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Background: Pancreatic cysts in autosomal dominant polycystic kidney disease (ADPKD) correlate with PKD2 mutations, which have a different phenotype than PKD1 mutations. However, pancreatic cysts are commonly overlooked by radiologists. Here, we automate the detection of pancreatic cysts on abdominal MRI in ADPKD. Methods: Eight nnU-Net-based segmentation models with 2D or 3D configuration and various loss functions were trained on positive-only or positive-and-negative datasets, comprising axial and coronal T2-weighted MR images from 254 scans on 146 ADPKD patients with pancreatic cysts labeled independently by two radiologists. Model performance was evaluated on test subjects unseen in training, comprising 40 internal, 40 external, and 23 test–retest reproducibility ADPKD patients. Results: Two radiologists agreed on 52% of cysts labeled on training data, and 33%/25% on internal/external test datasets. The 2D model with a loss of combined dice similarity coefficient and cross-entropy trained with the dataset with both positive and negative cases produced an optimal dice score of 0.7 ± 0.5/0.8 ± 0.4 at the voxel level on internal/external validation and was thus used as the best-performing model. In the test–retest, the optimal model showed superior reproducibility (83% agreement between scan A and B) in segmenting pancreatic cysts compared to six expert observers (77% agreement). In the internal/external validation, the optimal model showed high specificity of 94%/100% but limited sensitivity of 20%/24%. Conclusions: Labeling pancreatic cysts on T2 images of the abdomen in patients with ADPKD is challenging, deep learning can help the automated detection of pancreatic cysts, and further image quality improvement is warranted.

Objective: Intradural spinal metastases are considered rare. At present, limited information is available on incidence, surgical management, and outcomes. Methods: We conducted a retrospective patient chart review from 2002 to 2024, identifying all patients surgically treated for intradural spinal metastases. Clinical, surgical and survival data were collected and compared to literature data for patients surgically treated for extradural spinal metastases. Results: A total of 172 patients with spinal metastases were identified with 13 patients meeting inclusion criteria (7.6%). The mean age at diagnosis of intradural spinal metastases was 52 ± 22 years, with diverse primaries including lung (n = 3), breast (n = 2), sarcoma (n = 2), and six unique entities. Intradural spinal metastasis was diagnosed on average of 3.3 years after primary diagnosis. In total, we observed five (38%) intradural-extramedullary and eight (62%) intramedullary metastases, located in the cervical (38.5%), thoracic (46.1%) and lumbar spine (15.4%). The most common preoperative symptoms were pain, sensory changes, and gait ataxia (each 76.9%). Gross total resection was achieved in 54%, and local tumor control in 85%. Postoperatively, 92% exhibited clinical improvement or stability. Most frequent adjuvant treatment was radio- and/or chemotherapy in 85%. The average survival after operation for spinal intradural metastases was 5 months, ranging from 1 month to 120 months. The location of the intradural metastasis in the cervical spine was associated with a significantly more favorable survival outcome (compared to thoracic/lumbar location, p = 0.02). Conclusions: Intradural location of spinal metastases is rare (7.6%). Even so, surgical resection is safe and effective for neurological improvement, and survival appears lower compared to the reported survival of extradural spinal metastases.

Background: Cystic, sporadic hemangioblastomas (HBLs) represent a unique, therapeutically challenging subset of central nervous system tumors, mainly due to their unpredictable growth patterns and potential for symptomatic progression. This study aims to explore the complexities surrounding the diagnosis, treatment, and long-term management of these lesions. Methods: A comprehensive literature review was performed, and a detailed case study of a 56-year-old patient with a cystic, sporadic cerebellar HBL was produced. Results: The case highlights the multiphasic growth pattern typical of cystic, sporadic HBLs, characterized by periods of dormancy and subsequent rapid expansion. An initial surgical intervention offered temporary control. Tumor recurrence, mainly through cystic enlargement, was treated by SRS. A subsequent recurrence, again caused by cystic growth, eventually led to the patient’s death. The intricacies of treatment modalities, focusing on the transition from surgical resection to stereotactic radiosurgery (SRS) upon recurrence, are discussed. Parameters indicating impending tumor growth, coupled with symptomatic advances, are also explored. Conclusions: The management of cystic, sporadic cerebellar HBLs requires a strategic approach that can be informed by radiological characteristics and tumoral behavior. This study underscores the importance of a proactive, individualized management plan and suggests guidelines that could inform clinical decision making.

The cement industry contributes around 7% of global anthropogenic carbon dioxide emissions, mainly from the combustion of fuels and limestone decomposition during clinker production. Using alternative fuels derived from wastes is a key strategy to reduce these emissions. However, alternative fuels vary in composition and heating value, so selecting appropriate ones is crucial to maintain clinker quality and manufacturing processes while minimizing environmental impact. This study evaluated various biomass and industrial wastes as potential alternative fuels, characterizing them based on proximate analysis, elemental and oxide composition, lower heating value, and bulk density. Sawdust, pecan nutshell, industrial hose waste, and plastic waste emerged as viable options as they met the suggested thresholds for heating value, chloride, moisture, and ash content. Industrial hose waste and plastic waste were most favorable with the highest heating values while meeting all the criteria. Conversely, wind blade waste, tire-derived fuel, and automotive shredder residue did not meet all the recommended criteria. Therefore, blending them with alternative and fossil fuels is necessary to preserve clinker quality and facilitate combustion. The findings of this research will serve as the basis for developing a computational model to optimize the blending of alternative fuels with fossil fuels for cement production.

Background: The purpose of this study was to investigate the dependence of Intravoxel Incoherent Motion (IVIM) parameters measured in the human calf on B0. Methods: Diffusion-weighted image data of eight healthy volunteers were acquired using five b-values (0–600 s/mm2) at rest and after muscle activation at 0.55 and 7 T. The musculus gastrocnemius mediale (GM, activated) was assessed. The perfusion fraction f and diffusion coefficient D were determined using segmented fits. The dependence on field strength was assessed using Student’s t-test for paired samples and the Wilcoxon signed-rank test. A biophysical model built on the three non-exchanging compartments of muscle, venous blood, and arterial blood was used to interpret the data using literature relaxation times. Results: The measured perfusion fraction of the GM was significantly lower at 7 T, both for the baseline measurement and after muscle activation. For 0.55 and 7 T, the mean f values were 7.59% and 3.63% at rest, and 14.03% and 6.92% after activation, respectively. The biophysical model estimations for the mean proton-density-weighted perfusion fraction were 3.37% and 6.50% for the non-activated and activated states, respectively. Conclusions: B0 may have a significant effect on the measured IVIM parameters. The blood relaxation times suggest that 7 T IVIM may be arterial-weighted whereas 0.55 T IVIM may exhibit an approximately equal weighting of arterial and venous blood.

Coffee leaf diseases are a significant challenge for coffee cultivation. They can reduce yields, impact bean quality, and necessitate costly disease management efforts. Manual monitoring is labor-intensive and time-consuming. This research introduces a pioneering mobile application equipped with global positioning system (GPS)-enabled reporting capabilities for on-site coffee leaf disease detection. The application integrates advanced deep learning (DL) techniques to empower farmers and agronomists with a rapid and accurate tool for identifying and managing coffee plant health. Leveraging the ubiquity of mobile devices, the app enables users to capture high-resolution images of coffee leaves directly in the field. These images are then processed in real-time using a pre-trained DL model optimized for efficient disease classification. Five models, Xception, ResNet50, Inception-v3, VGG16, and DenseNet, were experimented with on the dataset. All models showed promising performance; however, DenseNet proved to have high scores on all four-leaf classes with a training accuracy of 99.57%. The inclusion of GPS functionality allows precise geotagging of each captured image, providing valuable location-specific information. Through extensive experimentation and validation, the app demonstrates impressive accuracy rates in disease classification. The results indicate the potential of this technology to revolutionize coffee farming practices, leading to improved crop yield and overall plant health.

