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Abstract How nicotine acts on developing neurocircuitry in adolescence to promote later addiction vulnerability remains largely unknown, but may hold the key for informing more effective intervention efforts. We found transient nicotine exposure in early adolescent (PND 21-28) male mice was sufficient to produce a marked vulnerability to nicotine in adulthood (PND 60 + ), associated with disrupted functional connectivity in dopaminergic circuits. These mice showed persistent adolescent-like behavioral and physiological responses to nicotine, suggesting that nicotine exposure in adolescence prolongs an immature, imbalanced state in the function of these circuits. Chemogenetically resetting the balance between the underlying dopamine circuits unmasked the mature behavioral response to acute nicotine in adolescent-exposed mice. Together, our results suggest that the perseverance of a developmental imbalance between dopamine pathways may alter vulnerability profiles for later dopamine-dependent psychopathologies.

Abstract During conversation, people often endeavor to convey information in an understandable way (finding common ground) while also sharing novel or surprising information (exploring new ground). Here, we test how friends and strangers balance these two strategies to connect with each other. Using fMRI hyperscanning, we measure a preference for common ground as convergence over time and exploring new ground as divergence over time by tracking dyads’ neural and linguistic trajectories over the course of semi-structured intimacy-building conversations. In our study, 60 dyads (30 friend dyads) engaged in a real-time conversation with discrete prompts and demarcated turns. Our analyses reveal that friends diverge neurally and linguistically: their neural patterns become more dissimilar over time and they explore more diverse topics. In contrast, strangers converge: neural patterns and language become more similar over time. The more a conversation between strangers resembles the exploratory conversations of friends, the more they enjoy it. Our results highlight exploring new ground as a strategy for a successful conversation.

Thromboembolic complications are common in severe COVID-19 and are thought to result from excessive neutrophil-extracellular-trap (NET)-driven immunothrombosis. Glycosylation plays a vital role in the efficiency of immunoglobulin A (IgA) effector functions, with significant implications for NET formation in infectious diseases. This study represents the first comprehensive analysis of plasma IgA glycosylation during severe SARS-CoV-2 or Influenza A infection, revealing lower sialylation and higher galactosylation of IgA1 O-glycans in acute respiratory distress syndrome (ARDS), regardless of the underlying cause of the disease. Importantly, N-glycans displayed an infection-specific pattern, with N47 of IgA2 showing diminished sialylation and bisection, and N340/N327 of IgA1/2 demonstrating lower fucosylation and antennarity along with higher non-complex glycans in COVID-19 compared to Influenza. Notably, COVID-19 IgA possessed strong ability to induce NET formation and its glycosylation patterns correlated with extracellular DNA levels in plasma of critically ill COVID-19 patients. Our data underscores the necessity of further research on the role of IgA glycosylation in the modulation of pathogen-specific immune responses in COVID-19 and other infectious diseases.

Highly excited Rydberg states and their interactions play an important role in quantum computing and simulation. These properties can be predicted accurately for alkali atoms with simple Rydberg level structures. However, an extension of these methods to more complex atoms such as alkaline-earth atoms has not been demonstrated or experimentally validated. Here, we present multichannel quantum defect models for highly excited ^{174}Yb and ^{171}Yb Rydberg states with L≤2. The models are developed using a combination of existing literature data and new, high-precision laser and microwave spectroscopy in an atomic beam, and validated by detailed comparison with experimentally measured Stark shifts and magnetic moments. We then use these models to compute interaction potentials between two Yb atoms, and find excellent agreement with direct measurements in an optical tweezer array. From the computed interaction potential, we identify an anomalous Förster resonance that likely degraded the fidelity of previous entangling gates in ^{171}Yb using F=3/2 Rydberg states. We then identify a more suitable F=1/2 state, and achieve a state-of-the-art controlled-z gate fidelity of F=0.994(1), with the remaining error fully explained by known sources. This work establishes a solid foundation for the continued development of quantum computing, simulation, and entanglement-enhanced metrology with Yb neutral atom arrays.

