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Background Anorexia nervosa (AN) is characterized by severe emaciation and drastic reductions of brain mass, but the underlying mechanisms remain unclear. The present study investigated the putative association between the serum-based protein markers of brain damage neurofilament light (NF-L), tau protein, and glial fibrillary acidic protein (GFAP) and cortical thinning in acute AN. Methods Blood samples and magnetic resonance imaging scans were obtained from 52 predominantly adolescent, female patients with AN before and after partial weight restoration (increase in body mass index >14%). The effect of marker levels before weight gain and change in marker levels on cortical thickness (CT) was modeled at each vertex of the cortical surface using linear mixed-effect models. To test whether the observed effects were specific to AN, follow-up analyses exploring a potential general association of marker levels with CT were conducted in a female healthy control (HC) sample (n = 147). Results In AN, higher baseline levels of NF-L, an established marker of axonal damage, were associated with lower CT in several regions, with the most prominent clusters located in bilateral temporal lobes. Tau protein and GFAP were not associated with CT. In HC, no associations between damage marker levels and CT were detected. Conclusions A speculative interpretation would be that cortical thinning in acute AN might be at least partially a result of axonal damage processes. Further studies should thus test the potential of serum NF-L to become a reliable, low-cost and minimally invasive marker of structural brain alterations in AN.

To assess changes in the prevalence of multidisciplinary cancer consultations (MDCc) over the last decade and examine patient, surgeon, hospital, and neighborhood factors associated with receipt of MDCc among individuals diagnosed with cancer.Surveillance, Epidemiology and End Results (SEER)-Medicare data from 2006 to 2016.We used time-series analysis to assess change in MDCc prevalence from 2007 to 2015. We also conducted multilevel logistic regression with random surgeon- and hospital-level effects to assess associations between patient, surgeon, neighborhood, and health care organization-level factors and receipt of MDCc during the cancer treatment planning phase, defined as the 2 months following cancer diagnosis.We identified Medicare beneficiaries65 years of age with surgically resected breast, colorectal (CRC), or non-small cell lung cancer (NSCLC) stages I-III (n = 103,250).From 2007 to 2015, the prevalence of MDCc increased from 35.0% to 61.2%. Overall, MDCc was most common among patients with breast cancer compared to CRC and NSCLC. Cancer patients who were Black, had comorbidities, had dual Medicare-Medicaid coverage, were residing in rural areas or in areas with higher Black and Hispanic neighborhood composition were significantly less likely to have received MDCc. Patients receiving surgery at disproportionate payment-sharing or rural-designated hospitals had 2% (95% CI: -3.55, 0.58) and 17.6% (95% CI: -21.45, 13.70), respectively, less probability of receiving MDCc. Surgeon- and hospital-level effects accounted for 15% of the variance in receipt of MDCc.The practice of MDCc has increased over the last decade, but significant geographical and health care organizational barriers continue to impede equitable access to and delivery of quality care across cancer patient populations. Multilevel and multicomponent interventions that target care coordination, health system, and policy changes may enhance equitable access to and receipt of MDCc.

Background The amygdala is a subcortical limbic structure consisting of histologically and functionally distinct subregions. New automated structural magnetic resonance imaging (MRI) segmentation tools facilitate the in vivo study of individual amygdala nuclei in clinical populations such as patients with anorexia nervosa (AN) who show symptoms indicative of limbic dysregulation. This study is the first to investigate amygdala nuclei volumes in AN, their relationships with leptin, a key indicator of AN-related neuroendocrine alterations, and further clinical measures. Methods T1-weighted MRI scans were subsegmented and multi-stage quality controlled using FreeSurfer. Left/right hemispheric amygdala nuclei volumes were cross-sectionally compared between females with AN (n = 168, 12–29 years) and age-matched healthy females (n = 168) applying general linear models. Associations with plasma leptin, body mass index (BMI), illness duration, and psychiatric symptoms were analyzed via robust linear regression. Results Globally, most amygdala nuclei volumes in both hemispheres were reduced in AN v. healthy control participants. Importantly, four specific nuclei (accessory basal, cortical, medial nuclei, corticoamygdaloid transition in the rostral-medial amygdala) showed greater volumetric reduction even relative to reductions of whole amygdala and total subcortical gray matter volumes, whereas basal, lateral, and paralaminar nuclei were less reduced. All rostral-medially clustered nuclei were positively associated with leptin in AN independent of BMI. Amygdala nuclei volumes were not associated with illness duration or psychiatric symptom severity in AN. Conclusions In AN, amygdala nuclei are altered to different degrees. Severe volume loss in rostral-medially clustered nuclei, collectively involved in olfactory/food-related reward processing, may represent a structural correlate of AN-related symptoms. Hypoleptinemia might be linked to rostral-medial amygdala alterations.

