tbuckley/cabot-search huggingface dataset:
Inverted triplications formed by iterative template switches generate structural variant diversity at genomic disorder loci
Authors: Christopher M. Grochowski, Jesse D. Bengtsson, Haowei Du, Mira Gandhi, Ming Yin Lun, Michele G. Mehaffey, KyungHee Park, Wolfram Höps, Eva Benito, Patrick Hasenfeld, Jan O. Korbel, Medhat Mahmoud, Luis F. Paulin, Shalini N. Jhangiani, James Paul Hwang, Sravya V. Bhamidipati, Donna M. Muzny, Jawid M. Fatih, Richard A. Gibbs, Matthew Pendleton, Eoghan Harrington, Sissel Juul, Anna Lindstrand, Fritz J. Sedlazeck, Davut Pehlivan, James R. Lupski, Claudia M.B. Carvalho
Journal: Cell Genomics (2024)

Highlights•Inverted triplications cause genomic disorders through alterations in gene dosage•Pairs of homologous inverted repeats generate varying structural haplotypes•Breakpoint junction mapping reveals template switches within repeats•Combining methodologies enhance the analysis of complex genomic aberrationsSummaryThe duplication-triplication/inverted-duplication (DUP-TRP/INV-DUP) structure is a complex genomic rearrangement (CGR). Although it has been identified as an important pathogenic DNA mutation signature in genomic disorders and cancer genomes, its architecture remains unresolved. Here, we studied the genomic architecture of DUP-TRP/INV-DUP by investigating the DNA of 24 patients identified by array comparative genomic hybridization (aCGH) on whom we found evidence for the existence of 4 out of 4 predicted structural variant (SV) haplotypes. Using a combination of short-read genome sequencing (GS), long-read GS, optical genome mapping, and single-cell DNA template strand sequencing (strand-seq), the haplotype structure was resolved in 18 samples. The point of template switching in 4 samples was shown to be a segment of ∼2.2–5.5 kb of 100% nucleotide similarity within inverted repeat pairs. These data provide experimental evidence that inverted low-copy repeats act as recombinant substrates. This type of CGR can result in multiple conformers generating diverse SV haplotypes in susceptible dosage-sensitive loci.Graphical abstract
Author Correction: A shifting role of thalamocortical connectivity in the emergence of cortical functional organization
Authors: Shinwon Park, Koen V. Haak, Stuart Oldham, Hanbyul Cho, Kyoungseob Byeon, Bo-yong Park, Phoebe Thomson, Haitao Chen, Wei Gao, Ting Xu, Sofie Valk, Michael P. Milham, Boris Bernhardt, Adriana Di Martino, Seok-Jun Hong
Journal: Nature Neuroscience (2024)
Global availability and uptake of psychological services for adults, caregivers and children with food allergy
Authors: R. C. Knibb, L. J. Herbert, C. J. Jones, J. L. P. Protudjer, C. Screti, C. Roleston, H. A. Brough, C. Warren, L. Lombard, A. F. Santos, R. Gupta, B. P. Vickery, M. J. Marchisotto
Journal: Allergy (2024)

Abstract Background Food allergy (FA) is associated with poor health‐related quality of life and high levels of psychological distress. Psychological support is extremely important but not always available. As part of the Global Access to Psychological Services for Food Allergy (GAPS) study, we aimed to assess psychological distress and service use among adults, caregivers and children with FA in a global survey. Methods Participants ( n = 1329 adults with FA; n = 1907 caregivers of children with FA) from &gt;20 countries were recruited through patient organisations, social media advertisements and online survey panels to complete an online survey. Surveys were available in six languages. Results A total of 67.7% of adults and 77.2% of caregivers reported direct experience, and 51.6% of caregivers said their child had experienced FA‐related psychological distress. The most commonly reported issue was anxiety about having an allergic reaction. Less than 20% had been assessed for FA‐related psychological distress. There were significant differences across countries for levels of distress, screening for distress, seeing a mental health professional and being diagnosed with a FA‐related mental health disorder (all p &lt; .001). The United Kingdom, Australia and Brazil had the highest number of participants reporting distress. The most commonly reported barrier to seeing a mental health professional was cost. Conclusions FA‐related distress is common across countries, but with substantial country‐to‐country variability. Allergy providers are encouraged to routinely assess families for psychological distress and provide access to appropriate mental health resources. Development and implementation of evidence‐based, patient‐informed accessible, affordable FA interventions in multiple languages is urgently needed.
Modulation of monocyte activity by hepatocellular MicroRNA delivery via hepatitis B virus surface antigen particles: Implications for pathobiology of chronic hepatitis B
Authors: Jin Li, Xiao Ma, Qinkao Xuan, Qiang Li, Min Wu, Bisheng Shi, Zhong Fang, Liang Chen, Jieliang Chen, Yumei Wen, Chuanwu Zhu, Li Zhu, Xiaonan Zhang, Zhenghong Yuan
Journal: Hepatology (2024)

