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Purpose/aim: This paper provides a pedagogical example for systematic machine learning optimization in small dataset image segmentation, emphasizing hyperparameter selections. A simple process is presented for medical physicists to examine hyperparameter optimization. This is also applied to a case-study, demonstrating the benefit of the method., Materials and Methods: An unrestricted public Computed Tomography (CT) dataset, with binary organ segmentation, was used to develop a multiclass segmentation model. To start the optimization process, a preliminary manual search of hyperparameters was conducted and from there a grid search identified the most influential result metrics. A total of 658 different models were trained in 2100 h, using 13 160 effective patients. The quantity of results was analyzed using random forest regression, identifying relative hyperparameter impact., Results: Metric implied segmentation quality (accuracy 96.8%, precision 95.1%) and visual inspection were found to be mismatched. In this work batch normalization was most important, but performance varied with hyperparameters and metrics selected. Targeted grid-search optimization and random forest analysis of relative hyperparameter importance, was an easily implementable sensitivity analysis approach., Conclusion: The proposed optimization method gives a systematic and quantitative approach to something intuitively understood, that hyperparameters change model performance. Even just grid search optimization with random forest analysis presented here can be informative within hardware and data quality/availability limitations, adding confidence to model validity and minimize decision-making risks. By providing a guided methodology, this work helps medical physicists to improve their model optimization, irrespective of specific challenges posed by datasets and model design., (© 2024 The Author(s). Journal of Applied Clinical Medical Physics published by Wiley Periodicals LLC on behalf of The American Association of Physicists in Medicine.)

A randomised open clinical/laboratory study was performed to evaluate the safety and cosmetic efficacy of facial cosmetics for females during the menopausal period. The cosmetics contain active ingredients of meristem cells derived from the medicinal plants Leontopodium alpinum , Buddeleja davidii , Centella asiatica , and Echinacea angustifolia . Recently, the major bioactive molecules of these medicinal plants (leontopodic acid, verbascoside, asiaticoside, and echinacoside, respectively) have been thoroughly evaluated in vitro for molecular pathways and cellular mechanisms and their preventive/curative effects on human skin cells exposed to factors promoting premature skin ageing and cellular senescence. Nevertheless, clinical data on their safety/efficacy to ageing human skin are scarce. This clinical study enrolled 104 Caucasian females in pre-menopause, menopause, or post-menopause periods. They applied cosmetic serums daily for 1 month. Questionnaires and instrumental and biochemical methods were used to assess dermatological/ophthalmological safety and cosmetic efficacy through changes of the skin physiology markers characteristic of ageing/menopause (elasticity, barrier functions, moisture, sebum, ultrasonic properties, and collagen content and structure). Quantitative microbiological tests were carried out for skin microbiota fluctuations. Data showed that the cosmetics were safe, and they shifted the skin physiology parameters to a younger biological age, enhanced collagen synthesis, inhibited lipid peroxidation, and favoured normal microbiota.

Background: Older adults discharged from the emergency department (ED) face elevated risk of falls and functional decline. Smartphones might enable remote monitoring of mobility after ED discharge, yet their application in this context remains underexplored., Objective: This study aimed to assess the feasibility of having older adults provide weekly accelerometer data from an instrumented Timed Up-and-Go (TUG) test over an 11-week period after ED discharge., Methods: This single-center, prospective, observational, cohort study recruited patients aged 60 years and older from an academic ED. Participants downloaded the GaitMate app to their iPhones that recorded accelerometer data during 11 weekly at-home TUG tests. We measured adherence to TUG test completion, quality of transmitted accelerometer data, and participants' perceptions of the app's usability and safety., Results: Of the 617 approached patients, 149 (24.1%) consented to participate, and of these 149 participants, 9 (6%) dropped out. Overall, participants completed 55.6% (912/1639) of TUG tests. Data quality was optimal in 31.1% (508/1639) of TUG tests. At 3-month follow-up, 83.2% (99/119) of respondents found the app easy to use, and 95% (114/120) felt safe performing the tasks at home. Barriers to adherence included the need for assistance, technical issues with the app, and forgetfulness., Conclusions: The study demonstrates moderate adherence yet high usability and safety for the use of smartphone TUG tests to monitor mobility among older adults after ED discharge. Incomplete TUG test data were common, reflecting challenges in the collection of high-quality longitudinal mobility data in older adults. Identified barriers highlight the need for improvements in user engagement and technology design., (© Brian Suffoletto, David Kim, Caitlin Toth, Waverly Mayer, Sean Glaister, Chris Cinkowski, Nick Ashenburg, Michelle Lin, Michael Losak. Originally published in JMIR Aging (https://aging.jmir.org).)

