Search

The purpose of this study was to investigate the effects of acute nitrate (NO3−)-rich beetroot juice ingestion on explosive and high-intensity exercise performance, oral microbiota composition, and cognitive flexibility (i.e., function), before and after maximal intermittent running exercise. Fifteen women team-sport athletes were assigned in a randomized, double-blind, crossover design to consume concentrated NO3–-depleted beetroot juice (PL; 0.1 mmol NO3−) and NO3−-rich beetroot juice (BR; 12.0 mmol NO3−) 2.5 h prior to performing a battery of exercise performance tasks and cognitive testing before and after the Yo–Yo intermittent recovery level 1 (YYIR1) running test. Resting plasma [NO3−] and plasma nitrite ([NO2−]) were elevated following BR (P < 0.001). BR did not impact global composition or relative abundance of taxa in the oral microbiome (P > 0.05) or cognitive flexibility before or after exercise (P > 0.05). There was no significant difference in performance during 20-m (PRE, PL: 4.38 ± 0.27 vs. BR: 4.38 ± 0.32 s; POST, PL: 4.45 ± 0.29 vs. BR: 4.43 ± 0.35 s) and 10-m sprints (PRE, PL 2.78 ± 0.15 vs. BR 2.79 ± 0.18 s; POST, PL: 2.82 ± 0.16 vs. BR: 2.81 ± 0.19 s), isokinetic handgrip dynamometry, medicine ball throw, horizontal countermovement jump, or YYIR1 (PL: 355 ± 163 m vs. BR: 368 ± 184 m) between BR and PL (P > 0.05). These findings indicate that acute dietary NO3− may not influence the oral microbiome, explosive and high-intensity exercise performance, or cognitive function in women team-sport athletes. [ABSTRACT FROM AUTHOR]

Current tests of hearing fail to diagnose pathologies in ~10% of patients seeking help for hearing difficulties. Neural ensemble responses to perceptually relevant cues in the amplitude envelope, termed envelope following responses (EFR), hold promise as an objective diagnostic tool to probe these 'hidden' hearing difficulties. But clinical translation is impeded by current measurement approaches involving static amplitude modulated (AM) tones, which are time-consuming and lack optimal spectrotemporal resolution. Here we develop a framework to rapidly measure EFRs using dynamically varying AMs combined with spectrally specific analyses. These analyses offer 5x improvement in time and 30x improvement in spectrotemporal resolution, and more generally, are optimal for analyzing time-varying signals with known spectral trajectories of interest. We validate this approach across several mammalian species, including humans, and demonstrate robust responses that are highly correlated with traditional static EFRs. Our analytic technique facilitates rapid and objective neural assessment of temporal processing throughout the brain that can be applied to track auditory neurodegeneration using EFRs, as well as tracking recovery after therapeutic interventions. Combining dynamic amplitude modulated stimuli with spectrally specific analyses yield rapid and robust diagnostic metrics for neural assessment of auditory temporal processing across multiple mammalian species. [ABSTRACT FROM AUTHOR]

Mendelian Randomization studies indicate that BMI contributes to various diseases, but it's unclear if this is entirely mediated by BMI itself. This study examines whether disease risk from BMI-associated sequence variants is mediated through BMI or other mechanisms, using data from Iceland and the UK Biobank. The associations of BMI genetic risk score with diseases like fatty liver disease, knee replacement, and glucose intolerance were fully attenuated when conditioned on BMI, and largely for type 2 diabetes, heart failure, myocardial infarction, atrial fibrillation, and hip replacement. Similar attenuation was observed for chronic kidney disease and stroke, though results varied. Findings were consistent across sexes, except for myocardial infarction. Residual effects may result from temporal BMI changes, pleiotropy, measurement error, non-linear relationships, non-collapsibility, or confounding. The attenuation extent of BMI genetic risk score on disease associations suggests the potential impact of reducing BMI on disease risk. BMI contributes to various diseases, but it was unclear whether the risk was mediated by BMI itself. Here, the authors demonstrate that BMI mediates most of this risk, and suggest an upper bound on disease risk that can be mitigated by lowering BMI. [ABSTRACT FROM AUTHOR]

Background: Tenuous blood supply carries a risk of wound-healing problems and subsequent infection following total knee arthroplasty (TKA). This risk may be increased by the presence of previous incisions. Performing a sham incision procedure allows for detection of wound-healing problems prior to performing TKA. The purpose of this retrospective case series is to describe the indications for and technique of a sham incision procedure in patients with previous knee incisions who underwent TKA following this procedure and to report the clinical outcomes observed in these patients following further surgery. Methods: Patients who had prior knee incisions, had undergone a sham incision prior to TKA, and had a minimum follow-up of 2 years were identified, and their cases were retrospectively reviewed. The identified cases typically adhered to the surgeon's standard protocol, which consisted of making a midline incision adventitious to TKA, dissecting down to deep fascia, and closing the wound with suture. Incisions were then observed for at least 4 weeks to determine the viability of the skin flaps before TKA was performed via the same incision. Results: A total of 47 knees in 47 patients were included in the study cohort. TKA was performed at an average of 21.1 weeks (range, 4 to 163 weeks) following the sham incision. There were no cases of skin necrosis or periprosthetic joint infection at an average follow-up of 4.6 years (range, 2 to 12 years) after sham incision. A total of 11 patients (23.4%) required manipulation under anesthesia for stiffness. Conclusions: In our series, no patients developed skin necrosis or periprosthetic joint infection following TKA subsequent to a sham incision procedure, suggesting that healed sham incisions are safe to use for TKA and may be considered prior to TKA in cases in which local previous incisions increase the risk of wound-healing problems. Level of Evidence: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

The reactions of a series of organic polynitriles with [Te4][AsF6]2 in liquid SO2 solution lead either to reduction of [Te4]2+ to elemental tellurium or to the formation of coordination polymers. With 1,3‐dicyanobenzene (1,3‐DCB), 1,4‐dicyanobenzene (1,4‐DCB), 1,2,4,5‐tetracyanobenzene (TCB), tetracyanoethylene (TCNE) and tetracyanochinodimethane (TCNQ) the coordination complexes [Te4][AsF6]2 ⋅ 2(1,3‐DCB), [Te4][AsF6]2 ⋅ 3(1,4‐DCB) ⋅ 2SO2, [Te4][AsF6]2 ⋅ TCB, [Te4][AsF6]2 ⋅ TCNE and [Te4][AsF6]2 ⋅ TCNQ ⋅ 8 SO2 were isolated and characterized by crystal structure analyses and vibrational Raman spectroscopy. The nitriles are coordinated to the square‐planar clusters forming 1D chains, 2D arrangements and 3D networks. Tetrakis(dicyanomethylene)cyclobutendiide [C4(C{CN}2)4]2− is oxidized by [Te4]2+ to the neutral cyanocarbon C4(C{CN}2)4, structurally representing a 4[radialene]. The ionization potentials and electron affinities of the cyanamide anion, cyanogen, 1,2‐DCB, 1,3‐DCB, 1,4‐DCB, TCB, C4(C{CN}2)4, TCNE and TCNQ and those polynitriles, which cause reduction of [Te4]2+, were calculated at coupled‐cluster level of theory in order to examine possible reasons for the stability of the coordination polymers based on electronic properties of the nitriles. [ABSTRACT FROM AUTHOR]