Patient-reported outcomes (PROs) offer a diverse array of potential applications within medical research and clinical practice. In comparative research, they can serve as tools for delineating the trajectories of health-related quality of life (HRQoL) across various cancer types. We undertook a secondary data analysis of a cohort of 1498 hospitalized cancer patients from 13 German cancer centers. We assessed the Physical and Mental Component Scores (PCS and MCS) of the 12-Item Short-Form Health Survey at baseline (t0), 6 (t1), and 12 months (t2), using multivariable generalized linear regression models. At baseline, the mean PCS and MCS values for all cancer patients were 37.1 and 44.3 points, respectively. We observed a significant improvement in PCS at t2 and in MCS at t1. The most substantial and significant improvements were noted among patients with gynecological cancers. We found a number of significant differences between cancer types at baseline, t1, and t2, with skin cancer patients performing best across all time points and lung cancer patients performing the worst. MCS trajectories showed less pronounced changes and differences between cancer types. Comparative analyses of HRQoL scores across different cancer types may serve as a valuable tool for enhancing health literacy, both among the general public and among cancer patients themselves.

Metabolic dysfunction-associated steatotic liver disease (MASLD) represents a growing health concern due to its increasing prevalence worldwide. Metabolic homeostasis encompasses the stable internal conditions vital for efficient metabolism. This equilibrium extends to the intestinal microbiota, whose metabolic activities profoundly influence overall metabolic balance and organ health. The metabolites derived from the gut microbiota metabolism can be defined as microbiota-related co-metabolites. They serve as mediators between the gut microbiota and the host, influencing various physiological processes. The recent redefinition of the term MASLD has highlighted the metabolic dysfunction that characterize the disease. Metabolic dysfunction encompasses a spectrum of abnormalities, including impaired glucose regulation, dyslipidemia, mitochondrial dysfunction, inflammation, and accumulation of toxic byproducts. In addition, MASLD progression has been linked to dysregulation in the gut microbiota and associated co-metabolites. Short-chain fatty acids (SCFAs), hippurate, indole derivatives, branched-chain amino acids (BCAAs), and bile acids (BAs) are among the key co-metabolites implicated in MASLD progression. In this review, we will unravel the relationship between the microbiota-related metabolites which have been associated with MASLD and that could play an important role for developing effective therapeutic interventions for MASLD and related metabolic disorders.

Vortex generators (VGs) attached to the leading edge of an agricultural aircraft are purported to control airflow over the upper surface of the wing by creating small vortices that delay boundary layer separation, thereby improving the performance of the aircraft. These devices are commercially available for use in the aviation industry, primarily to increase pilot control of the aircraft. The benefits attributed to VGs remain largely descriptive and anecdotal in nature without rigorous empirical assessment in the field. The intent of this study was to evaluate whether this aerodynamic device could improve deposition or reduce drift when mounted on an agricultural aircraft. Airborne drift and ground deposition were measured with monofilament lines and Mylar cards, respectively. Deposits were expressed as percent of fluorometric response using a spectrofluorophotometer. There were 46% fewer downwind drift deposits on monofilament lines when VGs were installed than when VGs were not installed. Whether or not VGs were installed on the aircraft was the predominant factor which influenced deposition on monofilament lines. Spray deposits on Mylar cards placed at ground level downwind of the applications at three different locations (5, 10, and 20 m) varied significantly (p < 0.0001) between treatments, with corresponding 31, 54, and 61% reductions in downwind deposits when VGs were installed. While these findings overall are positive, this is the first known study of its type, and more research is warranted to better understand the role of vortex generators in the reduction in drift relative to aerially applied sprays.

In controlled phase II trials, major prognostic factors need to be well balanced between arms. The main procedures used are SPBR (Stratified Permuted Block Randomization) and minimization. First, we provide a systematic review of the treatment allocation procedure used in gastrointestinal oncology controlled phase II trials published in 2019. Second, we performed simulations using data from six phase II studies to measure the impacts of imbalances and bias on the efficacy estimations. From the 40 articles analyzed, all mentioned randomization in both the title and abstract, the median number of patients included was 109, and 77.5% were multicenter. Of the 27 studies that reported at least one stratification variable, 10 included the center as a stratification variable, 10 used minimization, 9 used SBR, and 8 were unspecified. In real data studies, the imbalance increased with the number of centers. The total and marginal imbalances were higher with SBR than with minimization, and the difference increased with the number of centers. The efficiency estimates per arm were close to the original trial estimate in both procedures. Minimization is often used in cases of numerous centers and guarantees better similarity between arms for stratification variables for total and marginal imbalances in phase II trials.

Colorectal cancer (CRC) outcomes in terms of incidence and mortality are significantly worse in African Americans than other Americans. While differences in primary preventions for neoplasia (diet, obesity remediation, aspirin prophylaxis) are being elucidated, genetic mutations affecting premalignant lesions and immune response mechanisms may possibly also explain the increased incidence and mortality, particularly from right-sided disease. Objective: Our team therefore examined colonic segments seeking to test the hypothesis that the immune response and somatic genetic profiles of the colonic anatomic segments may vary and thus account for variations in neoplasia risk among the various colonic segments revealing an antigenic relationship with precancerous lesions. The p87 antigenic field effect is recognized via Adnab-9 antibody immunohistochemistry to be significantly less in the right colon in African Americans, particularly in the cecum. Method: Since small high-grade dysplastic adenomas (SHiGDA) likely missed by CRC screening may progress to cancer, we used Ion Torrent™ sequencing of DNA extracted from four normal colonic segments (two left-sided and two right) of patients with SHiGDAs. We also contrasted unique mutational fields in one patient with a large HiGDA (APC with unique mutations) and one patient who prospectively developed a SHiGDA (JAK3). Result: The SHiGDA (small high-grade dysplastic polyp) patient was p87 negative for any extracted stool, saliva, or colonic effluent via ELISA (enzyme linked immunoadsorbant assay). Furthermore, mean values of expression in segments from the right colon were reduced with respect to the means obtained from the left segments in 233 patients evaluated for a p87 field effect. This has recently been shown to be the case in a large cohort of AA and Caucasian 2294 patients, possibly explaining the right-sided CRC disparity in African Americans and the subsequent increase in mortality. This field effect disparity is also true for two cancers contracted by the SHiGDa patient (lung and prostate). Conclusion: Thus, this pilot study suggests that the reduction in p87 in the right colon is possibly correlated with JAK3 mutations. If confirmed, JAK3 mutations, known to be associated with immune aberrations, may provide a mechanistic explanation for the lack of a p87 (protein 87 kilodaltons) field in some patients with HGD polyps who might benefit from possible intervention such as more intensive screening. Limited microbiome studies were also performed on two patients with familial cancer syndromes and these compared favorably with controls available from the literature.

The soil response under the inherent cyclic loading conditions when dealing with offshore foundations can be considered by using contour plots. These plots are derived from several cyclic laboratory tests and characterize the general cyclic soil behaviour. In the design process with explicit numerical methods, such plots are needed in order to assess the soil behaviour under arbitrary loading conditions and hence estimate the cyclic foundation response. In the paper, excess pore pressure contour plots for a poorly graded medium sand are derived from numerous constant volume (CV) cyclic direct simple shear (DSS) tests and a new approach for parametrization of the plots is presented. Subsequently, the data are assessed regarding scaling for other sand soils, i.e., construction of contour plots with only a small number of test results by using the general trends observed.

In the wake of the COVID-19 pandemic and subsequent restrictions on face-to-face interaction, digital communication methods have undergone unprecedented breakthroughs, especially in the realm of higher education. The glaring differences between face-to-face seminars and the physical distance of participants in online seminars raise questions about the meaning of embodied presence of subjects in various formats. The understanding of body and lived body is often based on a dichotomous interpretation, in which the body-as-object is instrumentally subordinated to the mind. To revalorize the body, recent theories of education and Bildung-theoretical approaches, in particular, emphasize not only discursive, but also embodied, practices and increasingly focus on the potential of the body-as-subject as a medium for the subjective configuration of interactive situations. As the embodied perspective poses different challenges for qualitative research, it seems appropriate to validate the methodological approach. Utilizing a three-step method, we provide a phenomenological heuristic strategy through which our instrument underwent critical and intersubjective reflection. Ideally, subsequent research endeavors can expand upon and refine this methodology to further explore the concepts of embodiment and embodied presence in higher education.

