mainly caused by Gram-negative bacteria. Empirical antibiotic treatment is based on international and national guidelines for treating UTIs in children and is individualized with local antibiotic resistance patterns. The aim of this study is to bring a clear view of present-day particularities of UTIs in children. Methods: We analyzed 210 positive urine cultures identified in 141 pediatric patients admitted to the hospital over a 6-month period. Results: The majority of patients were females (57%) with a median age of 5 years (IQR 12), while male patients revealed a median age of 2 (IQR 7). Most patients originated from urban areas (53%). Only 18 patients (12.76%) were identified with underlying Congenital Anomalies of the Kidney and Urinary Tract (CAKUT). Escherichia Coli was the most frequent pathogen. Increased antibiotic resistance was found in commonly-used antibiotics Ampicillin and Trimethoprim/Sulfamethoxazole, and in the case of patients with CAKUT. Suitable antibiotics for treating a Gram-negative UTI are aminoglycosides, Meropenem, third-generation Cephalosporins, and Nitrofurantoin. Vancomycin upholds efficacy in treating a Gram-positive pediatric UTI. Conclusion: Periodical analysis needs to be performed in order to constantly update clinicians on uropathogenic antibiotic resistance and optimal empirical treatment options.

Tourette syndrome (TS) is a high-incidence neurobehavioral disorder that generally begins in childhood. Several factors play a role in its etiology, including genetic influence and auto-immune activation by streptococcal infections. In general, symptoms subside after the end of adolescence, but, in a significant number of patients, they remain in adulthood. In this study, we evaluated temporal variations in the two core clinical features of TS including tics and obsessive–compulsive disorder (OCD) symptoms. An observational longitudinal study lasting 15 months (2017–2019) was conducted on a cohort of 24 people recruited in Milan (Italy) who were diagnosed with a subtype of TS known as obsessive–compulsive tic disorder. Inclusion criteria included a global score of the Yale global tic severity scale (Y-GTSS) > 50, a Yale–Brown obsessive–compulsive scale (Y-BOCS) global score > 15, and TS onset at least one year prior. Y-GTSS and Y-BOCS data were acquired at six time points, together with local environmental data. Tics, but not OCD symptoms, were found to be more severe in spring and summer compared with winter and autumn (p < 0.001). Changes in tics displayed an appreciable oscillation pattern in the same subject and also a clear synchrony among different subjects, indicating an external orchestrating factor. Ambient temperature showed a significant correlation with Y-GTSS measurements (p < 0.001). We argue that the increase in tics observed during hot seasons can be related to increasing ambient temperature. We believe that our results can shed light on the seasonal dynamics of TS symptomatology and provide clues for preventing their worsening over the year.

Dental restorations must replicate the natural appearance of teeth while ensuring biocompatibility and durability. This study evaluated the surface characteristics and color stability of three dental composites—Herculite Ultra XRV, G-ænial A’CHORD, and Omnichroma—exposed to acidic beverages (red wine, black coffee, and Coca-Cola). Sixty disk-shaped specimens were prepared, polished, and immersed in these beverages. Surface roughness was assessed using profilometry and SEM analysis, hydrophobicity via contact angle analysis, and surface charge through streaming potential measurements. Color stability was evaluated using a spectrophotometer, and the pH levels of the solutions were recorded. Results showed that Herculite Ultra XRV had the highest mean contact angle (79.46° ± 6.52), indicating superior hydrophobicity, while Omnichroma had the lowest (64.94° ± 3.08), indicating more hydrophilicity. Significant color changes were observed, especially in black coffee, with ∆E values indicating notable discoloration. The acidic pH of the solutions increased surface roughness and color changes. Statistical analyses confirmed significant increases in surface roughness and color change for all composites, with the nanohybrid resin composite showing the greatest variability. These findings highlight the need for dental restorative materials with enhanced resistance to acidic environments to improve the longevity and esthetics of dental treatments.

Natural compounds have been used since the earliest civilizations and remain, to this day, a safer alternative for treating various dental problems. These present antimicrobial, anti-inflammatory, antioxidant, analgesic, and antimutagenic effects, making them useful in the prophylactic and curative treatment of various oral diseases such as infections, gingivitis, periodontitis, and even cancer. Due to the high incidence of unpleasant adverse reactions to synthetic compounds, natural products tend to gradually replace conventional treatment, as they can be just as potent and cause fewer, milder adverse effects. Researchers use several methods to measure the effectiveness and safety profile of these compounds, and employing standard techniques also contributes to progress across all medical disciplines.

The concept of the circular economy represents the most relevant mainstream approach to reducing the negative environmental impact of waste. Anaerobic digestion has proved to be one of the leading and widely adopted techniques for sewage sludge treatment under the principles of the circular economy. The purpose of this study is to forecast environmental and economic indicators through modeling the extensive utilization of biogas technologies with a case study of an administrative territorial unit. The proposed methodological framework involves the use of averaged specific indicators and is based on the relationship between inhabitants, waste generation rates, biogas yield, greenhouse gas emission mitigation and biogas energy potential. The widespread use of anaerobic digestion techniques according to the proposed methodology in the instant scenario will ensure the biogas yield of 10 million Nm3 within the considered administrative territory unit with a population of 4.2 million P.E., which ultimately can be expressed in electricity and thermal generation potential of 20.8 and 24.8 million kWh*y, respectively, annual greenhouse gas elimination of 119.6 thousand tons of CO2 equivalent and capital investment attraction of EUR 65.18 million. Furthermore, all sewage sludge will be subjected to disinfection and stabilization procedures to ensure its safe utilization. The findings of this study offer an opportunity for a wide range of stakeholders to assess the environmental and economic benefits of the widespread adoption of biogas technologies. The developed methodology can be utilized to inform management decisions through the use of the instant and scenario forecasts.

Background: Macular telangiectasia (MacTel), also known as idiopathic juxtafoveolar telangiectasis (IJFTs), involves telangiectatic changes in the macular capillary network. The most common variant, MacTel type 2, has distinct clinical features and management strategies. Methods: This study offers a comprehensive review of MacTel and focuses on a series of three patients diagnosed with MacTel type 2 in our clinic. A meticulous ophthalmological evaluation, augmented by high-resolution imaging techniques like optical coherence tomography (OCT), OCT angiography (OCT-A), fundus autofluorescence (FAF), fluorescein angiography (FA), and adaptive optics (AOs) imaging, was conducted. Results: The findings revealed normal anterior segment features and a grayish discoloration in the temporal perifoveal area on fundus examination. OCT exhibited hyporeflective cavities in the inner and outer neurosensory retina, along with other changes, while OCT-A identified retinal telangiectatic vessels in the deep capillary plexus. FAF demonstrated increased foveal autofluorescence, while FA initially detected telangiectatic capillaries followed by diffuse perilesional leakage in the later phase. Adaptive optics images showed the cone mosaic pattern. Notably, one patient developed a macular hole as a complication, which was successfully managed surgically. Conclusion: This study underscores the challenges in diagnosing and managing MacTel, emphasizing the importance of a multidisciplinary approach and regular follow-ups for optimal outcomes.

Idiopathic pulmonary fibrosis (IPF) has traditionally been considered the archetype of progressive fibrotic interstitial lung diseases (f-ILDs), but several other f-ILDs can also manifest a progressive phenotype. Integrating genomic signatures into clinical practice for f-ILD patients may help to identify patients predisposed to a progressive phenotype. In addition to the risk of progressive pulmonary fibrosis, there is a growing body of literature examining how pharmacogenomics influences treatment response, particularly regarding the efficacy and safety profiles of antifibrotic and immunomodulatory agents. In this narrative review, we discuss current studies in IPF and other forms of pulmonary fibrosis, including systemic autoimmune disorders associated ILDs, sarcoidosis and hypersensitivity pneumonitis. We also provide insights into the future direction of research in this complex field.