In the quest for possibilities to valorize the dairy by-product acid whey, we developed a sequential process comprising filtration and magnetic separation to isolate the valuable protein lactoferrin thereof. In the first step, we clarified whey by microfiltration, followed by selective lactoferrin enrichment through ultrafiltration. This process raises the initially low lactoferrin concentration (

Head and neck squamous cell carcinoma (HNSCC) is linked to significant morbidity, adversely affecting survival and functional capacity. Post-treatment challenges such as pain, dysphonia, and dysphagia are common, prompting increased attention in survivorship research. Quality of Life (QoL) questionnaires, especially the MD Anderson Dysphagia Inventory (MDADI), are prevalent outcome measures in clinical studies but often lack parallel objective swallowing function evaluations, leading to potential outcome discrepancies. This study aimed to illuminate the relationship between subjective QoL (EQ-5D-5L and MDADI) measures and objective swallowing function (evaluated via Fiberoptic Endoscopic Evaluation of Swallowing, FEES) in patients with HNSCC. The analysis revealed a notable discordance between objective measures of swallowing function, such as the Penetration–Aspiration Scale (PAS) and residue ratings in the vallecula or piriform sinus, and patients’ subjective QoL assessments (p = 0.21). Despite the lack of correlation, swallowing-related QoL, as measured by the MDADI, was more indicative of disease severity than generic QoL assessments. Generic QoL scores did not demonstrate substantial variation between patients. In contrast, MDADI scores significantly declined with advancing tumor stage, multimodal therapy, and reliance on feeding tubes. However, the clinical significance of this finding was tempered by the less than 10-point difference in MDADI scores. The findings of this study underline the limitations of QoL measures as standalone assessments in patients with HNSCC, given their reliance on patient-perceived impairment. While subjective QoL is a crucial aspect of evaluating therapeutic success and patient-centric outcomes, it may fail to capture critical clinical details such as silent aspirations. Consequently, QoL assessments should be augmented by objective evaluations of swallowing function in clinical research and practice to ensure a holistic understanding of patient well-being and treatment impact.

Iron oxide nanoparticles (IONs) are extensively used in biomedical applications due to their unique magnetic properties. This study optimized ION synthesis via the co-precipitation method, exploring the impact of the reactant concentrations (Fe(II) and Fe(III)), NaOH concentration, temperature (30 °C–80 °C), stirring speed (0–1000 rpm), and dosing rate (10–600 s) on particle size and growth. Using small-angle X-ray scattering (SAXS), we observed, for example, that higher temperatures (e.g., 67 °C compared with 53 °C) led to a 50% increase in particle size, while the stirring speed and NaOH concentration also influenced nucleation and aggregation. These results provide comprehensive insights into optimizing synthetic conditions for targeted applications in biomedical fields, such as drug delivery and magnetic resonance imaging (MRI), where precise control over nanoparticle size and properties is crucial.

The standard way to measure the performance of existing continuous variable quantum key distribution (CVQKD) protocols is by using the achievable secret key rate (SKR) with respect to one parameter while keeping all other parameters constant. However, this atomistic method requires many individual parameter analyses while overlooking the co-dependence of other parameters. In this work, a numerical tool is developed for comparing different CVQKD protocols while taking into account the simultaneous effects of multiple CVQKD parameters on the capability of protocols to produce positive SKRs. Using the transmittance, excess noise, and modulation amplitude parameter space, regions of positive SKR are identified to compare three discrete modulated (DM) CVQKD protocols. The results show that the M-QAM protocol outperforms the M-APSK and M-PSK protocols and that there is a non-linear increase in the capability to produce positive SKRs as the number of coherent states used for a protocol increases. The tool developed is beneficial for choosing the optimum protocol in unstable channels, such as free space, where the transmittance and excess noise fluctuate, providing a more holistic assessment of a protocol’s capability to produce positive SKRs.