Background and Aims: HBsAg serves as an important immune-modulatory factor in chronic hepatitis B. One aspect of such modulation may act through monocytes, which are the major Ag-presenting cells taking up HBsAg. There is evidence for the encapsulation of hepatocellular microRNAs (miRNAs) by HBsAg particles, while its pathobiological significance is unclear. Here, we characterized the miRNA profile in patients with chronic hepatitis B and probed their association with liver inflammation. Approaches and Results: We collected plasma from patients that are treatment-naive with chronic hepatitis B (n = 110) and quantified total/HBsAg-enveloped miRNAs by qRT-PCR and plasma cytokines by ELISA. The biological effects of HBsAg-delivered miRNAs in monocytes were evaluated using multiple approaches. The clinical significance of candidate miRNAs and cytokines was corroborated in patients with HBV-associated advanced liver diseases. The plasma miRNA profile showed 2 major clusters, one significantly associated with HBsAg titer and the other correlated with liver inflammation. Among HBsAg-carried miRNAs, miR-939 displayed the most significant correlation with IL-8. Mechanistically, miR-939 in subviral particles enters monocytes and significantly augments IL-8 production through the mitogen-activated protein kinase (MAPK) p38 signaling pathway. Finally, the findings that miR-939 positively correlated with IL-8 level and inflammation/fibrosis stage in the cohort of HBV-associated advanced liver diseases support its causative role in the progression of liver diseases. Conclusions: HBsAg particles carry hepatocellular miRNAs, including miR-939, which enter monocytes and alter their functional status, such as IL-8 secretion. Our findings demonstrate that the HBsAg-miR-939-IL-8 axis may play a crucial role in HBV-induced hepatic necro-inflammation and the progression of advanced liver diseases.
Adverse Cardiovascular Outcomes in Patients With Obstructive Sleep Apnea and Obesity
Authors: Ali Aminian, Lu Wang, Abdullah Al Jabri, Rickesha Wilson, James Bena, Alex Milinovich, Jian Jin, Catherine Heinzinger, Cinthya Pena-Orbea, Nancy Foldvary-Schaefer, Steven E. Nissen, Reena Mehra
Journal: Journal of the American College of Cardiology (2024)
Kneadable dough-type hydrogel transforming from dynamic to rigid network to repair irregular bone defects
Authors: Ningtao Wang, Jie Chen, Yanyang Chen, Liang Chen, Luhan Bao, Zhengmei Huang, Xiaoyu Han, Jiangkuo Lu, Zhengwei Cai, Wenguo Cui, Zhengwei Huang
Journal: Bioactive Materials (2024)
Biomedical Device Surface Treatment by Laser‐Driven Hydroxyapatite Penetration‐Synthesis Technique for Gapless PEEK‐to‐Bone Integration
Authors: Seung‐Hoon Um, Jaehong Lee, Minseong Chae, Carlo Paternoster, Francesco Copes, Pascale Chevallier, Dong‐Ho Lee, Suk‐Won Hwang, Yu‐Chan Kim, Hyung‐Seop Han, Kang‐Sik Lee, Diego Mantovani, Hojeong Jeon
Journal: Advanced Healthcare Materials (2024)

Polyetheretherketone (PEEK), a bioinert polymer known for its mechanical properties similar to bone, is capable of averting stress shielding. Due to these attributes, it finds applications in diverse fields like orthopedics, encompassing cervical disc replacement for the neck and spine, along with dentistry and plastic surgery. However, due to insufficient bonding with bone, various methods such as hydroxyapatite (HA) coating on the surface are attempted. Nonetheless, the interface between the polymer and ceramic, two different materials, tended to delaminate after transplantation, posing challenges in preventing implant escape or dislodgement. This research delves into the laser-driven hydroxyapatite penetration-synthesis technique. Differing from conventional coating methods that bond layers of dissimilar materials like HA and PEEK, this technology focuses on synthesizing and infiltrating ionized HA within the PEEK substrate resulting in an interface-free HA-PEEK surface. Conversely, HA-PEEK with this technology applied achieves complete, gap-free direct bone-implant integration. Our research involved the analysis of various aspects. By means of these, we quantitatively assesed the enhanced bone bonding characteristics of HA-PEEK surfaces treated with this approach and offered and explanation for the mechanism responsible for direct bone integration.
Recent Advances in Immune-Based Therapies for Acute Myeloid Leukemia
Authors: Cecilia Restelli, Marco Ruella, Luca Paruzzo, Corrado Tarella, Pier Giuseppe Pelicci, Emanuela Colombo
Journal: Blood Cancer Discovery (2024)