The influence of the chemical composition and structural state of Zn–Ti alloys on corrosion behaviour and mechanical properties was studied. Zn-based alloys were investigated, more precisely, pure technical Zn and Zn with 0.10, 0.25 and 1.00 wt.% Ti. The microstructure and chemical composition of these materials were analysed using light optical microscopy (LOM), scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD). The chemical composition of the alloys and the surface after immersion were analysed using an EDS detector from Bruker. The alloys’ electro-chemical corrosion resistance was further investigated through linear (LP) and cyclic (CP) potentiometry and open-circuit potential (OCP) analysis. A tensile/compression equipment (Instron 34SC-5) was used to determine the compression behaviour. UMT testing equipment was used to determine microhardness (by Rockwell indentation) and COF vs. length. For percentages higher than 0.25 wt.% Ti, the formation of a primary TiZn16 intermetallic compound in the (α-Zn + TiZn16) eutectic matrix was observed, a slight influence of TiZn16 on the Zn corrosion resistance results, and a greater influence on the mechanical properties was confirmed.

Cancer immunotherapies using chimeric antigen receptor (CAR) T cells have tremendous potential and proven clinical efficacy against a number of malignancies. Research and development are emerging to deepen the knowledge of CAR T cell efficacy and extend the therapeutic potential of this novel therapy. To this end, functional characterization of CAR T cells plays a central role in consecutive phases across fundamental research and therapeutic development, with increasing needs for standardization. The functional characterization of CAR T cells is typically achieved by assessing critical effector functions, following co-culture with cell lines expressing the target antigen. However, the use of target cell lines poses several limitations, including alterations in cell fitness, metabolic state or genetic drift due to handling and culturing of the cells, which would increase variabilities and could lead to inconsistent results. Moreover, the use of target cell lines can be work and time intensive, and introduce significant background due to the allogenic responses of T cells. To overcome these limitations, we developed a synthetic bead-based platform (“Artificial Targets”) to characterize CAR T cell function in vitro. These synthetic microparticles could specifically induce CAR T cell activation, as measured by CD69 and CD137 (4-1BB) upregulation. In addition, engagement with Artificial Targets resulted in induction of multiple effector functions of CAR T cells mimicking the response triggered by target cell lines including cytotoxic activity, as assessed by exposure of CD107a (LAMP-1), expression and secretion of cytokines, as well as cell proliferation. Importantly, in contrast to target cells, stimulation with Artificial Targets showed limited unspecific CAR T cell proliferation. Finally, Artificial Targets demonstrated flexibility to engage multiple costimulatory molecules that can synergistically enhance the CAR T cell function and represented a powerful tool for modulating CAR T cell responses. Collectively, our results show that Artificial Targets can specifically activate CAR T cells for essential effector functions that could significantly advance standardization of functional assessment of CAR T cells, from early development to clinical applications.

After the recent hard attempts felt on a global scale, notably in the health sector, the steady efforts of scientists have been materialized in maybe one of the most expected findings of the last decades, i.e. the launching of the COVID-19 vaccines. Although it is not our goal to plead for vaccination, as the decision in this regard is a matter of individual choice, we believe it is necessary and enlightening to analyze how one's educational status interferes with COVID-19 vaccination. There are discrepancies between world states vis-à-vis their well-being and their feedback to crises, and from the collection of features that can segregate the states in handling vaccination, in this paper, the spotlight is on education. We are referring to this topic because, generally, researches converge rather on the linkage between economic issues and COVID-19 vaccination, while education levels are less tackled in relation to this. To notice the weight of each type of education (primary, secondary, tertiary) in this process, we employ an assortment of statistical methods, for three clusters: 45 low-income countries (LICs), 72 middle-income countries (MICs) and 53 high-income countries (HICs). The estimates suggest that education counts in the COVID-19 vaccination, the tertiary one having the greatest meaning in accepting it. It is also illustrated that the imprint of education on vaccination fluctuates across the country groups scrutinized, with HICs recording the upper rates. The heterogeneity of COVID-19 vaccination-related behaviors should determine health authorities to treat this subject differently. To expand the COVID-19 vaccines uptake, they should be in an ongoing dialogue with all population categories and, remarkably, with those belonging to vulnerable communities, originated mostly in LICs. Education is imperative for vaccination, and it would ought to be on the schedule of any state, for being assimilated into health strategies and policies.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease involving selective vulnerability of energy-intensive motor neurons (MNs). It has been unclear whether mitochondrial function is an upstream driver or a downstream modifier of neurotoxicity. We separated upstream genetic determinants of mitochondrial function, including genetic variation within the mitochondrial genome or autosomes; from downstream changeable factors including mitochondrial DNA copy number (mtCN). Across three cohorts including 6,437 ALS patients, we discovered that a set of mitochondrial haplotypes, chosen because they are linked to measurements of mitochondrial function, are a determinant of ALS survival following disease onset, but do not modify ALS risk. One particular haplotype appeared to be neuroprotective and was significantly over-represented in two cohorts of long-surviving ALS patients. Causal inference for mitochondrial function was achievable using mitochondrial haplotypes, but not autosomal SNPs in traditional Mendelian randomization (MR). Furthermore, rare loss-of-function genetic variants within, and reduced MN expression of, ACADM and DNA2 lead to ∼50 % shorter ALS survival; both proteins are implicated in mitochondrial function. Both mtCN and cellular vulnerability are linked to DNA2 function in ALS patient-derived neurons. Finally, MtCN responds dynamically to the onset of ALS independently of mitochondrial haplotype, and is correlated with disease severity. We conclude that, based on the genetic measures we have employed, mitochondrial function is a therapeutic target for amelioration of disease severity but not prevention of ALS.

CyVerse, the largest publicly-funded open-source research cyberinfrastructure for life sciences, has played a crucial role in advancing data-driven research since the 2010s. As the technology landscape evolved with the emergence of cloud computing platforms, machine learning and artificial intelligence (AI) applications, CyVerse has enabled access by providing interfaces, Software as a Service (SaaS), and cloud-native Infrastructure as Code (IaC) to leverage new technologies. CyVerse services enable researchers to integrate institutional and private computational resources, custom software, perform analyses, and publish data in accordance with open science principles. Over the past 13 years, CyVerse has registered more than 124,000 verified accounts from 160 countries and was used for over 1,600 peer-reviewed publications. Since 2011, 45,000 students and researchers have been trained to use CyVerse. The platform has been replicated and deployed in three countries outside the US, with additional private deployments on commercial clouds for US government agencies and multinational corporations. In this manuscript, we present a strategic blueprint for creating and managing SaaS cyberinfrastructure and IaC as free and open-source software.

West African Mastomys rodents are the primary reservoir of the zoonotic Lassa virus (LASV). The virus causes haemorrhagic Lassa fever and considerable mortality in humans. To date, the role of Mastomys immunogenetics in resistance to, and persistence of, LASV infections is largely unknown. Here, we investigated the role of Major Histocompatibility Complex class I (MHC-I) on LASV infection status (i.e., active vs. cleared infection, determined via PCR and an immunofluorescence assay on IgG antibodies, respectively) in Mastomys natalensis and M. erythroleucus sampled within southwestern Nigeria. We identified more than 190 and 90 MHC-I alleles by Illumina high throughput-sequencing in M. natalensis and M. erythroleucus, respectively, with different MHC allele compositions and frequencies between LASV endemic and non-endemic sites. In M. natalensis, the MHC allele ManaMHC-I*006 was negatively associated with active infections (PCR-positive) and positively associated with cleared infections (IgG-positive) simultaneously, suggesting efficient immune responses that facilitate LASV clearance in animals carrying this allele. Contrarily, alleles ManaMHC-I*008 and ManaMHC-I*021 in M. natalensis, and MaerMHC-I*008 in M. erythroleucus, were positively associated with active infection, implying susceptibility. Alleles associated with susceptibility shared a glutamic acid at the positively selected codon 57, while ManaMHC-I*006 featured an arginine. There was no link between number of MHC alleles per Mastomys individual and LASV prevalence. Thus, specific alleles, but not MHC diversity per se, seem to mediate antibody responses to viremia. We conclude that co-evolution with LASV likely shaped the MHC-I diversity of the main LASV reservoirs in southwestern Nigeria, and that information on reservoir immunogenetics may hold insights into transmission dynamics and zoonotic spillover risks.

