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Previous in vitro and in situ studies have reported a shift in optimal muscle fibre length for force generation (L0) towards longer length at decreasing activation levels (also referred to as length‐dependent activation), yet the relevance for in vivo human muscle contractions with a variable activation pattern remains largely unclear. By a combination of dynamometry, ultrasound and electromyography (EMG), we experimentally obtained muscle force–fascicle length curves of the human soleus at 100%, 60% and 30% EMGmax levels from 15 participants aiming to investigate activation‐dependent shifts in L0 in vivo. The results showed a significant increase in L0 of 6.5 ± 6.0% from 100% to 60% EMGmax and of 9.1 ± 7.2% from 100% to 30% EMGmax (both P < 0.001), respectively, providing evidence of a moderate in vivo activation dependence of the soleus force–length relationship. Based on the experimental results, an approximation model of an activation‐dependent force–length relationship was defined for each individual separately and for the collective data of all participants, both with sufficiently high accuracy (R2 of 0.899 ± 0.056 and R2 = 0.858). This individual approximation approach and the general approximation model outcome are freely accessible and may be used to integrate activation‐dependent shifts in L0 in experimental and musculoskeletal modelling studies to improve muscle force predictions., Deutsche Forschungsgemeinschaft DFG, German Research Foundation, Peer Reviewed

An imbalanced adaptation of muscle strength and tendon stiffness in response to training may increase tendon strain (i.e., the mechanical demand on the tendon) and consequently tendon injury risk. This study investigated if personalized tendon loading inducing tendon strain within the effective range for adaptation (4.5%–6.5%) can reduce musculotendinous imbalances in male adolescent handball athletes (15–16 years). At four measurement time points during a competitive season, we assessed knee extensor muscle strength and patellar tendon mechanical properties using dynamometry and ultrasonography and estimated the tendon's structural integrity with a peak spatial frequency (PSF) analysis of proximal tendon ultrasound scans. A control group (n = 13) followed their usual training routine, an intervention group (n = 13) integrated tendon exercises into their training (3x/week for ~31 weeks) with a personalized intensity corresponding to an average of ~6.2% tendon strain. We found a significant time by group interaction (p < 0.005) for knee extensor muscle strength and normalized patellar tendon stiffness with significant increases over time only in the intervention group (p < 0.001). There were no group differences or time-dependent changes in patellar tendon strain during maximum voluntary contractions or PSF. At the individual level, the intervention group demonstrated lower fluctuations of maximum patellar tendon strain during the season (p = 0.005) and a descriptively lower frequency of athletes with high-level tendon strain (≥9%). The findings suggest that the personalized tendon loading program reduced muscle-tendon imbalances in male adolescent athletes, which may provide new opportunities for tendon injury prevention., Peer Reviewed

Identifying factors that influence age-related cognitive decline is crucial, given its severe personal and societal impacts. However, studying aging in human or animal models is challenging due to the significant variability in aging processes among individuals. Additionally, longitudinal and cross-sectional studies often produce differing results. In this context, home-cage-based behavioral analysis over lifespans has emerged as a significant method in recent years. This study aimed to explore how prior experience affects cognitive performance in mice of various age groups (4, 12, and 22 months) using a home-cage-based touchscreen test battery. In this automated system, group-housed, ID-chipped mice primarily obtain their food during task performance throughout the day, motivated by their own initiative, without being subjected to food deprivation. Spatial working memory and attention were evaluated using the trial unique non-matching to location (TUNL) and the five-choice serial reaction time task (5-CSRTT), respectively. The same set of mice learned both of these demanding tasks. While signs of cognitive decline were already apparent in middle-aged mice, older mice exhibited poorer performance in both tasks. Mice at both 12 and 22 months displayed an increase in perseverance and a decrease in the percentage of correct responses in the TUNL test compared to the 4-month-old mice. Furthermore, during the 5-CSRTT, they exhibited higher rates of omissions and premature responses compared to their younger counterparts. Additionally, the correct response rate in 22-month-old mice was lower than that of the 4-month-old ones. However, mice that had undergone cognitive training at 4 months maintained high-performance levels when re-tested at 12 months, showing an increase in correct responses during TUNL testing compared to their untrained controls. In the 5-CSRTT, previously trained mice demonstrated higher correct response rates, fewer omissions, and reduced premature re, Peer Reviewed

Background & Aims Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS. Methods Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non-invasive HSI, FLI, FIB-4 scores were determined to assess hepatic steatosis and fibrosis. Results A total of 42 German (age range 18–53 years) and 143 Polish (age range 18–40 years) women with PCOS, as well as 245 German and 289 Polish controls were recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p = .01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17-OH progesterone, total testosterone, and androstenedione (all p < .05). Conclusions FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS., Peer Reviewed

Imbalances between muscle strength and tendon stiffness may cause high‐level tendon strain during maximum effort muscle contractions and lead to tendon structural impairments and an increased risk for tendinopathy in adolescent athletes. However, it remains unclear whether the development of musculotendinous imbalances is influenced by sex. At four measurement time points during a competitive season, we measured quadriceps femoris muscle strength and patellar tendon mechanical properties in 15 female (14.3 ± 0.7 years) and 13 male (16.0 ± 0.6 years) elite handball players of similar maturity using dynamometry and ultrasonography. To estimate the tendon's structural integrity, the peak spatial frequency (PSF) of proximal tendon ultrasound scans was determined. Females demonstrated significantly lower muscle strength (p < 0.001) and patellar tendon stiffness (p < 0.001) than males with no significant changes over time (p > 0.05). Tendon strain during isometric maximum voluntary contractions and PSF neither differed between sexes nor changed significantly over time (p > 0.05). We found lower fluctuations in muscle strength (p < 0.001) in females during the season but no differences in the fluctuations of tendon strain, stiffness, and PSF (p > 0.05). Descriptively, there was a similar frequency (~40%) of athletes with high‐level tendon strain (>9%) in both sexes. These findings suggest that the lower strength capacity of female athletes is paralleled by lower tendon stiffness. Thereby, muscle–tendon imbalances occur to a similar extent in both sexes leading to increased strain levels during the season, which indicates the need for specific tendon training., Peer Reviewed

The synchronization of multiple oscillators serves as the central mechanism for maintaining stable circadian rhythms in physiology and behavior. Aging and disease can disrupt synchronization, leading to changes in the periodicity of circadian activities. While our understanding of the circadian clock under synchronization has advanced significantly, less is known about its behavior outside synchronization, which can also fall within a predictable domain. These states not only impact the stability of the rhythms but also modulate the period length. In C57BL/6 mice, aging, diseases, and removal of peripheral circadian oscillators often result in lengthened behavioral circadian periods. Here, we show that these changes can be explained by a surprisingly simple mathematical relationship: the frequency is the reciprocal of the period, and its distribution becomes skewed when the period distribution is symmetric. The synchronized frequency of a population in the skewed distribution and the macroscopic frequency of combined oscillators differ, accounting for some of the atypical circadian period outputs observed in networks without synchronization. Building on this finding, we investigate the dynamics of circadian outputs in the context of aging and disease, where synchronization is weakened., Peer Reviewed

Shear Wave Elastography (SWE) is currently used to detect tissue pathologies, i.e., tendinopathy. For preventive medicine, it is important to examine the sensitivity of SWE and to investigate how stiffness measures are affected by methodological variables. The aim of this study is to examine shear wave elastography (SWE) measures in order to compare the pre- and post-running values and to determine the correlation between the shear wave speed values (m/s). SWE examinations of the Achilles tendon (AT), soleus muscle (MS) and gastrocnemius muscle (MG)) were performed in 24 healthy professional female athletes. Measurements of the shear wave speed (m/s) were taken before and after incremental treadmill running until exhaustion. Correlations were investigated using the Pearson correlation coefficient and were examined for significance using the Student’s t-test. The pre- and post-exercise shear wave speed did not differ. The pre-exercise and post-exercise stiffness for MS (r = 0.613), MG (r = 0.609) and AT (r = 0.583) correlated strongly. The pre-exercise values and changes in stiffness showed a significant correlation (p < 0.001). In professional athletes, acute exercise induces different tissue stiffness changes in AT, MS and MG for each individual. Thus, exercise activity immediately prior to the SWE measurement needs to be factored in when evaluating tissue stiffness., Peer Reviewed

