bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of Incorrect Documentation of Initial Cardiac Rhythm in Survivors of Out of Hospital Cardiac Arrest
Authors: Kumar Sant , Hockstein Max , Papolos Alexander I. , Devraj Mithun , Khalid Nauman , Lipinski Michael J. , Kenigsberg Benjamin B. 
Published: April 2024

ABSTRACTBackgroundIn-hospital management of out-of-hospital cardiac arrest (OHCA) is heavily influenced by the initial rhythm (shockable vs. non-shockable). The prevalence of discordance between initial rhythm determination reported by emergency medical services (EMS) versus hospital teams is not well described. It is unclear whether such documentation discrepancies in OHCA influence inpatient clinical care including subsequent left heart catheterization (LHC). We hypothesized that discordance between EMS and hospital team documentation of OHCA initial rhythm was common and associated with differences in LHC frequency.MethodsThis was a retrospective, single-center study. OHCA patients from the Cardiac Arrest Registry to Enhance Survival (CARES) hospital database were linked by demographic and arrest history to OHCA patients identified by inpatient hospital billing codes from 2009 to 2017. Patients who expired within 24 hours of hospital presentation were excluded. Hospital documentation of OHCA initial rhythm and occurrence of LHC were manually reviewed. The relationship between EMS versus hospital team documentation of OHCA initial rhythm and occurrence of LHC were assessed by relative risk ratios with 95% confidence intervals.ResultsOut of 164 patients for analysis, 140 (85.4%) had concordant EMS and hospital documentation of OHCA initial rhythm. For OHCA with an EMS-documented shockable rhythm, the relative risk of LHC when hospital-documented concordant shockable vs. discordant non-shockable rhythm was 2.12 (95% RR CI: 0.76-5.93). For OHCA with an EMS-documented non-shockable rhythm, the relative risk of LHC when hospital-documented concordant non-shockable vs discordant shockable rhythm was 0.19 (95% CI: 0.05-0.69).ConclusionsIn patients with OHCA, discrepancy between EMS and hospital team documentation of the initial arrest rhythm is prevalent. This discrepancy may influence the incidence of LHC. Further research is needed to understand the clinical impact of discrepancies in rhythm communication between EMS and hospital teams.
SUN-domain proteins of the malaria parasitePlasmodium falciparumare essential for proper nuclear division and DNA repair
Authors: Kandelis-Shalev Sofiya , Goyal Manish , Elam Tal , Assaraf Shany , Dahan Noa , Farchi Omer , Berenshtein Eduard , Dzikowski Ron 
Published: April 2024

AbstractThe protozoan parasitePlasmodium falciparum, which is responsible for the deadliest form of human malaria, accounts for over half a million deaths a year. These parasites proliferate in human red blood cells by consecutive rounds of closed mitoses called schizogony. Their virulence is attributed to their ability to modify the infected red cells to adhere to the vascular endothelium and to evade immunity through antigenic switches. Spatial dynamics at the nuclear periphery were associated with regulation of processes that enable the parasites to establish long-term infection. However, our knowledge of components of the nuclear envelope (NE) inPlasmodiumremains limited. One of the major protein complexes at the NE is the LINC complex that forms a connecting bridge between the cytoplasm and the nucleus through the interaction of SUN and KASH domain proteins. Here we have identified two SUN-domain proteins as possible components of the LINC complex ofP. falciparumand show that their proper expression is essential for the parasite’s proliferation in human red blood cells and that their depletion leads to the formation of membranous whorls and morphological changes of the NE. In addition, their differential expression highlight different functions at the nuclear periphery as PfSUN2 is specifically associated with heterochromatin, while PfSUN1 expression is essential for activation of the DNA damage response. Our data provide indications for the involvement of the LINC complex in crucial biological processes in the intraerythrocytic development cycle of malaria parasites.
Inferring gene regulatory networks using DNA methylation data
Authors: Bartlett Thomas E. , Li Melodie , Huang Qiulin 
Published: April 2024

