bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visual electrophysiology and “the potential of the potentials”
Authors: Mahroo Omar A. 
Published: March 2023

AbstractVisual electrophysiology affords direct, quantitative, objective assessment of visual pathway function at different levels, and thus yields information complementary to, and not necessarily obtainable from, imaging or psychophysical testing. The tests available, and their indications, have evolved, with many advances, both in technology and in our understanding of the neural basis of the waveforms, now facilitating more precise evaluation of physiology and pathophysiology. After summarising the visual pathway and current standard clinical testing methods, this review discusses, non-exhaustively, several developments, focusing particularly on human electroretinogram recordings. These include new devices (portable, non-mydiatric, multimodal), novel testing protocols (including those aiming to separate rod-driven and cone-driven responses, and to monitor retinal adaptation), and developments in methods of analysis, including use of modelling and machine learning. It is likely that several tests will become more accessible and useful in both clinical and research settings. In future, these methods will further aid our understanding of common and rare eye disease, will help in assessing novel therapies, and will potentially yield information relevant to neurological and neuro-psychiatric conditions.
Potent acyl-CoA synthetase 10 inhibitors kill Plasmodium falciparum by disrupting triglyceride formation
Authors: Bopp Selina , Pasaje Charisse Flerida A. , Summers Robert L. , Magistrado-Coxen Pamela , Schindler Kyra A. , Corpas-Lopez Victoriano , Yeo Tomas , Mok Sachel , Dey Sumanta , Smick Sebastian , Nasamu Armiyaw S. , Demas Allison R. , Milne Rachel , Wiedemar Natalie , Corey Victoria , Gomez-Lorenzo Maria De Gracia , Franco Virginia , Early Angela M. , Lukens Amanda K. , Milner Danny , Furtado Jeremy , Gamo Francisco-Javier , Winzeler Elizabeth A. , Volkman Sarah K. , Duffey Maëlle , Laleu Benoît , Fidock David A. , Wyllie Susan , Niles Jacquin C. , Wirth Dyann F. 
Published: March 2023

AbstractIdentifying how small molecules act to kill malaria parasites can lead to new “chemically validated” targets. By pressuring Plasmodium falciparum asexual blood stage parasites with three novel structurally-unrelated antimalarial compounds (MMV665924, MMV019719 and MMV897615), and performing whole-genome sequence analysis on resistant parasite lines, we identify multiple mutations in the P. falciparum acyl-CoA synthetase (ACS) genes PfACS10 (PF3D7_0525100, M300I, A268D/V, F427L) and PfACS11 (PF3D7_1238800, F387V, D648Y, and E668K). Allelic replacement and thermal proteome profiling validates PfACS10 as a target of these compounds. We demonstrate that this protein is essential for parasite growth by conditional knockdown and observe increased compound susceptibility upon reduced expression. Inhibition of PfACS10 leads to a reduction in triacylglycerols and a buildup of its lipid precursors, providing key insights into its function. Analysis of the PfACS11 gene and its mutations point to a role in mediating resistance via decreased protein stability.
Mechanical overtone frequency combs
Authors: de Jong Matthijs H. J. , Ganesan Adarsh , Cupertino Andrea , Gröblacher Simon , Norte Richard A. 
Published: March 2023