The efficacy of two different online treatment programs for people with binge eating disorder (BED) was compared. One hundred and nineteen adults with BED were randomized to treatments based on the Healthy Approach to Weight Management and Food in Eating Disorders (HAPIFED) or cognitive behavioural therapy (CBT). The treatments were delivered via videoconferencing in 10 groups with approximately 12 participants in each group. Each group included 13 treatment sessions and two follow-up sessions. Participants’ self-reported eating disorder behaviours/psychopathology, general mental health, and weight were assessed at pre-treatment, the end of treatment, a 3-month follow-up, and a 6-month follow-up. The participants in both treatments similarly reduced objective and subjective binge eating episodes from pre-treatment to the end of treatment. There were no significant differences in weight loss for the participants in either treatment. The participants in both treatments had reduced levels of loss of control over eating, eating disorder psychopathology, depression, psychological stress, and difficulties in emotion regulation from pre-treatment to the end of treatment. Treatments based on the HAPIFED or CBT delivered via videoconferencing can reduce binge eating and improve mental health in people with BED.

Background: The effectiveness and reliability of diagnostic tests that detect DNA sequences largely hinge on the quality of the used primers and probes. This importance is especially evident when considering the specific sample being analyzed, as it affects the molecular background and potential for cross-reactivity, ultimately determining the test’s performance. Methods: Predicting primers based on the consensus sequence of the target has multiple advantages, including high specificity, diagnostic reliability, broad applicability, and long-term validity. Automated curation of the input sequences ensures high-quality primers and probes. Results: Here, we present a use case for developing a set of consensus primers and probes to identify antibiotic resistance and virulence genes in Staphylococcus (S.) aureus using the ConsensusPrime pipeline. Extensive qPCR experiments with several S. aureus strains confirm the exceptional quality of the primers designed using the pipeline. Conclusions: By improving the quality of the input sequences and using the consensus sequence as a basis, the ConsensusPrime pipeline pipeline ensures high-quality primers and probes, which should be the basis of molecular assays.

Background: Germany’s high density of under-equipped hospitals and anticipated surge in orthopedic and trauma surgery-related diseases by 2030, combined with personnel shortages, are expected to increase patient transfers between hospitals, an issue that urgently needs standardized protocols. Despite some existing cooperative agreements, such as between joint-replacement centers or within the Trauma Network DGU®, these measures do not adequately address the full range of patient-transfer cases, including those due to a lack of specialization or staff shortages, resulting in delayed treatment and potential health risks. This study aims to dissect the intricacies of interhospital transfers in orthopedics and trauma surgery across Germany, focusing on understanding the underlying reasons for transfers, comparing the operational structures of small and large hospitals, and laying the groundwork for future standardized protocols to enhance patient care. Material and Methods: A cross-sectional study was conducted in the form of an online survey via SoSci Survey, which was directed at orthopedic surgeons and trauma surgeons working in hospitals in Germany. The 22-question survey gathered information on participants’ clinic roles, departmental details, transfer processes, frequent diagnoses, perceptions of transfer quality, and improvement areas. The survey was sent to orthopedic and trauma surgeons in Germany by the specialist society. The data were analyzed using descriptive and inferential statistics to ensure a comprehensive insight into interhospital transfer practices. Results: The study involved 152 participants from various hospital ranks and located in different hospital sizes and types across rural and urban areas. A significant difference was observed between the care structures of basic/regular care and central/maximum care hospitals, especially regarding the available facilities and specialties. These findings suggest improvements such as better patient documentation, increased digital communication, optimized patient distribution, and standardization of transfer requests, among others. Conclusions: This study highlights the urgent need for improved protocols and resource allocation to eliminate inequalities in transfers between hospitals in orthopedics and trauma surgery in Germany.

Strategic communication can motivate target audiences to take conservation action. Yet, whether audiences are motivated by more information or more influential visuals is unclear. Using online surveys, we compared different visual communication strategies using text, graphics, and photographs for encouraging parrotfish-friendly conservation behaviors to see which one yields greater emotion, interest, and intended action. Experiment 1 explored whether a scientific-oriented poster would be more or less effective in promoting conservation behaviors than a graphical poster using social marketing techniques. Experiment 2 contrasted the two posters with a photograph and graphic icons without text against a blank control. Results revealed how engaging visuals can inspire reactions and behavioral intentions. The posters both elicited positive reactions, but with less text and content to process, the social marketing poster more efficiently inspired the desired reactions. This work highlights that conservation communications can strategically use psychology and graphics to efficiently inspire desired actions.

Randomised control trial data support the use of stereotactic radiosurgery (SRS) in up to 4 brain metastases (BMs), with non-randomised prospective data complementing this for up to 10 BMs. There is debate in the neuro-oncology community as to the appropriateness of SRS in patients with >10 BMs. We present data from a large single-centre cohort, reporting survival in those with >10 BMs and in a >20 BMs subgroup. A total of 1181 patients receiving SRS for BMs were included. Data were collected prospectively from the time of SRS referral. Kaplan–Meier graphs and logrank tests were used to compare survival between groups. Multivariate analysis was performed using the Cox proportional hazards model to account for differences in group characteristics. Median survival with 1 BM (n = 379), 2–4 BMs (n = 438), 5–10 BMs (n = 236), and >10 BMs (n = 128) was 12.49, 10.22, 10.68, and 10.09 months, respectively. Using 2–4 BMs as the reference group, survival was not significantly different in those with >10 BMs in either our univariable (p = 0.6882) or multivariable analysis (p = 0.0564). In our subgroup analyses, median survival for those with >20 BMs was comparable to those with 2–4 BMs (10.09 vs. 10.22 months, p = 0.3558). This study contributes a large dataset to the existing literature on SRS for those with multi-metastases and supports growing evidence that those with >10 BMs should be considered for SRS.

In an effort to reduce the occurrence of chlorine derived residues such as chlorate and trichloromethane (TCM) in milk and ultimately in dairy products, ‘chlorine-free’ cleaning of milking equipment became compulsory in the Republic of Ireland (ROI) from January 2021. While data exists on TCM levels in bulk tank milk, little is known about the prominence and typical levels (mg/kg) of chlorate residue in bulk tank milk. To address this, 3625 bulk milk samples were collected from six milk processors and were analysed for chlorate and TCM residues across 2020 and 2021, with 2020 representing a period before chlorine-free cleaning was introduced and 2021 being the period after chlorine removal. In 2020, 15% of the samples analysed had detectable levels of chlorate (0.0020–1.6 mg/kg), but this reduced to 8% in 2021 (0.0020–3.9 mg/kg), following the introduction of ‘chlorine-free’ cleaning. Chlorate and TCM residues have not been totally eliminated because sources of residue other than cleaning chemicals exist, i.e., chlorinated water.

Our study aimed to provide a description of the early childhood development of pediatric burn patients relative to Dutch reference values, using both pre- and post-burn data from the Dutch Development Instrument and the D-score. Data from the Dutch Development Instrument were used to calculate the D-score and age-standardized D-score. Similar to a growth chart, the D-score was used to plot pediatric burn patients’ development relative to Dutch reference values for their age. Pediatric burn patients’ (n = 38) median age at the time of injury was 1.0 (1.0–2.0) years old. Burn size ranged from 1.0% to 36.0% of the total body surface area. Ninety-five percent (± 6.0%) of pediatric burn patients passed each of the age-appropriate developmental milestones at the target age. The mean age-standardized D-score was just above the Dutch average (+0.49 SD [0.18, 0.80]) and did not vary depending on sex (p = 0.06) or burn size (p = 0.41). In conclusion, among pediatric patients aged up to two-and-a-half years old, with non-full thickness burns, development was on track relative to the Dutch reference values. Our findings offer valuable first insights into the early childhood development of pediatric burn patients and may alleviate some parental concerns.