Background: Acute and chronic pre-traumatic cigarette smoke exposure increases morbidity and mortality after trauma and hemorrhage. In mice with a genetic deletion of the H2S-producing enzyme cystathione-γ-lyase (CSE−/−), providing exogenous H2S using sodium thiosulfate (Na2S2O3) improved organ function after chest trauma and hemorrhagic shock. Therefore, we evaluated the effect of Na2S2O3 during resuscitation from blunt chest trauma and hemorrhagic shock on CSE−/− mice with pre-traumatic cigarette smoke (CS) exposure. Since H2S is well established as being able to modify energy metabolism, a specific focus was placed on whole-body metabolic pathways and mitochondrial respiratory activity. Methods: Following CS exposure, the CSE−/− mice underwent anesthesia, surgical instrumentation, blunt chest trauma, hemorrhagic shock for over 1 h (target mean arterial pressure (MAP) ≈ 35 ± 5 mmHg), and resuscitation for up to 8 h comprising lung-protective mechanical ventilation, the re-transfusion of shed blood, fluid resuscitation, and continuous i.v. noradrenaline (NoA) to maintain an MAP ≥ 55 mmHg. At the start of the resuscitation, the mice randomly received either i.v. Na2S2O3 (0.45 mg/gbodyweight; n = 14) or the vehicle (NaCl 0.9%; n = 11). In addition to the hemodynamics, lung mechanics, gas exchange, acid–base status, and organ function, we quantified the parameters of carbohydrate, lipid, and protein metabolism using a primed continuous infusion of stable, non-radioactive, isotope-labeled substrates (gas chromatography/mass spectrometry) and the post-mortem tissue mitochondrial respiratory activity ("high-resolution respirometry"). Results: While the hemodynamics and NoA infusion rates did not differ, Na2S2O3 was associated with a trend towards lower static lung compliance (p = 0.071) and arterial PO2 (p = 0.089) at the end of the experiment. The direct, aerobic glucose oxidation rate was higher (p = 0.041) in the Na2S2O3-treated mice, which resulted in lower glycemia levels (p = 0.050) and a higher whole-body CO2 production rate (p = 0.065). The mitochondrial respiration in the heart, kidney, and liver tissue did not differ. While the kidney function was comparable, the Na2S2O3-treated mice showed a trend towards a shorter survival time (p = 0.068). Conclusions: During resuscitation from blunt chest trauma and hemorrhagic shock in CSE−/− mice with pre-traumatic CS exposure, Na2S2O3 was associated with increased direct, aerobic glucose oxidation, suggesting a switch in energy metabolism towards preferential carbohydrate utilization. Nevertheless, treatment with Na2S2O3 coincided with a trend towards worsened lung mechanics and gas exchange, and, ultimately, shorter survival. [ABSTRACT FROM AUTHOR]

Early life stress (ELS) significantly increases the risk of chronic cardiovascular diseases and may cause neuroinflammation. This post hoc study, based on the material available from a previous study showing elevated "serum brain injury markers" in male control animals, examines the effect of sex and/or ELS on the cerebral and cardiac expression of the H2S and oxytocin systems. Following approval by the Regional Council of Tübingen, a randomized controlled study was conducted on 12 sexually mature, uncastrated German Large White swine of both sexes. The control animals were separated from their mothers at 28–35 days, while the ELS group was separated at day 21. At 20–24 weeks, animals underwent anesthesia, ventilation, and surgical instrumentation. An immunohistochemical analysis of oxytocin, its receptor, and the H2S-producing enzymes cystathionine-β-synthase and cystathionine-γ-lyase was performed on hypothalamic, prefrontal cortex, and myocardial tissue samples. Data are expressed as the % of positive tissue staining, and differences between groups were tested using a two-way ANOVA. The results showed no significant differences in the oxytocin and H2S systems between groups; however, sex influenced the oxytocin system, and ELS affected the oxytocin and H2S systems in a sex-specific manner. No immunohistochemical correlate to the elevated "serum brain injury markers" in male controls was identified. [ABSTRACT FROM AUTHOR]

Simple Summary: This research aims to improve the precision of particle therapy for lung cancer treatment. The heterogeneous, microscopic structure of lung tissue leads to a broadening of the very sharp dose profiles of protons and other light ions. This can result in higher doses in healthy tissue as well as a reduced dose in the target volume and thereby reducing the potential benefit of particle therapy for lung cancer. This review summarizes existing models that account for these lung tissue effects and explore how they can be better integrated into treatment planning. By taking into account these so called lung modulation effects, it is possible to target tumors more precisely while minimizing harm to surrounding healthy tissues, ultimately benefiting cancer patients. Particle therapy presents a promising alternative to conventional photon therapy for treating non-small cell lung cancer (NSCLC). However, the heterogeneous structure of lung tissue leads to the degradation of the Bragg peak and thereby to the degradation of the dose distribution. This review offers a comprehensive overview of the models developed to account for these modulation effects. It summarizes studies focused on determining modulation power as a predictor of this so-called lung modulation. In addition, the review covers early investigations on dose uncertainties caused by lung modulation in CT-based lung phantoms and patient anatomies and discusses future challenges in integrating these solutions into clinical treatment planning routines. [ABSTRACT FROM AUTHOR]

Purpose: Individuals with proximal 16p11.2 copy number variants (CNVs), either deletions (16p11.2DS) or duplications (16p11.2Dup), are predisposed to neuro-developmental difficulties and disorders, such as language disorders, intellectual disability, and autism spectrum disorder. The purpose of the current study was to characterize language profiles of school-age children with proximal 16p11.2 CNVs, in relation to the normative sample and unaffected siblings of children with 16p11.2DS. Method: Standardized language tests were conducted in 33 school-age children with BP4-BP5 16p11.2 CNVs and eight unaffected siblings of children with 16p11.2DS to evaluate language production and comprehension skills across various language domains. A standardized intelligence test was also administered, and parents completed a standardized questionnaire to assess autistic traits. Language profiles were compared across 16p11.2 CNVs and intrafamilial pairs. The influence of nonverbal intelligence and autistic traits on language outcomes was investigated. Results: No significant differences were found between children with 16p11.2DS and those with 16p11.2Dup, although both groups exhibited significantly poorer language skills compared to the normative sample and unaffected siblings of children with 16p11.2DS. Severe language deficits were identified in 70% of individuals with 16p11.2 CNVs across all language subdomains, with significantly better receptive vocabulary skills than overall receptive language abilities. In children with 16p11.2DS, expressive language deficits were more pronounced than receptive deficits. In contrast, only in children with 16p11.2Dup did nonverbal intelligence influence their language outcomes. Conclusions: The current study contributes to the deeper understanding of language profiles in 16p11.2 CNVs in a clinically ascertained cohort, indicating generalized deficits across multiple language domains, rather than a syndrome-specific pattern targeting specific subdomains. The findings underscore the importance of early diagnosis, targeted therapy, and monitoring of language skills in children with 16p11.2 CNVs. [ABSTRACT FROM AUTHOR]