Aim: To investigate a novel phacoemulsification system "EVA NEXUS" (D.O.R.C., Dutch Opthalmic Research Center) in comparison to the existing system "EVA" in clinical use. And to compare both phacoemulsification systems in terms of efficiency, safety and postoperative inflammatory activity., Methods: In this study standardized cataract surgery was performed on both eyes of the study participant, using the "EVA system" (control group, n =20) on one eye and the "EVA NEXUS system" (intervention group, n =20) on the other eye. Only patients with cataract LOCS Grading 1-3 and no accompanying eye diseases were included in this study. A total of 20 patients were included in this study, with each treatment arm including 20 eyes. During surgery a 0.1 mL aqueous humor sample was collected 1min after phacoemulsification to measure the total prostaglanin E2 concentrations using an enzyme-linked immunosorbent assay. The endothelial cell count, visual and refractive outcomes, and anterior chamber flare were evaluated preoperatively, and 1d, 1wk, and 3mo postoperatively., Results: There were no statistically significant differences between both groups regarding intraoperative safety parameters including effective phacoemulsification time ( P =0.904), balanced saline solution flow ( P =0.701) and total surgery time ( P =0.565). Postoperative prostaglandin E2 levels, anterior chamber flare as well as endothelial cell loss tended to be lower in the NEXUS-Group, however not being statistically significant ( P =0.718; 0.164; 0.486). Both systems provided similar clinical outcomes, regarding best corrected visual acuity and refractive parameters, showing no statistically significant differences between both groups., Conclusion: Both systems show a high level of safety and efficency with similar results in terms of safety parameters including postoperative inflammatory activity and endothelial cell loss as well as visual and refractive outcomes. Although statistically not significant, the EVA NEXUS system tends to cause less postoperative inflammation with lower prostaglandin E2 levels and lower anterior chamber flare values., Competing Interests: Conflicts of Interest: Feldhaus L, None; Ohlmann A, None; Kassumeh S, None; Priglinger S, Zeiss; Mayer W, DORC, Ziemer, Zeiss., (International Journal of Ophthalmology Press.)

This article explores the theological drivers of domestic and family violence (DFV)-specifically intimate partner violence-by engaging with ecclesiastical beliefs and practices of the Lutheran Church of Australia (LCA). Key theological, policy, and public documents were analyzed to understand gender relations, gender roles, marriage, ordination, ethical behavior, and responses to DFV. Findings from the document analysis demonstrate church practice and policy reforms underway in addressing violence against women and supporting safety. Simultaneously, the documents show contested and troubled positions regarding gender relations, the theological context to gender roles and responsibilities and the church's journey of debating (re)configuration of its organizational structure and responsibilities., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