AbstractMechanical frequency combs are poised to bring the applications and utility of optical frequency combs into the mechanical domain. So far, their main challenge has been strict requirements on drive frequencies and power, which complicate operation. We demonstrate a straightforward mechanism to create a frequency comb consisting of mechanical overtones (integer multiples) of a single eigenfrequency, by monolithically integrating a suspended dielectric membrane with a counter-propagating optical trap. The periodic optical field modulates the dielectrophoretic force on the membrane at the overtones of a membrane’s motion. These overtones share a fixed frequency and phase relation, and constitute a mechanical frequency comb. The periodic optical field also creates an optothermal parametric drive that requires no additional power or external frequency reference. This combination of effects results in an easy-to-use mechanical frequency comb platform that requires no precise alignment, no additional feedback or control electronics, and only uses a single, mW continuous wave laser beam. This highlights the overtone frequency comb as the straightforward future for applications in sensing, metrology and quantum acoustics.
Cryptosporidium uses CSpV1 to activate host type I interferon and attenuate antiparasitic defenses
Authors: Deng Silu , He Wei , Gong Ai-Yu , Li Min , Wang Yang , Xia Zijie , Zhang Xin-Tiang , Huang Pacheco Andrew S. , Naqib Ankur , Jenkins Mark , Swanson Patrick C. , Drescher Kristen M. , Strauss-Soukup Juliane K. , Belshan Michael , Chen Xian-Ming 
Published: March 2023

AbstractCryptosporidiuminfects gastrointestinal epithelium and is a leading cause of infectious diarrhea and diarrheal-related death in children worldwide. There are no vaccines and no fully effective therapy available for the infection. Type II and III interferon (IFN) responses are important determinants of susceptibility to infection but the role for type I IFN response remains obscure.Cryptosporidium parvumvirus 1 (CSpV1) is a double-stranded RNA (dsRNA) virus harbored byCryptosporidiumspp. Here we show that intestinal epithelial conditionalIfnar1−/−mice (deficient in type I IFN receptor) are resistant toC. parvuminfection. CSpV1-dsRNAs are delivered into host cells and trigger type I IFN response in infected cells. WhereasC. parvuminfection attenuates epithelial response to IFN-γ, loss of type I IFN signaling or inhibition of CSpV1-dsRNA delivery can restore IFN-γ-mediated protective response. Our findings demonstrate that type I IFN signaling in intestinal epithelial cells is detrimental to intestinal anti-C. parvumdefense andCryptosporidiumuses CSpV1 to activate type I IFN signaling to evade epithelial antiparasitic response.
Signature of quantum interference effect in inter-layer Coulomb drag in graphene-based electronic double-layer systems
Authors: Zhu Lijun , Liu Xiaoqiang , Li Lin , Wan Xinyi , Tao Ran , Xie Zhongniu , Feng Ji , Zeng Changgan 
Published: March 2023

AbstractThe distinguishing feature of a quantum system is interference arising from the wave mechanical nature of particles which is clearly central to macroscopic electronic properties. Here, we report the signature of quantum interference effect in inter-layer transport process. Via systematic magneto-drag experiments on graphene-based electronic double-layer systems, we observe low-field correction to the Coulomb-scattering-dominated inter-layer drag resistance in a wide range of temperature and carrier density, with its characteristics sensitive to the band topology of graphene layers. These observations can be attributed to a new type of quantum interference between drag processes, with the interference pathway comprising different carrier diffusion paths in the two constituent conductors. The emergence of such effect relies on the formation of superimposing planar diffusion paths, among which the impurity potentials from intermediate insulating spacer play an essential role. Our findings establish an ideal platform where the interplay between quantum interference and many-body interaction is essential.
B cell class switch recombination is regulated by DYRK1A through MSH6 phosphorylation
Authors: Stoler-Barak Liat , Harris Ethan , Peres Ayelet , Hezroni Hadas , Kuka Mirela , Di Lucia Pietro , Grenov Amalie , Gurwicz Neta , Kupervaser Meital , Yip Bon Ham , Iannacone Matteo , Yaari Gur , Crispino John D. , Shulman Ziv 
Published: March 2023