Purpose: A common spine surgery procedure involves decompression of the lumbar spine. The impact of the surgeon's learning curve on relevant clinical outcomes is currently not well examined in the literature. A variety of machine learning algorithms have been investigated in this study to determine how a surgeon's learning curve and other clinical parameters will influence prolonged lengths of stay (LOS), extended operating times (OT), and complications, as well as whether these clinical parameters can be reliably predicted. Methods: A retrospective monocentric cohort study of patients with lumbar spinal stenosis treated with microsurgical (MSD) and full-endoscopic (FED) decompression was conducted. The study included 206 patients with lumbar spinal stenosis who underwent FED (63; 30.6%) and MSD (118; 57.3%). Prolonged LOS and OT were defined as those exceeding the 75th percentile of the cohort. Furthermore, complications were assessed as a dependent variable. Using unsupervised learning, clusters were identified in the data, which helped distinguish between the early learning curve (ELC) and the late learning curve (LLC). From 15 algorithms, the top five algorithms that best fit the data were selected for each prediction task. We calculated the accuracy of prediction (Acc) and the area under the curve (AUC). The most significant predictors were determined using a feature importance analysis. Results: For the FED group, the median number of surgeries with case surgery type at the time of surgery was 72 in the ELC group and 274 in the LLC group. FED patients did not significantly differ in outcome variables (LOS, OT, complication rate) between the ELC and LLC group. The random forest model demonstrated the highest mean accuracy and AUC across all folds for each classification task. For OT, it achieved an accuracy of 76.08% and an AUC of 0.89. For LOS, the model reached an accuracy of 83.83% and an AUC of 0.91. Lastly, in predicting complications, the random forest model attained the highest accuracy of 89.90% and an AUC of 0.94. Feature importance analysis indicated that LOS, OT, and complications were more significantly affected by patient characteristics than the surgical technique (FED versus MSD) or the surgeon's learning curve. Conclusions: A median of 72 cases of FED surgeries led to comparable clinical outcomes in the early learning curve phase compared to experienced surgeons. These outcomes seem to be more significantly affected by patient characteristics than the learning curve or the surgical technique. Several study variables, including the learning curve, can be used to predict whether lumbar decompression surgery will result in an increased LOS, OT, or complications. To introduce the provided prediction tools into clinics, the algorithms need to be implemented into open-source software and externally validated through large-scale randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background and Study Aim: Data from the AWARE study (A Worldwide Antihistamine‐Refractory chronic urticaria patient Evaluation) illustrate a substantial disease burden in German patients with H1‐antihistamine (‐H1‐AH)‐refractory chronic spontaneous urticaria (CSU). Detrimental effects on patients' quality of life, poor disease control and impairment in the ability to work and perform other daily activities are reported. Based on these findings, this study aims to quantify the epidemiological and socio‐economic burden of H1‐AH‐refractory CSU in Germany. Methods: To determine the epidemiological burden of H1‐AH‐refractory CSU, the age‐ and gender‐specific prevalence of CSU and the proportion of H1‐AH‐refractory patients in Germany anonymized data from the InGef research database have been used. In a second step, the socio‐economic burden in terms of lost numbers of hours in paid and unpaid work was calculated by extrapolating the age‐ and gender‐specific work productivity and activity impairment (WPAI) observed in AWARE to the H1‐AH‐refractory CSU population in Germany. Finally, productivity losses in paid and unpaid work were monetized using the human capital and the friction cost approach respectively. Moreover, socio‐economic burden was calculated depending on symptom control of the patients (measured by urticaria control test [UCT]). Results: In Germany, over 203,000 patients (20 years or older) had H1‐AH‐refractory CSU in 2018. The avoided lost paid and unpaid work hours attributable to H1‐AH‐refractory CSU summed up to over 100 million. Overall, the socio‐economic burden of H1‐AH‐refractory CSU in monetary terms was evaluated at € 2.2 billion and the majority of this was due to unpaid work loss. Patients with poor disease control, as indicated by UCT score < 12, were more likely to suffer from high impairment than patients with controlled disease, resulting in a higher socio‐economic burden. Conclusions: The results of our analyses picture the substantial socio‐economic burden of H1‐AH‐refractory CSU and therefore the tremendous impact it has on daily lives of individuals and society overall. [ABSTRACT FROM AUTHOR]

Background: Current digital medical databases record systematically coded diagnoses, but many legacy databases are full of hand-written, free text diagnoses, which can only be meaningfully analysed after mapping them to a coding system. While diagnoses can be extracted from full medical notes with good accuracy, no algorithm using only an unstructured free text diagnosis with no additional data has been published to date. Objectives/methods: Therefore, we sought to create an algorithm which maps hand-written German diagnoses from our clinical photography database to ICD-10 diagnosis codes, validate its output manually by dermatologists and analyse diagnosis counts over time as a proof-of-concept of its application. Results: Our rule-based algorithm mapped 50,884 unprocessed hand-written German free-text diagnoses covering five decades to ICD-10 codes, while reaching an accuracy of 82% against 817 dermatologist-validated diagnoses. Out of 41,021 data points with the highest algorithm confidence the top 3 identified diagnosis classes were psoriasis, eczema, and non-melanoma skin cancer. The number of ICD-10 codes belonging to chronic inflammatory diseases showed a seasonal pattern with peaks in July, and when analysed aggregated by year, peaks correlated to events such as new therapy classes for these diseases. Conclusion: Using the presented algorithm, it is possible to reliably match hand-written free text of German dermatological diagnoses to ICD-10 codes, thus enabling systematic analysis of legacy databases, making past medical knowledge accessible to today's patient care. [ABSTRACT FROM AUTHOR]

Dermatophyte infections of the skin and nails are frequent, but current antimycotics have several drawbacks. In search of new treatments, we looked into the vast array of herbal active agents. Derived from plants, they are sustainable, agreeable for patients, and may have less side effects than traditional antimycotics. In this study, we assessed 43 herbal agents for their effectiveness against Trichophyton rubrum (T. rubrum), Trichophyton benhamiae (T. benhamiae), Trichophyton tonsurans (T. tonsurans), and Microsporum canis (M. canis), four major human dermatophyte pathogens. The antifungal effect was tested by incorporating the agents into agar plates and measuring the dermatophyte growth after 7 days. Against T. rubrum, 16 out of 43 herbal agents showed total inhibition of dermatophyte growth. 14 out of 43 herbal agents inhibited the growth of T. benhamiae completely. 18 out of 43 herbal agents were effective against T. tonsurans. Against M. canis, 15 out of 43 herbal agents showed total growth inhibition. Twelve herbal agents inhibited the growth of all tested dermatophytes completely. This study demonstrates the high antimycotic potential of herbal therapeutics and identified promising candidates for the topical treatment of dermatomycoses. Substances are highly agreeable and should be tolerated well. Some might even provide new options for the systemic treatment of fungal diseases. [ABSTRACT FROM AUTHOR]

Simple Summary: Ultra-high dose rate radiotherapy with particle beams such as proton and carbon is a major technical challenge. Fast beam delivery and the concentration of the Bragg peak to the tumor must be achieved in the order of milliseconds and can therefore only be realized with 3D range-modulators (3D RM). This work analyzed the robustness of the dose distribution, resulting from a 3D RM for a cube target volume. Firstly, a high-precision dose measurement was performed, and a very good agreement was found between the measured and Monte Carlo simulated dose distribution. Further simulations were conducted to determine how sensitively the resulting dose distribution responds to misalignments of the 3D RM. The results show that the 3D RM must be aligned with accuracy less than 1° to preserve the planned desired dose distribution. As the research and pre-clinical adoption of 3D RMs in particle therapy has become more widespread recently, these results are of high general utility. A 3D range-modulator (RM), optimized for a single energy and a specific target shape, is a promising and viable solution for the ultra-fast dose delivery in particle therapy. The aim of this work was to investigate the impact of potential beam and modulator misalignments on the dose distribution. Moreover, the FLUKA Monte Carlo model, capable of simulating 3D RMs, was adjusted and validated for the 250 MeV single-energy proton irradiation from a Varian ProBeam system. A 3D RM was designed for a cube target shape rotated 45° around two axes using a Varian-internal research version of the Eclipse treatment planning software, and the resulting dose distribution was simulated in a water phantom. Deviations from the ideal alignment were introduced, and the dose distributions from the modified simulations were compared to the original unmodified one. Finally, the FLUKA model and the workflow were validated with base-line data measurements and dose measurements of the manufactured modulator prototype at the HollandPTC facility in Delft. The adjusted FLUKA model, optimized particularly in the scope of a single-energy FLASH irradiation with a PMMA pre-absorber, demonstrated very good agreement with the measured dose distribution resulting from the 3D RM. Dose deviations resulting from modulator-beam axis misalignments depend on the specific 3D RM and its shape, pin aspect ratio, rotation angle, rotation point, etc. A minor modulator shift was found to be more relevant for the distal dose distribution than for the spread-out Bragg Peak (SOBP) homogeneity. On the other hand, a modulator tilt (rotation away from the beam axis) substantially affected not only the depth dose profile, transforming a flat SOBP into a broad, Gaussian-like distribution with increasing rotation angle, but also shifted the lateral dose distribution considerably. This work strives to increase awareness and highlight potential pitfalls as the 3D RM method progresses from a purely research concept to pre-clinical studies and human trials. Ensuring that gantry rotation and the combined weight of RM, PMMA, and aperture do not introduce alignment issues is critical. Given all the other range and positioning uncertainties, etc., not related to the modulator, the RM must be aligned with an accuracy below 1° in order to preserve a clinically acceptable total uncertainty budget. Careful consideration of critical parameters like the pin aspect ratio and possibly a novel robust modulator geometry optimization are potential additional strategies to mitigate the impact of positioning on the resulting dose. Finally, even the rotated cube 3D modulator with high aspect ratio pin structures (~80 mm height to 3 mm pin base width) was found to be relatively robust against a slight misalignment of 0.5° rotation or a 1.5 mm shift in one dimension perpendicular to the beam axis. Given a reliable positioning and QA concept, the additional uncertainties introduced by the 3D RM can be successfully managed adopting the concept into the clinical routine. [ABSTRACT FROM AUTHOR]