Oncoproteins of the MYC family drive the development of numerous human tumours

The need for high-level autonomy and robustness of autonomous systems for missions in dynamic and remote environment has pushed developers to come up with new software architectures. A common architecture style is to summarize the capabilities of the robotic system into elementary actions, called skills, on top of which a skill management layer is implemented to structure, test and control the functional layer. However, current available verification tools only provide either mission-specific verification or verification on a model that does not replicate the actual execution of the system, which makes it difficult to ensure its robustness to unexpected events. To that end, a tool, SkiNet, has been developed to transform the skill-based architecture of a system into a Petri net modeling the state-machine behaviors of the skills and the resources they handle. The Petri net allows the use of model-checking, such as Linear Temporal Logic (LTL) or Computational Tree Logic (CTL), for the user to analyze and verify the model of the system., Comment: In Proceedings FMAS2022 ASYDE2022, arXiv:2209.13181

Advances in super-resolution microscopy have demonstrated single-molecule localization precisions of a few nanometers. However, translation of such high localization precisions into sub-10-nm spatial resolution in biological samples remains challenging. Here we show that resonance energy transfer between fluorophores separated by less than 10 nm results in accelerated fluorescence blinking and consequently lower localization probabilities impeding sub-10-nm fluorescence imaging. We demonstrate that time-resolved fluorescence detection in combination with photoswitching fingerprint analysis can be used to determine the number and distance even of spatially unresolvable fluorophores in the sub-10-nm range. In combination with genetic code expansion with unnatural amino acids and bioorthogonal click labeling with small fluorophores, photoswitching fingerprint analysis can be used advantageously to reveal information about the number of fluorophores present and their distances in the sub-10-nm range in cells.

This paper introduces a conditional planning and execution system for an Earth monitoring satellite. This system builds plans containing optional acquisitions that are activated or not at execution time depending on the amount of energy actually available. One originality is that the energy activation thresholds computed on the ground take into account the capacity of the satellite to use an heliocentric pointing or switch off the payload when acquisitions are canceled. Another originality is that the conditional planner proposed uses several energy propagation models, from conservative models containing margins on power production to optimistic models that allow opportunistic acquisitions to be planned.

BACKGROUND: Transcranial magnetic stimulation (TMS) is a non-invasive neuromodulation modality that can treat depression, obsessive-compulsive disorder, or help smoking cessation. Research suggests that timing the delivery of TMS relative to an endogenous brain state may affect efficacy and short-term brain dynamics. OBJECTIVE: To investigate whether, for a multi-week daily treatment of repetitive TMS (rTMS), there is an effect on brain dynamics that depends on the timing of the TMS relative to individuals’ prefrontal EEG quasi-alpha rhythm (between 6 to 13 Hz). METHOD: We developed a novel closed-loop system that delivers personalized EEG-triggered rTMS to patients undergoing treatment for major depressive disorder. In a double blind study, patients received daily treatments of rTMS over a period of six weeks and were randomly assigned to either a synchronized or unsynchronized treatment group, where synchronization of rTMS was to their prefrontal EEG quasi-alpha rhythm. RESULTS: When rTMS is applied over the dorsal lateral prefrontal cortex (DLPFC) and synchronized to the patient’s prefrontal quasi-alpha rhythm, patients develop strong phase entrainment over a period of weeks, both over the stimulation site as well as in a subset of areas distal to the stimulation site. In addition, at the end of the course of treatment, this group’s entrainment phase shifts to be closer to the phase that optimally engages the distal target, namely the anterior cingulate cortex (ACC). These entrainment effects are not observed in the group that is given rTMS without initial EEG synchronization of each TMS train. CONCLUSIONS: The entrainment effects build over the course of days/weeks, suggesting that these effects engage neuroplastic changes which may have clinical consequences in depression or other diseases.

The angiotensin-converting enzyme 2 (ACE2) has been identified as entry receptor on cells enabling binding and infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via trimeric spike (S) proteins protruding from the viral surface1,2. It has been suggested that trimeric S proteins preferably bind to plasma membrane areas with high concentrations of preferably multimeric ACE2 receptors to achieve a higher binding and infection efficiency1,3. However, our current knowledge about the influence of ACE2 expression and organization in the plasma membrane on SARS-CoV-2 infection efficiency remains elusive. Here we useddirectstochastic optical reconstruction microscopy (dSTORM) in combination with different labeling approaches to visualize the distribution and quantify the expression of ACE2 on different cells. Our results reveal that endogenous ACE2 receptors are present as monomers in the plasma membrane with densities of only 1-2 receptors μm-2. In addition, binding of trimeric S proteins does not induce clustering of ACE2 receptors in the plasma membrane. Supported by infection studies using vesicular stomatitis virus (VSV) particles bearing S proteins our data demonstrate that a single S protein interaction per virus particle with a monomeric ACE2 receptor is sufficient for infection which attests SARS-CoV-2 a high infectivity.