Urolithiasis is a medically significant crystallization process affecting the urinary tract. Kidney stones exhibit considerable diversity as they form in complex environments containing various molecules and pathogens. Understanding the formation and occurrence of kidney stones is essential for developing strategies to prevent or reduce the invasiveness of treatments. In this study, we investigated over 300 cases of urolithiasis in Styria, Austria. The composition of the stones was evaluated using infrared spectroscopy and scanning electron microscopy. Most stones were found to be heterogeneous, predominantly composed of calcium oxalate, followed by calcium phosphate. Other components such as struvite, uric acid, and cystine were present to a lesser extent and were more likely to form homogeneous crystals. Analyzing the occurrence of these different stone types provides valuable insights into the formation processes of kidney stones and can aid in the prevention of urolithiasis in the future.

N-glycosylation influences the effectiveness of immune globulin G (IgG) and thus the immunological downstream responses of immune cells. This impact arises from the presence of N-glycans within the Fc region, which not only alters the conformation of IgG but also influences its steric hindrance. Consequently, these modifications affect the interaction between IgG and its binding partners within the immune system. Moreover, this posttranslational modification vary according to the physiological condition of each individual. In this study, we examined the N-glycosylation of IgG in pigs from birth to five months of age. Our analysis identified a total of 48 distinct N-glycan structures. Remarkably, we observed defined changes in the composition of these N-glycans during postnatal development. The presence of agalactosylated and sialylated structures increases in relation to the number of N-glycans terminated by galactose residues during the first months of life. This shift may indicate a transition from passively transferred antibodies from the colostrum of the sow to the active production of endogenous IgG by the pig’s own immune system.

Iron-containing metal–organic frameworks are promising Fenton catalysts. However, the absence of additional modifiers has proven difficult due to the low reaction rates and the inability to manipulate the catalysts. We hypothesize that the production of iron oxide NPs in the presence of a metal-organic framework will increase the rate of the Fenton reaction and lead to the production of particles that can be magnetically manipulated without changing the structure of the components. A comprehensive approach lead to a metal organic framework using the example of MIL-88b (Materials of Institute Lavoisier) modified with iron oxides NPs: formulation of iron oxide in the presence of MIL-88b and vice versa. The synthesis of MIL-88b consists of preparing a complexation compound with the respective structure and addition of terephthalic acid. The synthesis of MIL-88b facilitates to control the topology of the resulting material. Both methods for composite formulation lead to the preservation of the structure of iron oxide, however, a more technologically complex approach to obtaining MIL-88b in the presence of Fe3O4 suddenly turned out to be the more efficient for the release of iron ions.

Background: The COVID-19 pandemic forced medical programs to rapidly switch to remote teaching from scratch, impacting hands-on skills training. This study compared the efficacy of a hybrid online format to a regular in-person session for a mandatory surgical skills class. Methods: Third-year undergraduate medical students attending the surgical skills class in the winter semester of 2020/21 at the Medical University of Graz were randomly assigned to either the hybrid or in-person class, depending on their course schedule and government regulations. The hybrid class involved online videos, one-on-one peer tutoring, and an Objective Structured Clinical Examination (OSCE). Pre- and post-class self-assessments were conducted to evaluate their theoretical and practical knowledge of a single interrupted suture. Results: The study included 85 students in the regular in-person class and 50 in the hybrid class. A pre-class assessment revealed higher self-assessments in the hybrid class for theoretical and practical knowledge, but a post-class assessment showed no significant difference. The advantages and disadvantages of both modalities were identified, providing valuable insights for future curriculum development. Conclusions: Both teaching modes were effective for undergraduate surgical skills training. This study recommends implementing positive aspects of both the hybrid and in-person formats while recognizing their respective limitations.