AbstractProtection from viral infections depends on immunoglobulin isotype switching, which endows antibodies with effector functions. Here, we find that the protein kinase DYRK1A is essential for B cell-mediated protection from viral infection and effective vaccination through regulation of class switch recombination (CSR). Dyrk1a-deficient B cells are impaired in CSR activity in vivo and in vitro. Phosphoproteomic screens and kinase-activity assays identify MSH6, a DNA mismatch repair protein, as a direct substrate for DYRK1A, and deletion of a single phosphorylation site impaired CSR. After CSR and germinal center (GC) seeding, DYRK1A is required for attenuation of B cell proliferation. These findings demonstrate DYRK1A-mediated biological mechanisms of B cell immune responses that may be used for therapeutic manipulation in antibody-mediated autoimmunity.
Increasing the number of stressors reduces soil ecosystem services worldwide
Authors: Rillig Matthias C. , van der Heijden Marcel G. A. , Berdugo Miguel , Liu Yu-Rong , Riedo Judith , Sanz-Lazaro Carlos , Moreno-Jiménez Eduardo , Romero Ferran , Tedersoo Leho , Delgado-Baquerizo Manuel 
Published: March 2023

AbstractIncreasing the number of environmental stressors could decrease ecosystem functioning in soils. Yet this relationship has not been globally assessed outside laboratory experiments. Here, using two independent global standardized field surveys, and a range of natural and human factors, we test the relationship between the number of environmental stressors exceeding different critical thresholds and the maintenance of multiple ecosystem services across biomes. Our analysis shows that having multiple stressors, from medium levels (>50%), negatively and significantly correlates with impacts on ecosystem services and that having multiple stressors crossing a high-level critical threshold (over 75% of maximum observed levels) reduces soil biodiversity and functioning globally. The number of environmental stressors exceeding the >75% threshold was consistently seen as an important predictor of multiple ecosystem services, therefore improving prediction of ecosystem functioning. Our findings highlight the need to reduce the dimensionality of the human footprint on ecosystems to conserve biodiversity and function.
Partner choice, confounding and trait convergence all contribute to phenotypic partner similarity
Authors: Sjaarda Jennifer , Kutalik Zoltán 
Published: March 2023

AbstractPartners are often similar in terms of their physical and behavioural traits, such as their education, political affiliation and height. However, it is currently unclear what exactly causes this similarity—partner choice, partner influence increasing similarity over time or confounding factors such as shared environment or indirect assortment. Here, we applied Mendelian randomization to the data of 51,664 couples in the UK Biobank and investigated partner similarity in 118 traits. We found evidence of partner choice for 64 traits, 40 of which had larger phenotypic correlation than causal effect. This suggests that confounders contribute to trait similarity, among which household income, overall health rating and education accounted for 29.8, 14.1 and 11.6% of correlations between partners, respectively. Finally, mediation analysis revealed that most causal associations between different traits in the two partners are indirect. In summary, our results show the mechanisms through which indirect assortment increases the observed partner similarity.
Multiomic analysis of malignant pleural mesothelioma identifies molecular axes and specialized tumor profiles driving intertumor heterogeneity
Authors: Mangiante Lise , Alcala Nicolas , Sexton-Oates Alexandra , Di Genova Alex , Gonzalez-Perez Abel , Khandekar Azhar , Bergstrom Erik N. , Kim Jaehee , Liu Xiran , Blazquez-Encinas Ricardo , Giacobi Colin , Le Stang Nolwenn , Boyault Sandrine , Cuenin Cyrille , Tabone-Eglinger Severine , Damiola Francesca , Voegele Catherine , Ardin Maude , Michallet Marie-Cecile , Soudade Lorraine , Delhomme Tiffany M. , Poret Arnaud , Brevet Marie , Copin Marie-Christine , Giusiano-Courcambeck Sophie , Damotte Diane , Girard Cecile , Hofman Veronique , Hofman Paul , Mouroux Jérôme , Cohen Charlotte , Lacomme Stephanie , Mazieres Julien , de Montpreville Vincent Thomas , Perrin Corinne , Planchard Gaetane , Rousseau Nathalie , Rouquette Isabelle , Sagan Christine , Scherpereel Arnaud , Thivolet Francoise , Vignaud Jean-Michel , Jean Didier , Ilg Anabelle Gilg Soit , Olaso Robert , Meyer Vincent , Boland-Auge Anne , Deleuze Jean-Francois , Altmuller Janine , Nuernberg Peter , Ibáñez-Costa Alejandro , Castaño Justo P. , Lantuejoul Sylvie , Ghantous Akram , Maussion Charles , Courtiol Pierre , Hernandez-Vargas Hector , Caux Christophe , Girard Nicolas , Lopez-Bigas Nuria , Alexandrov Ludmil B. , Galateau-Salle Françoise , Foll Matthieu , Fernandez-Cuesta Lynnette 
Published: March 2023