Despite advancements, acute myeloid leukemia (AML) remains unconquered by current therapies. Evidence of immune evasion during AML progression, such as HLA loss and T-cell exhaustion, suggests that antileukemic immune responses contribute to disease control and could be harnessed by immunotherapy. In this review, we discuss a spectrum of AML immunotherapy targets, encompassing cancer cell-intrinsic and surface antigens as well as targeting in the leukemic milieu, and how they can be tailored for personalized approaches. These targets are overviewed across major immunotherapy modalities applied to AML: immune checkpoint inhibitors, antibody-drug conjugates, therapeutic vaccines, bispecific/trispecific antibodies, and chimeric antigen receptor (CAR)-T and CAR-NK cells. Significance: Immune therapies in AML treatment show evolving promise. Ongoing research aims to customize approaches for varied patient profiles and clinical scenarios. This review covers immune surveillance mechanisms, therapy options like checkpoint inhibitors, antibodies, CAR-T/NK cells, and vaccines, as well as resistance mechanisms and microenvironment considerations.
Perceptions of the Portuguese population on vaccination – The specific view of Chronic Respiratory Disease patients
Authors: G.M. Victorino, I. Saraiva, B. Pereira, P. Borrego, J.V. Cordeiro, F.C. Sousa, M. Morais-Almeida, J.R. Ferreira, P.S. Coelho
Journal: Pulmonology (2024)
An unusual outbreak of parvovirus B19 infections, France, 2023 to 2024
Authors: Camille d’Humières, Anne Fouillet, Laura Verdurme, Stevens-Boris Lakoussan, Yves Gallien, Catherine Coignard, Marie Hervo, Anne Ebel, Anaïs Soares, Benoit Visseaux, Bruno Maire, Pierre-Henry Juan, Isabelle Parent du Châtelet, Jean-Paul Guthmann, Julien Durand
Journal: Eurosurveillance (2024)

From April 2023 to May 2024, an unusual epidemic of parvovirus B19 (B19V) infections occurred in France. The number of B19V IgM-positive serologies was four times higher than in the previous epidemic in 2019. Clinical data from emergency networks corroborated this observation. Morbidity and mortality consequences were observed in children through all data sources. In adults, the increase was only observed in laboratory-confirmed data. Physicians and decisionmakers should be informed in order to better prevent, diagnose and manage at-risk patients.
Using games to understand the mind
Authors: Kelsey Allen, Franziska Brändle, Matthew Botvinick, Judith E. Fan, Samuel J. Gershman, Alison Gopnik, Thomas L. Griffiths, Joshua K. Hartshorne, Tobias U. Hauser, Mark K. Ho, Joshua R. de Leeuw, Wei Ji Ma, Kou Murayama, Jonathan D. Nelson, Bas van Opheusden, Thomas Pouncy, Janet Rafner, Iyad Rahwan, Robb B. Rutledge, Jacob Sherson, Özgür Şimşek, Hugo Spiers, Christopher Summerfield, Mirko Thalmann, Natalia Vélez, Andrew J. Watrous, Joshua B. Tenenbaum, Eric Schulz
Journal: Nature Human Behaviour (2024)
One health, many interpretations: vaccinating risk groups against H5 avian influenza in Finland
Authors: Hanna Nohynek, Otto Matias Helve
Journal: Eurosurveillance (2024)

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WILDbase: towards a common database to improve wildlife disease surveillance in Europe
Authors: Marieke P de Cock, Valérie O Baede, Sara R Wijburg, Sara A Burt, Robert FNA van Tiel, Kim K Wiskerke, Jens RJ van der Post, Wim HM van der Poel, Hein Sprong, Miriam Maas
Journal: Eurosurveillance (2024)