Background The colonization of skin with pathogenic, partially antibiotic-resistant bacteria is frequently a severe problem in dermatological therapies. For instance, skin colonization with Staphylococcus aureus is even a disease-promoting factor in atopic dermatitis. The photodynamic inactivation (PDI) of bacteria could be a new antibacterial procedure. Upon irradiation with visible light, a special photosensitizer exclusively generates singlet oxygen. This reactive oxygen species kills bacteria via oxidation independent of species or strain and their antibiotic resistance profile causing no bacterial resistance on its part. Objective To investigate the antibacterial potential of a photosensitizer, formulated in a new hydrogel, on human skin ex vivo. Methods The photochemical stability of the photosensitizer and its ability to generate singlet oxygen in the hydrogel was studied. Antimicrobial efficacy of this hydrogel was tested step by step, firstly on inanimate surfaces and then on human skin ex vivo against S. aureus and Pseudomonas aeruginosa using standard colony counting. NBTC staining and TUNEL assays were performed on skin biopsies to investigate potential necrosis and apoptosis effects in skin cells possibly caused by PDI. Results None of the hydrogel components affected the photochemical stability and the life time of singlet oxygen. On inanimate surfaces as well as on the human skin, the number of viable bacteria was reduced by up to 4.8 log10 being more effective than most other antibacterial topical agents. Histology and assays showed that PDI against bacteria on the skin surface caused no harmful effects on the underlying skin cells. Conclusion Photodynamic inactivation hydrogel proved to be effective for decolonization of human skin including the potential to act against superficial skin infections. Being a water-based formulation, the hydrogel should be also suitable for the mucosa. The results of the present ex vivo study form a good basis for cond, Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659, Peer Reviewed

Being the sixth most diagnosed cancer and the fourth leading cause of cancer-related deaths worldwide, liver cancer is considered as a serious disease with a high prevalence and poor prognosis. Current anticancer drugs for liver cancer have drawbacks, such as limited efficacy in later stages of the disease, toxicity to healthy cells, and the potential for drug resistance. There is ample evidence that coumarin-based compounds are potent anticancer agents, with numerous analogues currently being investigated in preclinical and clinical studies. The current study aimed to explore the antitumor potency of a new class of 8-methoxycoumarin-3-carboxamides against liver cancer. Toward this aim, we have designed, synthesized, and characterized a new set of N-(substituted-phenyl)-8-methoxycoumarin-3-carboxamide analogues. The assessment of antitumor activity revealed that the synthesized class of compounds possesses substantial cytotoxicity toward Hep-G2 cells when compared to staurosporine, without significant impact on normal cells. Out of the synthesized compounds, compound 7 demonstrated the most potent cytotoxic effect against Hep-G2 cells with an IC50 of 0.75 µM, which was more potent than the drug staurosporine (IC50 = 8.37 µM). The investigation into the mechanism behind the antiproliferative activity of compound 7 revealed that it interferes with DNA replication and induces DNA damage, leading to cell cycle arrest as demonstrated by a significant decrease in the percentage of cells in the G1 and G2/M phases, along with an increase in the percentage of cells in the S phase. Flow cytometric analysis further revealed that compound 7 has the ability to trigger programmed cell death by inducing necrosis and apoptosis in HepG-2 cells. Further explorations into the mechanism of action demonstrated that compound 7 displays a potent dual-inhibitory activity toward cytochrome P450 and vascular endothelial growth factor receptor-2 (VEGFR-2) proteins, as compared to sorafenib dr, Peer Reviewed

Over sixty years, laser technologies have undergone a technological revolution and become one of the main tools in biomedicine, particularly in neuroscience, neurodegenerative diseases and brain tumors. Glioblastoma is the most lethal form of brain cancer, with very limited treatment options and a poor prognosis. In this study on rats, we demonstrate that glioblastoma (GBM) growth can be suppressed by photosensitizer-free laser treatment (PS-free-LT) using a quantum-dot-based 1267 nm laser diode. This wavelength, highly absorbed by oxygen, is capable of turning triplet oxygen to singlet form. Applying 1267 nm laser irradiation for a 4 week course with a total dose of 12.7 kJ/cm2 firmly suppresses GBM growth and increases survival rate from 34% to 64%, presumably via LT-activated apoptosis, inhibition of the proliferation of tumor cells, a reduction in intracranial pressure and stimulation of the lymphatic drainage and clearing functions. PS-free-LT is a promising breakthrough technology in non- or minimally invasive therapy for superficial GBMs in infants as well as in adult patients with high photosensitivity or an allergic reaction to PSs., Russian Science Foundation, Russian Ministry of Science and Higher Education, NIH, HE Pathfinder GlioLight project, IBPPM RAS, Peer Reviewed

Cardiovascular diseases are the leading cause of morbidity and mortality in adults worldwide. There is one common pathophysiological aspect present in all cardiovascular diseases—dysfunctional heart rhythm regulation. Taking this aspect into consideration for cardiovascular risk predictions opens important research perspectives, allowing for the development of preventive treatment techniques. The aim of this study was to find out whether certain pathologically appearing signs in the heart rate variability (HRV) of an apparently healthy person, even with high HRV, can be defined as biomarkers for a disturbed cardiac regulation and whether this can be treated preventively by a drug-free method. This multi-phase study included 218 healthy subjects of either sex, who consecutively visited the physician at Gesundheit clinic because of arterial hypertension, depression, headache, psycho-emotional stress, extreme weakness, disturbed night sleep, heart palpitations, or chest pain. In study phase A, baseline measurement to identify individuals with cardiovascular risks was done. Therefore, standard HRV, as well as the new cardiorhythmogram (CRG) method, were applied to all subjects. The new CRG analysis used here is based on the recently introduced LF drops and HF counter-regulation. Regarding the mechanisms of why these appear in a steady-state cardiorhythmmogram, they represent non-linear event-based dynamical HRV biomarkers. The next phase of the study, phase B, tested whether the pathologically appearing signs identified via CRG in phase A could be clinically influenced by drug-free treatment. In order to validate the new CRG method, it was supported by non-linear HRV analysis in both phase A and in phase B. Out of 218 subjects, the pathologically appearing signs could be detected in 130 cases (60%), p < 0.01, by the new CRG method, and by the standard HRV analysis in 40 cases (18%), p < 0.05. Thus, the CRG method was able to detect 42% more cases with pathologically app, Peer Reviewed

Communication is a basic need for all people to fully participate in life. Persons with disabilities may face particular challenges in developing their communication skills and using them appropriately in different situations. Augmentative and Alternative Communication (AAC) tools and methods can assist individuals in this process. Increasing digitization has changed the way everyone communicates, and this offers opportunities for persons using AAC. This paper briefly outlines what has been achieved in terms of digitalization in AAC. The need for full, adapted access to technology is highlighted and research desiderata are identified., Peer Reviewed

Non-communicable diseases (NCDs), including coronary heart disease, stroke, hypertension, type 2 diabetes, dementia, depression and cancers, are on the rise worldwide and are often associated with a lack of physical activity (PA). Globally, the levels of PA among individuals are below WHO recommendations. A lack of PA can increase morbidity and mortality, worsen the quality of life and increase the economic burden on individuals and society. In response to this trend, numerous organisations came together under one umbrella in Hamburg, Germany, in April 2021 and signed the ‘Hamburg Declaration’. This represented an international commitment to take all necessary actions to increase PA and improve the health of individuals to entire communities. Individuals and organisations are working together as the ‘Global Alliance for the Promotion of Physical Activity’ to drive long-term individual and population-wide behaviour change by collaborating with all stakeholders in the community: active hospitals, physical activity specialists, community services and healthcare providers, all achieving sustainable health goals for their patients/clients. The ‘Hamburg Declaration’ calls on national and international policymakers to take concrete action to promote daily PA and exercise at a population level and in healthcare settings., Peer Reviewed

Alternative medicine methods and treatments enjoy great popularity. However, many users fail to recognise the dangers associated with these methods. One of these is called Black Ointment or Black Salve. Oncologists and attending physicians should be aware of alternative medical methods such as these and be in a position to provide appropriate advice, intervention, if necessary, at any time when counselling patients in difficult situations., This research received no specific grant from any funding agency in the public, commercial, or not‐for‐profit sectors, Peer Reviewed