In this review article, we summarize the most common clinical manifestations of Primary biliary cholangitis (PBC): pruritus, fatigue, osteoporosis, and dyslipoproteinemia and discuss their impact of the patients’ quality of life. More than half of PBC patients suffer from pruritus or fatigue at the time of diagnosis. We discuss the pathophysiological aspects of the PBC clinical manifestations and treatment options. The pathophysiology of pruritus and fatigue is not adequately elucidated, but IL-31 is associated with the severity of pruritus and could be used to objectify the subjective reporting by questionnaires. Although PBC patients suffer from atherogenic dyslipidemia, they do not seem to have a higher cardiovascular risk; however, this observation needs to be clarified by further clinical studies. The second-line of PBC treatment affects pruritus severity: Obeticholic acid (OCA) worsens pruritus while fibrates improve it. Itching can be alleviated by both non-pharmacological and pharmacological approach, however the are multiple barriers to pharmacological treatment. There is no adequate treatment for fatigue today. Treatment of osteoporosis and dyslipidemia is similar for non-PBC patients; stage of liver disease should be considered in treatment. Further research to clarify the pathophysiology and to eventually discover an effective treatment to improve survival and quality of life (especially pruritus and fatigue) in PBC patients is needed.

The treatment of relapsed and refractory multiple myeloma has improved substantially in the last 5–10 years based on the development and use of several novel classes of drugs and drug combinations. These advances have led to improvements in progression-free and overall survival as well as quality of life. The general tendency has been to advance drugs/combinations that have performed well in advanced disease to the earlier line settings (frontline, first/early relapse). There are several triplet drug combinations that, when used as part of first or early relapse, can provide remission durations of 3 years or longer. More recently, impressive responses have been seen with the use of targeted immunotherapeutics (chimeric antigen receptor T-cells and bispecific antibodies) in heavily pretreated patients with MM. These treatments, however, have been associated with some new and occasionally severe toxicities, including cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, and severe infections, including opportunistic infections and profound cytopenias. These potential toxicities bring into question whether these immune-targeting drugs should remain as late-line therapeutics or whether the high single-agent overall response rates mandate that these agents be used in earlier line settings. Herein, the authors provide a point and counterpoint about the future use of these agents.

Acute graft-versus-host disease (aGVHD) remains a barrier to successful allogeneic hematopoietic stem cell transplantation (HSCT) outcomes. Contemporary comprehensive analyses of real-world clinical outcomes among patients who develop aGVHD post-HSCT are needed to better understand the unmet needs of this patient population. This multicenter, retrospective chart review describes treatment patterns and clinical outcomes among patients (≥18 years old) from Finland, Sweden, and France who developed grades II–IV aGVHD after their first HSCT (January 2016–June 2017). From 13 participating centers, 151 patients were included. The median (Q1, Q3) age at HSCT was 56 (45, 62) years old. One line of aGVHD treatment was received by 47.7%, and the most common first-line treatment was methylprednisolone (alone or in a combination regimen, 74.2%; monotherapy, 25.8%). Among patients treated with methylprednisolone, 79.5% achieved a complete or partial response. The median (Q1, Q3) number of treatment lines was 2.0 (1.0, 3.0). The median (Q1, Q3) time to obtain an aGVHD diagnosis from transplant was 29.5 (21.0, 44.0) days, and 14.5 (7.0, 34.0) days to achieve the best response for 110 evaluable patients. At 6 and 12 months, 53.6% and 49.0%, respectively, achieved a complete response. Chronic GVHD occurred in 37.7% of patients, and aGVHD reoccurred in 26.5%. Following aGVHD diagnosis, mortality rates were 30.0% at 6 months and 37.3% at 12 months. Findings from this study demonstrate a continuing unmet need for new therapies that control aGVHD and improve mortality.

Developing a security solution for spatial files within today’s enterprise Geographical Information System (GIS) that is also usable presents a multifaceted challenge. These files exist in “data silos” of different file server types, resulting in limited collaboration and increased vulnerability. While cloud-based data storage offers many benefits, the associated security concerns have limited its uptake in GIS, making it crucial to explore comparable alternative security solutions that can be deployed on-premise and are also usable. This paper introduces a reasonably usable security solution for spatial files within collaborative enterprise GIS. We explore a Database File System (DBFS) as a potential repository to consolidate and manage spatial files based on its enterprise document management capabilities and security features inherited from the underlying legacy DBMS. These files are protected using the Advanced Encryption Standard (AES) algorithm with practical encryption times of 8 MB per second. The final part focuses on an automated encryption solution with schemes for single- and multi-user files that is compatible with various GIS programs and protocol services. Usability testing is carried out to assess the solution’s usability and focuses on effectiveness, efficiency, and user satisfaction, with the results demonstrating its usability based on the minimal changes it makes to how users work in a collaborative enterprise GIS environment. The solution furnishes a viable means for consolidating and protecting spatial files with various formats at the storage layer within enterprise GIS.

Classification, the task of discerning the class of an unlabeled data point using information from a set of labeled data points, is a well-studied area of machine learning with a variety of approaches. Many of these approaches are closely linked to the selection of metrics or the generalizing of similarities defined by kernels. These metrics or similarity measures often require their parameters to be tuned in order to achieve the highest accuracy for each dataset. For example, an extensive search is required to determine the value of K or the choice of distance metric in K-NN classification. This paper explores a method of kernel construction that when used in classification performs consistently over a variety of datasets and does not require the parameters to be tuned. Inspired by dimensionality reduction techniques (DRT), we construct a kernel-based similarity measure that captures the topological structure of the data. This work compares the accuracy of K-NN classifiers, computed with specific operating parameters that obtain the highest accuracy per dataset, to a single trial of the here-proposed kernel classifier with no specialized parameters on standard benchmark sets. The here-proposed kernel used with simple classifiers has comparable accuracy to the ‘best-case’ K-NN classifiers without requiring the tuning of operating parameters.

Lactic acid bacteria (LAB) can produce peptides known as bacteriocins with antagonistic activity against foodborne pathogens. The potential of LAB isolated from the surface of jalapeno peppers to produce bacteriocins with antagonistic activity against Listeria monocytogenes, Staphylococcus aureus, Escherichia coli O157:H7, and Salmonella Typhimurium was evaluated. Previously isolated LAB strains were reactivated, and their cell-free supernatants (CFSs) were evaluated. Out of 390 reactivated strains, 60 produced bacteriocin-like inhibitory substances (BLIS) since their antagonistic activity was lost after proteases addition. Subsequently, 16 BLIS showed heat resistance (HR-BLIS), retaining their bioactivity after heat treatment (121 °C for 15 min). By 16S rRNA gene sequencing and antibiotic susceptibility tests, LAB strains producing HR-BLIS were identified as Enterococcus lactis. Four HR-BLIS exhibited a minimum inhibitory concentration (MIC) of 80 mg/mL against L. monocytogenes. MIC and minimum bactericidal concentration (MBC) of HR-BLIS-67 for S. aureus (MIC = 80 mg/mL; MBC = 320 mg/mL), S. Typhimurium (MIC = 150 mg/mL; MBC = 250 mg/mL), and E. coli O157:H7 (MIC = 250 mg/mL; MBC = 400 mg/mL) were determined. LAB isolated from the surface of jalapeno pepper produced HR-BLIS (possibly enterocin) that exhibited broad-spectrum antagonistic activity against foodborne pathogens; therefore, they are a promising source of natural antimicrobials to ensure food safety.