Magnetic resonance spectroscopy is a powerful, non-invasive, quantitative imaging technique that allows for the measurement of brain metabolites that has demonstrated utility in diagnosing and characterizing a broad range of neurological diseases. Its impact, however, has been limited due to small sample sizes and methodological variability in addition to intrinsic limitations of the method itself such as its sensitivity to motion. The lack of standardization from a data acquisition and data processing perspective makes it difficult to pool multiple studies and/or conduct multisite studies that are necessary for supporting clinically relevant findings. Based on the experience of the ENIGMA MRS work group and a review of the literature, this manuscript provides an overview of the current state of MRS data harmonization. Key factors that need to be taken into consideration when conducting both retrospective and prospective studies are described. These include (1) MRS acquisition issues such as pulse sequence, RF and B0 calibrations, echo time, and SNR; (2) data processing issues such as pre-processing steps, modeling, and quantitation; and (3) biological factors such as voxel location, age, sex, and pathology. Various approaches to MRS data harmonization are then described including meta-analysis, mega-analysis, linear modeling, ComBat and artificial intelligence approaches. The goal is to provide both novice and experienced readers with the necessary knowledge for conducting MRS data harmonization studies.

Coordination of quality care for the growing population of cancer survivors with comorbidities remains poorly understood, especially among health disparity populations who are more likely to have comorbidities at the time of cancer diagnosis. This systematic review synthesized the literature from 2000 to 2022 on team-based care for cancer survivors with comorbidities and assessed team-based care conceptualization, teamwork processes, and outcomes. Six databases were searched for original articles on adults with cancer and comorbidity, which defined care team composition and comparison group, and assessed clinical or teamwork processes or outcomes. We identified 1,821 articles of which 13 met the inclusion criteria. Most studies occurred during active cancer treatment and nine focused on depression management. Four studies focused on Hispanic or Black cancer survivors and one recruited rural residents. The conceptualization of team-based care varied across articles. Teamwork processes were not explicitly measured, but teamwork concepts such as communication and mental models were mentioned. Despite team-based care being a cornerstone of quality cancer care, studies that simultaneously assessed care delivery and outcomes for cancer and comorbidities were largely absent. Improving care coordination will be key to addressing disparities and promoting health equity for cancer survivors with comorbidities.

We plan to investigate Myelin Water Fraction (MWF) in the acute state of Anorexia Nervosa (AN). Our study will further the understanding of structural alterations in the brain of patients acutely suffering from anorexia nervosa and possible changes in myelin content in white, cortical and intracortical gray mater areas of the brain. Recent studies suggested decreased intracortical myelin concentration (measured as quantitative T1 values) in AN (Pappaianni et al., 2022) and lower cortical myelin (measured as T1w/T2w ratio) in regions associated with cognitive control (Bischoff-Grethe et al., 2021). We will use a 3D gradient spin echo sequences (GRASE) (Prasloski et al., 2012) to measure MWF in patients acutely suffering from AN and age matched healthy controls.

ZusammenfassungBereits im Kindes- und Jugendalter gilt die motorische Leistungsfähigkeit als wichtiger Gesundheitsmarker. Auf Basis von Daten der Motorik Modul-Studie wird in diesem Artikel längsschnittlich über die Jahre 2003–2017 untersucht, inwieweit sich Sportvereinsmitglieder, die konstant im Sportverein aktiv waren, hinsichtlich ihrer motorischen Entwicklung von denjenigen unterscheiden, die nie im Sportverein aktiv waren. Es wurden Daten aus drei Messwellen untersucht: T1 (2003–2006), T2 (2009–2012) und T3 (2014–2017). Aus insgesamt N = 1092 Teilnehmenden, von denen über T1 bis T3 Daten zur Motorik vorlagen, wurden all diejenigen mit konstanter Mitgliedschaft und Nicht-Mitgliedschaft im Sportverein über drei Messwellen ausgewählt. Das sind 46 % der Gesamtstichprobe (N = 498). Von den N = 498 Teilnehmer*innen (Alter T1: 8,9 ± 3,8 Jahre, T2: 15,1 ± 3,9 Jahre, T3: 20,3 ± 4,0 Jahre) waren 15 % dauerhafte Sportvereinsmitglieder mit Wettkampfengagement, 53 % dauerhafte Sportvereinsmitglieder ohne Wettkampfengagement sowie 32 % dauerhaft Sportvereinsabstinente. Zur Ermittlung der motorischen Leistungsfähigkeit wurden konditionelle und koordinative Fähigkeiten anhand des MoMo-Testprofils erhoben (Kondition: Standweitsprung, Liegestütz, Fahrrad-Ausdauertest, Koordination: Seitliches Hin- und Herspringen, Einbeinstand, Balancieren rückwärts). Die Unterschiede in der Entwicklung wurden anhand von alters- und geschlechtsadjustierten Perzentilen mittels Varianzanalysen mit Messwiederholung berechnet, mit dem Sozialstatus als Kovariate. Innerhalb der Sportvereinsmitglieder waren Teilnehmende mit niedrigem Sozialstatus deutlich unterrepräsentiert. Insgesamt betrachtet, ist die Entwicklung der koordinativen und konditionellen Fähigkeiten bei Sportvereinsmitgliedern als signifikant besser zu beurteilen im Vergleich zu Sportvereinsabstinenten (Modell Koordination * Sportverein: df = 3,870 | F = 2,931 | p = 0,021 | ETA = 0,015 | f = 0,123; Modell Kondition * Sportverein: df = 4 | F = 3,794 | p = 0,005 | ETA = 0,048 | f = 0,225). Die Ergebnisse untermauern die Wichtigkeit der Sportvereine für die motorische Entwicklung von Kindern, Jugendlichen und jungen Erwachsenen in Deutschland.