Cognitive training primarily aims to improve executive functions (EFs). It has become a popular research topic, as previous studies have provided preliminary evidence that EFs relate to sports performance. However, whether a domain-generic cognitive training intervention can improve EFs in high-performance athletes is still unclear. The present randomized controlled study aimed to examine the effects of an eight-week (5 min/day, 5 days/week) smartphone-based domain-generic cognitive training intervention (i.e., the smartphone game “Fruit Ninja”) on EFs in youth soccer athletes (N = 33; intervention: n = 15, passive control: n = 18; German youth soccer academy). We assessed working memory (3-back task), inhibition (Flanker & Go/NoGo task), and cognitive flexibility (number-letter task) in a pre-post design with computerized tasks. The results showed no significant time x group differences attributable to the cognitive training between the intervention group and the control group, except for a response time variable of the Go/NoGo task. These preliminary results do not suggest an application of CT as a smartphone-based game to improve EFs performance in soccer players. However, more research is needed to establish the efficacy of domain-specific interventions in high-level team sport athletes., Peer Reviewed

Data integration, data sharing, and standardized analyses are important enablers for data-driven medical research. Circadian medicine is an emerging field with a particularly high need for coordinated and systematic collaboration between researchers from different disciplines. Datasets in circadian medicine are multimodal, ranging from molecular circadian profiles and clinical parameters to physiological measurements and data obtained from (wearable) sensors or reported by patients. Uniquely, data spanning both the time dimension and the spatial dimension (across tissues) are needed to obtain a holistic view of the circadian system. The study of human rhythms in the context of circadian medicine has to confront the heterogeneity of clock properties within and across subjects and our inability to repeatedly obtain relevant biosamples from one subject. This requires informatics solutions for integrating and visualizing relevant data types at various temporal resolutions ranging from milliseconds and seconds to minutes and several hours. Associated challenges range from a lack of standards that can be used to represent all required data in a common interoperable form, to challenges related to data storage, to the need to perform transformations for integrated visualizations, and to privacy issues. The downstream analysis of circadian rhythms requires specialized approaches for the identification, characterization, and discrimination of rhythms. We conclude that circadian medicine research provides an ideal environment for developing innovative methods to address challenges related to the collection, integration, visualization, and analysis of multimodal multidimensional biomedical data., Peer Reviewed

The article processing charge was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 491192747 and the Open Access Publication Fund of Humboldt-Universität zu Berlin., Background: Ankle joint functional assessment tool (AJFAT) is gradually becoming a popular tool for diagnosing functional ankle instability (FAI). However, due to the lack of standard Chinese versions of AJFAT and reliability and validity tests, the use of AJFAT in the Chinese population is limited. This study aimed to translate and cross-culturally adapt the AJFAT from English into Chinese, and evaluate the reliability and validity of the Chinese version of AJFAT and to investigate its psychometric properties. Methods: The translation and cross-cultural adaptation of AJFAT was performed according to guidelines for cross-cultural adaptation of self-report measures. 126 participants with a history of ankle sprain completed the AJFAT-C twice within 14 days and completed the Cumberland ankle instability tool (CAIT-C) once. Test–retest reliability, internal consistency, ceiling and floor effects, convergent and structure validity and discriminative ability were investigated. Results: The test–retest reliability (ICC = 0.91, 95%CI = 0.87–0.94) and internal consistency (Cronbach’s alpha = 0.87) of the AJFAT-C were excellent. No ceiling or floor effects were detected. A moderate correlation between the AJFAT-C and the CAIT-C suggested a moderate convergent validity. The AJFAT-C had a two-factor structure: 1. function of the unstable side of the ankle joint (9 items) and 2. symptoms of the unstable side of the ankle (2 items). The ideal cut-off point of the AJFAT-C was calculated as 26 points. Conclusion: The Chinese version of AJFAT can be considered as a valid and reliable ankle joint function evaluation tool that can be applied in clinical and research work., Peer Reviewed

The article processing charge was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) – 491192747 and the Open Access Publication Fund of Humboldt-Universität zu Berlin., The human penis transmits behaviorally important sensory information via the dorsal penile nerve, which is required for initiation and maintenance of erection. The human penis differs from the penes of other hominids. The lack of a baculum makes the human penis dependent on erectile tissue, which is under control of neural signals activated by tactile stimulation. Accordingly, the penile sensory innervation is crucial for human sexual behavior. To clarify penile innervation, we analyzed the architecture of the dorsal penile nerve of five male subjects who donated their body. We stained the sensory fibers in the penile dorsal nerve with anti-neurofilament H antibody, and identified myelinated axons with Luxol fast blue staining. Furthermore, we visualized nerve bundles as they travel along the shaft of the penis by performing microfocus computed tomography scans after counterstaining penes with iodine. Our results show that the dorsal penile nerve is organized in 25–45 loosely packed nerve bundles, running mediodorsally in the shaft of the penis. This organization corresponds to that in penes of other mammalian species, but differs from the organization of the other peripheral sensory nerves. Around half of the dorsal penile nerve fibers were myelinated and a human hemipenis contained a total of 8290 ± 2553 (mean ± SD) axons. Thus, the number of sensory axons in the human dorsal penile nerve is higher than in other species described so far. The large fraction of unmyelinated nerve fibers suggests that the conduction speed is not a crucial aspect of penile sensory transmission., Peer Reviewed

Finale Version folgendermaßen veröffentlicht: Annekatrin Hoppe, Malte Roswag, Dirk Lehr: „Digitale Interventionen in der betrieblichen Gesundheitsförderung“. In: Handbuch Gesundheitsförderung bei der Arbeit: Interventionen für Individuen, Teams und Organisationen. Hrsg. von Alexandra Michel und Annekatrin Hoppe. Wiesbaden: Springer, 2022, Seiten 351–369. DOI: https://doi.org/10.1007/978-3-658-28651-4_23, Digitale Interventionen für Berufstätige greifen die Potenziale neuer Technologien auf und können genutzt werden, um auf neue Anforderungen in einer digitalisierten Arbeitswelt zu reagieren. In diesem Kapitel stellen wir verschiedene digitale Interventionen zur Gesundheitsförderung vor und gehen auf Unterschiede im Übungsformat, der Dauer der Interventionen, der persönlichen Begleitung sowie deren Wirksamkeit ein. Schließlich werden potenzielle Chancen und Risiken digitaler Interventionen für Berufstätige diskutiert.

Hintergrund: Heutzutage ist es durch den Fortschritt der medizinischen und technischen Entwicklung möglich, dass bereits sehr früh geborene sowie an schweren Erkrankungen leidende Kinder eine höhere Überlebenschance haben. Dafür erfolgten die Aufnahme und Behandlung auf einer neonatologischen oder pädiatrischen Intensivstation. Sowohl für die Kinder, aber auch insbesondere für die Eltern steht dieser Ort in engen Zusammenhang mit Stress und dessen entsprechenden Auswirkungen. Ziel dieser Thesis ist es daher, die Belastungen der Eltern sowie deren Auswirkungen zu identifizieren und zugleich Strategien zur Bewältigung aufzuzeigen. Methodik: Die vorliegende Thesis wurde mittels einer systematischen Literaturrecherche verfasst. Dafür wurden die beiden medizinischen Datenbanken PubMed und CINAHL mithilfe definierter Ein- und Ausschlusskriterien durchsucht sowie ergänzend dazu eine Handsuche durchgeführt. Dies führte zum Eischluss von acht Studien in die Arbeit. Ergebnisse: Eltern in der pädiatrischen Intensivstation werden mit vielen verschiedenen Stressquellen konfrontiert. Besonders häufig erwähnt werden die Ungewissheit über die Zukunft und die Entscheidungskonflikte im Behandlungsprozess, die Umgebung der Intensivstation, die durch die Aufnahme bedingten Veränderungen der elterlichen Rolle, die Konfrontation mit einer hohen emotionalen Intensität, die veränderten Familien- und Beziehungsbedürfnisse sowie die Kommunikation mit dem Gesundheitspersonal. Als körperliche und psychische Folgen dieser Stressoren sind die Entwicklung einer posttraumatischen Belastungsstörung, ein erhöhtes Angstempfinden bzw. eine Angststörung, die Erkrankung an einer Depression sowie ein massiv erhöhtes Stressempfinden zu nennen. Zur Bewältigung und Reduktion der stressbedingten Belastungen helfen die Coping - Mechanismen soziale Unterstützung, Erziehungsprogramme, die Methode der Känguru – Pflege, die angemessene Kommunikation, sowie das problemfokussierte und das emotionsfokussierte Coping

3D technology is used in a variety of ways, including in medicine and especially in dermatology in the form of the 3D full-body scanner. This versatile technology is also implemented in smartphone apps to create digital 3D models of objects of all types and sizes in a very short time using photogrammetry. So far, smartphone applications are not yet an integral part of dermatological care in Germany. This raises the question of potential applications of 3D scanner apps for dermatology. In this paper, the potential of 3D scanner apps for dermatological care in Germany is investigated. To this end, semi-structured interviews were conducted with health care professionals in university hospitals and evaluated using qualitative content analysis to investigate how such an app is accepted and what requirements must be met. It was found that the app, when appropriately embedded in cost and technology structures and health policy, with medical history functions, data security, and intuitive design, can increase regular skin examinations in the population and serve as a preselection tool. Through its application opportunities in teledermatology, it contributes to nationwide dermatological care, especially important for rural regions. It is not only a valuable addition, but can transform dermatological care in Germany by improving resource allocation in the German healthcare system.

