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BackgroundThere remains significant uncertainty in the definition of the long COVID disease, its expected clinical course, and its impact on daily functioning. Social media platforms can generate valuable insights into patient-reported health outcomes as the content is produced at high resolution by patients and caregivers, representing experiences that may be unavailable to most clinicians.ObjectiveWe aim to determine the validity and effectiveness of advanced NLP approaches built to derive insight into Long COVID-related patient-reported health outcomes from social media platforms.MethodologyWe use Transformer-based BERT models to extract and normalize long COVID Symptoms and Conditions (SyCo) from English posts on Twitter and Reddit. Furthermore, we estimate the occurrence and co-occurrence of SyCo terms at any point or across time and locations. Finally, we compare the extracted health outcomes with human annotations and highly utilized clinical outcomes grounded in the medical literature.ResultBased on our findings, the top three most commonly occurring groups of long COVID symptoms are systemic (such as “fatigue”), neuropsychiatric (such as “anxiety” and “brain fog”), and respiratory (such as “shortness of breath”). Regarding the co-occurring symptoms, the pair of ‘fatigue & headaches’ is most common. In addition, we show that other conditions, such as infection, hair loss, and weight loss, as well as mentions of other diseases, such as flu, cancer, or Lyme disease, are among the top reported terms by social media users.ConclusionThe outcome of our social media-derived pipeline is comparable with the outcomes of peer-reviewed articles relevant to long COVID symptoms. Overall, this study provides unique insights into patient-reported health outcomes from long COVID and valuable information about the patient’s journey that can help healthcare providers anticipate future needs.

Genomic medicine holds great promise for improving health care, but integrating searchable and actionable genetic data into electronic health records (EHRs) remains a challenge. Here we describe Neptune, a system for managing the interaction between a clinical laboratory and an EHR system during the clinical reporting process. We developed Neptune and applied it to two clinical sequencing projects that required report customization, variant reanalysis, and EHR integration. Neptune has been applied for the generation and delivery of over 15,000 clinical genomic reports. This work spans two clinical tests based on targeted gene panels that contain 68 and 153 genes respectively. These projects demanded customizable clinical reports that contained a variety of genetic data types including single-nucleotide variants (SNVs), copy-number variants (CNVs), pharmacogenomics, and polygenic risk scores. Two variant reanalysis activities were also supported, highlighting this important workflow. Methods are needed for delivering structured genetic data to EHRs. This need extends beyond developing data formats to providing infrastructure that manages the reporting process itself. Neptune was successfully applied on two high-throughput clinical sequencing projects to build and deliver clinical reports to EHR systems. The software is open source and available at https://gitlab.com/bcm-hgsc/neptune .

The current study assesses prevalence rates, circumstances and consequences of sexual abuse in childhood and adolescence.A random sample from an urban population (18-69 years) was surveyed by postal or online questionnaire. Instruments included WHO-5 well-being index, knowledge on support services for children and adolescents experiencing sexual abuse, incidents and consequences of sexual abuse.159 persons returned the questionnaire (17.3%). 18.2% experienced sexual abuse. Of these, 34.5% disclosed sexual abuse for the first time. Psychological well-being was significantly lower in sexually abused persons. There was a lack of knowledge regarding support services for sexually abused ones.The present design is applicable in the context of a nationwide representative survey on childhood sexual abuse and provides insights into the field of concealed sexual abuse.ZIEL DER STUDIE: war die Erfassung des Ausmaßes sexualisierter Gewalt gegen Kinder und Jugendliche, der unterschiedlichen Tatkontexte und Folgen sexualisierter Gewalt.Es wurde eine Zufallsstichprobe aus einer städtischen Bevölkerung (18–69 Jahre) erhoben, die zum aktuellen Wohlbefinden, zu Hilfsangeboten für Kinder und Jugendliche bei sexualisierter Gewalt und zu Erfahrungen mit sexualisierter Gewalt im Kindes- und Jugendalter mittels einer Hybridumfrage befragt wurden.Der Rücklauf betrug n=159 (17,3%). Es gaben 18,2% an, mindestens einmal in der Kindheit oder Jugend Opfer sexualisierter Gewalt geworden zu sein. Davon berichteten 34,5% zum ersten Mal von diesen Ereignissen. Das psychische Wohlbefinden war in der Gruppe der von sexualisierter Gewalt Betroffenen signifikant geringer. Die Kenntnis zu Hilfsangeboten war bei allen Teilnehmenden eher gering.Die gewählte Methode ließe sich im Rahmen einer bundesweiten repräsentativen Befragung anwenden, um Einblicke in das Dunkelfeld der sexualisierten Gewalt zu geben.

Subseasonal forecasts of opportunity (SFOs) for precipitation over southwest Asia during January–March at lead times of 3–6 weeks are identified using elevated expected forecast skill from a linear inverse model (LIM), an empirical dynamical model that uses statistical relationships to infer the predictable dynamics of a system. The expected forecast skill from this LIM, which is based on the atmospheric circulation, tropical outgoing longwave radiation, and sea surface temperatures, captures the predictability associated with many relevant signals as opposed to just one. Two modes of variability, El Niño–Southern Oscillation (ENSO) and the Madden–Julian Oscillation (MJO), which themselves are predictable because of their slow variations, are related to southwest Asia precipitation SFOs. Strong El Niño events, as observed in 1983, 1998, and 2016, significantly increase the likelihood by up to 3-fold of an SFO 3–4 and 5–6 weeks in advance. Strong La Niña events, as observed in 1989, 1999, 2000, also significantly increase the likelihood of an SFO at those same lead times. High-amplitude MJO events in phases 2–4 and 6–8 of greater than one standardized departure also significantly increase the likelihood of an SFO 3–4 weeks in advance. Predictable atmospheric circulation patterns preceding anomalously wet periods indicate a role for enhanced tropical convection in the South Pacific convergence zone (SPCZ) region, while suppressed convection is observed preceding predictable dry periods. Anomalous heating in this region is found to distinguish wet and dry periods during both El Niño and La Niña conditions, although the atmospheric circulation response to the heating differs between each ENSO phase.