This paper reports on a monolithically integrated gallium arsenide (GaAs)-based photonic integrated circuit platform for wavelengths around 1064 nm. Enabled by spatially selective quantum well removal and two-step epitaxial growth, it supports on-chip gain as well as passive waveguides. In addition, shallow- and deep-etched waveguides are realized. The former result in waveguide losses of less than 2 dB/cm, while the latter enable compact integrated waveguide components. To demonstrate the performance of the platform, racetrack ring resonators based on deep-etched Euler bends and shallow-etched directional couplers are realized, achieving high intrinsic quality factors of 2.6 × 105 and 3.2 × 105 for the fundamental TE and TM mode, respectively. To demonstrate the use of these resonators, ring-resonator-coupled lasers are fabricated, resulting in one-sided output powers of up to 14 mW and single-mode operation with 40 dB side-mode suppression. The successful integration of ring resonators on a GaAs-based active/passive photonic integrated circuit platform paves the way for the realization of fully monolithic, widely tunable, and narrow linewidth ring-resonator-coupled laser sources. [ABSTRACT FROM AUTHOR]

Social anxiety is common in childhood and potentially transitions into clinical disorders including depression. The present study aimed to examine the effectiveness of an indicated prevention program for children screened in routine care. Data came from the PROMPt project, a prospective implementation study (10/2018-09/2022) that explored a novel care chain, starting with screening with the Strengths and Difficulties Questionnaire (SDQ) as part of regular health check-ups, followed by indicated assignment and participation in a prevention program. Questionnaires assessing anxiety and depression symptoms were administered shortly after screening or before program participation (T0), six months after screening or after program participation (T1) and at a follow-up, six months after T1 (T2). Children who participated in a group cognitive-behavioral social skills program (TT; n = 145) were compared using mixed model analyses with non-participating children who were either screened as normal (NOR; n = 894) or refused program participation despite indication (NoTT; n = 67). TT scores improved from T0 to T1 compared to NOR and NoTT (anxiety β = -0.71 and β = -0.71, social anxiety β = -0.46 and β = -0.52, depression β = -0.52 and β = -0.73). Improvement was maintained at T2. Moderation analyses showed a trend toward greater benefit for participants with higher baseline scores. Indicated prevention can improve anxiety and depression symptoms in children identified by screening in routine care. Systematic screening and targeted prevention may positively affect mental health of children on a population level. [ABSTRACT FROM AUTHOR]

Background: Biologics are among the most effective therapies for psoriasis. However, many patients are only introduced to them at advanced stages of the disease course. Objectives: Our aim was to identify predictors of initiating biologic therapy in patients with psoriasis and compare patients initiating biologics early versus late in their disease course. Methods: Kaplan–Meier curves visualized time to biologic initiation, while Cox regression models further explored variables as predictors of biologic initiation. Mann–Whitney U and chi‐squared tests compared patients who started biologics early with those who began biologics later in the disease course. Results: Our primary analysis included 233 psoriasis patients. Cox regression showed that age at diagnosis (P = 0.007), general physical well‐being (P = 0.02), and nail psoriasis severity (P = 0.02) were significantly associated with time to biologic initiation. Our secondary analysis, the comparisons between patients starting biologics early versus later in the disease course, included a total of 378 patients. The median (interquartile range [IQR]) age at diagnosis was 34.5 (25.0–51.2) years for patients initiating biologics within 5 years, compared to 22.0 (15.0–32.8) years for patients initiating biologics later (P < 0.0001). The median (IQR) age at initiation was 37.0 (27.0–53.2) and 45.0 (36.0–55.0) years for patients initiating biologics earlier versus later than 5 years (P = 0.04). Conclusions: Age at diagnosis, general well‐being, and severity of nail psoriasis significantly predicted future initiation of biologic treatment. Patients initiating biologics early in their disease course were generally older at diagnosis but younger at the time of biologic initiation compared to patients initiating biologics later in their disease course. [ABSTRACT FROM AUTHOR]

Copyright of Journal der Deutschen Dermatologischen Gesellschaft is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Summary: Vitiligo is a common disorder characterized by the visible loss of skin pigmentation. Non‐segmental vitiligo (NSV) is the major subtype. The disease is caused by autoimmune‐mediated destruction of melanocytes. Vitiligo leads to stigmatization and a significant reduction in quality of life. Disregarding the psychosocial burden, vitiligo is sometimes viewed solely as a cosmetic problem and, according to a global survey, is diagnosed on average only after 2.4 years. This delay contributes to a considerable burden of disease, including suicidal ideation. Stigmatization promotes the development of psychological comorbidities such as anxiety and depressive disorders, with prevalence rates varying by country and study (0.1%–67.9%). Data for Germany are heterogeneous and largely based on estimates. Due to psychosocial factors, the inflammatory component, and a higher incidence of somatic comorbidities, NSV may be regarded as an inflammatory systemic disease. We recommend optimizing care by incorporating the assessment of quality of life as a standard in routine care, in addition to monitoring disease activity. Moreover, early screening for psychological comorbidities is crucial to initiate appropriate treatment before the condition becomes chronic and cumulative (irreversible) impairments occur. The goal is a personalized and patient‐centered integrated care approach that sustainably improves the health status of those affected. [ABSTRACT FROM AUTHOR]