The resumption of professional sports during the COVID-19 pandemic has been described in team sports but less in individual sports. The International Biathlon Union implemented a COVID-19 concept for the 2020–2021 season aimed to mitigate the risks of transmission by rules designated for the professional biathlon environment. The “bubble” model was based on regular reverse transcript polymerase chain reaction (PCR) testing with rapid results and efficient result management protocol. The objective of this study was report incidence and transmission of SARS-CoV-2 among professional biathletes and staff undergoing frequent PCR testing and risk reduction measures during the international season 2020–2021. The efficiency of risk mitigation measures was also evaluated based on the incidence data. During the 4-month season, altogether 22,182 SARS-CoV-2 PCR tests were conducted on all individuals participating in international biathlon season (athletes, team staff and organizing committee). Ninety-six (0.4%) PCR tests were positive and 30% of the positive PCR tests were considered “persistent positive” following recovery from a recent COVID-19 infection. No transmission events were detected following contact with “persistent positive” cases during the season. A great majority of the positive PCR tests were recorded during the first days after arrival in the “bubble”, often in the first entry test taken by the on-site laboratory. In conclusion, a “bubble model” based on frequent PCR testing and hygiene rules was efficient in keeping the infection rate low. The competition activity including international travel was safe, and most of the infections seemed to originate from outside of the “bubble”., Peer Reviewed

Sleep disorders are risk factors for diseases such as dementia or diabetes, and cause enormous costs. Despite the crucial impacts of sleep on human health, there is little to no research on sleep and health in the field of science education. Although health education is an overarching goal of science education in school, the topic of sleep is rarely addressed. In the related field of medical education, empirical studies shed light on the impact of school projects concerning sleep health but are yet unrecognized by science education research. Systematic reviews demonstrate the effectiveness of school-based sleep education programs for increasing sleep knowledge but show contradicting findings regarding the impact on sleep behaviors. Lacking knowledge about healthy sleep is related to unhealthy sleep behavior. In this perspective article, we prepare the topic of sleep for the field of science education by presenting the state of research concerning sleep education. Using the connection between light pollution and sleep disruption, we present a concept of sleep health literacy in science education, argue for the implementation of sleep health literacy in science education curricula, and describe how the topics of sleep and light can serve as a link between health education and Education for Sustainable Development., Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), Open Access Publication Fund of Humboldt-Universität zu Berlin, Peer Reviewed

The use of traditional medicinal plants plays an important role especially in remote rural and marginalized landscapes at different latitudes. In the development of nature conservation strategies based on local knowledge and sustainable resource management, medicinal herbs have been hypothesized to be cultural key stone species. Environmental education is a crucial driver for fostering environmental literacy and preserving local knowledge across generations. We conducted semi-structured interviews with stakeholders in the Autonomous Province of Bozen-South Tyrol (N Italy) to gain insights into, and reflections on, the cultural value of traditional medicinal plants and their interplay within the local landscape, nature conservation and their role in environmental education and knowledge transfer across generations. We also used a combination of purposive and snowball sampling to identify relevant actors. The different voices collected in the study clearly highlight the role of medicinal herbs in healthcare, for cultural identity of local communities and demonstrate a growing commercial market niche that maintains the local economy and services, including widespread offers related to environmental education, that have not, unfortunately, been used yet in the formal curricula of local schools. The latter is crucial for a holistic approach taking medicinal plants as an ideal vehicle to connect especially children with nature and history of South Tyrol, strengthening health education and overall environmental literacy, including species knowledge. However, the revival of herbal medicine and related knowledge do not prevent the continuous loss of local traditional knowledge regarding medicinal plants, recipes and use. More species and their uses are being forgotten due to superficialisation of knowledge and of mainstreaming and homogenization of the global market of herbal medicine. Safeguarding the natural and cultural treasures of South Tyrol for future generations is i, Peer Reviewed

Background: Entamoeba gingivalis (E. gingivalis) is an anaerobic protozoan that is strongly associated with inflamed periodontal pockets. It is able to invade the mucosal epithelium of the human host, where it can feed on epithelial cells and elicit a severe innate immune response. Unlike other Entamoeba species, it is considered that E. gingivalis cannot form cysts, because it is a non-infectious protozoan. The lack of encystation capability would make it susceptible to periodontal treatment. However, it is not clear how the human host becomes infected with E. gingivalis trophozoites. We investigated the ability of E. gingivalis to encapsulate in response to an unfavorable environment in vitro. Methods: Different strains of E. gingivalis, isolated from inflamed periodontal pocket samples, were cultured for 8 days in the presence or absence of the antimicrobials amoxycillin and metronidazole. To reveal cyst formation, we investigated the morphology and ultrastructure of the amoeba by light, fluorescence, transmission and scanning electron microscopy. We also used the fluorescent dye calcofluor white M2R to demonstrate chitin present in the cyst wall. Results: We observed exocysts and an intra-cystic space separating the encapsulated trophozoite from the environment. Remarkably, cysts showed a smooth surface, polygonal edges and smaller size compared to free-living trophozoites. In addition, encapsulated trophozoites that detached from the cyst wall had a dense cytoplasma without phagocytic vesicles. The cyst walls consisted of chitin as in other Entamoba species. The encapsulated trophozoids were mononuclear after antibioticinduced encapsulation. Discussion: We conclude that E. gingivalis cyst formation has significant implications for dissemination and infection and may explain why established treatment approaches often fail to halt periodontal tissue destruction during periodontitis and peri-implantitis., Peer Reviewed

Sugar beet is one of the greatest sources for producing sugar worldwide. However, a group of bacteria grows on beets during the storage process, leading to a reduction in sucrose yield. Our study focused on identifying common bacterial species that grow on beets during manufacturing and contribute to sucrose loss. The ultimate goal was to find a potential antibacterial agent from various plant extracts and oils to inhibit the growth of these harmful bacteria and reduce sucrose losses. The screening of bacterial species that grow on beet revealed that a large group of mesophilic bacteria, such as Bacillus subtilis, Leuconostoc mesenteroides, Pseudomonas fluorescens, Escherichia coli, Acinetobacter baumannii, Staphylococcus xylosus, Enterobacter amnigenus, and Aeromonas species, in addition to a dominant thermophilic species called Bacillus thermophilus, were found to be present during the manufacturing of beets. The application of 20 plant extracts and 13 different oils indicated that the extracts of Geranium gruinum, Datura stramonium, and Mentha spicata were the best antibacterials to reduce the growth of B. thermophilus with inhibition zones equal to 40, 39, and 35 mm, respectively. In contrast, the best active oils for inhibiting the growth of B. thermophilus were Mentha spicata and Ocimum bacilicum, with an inhibitory effect of 50 and 45 mm, respectively. RAPD-PCR with different primers indicated that treating sugar juice with the most effective oils against bacteria resulted in new recombinant microorganisms, confirming their roles as strong antibacterial products. The characterization of Mentha spicata and Ocimum bacilicum oils using GC/MS analysis identified cis-iso pulegone and hexadecanoic acid as the two main bioactive compounds with potential antibacterial activity. An analysis of five genes using DD-PCR that have been affected due to antibacterial activity from the highly effective oil from Mentha spicata concluded that all belonged to the family of prot, Peer Reviewed

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Abundant studies have examined mental health in the early periods of the COVID-19 pandemic. However, empirical work examining the mental health impact of the pandemic’s subsequent phases remains limited. In the present study, we investigated how mental vulnerability and resilience evolved over the various phases of the pandemic in 2020 and 2021 in Germany. Data were collected (n = 3522) across seven measurement occasions using validated and self-generated measures of vulnerability and resilience. We found evidence for an immediate increase in vulnerability during the first lockdown in Germany, a trend towards recovery when lockdown measures were eased, and an increase in vulnerability with each passing month of the second lockdown. Four different latent trajectories of resilience–vulnerability emerged, with the majority of participants displaying a rather resilient trajectory, but nearly 30% of the sample fell into the more vulnerable groups. Females, younger individuals, those with a history of psychiatric disorders, lower income groups, and those with high trait vulnerability and low trait social belonging were more likely to exhibit trajectories associated with poorer mental well-being. Our findings indicate that resilience–vulnerability responses in Germany during the COVID-19 pandemic may have been more complex than previously thought, identifying risk groups that could benefit from greater support., Social Neuroscience Lab of the Max Planck Society, Berlin University Alliance (BUA), Max Planck Society, Peer Reviewed