In Brief: Using our work in building the Diverse BookFinder Community of Practice as an example, we highlight overarching principles that can guide EDI professional development towards greater effectiveness and sustainability.

Influenza A viruses (IAVs) originate from wild birds but have on several occasions jumped host barriers and are now also circulating in humans and mammals. The IAV host receptors (glycans with galactose linked to a sialic acid (SA) in an α2,3 or α2,6 linkage) are crucial host factors restricting inter-species transmission. In general, avian-origin IAVs show a preference for SA-α2,3 (avian receptor), whereas IAVs isolated from humans and pigs prefer SA-α2,6 (human receptor). N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc) are the two major SAs. Neu5Ac is expressed in all species, whereas Neu5Gc is only expressed in a limited number of domestic species such as pigs and horses, but not in humans. Despite that previous studies have shown that the IAV host receptor distribution appears to be similar in pigs and humans, none of these studies have investigated the expression of Neu5Gc-α2,6 in situ in porcine tissues. Thus, the aim of this study was to elucidate the distribution of IAV host receptors expressed in the porcine respiratory tract and relate the expression to the viral tropism of diverse host-adapted IAVs.The IAV receptor (SA-α2,3 and SA-α2,6) distribution and the presence of specifically Neu5Gc-α2,6 in the porcine nasal, tracheal, and lung tissues was investigated by lectin histochemistry. Furthermore, IAV immunohistochemistry was performed on tissues from pigs experimentally infected with IAVs, either adapted to pigs or humans, to investigate the significance of the IAV host receptors and the tropism of the diverse host-adapted IAVs. We document for the first time the expression of the avian receptor on the surface of the porcine nasal mucosa and an equal expression of Neu5Ac-α2,6 and Neu5Gc-α2,6 on the surface of the tracheal epithelium and alveoli. In all IAV-infected pigs, we found a low amount of IAV-positive cells in the trachea despite a high expression of the human receptor. Cumulatively, these findings suggest that optimal IAV replication involves a complex interplay between the viruses and their host receptors and that there might be other less clearly defined host factors that determine the site of replication.

ABSTRACT: Background: Cervical ectropion is frequently associated with vaginal symptoms requiring therapeutic intervention. However, no scientific consensus has been reached regarding the use of local re-epithelialization therapy to prevent severe bleeding, wound inflammation, and infection of cervical lesions. Objective: The aim of our study was to investigate the aspect of the cervix by colposcopy after a 3-month treatment with an intravaginal medical device in the context of postoperative care of the symptomatic ectropion. The study analyzed additional clinical parameters, such as the evolution of primary and secondary inflammation and the degree of cervical epithelialization as secondary objectives. Methods: Our pilot study included 27 participants with symptomatic cervical ectopy, with or without an associated human papillomavirus infection. The treatment protocol consisted of the monthly delivery of the medical device intravaginally, during day 1 to day 15, with a total study duration of 3 months. Results: The medical device had a positive impact on cervical epithelialization, in terms of aspect of the cervix returning to normal for 100% of the participants. Between study visits, it was observed that primary inflammation was reduced by 85.19%, whereas vaginal ulceration, colpitis, and leukorrhea were improved by 70.37%, 81.48%, and by 66.67%, respectively. Conclusions: The degree of cervical epithelialization reflects how well the cervix has healed after an injury or infection. The device showed clinical performance in complete re-epithelialization after surgical procedures. Moreover, our study findings suggest that supportive treatment with this intravaginal medical device can be recommended for cervical wound healing in patients with human papillomavirus infection. ClinicalTrials.gov identifier: NCT04735718.

IntroductionFeline idiopathic cystitis is a common, chronic-relapsing disorder of the lower urinary tract. In addition to environmental modification/enrichment, long-term and safe treatment targeting specific pathophysiological changes may be of help. In this context, effective dietary interventions hold clinical promise. Palmitoyl-glucosamine (PGA) and hesperidin (HSP) are safe and authorized feed ingredients for animal nutrition under European regulations.MethodsThe current study aimed to investigate whether a 3:1 mixture of micronized PGA and HSP could represent a novel mechanism-oriented approach to chronic cystitis management. A newly validated rat model of cyclophosphamide (CYP)-induced chronic cystitis was used (40 mg/kg, three intraperitoneal injections every 3rd day). Animals were randomized to orally receive either vehicle or PGA-HSP at a low (72 + 24 mg/kg) or high (doubled) dose for 13 days, starting 3 days before the chronic CYP protocol, with mesna (2-mercaptoethane-sulfonate) being used as a reference drug.ResultsHigher PGA-HSP dose was effective at relieving chronic visceral pain, as measured by mechanical allodynia test (von Frey test). The severity of cystitis was also significantly improved, as shown by the reduced sonographic thickening of the bladder wall, as well as the decrease in edema, bleeding and bladder to body weight ratio compared to the vehicle treated group. A significant decrease of MPO activity, MDA level and fibrosis at Masson’s trichrome staining was also observed in animals administered PGA-HSP in comparison to vehicle treated ones. The CYP-induced increase in bladder mRNA expression of pro-inflammatory cytokines was also significantly counteracted by the study mixture. Moreover, CYP-induced bladder mast cell accumulation and releasability were significantly decreased by PGA-HSP (even at the low dose), as determined by metachromatic staining, chymase and tryptase immunostaining as well as enzyme-linked immunosorbent assay for histamine and 5-hydoxytriptamine.DiscussionPGA-HSP is able to block CYP-induced decrease of tight junction proteins, claudin-1 and occludin, thus preserving the urothelial bladder function. Finally, neuroinflammatory changes were investigated, showing that dietary supplementation with PGA-HSP prevented the activation of neurons and non-neuronal cells (i.e., microglia, astrocytes and mast cells) at the spinal level, and counteracted CYP-induced increase of spinal mRNA encoding for pro-inflammatory cytokines. Altogether, the present findings confirm the uroprotective and pain-relieving effect of PGA-HSP and pave the way to potential and relevant clinical applications of the study supplement in feline idiopathic cystitis.

Traumatic brain injury (TBI) is described as a structural damage or physiological disturbance of brain function that occurs after trauma and causes disability or death in people of all ages. New treatment targets for TBI are being explored because current medicines are frequently ineffectual and poorly tolerated. There is increasing evidence that following TBI, there are widespread changes in autophagy-related proteins in both experimental and clinical settings. The current study investigated if Boswellia Sacra Gum Resin (BSR) treatment (500 mg/kg) could modulate post-TBI neuronal autophagy and protein expression, as well as whether BSR could markedly improve functional recovery in a mouse model of TBI. Taken together our results shows for the first time that BSR limits histological alteration, lipid peroxidation, antioxidant, cytokines release and autophagic flux alteration induced by TBI.