Among other bioactive molecules, milk contains high amounts of sialylated milk oligosaccharides (MOs) that influence numerous processes in the offspring. For instance, sialylated MOs inhibit the invasion of pathogens and positively influence the gut microbiome to support the optimal development of the offspring. For these reasons, sialylated MOs are also used in infant formula as well as food supplements and are potential therapeutic substances for humans and animals. Because of the high interest in sialylated bovine MOs (bMOs), we used several analytical approaches, such as gas and liquid chromatography in combination with mass spectrometry, to investigate in detail the profile of sialylated bMOs in the milk of Holstein Friesian cows during early lactation. Most of the 40 MOs identified in this study were sialylated, and a rapid decrease in all detected sialylated bMOs took place during the first day of lactation. Remarkably, we observed a high variance within the sialylation level during the first two days after calving. Therefore, our results suggest that the content of sialylated MOs might be an additional quality marker for the bioactivity of colostrum and transitional milk to ensure its optimized application for the production of milk replacer and food supplements.

Discrete-variable (DV) quantum key distribution (QKD) based on single-photon detectors and sources have been successfully deployed for long-range secure key distribution. On the other hand, continuous-variable (CV) quantum key distribution (QKD) based on coherent detectors and sources is currently lagging behind in terms of loss and noise tolerance. An important discerning factor between DV-QKD and CV-QKD is the effect of phase noise, which is known to be more relevant in CV-QKD. In this article, we investigate the effect of phase noise on DV-QKD and CV-QKD protocols, including the six-state protocol and squeezed-state protocol, in a thermal-loss channel but with the assumed availability of perfect sources and detectors. We find that in the low phase noise regime but high thermal noise regime, CV-QKD can tolerate more loss compared to DV-QKD. We also compare the secret key rate as an additional metric for the performance of QKD. Requirements for this quantity to be high vastly extend the regions at which CV-QKD performs better than DV-QKD. Our analysis addresses the questions of how phase noise affects DV-QKD and CV-QKD and why the former has historically performed better in a thermal-loss channel.

Abstract In daily life we regularly must decide whether to act dishonestly for personal gain or to be honest and maintain a positive image of ourselves. While evidence suggests that acute stress influences moral decisions, it is unclear whether stress increases or decreases immoral behavior. Here, we hypothesize that stress, through its effects on cognitive control, has different effects on moral decision making for different individuals, depending on their moral default. We test this hypothesis by combining a task which allows for inconspicuously measuring spontaneous cheating with a well-established stress induction task. Our findings confirm our hypothesis, revealing that effects of stress on dishonesty are not uniform, but instead depend on the individual: for those who are relatively dishonest, stress increases dishonesty, whereas for participants who are relatively honest stress makes them more honest. These findings go a long way in resolving the conflicting findings in the literature on the effects of stress on moral decisions, suggesting that stress affects dishonesty differently for different individuals, depending on their moral default.

How we juggle morally conflicting outcomes during learning remains unknown. Here, by comparing variants of reinforcement learning models, the authors show that participants differ substantially in their preference, with some choosing actions that benefit themselves while others choose actions that prevent harm.