AbstractWe show much-improved accuracy of inference of GRN (gene regulatory network) structure, resulting from the use of an epigenomic prior network. We also find that DNAme data are very effective for inferring the epigenomic prior network, recapitulating known epigenomic network structure found previously from chromatin accessibility data, and typically providing potential TF cis-regulations for at least eight times as many genes when compared with chromatin accessibility data. When our proposed methodology is applied to real datasets from human embryonic development and from women at risk of breast cancer, we find patterns of differential cis-regulation that are in line with expectations under appropriate biological models, and that can be used to identify pre-cancerous epigenomic changes with valid functional genomic interpretations.
MARK2variants cause autism spectrum disorderviathe downregulation of WNT/β-catenin signaling pathway
Authors: Gong Maolei , Li Jiayi , Liu Yijun , Wilke Matheus Vernet Machado Bressan , Li Qian , Liu Haoran , Liang Chen , Morales-Rosado Joel A , Cohen Ana S.A. , Hughes Susan S. , Sullivan Bonnie R. , Waddell Valerie , van den Boogaard Marie-José H. , van Jaarsveld Richard H. , van Binsbergen Ellen , van Gassen Koen L , Wang Tianyun , Hiatt Susan M. , Amaral Michelle D. , Kelley Whitley V. , Zhao Jianbo , Feng Weixing , Ren Changhong , Yu Yazhen , Boczek Nicole J , Ferber Matthew J. , Lahner Carrie , Elliott Sherr , Ruan Yiyan , Cyril Mignot , Keren Boris , Xie Hua , Wang Xiaoyan , Popp Bernt , Zweier Christiane , Piard Juliette , Coubes Christine , Mau-Them Frederic Tran , Safraou Hana , Innes Micheil , Gauthier Julie , Michaud Jacques , Koboldt Daniel C. , Sylvie Odent , Willems Marjolaine , Tan Wen-Hann , Cogne Benjamin , Rieubland Claudine , Braun Dominique , McLean Scott Douglas , Platzer Konrad , Zacher Pia , Oppermann Henry , Evenepoel Lucie , Blanc Pierre , Khattabi Laïla El , Haque Neshatul , Dsouza Nikita R. , Zimmermann Michael T. , Urrutia Raul , Klee Eric W , Shen Yiping , Du Hongzhen , Qin Zailong , Liu Chang-Mei , Chen Xiaoli 
Published: April 2024

AbstractMARK2, a member of the evolutionarily conserved PAR1/MARK serine/threonine kinase family, has been identified as a novel risk gene for autism spectrum disorder (ASD) based on the enrichment ofde novoloss-of-function (Lof) variants in large-scale sequencing studies of ASD individuals. However, the features shared by affected individuals and the molecular mechanism ofMARK2variants during early neural development remained unclear. Here, we report 31 individuals carrying heterozygousMARK2variants and presenting with ASD, other neurodevelopmental disorders, and typical facial dysmorphisms. Lof variants predominate (81%) in affected individuals, while computational analysis andin vitrotransfection assay also point toMARK2loss resulting from missense variants. Using patient-derived and CRISPR-engineered isogenic induced pluripotent stem cells (iPSCs), andMark2+/-(HET) mice, we show thatMARK2loss leads to systemic neurodevelopmental deficits, including anomalous polarity in neural rosettes, imbalanced proliferation and differentiation in neural progenitor cells (NPCs), abnormal cortical development and ASD-like behaviors in mice. Further using RNA-Seq and lithium treatment, we linkMARK2loss to the downregulated WNT/β-catenin signaling pathway and identify lithium as a potential drug for treatingMARK2-related ASD.
Prediction of Central Post-Stroke Pain by Quantitative Sensory Testing
Authors: Asseyer Susanna , Panagoulas Eleni , Maidhof Jana , Villringer Kersten , Al Esra , Chen Xiuhui , Krause Thomas , Hardikar Samyogita , Villringer Arno , Jungehülsing Gerhard Jan 
Published: April 2024