PURPOSE: Sixty percent of adults have multiple chronic conditions at cancer diagnosis. These patients may require a multidisciplinary clinical team-of-teams, or a multiteam system (MTS), of high-complexity involving multiple specialists and primary care, who, ideally, coordinate clinical responsibilities, share information, and align clinical decisions to ensure comprehensive care needs are managed. However, insights examining MTS composition and complexity among individuals with cancer and comorbidities at diagnosis using US population-level data are limited. METHODS: Using SEER-Medicare data (2006-2016), we identified newly diagnosed patients with breast, colorectal, or lung cancer who had a codiagnosis of cardiopulmonary disease and/or diabetes (n = 75,201). Zaccaro's theory-based classification of MTSs was used to categorize clinical MTS complexity in the 4 months following cancer diagnosis: high-complexity (≥ 4 clinicians from ≥ 2 specialties) and low-complexity (1-3 clinicians from 1-2 specialties). We describe the proportions of patients with different MTS compositions and quantify the incidence of high-complexity MTS care by patient groups. RESULTS: The most common MTS composition was oncology with primary care (37%). Half (50.3%) received high-complexity MTS care. The incidence of high-complexity MTS care for non-Hispanic Black and Hispanic patients with cancer was 6.7% (95% CI, −8.0 to −5.3) and 4.7% (95% CI, −6.3 to −3.0) lower than non-Hispanic White patients with cancer; 13.1% (95% CI, −14.1 to −12.2) lower for rural residents compared with urban; 10.4% (95% CI, −11.2 to −9.5) lower for dual Medicaid-Medicare beneficiaries compared with Medicare-only; and 16.6% (95% CI, −17.5 to −15.8) lower for colorectal compared with breast cancer. CONCLUSION: Incidence differences of high-complexity MTS care were observed among cancer patients with multiple chronic conditions from underserved populations. The results highlight the need to further understand the effects of and mechanisms through which care team composition, complexity, and functioning affect care quality and outcomes.

Summary Single-molecule localization microscopy has become an important part of the super-resolution microscopy toolbox in biomedical research. Software platforms for applying analytical methods to the point-based data structures are needed that offer both routine application and flexible customization of analysis procedures. We present a python library called LOCAN that consists of well-defined data structures and analysis methods for analyzing localization data in a script or computable notebook. Availability and implementation The package source code is released open-source under a BSD-3 license at https://github.com/super-resolution/Locan. It can be installed from the Python Package Index at https://pypi.org/project/locan. Documentation is available at https://locan.readthedocs.io.