5-Methyluridine (m5U) is one of the most abundant RNA modifications found in cytosolic tRNA. tRNA methyltransferase 2 homolog A (hTRMT2A) is the dedicated mammalian enzyme for m5U formation at tRNA position 54. However, its RNA binding specificity and functional role in the cell are not well understood. Here we dissected structural and sequence requirements for binding and methylation of its RNA targets. Specificity of tRNA modification by hTRMT2A is achieved by a combination of modest binding preference and presence of a uridine in position 54 of tRNAs. Mutational analysis together with cross-linking experiments identified a large hTRMT2A-tRNA binding surface. Furthermore, complementing hTRMT2A interactome studies revealed that hTRMT2A interacts with proteins involved in RNA biogenesis. Finally, we addressed the question of the importance of hTRMT2A function by showing that its knockdown reduces translation fidelity. These findings extend the role of hTRMT2A beyond tRNA modification towards a role in translation., (© The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Background: Extracorporeal photopheresis (ECP) treatment, mostly based on apheresis technology, is used for immunomodulation in various diseases such as cutaneous T-cell lymphoma, graft versus host disease and other (auto)immune disorders. The aim of this study was to collect high cell counts and purity in shorter procedure times using an ECP off-line system with an increased collection flow rate of 2 mL/min to a target volume of 200 mL buffy coat., Study Design and Methods: In this prospective study, data of routinely performed off-line photopheresis treatments were collected and analyzed at the Central Institute for Blood Transfusion & Department of Immunology (ZIB) of the Tirol Kliniken, to assess absolute cell counts and procedure times and to calculate collection efficiencies (CE2)., Results: A total of 22 patients participated in this study. The processed blood volume was 4312 mL, the collection time 120 min, overall procedure time 157 min and the absolute cell counts of treated white blood cells (WBC) and mononuclear cells (MNC) were 5.0 and 4.3 × 10 9 respectively (median values). The calculated CE2 for WBC and MNC was 21.1% and 58.5%, the proportion of treated MNCs of the total number of MNCs present was 55.0%., Conclusion: The data presented in this study show high therapeutically effective cell counts collected with a high MNC purity within a shorter overall collection/procedure time due to an increased collection flow rate., (© 2023 The Authors. Transfusion published by Wiley Periodicals LLC on behalf of AABB.)

Conducting safety evaluations of new drugs using conscious animals has been a specialty of our working group for thirty years. In this article, we review the various technical challenges and solutions dealt with over the years to improve both the data quality and the well being of our animal subjects. Of particular interest for us has been the use of telemetry-based data acquisition for conducting studies on cardiovascular (CV) function. This includes the evolving technical aspects of the studies, as well as the development of new applications that take advantage of this technical approach., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Plant-derived secondary metabolites (polyphenols/terpenes/alkaloids) and microbial exometabolites/membrane components of fermented tropical fruits are known as highly bioavailable biomolecules causing skin and hair improvement effects (wound healing, anti-inflammatory, antioxidant, antidiabetic, antiacne, skin/hair microbiota balancing, hair growth-promoting, and hair loss-inhibiting). Caffein is considered as a hair growth promoter. A randomized placebo- and caffein-controlled clinical trial on the efficacy of fermented papaya (FP) plus fermented mangosteen (FM) towards human hair quality and loss was conducted. Shampoo and lotion hair care products containing FP, FM, and caffein as active agents were developed and applied to 154 subjects of both sexes with clinically confirmed androgenic or diffuse alopecia for 3 months. Their clinical efficacy was assessed subjectively by questionnaires filled in by dermatologists/trichologists, and by the objective trichomicroscopical calculations. Hair and scalp skin quality was determined by microbiota pattern and ATP, SH-groups, protein, and malonyl dialdehyde quantification. Comparative clinical data showed that the experimental hair care cosmetics significantly inhibited hair loss, increased hair density/thickness, and improved hair follicle structure versus placebo and caffein controls. The cosmetics with FP and FM substantially normalized the microbiota pattern and increased ATP content in hair follicle, while inhibiting lipid peroxidation in the scalp skin, and SH-group formation in the hair shaft.