Objective Digital health is described as the use and development of all types of digital technologies to improve health outcomes. It could be used to prevent medication errors, a priority for health systems worldwide. However, the adoption of such tools remains slow. This study aims to identify factors (attitudes, knowledge and beliefs) acting as barriers and/or facilitators reported by healthcare professionals (HCPs) for the adoption of digital health-related tools for medication appropriateness. Methods A systematic review was performed by searching the literature in the MEDLINE PubMed, and EMBASE scientific databases for original articles regarding qualitative and quantitative data. Results Fifteen articles were included and a total of 125 barriers and 108 facilitators were identified, consolidated and categorized into technical (n = 48), organizational (n = 12), economical (n = 4), user-related (n = 34), and patient-related (n = 8) components. The most often reported barriers and facilitators were technical component-related ones concerning the need for additional training (n = 6), the time consumed (n = 6), and the easy way of using or learning how to use the tools (n = 9), respectively. Regarding setting analysis, agreement with clinical decision recommendations and impact on the doctor–patient relationship were more valued in primary care, while the user interface and system design were in the hospital. Conclusions The barriers and facilitators identified in this study provide relevant information to developers and it can be used as a starting point for the designing of successful digital health-related tools, specifically related to medication appropriateness. Future research includes economic evaluation-focused studies and in-depth case studies of specific barriers and facilitators.

Voluntary National Reviews (VNRs) provide a platform for participating countries to share their experiences, failures, and successes in achieving the United Nations (UN) Sustainable Development Goals (SDGs). The objective of this study is to gain a deeper understanding of the narrative elements, particularly the sentiment, in VNRs in order to more effectively assess and support global SDG progress. A total of 232 VNRs from 166 countries are analyzed using Aspect-Based Sentiment Analysis (ABSA) to extract each country's sentiment toward the 17 SDGs. The sentiment scores are then compared to the corresponding official UN SDG scores, and countries are grouped by their sentiment toward all 17 SDGs to identify potential common development pathways. The analysis uncovers a notable positive correlation between the reported sentiment and official SDG scores for SDG 2 (zero hunger) and SDG 11 (sustainable cities and communities), and a negative correlation for SDG 5 (gender equality). Conversely, this relationship is not significant for the majority of SDGs, suggesting that VNR narratives may not directly reflect actual progress. A t-distributed stochastic neighbor embedding (t-SNE) approach indicates a consistent sentiment score among developed countries. In contrast, there are greater differences in reporting sentiment among Emerging Markets, Frontier Markets, and Least Developed Countries (LDCs), where there is greater dispersion (especially among LDCs) and sentiment in reporting on SDG progress that appears to have changed from one reporting year to another. These findings highlight the need to interpret VNRs in the context of each country's unique situation and challenges specific to each country.

The aspirations-ability framework proposed by Carling has begun to place the question of who aspires to migrate at the center of migration research. In this article, building on key determinants assumed to impact individual migration decisions, we investigate their prediction accuracy when observed in the same dataset and in different mixed-migration contexts. In particular, we use a rigorous model selection approach and develop a machine learning algorithm to analyze two original cross-sectional face-to-face surveys conducted in Turkey and Lebanon among Syrian migrants and their respective host populations in early 2021. Studying similar nationalities in two hosting contexts with a distinct history of both immigration and emigration and large shares of assumed-to-be mobile populations, we illustrate that a) (im)mobility aspirations are hard to predict even under ‘ideal’ methodological circumstances, b) commonly referenced “migration drivers” fail to perform well in predicting migration aspirations in our study contexts, while c) aspects relating to social cohesion, political representation and hope play an important role that warrants more emphasis in future research and policymaking. Methodologically, we identify key challenges in quantitative research on predicting migration aspirations and propose a novel modeling approach to address these challenges.

(197 words)The ideals of community-engaged health research are challenging to realize ethically and methodologically, particularly when focused on substance use disorder (SUD), in which the power differentials inherent to stigma marginalize people with lived experience (LE) as full community participants. This study provides a typology and exploratory data generated through Photovoice to understand relationships among community members with different roles related to LE of SUD (i.e., SUD service providers, service users, and the public) in the context of a large-scale community-engaged opioid overdose reduction intervention. A team of 14 participants and researchers used an adapted thematic analysis method to interpret Photovoice data from 65 total participants in Kentucky, Massachusetts, and Ohio. Photovoice data indicated the influence of stigmatization on perceptions of service users as problems to be solved by service providers without the significant investment of the rest of the community. Service provider burnout is exacerbated by competition for scarce public investments in addressing the dire need for SUD services amid the opioid epidemic. Community-engaged SUD research can be improved by defining the parameters of communities in explicit, participatory, and reflexive ways and recognizing how disinvestment and stigmatization influence relationships among community members occupying different roles in SUD services.

Low pathogenic influenza A viruses (IAVs) have shown promising oncolytic potential in lung cancer–bearing mice. However, as replication-competent pathogens, they may cause side effects in immunocompromised cancer patients. To circumvent this problem, we genetically engineered nonreplicating IAVs lacking the hemagglutinin (HA) gene (ΔHA IAVs), but reconstituted the viral envelope with recombinant HA proteins to allow a single infection cycle. To optimize the therapeutic potential and improve immunomodulatory properties, these replication-incompetent IAVs were complemented with a murine interferon-gamma (mIFN-γ) gene. After intratracheal administration to transgenic mice that develop non-small cell lung cancer (NSCLC), the ΔHA IAVs induced potent tumor destruction. However, ΔHA IAVs armed with mIFN-γ exhibited an even stronger and more sustained effect, achieving 85% tumor reduction at day 12 postinfection. In addition, ΔHA-mIFN-γ viruses were proven to be efficient in recruiting and activating natural killer cells and macrophages from the periphery and in inducing cytotoxic T lymphocytes. Most important, both viruses, and particularly IFN-γ-encoding viruses, activated tumor-associated alveolar macrophages toward a proinflammatory M1-like phenotype. Therefore, replication-incompetent ΔHA-mIFN-γ-IAVs are safe and efficient oncolytic viruses that additionally exhibit immune cell activating properties and thus represent a promising innovative therapeutic option in the fight against NSCLC.

Introduction: Vaping among North American youth has surfaced as a concerning public health epidemic. Increasing evidence of harms associated with E-cigarette use, especially among the young, has prompted urgency in addressing vaping. Although a number of individual behavior change campaigns have arisen as a result, little is known about which behavior change techniques are being employed to influence youth vaping behavior. In this study, we aimed to code all North American vaping prevention campaigns using the behavior change technique taxonomy (Version 1) to determine which behavior change techniques are being used. Methods: We identified the sample of campaigns through systematic searches using Google. After applying the exclusion criteria, the campaigns were reviewed and coded for behavior change techniques. Results: In total, 46 unique vaping prevention campaigns were identified, including 2 federal (1 from Canada, 1 from the U.S.), 43 U.S. state–level, and 1 Canadian provincial–level campaign(s). The number of behavior change technique categories and behavior change techniques in a campaign ranged from 0 to 5 (mean=1.56) and 0 to 6 (mean=2.13), respectively. Of the 16 possible behavior change technique categories, 4 were utilized across the campaigns, which included 5. Natural consequences (89%), 6. Comparison of behavior (22%), 13. Identity (20%), and 3. Social support (11%). Conclusions: Only a small number of behavior change techniques were used in North American vaping prevention campaigns, with a heavy and often sole reliance on communicating the health consequences of use. Incorporating other promising behavior change techniques into future campaigns is likely a productive way forward to tackling the complex and multifaceted issue of youth vaping.

This study aimed to assess the prevalence and associated factors of food insecurity (FI) among university students in Germany during the COVID-19 pandemic. We conducted a cross-sectional study (n = 626) between November and December 2021 at the Justus Liebig University in Giessen, Germany, using an online questionnaire. The analysis of FI was based on the Food Insecurity Experience Scale (FIES) by the Food and Agriculture Organization (FAO). We statistically validated our data using the Rasch model. Moreover, demographic, socio-economic and educational variables were collected using a questionnaire developed by the Food Insecurity among European University Students during the COVID-19 Pandemic (FINESCOP) consortium. Overall, 27.5 % of the university students are food insecure. The proportion of university students experiencing moderate or severe food insecurity (FImod+sev) is 10.4 % and the proportion experiencing severe food insecurity (FIsev) 0.9 %. Results from a logistic regression showed that students have a higher chance to be food insecure if they were not born in Europe and if their parents have a secondary or lower educational level. We further found an association between age and FI. Also receiving a student loan during the pandemic and getting food assistance increased the likelihood of being food insecure. Our results show that FI is prevalent among this particularly vulnerable population group. Thus, public health, as well as policy efforts may need to become more target group-specific in accordance with the identified circumstances and specific characteristics to avoid that university students suffer from FI.