B cells have the unique property to somatically alter their immunoglobulin (IG) genes by V(D)J recombination, somatic hypermutation (SHM) and class-switch recombination (CSR). Aberrant targeting of these mechanisms is implicated in lymphomagenesis, but the mutational processes are poorly understood. By performing whole genome and transcriptome sequencing of 181 germinal center derived B-cell lymphomas (gcBCL) we identified distinct mutational signatures linked to SHM and CSR. We show that not only SHM, but presumably also CSR causes off-target mutations in non-IG genes. Kataegis clusters with high mutational density mainly affected early replicating regions and were enriched for SHM- and CSR-mediated off-target mutations. Moreover, they often co-occurred in loci physically interacting in the nucleus, suggesting that mutation hotspots promote increased mutation targeting of spatially co-localized loci (termed hypermutation by proxy). Only around 1% of somatic small variants were in protein coding sequences, but in about half of the driver genes, a contribution of B-cell specific mutational processes to their mutations was found. The B-cell-specific mutational processes contribute to both lymphoma initiation and intratumoral heterogeneity. Overall, we demonstrate that mutational processes involved in the development of gcBCL are more complex than previously appreciated, and that B cell-specific mutational processes contribute via diverse mechanisms to lymphomagenesis. This study has been supported by the German Ministry of Science and Education (BMBF) in the framework of the ICGC MMML-Seq project (01KU1002A-J) the MMML-MYC-SYS project (036166B) and the project ICGC DE-MINING (01KU1505E), the European Union in the framework of the BLUEPRINT Project (HEALTH-F5-2011-282510) and the KinderKrebsInitiative Buchholz/Holm-Seppensen. This work was supported by the BMBF-funded Heidelberg Center for Human Bioinformatics (HD-HuB) within the German Network for Bioinformatics Infrastructure (de.NBI) (#031A537A, #031A537C). Former grant support of MMML by the Deutsche Krebshilfe (2003–2011) is gratefully acknowledged. We acknowledge COSMIC and use of Cancer Gene Census. Part of the work was performed in association with SFB1074 (particularly subproject B1) funded by DFG. We wish to thank Barbara Hutter, Ivo Buchhalter, Zuguang Gu, and Natalie Jäger for skillful technical assistance. We thank the High-Throughput Sequencing Unit of the Genome and Proteome Core Facility and the Omics IT and Data Management Core Facility of the German Cancer Research Center (DKFZ, Heidelberg) as well as the Institute of Clinical Molecular Biology (IKMB, Christian-Albrechts-University Kiel) for excellent technical support and expertise. DH is a member of the Hartmut Hoffmann-Berling International Graduate School of Molecular and Cellular Biology (HBIGS) and of the MD/PhD-program of the University of Heidelberg. KK and UHT are funded by the Helmholtz International Graduate School for Cancer Research at the German Cancer Research Center. SHB, HK, and SH acknowledge support by LIFE (Leipzig Research Center for Civilization Diseases), Leipzig University. LIFE is funded by the European Union, the European Regional Development Fund (ERDF), the European Social Fund (ESF), and the Free State of Saxony. This work has been carried out with the help of the Interdisciplinary Bank of Biomaterials and Data of the University Hospital of Würzburg and the Julius Maximilian University of Würzburg (idbw). Peer Reviewed "Article signat per 70 autors/es:Daniel Hübschmann, Kortine Kleinheinz, Rabea Wagener, Stephan H. Bernhart, Cristina López, Umut H. Toprak, Stephanie Sungalee, Naveed Ishaque, Helene Kretzmer, Markus Kreuz, Sebastian M. Waszak, Nagarajan Paramasivam, Ole Ammerpohl, Sietse M. Aukema, Renée Beekman, Anke K. Bergmann, Matthias Bieg, Hans Binder, Arndt Borkhardt, Christoph Borst, Benedikt Brors, Philipp Bruns, Enrique Carrillo de Santa Pau, Alexander Claviez, Gero Doose, Andrea Haake, Dennis Karsch, Siegfried Haas, Martin-Leo Hansmann, Jessica I. Hoell, Volker Hovestadt, Bingding Huang, Michael Hummel, Christina Jäger-Schmidt, Jules N. A. Kerssemakers, Jan O. Korbel, Dieter Kube, Chris Lawerenz, Dido Lenze, Joost H. A. Martens, German Ott, Bernhard Radlwimmer, Eva Reisinger, Julia Richter, Daniel Rico, Philip Rosenstiel, Andreas Rosenwald, Markus Schillhabel, Stephan Stilgenbauer, Peter F. Stadler, José I. Martín-Subero, Monika Szczepanowski, Gregor Warsow, Marc A. Weniger, Marc Zapatka, Alfonso Valencia, Hendrik G. Stunnenberg, Peter Lichter, Peter Möller, Markus Loeffler, Roland Eils, Wolfram Klapper, Steve Hoffmann, Lorenz Trümper, ICGC MMML-Seq consortium, ICGC DE-Mining consortium, BLUEPRINT consortium, Ralf Küppers, Matthias Schlesner & Reiner Siebert"

178 Background: Care coordination represents deliberate efforts to harmonize and organize patient care activities. This study examined sociodemographic and clinical predictors of patient-reported care coordination among Medicare beneficiaries older than 65 with a history of cancer. Methods: This study utilized the Surveillance, Epidemiology, and End Results-Consumer Assessment of Healthcare Providers and Systems (SEER-CAHPS) linked data, including SEER cancer registry data, Medicare CAHPS patient experience surveys, and Medicare claims. We identified Medicare beneficiaries who completed a CAHPS survey within ten years after their most recent cancer diagnosis and reported visiting a personal doctor within six months before their survey (n = 14,646). Multivariable regression models examined associations between cancer survivor characteristics and care coordination, with higher scores indicating better coordination (scale of 0-100). Results: Residing in a rural area at time of diagnosis (1.2-points greater score than urban; p= 0.04) and reporting > 4 visits with a personal doctor within 6 months (3.0-points greater than 1-2 visits; p< 0.001) were significantly associated with higher care coordination scores. Older age ( p< 0.001) and seeing more specialists ( p= 0.006) were associated with significantly lower care coordination scores. Patients with melanoma (women: 5.2-point difference, p< 0.001; men: 2.8 points, p= 0.01) and breast cancer (women: 2.4 points; p< 0.001) also reported significantly lower care coordination scores than did men with prostate cancer (reference group). Conclusions: Adult cancer survivors who are older, have a history of breast, lung, or melanoma cancers, or see more specialists report worse care coordination. Future research should explore and address the multilevel influences that lead to worse care coordination for older adult cancer survivors.