Increasing walking speed is accompanied by an increase of the mechanical power and work performed at the ankle joint despite the decrease of the intrinsic muscle force potential of the soleus (Sol) and gastrocnemius medialis (GM) muscles. In the present study, we measured Achilles tendon (AT) elongation and, based on an experimentally determined AT force–elongation relationship, quantified AT force at four walking speeds (slow 0.7 m.s−1, preferred 1.4 m.s−1, transition 2.0 m.s−1, and maximum 2.6 ± 0.3 m.s−1). Further, we investigated the mechanical power and work of the AT force at the ankle joint and, separately, the mechanical power and work of the monoarticular Sol at the ankle joint and the biarticular gastrocnemii at the ankle and knee joints. We found a 21% decrease in maximum AT force at the two higher speeds compared to the preferred; however, the net work of the AT force at the ankle joint (ATF work) increased as a function of walking speed. An earlier plantar flexion accompanied by an increased electromyographic activity of the Sol and GM muscles and a knee-to-ankle joint energy transfer via the biarticular gastrocnemii increased the net ATF mechanical work by 1.7 and 2.4-fold in the transition and maximum walking speed, respectively. Our findings provide first-time evidence for a different mechanistic participation of the monoarticular Sol muscle (i.e., increased contractile net work carried out) and the biarticular gastrocnemii (i.e., increased contribution of biarticular mechanisms) to the speed-related increase of net ATF work., Peer Reviewed

Background In environmental health research, sex and gender are not yet adequately considered. There is a need to improve data collection in population-based environmental health studies by comprehensively surveying sex/gender-related aspects according to gender theoretical concepts. Thus, within the joint project INGER we developed a multidimensional sex/gender concept which we aimed to operationalize and to test the operationalization for feasibility. Methods In an iterative process, we created questionnaire modules which quantitatively captured the requirements of the INGER sex/gender concept. We deployed it in the KORA cohort (Cooperative Health Research in the Region of Augsburg, Germany) in 2019 and evaluated response and missing rates. Results The individual sex/gender self-concept was surveyed via a two-step approach that asked for sex assigned at birth and the current sex/gender identity. Additionally, we used existing tools to query internalized sex/gender roles and externalized sex/gender expressions. Adapted to the KORA population, we asked for discrimination experiences and care and household activities contributing to explain structural sex/gender relations. Further intersectionality-related social categories (e.g., socio-economic position), lifestyle and psychosocial factors were covered through data available in KORA. We could not identify appropriate tools to assess the true biological sex, sexual orientation and ethnic/cultural identity, which have yet to be developed or improved. The response-rate was 71%, the evaluation of 3,743 questionnaires showed a low missing rate. Prevalence of marginalized groups regarding sex/gender identity and definable by experiences of discrimination was very low. Conclusion We have shown how the multidimensional INGER sex/gender concept can be operationalized according to an European and North American understanding of sex/gender for use in quantitative research. The questionnaire modules proved feasible in an epidem, Peer Reviewed

Recently, we reported induced anoxia as a limiting factor for photodynamic tumor therapy (PDT). This effect occurs in vivo if the amount of generated singlet oxygen that undergoes chemical reactions with cellular components exceeds the local oxygen supply. The amount of generated singlet oxygen depends mainly on photosensitizer (PS) accumulation, efficiency, and illumination intensity. With illumination intensities above a certain threshold, singlet oxygen is limited to the blood vessel and the nearest vicinity; lower intensities allow singlet oxygen generation also in tissue which is a few cell layers away from the vessels. While all experiments so far were limited to light intensities above this threshold, we report experimental results for intensities at both sides of the threshold for the first time, giving proof for the described model. Using time-resolved optical detection in NIR, we demonstrate characteristic, illumination intensity-dependent changes in signal kinetics of singlet oxygen and photosensitizer phosphorescence in vivo. The described analysis allows for better optimization and coordination of PDT drugs and treatment, as well as new diagnostic methods based on gated PS phosphorescence, for which we report a first in vivo feasibility test., Brigitte and Konstanze Wegener Foundation, Sojo University, Grant-in-Aid for Scientific Research on Scientific Research (C), Ministry of Health of Czech Republic, European Union—Next Generation EU, Peer Reviewed

The COVID-19 pandemic represents a worldwide threat to health. Since its onset in 2019, the pandemic has proceeded in different phases, which have been shaped by a complex set of influencing factors, including public health and social measures, the emergence of new virus variants, and seasonality. Understanding the development of COVID-19 incidence and its spatiotemporal patterns at a neighborhood level is crucial for local health authorities to identify high-risk areas and develop tailored mitigation strategies. However, analyses at the neighborhood level are scarce and mostly limited to specific phases of the pandemic. The aim of this study was to explore the development of COVID-19 incidence and spatiotemporal patterns of incidence at a neighborhood scale in an intra-urban setting over several pandemic phases (March 2020–December 2021). We used reported COVID-19 case data from the health department of the district Berlin-Neukölln, Germany, additional socio-demographic data, and text documents and materials on implemented public health and social measures. We examined incidence over time in the context of the measures and other influencing factors, with a particular focus on age groups. We used incidence maps and spatial scan statistics to reveal changing spatiotemporal patterns. Our results show that several factors may have influenced the development of COVID-19 incidence. In particular, the far-reaching measures for contact reduction showed a substantial impact on incidence in Neukölln. We observed several age group-specific effects: school closures had an effect on incidence in the younger population (< 18 years), whereas the start of the vaccination campaign had an impact primarily on incidence among the elderly (> 65 years). The spatial analysis revealed that high-risk areas were heterogeneously distributed across the district. The location of high-risk areas also changed across the pandemic phases. In this study, existing intra-urban studies were supplemen, Peer Reviewed

The progress in brain diseases treatment is limited by the blood-brain barrier (BBB), which prevents delivery of the vast majority of drugs from the blood into the brain. In this study, we discover unknown phenomenon of opening of the BBBB (BBBO) by low-level laser treatment (LLLT, 1268 nm) in the mouse cortex. LLLT-BBBO is accompanied by activation of the brain drainage system contributing effective delivery of liposomes into glioblastoma (GBM). The LLLT induces the generation of singlet oxygen without photosensitizers (PSs) in the blood endothelial cells and astrocytes, which can be a trigger mechanism of BBBO. LLLT-BBBO causes activation of the ABC-transport system with a temporal decrease in the expression of tight junction proteins. The BBB recovery is accompanied by activation of neuronal metabolic activity and stabilization of the BBB permeability. LLLT-BBBO can be used as a new opportunity of interstitial PS-free photodynamic therapy (PDT) for modulation of brain tumor immunity and improvement of immuno-therapy for GBM in infants in whom PDT with PSs, radio- and chemotherapy are strongly limited, as well as in adults with a high allergic reaction to PSs., Russian Ministry of Science and High Education, RSF, NIH, EU’s H2020 FET OPEN NEUROPA project, RSF, Peer Reviewed

Identifying areas with high and low infection rates can provide important etiological clues. Usually, areas with high and low infection rates are identified by aggregating epidemiological data into geographical units, such as administrative areas. This assumes that the distribution of population numbers, infection rates, and resulting risks is constant across space. This assumption is, however, often false and is commonly known as the modifiable area unit problem. This article develops a spatial relative risk surface by using kernel density estimation to identify statistically significant areas of high risk by comparing the spatial distribution of address-level COVID-19 cases and the underlying population at risk in Berlin-Neukölln. Our findings show that there are varying areas of statistically significant high and low risk that straddle administrative boundaries. The findings of this exploratory analysis further highlight topics such as, e.g., Why were mostly affluent areas affected during the first wave? What lessons can be learned from areas with low infection rates? How important are built structures as drivers of COVID-19? How large is the effect of the socio-economic situation on COVID-19 infections? We conclude that it is of great importance to provide access to and analyse fine-resolution data to be able to understand the spread of the disease and address tailored health measures in urban settings., Deutsche Forschungsgemeinschaft, Peer Reviewed