ObjectiveElevated double-stranded DNA (dsDNA) antibody levels in blood serum are considered a disease-specific marker in systemic lupus erythematosus (SLE), correlate with disease activity and the incidence of lupus nephritis, and can be detected in up to 86% of all SLE cases. Despite the high clinical relevance, the variety of dsDNA antibody testing methods with heterogenous performance in clinical use remains challenging. This study is the first to prospectively investigate the performance of two of today’s most commonly applied anti-dsDNA testing methods head-to-head under real-world conditions, as well as their correlation with other clinical and serological disease parameters in SLE patients.MethodsIn this prospective study, all SLE patients undergoing treatment at the Department of Rheumatology at the University Hospital Bonn within a 13-months period (n=41) and control patients without connective-tissue disease (n=51) were consecutively enrolled and examined. For all study participants’ serum samples both anti-dsDNA-NcX enzyme-linked immunoassay testing EUROIMMUN, Luebeck, Germany) and the fluorescence immunoassay ELiA dsDNA (Thermo Fisher Scientific, Waltham, USA) were performed. In addition, demographic data, further laboratory values and disease activity parameters were recorded. Clinical disease activity was assessed by SLEDAI-2K.ResultsBoth assays showed high specificity (anti-dsDNA-NcX ELISA: 0.9, ELiA dsDNA: 0.959), but there were notable differences in sensitivity (anti-dsDNA-NcX ELISA: 0.51, ELiA dsDNA: 0.38). Pearsons’s correlation yielded a positive correlation between anti-dsDNA concentrations and CRP concentrations for the anti-dsDNA-NcX ELISA (R=0.22; p=0.038) and a mild-to-moderate inverse correlation between concentrations of anti-dsDNA and complement C4 for the ELiA dsDNA test (R=-0.22; p=0.045) when SLE and control patients were considered together. Other than, no significant correlation between anti-dsDNA concentrations and clinical or laboratory findings was found for either test procedure.ConclusionBoth anti-dsDNA antibody assays represent reliable examination methods with high specificity for the diagnosis of SLE that fulfill EULAR/ACR requirements. However, the anti-dsDNA-NcX ELISA showed superior sensitivity and significant correlation with disease activity (as measured by CRP concentrations).

BackgroundTobacco use has shifted in recent years, especially with the introduction of e-cigarettes. Despite the current variable and intersecting tobacco product use among tobacco users, most want to quit, which necessitates cessation programs to adapt to these variable trends (vs focusing on combustible cigarettes alone). The use of web-based modalities for cessation support has become quite popular in recent years and has been compounded by the COVID-19 pandemic. Therefore, understanding the current strengths and limitations of existing programs to meet the needs of current various tobacco users is critical for ensuring the saliency of such programs moving forward. ObjectiveThe purpose of this study was to understand the strengths and limitations of web-based cessation support offered through QuitNow to better understand the needs of a variety of end users who smoke, dual use, or vape. MethodsSemistructured interviews were conducted with 36 nicotine product users in British Columbia. Using conventional content analysis methods, we inductively derived descriptive categories and themes related to the strengths and limitations of QuitNow for those who smoke, dual use, or vape. We analyzed the data with the support of NVivo (version 12; QSR International) and Excel (Microsoft Corporation). ResultsParticipants described several strengths and limitations of QuitNow and provided suggestions for improvement, which fell under 2 broad categories: look and feel and content and features. Shared strengths included the breadth of information and the credible nature of the website. Individuals who smoke were particularly keen about the site having a nonjudgmental feeling. Moreover, compared with individuals who smoke, individuals who dual use and individuals who vape were particularly keen about access to professional quit support (eg, quit coach). Shared limitations included the presence of too much text and the need to create an account. Individuals who dual use and individuals who vape thought that the content was geared toward older adults and indicated that there was a lack of information about vaping and personalized content. Regarding suggestions for improvement, participants stated that the site needed more interaction, intuitive organization, improved interface esthetics, a complementary smartphone app, forum discussion tags, more information for different tobacco user profiles, and user testimonials. Individuals who vape were particularly interested in website user reviews. In addition, individuals who vape were more interested in an intrinsic approach to quitting (eg, mindfulness) compared with extrinsic approaches (eg, material incentives), the latter of which was endorsed by more individuals who dual use and individuals who smoke. ConclusionsThe findings of this study provide directions for enhancing the saliency of web-based cessation programs for a variety of tobacco use behaviors that hallmark current tobacco use.

BackgroundPhysical activity is central to maintaining the quality of life for patients with complex chronic conditions and is thus at the core of neurorehabilitation. However, maintaining activity improvements in daily life is challenging. The novel Stay With It program aims to promote physical activity after neurorehabilitation by cultivating self-monitoring skills and habits. ObjectiveWe examined the implementation of the Stay With It program at the Valens Rehabilitation Centre in Switzerland using the normalization process theory framework, focusing on 3 research aims. We aimed to examine the challenges and facilitators of program implementation from the perspectives of patients and health care professionals. We aimed to evaluate the potential of activity sensors to support program implementation and patient acceptance. Finally, we aimed to evaluate patients’ engagement in physical activity after rehabilitation, patients’ self-reported achievement of home activity goals, and factors influencing physical activity. MethodsPatients were enrolled if they had a disease that was either chronic or at risk for chronicity and participated in the Stay With It program. Patients were assessed at baseline, the end of rehabilitation, and a 3-month follow-up. The health care professionals designated to deliver the program were surveyed before and after program implementation. We used a mixed methods approach combining standardized questionnaires, activity-sensing data (patients only), and free-text questions. ResultsThis study included 23 patients and 13 health care professionals. The diverse needs of patients and organizational hurdles were major challenges to program implementation. Patients’ intrinsic motivation and health care professionals’ commitment to refining the program emerged as key facilitators. Both groups recognized the value of activity sensors in supporting program implementation and sustainability. Although patients appreciated the sensor’s ability to monitor, motivate, and quantify activity, health care professionals saw the sensor as a motivational tool but expressed concerns about technical difficulties and potential inaccuracies. Physical activity levels after patients returned home varied considerably, both within and between individuals. The self-reported achievement of activity goals at home also varied, in part because of vague definitions. Common barriers to maintaining activity at home were declining health and fatigue often resulting from heat and pain. At the 3-month follow-up, 35% (8/23) of the patients withdrew from the study, with most citing deteriorating physical health as the reason and that monitoring and discussing their low activity would negatively affect their mental health. ConclusionsIntegrating aftercare programs like Stay With It into routine care is vital for maintaining physical activity postrehabilitation. Although activity trackers show promise in promoting motivation through monitoring, they may lead to frustration during health declines. Their acceptability may also be influenced by an individual’s health status, habits, and technical skills. Our study highlights the importance of considering health care professionals’ perspectives when integrating new interventions into routine care.