The microphytobenthos (MPB) is a microbial community of primary producers playing a key role in coastal ecosystem functioning. The intertidal mudflats are subject to challenging variations of irradiance, forcing the micro-organisms to develop photoprotective mechanisms. Two major adaptations to light are well described in literature: the excess of light energy dissipation through non-photochemical quenching (NPQ), and the vertical migration in the sediment. These mechanisms trigger a lot of scientific interest, but the biological processes and metabolic mechanisms involved in light-driven vertical migration remain largely unknown. To our knowledge, this study investigates for the first time metabolomic responses of a migrational mudflat biofilm exposed for 30 min to a light gradient of photosynthetically active radiation (PAR) from 50 to 1000 µmol photons m− 2 s− 1. The untargeted metabolomic analysis allowed to identify metabolites involved in two types of responses to light exposures. On the one hand, the production of FAs from bacterial origin corresponding to good photosynthesis state of MPB under low light (LL) and medium light (ML). On the other hand, alka(e)nes and a fatty alcohol were produced under light-induced stress triggered by high light (HL). The physiological and ecological roles of these compounds are poorly described in literature. This study showed that they seem to play important unexplored roles in light-induced stress adaptation of migrational MPB biofilms. Since alka(e)nes are produced from FAs decarboxylation, these results thus emphasize for the first time the importance of FAs pathways in microphytobenthic biofilms adaptation to light.

ELOM-080 is a phytomedicine approved for the treatment of acute and chronic inflammatory diseases of the respiratory tract, sinusitis, and bronchitis in particular. This prospective, randomized, placebo-controlled, double-blind clinical trial was conducted to assess efficacy and safety of ELOM-080 in the treatment of acute viral rhinosinusitis (AVRS).Patients with AVRS received oral treatment (4 × 1 capsule per day) with either ELOM-080 or matching placebo. Primary endpoints were the change in major symptom score (MSS) after 7 and 14 days of treatment assessed by the investigator (MSSFour hundred and sixty-three patients were randomized. At day 4, subjective burden of disease (MSS) was significantly ameliorated compared to placebo (p = 0.012). During the first treatment week MSS scores improved about 1 day earlier, and 3 days earlier in the second week. Effect with ELOM-080 on mean MSSELOM-080 improves the burden of AVRS significantly in comparison to placebo, remission of symptoms occurred 3 days earlier. The results confirm the efficacy and safety of ELOM-080 for treatment of AVRS.1 Laryngoscope, 2022.

PURPOSE: Diabetes and hypertension are two common comorbidities that affect breast cancer patients, particularly Black women. Disruption of chronic disease management during cancer treatment has been speculated. Therefore, this study examined the implementation of clinical practice guidelines and health outcomes for these comorbidities before and during cancer treatment. METHODS: We used a population-based, prospective cohort of Black women diagnosed with breast cancer (2012–2016) in New Jersey (N=563). Chronic disease management for diabetes and hypertension were examined 12-months before and after breast cancer diagnosis and compared using McNemar’s test for matched paired and paired t-tests. RESULTS: Among this cohort, 18.1% had a co-diagnosis of diabetes and 47.2% had a co-diagnosis of hypertension. Implementation of clinical practice guidelines and health outcomes that differed in the 12-months before and after cancer diagnosis included: lipid screening (64.5% before versus 50.0% after diagnosis; p=0.004), glucose screening (72.7% versus 90.7%; p

BACKGROUND: Black women are more likely to have comorbidity at breast cancer diagnosis compared with White women, which may account for half of the Black-White survivor disparity. Comprehensive disease management requires a coordinated team of healthcare professionals including primary care practitioners, but few studies have examined shared care in the management of comorbidities during cancer care, especially among racial/ethnic minorities. OBJECTIVE: To examine whether the type of medical team composition is associated with optimal clinical care management of comorbidities. DESIGN: We used the Women’s Circle of Health Follow-up Study, a population-based cohort of Black women diagnosed with breast cancer. The likelihood of receiving optimal comorbidity management after breast cancer diagnosis was compared by type of medical team composition (shared care versus cancer specialists only) using binomial regression. PARTICIPANTS: Black women with a co-diagnosis of diabetes and/or hypertension at breast cancer diagnosis between 2012 and 2016 (N = 274). MAIN MEASURES: Outcome—optimal clinical care management of diabetes (i.e., A1C test, LDL-C test, and medical attention for nephropathy) and hypertension (i.e., lipid screening and prescription for hypertension medication). Main predictor—shared care, whether the patient received care from both a cancer specialist and a primary care provider and/or a medical specialist within the 12 months following a breast cancer diagnosis. KEY RESULTS: Primary care providers were the main providers involved in managing comorbidities and 90% of patients received shared care during breast cancer care. Only 54% had optimal comorbidity management. Patients with shared care were five times (aRR: 4.62; 95% CI: 1.66, 12.84) more likely to have optimal comorbidity management compared with patients who only saw cancer specialists. CONCLUSIONS: Suboptimal management of comorbidities during breast cancer care exists for Black women. However, our findings suggest that shared care is more beneficial at achieving optimal clinical care management for diabetes and hypertension than cancer specialists alone.