Copyright of Anaesthesiologie & Intensivmedizin is the property of DGAI e.V. - Deutsche Gesellschaft fur Anasthesiologie und Intensivmedizin e.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Ultrahigh dose‐rate radiation (UHDR) produces less hydrogen peroxide (H2O2) in pure water, as suggested by some experimental studies, and is used as an argument for the validity of the theory that FLASH spares the normal tissue due to less reactive oxygen species (ROS) production. In contrast, most Monte Carlo simulation studies suggest the opposite. Purpose: We aim to unveil the effect of UHDR on H2O2 production in pure water and its underlying mechanism, to serve as a benchmark for Monte Carlo simulation. We hypothesized that the reaction of solvated electrons (eaq−${\mathrm{e}}_{{\mathrm{aq}}}^ - $) removing hydroxyl radicals (•OH), the precursor of H2O2, is the reason why UHDR leads to a lower G‐value (molecules/100 eV) for H2O2 (G[H2O2]), because: 1, the third‐order reaction between eaq−${\mathrm{e}}_{{\mathrm{aq}}}^ - $ and •OH is more sensitive to increased instantaneous ROS concentration by UHDR than a two‐order reaction of •OH self‐reaction producing H2O2; 2, eaq−${\mathrm{e}}_{{\mathrm{aq}}}^ - $ has two times higher diffusion coefficient and higher reaction rate constant than that of •OH, which means eaq−${\mathrm{e}}_{{\mathrm{aq}}}^ - $ would dominate the competition for •OH and benefit more from the inter‐track effect of UHDR. Meanwhile, we also experimentally verify the theory of long‐lived radicals causing lower G(H2O2) in conventional irradiation, which is mentioned in some simulation studies. Methods and materials: H2O2 was measured by Amplex UltraRed assay. 430.1 MeV/u carbon ions (50 and 0.1 Gy/s), 9 MeV electrons (600 and 0.62 Gy/s), and 200 kV x‐ray tube (10 and 0.1 Gy/s) were employed. For three kinds of water (real hypoxic: 1% O2; hypoxic: 1% O2 and 5% CO2; and normoxic: 21% O2), unbubbled and bubbled samples with N2O, the scavenger of eaq−${\mathrm{e}}_{{\mathrm{aq}}}^ - $, were irradiated by carbon ions and electrons with conventional and UHDR at different absolute dose levels. Normoxic water dissolved with sodium nitrate (NaNO3), another scavenger of eaq−${\mathrm{e}}_{{\mathrm{aq}}}^ - $, and bubbled with N2O was irradiated by x‐ray to verify the results of low‐LET electron beam. Results: UHDR leads to a lower G(H2O2) than conventional irradiation. O2 and CO2 can both increase G(H2O2). N2O increases G(H2O2) of both UHDR and conventional irradiation and eliminates the difference between them for carbon ions. However, N2O decreases G(H2O2) in electron conventional irradiation but increases G(H2O2) in the case of UHDR, ending up with no dose‐rate dependency of G(H2O2). Three‐spilled carbon UHDR does not have a lower G(H2O2) than one‐spilled UHDR. However, the electron beam shows a lower G(H2O2) for three‐spilled UHDR than for one‐spilled UHDR. Normoxic water with N2O or NaNO3 can both eliminate the dose rate dependency of H2O2 production for x‐ray. Conclusions: UHDR has a lower G(H2O2) than the conventional irradiation for both high LET carbon and low LET electron and x‐ray beams. Both scavengers for eaq−${\mathrm{e}}_{{\mathrm{aq}}}^ - $, N2O and NaNO3, eliminate the dose‐rate dependency of G(H2O2), which suggests eaq−${\mathrm{e}}_{{\mathrm{aq}}}^ - $ is the reason for decreased G(H2O2) for UHDR. Three‐spilled UHDR versus one‐spilled UHDR indicates that the assumption of residual radicals reducing G(H2O2) of conventional irradiation may only be valid for low LET electron beam. [ABSTRACT FROM AUTHOR]

Purpose: To summarize the evidence on associations of adiposity and cardiorespiratory fitness (CRF) with arterial structure and function in nonclinical children and adolescents. Methods: Two researchers conducted a search in 5 electronic databases in April 2022 to find studies in nonclinical youth (age 5–17.9 y) reporting multivariable associations. Studies were eligible if adiposity and/or CRF were used as the predictor and arterial structure and/or function was the outcome. The Quality Assessment Tool for Quantitative Studies was used to assess methodological quality for experimental studies, and a modified version was used for observational studies. Results: Ninety-nine studies (72.7% cross-sectional) were included. Ninety-four assessed associations between adiposity and arterial outcomes, most using overall body proportion (n = 71), abdominal (n = 52), or whole-body adiposity (n = 40). Most evidence was inconsistent or nonsignificant, but 59 studies suggested higher abdominal adiposity and worse body proportion were associated with adverse arterial outcomes. Twenty-one assessed associations between CRF and arterial outcomes, with findings inconsistent. Most evidence was rated weak in quality. Conclusion: While high adiposity may contribute to poor arterial outcomes, evidence is limited regarding CRF. Future studies should disentangle these associations by studying youth with healthy adiposity but poor CRF, or vice versa, using longitudinal or experimental study designs. [ABSTRACT FROM AUTHOR]

We present magnetic characterization, charge resistivity, and optical photoluminescence measurements on amorphous yttrium iron oxide thin films (a -Y–Fe–O), with supporting comparisons to amorphous germanium (a -Ge) films. We measured magnetic properties with both SQUID magnetometry and polarized neutron reflectometry. These results not only confirm that a -Y–Fe–O is a disordered magnetic material with strong predominantly antiferromagnetic exchange interactions and a high degree of frustration, but also that it is best understood electrically as a disordered semiconductor. As with amorphous germanium, a -Y–Fe–O obeys expectations for variable-range hopping through localized electron states over a wide range of temperature. We also clarify the consequences of charge transport through such a semiconducting medium for non-local voltage measurements intended to probe spin transport in nominally insulating magnetic materials. We further compare non-local resistance measurements made with "quasi-dc" automated current reversal to ac measurements made with a lock-in amplifier. These show that the "quasi-dc" measurement has an effective ac current excitation with frequency up to approximately 22 Hz, and that this effective ac excitation can cause artifacts in these measurements including incorrect sign of the non-local resistance. This comprehensive investigation of non-local resistance measurements in a -Y–Fe–O shows no evidence of spin transport on micrometer length scales, which is contrary to our original work, and in line with more recent investigations by other groups. [ABSTRACT FROM AUTHOR]

Background: During the coronavirus disease 2019 (COVID-19) pandemic, inpatient nurses faced various work stressors. Little is known about organizational interventions that can mitigate the negative consequences of pandemic-related stressors. Objective: The aim was to provide a synopsis of the literature concerning the types and outcomes of organizational interventions performed during the COVID-19 pandemic that directly (re)organized the work structures of inpatient nurses to address pandemic-related work stressors or to increase nurses' ability to cope. Methods: Within this preregistered systematic literature review, we searched four databases (PubMed, PsycINFO, PsycARTICLES, CINAHL) and two preprint databases (MedRxiv, PsyArXiv) for interventional studies of organizational interventions published between 01/2020 and 03/2023 (k = 990 records). We included 12 primary studies after title-abstract and full-text screening. A synthesis of results without meta-analysis was conducted. Risk of bias was assessed with the Cochrane risk-of-bias tool for randomized trials – version 2 (RoB-2) and Risk Of Bias In Non-randomized Studies - of Interventions (ROBINS-I) tool. Results: All interventions were implemented in hospitals. The reasons given for implementation included pandemic-related work stressors such as a high workload, understaffing, and a lack of medical resources. To respond to the various work stressors, half of the studies took a multilevel approach combining organizational and person-oriented interventions (k = 6). Most studies (k = 8) took a secondary prevention approach, focusing on the organization of rest breaks (k = 5). With respect to outcomes, the studies examined nurse-related stress and resilience, turnover intention, job satisfaction, and other factors. Risk-of-bias analyses revealed that conclusions about the effectiveness of the interventions are limited due to confounding factors and self-selection. Conclusions: The identified interventions provide a basis for future research to draw conclusions on the effectiveness of organizational interventions during pandemics. The promotion of adequate work breaks could be useful if the work stressors associated with strain and negative consequences cannot be changed directly. However, the same stressors (e.g., high workload) can hinder nurses from participating in offered interventions. This emphasizes the importance of directly addressing inpatient nurses' work stressors. Registration: Prospero-ID CRD42023364807 (March 2023). [ABSTRACT FROM AUTHOR]

Modern healthcare systems are increasingly organized according to diagnosis-specific clinical pathways and treatment protocols. At the same time, the number of patients with complex problems and needs that do not fit the single-diagnosis approach is rising, contributing to a high prevalence of diagnostic errors. In this article, we focus on the risk of diagnostic errors arising from missed or incomplete diagnosis and assessment of older adult patients' care needs in the first hours of acute hospitalizations in EDs. This focus is important for improving patient safety, as clinical decisions made in EDs impact patient safety in the subsequent steps of the process, thereby potentially causing new risks to arise. Based on our discussion of clinical decision-making and diagnostic errors in the acute care context, we propose a more comprehensive interdisciplinary approach to improvements in patient safety that integrates organizational and clinical research and examines where, when, how, and why risks to patient safety arise in and across different clinical–organizational contexts. [ABSTRACT FROM AUTHOR]