AbstractMalignant pleural mesothelioma (MPM) is an aggressive cancer with rising incidence and challenging clinical management. Through a large series of whole-genome sequencing data, integrated with transcriptomic and epigenomic data using multiomics factor analysis, we demonstrate that the current World Health Organization classification only accounts for up to 10% of interpatient molecular differences. Instead, the MESOMICS project paves the way for a morphomolecular classification of MPM based on four dimensions: ploidy, tumor cell morphology, adaptive immune response and CpG island methylator profile. We show that these four dimensions are complementary, capture major interpatient molecular differences and are delimited by extreme phenotypes that—in the case of the interdependent tumor cell morphology and adapted immune response—reflect tumor specialization. These findings unearth the interplay between MPM functional biology and its genomic history, and provide insights into the variations observed in the clinical behavior of patients with MPM.
Exhausted intratumoral Vδ2− γδ T cells in human kidney cancer retain effector function
Authors: Rancan Chiara , Arias-Badia Marcel , Dogra Pranay , Chen Brandon , Aran Dvir , Yang Hai , Luong Diamond , Ilano Arielle , Li Jacky , Chang Hewitt , Kwek Serena S. , Zhang Li , Lanier Lewis L. , Meng Maxwell V. , Farber Donna L. , Fong Lawrence 
Published: March 2023

AbstractGamma delta (γδ) T cells reside within human tissues including tumors, but their function in mediating antitumor responses to immune checkpoint inhibition is unknown. Here we show that kidney cancers are infiltrated by Vδ2− γδ T cells, with equivalent representation of Vδ1+ and Vδ1− cells, that are distinct from γδ T cells found in normal human tissues. These tumor-resident Vδ2− T cells can express the transcriptional program of exhausted αβ CD8+ T cells as well as canonical markers of terminal T-cell exhaustion including PD-1, TIGIT and TIM-3. Although Vδ2− γδ T cells have reduced IL-2 production, they retain expression of cytolytic effector molecules and co-stimulatory receptors such as 4-1BB. Exhausted Vδ2− γδ T cells are composed of three distinct populations that lack TCF7, are clonally expanded and express cytotoxic molecules and multiple Vδ2− T-cell receptors. Human tumor-derived Vδ2− γδ T cells maintain cytotoxic function and pro-inflammatory cytokine secretion in vitro. The transcriptional program of Vδ2− T cells in pretreatment tumor biopsies was used to predict subsequent clinical responses to PD-1 blockade in patients with cancer. Thus, Vδ2− γδ T cells within the tumor microenvironment can contribute to antitumor efficacy.
Preclinical models for prediction of immunotherapy outcomes and immune evasion mechanisms in genetically heterogeneous multiple myeloma
Authors: Larrayoz Marta , Garcia-Barchino Maria J. , Celay Jon , Etxebeste Amaia , Jimenez Maddalen , Perez Cristina , Ordoñez Raquel , Cobaleda Cesar , Botta Cirino , Fresquet Vicente , Roa Sergio , Goicoechea Ibai , Maia Catarina , Lasaga Miren , Chesi Marta , Bergsagel P. Leif , Larrayoz Maria J. , Calasanz Maria J. , Campos-Sanchez Elena , Martinez-Cano Jorge , Panizo Carlos , Rodriguez-Otero Paula , Vicent Silvestre , Roncador Giovanna , Gonzalez Patricia , Takahashi Satoru , Katz Samuel G. , Walensky Loren D. , Ruppert Shannon M. , Lasater Elisabeth A. , Amann Maria , Lozano Teresa , Llopiz Diana , Sarobe Pablo , Lasarte Juan J. , Planell Nuria , Gomez-Cabrero David , Kudryashova Olga , Kurilovich Anna , Revuelta Maria V. , Cerchietti Leandro , Agirre Xabier , San Miguel Jesus , Paiva Bruno , Prosper Felipe , Martinez-Climent Jose A. 
Published: March 2023