Practice-based guidelines recommend HIV testing during initial invasive cervical cancer (ICC) workup. Determinants of HIV testing during diagnosis of AIDS-defining cancers in vulnerable populations, where risk for HIV infection is higher, are under-explored. We examine factors associated with patterns of HIV testing among Medicaid enrollees diagnosed with ICC. Using linked data from the New Jersey State Cancer Registry and New Jersey Medicaid claims and enrollment files, we evaluated HIV testing among 242 ICC cases diagnosed from 2012 to 2014 in ages 21–64 at (a) any point during Medicaid enrollment (2011–2014) and (b) during cancer workup 6 months pre ICC diagnosis to 6 months post ICC diagnosis. Logistic regression models identified factors associated with HIV testing. Overall, 13% of women had a claim for HIV testing during ICC workup. Two-thirds (68%) of women did not have a claim for HIV testing (non-receipt of HIV testing) while enrolled in Medicaid. Hispanic/NH-API/Other women had lower odds of non-receipt of HIV testing compared with NH-Whites (OR: 0.40; 95% CI: 0.17–0.94). Higher odds of non-receipt of HIV testing were observed among cases with no STI testing (OR: 4.92; 95% CI 2.27–10.67) and

Physical fitness is an important health resource. From 2003 onwards, the MoMo study, a part of the German Health Interview and Examination Survey for Children and Adolescents (KiGGS), has investigated physical fitness on the basis of nationally representative data. The objective of this paper was to analyse trends in physical fitness of three cohorts at the ages of 4-17 years. Changes within 10 test items of the MoMo-test profile are reported. The mean values of physical fitness and the relevant influencing factors were directly compared across cohorts (in the total group and in age-and sex-subgroups). Statistical significance of differences was examined by calculating the confidence intervals (95% CI) for complex samples; effect sizes were determined using Cohen's d. The results indicated that physical fitness levels of German children and adolescents initially slightly increased between MoMo baseline (2003-2006) and wave 1 (2009-2012). This could partly be attributed to increased physical activity in sports clubs and in extracurricular sports at school. Then, between MoMo wave 1 and MoMo wave 2 (2014-2017) the physical fitness of children and adolescents in Germany remained the same, as did all influencing factors with the exception of extracurricular sport. From a public health perspective, programmes and measures that can increase the chances for all children and adolescents to strive for greater physical fitness should be of the highest priority.

Background Axonal degeneration and defects in neuromuscular neurotransmission represent a pathological hallmark in spinal muscular atrophy (SMA) and other forms of motoneuron disease. These pathological changes do not only base on altered axonal and presynaptic architecture, but also on alterations in dynamic movements of organelles and subcellular structures that are not necessarily reflected by static histopathological changes. The dynamic interplay between the axonal endoplasmic reticulum (ER) and ribosomes is essential for stimulus-induced local translation in motor axons and presynaptic terminals. However, it remains enigmatic whether the ER and ribosome crosstalk is impaired in the presynaptic compartment of motoneurons with Smn (survival of motor neuron) deficiency that could contribute to axonopathy and presynaptic dysfunction in SMA. Methods Using super-resolution microscopy, proximity ligation assay (PLA) and live imaging of cultured motoneurons from a mouse model of SMA, we investigated the dynamics of the axonal ER and ribosome distribution and activation. Results We observed that the dynamic remodeling of ER was impaired in axon terminals of Smn-deficient motoneurons. In addition, in axon terminals of Smn-deficient motoneurons, ribosomes failed to respond to the brain-derived neurotrophic factor stimulation, and did not undergo rapid association with the axonal ER in response to extracellular stimuli. Conclusions These findings implicate impaired dynamic interplay between the ribosomes and ER in axon terminals of motoneurons as a contributor to the pathophysiology of SMA and possibly also other motoneuron diseases.

Motivation Single-molecule localization microscopy resolves individual fluorophores or fluorescence-labeled biomolecules. Data are provided as a set of localizations that distribute normally around the true fluorophore position with a variance determined by the localization precision. Characterizing the spatial fluorophore distribution to differentiate between resolution-limited localization clusters, which resemble individual biomolecules, and extended structures, which represent aggregated molecular complexes, is a common challenge. Results We demonstrate the use of the convex hull and related hull properties of localization clusters for diagnostic purposes, as a parameter for cluster selection or as a tool to determine localization precision. Availability and implementation https://github.com/super-resolution/Ebert-et-al-2022-supplement. Supplementary information Supplementary data are available at Bioinformatics online.