Through emission processes, palladium (Pd) particulates from industrial sources are introduced into a range of ecosystems including freshwater environments. Despite this, research on Pd‐induced bioaccumulation, uptake, and toxicity is limited for freshwater fishes. Unlike other metals, there are currently no regulations or protective guidelines to limit Pd release into aquatic systems, indicating a global absence of measures addressing its environmental impact. To assess the olfactory toxicity potential of Pd, the present study aimed to explore Pd accumulation in olfactory tissues, olfactory disruption, and oxidative stress in rainbow trout (Oncorhynchus mykiss) following waterborne Pd exposure. Olfactory sensitivity, measured by electro‐olfactography, demonstrated that Pd inhibits multiple pathways of the olfactory system following 96 h of Pd exposure. In this study, the concentrations of Pd for inhibition of olfactory function by 20% (2.5 μg/L; IC20) and 50% (19 μg/L; IC50) were established. Rainbow trout were then exposed to IC20 and IC50 Pd concentrations in combination with varying exposure conditions, as changes in water quality alter the toxicity of metals. Independent to Pd, increased water hardness resulted in decreased olfactory perception owing to ion competition at the olfactory epithelium. No other environmental parameter in this study significantly influenced Pd‐induced olfactory toxicity. Membrane‐associated Pd was measured at the olfactory rosette and gill following exposure; however, this accumulation did not translate to oxidative stress as measured by the production of malondialdehyde. Our data suggest that Pd is toxic to rainbow trout via waterborne contamination near field‐measured levels. This study further demonstrated Pd bioavailability and uptake at water‐adjacent tissues, adding to our collective understanding of the toxicological profile of Pd. Taken together, our results provide novel insights into the olfactory toxicity in fish following Pd exposure. Integr Environ Assess Manag 2024;20:1407–1419. © 2024 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Key Points: Palladium (Pd) inhibits multiple fish olfaction pathways. Shifts in water quality did not alter Pd olfactory inhibition. [ABSTRACT FROM AUTHOR]

Purpose: The Marburg Ion-Beam Therapy Center (MIT) is one of two particle therapy centers in Germany that enables the treatment of patients with both protons and carbon ions. The facility was build by Siemens Healthineers and is one of only two centers worldwide built by Siemens (Marburg, Germany and Shanghai, China). The present report provides an overview of technical and clinical operations as well as research activities at MIT. Methods: The MIT was completed in 2011 and uses a synchrotron for accelerating protons and carbon ions up to energies of 250 MeV/u and 430 MeV/u respectively. Three treatment rooms with a fixed horizontal beam-line and one room with a 45 degree beam angle are available. Results: Since the start of clinical operations in 2015, around 2.500 patients have been treated at MIT, about 40% with carbon ions and 60% with protons. Currently around 400 patients are treated each year. The majority of the patients suffered from benign and malign CNS tumors (around 40%) followed by head and neck tumors (around 23%). MIT is actively involved in clinical studies with its patients. In addition to clinical operations, there is active research at MIT in the fields of radiation biology and medical physics. The focus is on translational research to improve the treatment of H & N carcinomas and lung cancer (NSCLC). Moreover, intensive work is being carried out on the technical implementation of FLASH irradiation for research purposes. Conclusion: The MIT is one of two centers worldwide that were built by Siemens Healtineers and has been successfully in clinical operation since 2015. The service provided by Siemens is guaranteed until 2030, the future after 2030 is currently under discussion. [ABSTRACT FROM AUTHOR]

Background: Health-related internet use presents both opportunities and challenges for patients and physicians and requires a comprehensive understanding to improve individual health care in atopic dermatitis (AD). Objective: To explore differences between regular and irregular disease-related internet users, reasons for disease-related internet use, and its relevance to the patient-physician relationship in AD. Methods: This cross-sectional study recruited 221 adults with AD online and from a German university clinic between August 2021 and February 2022. The questionnaire queried sociodemographic and disease-related information, reasons for and against using the internet, types of channels used, and the impact on the patient-physician relationship. Participants were categorized as regular (≥once per month) and irregular (

Despite ethical and historical arguments for removing race from clinical algorithms, the consequences of removal remain unclear. Here, we highlight a largely undiscussed consideration in this debate: varying data quality of input features across race groups. For example, family history of cancer is an essential predictor in cancer risk prediction algorithms but is less reliably documented for Black participants and may therefore be less predictive of cancer outcomes. Using data from the Southern Community Cohort Study, we assessed whether race adjustments could allow risk prediction models to capture varying data quality by race, focusing on colorectal cancer risk prediction. We analyzed 77,836 adults with no history of colorectal cancer at baseline. The predictive value of self-reported family history was greater for White participants than for Black participants. We compared two cancer risk prediction algorithms--a race-blind algorithm which included standard colorectal cancer risk factors but not race, and a race-adjusted algorithm which additionally included race. Relative to the race-blind algorithm, the race-adjusted algorithm improved predictive performance, as measured by goodness of fit in a likelihood ratio test (P-value: <0.001) and area under the receiving operating characteristic curve among Black participants (P-value: 0.006). Because the race-blind algorithm underpredicted risk for Black participants, the race-adjusted algorithm increased the fraction of Black participants among the predicted high-risk group, potentially increasing access to screening. More broadly, this study shows that race adjustments may be beneficial when the data quality of key predictors in clinical algorithms differs by race group. [ABSTRACT FROM AUTHOR]

Objective. To enhance the investigations on MC calculated beam quality correction factors of thimble ionization chambers from high-energy brachytherapy sources and to develop reliable reference conditions in source and detector setups in water. Approach. The response of five different ionization chambers from PTW-Freiburg and Standard Imaging was investigated for irradiation by a high dose rate Ir-192 Flexisource in water. For a setup in a Beamscan water phantom, Monte Carlo simulations were performed to calculate correction factors for the chamber readings. After exact positioning of source and detector the absorbed dose rate at the TG-43 reference point at one centimeter nominal distance from the source was measured using these factors and compared to the specification of the calibration certificate. The Monte Carlo calculations were performed using the restricted cema formalism to gain further insight into the chamber response. Calculations were performed for the sensitive volume of the chambers, determined by the methods currently used in investigations of dosimetry in magnetic fields. Main results. Measured dose rates and values from the calibration certificate agreed within the combined uncertainty (k = 2) for all chambers except for one case in which the full air cavity was simulated. The chambers showed a distinct directional dependence. With the restricted cema formalism calculations it was possible to examine volume averaging and energy dependence of the perturbation factors contributing to the beam quality correction factor also differential in energy. Significance. This work determined beam quality correction factors to measure the absorbed dose rate from a brachytherapy source in terms of absorbed dose to water for a variety of ionization chambers. For the accurate dosimetry of brachytherapy sources with ionization chambers it is advisable to use correction factors based on the sensitive volume of the chambers and to take account for the directional dependence of chamber response. [ABSTRACT FROM AUTHOR]