Intense drought has occurred in the United States Southwest this century, causing unprecedented stress to water resources. Here we use paleoclimate and instrumental records to establish that the recent temperature rise is incompatible with random draws from past fluctuations, including the current period of warming. Consistent with and extending previous reconstructions, we find that the ongoing drought is the most intense at the 21-year scale back to 600 CE. Evaluation using standardized regression coefficients shows that recent warming damps the effect of moisture delivery on the Standardized Precipitation-Evaporation Index by approximately one-third. The probability of full recovery of the current moisture deficit is unlikely even by mid-century and about five percent in 10-15 years. Evaluation of future climate simulations indicates increasing regional temperature stress and soil moisture depletion, and coupled with long recovery periods for moisture delivery, very low chance for regional mega-reservoirs to regain full-capacity levels assuming current demand.

Persistence of malignant clones is a major determinant of adverse outcome in patients with hematologic malignancies. Despite the fact that the majority of patients with acute myeloid leukemia (AML) achieve complete remission after chemotherapy, a large proportion of them relapse as a result of residual malignant cells. These persistent clones have a competitive advantage and can re-establish disease. Therefore, targeting strategies that specifically diminish cell competition of malignant cells while leaving normal cells unaffected are clearly warranted. Recently, our group identified YBX1 as a mediator of disease persistence in JAK2-mutated myeloproliferative neoplasms. The role of YBX1 in AML, however, remained so far elusive. Here, inactivation of YBX1 confirms its role as an essential driver of leukemia development and maintenance. We identify its ability to amplify the translation of oncogenic transcripts, including MYC, by recruitment to polysomal chains. Genetic inactivation of YBX1 disrupts this regulatory circuit and displaces oncogenic drivers from polysomes, with subsequent depletion of protein levels. As a consequence, leukemia cells show reduced proliferation and are out-competed in vitro and in vivo, while normal cells remain largely unaffected. Collectively, these data establish YBX1 as a specific dependency and therapeutic target in AML that is essential for oncogenic protein expression.

The Genetic Counselor SARS‐CoV‐2 Impact Survey (GCSIS) describes the impact of the pandemic on genetic counselors and genetic counseling services. With this information, the National Society of Genetic Counselors (NSGC) can better: (1) support advocacy and access efforts for genetic counseling services at both federal‐ and state‐level; (2) promote effective billing and reimbursement for genetic counseling services provided via telemedicine; and (3) make decisions about how to best support genetic counselors. The survey was hosted on a novel data collection and analysis platform from LunaDNA and was open to all genetic counselors (n = 5,531 based on professional society membership). Survey response rate was approximately 3.8% (n = 212/5,531), with a demographic distribution broadly representative of the North American genetic counseling field. Genetic counselors remained largely employed, providing genetic counseling services throughout the pandemic, although almost one in five respondents (17%, n = 35/211) reported experiencing some degree of pandemic‐related financial hardship. Nearly all respondents (90%, n = 104/115) transitioned, at least in part, to remote work settings, with about half (47%. n = 88/189) reporting restrictions in the care they were able to provide. These shifts came at a cost: existing gaps in Medicare status for genetic counselors and attendant reimbursement concerns led to uncertainty about whether genetic counselors' work will be reimbursed. Outside of work, caregiving responsibilities increased for 34% (n = 74/212) of respondents. The results of the GCSIS amplify the importance of federal‐ and state‐level advocacy efforts for genetic counselors and their employers. They also highlight the impact of broader cultural intransigence on our majority‐female profession. During the pandemic, genetic counselors continued to provide care, but without consistent financial support or expectation of reimbursement. The ability to attract and retain talented professionals to the genetic counseling field will hinge on the success of continued advocacy efforts.

Zinn ist der Top-Favorit für den Ersatz von giftigem Blei in Perowskit-Solarzellen. Allerdings kommt es dabei verstärkt zu der unerwünschten Oxidation von SnII zu SnIV. Die herkömmlichen Verfahren verwenden SnF2 in der Perowskit-Vorläuferlösung, um die Bildung von SnIV zu verhindern. Dennoch bleibt der Wirkmechanismus des Additivs unklar. Um diesen eingehender zu erläutern, untersuchen wir die Fluoridchemie in Zinn-Halogenid-Perowskiten mit einander ergänzenden Analyseverfahren. NMR-Spektroskopie der Vorläuferlösung offenbart eine stark bevorzugte Affinität der Fluoridanionen für SnIV gegenüber SnII, wodurch dieses selektiv als SnF4 komplexiert wird. Harte Röntgenphotoelektronenspektroskopie an Dünnschichten zeigt die geringere Bereitschaft von SnF4 gegenüber SnI4, in die Perowskit-Struktur eingebaut zu werden und verhindert somit den Einschluss von SnIV in der Dünnschicht. Abschließend offenbart Röntgen-Kleinwinkelstreuung den starken Einfluss vom Fluorid auf die kolloidale Chemie der Vorläuferlösungen, der sich direkt auf die darauffolgende Kristallisation auswirkt. European Research Council (ERC)

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"