ABSTRACT Aromatoleum aromaticum EbN1T anaerobically degrades phenol, p-cresol, and p-ethylphenol, each via a distinct peripheral pathway. The compound-specific regulation of each pathway is proposed to occur on the transcriptional level in the case of phenol supposedly mediated by the one-component system PheR. To confirm its predicted function, we generated an unmarked, in-frame deletion mutant (ΔpheR). This mutant did not express the ppsA1 gene, which encodes the A1 subunit of phenol-activating phenylphosphate synthase. The expression of ppsA1 was restored by in trans complementation of pheR into the ΔpheR background. The responsiveness to phenol was studied in vivo in benzoate-limited anaerobic cultures by adding, upon benzoate depletion, single defined pulses of phenol (from 100 µM down to 0.1 nM). Time-resolved, targeted transcript profiling by qRT-PCR revealed a response threshold for ppsA1 expression of 30‒50 nM phenol. Notably, ppsA1 expression could not be induced by p-cresol or p-ethylphenol. Conversely, lack of expression was also observed for the additional target genes cmh (p-cresol degradation) and acsA1 (p-ethylphenol degradation) applying phenol or p-ethylphenol as well as phenol or p-cresol as stimuli. Thus, the sensory proteins PheR, PcrS, and EtpR should be highly selective for phenol, p-cresol, and p-ethylphenol, respectively. The implicated incapability of cross-stimulus binding was corroborated by comparing the predicted 3D structural models of the proteins’ sensory domains. While the ligand-binding pockets share the conserved hydroxy group-anchoring histidine and tryptophane, their distal faces in PcrS and EtpR are, compared to PheR, enlarged to accommodate the bulkier methyl (p-cresol) and ethyl group (p-ethylphenol), respectively. IMPORTANCE Aromatic compounds are globally abundant organic molecules with a multitude of natural and anthropogenic sources, underpinning the relevance of their biodegradation. A. aromaticum EbN1T is a well-studied environmental betaproteobacterium specialized on the anaerobic degradation of aromatic compounds. The here studied responsiveness toward phenol in conjunction with the apparent high ligand selectivity (non-promiscuity) of its PheR sensor and those of the related p-cresol (PcrS) and p-ethylphenol (EtpR) sensors are in accord with the substrate-specificity and biochemical distinctiveness of the associated degradation pathways. Furthermore, the present findings advance our general understanding of the substrate-specific regulation of the strain’s remarkable degradation network and of the concentration thresholds below which phenolic compounds become essentially undetectable and as a consequence should escape substantial biodegradation. Furthermore, the findings may inspire biomimetic sensor designs for detecting and quantifying phenolic contaminants in wastewater or environments.

El modelo TPACK (Conocimiento Tecnológico Pedagógico y de Contenido) reflexiona sobre los diferentes tipos de conocimiento que deben desarrollar los profesores para incorporar las TIC de forma efectiva en sus prácticas educativas; por lo tanto, el propósito de este trabajo fue presentar los resultados de la adaptación y validación de un instrumento TPACK para profesores universitarios. La muestra final se conformó por 204 docentes de dos instituciones del sur de Sonora. Como parte de este proceso, se obtuvo un Alfa de Cronbach de .96 para los 36 ítems de la escala. Para determinar la validez de constructo se realizó el análisis factorial exploratorio (AFE), que mostró cuatro factores que explican el 68.57% de la varianza total. El instrumento original se compone de siete dimensiones, para comprobarlo se realizó el análisis factorial confirmatorio (AFC) y se confirmó un modelo de cuatro factores. Los resultados indican que es un instrumento válido y confiable para medir el TPACK en docentes universitarios. Se sugiere para futuras investigaciones ajustar el instrumento para áreas de estudio o tecnologías específicas.

AbstractThis research paper investigates the enablers of Sustainable Development Goals (SDG) leadership among Small and Medium Enterprises (SMEs) in South Asian nations using Interpretive Structural Modelling (ISM). The study focuses on identifying the factors that facilitate SDG leadership in SMEs, including shared vision, long-term perspective, co-creation, shared responsibility, empowering people, eco-centric values, creativity and innovation, bonding and trust, knowledge sharing, strategic adaption, and progressive culture. The research findings show that these factors are interrelated, and their integration can help SMEs to achieve sustainable development and become SDG leaders in their respective industries. The study contributes to the existing literature by providing insights into the enablers of SDG leadership among SMEs in South Asian nations and proposing a framework for their successful implementation. The proposed framework can be used as a guide for policymakers, managers, and entrepreneurs to promote sustainable development in their organizations and the region.

BackgroundThe Psychiatry, Neurology, Psychosomatics and Psychotherapy (PNP) program of the German statutory health insurance AOK BW promotes coordinated and evidence-based specialist care with the aim of providing individualized, guideline-based outpatient care, strengthening the collaboration between health care providers, as well as reducing care costs. The purpose of this study was to evaluate its effectiveness regarding patient-reported outcomes compared to the less specialized general practitioner program (GP) and usual care (UC).Materials and methodsAOK insured patients, who were on sick leave due to a mental disorder (affective disorder, anxiety disorder, adjustment disorder, somatoform disorder, alcohol abuse disorder, schizophrenia) or multiple sclerosis were included in the prospective non-randomized controlled study. All patients either participated in the PNP program (intervention group, IG-PNP), the general practitioner program (control group, CG-GP) or usual care (control group, CG-UC). Entropy balancing was used to adjust for baseline imbalance between groups. Primary outcome was health-related quality of life, assessed by the Short-form health survey (SF-36) 12 months after diagnosis. Secondary outcomes included symptom severity, functional health, and treatment satisfaction.ResultsOf the 14,483 insured patients who were contacted, 1,104 patients participated at baseline and 725 at follow-up. The adjusted mean differences of SF-36 sum score did not significantly differ between groups: −1.89 (95%-CI = −4.60; 0.81, p = 0.170) between IG-PNP and CG-GP, and −1.42 (95%-CI = −4.05; 1.22, p = 0.293) between PNP and CG-UC. The adjusted mean differences of secondary outcomes did not differ between groups, except for a slightly higher increase of functional health in CG-UC.ConclusionWe found no evidence that the PNP program is superior to the GP program or to usual care in terms of patient-reported outcomes or treatment satisfaction. The results are limited by the low response rate. Accordingly, future studies should strive for more representative samples. To improve the program, an integration of further collaborative care elements and guideline recommendations might be useful.Clinical trial registrationDRKS (German Clinical Trials Register https://drks.de/search/en); identifier (DRKS00013114).

BackgroundEffective immune surveillance requires a functioning immune system and natural killer (NK) and T cells for adequate innate and antigen-specific immune responses critically depending on human leukocyte antigens (HLAs) and haplotypes representing advantageous combinations of HLA antigens. Recently, we reported a link between altered frequencies of HLA alleles and haplotypes and developing head and neck squamous cell carcinoma (HNSCC). Whereas the majority of HNSCCs seem to be related to classical risk factors alcohol and tobacco, a subset of HNSCC and especially oropharyngeal squamous cell carcinoma (OPSCC) were etiologically linked to human papillomavirus (HPV) recently. Here, we demonstrate in HPV-driven (p16-positive high risk-HPV DNA-positive) HNSCC a deviating distribution of HLA antigens and haplotypes and their relevance to outcome.MethodsLeukocyte DNA of n = 94 HPV-driven HNSCC patients (n = 57 OPSCC, n = 37 outside oropharynx) underwent HLA SSO typing, allowing allele, antigen (allele group), and haplo-typing. Besides comparing these frequencies with those of German blood donors, we analyzed their impact on outcome using Kaplan–Meier plots and Cox proportional hazard regression.ResultsAntigen and haplotype frequencies demonstrate enrichment of rare antigens and haplotypes. The HLA score for unselected HNSCC patients was not predictive for outcome here. However, together with alcohol consumption, tobacco smoking, T category, and extranodal extension of locoregional metastases and treatment applied, eight HLA traits allow for predicting progression-free and tumor-specific survival.ConclusionPatients can be categorized into low, intermediate-low, intermediate-high, and high risk groups. Using a new PFS risk score for HPV-driven HNSCC may allow to improve prognostication.

Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling, respiratory muscle and cardiac impairments, and exercise intolerance. Specifically, impaired gas exchange increases work of the diaphragm; however, compromised contractile function precludes the diaphragm from meeting the increased metabolic demand of chronic hyperventilation in PH. Given that muscle contractile function is in part, dependent upon adequate blood flow (Q˙), diaphragmatic dysfunction may be predicated by an inability to match oxygen delivery with oxygen demand. We hypothesized that PH rats would demonstrate a decreased hyperemic response to contractions compared to healthy controls.Methods: Sprague-Dawley rats were randomized into healthy (HC, n = 7) or PH (n = 7) groups. PH rats were administered monocrotaline (MCT) while HC rats received vehicle. Disease progression was monitored via echocardiography. Regional and total diaphragm blood flow and vascular conductance at baseline and during 3 min of electrically-stimulated contractions were determined using fluorescent microspheres.Results: PH rats displayed morphometric and echocardiographic criteria for disease (i.e., acceleration time/ejection time, right ventricular hypertrophy). In all rats, total costal diaphragm Q˙ increased during contractions and did not differ between groups. In HC rats, there was a greater increase in medial costal Q˙ compared to PH rats (55% ± 3% vs. 44% ± 4%, p < 0.05), who demonstrated a redistribution of Q˙ to the ventral costal region.Conclusion: These findings support a redistribution of regional diaphragm perfusion and an impaired medial costal hyperemic response in PH, suggesting that PH alters diaphragm vascular function and oxygen delivery, providing a potential mechanism for PH-induced diaphragm contractile dysfunction.

Taxus L. is accepted in the literature as natural resources of biologically active compounds and volatile oils, with applications in medicine, pharmaceuticals, food, cosmetics, and with ecological impact on the natural living environment. In this context, the present work aims to analyze by GS/MS techniques the chemical composition of volatile oil obtained by hydrodistillation of leaves harvested from spontaneous and cultivated female individuals of Taxus (dried and fresh plant material) and to spectrophotometrically evaluate the hydrosols resulting from their hydrodistillation. The compounds with the highest concentrations in the volatile oil obtained from the spontaneous taxon Taxus baccata L. were hexahydrofarnesyl acetone (33.03% fresh leaves; 20.09% dried leaves); ar-abietatriene (14.98% dried leaves; 3.03% fresh leaves); phthalic acid, hex-3-yl isobutyl ester (10.51% dried leaves); salicylic acid, benzyl ester (8.11% dried leaves). In the cultivated taxon Taxus baccata the compounds identified with the highest concentrations were 1-octen-3-ol (25.61% fresh leaves); phytol (12.50% dry leaves); geranyl acetone (11.90% dry leaves); manoyl oxide (11.85% dry leaves; 10.86% fresh leaves); 1,9-decadence (7.92% fresh leaves). The compounds with the highest concentrations in the oil extracted from the leaves of Taxus baccata ‘Robusta’ were hexahydrofarnesyl acetone (17.81% fresh leaves); pentacosane (11.28% dry leaves); heptacosane (11.27% fresh leaves); tetracosane (11.13% dry leaves); tricosane (8.45% fresh leaves). The chemical composition of volatile oils from yew is influenced by many exogenous factors such as soil, light, and endogenous factors such as age, DNA.

Influenza A viruses are RNA viruses that cause epidemics in humans and are enzootic in the pig population globally. In 2009, pig-to-human transmission of a reassortant H1N1 virus (H1N1pdm09) caused the first influenza pandemic of the 21st century. This study investigated the infection dynamics, pathogenesis, and lesions in pigs and ferrets inoculated with natural isolates of swine-adapted, human-adapted, and "pre-pandemic" H1N1pdm09 viruses. Additionally, the direct-contact and aerosol transmission properties of the three H1N1pdm09 isolates were assessed in ferrets. In pigs, inoculated ferrets, and ferrets infected by direct contact with inoculated ferrets, the pre-pandemic H1N1pdm09 virus induced an intermediary viral load, caused the most severe lesions, and had the highest clinical impact. The swine-adapted H1N1pdm09 virus induced the highest viral load, caused intermediary lesions, and had the least clinical impact in pigs. The human-adapted H1N1pdm09 virus induced the highest viral load, caused the mildest lesions, and had the least clinical impact in ferrets infected by direct contact. The discrepancy between viral load and clinical impact presumably reflects the importance of viral host adaptation. Interestingly, the swine-adapted H1N1pdm09 virus was transmitted by aerosols to two-thirds of the ferrets. Further work is needed to assess the risk of human-to-human aerosol transmission of swine-adapted H1N1pdm09 viruses.

This systematic review aims to investigate the literature on the relationship between time perspective and death anxiety in the elderly population. Time perspective is a fundamental process by which the flow of personal experiences is categorized into temporal dimensions, while death anxiety refers to the fear associated with the inevitability of death. The review systematically assesses and critically discusses the literature on time perspective and death anxiety and highlights the implications for future research and practice. A comprehensive search of relevant databases (PubMed, Web of Science, Scopus, Science Direct) was conducted to identify quantitative studies published up to date in this review. The initial search yielded a considerable number of studies (N=401). After applying rigorous inclusion criteria, a final selection of studies (N=5) was examined in detail. Results of our systematic review show that time perspective is related to death anxiety in some circumstances, but extensive research is needed to explore this relationship. Future research efforts should focus on refining assessment methodologies from time perspective and investigating potential interventions that can alleviate death anxiety among the elderly population. Understanding the interplay between time perspective and death anxiety may hold valuable implications for mental health interventions and geriatric care, promoting enhanced well-being and psychological resilience in later life.

AbstractPromoting women’s economic participation and empowerment is essential for sustainable development in South Asian Countries. Studies have established that women entrepreneurs in South Asia face a noteworthy challenge with many lacking formal education, lack of entrepreneurship education, capital, skilled and trained manpower, management skills, networking, infrastructural support, fear of failure, gender discrimination, and loaded with family responsibilities. This research aims to evaluate the contextual relationships among identified key challenges and develop a hierarchical framework of key challenges for addressing barriers to promote women entrepreneurship in South Asian Countries. The primary study was conducted using Interpretive Structural Modelling on 31 women entrepreneurs from India, Nepal, Sri Lanka, Pakistan, and Bangladesh. The study proposed that multi-dimensional efforts are needed to ensure that women have equal access to economic opportunities and can fully participate in and contribute to the region’s economic development.

ABSTRACTRecently, there has been a co-evolution of mammalian libraries and diverse microfluidic approaches for therapeutic antibody hit discovery. Mammalian libraries enable the preservation of full immune repertoires, produce hit candidates in final format and facilitate broad combinatorial bispecific antibody screening, while several available microfluidic methodologies offer opportunities for rapid high-content screens. Here, we report proof-of-concept studies exploring the potential of combining microfluidic technologies with mammalian libraries for antibody discovery. First, antibody secretion, target co-expression and integration of appropriate reporter cell lines enabled the selection of in-trans acting agonistic bispecific antibodies. Second, a functional screen for internalization was established and comparison of autocrine versus co-encapsulation setups highlighted the advantages of an autocrine one cell approach. Third, synchronization of antibody-secreting cells prior to microfluidic screens reduced assay variability. Furthermore, a display to secretion switchable system was developed and applied for pre-enrichment of antibody clones with high manufacturability in conjunction with subsequent screening for functional properties. These case studies demonstrate the system’s feasibility and may serve as basis for further development of integrated workflows combining manufacturability sorting and functional screens for the identification of optimal therapeutic antibody candidates.