Background: Peptide receptor radionuclide therapy (PRRT) uses [177Lu]Lu-[DOTA0-Tyr3]octreotate ([177Lu]Lu-DOTA-TATE) to treat patients with neuroendocrine tumours (NETs) overexpressing the somatostatin receptor 2A (SSTR2A). It has shown significant short-term improvements in survival and symptom alleviation, but there remains room for improvement. Here, we investigated whether combining [177Lu]Lu-DOTA-TATE with chemotherapeutics enhanced the in vitro therapeutic efficacy of [177Lu]Lu-DOTA-TATE. Results: Transfected human osteosarcoma (U2OS + SSTR2A, high SSTR2A expression) and pancreatic NET (BON1 + STTR2A, medium SSTR2A expression) cells were subjected to hydroxyurea, gemcitabine or triapine for 24 h at 37oC and 5% CO2. Cells were then recovered for 4 h prior to a 24-hour incubation with 0.7–1.03 MBq [177Lu]Lu-DOTA-TATE (25 nM) for uptake and metabolic viability studies. Incubation of U2OS + SSTR2A cells with hydroxyurea, gemcitabine, and triapine enhanced uptake of [177Lu]Lu-DOTA-TATE from 0.2 ± 0.1 in untreated cells to 0.4 ± 0.1, 1.1 ± 0.2, and 0.9 ± 0.2 Bq/cell in U2OS + SSTR2A cells, respectively. Cell viability post treatment with [177Lu]Lu-DOTA-TATE in cells pre-treated with chemotherapeutics was decreased compared to cells treated with [177Lu]Lu-DOTA-TATE monotherapy. For example, the viability of U2OS + SSTR2A cells incubated with [177Lu]Lu-DOTA-TATE decreased from 59.5 ± 22.3% to 18.8 ± 5.2% when pre-treated with hydroxyurea. Control conditions showed no reduced metabolic viability. Cells were also harvested to assess cell cycle progression, SSTR2A expression, and cell size by flow cytometry. Chemotherapeutics increased SSTR2A expression and cell size in U2OS + SSTR2A and BON1 + STTR2A cells. The S-phase sub-population of asynchronous U2OS + SSTR2A cell cultures was increased from 45.5 ± 3.3% to 84.8 ± 2.5%, 85.9 ± 1.9%, and 86.6 ± 2.2% when treated with hydroxyurea, gemcitabine, and triapine, respectively. Conclusions: Hydroxyurea, gemcitabine and triapine all increased cell size, SSTR2A expression, and [177Lu]Lu-DOTA-TATE uptake, whilst reducing cell metabolic viability in U2OS + SSTR2A cells when compared to [177Lu]Lu-DOTA-TATE monotherapy. Further investigations could transform patient care and positively increase outcomes for patients treated with [177Lu]Lu-DOTA-TATE. [ABSTRACT FROM AUTHOR]

Purpose: The pressure on professionals within the healthcare workforce is increasing due to staffing shortages, economic demands and changing care models. Through boundary work theories, our study explores how task-shifting in hand osteoarthritis (OA) care impacts the professional boundaries and division of labor between rheumatologists and occupational therapists (OTs) in Norwegian specialist healthcare. Methodology: Seventeen semi-structured qualitative interviews were conducted at two hospitals in Norway. Participants included ten rheumatologists and five OTs. Data were analyzed using reflexive thematic analysis. Results: The analysis resulted in three themes (1) Forms of responsibility and task transfers, (2) Circumventing the rules to ensure efficient practices and appropriate patient care, (3) Broadening and specializing; movement of professional demarcations. Overall, we found that medical tasks in hand OA care are increasingly delegated to, and adopted by, OTs, blurring the rheumatologist-OT boundary. Some of the task delegations skirted Norwegian legal boundaries, in efforts to streamline clinic operations. OTs expanded their scope of practice by adopting new tasks, whereas rheumatologist increased their specialist status by shedding unwanted tasks. Conclusion: Task shifting between rheumatologists and OTs in hand OA care was characterized by boundary blurring activities. The results support a shift in hand OA management from rheumatologists to OTs. [ABSTRACT FROM AUTHOR]

Simple Summary: Old World bollworm is a moth species that causes significant damage to a wide range of agricultural crops. This species was once confined to the eastern hemisphere but has recently spread throughout South America and the Caribbean and has the potential to establish in North America. Molecular detection methods for Old World bollworm have been developed to track its spread and rapidly differentiate it from the native sibling species, corn earworm. Currently, droplet digital PCR (ddPCR) is a preferred method for bulk screening as it is highly accurate and tolerant of PCR inhibitors; however, real-time PCR is less expensive and more widely available in molecular labs. Improvements to DNA extraction yield and purity are crucial for real-time PCR assay optimization, but these improvements must be time- and cost-efficient. In this study, we improve upon previously published bulk DNA extraction methods by reducing bench time and costly materials. Our results indicate that the addition of caffeine and RNase A improves DNA extraction, resulting in higher amounts of target DNA in real-time PCR. Such improvements will enable the use of high throughput screening methods across multiple platforms to improve the probability of detection of Old World bollworm. Helicoverpa armigera is among the most problematic agricultural pests worldwide due to its polyphagy and ability to evolve pesticide resistance. Molecular detection methods for H. armigera have been developed to track its spread, as such methods allow for rapid and accurate differentiation from the native sibling species H. zea. Droplet digital PCR (ddPCR) is a preferred method for bulk screening due to its accuracy and tolerance to PCR inhibitors; however, real-time PCR is less expensive and more widely available in molecular labs. Improvements to DNA extraction yield, purity, and throughput are crucial for real-time PCR assay optimization. Bulk DNA extractions have recently been improved to where real-time PCR sensitivity can equal that of ddPCR, but these new methods require significant time and specialized equipment. In this study, we improve upon previously published bulk DNA extraction methods by reducing bench time and materials. Our results indicate that the addition of caffeine and RNase A improves DNA extraction, resulting in lower Cq values during real-time PCR while reducing the processing time and cost per specimen. Such improvements will enable the use of high throughput screening methods across multiple platforms to improve the probability of detection of H. armigera. [ABSTRACT FROM AUTHOR]

Background: Despite the established knowledge that recurrent copy number variants (CNVs) at the 16p11.2 locus BP4–BP5 confer risk for behavioural and language difficulties, limited research has been conducted on the association between behavioural and social–communicative profiles. The current study aims to further delineate the prevalence, nature and severity of, and the association between, behavioural and social–communicative features of school‐aged children with 16p11.2 deletion syndrome (16p11.2DS) and 16p11.2 duplication (16p11.2Dup). Methods: A total of 68 individuals (n = 47 16p11.2DS and n = 21 16p11.2Dup) aged 6–17 years participated. Standardised intelligence tests were administered, and behavioural and social–communicative skills were assessed by standardised questionnaires. Scores of both groups were compared with population norms and across CNVs. The influence of confounding factors was investigated, and correlation analyses were performed. Results: Compared with the normative sample, children with 16p11.2DS showed high rates of social responsiveness (67%) and communicative problems (69%), while approximately half (52%) of the patients displayed behavioural problems. Children with 16p11.2Dup demonstrated even higher rates of social–communicative problems (80–90%) with statistically significantly more externalising and overall behavioural challenges (89%). In both CNV groups, there was a strong positive correlation between behavioural and social–communicative skills. Conclusions: School‐aged children with 16p11.2 CNVs show high rates of behavioural, social responsiveness and communicative problems compared with the normative sample. These findings point to the high prevalence of autistic traits and diagnoses in these CNV populations. Moreover, there is a high comorbidity between behavioural and social–communicative problems. Patients with difficulties in both domains are vulnerable and need closer clinical follow‐up and care. [ABSTRACT FROM AUTHOR]