Advances in therapy 39(6), 3011-3018 (2022). doi:10.1007/s12325-022-02135-z, Published by Springer Healthcare Communications, Tarporley

BACKGROUNDThe communication through coherence model posits that brain rhythms are synchronized across different frequency bands and that effective connectivity strength between interacting regions depends on their phase relation. Evidence to support the model comes mostly from electrophysiological recordings in animals while evidence from human data is limited.METHODSHere, an fMRI-EEG-TMS (fET) instrument capable of acquiring simultaneous fMRI and EEG during noninvasive single pulse TMS applied to dorsolateral prefrontal cortex (DLPFC) was used to test whether prefrontal EEG alpha phase moderates TMS-evoked top-down influences on subgenual, rostral and dorsal anterior cingulate cortex (ACC). Results in healthy volunteers (n=11) were compared to those from patients with major depressive disorder (MDD) (n=17) collected as part of a ongoing clinical trial investigation.RESULTSIn both groups, TMS-evoked functional connectivity between DLPFC and subgenual ACC (sgACC) depended on the EEG alpha phase. TMS-evoked DLPFC to sgACC effective connectivity (EC) was moderated by EEG alpha phase in healthy volunteers, but not in the MDD patients. Top-down EC was inhibitory for TMS onsets during the upward slope of the alpha wave relative to TMS timed to the downward slope of the alpha wave. Prefrontal EEG alpha phase dependent effects on TMS-evoked fMRI BOLD activation of the rostral anterior cingulate cortex were detected in the MDD patient group, but not in the healthy volunteer group.DISCUSSIONResults demonstrate that TMS-evoked top-down influences vary as a function of the prefrontal alpha rhythm, and suggest clinical applications whereby TMS is synchronized to the brain’s internal rhythms in order to more efficiently engage deep therapeutic targets.

Advances in superresolution microscopy demonstrated single-molecule localization precisions of a few nanometers. However, translation of such high localization precisions into sub-10 nm spatial resolution in biological samples remains challenging. Here, we show that resonance energy transfer between fluorophores separated by less than 10 nm results in accelerated fluorescence blinking and consequently lower localization probabilities impeding sub-10 nm fluorescence imaging. We demonstrate that time-resolved fluorescence detection in combination with photoswitching fingerprint analysis can be used advantageously to determine the number and distance even of spatially unresolvable fluorophores in the sub-10 nm range. In combination with genetic code expansion (GCE) with unnatural amino acids and bioorthogonal click-labeling with small fluorophores photoswitching fingerprint analysis enables sub-10 nm resolution fluorescence imaging in cells.

This study examined the development of muscular fitness and coordination in children and adolescents with and without attention deficit hyperactivity disorder (ADHD) over a period of 11 years. Data was collected in three measurement waves as part of the longitudinal, representative Motorik-Modul (MoMo) study in Germany (2003–2006, 2009–2012, 2014–2017). The overall sample comprised 2988 participants (253 with ADHD, 65% males; 2735 non-ADHD, 47% males; mean age 9 years). Structural equation modeling was conducted, and the estimated models had a good fit. No differences in muscular fitness were observed between participants with and without ADHD. Participants with ADHD had a lower coordinative performance at first measurement than those without ADHD. The difference in coordinative performance persisted throughout the study period.

Casey J. Dawkins: Just Housing - The Moral Foundations of American Housing Policy. Cambridge, MA: MIT Press 2021. 9780262543071

Additional file 1. Methods: Protocol of instillations and antibiotic treatment. Table S1: Baseline patient characteristics (n = 50/51 per group). Table S2: Prevalence of bacterial pathogens in confirmed UTIs. Figure S1: Number of rUTI-induced visits to the urologist 12 months before and after treatment. Shown are mean values for number of visits per group; CS (n = 50, black bars), LDLTABCS (n = 50, grey bars); ** p = 0.009; *** p < 0.00001.

International audience; Software architectures for autonomous systems are generally structured with 3 layers: a decisional layer managing autonomous reasoning, a functional layer managing reactive tasks and processing, and an executive layer bridging the gap between both. The executive layer plays a central role, as it links high-level tasks with lowlevel processing, and is generally responsible for the robustness or the fault-tolerance of the overall system. In this paper, we propose a development process for such an executive layer that emphasizes on the dependability of this layer. To do so, we structure the executive layer using skills, that are formally defined using a specific language, and we then provide some tools to verify these models, generate some code, and a methodology to assess the fault-tolerance of the resulting architecture.; Les architectures logicielles pour les systèmes autonomes sont généralement structurées en 3 couches : une couche décisionnelle qui gère le raisonnement autonome, une couche fonctionnelle qui gère les tâches réactives et le fonctionnement, et une couche d'exécution qui fait le lien entre les deux. Cette dernière joue un rôle central, car elle relie les tâches de haut niveau aux traitements de bas niveau, et est généralement responsable de la robustesse ou de la tolérance aux pannes du système global.Dans cet article, nous proposons un processus de développement pour une couche d'exécution qui met l'accent sur la fiabilité de celle-ci. Pour ce faire, nous structurons la couche d'exécution en utilisant des "skills", qui sont formellement définis à l'aide d'un langage dédié, et nous fournissons ensuite des outils pour vérifier ces modèles, générer du code, et une méthodologie pour évaluer la tolérance aux pannes de l'architecture résultante.