The gut–brain axis (GBA) represents a complex, bidirectional communication network that intricately connects the gastrointestinal tract with the central nervous system (CNS). Understanding and intervening in this axis opens a pathway for therapeutic advancements for neurological and gastrointestinal diseases where the GBA has been proposed to play a role in the pathophysiology. In light of this, the current review assesses the effectiveness of neuromodulation techniques in treating neurological and gastrointestinal disorders by modulating the GBA, involving key elements such as gut microbiota, neurotrophic factors, and proinflammatory cytokines. Through a comprehensive literature review encompassing PubMed, Google Scholar, Web of Science, and the Cochrane Library, this research highlights the role played by the GBA in neurological and gastrointestinal diseases, in addition to the impact of neuromodulation on the management of these conditions which include both gastrointestinal (irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and gastroesophageal reflux disease (GERD)) and neurological disorders (Parkinson’s disease (PD), Alzheimer’s disease (AD), autism spectrum disorder (ASD), and neuropsychiatric disorders). Despite existing challenges, the ability of neuromodulation to adjust disrupted neural pathways, alleviate pain, and mitigate inflammation is significant in improving the quality of life for patients, thereby offering exciting prospects for future advancements in patient care.

Background: Taeniosis and cysticercosis are human infections caused by the pork tapeworm, Taenia solium. This study is a baseline for community-based intervention. We determined the prevalence of human cysticercosis and associated risk factors following a deworming program conducted throughout the country, with Mbulu District being among the districts in Northern Tanzania. Methods: Human cysticercosis was determined by enzyme-linked immunosorbent assay (Ag- ELISA). Household interviews and observations were conducted to identify risk factors for cysticercosis transmissions among households and communities. Results: Three hundred individuals participated in this study. The age ranged from 5 to 89 years, with a median of 19 years. The prevalence of human cysticercosis was 23 (7.67%). The prevalence was high with 6 (11.76%) among individuals aged 26 to 35 years and ±45 years. There was no statistically significant difference in the prevalence by age group, sex, or occupation. Among the 300 participants, 82 (27.3%) had received anthelmintics during the previous year; among these, 5 (21.7%) were infected. The likelihood of infection was low among anthelmintic users by 28% [0.72 (0.26–2.01)], but the protection was not significant. The communities differed in risk factors on the availability of a clean and safe water supply; 52.7% (46/86) of households visited had no pit latrine. The cysticercosis prevalence showed a significant difference in communities. Conclusions: The prevalence of human cysticercosis was high and associated with higher age groups. The prevalence was low among those who had taken anthelmintics and was associated with lower age groups. The current school deworming program has a positive effect on school children, while the elderly are at higher risk because the intervention did not target them. It is recommended to scale up anthelmintic intervention to higher age groups.

(1) Background: Bacterial contamination has been shown to occur during angiographies, although data on its frequency and relevance are sparse. Our aim was to evaluate the incidence of bacterial contamination of syringes used under sterile conditions during neuroangiographies. We sought to differentiate between contamination of the outside of the syringes and the inside and to detect the frequency, extent and germ spectrum of bacterial contamination. (2) Methods: We prospectively collected 600 samples from 100 neuroangiographies. Per angiography, fluid samples from the three routinely used syringes as well as the syringes themselves were analyzed. We analyzed the frequency and extent of contamination and determined the germ spectrum. (3) Results: The majority of samples (56.9%) were contaminated. There was no angiography that showed no contamination (0%). The outer surfaces of the syringes were contaminated significantly more frequently and to a higher extent than the inner surfaces. Both the frequency and extent of contamination of the samples increased with longer duration of angiographic procedures. Most of the bacterial species were environmental or skin germs (87.7%). (4) Conclusions: Bacterial contamination is a frequent finding during neuroangiographies, although its clinical significance is believed to be small. Bacterial contamination increases with longer duration of angiographic procedures.

The partial discharge (PD) event in high-voltage insulation releases energy, exerts mechanical pressure, and generates elastic waves. Detecting and locating these PD events through short-duration acoustic pulses is well established, particularly in gas-insulated systems and oil-insulated transformers. However, its full potential remains untapped in solid insulation systems, where the propagation capability of the acoustic pulse and the acoustic reflections pose fundamental challenges to the acoustic emission (AE) detection technique. This study investigates the influence of reflections and multiple paths on the propagating acoustic pulse in polymeric insulating materials using a finite element method (FEM) in COMSOL. It was observed that the reflections from the boundary influence the propagating pulse’s shape, peak magnitude, and arrival time. An analytical MATLAB model further quantifies the impact of multiple propagation paths on the shape, magnitude, and arrival time of the pulse travelling in a cylinder. Additionally, a Perfect Matched Layer (PML) was implemented in the COMSOL model to eliminate the reflections from the boundary, and it revealed that the acoustic pulse magnitude decreases with distance following the inverse square law. In essence, the models aid in measuring how reflections contribute to the observed signals, facilitating the precise identification of the source of the PD event in the tested system.

Anderson–Fabry Disease (AFD) is a rare, X-linked lysosomal storage disorder caused by a mutation in the α-Galactosidase A gene resulting in α-Galactosidase A enzyme (α-Gal A) deficiency. The metabolic defect leads to the progressive accumulation of glycosphingolipids and the structural and functional impairment of affected organs. Due to the inheritance pattern, male patients are hemizygous with more severe manifestations of the disease as compared to females who, in most cases, are heterozygous with delayed and variable clinical presentation caused by uneven X-chromosome inactivation. Fabry disease cases are often identified by targeted screening programs in high-risk groups, such as in patients with end-stage renal disease, premature stroke, or unexplained cardiomyopathy. Here, we describe a unique case of a homozygous female patient identified by a nationwide screening program in hypertrophic cardiomyopathy patients. Before the systematic screening, the patient had a diagnosis of hypertrophic obstructive cardiomyopathy and was treated accordingly, including with alcohol septal ablation to reduce the obstructive gradient. The confirmation of Fabry disease led to the discovery of the same variant in several members of her family. The identified variant was c.644A>G, p.Asn215Ser (p.N215S), which is known to cause predominant cardiac involvement with late onset of the disease. This variant is amenable to oral therapy with the small-molecule chaperone migalastat, which was started and then interrupted due to the recurrence of the patient’s migraine and then re-initiated again after two years. During this period, the patient received enzyme replacement therapy with agalsidase beta but developed progressively worsening venous access. Our case illustrates the importance of the systematic screening of patients with clinical evidence of hypertrophic cardiomyopathy in whom the routine diagnostic process fails to discover Fabry disease, in particular variants with late-onset cardiac manifestations. Many of the late-onset variants are amenable to orally active therapy with migalastat, which significantly improves the comfort of the treatment. Its long-term results are being analyzed by a large international “Follow-me” registry, which was designed to verify the validity of pivotal trials with migalastat in Fabry disease.

There is an urgent need for valid and reliable measures of physical activity (PA) participation for use among people with physical and/or sensory disabilities. This study involved adapting the Leisure Time PA Questionnaire for People with Spinal Cord Injury for use in individuals with disabilities (i.e., the LTPAQ-D) and performing a preliminary evaluation of its content validity, construct validity, and same-day test–retest reliability in people with disabilities. User interviews assessed the content validity (n = 5). A cross-sectional study assessed the construct validity and same-day test–retest reliability (n = 27, 45 ± 21 years). Participants completed the LTPAQ-D, other self-report measures of aerobic and strength training PA, as well as tests of cardiorespiratory fitness (i.e., peak oxygen consumption (V˙O2peak)) and muscular strength. LTPAQ-D measures of min/week of aerobic LTPA, aerobic moderate-to-vigorous PA (MVPA), and strength training shared medium-to-large correlations with other self-report measures of aerobic and strength training PA (r = 0.458–0.942, ps < 0.01). After controlling for age, aerobic LTPA and MVPA shared moderate partial correlations with V˙O2peak (r = 0.341 and 0.356, respectively). Min/week of strength training, measured by the LTPAQ-D, was associated with predicted maximal strength on the chest press (r = 0.621, p = 0.009). All LTPAQ-D measures demonstrated good-to-excellent test–retest reliability (intraclass correlations = 0.709–0.948, ps < 0.01). This study provides preliminary evidence of the validity and reliability of the LTPAQ-D as a measure of LTPA among people with disabilities.