AbstractObjectiveAmong patients with acute stroke, we aimed to identify those who will later develop central post-stroke pain (CPSP) versus those who will not (non-pain sensory stroke: NPSS) by assessing potential differences in somatosensory profile patterns and evaluating their potential as predictors of CPSP.MethodsWe performed a prospective longitudinal quantitative sensory testing (QST) study in 75 stroke patients with somatosensory symptoms, recruited in the acute phase and followed up for 12 months. Based on previous QST studies in chronic stroke, we hypothesised that QST values of cold detection threshold (CDT) and dynamic mechanical allodynia (DMA) would differ between CPSP and NPSS patients before the onset of pain. Mann-Whitney U-tests and mixed ANOVAs with Bonferroni corrections were performed to compare z-normalised QST scores between both groups.ResultsIn total 26 patients (34.7%) developed CPSP. In the acute phase, CPSP patients showed significant contralesional cold hypoesthesia compared to NPSS patients (P= 0.04), but no significant DMA differences. Additional exploratory analysis showed NPSS patients exhibit cold hyperalgesia on the contralesional side compared to the ipsilesional side, not seen in CPSP patients (P= 0.011). A gradient-boosting approach to predicting CPSP from QST patterns prior to pain onset, had an overall accuracy of 84.6, with a recall and precision of 0.75. Notably, both in the acute and the chronic phase, about 80% of CPSP and NPSS patients showed bilateral QST abnormalities.InterpretationCold perception differences between CPSP and NPSS patients appear early post stroke before pain. Prediction of CPSP through QST patterns seems feasible.
Associations of adolescent menstrual symptoms with school absences and educational attainment: analysis of a prospective cohort study
Authors: Sawyer Gemma , Fraser Abigail , Lawlor Deborah A. , Sharp Gemma C. , Howe Laura D. 
Published: April 2024

AbstractBackgroundMenstrual symptoms may negatively impact pupils’ attendance and educational attainment, but rigorous population-based studies are lacking.MethodsIn a prospective cohort study in England, we assessed associations of self-reported heavy or prolonged bleeding and menstrual pain with school absences and attainment, adjusting for potential confounders.FindingsOf 2,698 participants, 36% reported heavy or prolonged bleeding and 56% reported menstrual pain. Heavy or prolonged bleeding was associated with missing 1·7 additional days of school per year (16·58%; 95% CI: 9·43, 24·20), and 48% higher odds of being persistently absent (≥10% absent) (OR 1·48; 95% CI: 1·45, 1·52). Menstrual pain was associated with missing 1·2 additional days of school per year (12·83%; 95% CI: 6·14, 19·95), and 42% higher odds of being persistently absent (OR 1·42; 95% CI: 1·39, 1·46). Heavy or prolonged bleeding was associated with lower scores in compulsory examinations taken at age 16 (−5·7 points; 95% CI: −10·1, −1·2, equating to one lower grade), and with 27% lower odds of achieving five standard passes (OR 0·73; 95% CI: 0·71, 0·75). There was less evidence of an association between menstrual pain and examination scores (−3·14 points; 95% CI: - 7·46, 1·17), but menstrual pain was associated with 16% lower odds of achieving five standard passes (OR 0·84; 95 CI: 0·81, 0·86).InterpretationBoth heavy or prolonged bleeding and menstrual pain were associated with lower school attendance and educational attainment. Greater research and support are needed to enable girls to achieve their full academic potential.FundingWellcome Trust and UK Medical Research Council.
Enigmatic missense mutations can cause disease via creation ofde novonuclear export signals
Authors: McConville By Michael , Thomas Toby , Beckner Ryan , Valadez Catherine , Chook YuhMin , Chung Stephen , Liszczak Glen 
Published: April 2024

SummaryDisease-causing missense mutations that occur within structurally and functionally unannotated protein regions can guide researchers to new mechanisms of protein regulation and dysfunction. Here, we report that the thrombocytopenia-, myelodysplastic syndromes-, and leukemia-associated P214L mutation in the transcriptional regulator ETV6 creates an XPO1-dependent nuclear export signal to cause protein mislocalization. Strategies to disrupt XPO1 activity fully restore ETV6 P214L protein nuclear localization and transcription regulation activity. Mechanistic insight inspired the design of a ‘humanized’ ETV6 mice, which we employ to demonstrate that the germline P214L mutation is sufficient to elicit severe defects in thrombopoiesis and hematopoietic stem cell maintenance. Beyond ETV6, we employed computational methods to uncover rare disease-associated missense mutations in unrelated proteins that create a nuclear export signal to disrupt protein function. Thus, missense mutations that operate through this mechanism should be predictable and may suggest rational therapeutic strategies for associated diseases.
Quinolone resistance genesqnr,aac(6′)-Ib-cr,oqxAB, andqepAin environmentalEscherichia coli: insights into their genetic contexts from comparative genomics
Authors: Gomi Ryota , Adachi Fumie 
Published: April 2024