AbstractThe historical lack of preclinical models reflecting the genetic heterogeneity of multiple myeloma (MM) hampers the advance of therapeutic discoveries. To circumvent this limitation, we screened mice engineered to carry eight MM lesions (NF-κB, KRAS, MYC, TP53, BCL2, cyclin D1, MMSET/NSD2 and c-MAF) combinatorially activated in B lymphocytes following T cell-driven immunization. Fifteen genetically diverse models developed bone marrow (BM) tumors fulfilling MM pathogenesis. Integrative analyses of ∼500 mice and ∼1,000 patients revealed a common MAPK–MYC genetic pathway that accelerated time to progression from precursor states across genetically heterogeneous MM. MYC-dependent time to progression conditioned immune evasion mechanisms that remodeled the BM microenvironment differently. Rapid MYC-driven progressors exhibited a high number of activated/exhausted CD8+ T cells with reduced immunosuppressive regulatory T (Treg) cells, while late MYC acquisition in slow progressors was associated with lower CD8+ T cell infiltration and more abundant Treg cells. Single-cell transcriptomics and functional assays defined a high ratio of CD8+ T cells versus Treg cells as a predictor of response to immune checkpoint blockade (ICB). In clinical series, high CD8+ T/Treg cell ratios underlie early progression in untreated smoldering MM, and correlated with early relapse in newly diagnosed patients with MM under Len/Dex therapy. In ICB-refractory MM models, increasing CD8+ T cell cytotoxicity or depleting Treg cells reversed immunotherapy resistance and yielded prolonged MM control. Our experimental models enable the correlation of MM genetic and immunological traits with preclinical therapy responses, which may inform the next-generation immunotherapy trials.
Multiomic neuropathology improves diagnostic accuracy in pediatric neuro-oncology
Authors: Sturm Dominik , Capper David , Andreiuolo Felipe , Gessi Marco , Kölsche Christian , Reinhardt Annekathrin , Sievers Philipp , Wefers Annika K. , Ebrahimi Azadeh , Suwala Abigail K. , Gielen Gerrit H. , Sill Martin , Schrimpf Daniel , Stichel Damian , Hovestadt Volker , Daenekas Bjarne , Rode Agata , Hamelmann Stefan , Previti Christopher , Jäger Natalie , Buchhalter Ivo , Blattner-Johnson Mirjam , Jones Barbara C. , Warmuth-Metz Monika , Bison Brigitte , Grund Kerstin , Sutter Christian , Hirsch Steffen , Dikow Nicola , Hasselblatt Martin , Schüller Ulrich , Koch Arend , Gerber Nicolas U. , White Christine L. , Buntine Molly K. , Kinross Kathryn , Algar Elizabeth M. , Hansford Jordan R. , Gottardo Nicholas G. , Schuhmann Martin U. , Thomale Ulrich W. , Hernáiz Driever Pablo , Gnekow Astrid , Witt Olaf , Müller Hermann L. , Calaminus Gabriele , Fleischhack Gudrun , Kordes Uwe , Mynarek Martin , Rutkowski Stefan , Frühwald Michael C. , Kramm Christof M. , von Deimling Andreas , Pietsch Torsten , Sahm Felix , Pfister Stefan M. , Jones David. T. W. 
Published: March 2023