Summary: The transcription factor GATA2 has a pivotal role in haematopoiesis. Heterozygous germline GATA2 mutations result in a syndrome characterized by immunodeficiency, bone marrow failure and predispositions to myelodysplastic syndrome (MDS) and acute myeloid leukaemia. Clinical symptoms in these patients are diverse and mechanisms driving GATA2‐related phenotypes are largely unknown. To explore the impact of GATA2 haploinsufficiency on haematopoiesis, we generated a zebrafish model carrying a heterozygous mutation of gata2b (gata2b+/−), an orthologue of GATA2. Morphological analysis revealed myeloid and erythroid dysplasia in gata2b+/− kidney marrow. Because Gata2b could affect both transcription and chromatin accessibility during lineage differentiation, this was assessed by single‐cell (sc) RNA‐seq and single‐nucleus (sn) ATAC‐seq. Sn‐ATAC‐seq showed that the co‐accessibility between the transcription start site (TSS) and a −3.5–4.1 kb putative enhancer was more robust in gata2b+/− zebrafish HSPCs compared to wild type, increasing gata2b expression and resulting in higher genome‐wide Gata2b motif use in HSPCs. As a result of increased accessibility of the gata2b locus, gata2b+/− chromatin was also more accessible during lineage differentiation. scRNA‐seq data revealed myeloid differentiation defects, that is, impaired cell cycle progression, reduced expression of cebpa and cebpb and increased signatures of ribosome biogenesis. These data also revealed a differentiation delay in erythroid progenitors, aberrant proliferative signatures and down‐regulation of Gata1a, a master regulator of erythropoiesis, which worsened with age. These findings suggest that cell‐intrinsic compensatory mechanisms, needed to obtain normal levels of Gata2b in heterozygous HSPCs to maintain their integrity, result in aberrant lineage differentiation, thereby representing a critical step in the predisposition to MDS. [ABSTRACT FROM AUTHOR]

In pharmacoepidemiology, robust data are needed to judge the impact of drug treatment on pregnancy, pregnancy outcomes and breast‐fed infants. As pregnant and breastfeeding women are usually excluded from randomised clinical trials, observational studies are required. One of those data sources are pregnancy registers specifically developed to focus on certain diseases or disease groups. The German Rhekiss register investigates pregnancies in women with chronic inflammatory rheumatic diseases (IRD). Rhekiss is a nationwide, multicentre, longitudinal study, in which women aged 18 years or older with an underlying IRD can be enrolled by a rheumatologist either when planning a pregnancy or in the first half of pregnancy. Data are collected prospectively at regular follow‐up visits. Rheumatologists and patients provide information in a web‐based system before conception (if enrolment was at the time of pregnancy planning), during and after pregnancy. A smartphone app is available for patients. Maternal and clinical information, general laboratory markers, treatment with antirheumatic and other drugs, adverse events, items related to course and outcome of pregnancy and the health of the child are uniformly assessed for all diseases. Individual information on the IRD includes classification criteria, diagnosis‐specific laboratory parameters, clinical parameters and validated instruments to measure disease activity or damage. Furthermore, patient‐reported outcome measures are captured. A total of 2013 individual patients have been enrolled in the register, and data on 1801 completed pregnancies are available. In summary, Rhekiss is a comprehensive and complex register that can answer various research questions about pregnancy in women with chronic IRDs. [ABSTRACT FROM AUTHOR]

Background: The complexity, high prevalence, and substantial personal and socioeconomic burden collectively render atopic dermatitis (AD) a major public health concern. Using crowdsourced Internet data has the potential to provide unique insights into this concern, as demonstrated by several previous studies. However, a comprehensive comparison across European countries remains lacking. Objectives: The study aimed to investigate AD‐related web searches across Europe to assess spatiotemporal variations and associations between disease‐related and external factors. Methods: AD‐related web search data were extracted for 21 European countries between February 2019 and January 2023. Descriptive analysis and autocorrelation functions were performed to examine spatiotemporal patterns. Correlations (r) were used to evaluate the associations between web searches and disease‐related, socioeconomic and meteorological data. Results: Over 241 million AD‐related web searches were identified, with search volume varying substantially among European countries (p < 0.001) and correlating with AD prevalence and disease burden (both r = 0.51, p = 0.019). Search volume increased between 2019 and 2023 in all countries and seasonally peaked in January and March. Negative correlations with median population age (r = −0.46, p = 0.039), number of general practitioners (r = −0.29, p = 0.226) and specialists (r = −0.27, p = 0.270) were observed. Moderate to strong correlations were found between search volume and cold, humid and windy weather with fewer sunshine hours, while higher online interest typically occurred 1–3 months after such weather conditions. Conclusion: The study highlights the great potential of online crowdsourced data analysis, for example, to investigate the impact of climate change or to identify unmet needs at a population level. Furthermore, the growing online interest in AD and the corresponding seasonal peaks emphasize the necessity of adapting treatment plans, intensifying public health campaigns, and disseminating reliable online information by governments and healthcare providers, especially during these periods. [ABSTRACT FROM AUTHOR]

Background: Malassezia yeasts are almost universally present on human skin worldwide. While they can cause diseases such as pityriasis versicolor, their implication in skin homeostasis and pathophysiology of other dermatoses is still unclear. Their analysis using native microscopy of skin tape strips is operator dependent and requires skill, training and significant amounts of hands‐on time. Objectives and Methods: To standardise and improve the speed and quality of diagnosis of Malassezia in skin tape strip samples, we sought to create an artificial intelligence‐based algorithm for this image classification task. Three algorithms, each using different internal architectures, were trained and validated on a manually annotated dataset of 1113 images from 22 samples. Results: The Vision Transformer‐based algorithm performed the best with a validation accuracy of 94%, sensitivity of 94.0% and specificity of 93.5%. Visualisations providing insight into the reasoning of the algorithm were presented and discussed. Conclusion: Our image classifier achieved very good performance in the diagnosis of the presence of Malassezia yeasts in tape strip samples of human skin and can therefore improve the speed and quality of, and access to this diagnostic test. By expanding data sources and explainability, the algorithm could also provide teaching points for more novice operators in future. [ABSTRACT FROM AUTHOR]

Mortality of patients hospitalized with COVID-19 has remained high during the consecutive SARS-CoV-2 pandemic waves. Early discrimination of patients at high mortality risk is crucial for optimal patient care. Symmetric (SDMA) and asymmetric dimethylarginine (ADMA) have been proposed as possible biomarkers to improve risk prediction of COVID-19 patients. We measured SDMA, ADMA, and other L-arginine-related metabolites in 180 patients admitted with COVID-19 in four German university hospitals as compared to 127 healthy controls. Patients were treated according to accepted clinical guidelines and followed-up until death or hospital discharge. Classical inflammatory markers (leukocytes, CRP, PCT), renal function (eGFR), and clinical scores (SOFA) were taken from hospital records. In a small subgroup of 23 COVID-19 patients, sequential blood samples were available and analyzed for biomarker trends over time until 14 days after admission. Patients had significantly elevated SDMA, ADMA, and L-ornithine and lower L-citrulline concentrations than controls. Within COVID-19 patients, SDMA and ADMA were significantly higher in non-survivors (n = 41, 22.8%) than in survivors. In ROC analysis, the optimal cut-off to discriminate non-survivors from survivors was 0.579 µmol/L for SDMA and 0.599 µmol/L for ADMA (both p < 0.001). High SDMA and ADMA were associated with odds ratios for death of 11.45 (3.37–38.87) and 5.95 (2.63–13.45), respectively. Analysis of SDMA and ADMA allowed discrimination of a high-risk (mortality, 43.7%), medium-risk (15.1%), and low-risk group (3.6%); risk prediction was significantly improved over classical laboratory markers. We conclude that analysis of ADMA and SDMA after hospital admission significantly improves risk prediction in COVID-19. [ABSTRACT FROM AUTHOR]

This article, published in the European Heart Journal, presents the findings of the HORUS study, which aimed to investigate the presence of atherosclerosis in ancient mummified humans. The study analyzed whole body CT scans of mummies from seven different cultures, including Egyptian, Peruvian, Bolivian, Unangan/Aleutian Islander, Greenlandic Inuit, ancestral Puebloan, and Middle-Ages Gobi Desert pastoralists. The results showed that atherosclerosis was present in all cultures except for one Indigenous Australian mummy. The study suggests that atherosclerosis has been a part of human populations for thousands of years and supports the existence of an innate human predisposition to the disease. [Extracted from the article]