The concept of nature positive has recently emerged from the widespread recognition of the global scale at which nature is being lost and the threat this poses to the collective survival of the human race. Much of the interest in nature positive reflects the initial commitment to it by conservation organisations and by a number of international political initiatives. However, the pursuit of nature positive approaches by businesses has received little attention in the business and management literature. Building upon an analysis of secondary sources, this entry paper first examines how three international organisations suggest a nature positive strategy could be pursued. This paper then focuses on two multinational companies and how they plan to pursue a nature positive approach to their business activities. This article identifies a number of critical factors in developing a nature positive strategy: incorporating suppliers in this strategy, assessing corporate dependencies and impacts on nature, and reporting on nature positive initiatives and outcomes. At the same time, this article raises concerns that nature positive approaches could be driven more by business imperatives rather than fundamental corporate concerns about biodiversity and that many business commitments to nature positive could be seen as mainly aspirational.

The growing importance of hydrogen as an energy carrier in a future decarbonised energy system has led to a surge in its production plans. However, the development of infrastructure for hydrogen delivery, particularly in the hard-to-abate sectors, remains a significant challenge. While constructing new pipelines entails substantial investment, repurposing existing pipelines offers a cost-effective approach to jump-starting hydrogen networks. Many European countries and, more recently, other regions are exploring the possibility of utilising their current pipeline infrastructure for hydrogen transport. Despite the recent efforts to enhance the understanding of pipeline compatibility and integrity for hydrogen transportation, including issues such as embrittlement, blend ratios, safety concerns, compressor optimisation, and corrosion in distribution networks, there has been limited or no focus on pipeline expansion options to address the low-energy density of hydrogen blends and associated costs. This study, therefore, aims to explore expansion options for existing natural gas high-pressure pipelines through additional compression or looping. It seeks to analyse the corresponding cost implications to achieve an affordable and sustainable hydrogen economy by investigating the utilisation of existing natural gas pipeline infrastructure for hydrogen transportation as a cost-saving measure. It explores two expansion strategies, namely pipeline looping (also known as pipeline reinforcement) and compression, for repurposing a segment of a 342 km × 36 inch existing pipeline, from the Escravos–Lagos gas pipeline system (ELPS) in Nigeria, for hydrogen transport. Employing the Promax® process simulator tool, the study assesses compliance with the API RP 14E and ASME B31.12 standards for hydrogen and hydrogen–methane blends. Both expansion strategies demonstrate acceptable velocity and pressure drop characteristics for hydrogen blends of up to 40%. Additionally, the increase in hydrogen content leads to heightened compression power requirements until approximately 80% hydrogen in the blends for compression and a corresponding extension in looping length until around 80% hydrogen in the blend for looping. Moreover, the compression option is more economically viable for all investigated proportions of hydrogen blends for the PS1–PS5 segment of the Escravos–Lagos gas pipeline case study. The percentage price differentials between the two expansion strategies reach as high as 495% for a 20% hydrogen proportion in the blend. This study offers valuable insights into the technical and economic implications of repurposing existing natural gas infrastructure for hydrogen transportation.

LED devices are increasingly gaining importance in lithography approaches due to the fact that they can be used flexibly for mask-less patterning. In this study, we briefly report on developments in mask-free lithography approaches based on nano-LED devices and summarize our current achievements in the different building blocks needed for its application. Individually addressable nano-LED structures can form the basis for an unprecedented fast and flexible patterning, on demand, in photo-chemically sensitive films. We introduce a driving scheme for nano-LEDs in arrays serving for a singularly addressable approach. Furthermore, we discuss the challenges facing nano-LED fabrication and possibilities to improve their performance. Additionally, we introduce LED structures based on a hybrid nanocrystal/nano-LED approach. Lastly, we provide an outlook how this approach could further develop for next generation lithography systems. This technique has a huge potential to revolutionize the field and to contribute significantly to energy and resources saving device nanomanufacturing.

Despite the limited coverage of coral reefs in the world’s oceans, they play a crucial role in global marine biodiversity and providing essential ecosystem services. This study explores the influence of chlorophyll-a (Chl-a) concentration in the water column on the estimation of bottom reflectance (rb) in coral reefs monitored by the Allen Coral Atlas coral reef monitoring system, using satellite imagery from a Sentinel-2 MSI sensor. We conducted a comprehensive analysis, considering Chl-a global distribution and variability, and its combined effect with water column depth over rb calculation. Our results demonstrated that the impact of Chl-a on rb estimation becomes significant when the water column depth exceeds 3 m. While suggesting the optionality of using regional Chl-a values, our study highlights potential overestimations of Chl-a in optically complex environments, such as along the Brazilian coast. This research contributes to refining coral reef monitoring systems and underscores the importance of accurate Chl-a assessments for robust environmental evaluations.

Buprenorphine is a safe and effective medication to treat opioid use disorder (OUD) in pregnant patients and is intended to be continued throughout pregnancy, delivery, and at least the one-year postpartum period. However, delivery often involves the need for acute pain management with opioid medications, such as after a cesarean section. For patients receiving buprenorphine, the provision of prescription opioids may negatively impact OUD treatment outcomes; however, not optimally managing acute pain may also impede OUD treatment benefit. Evidence is needed to disentangle the impacts of opioid prescription provision and methods of pain management in the immediate postpartum period on OUD treatment trajectories, ultimately to inform clinical guidelines tailored to the unique needs of pregnant and postpartum people receiving buprenorphine. Accordingly, this study took an initial step towards this goal to conduct a secondary analysis of a retrospective cohort of pregnant patients taking buprenorphine for OUD at the time of delivery (n = 142) to determine whether receipt of an opioid prescription at birth hospitalization discharge was associated with the time of buprenorphine discontinuation within the 12 months following delivery. Among the sample, 26% (n = 37) were prescribed an opioid at the time of birth hospitalization discharge. The number of weeks post-delivery until buprenorphine discontinuation occurred was shorter amongst patients who were prescribed an opioid (median 11 weeks) compared to patients who were not prescribed an opioid (median 39 weeks; p < 0.001 by Mann–Whitney U test). However, a Cox regression model reported that receipt of an opioid prescription following delivery did not significantly increase the hazard ratio for buprenorphine discontinuation. In other words, OUD patients not prescribed an opioid at birth hospitalization discharge continued their buprenorphine for a longer median duration after delivery compared to their counterparts who received prescription opioids; yet, this finding did not reach statistical significance when taking into account additional clinical variables. The findings indicate how further research is warranted to inform evidence-based post-delivery pain practices for postpartum OUD treatment patients.

The study of the phenomena occurring in the plantar region is remarkably intriguing, especially when performing a normal gait cycle where the foot is under loading conditions. The effects presented in the foot while walking provide relevant indicators regarding clinical means for enhancing regular performance or rehabilitation therapies. Nevertheless, more than traditional methods are needed to biomechanically evaluate foot structural conditions, leading to an incomplete database for determining the patient’s needs so that advanced methodologies provide detailed medical assessment. Therefore, it is necessary to employ technological engineering tools to optimize biomechanical plantar pressure evaluations to reach suitable personalized treatments. This research initially evaluated numerically the pressure points in the foot sole region in each one of the five stance phases in a normal gait cycle. Medical imaging techniques were utilized to construct an anatomically accurate biomodel of the soft tissues of the right foot. The Finite Element Method was employed to predict peak plantar pressure in barefoot conditions for all stance phases; results from this case study presented a close alignment with gait experimental testing implemented to analyze the feasibility and validation of all mechanical considerations for the numerical analyses. Hence, having a solid foundation in the biomechanical behavior from the first case study close estimates, a 3D-printable patient-specific insole was designed and numerically analyzed to observe the mechanical response in the plantar critical zones utilizing a personalized orthotic device. Results from the second case study notably demonstrated a crucial decrement in excessive pressure values. Employing morphological customization orthopedics modeling combined with 3D-printable materials is revolutionizing assistive device design and fabrication techniques. The fundamental contribution of this research relies on deepening the knowledge of foot biomechanics from an interdisciplinary approach by numerically analyzing pressure distribution in critical regions for all five stances phases; thus, based on the methods employed, the results obtained contribute to the advances of patient-specific foot orthopedics.