Objective: Early identification of health-related risk factors is of great importance for maintaining workability. Screening examinations can help to detect diseases at an early stage and provide more needs-based recommendations. This study aims (1) to assess the individual need for prevention or rehabilitation based on preventive health examinations compared to a questionnaire survey, (2) to assess the results of the preventive health examinations compared to the Risk Index – Disability Pension (RI-DP), (3) to assess the results of the questionnaire survey compared to the RI-DP, (4) to assess the general health status of the sample (target population > 1,000) in German employees aged 45–59, (5) to identify the most common medical conditions. A further study question aims, and (6) to investigate the general health status of the specific occupational groups. Methods: Comprehensive diagnostics including medical examination, anamnesis, anthropometric measurements, bioelectrical impedance analysis (BIA), handgrip strength, resting electrocardiogram (ECG), resting blood pressure, pulse wave velocity (PWV), and laboratory blood analyses added by a questionnaire are conducted. The research questions are analyzed in an exploratory manner. Results and conclusion: We expect that the results will allow us to formulate recommendations regarding screening for prevention and rehabilitation needs on a more evidence-based level. Clinical Trial Registration: DRKS ID: DRKS00030982., Peer Reviewed

Background: Non-invasive tracking of beat-to-beat pulse transit time (PTT) via piezoelectric/piezocapacitive sensors (PES/PCS) may expand perioperative hemodynamic monitoring. This study evaluated the ability for PTT via PES/PCS to correlate with systolic, diastolic, and mean invasive blood pressure (SBPIBP, DBPIBP, and MAPIBP, respectively) and to detect SBPIBP fluctuations. Methods: PES/PCS and IBP measurements were performed in 20 patients undergoing abdominal, urological, and cardiac surgery. A Pearson’s correlation analysis (r) between 1/PTT and IBP was performed. The predictive ability of 1/PTT with changes in SBPIBP was determined by area under the curve (reported as AUC, sensitivity, specificity). Results: Significant correlations between 1/PTT and SBPIBP were found for PES (r = 0.64) and PCS (r = 0.55) (p < 0.01), as well as MAPIBP/DBPIBP for PES (r = 0.6/0.55) and PCS (r = 0.5/0.45) (p < 0.05). A 7% decrease in 1/PTTPES predicted a 30% SBPIBP decrease (0.82, 0.76, 0.76), while a 5.6% increase predicted a 30% SBPIBP increase (0.75, 0.7, 0.68). A 6.6% decrease in 1/PTTPCS detected a 30% SBPIBP decrease (0.81, 0.72, 0.8), while a 4.8% 1/PTTPCS increase detected a 30% SBPIBP increase (0.73, 0.64, 0.68). Conclusions: Non-invasive beat-to-beat PTT via PES/PCS demonstrated significant correlations with IBP and detected significant changes in SBPIBP. Thus, PES/PCS as a novel sensor technology may augment intraoperative hemodynamic monitoring during major surgery., German Government sponsored ZIM (Zentrales Innovationsprogramm Mittelstand) program, Peer Reviewed

Background: Tumour heterogeneity in high-grade serous ovarian cancer (HGSOC) is a proposed cause of acquired resistance to treatment and high rates of relapse. Among the four distinct molecular subtypes of HGSOC, the mesenchymal subtype (MES) has been observed with high frequency in several study cohorts. Moreover, it exhibits aggressive characteristics with poor prognosis. The failure to adequately exploit such subtypes for treatment results in high mortality rates, highlighting the need for effective targeted therapeutic strategies that follow the idea of personalized medicine (PM). Methods: As a proof-of-concept, bulk and single-cell RNA data were used to characterize the distinct composition of the tumour microenvironment (TME), as well as the cell–cell communication and its effects on downstream transcription of MES. Moreover, transcription factor activity contextualized with causal inference analysis identified novel therapeutic targets with potential causal impact on transcription factor dysregulation promoting the malignant phenotype. Findings: Fibroblast and macrophage phenotypes are of utmost importance for the complex intercellular crosstalk of MES. Specifically, tumour-associated macrophages were identified as the source of interleukin 1 beta (IL1B), a signalling molecule with significant impact on downstream transcription in tumour cells. Likewise, signalling molecules tumour necrosis factor (TNF), transforming growth factor beta (TGFB1), and C-X-C motif chemokine 12 (CXCL12) were prominent drivers of downstream gene expression associated with multiple cancer hallmarks. Furthermore, several consistently hyperactivated transcription factors were identified as potential sources for treatment opportunities. Finally, causal inference analysis identified Yes-associated protein 1 (YAP1) and Nuclear Receptor Subfamily 2 Group F Member 6 (NR2F6) as novel therapeutic targets in MES, verified in an independent dataset. Interpretation: By utilizing a sophisticated, Deutsche Krebshilfe, Peer Reviewed

During the last years the need to integrate sex and gender in health-related research for better and fairer science became increasingly apparent. Various guidelines and checklists were developed to encourage and support researchers in considering the entangled dimensions of sex/gender in their research. However, a tool for the assessment of sex/gender consideration and its visualization is still missing. We aim to fill this gap by introducing an assessment matrix that can be used as a flexible instrument for comprehensively evaluating the sex/gender consideration in quantitative health-related research. The matrix was developed through an iterative and open process based on the interdisciplinary expertise represented in our research team and currently published guidelines. The final matrix consists of 14 different items covering the whole research process and the publication of results. Additionally, we introduced a method to graphically display this evaluation. By developing the matrix, we aim to provide users with a tool to systematically compare sex/gender consideration qualitatively between different publications and even different fields of study. This way, the assessment matrix represents a tool to identify research gaps and a basis for future research. In the long term, the implementation of this tool to evaluate the consideration of sex/gender should contribute to more sex/gender equitable health-related research., Peer Reviewed

Objectives: We aimed to assess the predictive value of the total metabolic tumor burden prior to treatment in patients with advanced non-small-cell lung cancer (NSCLC) receiving immune checkpoint inhibitors (ICIs). Methods: Pre-treatment 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography (PET/CT) scans performed in two consecutive years for staging in adult patients with confirmed NSCLC were considered. Volume, maximum/mean standardized uptake value (SUVmax/SUVmean), metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were assessed per delineated malignant lesion (including primary tumor, regional lymph nodes and distant metastases) in addition to the morphology of the primary tumor and clinical data. Total metabolic tumor burden was captured by totalMTV and totalTLG. Overall survival (OS), progression-free survival (PFS) and clinical benefit (CB) were used as endpoints for response to treatment. Results: A total of 125 NSCLC patients were included. Osseous metastases were the most frequent distant metastases (n = 17), followed by thoracal distant metastases (pulmonal = 14 and pleural = 13). Total metabolic tumor burden prior to treatment was significantly higher in patients treated with ICIs (mean totalMTV ± standard deviation (SD) 72.2 ± 78.7; mean totalTLG ± SD 462.2 ± 538.9) compared to those without ICI treatment (mean totalMTV ± SD 58.1 ± 233.8; mean totalTLG ± SD 290.0 ± 784.2). Among the patients who received ICIs, a solid morphology of the primary tumor on imaging prior to treatment was the strongest outcome predictor for OS (Hazard ratio HR 28.04, p < 0.01), PFS (HR 30.89, p < 0.01) and CB (parameter estimation PE 3.46, p < 0.01), followed by the metabolic features of the primary tumor. Interestingly, total metabolic tumor burden prior to immunotherapy showed a negligible impact on OS (p = 0.04) and PFS (p = 0.01) after treatment given the hazard ratios of 1.00, but also on CB (p = 0.01) given the PE < 0.01. Overall, Peer Reviewed

The publication of this work was supported by the Open Access Publication Fund of Humboldt-Universität zu Berlin., Schon Jahre bevor der Hormonwirkstoff Insulin die Diabetestherapie Anfang der 1920er revolutionierte und das Leben abertausender Diabetiker weltweit von Grund auf verändern sollte, vertrat der renommierte US-amerikanische Diabetesspezialist Elliott Proctor Joslin (1869-1962) die Auffassung, dass ein diabetischer Patient seine eigene Krankenschwester, sein eigener Chemiker und der Assistent seines behandelnden Arztes sein solle. Eine bemerkenswerte Position zu einer Zeit, die gemeinhin als eine gilt, in der die Verwissenschaftlichungstendenzen einer ohnehin paternalistisch geprägten Medizin zu einer weitreichenden Marginalisierung von Patienten und Patientinnen geführt habe. Auf der Suche nach den Gründen dieser für die erste Hälfte des 20. Jahrhunderts ungewöhnlichen Interaktionspraxis zwischen Ärzten und Patienten leuchtet Oliver Falk in seinem Buch die Herausbildung und Konstituierung dieses kooperierenden, aktiven, sich selbst behandelnden Patient:innentypus aus, der lange vor organisierten Patientenbewegungen und »Citizen Science« konstitutiv für die moderne Diabetestherapie werden sollte. Dabei zeigt er detailliert den engen epistemologischen Zusammenhang zwischen therapeutischem Handeln und wissenschaftlichem Erkenntnisstreben auf und verdeutlicht, dass alltägliches therapeutisches Handeln nicht allein Resultat laborwissenschaftlicher und klinischer Forschungspraxis ist, sondern selbst zum Kern medizinisch-wissenschaftlicher Erkenntnisprozesse gezählt werden muss.