Gut microbiota plays a crucial role in modulating pig development and health, and gut microbiota characteristics are associated with differences in feed efficiency. To answer open questions in feed efficiency analysis, biologists seek to retrieve information across multiple heterogeneous data sources. However, this is error-prone and time-consuming work since the queries can involve a sequence of multiple sub-queries over several databases. We present an implementation of an ontology-based Swine Gut Microbiota Federated Query Platform (SGMFQP) that provides a convenient, automated, and efficient query service about swine feeding and gut microbiota. The system is constructed based on a domain-specific Swine Gut Microbiota Ontology (SGMO), which facilitates the construction of queries independent of the actual organization of the data in the individual sources. This process is supported by a template-based query interface. A Datalog + -based federated query engine transforms the queries into sub-queries tailored for each individual data source, and an automated workflow orchestration mechanism executes the queries in each source database and consolidates the results. The efficiency of the system is demonstrated on several swine feeding scenarios., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background:  Modern preoperative diagnostics as well as current surgical techniques allow cataract and refractive surgery to deliver precise refractive results.Occasionally, unsatisfactory refractive and visual results occur despite all the care taken. In these cases, subsequent improvement is required to achieve the best final visual outcome. This article shows the therapeutic options for the treatment of residual refractive errors after lens and corneal refractive surgery., Key Messages:  The causes of postoperative refractive errors after refractive laser- or lens-based procedures are very diverse and require extensive workup of the cause as well as an individual solution to achieve the desired result. Before any further surgical intervention, specific complications of the primary procedure as well as concomitant ocular diseases must be excluded or treated. The appropriate enhancement after keratorefractive surgery depends primarily on the type of primary surgery, residual stromal thickness, possible complications from the initial surgery, and the patient's personal preference. For enhancements using surface treatments, such as PRK, the use of mitomycin C is recommended for prophylaxis of haze formation. After lens surgery, for low-grade postoperative refractive errors (spherical and astigmatic), keratorefractive enhancements provide the most accurate results. For higher refractive errors, lens-based procedures can be used, with add-on IOLs being safer and more precise compared with one IOL exchange. Low astigmatisms can be successfully treated with LRI or keratorefractive surgery, but higher astigmatisms should be corrected with an IOL exchange in the early postoperative period and with an add-on IOL in the later postoperative period. IOL explantations should be performed very cautiously, especially in cases of pronounced capsular fibrosis, previous posterior capsulotomy, and existing weakness of the zonular apparatus., Competing Interests: Erklärung zu finanziellen Interessen Forschungsförderung erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Honorar/geldwerten Vorteil für Referententätigkeit erhalten: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Bezahlter Berater/interner Schulungsreferent/Gehaltsempfänger: ja, von einer anderen Institution (Pharma- oder Medizintechnikfirma usw.); Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an im Bereich der Medizin aktiven Firma: nein; Patent/Geschäftsanteile/Aktien (Autor/Partner, Ehepartner, Kinder) an zu Sponsoren dieser Fortbildung bzw. durch die Fortbildung in ihren Geschäftsinteressen berührten Firma: nein. Erklärung zu nichtfinanziellen Interessen Lukas Feldhaus: keine finanziellen Interessenkonflikte.Nikolaus Luft: Consultant & Speaker für Carl Zeiss Meditec.Wolfgang Mayer: Alcon (F/C/R); Zeiss (F/C/R); Ziemer (F/C/R); DORC (F/R); Allergan (F/R); Teleon Surgical (F/R); Novartis (F/R); Bausch & Lomb (F/R); Heidelberg Engineering (R); Örtli (R); Staar Surgical (R); CSO (R); Humanoptics (R); Ophtec (R) [F: Financial Support; C: Consultant; R: Recipient], (Thieme. All rights reserved.)