BackgroundTo be better prepared for emerging wildlife-borne zoonoses, we need to strengthen wildlife disease surveillance.AimThe aim of this study was to create a topical overview of zoonotic pathogens in wildlife species to identify knowledge gaps and opportunities for improvement of wildlife disease surveillance.MethodsWe created a database, which is based on a systematic literature review in Embase focused on zoonotic pathogens in 10 common urban wildlife mammals in Europe, namely brown rats, house mice, wood mice, common voles, red squirrels, European rabbits, European hedgehogs, European moles, stone martens and red foxes. In total, we retrieved 6,305 unique articles of which 882 were included.ResultsIn total, 186 zoonotic pathogen species were described, including 90 bacteria, 42 helminths, 19 protozoa, 22 viruses and 15 fungi. Most of these pathogens were only studied in one single animal species. Even considering that some pathogens are relatively species-specific, many European countries have no (accessible) data on zoonotic pathogens in these relevant animal species. We used the Netherlands as an example to show how this database can be used by other countries to identify wildlife disease surveillance gaps on a national level. Only 4% of all potential host-pathogen combinations have been studied in the Netherlands.ConclusionsThis database comprises a comprehensive overview that can guide future research on wildlife-borne zoonotic diseases both on a European and national scale. Sharing and expanding this database provides a solid starting point for future European-wide collaborations to improve wildlife disease surveillance.
Anakinra in Sanfilippo syndrome: a phase 1/2 trial
Authors: Lynda E. Polgreen, Agnes H. Chen, Youngju Pak, Anna Luzzi, Adolfo Morales Garval, Jonathan Acevedo, Gal Bitan, Michelina Iacovino, Cara O’Neill, Julie B. Eisengart
Journal: Nature Medicine (2024)

Sanfilippo syndrome is a fatal childhood neurodegenerative disorder involving neuroinflammation among multiple pathologies. We hypothesized that anakinra, a recombinant interleukin-1 receptor antagonist, could improve neurobehavioral and functional symptoms owing to its capacity to treat neuroinflammation. This phase 1/2 trial aimed to test the safety, tolerability and effects of anakinra on neurobehavioral, functional and quality-of-life outcomes in patients and their caregivers. The primary outcome was the percent of participants requiring a dose increase at week 8 or week 16. Secondary efficacy outcomes included a multi-domain responder index (MDRI). Twenty-three participants (6-26 years of age) were enrolled. Twenty continued treatment to week 8, and 15 (75%) required an increased dose at week 8 or week 16. There was an improvement in at least one domain in the MDRI in 18 of 21 (86%) at week 8 and in 15 of 16 (94%) at week 36. Seven participants withdrew (intolerability of daily injections and lost to follow-up) before week 36. Adverse events occurred in 22 of 23 (96%) participants, most commonly mild injection site reactions. No serious adverse events were related to anakinra. In conclusion, anakinra was safe and associated with improved neurobehavioral and functional outcomes, supporting continued investigation of anakinra in Sanfilippo syndrome and other mucopolysaccharidoses. ClinicalTrials.gov identifier: NCT04018755 .
Derivation and transcriptional reprogramming of border-forming wound repair astrocytes after spinal cord injury or stroke in mice
Authors: Timothy M. O’Shea, Yan Ao, Shinong Wang, Yilong Ren, Amy L. Cheng, Riki Kawaguchi, Zechuan Shi, Vivek Swarup, Michael V. Sofroniew
Journal: Nature Neuroscience (2024)

Central nervous system (CNS) lesions become surrounded by neuroprotective borders of newly proliferated reactive astrocytes; however, fundamental features of these cells are poorly understood. Here we show that following spinal cord injury or stroke, 90% and 10% of border-forming astrocytes derive, respectively, from proliferating local astrocytes and oligodendrocyte progenitor cells in adult mice of both sexes. Temporal transcriptome analysis, single-nucleus RNA sequencing and immunohistochemistry show that after focal CNS injury, local mature astrocytes dedifferentiate, proliferate and become transcriptionally reprogrammed to permanently altered new states, with persisting downregulation of molecules associated with astrocyte-neuron interactions and upregulation of molecules associated with wound healing, microbial defense and interactions with stromal and immune cells. These wound repair astrocytes share morphologic and transcriptional features with perimeningeal limitans astrocytes and are the predominant source of neuroprotective borders that re-establish CNS integrity around lesions by separating neural parenchyma from stromal and immune cells as occurs throughout the healthy CNS.
Association between adverse events after COVID-19 vaccination and anti-SARS-CoV-2 antibody concentrations, the Netherlands, May 2021 to November 2022: a population-based prospective cohort study
Authors: Minke R Holwerda, Christina E Hoeve, Anne J Huiberts, Gerco den Hartog, Hester E de Melker, Susan van den Hof, Mirjam J Knol
Journal: Eurosurveillance (2024)