Abstract: The paper aims to analyse how self-translation fits into the discourse of translingual writing in German-language literature produced since the second half of the 20th century. The paper shows that the phenomenon can be conceived in different ways, along a continuum ranging from more ‘literal’ understandings to metaphorical extensions of the term. The complexity of self-translation will be examined through the example of the following authors: Carmine Abate, Franco Biondi, Zwetelina Damjanova, Sabine Eschgfäller, Gerhard Kofler, Pavel Kohout, Yüksel Pazarkaya, Barbara Pumhösel, Milan Ráček, Yoko Tawada and Vladimir Vertlib. Ennast tõlkivad autorid saksakeelses nüüdiskirjanduses Käesolevas artiklis vaatlen enesetõlget saksakeelses nüüdiskirjanduses kui üht konkreetset aspekti kirjanduslikus keeleülesuses, mida on defineeritud kui „kirjanike fenomeni, kes loovad tekste rohkem kui ühes keeles või muus keeles kui nende esimene keel“ (Kellmann 2019, 337). • sajandi viimastel kümnenditel on germanistikas üha enam keskendutud saksakeelsetele autorite loomingule, kelle esimene keel ei ole saksa keel. Saksa keelt kõnelevates riikides on asutatud kirjandusauhindu nimelt selliseid autoreid silmas pidades; neist tähelepanuväärseimad on Adelbert-von-Chamisso-Preis (anti välja aastatel 1985–2017) Saksamaal ja auhind „Schreiben zwischen den kulturen“ (asutatud 1997) Austrias, mis näitab, et keeleülene kirjandus on pakkunud suurt huvi nii teadlastele kui ka saksakeelse kirjanduse lugejatele ning kirjandusturule. Nende auhindade võitjate ja teiste saksakeelset nüüdiskirjandust loovate keeleüleste kirjanike loomingut uurides selgub, et enesetõlkimine on korduv aspekt, mida esineb eri kujudel ja taustadel, millest kõige ilmsem on see, kui autorid tõlgivad oma tekste teise keelde. Mis puutub enesetõlkesse, siis 21. sajandil on seda nähtust üha enam analüüsitud, mis on tulemuseks andnud rea publikatsioone, mida süstemaatiliselt loetleb Eva Gentesi toimetatud teos „Bibliography of Self-Translation“ („Enesetõlke bibliograafia“). Olemasolev teadustöö enesetõlkimise vallas koosneb arvukatest üksikuurimustest, millest enamik tegelevad kuulsaimate nüüdisaegsete enesetõlkijatega, eriti Vladimir Nabokovi ja Samuel Beckettiga (vt ülevaadet Gentes 2016). Postkoloniaalsete uuringute kontekstis on üha enam uurimusi pühendatud Aafrika ja Lõuna-Ameerika autoritele (Weigel 2019), teoreetilises diskursuses on rõhutatud hübriidsust (hübriidkultuurid, hübriidkeeled ja hübriididentiteedid), eriti kirjanduse, migratsiooni ja mitmekeelsuse vahelises seoses (Falceri, Gentes ja Manterola 2017). Selle tulemusena on üha enam rõhutama hakatud „enesetõlke“ „ennast“ – see tähendab seda, kuidas enesetõlkija tekstis avaldub. Neid lähtekohti arvesse võttes analüüsitakse artiklis, kuidas enesetõlge sobitub 20. sajandi teisel poolel saksakeelse kirjanduse väljal loodud keeleülese kirjutamise diskursusesse. Esimeses osas antakse ülevaade peamistest välja pakutud enesetõlke definitsioonidest, näidates, millised on selle nähtuse võimalikud eesmärgid keeleüleses kirjanduses. Enesetõlke definitsioon ei ole sugugi selge, mis esmalt tuleneb tõigast, et seda ei saa üheselt ja selgepiiriliselt liigitada ei tõlkeuuringute ega kirjandusteaduse valdkonda kuuluvaks. Käesolevas artiklis rakendatav perspektiiv sarnaneb rohkem teise lähenemisega, sest võimaldab avardada enesetõlke tähendust, hõlmamaks selle avaramat mõistmist. Analüüsitakse teisigi tõlgendusi ja kontseptsioone, alates Oleksandr Finkeli 1929. aastal välja pakutud definitsioonist (ta kasutas tegelikult terminit auto-tõlge). Näidatakse, et enesetõlkenähtust võib mõista eri moel, kontiinumil, mis ulatub „sõnasõnalisematest“ arusaamadest (nimelt siis, kui on olemas lähtetekst ning autor tõlgib selle teise keelde, olgu see siis tema esimene, teine, kolmas vm keel) termini metafoorsete laiendusteni (milles ainuüksi teises, kolmandas jne keeles kirjutamist peetakse juba enesetõlke esinemiskujuks). Teises osas uuritakse enesetõlke komplekssust saksakeelses nüüdiskirjanduses, kasutades näidetena järgmisi keeleüleseid autoreid: Carmine Abate, Franco Biondi, Zwetelina Damjanova, Sabine Eschgfäller, Gerhard Kofler, Pavel Kohout, Yüksel Pazarkaya, Barbara Pumhösel, Milan Ráček, Yoko Tawada ja Vladimir Vertlib. Nad kuuluvad eri põlvkondadesse, neil on erisugused kultuurilised ja kunstilised taustad, nad on tõlkinud oma teoseid eri eesmärkidel (kas poeetilistel, toimetuslikel, kommertslikel, ideoloogilistel vm põhjustel) ning eri keeltest või eri keeltesse (ühisnimetajaks saksa keel) ning seega on nad representatiivsed laiaulatuslike enesetõlkevormide osas, mida enesetõlkimine võib mitmekeelsete autorite hulgas saksakeelses kontekstis võtta. Vaadatakse, mil määral nad sobituvad ühe või teise definitsiooniga ning kuidas nad end enesetõlkijatena positsioneerivad. Näidatakse, kelle kohta kehtivad „sõnasõnalisemad“ definitsioonid, kes kehastavad selle nähtuse avaramat tõlgendamist, ja vaadeldakse mõningaid juhtusid, mida ei ole võimalik hõlpsasti kummassegi kategooriasse paigutada. Viimases, kolmandas osas keskendutakse jaapani päritolu saksa kirjanikule Yoko Tawadale, kelle teosed esindavad enesetõlke mõistmise eri võimalusi.

Abstract Our objective was to test whether p53 expression status is associated with survival for women diagnosed with the most common ovarian carcinoma histotypes (high‐grade serous carcinoma [HGSC], endometrioid carcinoma [EC], and clear cell carcinoma [CCC]) using a large multi‐institutional cohort from the Ovarian Tumor Tissue Analysis (OTTA) consortium. p53 expression was assessed on 6,678 cases represented on tissue microarrays from 25 participating OTTA study sites using a previously validated immunohistochemical (IHC) assay as a surrogate for the presence and functional effect of TP53 mutations. Three abnormal expression patterns (overexpression, complete absence, and cytoplasmic) and the normal (wild type) pattern were recorded. Survival analyses were performed by histotype. The frequency of abnormal p53 expression was 93.4% (4,630/4,957) in HGSC compared to 11.9% (116/973) in EC and 11.5% (86/748) in CCC. In HGSC, there were no differences in overall survival across the abnormal p53 expression patterns. However, in EC and CCC, abnormal p53 expression was associated with an increased risk of death for women diagnosed with EC in multivariate analysis compared to normal p53 as the reference (hazard ratio [HR] = 2.18, 95% confidence interval [CI] 1.36–3.47, p = 0.0011) and with CCC (HR = 1.57, 95% CI 1.11–2.22, p = 0.012). Abnormal p53 was also associated with shorter overall survival in The International Federation of Gynecology and Obstetrics stage I/II EC and CCC. Our study provides further evidence that functional groups of TP53 mutations assessed by abnormal surrogate p53 IHC patterns are not associated with survival in HGSC. In contrast, we validate that abnormal p53 IHC is a strong independent prognostic marker for EC and demonstrate for the first time an independent prognostic association of abnormal p53 IHC with overall survival in patients with CCC.