In our single-center study, 357 myeloma and lymphoma patients between 2009 and 2019 were mobilized with granulocyte colony-stimulating factor (G-CSF 7.5 µg/kg bid for four days) plus a fixed dose of 24 mg Plerixafor when indicated (Plerixafor Group, n = 187) or G-CSF alone (G-CSF Group, n = 170). The target CD34 cell yields were ≥2.0 × 10 6 CD34+ cells/kg in lymphoma and ≥4.0 × 10 6 CD34+ cells/kg in myeloma patients to enable putative second transplants in the latter. There were no significant differences in engraftment kinetics or transfusion requirements between the Plerixafor Group and the control group in the myeloma cohort, with lymphoma patients not requiring Plerixafor showing significantly faster neutrophil recovery, a trend to faster platelet recovery, and a significantly lower need for platelet transfusions, probably due to the significantly lower number of CD34-positive cells re-transfused. While in myeloma patients the outcome (overall survival, progression-free survival) following autologous stem cell transplantation (ASCT) was similar between the Plerixafor Group and the control group, hard to mobilize lymphoma patients had significantly poorer progression-free survival (47% vs. 74% at 36 months after ASCT, p = 0.003) with a trend also to poorer overall survival (71% vs. 84%). In conclusion, while there seem to be no differences in stemness capacity and long-term engraftment efficiency between the Plerixafor and the G-CSF Group in lymphoma as well as myeloma patients, poor mobilizing lymphoma patients per se constitute a high-risk population with a poorer outcome after ASCT. Whether disease characteristics and/or a more intense or stem cell-toxic pre-mobilization chemo-/radiotherapy burden in this cohort are responsible for this observation remains to be shown in future studies.

The incidence of human papillomavirus (HPV)-associated anogenital and oropharyngeal cancer in human immunodeficiency virus (HIV)-infected individuals is substantially higher than in HIV-uninfected individuals. HIV may also be a risk factor for the development of HPV-negative head and neck, liver, lung, and kidney cancer. However, the molecular mechanisms underlying HIV-1-associated increase of epithelial malignancies are not fully understood. Here, we showed that HPV-16-immortalized anal AKC-2 and cervical CaSki epithelial cells that undergo prolonged exposure to cell-free HIV-1 virions or HIV-1 viral proteins gp120 and tat respond with the epithelial-mesenchymal transition (EMT) and increased invasiveness. Similar responses were observed in HPV-16-infected SCC-47 and HPV-16-negative HSC-3 oral epithelial cancer cells that were cultured with these viral proteins. EMT induced by gp120 and tat led to detachment of poorly adherent cells from the culture substratum; these cells remained capable of reattachment, upon which they coexpressed both E-cadherin and vimentin, indicative of an intermediate stage of EMT. The reattached cells also expressed stem cell markers CD133 and CD44, which may play a critical role in cancer cell invasion and metastasis. Inhibition of transforming growth factor (TGF)-β1 and MAPK signaling and vimentin expression, and restoration of E-cadherin expression reduced HIV-induced EMT and the invasive activity of HPV-16-immortalized anal and cervical epithelial cells. Collectively, our results suggest that these approaches along with HIV viral suppression with antiretroviral therapy (ART) might be useful to limit the role of HIV-1 infection in the acceleration of HPV-associated or HPV-independent epithelial neoplasia. IMPORTANCE HPV-16-immortalized genital and oral epithelial cells and HPV-negative oral cancer cells that undergo prolonged contact with cell-free HIV-1 virions or with viral proteins gp120 and tat respond by becoming more invasive. EMT cells induced by HIV-1 in cultures of HPV-16-immortalized anal and cervical epithelial cells express the stem cell markers CD133 and CD44. These results suggest that the interaction of HIV-1 with neoplastic epithelial cells may lead to their de-differentiation into cancer stem cells that are resistant to apoptosis and anti-cancer drugs. Thus, this pathway may play a critical role in the development of invasive cancer. Inhibition of TGF-β1 and MAPK signaling and vimentin expression, and restoration of E-cadherin expression reduced HIV-induced EMT and the invasiveness of HPV-16-immortalized anal and cervical epithelial cells. Taken together, these results suggest that these approaches might be exploited to limit the role of HIV-1 infection in the acceleration of HPV-associated or HPV-independent epithelial neoplasia.