Cellular Vehicle-to-Everything (C-V2X) communications is a technology that enables intelligent vehicles to exchange information and thus coordinate with other vehicles, road users, and infrastructure. However, despite advancements in cellular technology for V2X applications, significant challenges remain regarding the ability of the system to meet stringent Quality-of-Service (QoS) requirements when deployed at scale. Thus, smaller-scale V2X use case deployments may embody a necessary stepping stone to address these challenges. This work assesses network architectures for an Intelligent Perception System (IPS) blind road junction or blind corner scenarios. Measurements were collected using a private 5G NR network with Sub-6GHz and mmWave connectivity, evaluating the feasibility and trade-offs of IPS network configurations. The results demonstrate the feasibility of the IPS as a V2X application, with implementation considerations based on deployment and maintenance costs. If computation resources are co-located with the sensors, sufficient performance is achieved. However, if the computational burden is instead placed upon the intelligent vehicle, it is questionable as to whether an IPS is achievable or not. Much depends on image quality, latency, and system performance requirements.

This study aimed to evaluate the safety and efficacy of a novel Poly-Ether-Ether-Ketone (PEEK) expandable vertebral body replacement (VBR) for anterior cervico-thoracic vertebral column reconstruction in patients with metastatic, traumatic, or degenerative diseases. Radiographic and clinical outcomes, as well as complication rates, were analyzed in a retrospective analysis of 28 patients (61 ± 13 years; 64% female) who underwent an anterior cervical corpectomy and fusion (ACCF) with the Expandable Corpectomy Device (ECD) from DePuy/Synthes (2011–2020). Correction of the bisegmental kyphotic angle (BKA) was chosen as the primary outcome. Bony fusion, loss of device height, and implant subsidence were evaluated additionally. Clinical outcome was assessed using Odom’s criteria, the numerical pain rating scale (NRS), the American Spinal Injury Association Impairment Scale (AIS), and the Karnofsky Performance Status Scale (KPSS). Our study found a significant improvement in the BKA (12.3° ± 9.6°; p = 0.0002) at the last follow-up with no statistically relevant loss of device height (p = 0.96) or implant subsidence (p = 0.99). Successful bony fusion was observed in all patients. The KPSS significantly improved in patients with a tumorous disease at the time of discharge (p = 0.0009), and the sensation of pain showed significant improvement at six months post-operatively and at the final follow-up (p = 0.004; p = 0.021). However, four patients needed further secondary posterior stabilization, and one ECD was explanted due to a severe surgical site infection after an accidental esophageal lesion. In conclusion, the ECD proofed the radiographic stability for the anterior column reconstruction of the cervico-thoracic spine with significantly improved clinical outcome.

Focused ultrasound (FUS) is a minimally invasive treatment that utilizes high-energy ultrasound waves to thermally ablate tissue. Magnetic resonance imaging (MRI) guidance may be combined with FUS (MRgFUS) to increase its accuracy and has been proposed for lung tumor ablation/debulking. However, the lungs are predominantly filled with air, which attenuates the strength of the FUS beam. This investigation aimed to test the feasibility of a new approach using an intentional lung collapse to reduce the amount of air inside the lung and a controlled hydrothorax to create an acoustic window for transcutaneous MRgFUS lung ablation. Eleven pigs had one lung mechanically ventilated while the other lung underwent a controlled collapse and subsequent hydrothorax of that hemisphere. The MRgFUS lung ablations were then conducted via the intercostal space. All the animals recovered well and remained healthy in the week following the FUS treatment. The location and size of the ablations were confirmed one week post-treatment via MRI, necropsy, and histological analysis. The animals had almost no side effects and the skin burns were completely eliminated after the first two animal studies, following technique refinement. This study introduces a novel methodology of MRgFUS that can be used to treat deep lung parenchyma in a safe and viable manner.

Transarterial chemoembolization (TACE) is a minimally invasive treatment for liver cancer, often employed as a bridging therapy or destination treatment for non-operable cases. This case report discusses an 82-year-old woman with a large hepatocellular carcinoma (HCC) who underwent elective TACE due to the high surgical risk associated with her tumor size. Unexpectedly, the patient experienced liver rupture 20 h post-procedure, leading to acute surgical intervention. Despite successful hemostasis during surgery, the patient succumbed to progressive multi-organ failure. We aimed to search the PubMed database for documented cases of ruptured HCC after TACE. This study highlights risk factors for spontaneous HCC rupture and specific factors associated with TACE-induced rupture. Transarterial embolization (TAE) is currently favored as the treatment method for spontaneous ruptures, while the optimal therapy for TACE-induced ruptures remains unclear. In conclusion, this case underscores the importance of recognizing the rare complication of HCC rupture post-TACE and the need for personalized risk assessment. While TAE emerges as a primary treatment choice, the lack of consensus necessitates further studies to establish evidence-based approaches for managing this uncommon yet life-threatening complication.

Background: In recent years, there has been a growing interest in the therapeutic potential of classical psychedelics like ayahuasca for mental health improvement. Naturalistic studies at ayahuasca retreats have shown (short-term) improvements in mental well-being but understanding the psychological mechanisms is crucial. We are interested in psychological processes such as resilience, self-compassion, and personality traits. Additionally, it is unclear whether changes are solely due to ayahuasca or influenced by the social setting. To address this, a control group participating in a breathwork session, similar to ayahuasca retreats, was included. Methods: In this observational study, individuals who attended an ayahuasca retreat (n = 69) and individuals who participated in a breathwork session (n = 30) completed an online survey one week before (baseline) and one, six, and twelve weeks after they entered the retreat/session. The survey included a series of questionnaires, i.e., the World Health Organisation-Five Well-Being Index, 14-item Resilience Scale, Self-Compassion Scale–Short Form, and Big Five Inventory-10. A linear mixed model (LMM) was used to analyze the outcome data. Results: It was shown that well-being, resilience, and self-compassion increased and remained stable over 12 weeks compared to baseline, regardless of group (ayahuasca or breathwork). Older participants generally reported higher resilience and self-compassion. Self-compassion was also higher in the ayahuasca group overall. Neuroticism decreased in both groups, with lower scores in the ayahuasca group. Agreeableness increased over time, also not influenced by group membership, while there were no changes in extraversion, conscientiousness, or openness. Discussion: Both interventions improved well-being, aligning with prior research. Importantly, this study unveils a novel finding: both interventions enhance resilience and self-compassion for up to three months, offering promise for conditions marked by low well-being, resilience, and self-compassion like depression and anxiety-related disorders. While acknowledging its limitations (e.g., self-selected sample, no specific information of the ayahuasca brew or the breathwork technique), it emphasizes the need for controlled studies with control groups, attention to social contexts in research on these interventions, and to assess other variables like depth of altered states of consciousness that might explain improvement in psychological processes and wellbeing.

Parents’ emotions after their child’s burn might be influenced by the injury circumstances or demographic characteristics of the patient and family. Parents’ post-traumatic stress symptoms and their child’s distress may interact and affect emotional states. The psychosocial outcomes of parents were measured using the Impact of Event Scale-Revised, the CARe Burn Scale, and the Post-traumatic Growth Inventory-Brief. The psychosocial quality of life outcomes of the pediatric burn patients were measured using the Pediatric Quality of Life Inventory (PedsQL). Regression analysis was used to assess the relationship between patient psychosocial quality of life and the related parent scores. A total of 48 patients and parents participated, with 36 giving full data at 12 months. Parental post-traumatic stress symptoms were initially high, settling by six months, although outliers remained. Parents reported higher IESR scores if their child was female, if they felt helpless at the time of the incident, and if a language other than English was spoken in the home. Parents’ scores of their child’s psychosocial function were similar to their child’s self-scores. Parents who perceived poorer emotional functioning in their child reported higher IESR scores.