Abstract In 2020, the COVID-19 pandemic impacted global life and transitioned economies and societal perceptions of life as we knew it. Professional and social life mostly ground to a nadir during the first lockdown in Europe in March. As a consequence, measures aimed at preventing the spread of the virus were established in medical facilities also and elective plastic surgery procedures were temporarily suspended in our clinic and others. A majority of the population, including those potentially contemplating plastic surgery procedures, spent most of their time at home with ample time available to research information about surgical procedures and other topics online. This investigation analyzes the relevance of plastic surgery during the pandemic on the basis of online search behavior patterns. Online traffic data from the online platform http://www.mooci.org were extracted using Google Analytics over a period of 6 months. The parameters analyzed were: pageviews, session duration, and bounce rate. Additionally, differentiation by areas of interest has been obtained. The data were compared and analyzed before and after the beginning of the first hard lockdown in Austria, Germany, and Switzerland. There were no significant differences in regard to pageviews and session duration when comparing time points before and after the beginning of the hard lockdown. The bounce rate exhibited a significant decrease after the beginning of the lockdown, implying a more conscious search for information and greater absorption and retention. There was no difference that could conclusively be attributed to the pandemic in terms of specific areas of interest researched. Society’s demand for information about plastic-surgical procedures continues to be steadily prevalent—despite, or even in particular, during a global pandemic. Providing reliable and readily available information about plastic surgery procedures is an important component of a functioning doctor–patient relationship and informed consent. This information may reflect society’s increased interest in plastic surgery during the pandemic, or be simply reflective of more spare time at hand to allow for such research. Further studies should investigate the relevance of elective procedures over the entire course of the pandemic.

Abstract Flap loss through limited perfusion remains a major complication in reconstructive surgery. Continuous monitoring of perfusion will facilitate early detection of insufficient perfusion. Remote or imaging photoplethysmography (rPPG/iPPG) as a non-contact, non-ionizing, and non-invasive monitoring technique provides objective and reproducible information on physiological parameters. The aim of this study is to establish rPPG for intra- and postoperative monitoring of flap perfusion in patients undergoing reconstruction with free fasciocutaneous flaps (FFCF). We developed a monitoring algorithm for flap perfusion, which was evaluated in 15 patients. For 14 patients, ischemia of the FFCF in the forearm and successful reperfusion of the implanted FFCF was quantified based on the local signal. One FFCF showed no perfusion after reperfusion and devitalized in the course. Intraoperative monitoring of perfusion with rPPG provides objective and reproducible results. Therefore, rPPG is a promising technology for standard flap perfusion monitoring on low costs without the need for additional monitoring devices.

Summary: Harnessing the differences between cancer and non-cancer tissues presents new opportunities for selective targeting by anti-cancer drugs. CD13, a heavily glycosylated protein, is one example with significant unmet clinical potential in cancer drug discovery. Despite its high expression and activity in cancers, CD13 is also expressed in many normal tissues. Here, we report differential tissue glycosylation of CD13 across tissues and demonstrate for the first time that the nature and pattern of glycosylation of CD13 in preclinical cancer tissues are distinct compared to normal tissues. We identify cancer-specific O-glycosylation of CD13, which selectively blocks its detection in cancer models but not in normal tissues. In addition, the metabolism activity of cancer-expressed CD13 was observed to be critically dependent on its unique glycosylation. Thus, our data demonstrate the existence of discrete cancer-specific CD13 glycoforms and propose cancer-specific CD13 glycoforms as a clinically useful target for effective cancer-targeted therapy.

This review systematically investigates the critical role of natural binding proteins (NBPs), encompassing DNA-, RNA-, carbohydrate-, fatty acid-, and chitin-binding proteins, in the realms of oncology and diagnostics. In an era where cancer continues to pose significant challenges to healthcare systems worldwide, the innovative exploration of NBPs offers a promising frontier for advancing both the diagnostic accuracy and therapeutic efficacy of cancer management strategies. This manuscript provides an in-depth examination of the unique mechanisms by which NBPs interact with specific molecular targets, highlighting their potential to revolutionize cancer diagnostics and therapy. Furthermore, it discusses the burgeoning research on aptamers, demonstrating their utility as ‘nucleic acid antibodies’ for targeted therapy and precision diagnostics. Despite the promising applications of NBPs and aptamers in enhancing early cancer detection and developing personalized treatment protocols, this review identifies a critical knowledge gap: the need for comprehensive studies to understand the diverse functionalities and therapeutic potentials of NBPs across different cancer types and diagnostic scenarios. By bridging this gap, this manuscript underscores the importance of NBPs and aptamers in paving the way for next-generation diagnostics and targeted cancer treatments.