In den letzten Jahrzehnten ist die Zahl der Erwachsenen und Jugendlichen, die an nicht organisierten oder wettbewerbsorientierten Sportarten teilnehmen, gestiegen. In der Pubertät beeinflussen sowohl hormonelle Veränderungen als auch mechanische Belastungen die Entwicklung von Muskeln und Sehnen. Derzeit gibt es keine Informationen über die Interaktion dieser beiden Stimuli, aber es besteht die Vermutung, dass im Zuge der Pubertät bei Athleten und Nicht-Athleten im Vergleich zu Muskelkraft und Sehnensteifigkeit ungleiche Verhältnisse auftreten können. Die Folge dieses Ungleichgewichts könnte eine höhere mechanische Belastung für die Sehnen sein, was weiter zu Verletzungen führen kann. Angesichts der unzureichenden Beweise für die Entwicklung des muskulotendinösen Gewebes während der Pubertät und des Mangels an Kenntnissen darüber, wie die Reifung die Muskel-Sehnen-Einheit, insbesondere die Interaktion mit überlagerten mechanischen Belastungen, beeinflusst, untersucht diese Arbeit die morphologische und mechanische Entwicklung von Knieextensoren und Patellasehne, indem Nicht-Athleten und Athleten aus drei Altersgruppen verglichen werden (frühe Pubertät: 12–14 Jahre, engl.:EA; späte Pubertät: 16–18 Jahre, engl.: LA; Erwachsene: 20–35 Jahre, engl.: YA). Athleten erreichten häufiger Dehnungsgrößen von mehr als 9% Dehnung im Vergleich zu Nicht-Athleten, was auf einen erhöhten mechanischen Bedarf an der Sehne hinweist. Obwohl das Training die Eigenschaften der M. quadriceps femoris-Sehnen-Einheit verbessert, bleibt ihre Entwicklung von früher Pubertät bis zum Erwachsenenalter bei Athleten und Nicht-Athleten ähnlich, mit dem Hauptunterschied zwischen früher Pubertät und später Pubertät. Alter und sportliches Training waren jedoch mit einer höheren Prävalenz von Ungleichgewichten innerhalb der Muskel-Sehnen-Einheit und einer damit einhergehenden erhöhten mechanischen Belastung oder Beanspruchung für die Patellasehne verbunden., In recent decades, the number of adults and especially adolescents who participate in some kind of non-organized or competitive sports has been increasing. During adolescence, the development of muscle and tendons is affected both by maturation, due to hormonal changes, and by mechanical loading. However, there is no information currently on the interaction of this double fold stimulus although there is reason to believe that during adolescence in athletes and non-athletes there may be imbalances developing between muscle strength capacity and tendon stiffness. The result of this imbalance could be the tendon exposure to high mechanical demand by the associated working muscles, which might further lead to tendon injury. Considering the not satisfactory evidence of the musculotendinous tissue development during adolescence, and the lack of knowledge about how maturation affects the muscle-tendon unity, especially in interaction with superimposed mechanical loading, this thesis investigates the morphological and mechanical development of the knee extensors and patellar tendon, by comparing non-athletes and athletes in three different age groups (i.e., early adolescents: EA 12–14 years; late adolescents: LA 16–18 years, and young adults: YA 20–35 years). Athletes were more likely to reach strain magnitudes higher than 9% strain compared to non-athlete controls indicating an increased mechanical demand for the tendon. Although athletic training enhances the properties of the quadriceps femoris muscle-tendon unit, their development from early-adolescence to adulthood remains similar in athletes and non-athletes with the major alterations between early and LA. However, both age and athletic training were associated with a higher prevalence of imbalances within the muscle-tendon unit and a resultant increased mechanical demand for the patellar tendon.

This article was supported by the German Research Foundation (DFG) and the Open Access Publication Fund of Humboldt-Universität zu Berlin., Pancreatic neuroendocrine neoplasms (panNENs) are a rare yet diverse type of neoplasia whose precise clinical–pathological classification is frequently challenging. Since incorrect classifications can affect treatment decisions, additional tools which support the diagnosis, such as machine learning (ML) techniques, are critically needed but generally unavailable due to the scarcity of suitable ML training data for rare panNENs. Here, we demonstrate that a multi-step ML framework predicts clinically relevant panNEN characteristics while being exclusively trained on widely available data of a healthy origin. The approach classifies panNENs by deconvolving their transcriptomes into cell type proportions based on shared gene expression profiles with healthy pancreatic cell types. The deconvolution results were found to provide a prognostic value with respect to the prediction of the overall patient survival time, neoplastic grading, and carcinoma versus tumor subclassification. The performance with which a proliferation rate agnostic deconvolution ML model could predict the clinical characteristics was found to be comparable to that of a comparative baseline model trained on the proliferation rate-informed MKI67 levels. The approach is novel in that it complements established proliferation rate-oriented classification schemes whose results can be reproduced and further refined by differentiating between identically graded subgroups. By including non-endocrine cell types, the deconvolution approach furthermore provides an in silico quantification of panNEN dedifferentiation, optimizing it for challenging clinical classification tasks in more aggressive panNEN subtypes., Peer Reviewed

(1) Background: Radial RARE-EPI MRI facilitates simultaneous T2 and T2* mapping (2in1-RARE-EPI). With modest undersampling (R = 2), the speed gain of 2in1-RARE-EPI relative to Multi-Spin-Echo and Multi-Gradient-Recalled-Echo references is limited. Further reduction in scan time is crucial for clinical studies investigating T2 and T2* as imaging biomarkers. We demonstrate the feasibility of further acceleration, utilizing compressed sensing (CS) reconstruction of highly undersampled 2in1-RARE-EPI. (2) Methods: Two-fold radially-undersampled 2in1-RARE-EPI data from phantoms, healthy volunteers (n = 3), and multiple sclerosis patients (n = 4) were used as references, and undersampled (Rextra = 1–12, effective undersampling Reff = 2–24). For each echo time, images were reconstructed using CS-reconstruction. For T2 (RARE module) and T2* mapping (EPI module), a linear least-square fit was applied to the images. T2 and T2* from CS-reconstruction of undersampled data were benchmarked against values from CS-reconstruction of the reference data. (3) Results: We demonstrate accelerated simultaneous T2 and T2* mapping using undersampled 2in1-RARE-EPI with CS-reconstruction is feasible. For Rextra = 6 (TA = 01:39 min), the overall MAPE was ≤8% (T2*) and ≤4% (T2); for Rextra = 12 (TA = 01:06 min), the overall MAPE was <13% (T2*) and <5% (T2). (4) Conclusion: Substantial reductions in scan time are achievable for simultaneous T2 and T2* mapping of the brain using highly undersampled 2in1-RARE-EPI with CS-reconstruction., European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program, Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany, Peer Reviewed

Seeking and consuming nutrients is essential to survival and the maintenance of life. Dynamic and volatile environments require that animals learn complex behavioral strategies to obtain the necessary nutritive substances. While this has been classically viewed in terms of homeostatic regulation, recent theoretical work proposed that such strategies result from reinforcement learning processes. This theory proposed that phasic dopamine (DA) signals play a key role in signaling potentially need-fulfilling outcomes. To examine links between homeostatic and reinforcement learning processes, we focus on sodium appetite as sodium depletion triggers state- and taste-dependent changes in behavior and DA signaling evoked by sodium-related stimuli. We find that both the behavior and the dynamics of DA signaling underlying sodium appetite can be accounted for by a homeostatically regulated reinforcement learning framework (HRRL). We first optimized HRRL-based agents to sodium-seeking behavior measured in rodents. Agents successfully reproduced the state and the taste dependence of behavioral responding for sodium as well as for lithium and potassium salts. We then showed that these same agents account for the regulation of DA signals evoked by sodium tastants in a taste- and state-dependent manner. Our models quantitatively describe how DA signals evoked by sodium decrease with satiety and increase with deprivation. Lastly, our HRRL agents assigned equal preference for sodium versus the lithium containing salts, accounting for similar behavioral and neurophysiological observations in rodents. We propose that animals use orosensory signals as predictors of the internal impact of the consumed good and our results pose clear targets for future experiments. In sum, this work suggests that appetite-driven behavior may be driven by reinforcement learning mechanisms that are dynamically tuned by homeostatic need., NIH, ANR, Peer Reviewed