In the observational clinical study, we identified the oxidative markers of HPV-associated cervical carcinogenesis and the local/circulating ligands of TNF-alpha-induced apoptosis. Cervical biopsies of 196 females infected with low-cancer-risk HPV10/13 or high-cancer-risk HPV16/18 (healthy, pre-cancerous CIN I and CIN II, and CIN III carcinoma) were analysed for OH radical scavenging, catalase, GSH-peroxidase, myeloperoxidase (MPO), nitrate/nitrite, nitrotyrosine, and isoprostane. Ligands of TNF-alpha-dependent apoptosis (TNF-alpha, TRAIL, IL-2, and sFAS) were determined in cervical fluid, biopsies, and serum. Cervical MPO was highly enhanced, while nitrotyrosine decreased in CIN III. Local/circulating TRAIL was remarkably decreased, and higher-than-control serum TNF-alpha and IL-2 levels were found in the CIN I and CIN III groups. Then, 250 females infected with HPV16/18 (healthy and with CIN I and CIN II) were recruited into a placebo-controlled clinical study of supplementation with fermented mangosteen (FM, 28g/day, daily) for three months. Post-trial colposcopy revealed normal patterns in 100% of the FM group versus 62% of the placebo group. Inflammatory cells in cervical fluid were found in 21% of the FM group versus 40% of the placebo group. Locally, FM drastically diminished MPO and NO 2 /NO 3 , while it remarkably increased TRAIL. Additionally, FM supplementation normalised serum TRAIL, TNF-alpha, and IL-2.

Background: Extracorporeal photopheresis (ECP) is a blood-based therapeutic procedure increasingly used for modulation of immune dysregulation in various underlying disease settings. The aim of this study was to compare the procedure times and blood collection efficiencies between the two approaches currently utilized in European centers: the integrated versus the multistep nonintegrated procedures., Methods: A retrospective data analysis was conducted, comparing treatment data from patients who received ECP therapy at the Central Institute for Blood Transfusion & Department of Immunology (ZIB) of the Tirol Kliniken GmbH, where the integrated and multistep nonintegrated procedures are routinely used in an approximated setup., Results: During the observation period, a total of 15 patients who were treated with alternating systems on 2 consecutive days were identified. This allowed treatment pair comparisons with minimal interpatient variabilities, similar to a cross-over design even though analyzed retrospectively. Total average procedure times with the integrated system were 99.3 vs 122.0 minutes with the multistep nonintegrated procedures, respectively. Significant differences were observed for all steps of the ECP procedure: (a) time for buffy coat collection, 66.5 vs 74.7; (b) handling/transfer, 2.8 vs 18.7; (c) irradiation, 20.3 vs 11.7; and (d) reinfusion/handling time, 9.6 vs 16.3 minutes. The calculated collection throughput was 7.79 mL/min for the integrated and 7.84 mL/min for the multistep nonintegrated procedures, and with a white blood cell (WBC) collection efficiency of 34.2% and 21.0%, respectively., Conclusion: The data presented in this study show a significant shorter overall procedure time and higher WBC collection efficiency for the integrated ECP system., (© 2022 Therakos UK Ltd. Journal of Clinical Apheresis published by Wiley Periodicals LLC.)

Food supplements based on fermented Carica papaya and Morinda citrifolia , known for their immune modulating, redox balancing, and anti-inflammatory effects, were added to conventional treatment protocols prescribed to patients recovering after severe and moderate COVID-19 disease in order to alleviate long-lasting post-COVID symptoms. A randomized single-center placebo-controlled clinical laboratory study was designed and performed (total number of participants 188, with delta variant of virus 157, with omicron 31). Clinical statuses were assessed using computer tomography, electrocardiography, a questionnaire, and physical endurance. Plasma cytokines (IL-6, IL-8, IL-17A, and INF-gamma), nitrate/nitrite ratio, antioxidant activity (AOA), and polymorphonuclear leukocyte (PMN) ATP levels were determined before and 20 days following the addition of 28 g of fermented supplements twice per day. The capacity of PMN to phagocyte and the oral-nasal-pharyngeal microbiota were assessed. Clinical symptoms, IL-6, IL-8, and nitric oxide metabolites diminished significantly compared to the placebo group and their background expression. The PMN capacity to phagocyte, AOA, and ATP content remarkably increased. The oral-nasal-pharyngeal microbiota were unchanged. On these grounds, we suggest that fermented tropical fruits could efficiently diminish post-COVID clinical symptoms through several immune-modulating, redox balancing, and pro-energy mechanisms.