AbstractThe large diversity of central nervous system (CNS) tumor types in children and adolescents results in disparate patient outcomes and renders accurate diagnosis challenging. In this study, we prospectively integrated DNA methylation profiling and targeted gene panel sequencing with blinded neuropathological reference diagnostics for a population-based cohort of more than 1,200 newly diagnosed pediatric patients with CNS tumors, to assess their utility in routine neuropathology. We show that the multi-omic integration increased diagnostic accuracy in a substantial proportion of patients through annotation to a refining DNA methylation class (50%), detection of diagnostic or therapeutically relevant genetic alterations (47%) or identification of cancer predisposition syndromes (10%). Discrepant results by neuropathological WHO-based and DNA methylation-based classification (30%) were enriched in histological high-grade gliomas, implicating relevance for current clinical patient management in 5% of all patients. Follow-up (median 2.5 years) suggests improved survival for patients with histological high-grade gliomas displaying lower-grade molecular profiles. These results provide preliminary evidence of the utility of integrating multi-omics in neuropathology for pediatric neuro-oncology.
Establishing an RNA fusions panel in soft tissue sarcoma with clinical validation
Authors: Huang Xiaoqiang , Li Guibin , Li Linghua , Wang Jian , Shen Jianru , Chen Yao , Yu Wuzhong , Chen Ailin , Wu Tao , Ma Ji , Ling Bao , He Liang , Chen Xudan 
Published: March 2023

AbstractThe diagnosis and classification of soft tissue sarcomas (STS) remain challenging because of the rarity and overlapping morphologic manifestations of diverse STS subtypes. Characteristic gene fusions are commonly detected in STS and represent useful diagnostic markers. This study established and validated a custom-designed RNA sequencing panel that identified 64 gene fusions in STS. The analytical performance validation yielded excellent accuracy, with 100% (95% CI, 94.40%-100%) sensitivity and 93.33% (95% CI, 68.05%-99.83%) specificity. Clinical performances were further confirmed with 145 clinical formalin-fixed and paraffin-embedded (FFPE) samples from STS patients. Fusions were detected in 40% of samples (58/145). The common fusions SS18-SSX family, EWSR1-related fusions, COL1A1-PDGFB, FOXO1-associated fusions, and FUS-associated fusions were identified in corresponding STS subtypes. The RNA panel detected specific fusions in several cases where no conclusive diagnosis can be made based on the morphology and immunohistochemistry results. Data collected in this study demonstrate that the RNA fusions panel can better classify STS subtypes and serve as a good supplement for histopathology, exhibiting a great potential for the STS precise diagnosis.
The propensity to sign-track is associated with externalizing behavior and distinct patterns of reward-related brain activation in youth
Authors: Colaizzi Janna M. , Flagel Shelly B. , Gearhardt Ashley N. , Borowitz Michelle A. , Kuplicki Rayus , Zotev Vadim , Clark Grace , Coronado Jennifer , Abbott Talia , Paulus Martin P. 
Published: March 2023

AbstractExternalizing behaviors in childhood often predict impulse control disorders in adulthood; however, the underlying bio-behavioral risk factors are incompletely understood. In animals, the propensity to sign-track, or the degree to which incentive motivational value is attributed to reward cues, is associated with externalizing-type behaviors and deficits in executive control. Using a Pavlovian conditioned approach paradigm, we quantified sign-tracking in 40 healthy 9–12-year-olds. We also measured parent-reported externalizing behaviors and anticipatory neural activations to outcome-predicting cues using the monetary incentive delay fMRI task. Sign-tracking was associated with attentional and inhibitory control deficits and the degree of amygdala, but not cortical, activation during reward anticipation. These findings support the hypothesis that youth with a propensity to sign-track are prone to externalizing tendencies, with an over-reliance on subcortical cue-reactive brain systems. This research highlights sign-tracking as a promising experimental approach delineating the behavioral and neural circuitry of individuals at risk for externalizing disorders.