We aimed to assess the frequency of additional primary malignancies detected incidentally on [18F]fluoro-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) at staging in NSCLC patients. Moreover, their impact on patient management and survival was assessed. Consecutive NSCLC patients with available staging FDG-PET/CT between 2020 and 2021 were retrospectively enrolled. We reported whether further investigations of suspicious findings presumably not related to NSCLC were recommended and performed after FDG-PET/CT. Any additional imaging, surgery or multimodal management was considered as an impact on patient management. Patient survival was defined using overall survival OS and progression-free survival PFS. A total of 125 NSCLC patients were included, while 26 findings in 26 different patients were suspicious for an additional malignancy on FDG-PET/CT at staging. The most frequent anatomical site was the colon. A total of 54.2% of all additional suspicious lesions turned out to be malignant. Almost every malignant finding had an impact on patient management. No significant differences were found between NSCLC patients with suspicious findings versus no suspicious findings with regards to their survival. FDG-PET/CT performed for staging might be a valuable tool to identify additional primary tumors in NSCLC patients. Identification of additional primary tumors might have substantial implications for patient management. An early detection together with interdisciplinary patient management could prevent a worsening of survival compared to patients with NSCLC only., Peer Reviewed

(1) Background: Strong evidence supports the persuasive positive effects of exercise for cancer patients and survivors. Different approaches of exercise programs have been established; however, the special interests of young adults (YAs) with cancer have rarely been considered in exercise interventions. Therefore, the study YOUng EXercisers (YOUEX) aimed to investigate exercise preferences in YAs. (2) Methods: YOUEX was a three-arm, patient preference-based non-randomized, longitudinal, pre–post exercise intervention, offering three different exercise modules to YAs during or after acute therapy (Module 1: online supervised group-based (M1); Module 2: online unsupervised (M2); Module 3: in-person supervised (M3)). The intervention period was 12 weeks with another 12-week follow-up period, the modules could be changed or amended after 6 and 12 weeks. (3) Results: 92 YAs were allocated to the study. At baseline, 50 YAs (54%) chose M2, 32 YAs (35%) M1 and 10 YAs (11%) M3. The analysis revealed high acceptability and feasibility of the online exercise programs (M1, M2). There was a high impact of the COVID-19 pandemic on the execution of M3. YAs showed diverse preferences in module selection due to differences in, e.g., cancer therapy status or favored level of supervision. (4) Conclusions: YAs need personalized exercise programs that consider their individual interests and needs. Online exercise programs can be a promising addition to existing exercise opportunities. They are an effective way to increase physical activity levels in YAs., German Foundation of Young Adults with Cancer, Peer Reviewed

Case reports indicate that magnets in smartphones could be a source of electromagnetic interference (EMI) for active implantable medical devices (AIMD), which could lead to device malfunction, compromising patient safety. Recognizing this challenge, we implemented a high-fidelity 3D magnetic field mapping (spatial resolution 1 mm) setup using a three-axis Hall probe and teslameter, controlled by a robot (COSI Measure). With this setup, we examined the stray magnetic field of an iPhone 13 Pro, iPhone 12, and MagSafe charger to identify sources of magnetic fields for the accurate risk assessment of potential interferences with AIMDs. Our measurements revealed that the stray fields of the annular array of magnets, the wide-angle camera, and the speaker of the smartphones exceeded the 1 mT limit defined by ISO 14117:2019. Our data-driven safety recommendation is that an iPhone 13 Pro should be kept at least 25 mm away from an AIMD to protect it from unwanted EMI interactions. Our study addresses safety concerns due to potential device–device interactions between smartphones and AIMDs and will help to define data-driven safety guidelines. We encourage vendors of electronic consumer products (ECP) to provide information on the magnetic fields of their products and advocate for the inclusion of smartphones in the risk assessment of EMI with AIMDs., European Research Council (ERC), European Horizon 2020 MSCA-Innovative Training Network, Peer Reviewed

Background: As inter-limb asymmetries can be associated with higher injury risk, we aimed to investigate their role in Achilles tendinopathy patients. Methods: In Achilles tendinopathy patients (n = 41), we assessed inter-limb asymmetries of mechanical, material, and morphological musculoskeletal properties and function and how those were affected by 12 weeks of exercise intervention (high-load protocol, n = 13; Alfredson protocol, n = 11). Moreover, we assessed whether asymmetry reductions correlated with improved Patient-Reported Outcomes (VISA-A score). Results: At baseline, tendinopathic tendons demonstrated lower tendon force (p = 0.017), lower tendon stress (p < 0.0001), larger tendon cross-sectional area (CSA) (p < 0.001), and increased intratendinous (p = 0.042) and tendon overall (p = 0.021) vascularization. For the high-load group, PRE-to-POST asymmetry comparisons revealed an asymmetry increase for the counter-movement jump (CMJ) (p = 0.034) and PRE-to-POST VISA-A score improvements correlated with CSA asymmetry reductions (p = 0.024). Within the Alfredson group, PRE-to-POST VISA-A score improvements correlated with CMJ asymmetry reductions (p = 0.044) and tendon stiffness asymmetry increases (p = 0.037). POST-to-POST in-between group comparisons revealed lower asymmetry in the high-load group for tendon elongation (p = 0.021) and tendon strain (p = 0.026). Conclusions: The tendinopathic limb differs from the asymptomatic limb while therapeutic exercise interventions have little effect on asymmetries. Asymmetry reductions are not necessarily associated with tendon health improvements., Federal Institute of Sport Science (BISp) Germany, foundation Stiftung Oskar-Helene-Heim, Berlin, Germany, Peer Reviewed

Introduction: Human papillomavirus (HPV) infection is the leading cause of cervical cancer, and vaccination with HPV L1 capsid proteins has been successful in controlling it. However, vaccination coverage is not universal, particularly in developing countries, where 80% of all cervical cancer cases occur. Cost-effective vaccination could be achieved by expressing the L1 protein in plants. Various efforts have been made to produce the L1 protein in plants, including attempts to express it in chloroplasts for high-yield performance. However, manipulating chloroplast gene expression requires complex and difficult-to-control expression elements. In recent years, a family of nuclear-encoded, chloroplast-targeted RNA-binding proteins, the pentatricopeptide repeat (PPR) proteins, were described as key regulators of chloroplast gene expression. For example, PPR proteins are used by plants to stabilize and translate chloroplast mRNAs. Objectives: To demonstrate that a PPR target site can be used to drive HPV L1 expression in chloroplasts. Methods: To test our hypothesis, we used biolistic chloroplast transformation to establish tobacco lines that express two variants of the HPV L1 protein under the control of the target site of the PPR protein CHLORORESPIRATORY REDUCTION2 (CRR2). The transgenes were inserted into a dicistronic operon driven by the plastid rRNA promoter. To determine the effectiveness of the PPR target site for the expression of the HPV L1 protein in the chloroplasts, we analyzed the accumulation of the transgenic mRNA and its processing, as well as the accumulation of the L1 protein in the transgenic lines. Results: We established homoplastomic lines carrying either the HPV18 L1 protein or an HPV16B Enterotoxin::L1 fusion protein. The latter line showed severe growth retardation and pigment loss, suggesting that the fusion protein is toxic to the chloroplasts. Despite the presence of dicistronic mRNAs, we observed very little accumulation of monocistronic tr, German Research Foundation, DFG, Peer Reviewed

Antimicrobial resistance (AMR) is one of the most important global public health problems. The imprudent use of antibiotics in humans and animals has resulted in the emergence of antibiotic-resistant bacteria. The dissemination of these strains and their resistant determinants could endanger antibiotic efficacy. Therefore, there is an urgent need to identify and develop novel strategies to combat antibiotic resistance. This review provides insights into the evolution and the mechanisms of AMR. Additionally, it discusses alternative approaches that might be used to control AMR, including probiotics, prebiotics, antimicrobial peptides, small molecules, organic acids, essential oils, bacteriophage, fecal transplants, and nanoparticles., Peer Reviewed