BackgroundNon-severe adverse events (AE) including pain at injection site or fever are common after COVID-19 vaccination.AimTo describe determinants of AE after COVID-19 vaccination and investigate the association between AE and pre- and post-vaccination antibody concentrations.MethodsParticipants of an ongoing prospective cohort study (VASCO) completed a questionnaire on AE within 2 months after vaccination and provided 6 monthly serum samples during May 2021-November 2022. Logistic regression analyses were performed to investigate AE determinants after mRNA vaccination, including pre-vaccination Ig antibody concentrations against the SARS-CoV-2 spike protein receptor binding domain. Multivariable linear regression was performed in SARS-CoV-2-naive participants to assess the association between AE and log-transformed antibody concentrations 3-8 weeks after mRNA vaccination.ResultsWe received 47,947 completed AE questionnaires by 28,032 participants. In 42% and 34% of questionnaires, injection site and systemic AE were reported, respectively. In 2.2% of questionnaires, participants sought medical attention. AE were reported more frequently by women, younger participants (< 60 years), participants with medical risk conditions and Spikevax recipients (vs Comirnaty). Higher pre-vaccination antibody concentrations were associated with higher incidence of systemic AE after the second and third dose, but not with injection site AE or AE for which medical attention was sought. Any AE after the third dose was associated with higher post-vaccination antibody concentrations (geometric mean concentration ratio: 1.38; 95% CI: 1.23-1.54).ConclusionsOur study suggests that high pre-vaccination antibody levels are associated with AE, and experiencing AE may be a marker for higher antibody response to vaccination.
Neoadjuvant pembrolizumab, dabrafenib and trametinib in BRAFV600-mutant resectable melanoma: the randomized phase 2 NeoTrio trial
Authors: Georgina V. Long, Matteo S. Carlino, George Au-Yeung, Andrew J. Spillane, Kerwin F. Shannon, David E. Gyorki, Edward Hsiao, Rony Kapoor, Jake R. Thompson, Iris Batula, Julie Howle, Sydney Ch’ng, Maria Gonzalez, Robyn P. M. Saw, Thomas E. Pennington, Serigne N. Lo, Richard A. Scolyer, Alexander M. Menzies
Journal: Nature Medicine (2024)

Immune checkpoint inhibitors and BRAF-targeted therapy each improve survival in melanoma. Immune changes early during targeted therapy suggest the mechanisms of each drug class could work synergistically. In the non-comparative, randomized, phase 2 NeoTrio trial, we investigated whether targeted therapy could boost the proportion of patients achieving long-term recurrence-free survival with neoadjuvant immunotherapy in resectable stage III BRAF
Authors’ correction for Euro Surveill. 2024;29(13)
Journal: Eurosurveillance (2024)

© This work is licensed under a Creative Commons Attribution 4.0 International License. Closure This is a corrected article applying to the following content: Molecular epidemiology identifies the expansion of the DENV2 epidemic lineage from the French Caribbean Islands to French Guiana and mainland France, 2023 to 2024
Single-nucleus sequencing reveals enriched expression of genetic risk factors in extratelencephalic neurons sensitive to degeneration in ALS
Authors: Francesco Limone, Daniel A. Mordes, Alexander Couto, Brian J. Joseph, Jana M. Mitchell, Martine Therrien, Sulagna Dia Ghosh, Daniel Meyer, Yingying Zhang, Melissa Goldman, Laura Bortolin, Inma Cobos, Beth Stevens, Steven A. McCarroll, Irena Kadiu, Aaron Burberry, Olli Pietiläinen, Kevin Eggan
Journal: Nature Aging (2024)

Abstract Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by a progressive loss of motor function linked to degenerating extratelencephalic neurons/Betz cells (ETNs). The reasons why these neurons are selectively affected remain unclear. Here, to understand the unique molecular properties that may sensitize ETNs to ALS, we performed RNA sequencing of 79,169 single nuclei from cortices of patients and controls. In both patients and unaffected individuals, we found significantly higher expression of ALS risk genes in THY1 + ETNs, regardless of diagnosis. In patients, this was accompanied by the induction of genes involved in protein homeostasis and stress responses that were significantly induced in a wide collection of ETNs. Examination of oligodendroglial and microglial nuclei revealed patient-specific downregulation of myelinating genes in oligodendrocytes and upregulation of an endolysosomal reactive state in microglia. Our findings suggest that selective vulnerability of extratelencephalic neurons is partly connected to their intrinsic molecular properties sensitizing them to genetics and mechanisms of degeneration.