This work aimed to investigate a potential link between serum IL-1β levels in patients with giant cell arteritis (GCA) and their responsiveness to combined anti-IL-6 receptor (IL-6R) and glucocorticoid (GC) treatments within the context of two separate clinical trials. IL-1β levels were analyzed in serum samples of two prospective clinical trials investigating tocilizumab in GCA patients using quantitative Polymerase Chain Reaction (qPCR) based Proximity Ligation Assays (PLA). In the phase II randomized controlled trial, serum samples from five patients were quantified at two critical time points: the commencement of the trial (Week 2) and the conclusion of the trial (Week 52). In the GUSTO trial, serum samples from nine patients were similarly analyzed using PLA at Day 0 and Week 52. Furthermore, for the GUSTO trial, serum samples from 18 patients were assessed for IL-1β and IL-1RN at six time points: days 0, 3, and 10, weeks 4, 24, and 52 by a second assay (Proximity Extension Assay, PEA). PLA results from both studies indicated that IL-1β levels were below 1 pg/mL in most of the patients, resulting in notable signal deviations within the same samples. In the analysis of the GUSTO trial, both PLA and PEA exhibited similar trends in IL-1β variations among patients from day 0 to week 52. Notably, the PEA analysis did not show significant variation over time. Furthermore, we did not find a correlation of IL-1β levels with active disease as compared to remission, but interestingly, the measurement of IL-1β receptor antagonist (IL-1RN) revealed a substantial decrease over time. Our study shows that IL-1RN but not IL-1β concentration in serum samples could be directly related to anti-IL-6R treatment in patients diagnosed with GCA.

A hepatocyte cell line was used to determine the hepatotoxicity of sedatives and opioids, as the hepatotoxicity of these drugs has not yet been well characterized. This might pose a threat, especially to critically ill patients, as they often receive high cumulative doses for daily analgosedation and often already have impaired liver function due to an underlying disease or complications during treatment. A well-established biosensor based on HepG2/C3A cells was used for the determination of the hepatotoxicity of commonly used sedatives and opioids in the intensive care setting (midazolam, propofol, s-ketamin, thiopental, fentanyl, remifentanil, and sufentanil). The incubation time was 2 × 3 days with clinically relevant (Cmax) and higher concentrations (C5× and C10×) of each drug in cell culture medium or human plasma. Afterward, we measured the cell count, vitality, lactate dehydrogenase (LDH), mitochondrial dehydrogenase activity, cytochrome P 450 1A2 (CYP1A2), and albumin synthesis. All tested substances reduced the viability of hepatocyte cells, but sufentanil and remifentanil showed more pronounced effects. The cell count was diminished by sufentanil in both the medium and plasma and by remifentanil only in plasma. Sufentanil and remifentanil also led to higher values of LDH in the cell culture supernatant. A reduction of mitochondrial dehydrogenase activity was seen with the use of midazolam and s-ketamine. Microalbumin synthesis was reduced in plasma after its incubation with higher concentrations of sufentanil and remifentanil. Remifentanil and s-ketamine reduced CYP1A2 activity, while propofol and thiopental increased it. Our findings suggest that none of the tested sedatives and opioids have pronounced hepatotoxicity. Sufentanil, remifentanil, and s-ketamine showed moderate hepatotoxic effects in vitro. These drugs should be given with caution to patients vulnerable to hepatotoxic drugs, e.g., patients with pre-existing liver disease or liver impairment as part of their underlying disease (e.g., hypoxic hepatitis or cholestatic liver dysfunction in sepsis). Further studies are indicated for this topic, which may use more complex cell culture models and global pharmacovigilance reports, addressing the limitation of the used cell model: HepG2/C3A cells have a lower metabolic capacity due to their low levels of CYP enzymes compared to primary hepatocytes. However, while the test model is suitable for parental substances, it is not for toxicity testing of metabolites.

Background: This study aimed to evaluate age-specific variations in the blood levels of micronutrients, homocysteine, and CoQ10, along with physical activity (PA) patterns, among 123 Austrian adult bankers in operational and frontline roles (mean age: 43 years; 50% female). Methods: Blood analysis was conducted to assess micronutrients and the serum concentrations of homocysteine and CoQ10. The micronutrient values in whole blood were compared to sex-specific reference ranges and categorized as below, within, or above them. The Global Physical Activity Questionnaire was utilized to assess PA patterns. Participants were classified as young adults (18–34 years), middle-aged adults (35–49 years), and older adults (50–64 years). Results: Significant age-based differences were found in participants’ mean homocysteine levels (p = 0.039) and homocysteine categories (p = 0.034), indicating an increasing prevalence of hyperhomocysteinemia with age. No significant difference between age categories was observed for sex, BMI, diet types, PA levels, sedentary behavior, and CoQ10 (p > 0.05). There was no significant age-based difference in the blood concentrations of most minerals and vitamins (p > 0.05), except for magnesium among females (p = 0.008) and copper among males (p = 0.042). Conclusion: The findings offer initial evidence of the age-related differences in the health status of adult bankers, providing insights for customized approaches to occupational health that support the importance of metabolic health and overall well-being across adulthood.

Fingerprints are essential for human identification and are valuable tools in criminal investigations. The pursuit of new materials for digital printing is expanding, with increasing interest in natural compounds such as bixin, sourced from annatto seeds. Despite its traditional use as a natural dye with medicinal properties, the potential of bixin in papilloscopy remains largely untapped. In this study, we meticulously extracted bixin from annatto seeds and meticulously developed composites incorporating zinc carbonate (bixin/ZnCO3) and kaolinite (bixin/kaolinite). UV-visible spectroscopy was used for characterization, and the extracted bixin showed absorption peaks at 429, 453, and 481 nm, which were very similar to standard peaks at 429, 457, and 487 nm. The two samples also had the same retention times (7.07 min) according to further liquid chromatography analysis. Sweat pores were easier to detect thanks to the effectiveness of the bixin/ZnCO3 and bixin/kaolinite composites in creating high contrast sebaceous and natural latent fingerprints. These results highlight the composites’ potential as novel and fascinating instruments for papilloscopy applications, which might also improve forensic investigations.

Background: Annually, approximately 200 new ovarian cancer cases are diagnosed in Armenia, which is considered an upper-middle-income country. This study aimed to summarize the survival outcomes of patients with relapsed ovarian cancer in Armenia based on the type of recurrence, risk factors, and choice of systemic treatment. Methods: This retrospective case-control study included 228 patients with relapsed ovarian cancer from three different institutions. Results: The median age of the patients was 55. The median follow-up times from relapse and primary diagnosis were 21 and 48 months, respectively. The incidence of platinum-sensitive relapse was 81.6% (186), while platinum-resistant relapse was observed in only 18.4% (42) of patients. The median post-progression survival of the platinum-sensitive group compared to the platinum-resistant group was 54 vs. 25 months (p < 0.001), respectively, while the median survival after relapse was 25 vs. 13 months, respectively; three- and five-year post-progression survival rates in these groups were 31.2% vs. 23.8%, and 15.1% vs. 9.5%, respectively (p = 0.113). Conclusions: Overall, despite new therapeutic approaches, ovarian cancer continues to be one of the deadly malignant diseases affecting women, especially in developing countries with a lack of resources, where chemotherapy remains the primary available systemic treatment for the majority of patients. Low survival rates demonstrate the urgent need for more research focused on this group of patients with poor outcomes.

Ductal adenocarcinoma of the prostate (DAP) is an uncommon variant of prostate cancer associated with aggressive disease and poor outcome. It presents most frequently as a mixed tumor combined with acinar adenocarcinoma. Although the histopathological features of DAP are well known, its genomic characteristics are still evolving, prompting the suggestion that all DAP would benefit from molecular analysis with the purpose of improving tumor recognition, genetic classification, and, ultimately, personalized therapy. Herein, we report a case of DAP with novel genetic alterations (BCOR P1153S, ERG M219I, KDR A750E, POLE S1896P, and RAD21 T461del).