Crystallization plays a crucial role in defining the quality and functionality of products across various industries, including pharmaceutical, food and beverage, and chemical manufacturing. The process’s efficiency and outcome are significantly influenced by solute–solvent interactions, which determine the crystalline product’s purity, size, and morphology. These attributes, in turn, impact the product’s efficacy, safety, and consumer acceptance. Traditional methods of optimizing crystallization conditions are often empirical, time-consuming, and less adaptable to complex chemical systems. This research addresses these challenges by leveraging machine learning techniques to predict and optimize solute–solvent interactions, thereby enhancing crystallization outcomes. This review provides a novel approach to understanding and controlling crystallization processes by integrating supervised, unsupervised, and reinforcement learning models. Machine learning not only improves product the quality and manufacturing efficiency but also contributes to more sustainable industrial practices by minimizing waste and energy consumption.

After setting out the background of the early history of the Church of the East, this contribution focuses on the Syriac sources of the fifth to seventh centuries which are witnesses to the development of the ‘two-nature’ Christology of the Church of the East, situated outside the Roman Empire during this formative period. Special attention is paid to the ambiguous term qnoma, which is used to render hypostasis in the Chalcedonian Definition, but which, for native Syriac authors, has the different sense of ‘defining characteristic’. The problematic designation ‘Nestorian’ should be avoided since it implies completely different things to different parties. Some final thoughts are given to the ongoing significance of the tradition of the Church of the East in its various present-day manifestations.

Abstract Numerous studies demonstrate that moment-to-moment neural variability is behaviorally relevant and beneficial for tasks and behaviors requiring cognitive flexibility. However, it remains unclear whether the positive effect of neural variability also holds for cognitive persistence. Moreover, different brain variability measures have been used in previous studies, yet comparisons between them are lacking. In the current study, we examined the association between resting-state BOLD signal variability and two metacontrol policies (i.e., persistence vs. flexibility). Brain variability was estimated from resting-state fMRI (rsfMRI) data using two different approaches (i.e., Standard Deviation (SD), and Mean Square Successive Difference (MSSD)) and metacontrol biases were assessed by three metacontrol-sensitive tasks. Results showed that brain variability measured by SD and MSSD was highly positively related. Critically, higher variability measured by MSSD in the attention network, parietal and frontal network, frontal and ACC network, parietal and motor network, and higher variability measured by SD in the parietal and motor network, parietal and frontal network were associated with reduced persistence (or greater flexibility) of metacontrol (i.e., larger Stroop effect or worse RAT performance). These results show that the beneficial effect of brain signal variability on cognitive control depends on the metacontrol states involved. Our study highlights the importance of temporal variability of rsfMRI activity in understanding the neural underpinnings of cognitive control.

The Northern Calcareous Alps in the Western Tethys realm were affected in Middle to Late Jurassic times by a mountain building process triggered by ophiolite obduction similar to that in the Inner Western Carpathians or Inner Dinarides. In contrast to these other mountain ranges, in the Northern Calcareous Alps the obducted ophiolites or ophiolite derived components in the Bathonian-Oxfordian mélanges are missing. Cr-spinels in Kimmeridgian basinal deposits are the oldest known relics of a Jurassic ophiolite obduction. This study reveals new data from a newly detected Hallstatt Mélange below the Late Jurassic Plassen Platform in the southeastern Northern Calcareous Alps (Raucherschober/Schafkogel area). Upper Triassic Hallstatt Limestone blocks from the former distal northwestern continental margin of the Neo-Tethys Ocean, as well as ophiolite and radiolarite blocks from the Neo-Tethys Ocean floor rest within an upper Middle to lower Upper Jurassic radiolaritic-argillaceous matrix. Ophiolitic blocks show calc-alkaline volcanic arc affinity, defining the rocks as the product of intra-oceanic subduction and the formation of an early arc during stacking of the oceanic crust. Resedimented ribbon radiolarite blocks deposited above the newly formed suprasubduction (SSZ) ophiolites in the Neo-Tethys Ocean east of the island arc have a Middle Jurassic age. Later, at a time of decreasing tectonic activity, the Hallstatt Mélange was sealed by the Kimmeridgian-Tithonian Plassen Carbonate Platform, showing a shallowing-upward trend.

Polysialic acid (polySia) is a carbohydrate polymer that modulates several cellular processes, such as migration, proliferation and differentiation processes. In the brain, its essential impact during postnatal development is well known. However, in most other polySia positive organs, only its localization has been described so far. For instance, in the murine epididymis, smooth muscle cells of the epididymal duct are polysialylated during the first 2 weeks of postnatal development. To understand the role of polySia during the development of the epididymis, the consequences of its loss were investigated in postnatal polySia knockout mice. As expected, no polysialylation was visible in the absence of the polysialyltransferases ST8SiaII and ST8SiaIV. Interestingly, cGMP-dependent protein kinase I (PGK1), which is essentially involved in smooth muscle cell relaxation, was not detectable in peritubular smooth muscle cells when tissue sections of polySia knockout mice were analyzed by immunohistochemistry. In contrast to this signaling molecule, the structural proteins smooth muscle actin (SMA) and calponin were expressed. As shown before, in the duct system of the testis, even the expression of these structural proteins was impaired due to the loss of polySia. We now found that the rete testis, connecting the duct system of the testis and epididymis, was extensively dilated. The obtained data suggest that less differentiated smooth muscle cells of the testis and epididymis result in disturbed contractility and thus, fluid transport within the duct system visible in the enlarged rete testis.

Prescreening of participants in clinical trials that use adeno-associated virus (AAV) vectors is required to identify naive participants, as preexisting neutralizing antibodies can limit the efficacy of AAV gene therapies. The presence of antibodies to individual AAV serotypes is typically detected by neutralization assay. To streamline the screening process, we compared an ELISA-based screening method with a neutralization assay for the detection of antibodies against AAV1, AAV8, and AAV9 in a collection of 50 rhesus macaque sera and 20 human sera. We observed a high level of concordance between the two assays (Pearson r > 0.8) for all three serotypes in both sample sets. We thus investigated pre- vs post-vector inoculation sera samples from rhesus macaques that received AAV1 or AAV8 vector inoculations for cross-reactive anti-AAV antibodies. All 12 macaques seroconverted to the vector they received, but many also reacted to the other serotypes. Our results validate an easy-to-use ELISA for reliable detection of antibodies to individual serotypes of AAV. Our results also demonstrate that an antibody response post-AAV inoculation may partially cross-react with other AAV serotypes. Overall, these results suggest that either assay can be used by academic labs for prescreening samples for preexisting anti-AAV antibodies.

Circadian medicine, the study of the effects of time on health and disease has seen an uprising in recent years as a means to enhance health and performance, and optimize treatment timing. Our endogenous time generating system -the circadian clock- regulates behavioural, physiological and cellular processes. Disruptions of the clock, via external factors like shift work or jet lag, or internal perturbations such as genetic alterations, are linked to an increased risk of various diseases like obesity, diabetes, cardiovascular diseases and cancer. By aligning an individual's circadian clock with optimal times for performing daily routines, physical and mental performance, and also the effectiveness of certain therapies can be improved. Despite the benefits of circadian medicine, the lack of non-invasive tools for characterizing the clock limits the potential of the field. TimeTeller is a non-invasive molecular/digital tool for the characterization of circadian rhythms and prediction of daily routines, including treatment timing, to unlock the potential of circadian medicine and implementing it in various settings. Given the multiple known and potentially yet unknown dependent health factors of individual circadian rhythms, the utility of this emerging biomarker is best exploited in data driven, personalized medicine use cases, using health information across lifestyle, care, and research settings.