ABSTRACTPrevious studies have reported the occurrence of transferable quinolone resistance determinants in environmentalEscherichia coli. However, little is known about their vectors and genetic contexts. To gain insights into these genetic characteristics, we analyzed the complete genomes of 53 environmentalE. coliisolates containing one or more transferable quinolone resistance determinants, including 20 sequenced in this study and 33 sourced from RefSeq. The studied genomes carried the following transferable quinolone resistance determinants alone or in combination:aac(6′)-Ib-cr,oqxAB,qepA1,qnrA1,qnrB4,qnrB7,qnrB19,qnrD1,qnrS1, andqnrS2, withqnrS1being predominant. These resistance genes were detected on plasmids of diverse replicon types; however,aac(6′)-Ib-cr,qnrS1, andqnrS2were also detected on the chromosome. The genetic contexts surrounding these genes included not only those found in clinical isolates but also novel contexts, such asqnrD1embedded within a composite transposon-like structure bounded by Tn3-derived inverted-repeat miniature elements (TIMEs). This study provides deep insights into mobile genetic elements associated with transferable quinolone resistance determinants, highlighting the importance of genomic surveillance of antimicrobial resistant bacteria in the environment.
A library-based approach allows systematic and rapid evaluation of seed region length and reveals design rules for synthetic bacterial small RNAs
Authors: Brück Michel , Köbel Tania S. , Dittmar Sophie , Rojas Adán A. Ramírez , Georg Jens , Berghoff Bork A. , Schindler Daniel 
Published: April 2024

AbstractAll organisms must respond to environmental changes. In bacteria, small RNAs (sRNAs) are an important aspect of the regulation network underlying the adaptation to such changes. sRNAs base-pair with their target mRNAs, allowing rapid modulation of the proteome. This post-transcriptional regulation is usually facilitated by RNA chaperones, such as Hfq. sRNAs have a potential as synthetic regulators that can be modulated by rational design. In this study, we use a library-based approach and an oxacillin susceptibility assays to investigate the importance of the seed region length for synthetic sRNAs based on RybB and SgrS scaffolds inEscherichia coli. In the presence of Hfq we show that 12 nucleotides are sufficient for regulation. Furthermore, we observe a scaffold-specific Hfq-dependency and processing by RNase E. Our results provide information for design considerations of synthetic sRNAs in basic and applied research.
Identification of Suitable Target/E3 Ligase Pairs for PROTAC Development using a Rapamycin-induced Proximity Assay (RiPA)
Authors: Adhikari Bikash , Schneider Katharina , Diebold Mathias , Sotriffer Christoph , Wolf Elmar 
Published: April 2024

AbstractThe development of proteolysis targeting chimeras (PROTACs), which induce the degradation of target proteins by bringing them into proximity with cellular E3 ubiquitin ligases, has revolutionized drug development. While the human genome encodes more than 600 different E3 ligases, current PROTACs use only a handful of them, drastically limiting their full potential. Furthermore, many PROTAC development campaigns fail because the selected E3 ligase candidates are unable to induce degradation of the particular target of interest. As more and more ligands for novel E3 ligases are discovered, the chemical effort to identify the best E3 ligase for a given target is exploding. Therefore, a genetic system to identify degradation-causing E3 ligases and suitable target/E3 ligase pairs is urgently needed. Here we used the well-established dimerization of the FKBP12 protein and FRB domain by rapamycin to bring the target protein WDR5 into proximity with candidate E3 ligases. Strikingly, this rapamycin-induced proximity assay (RiPA) revealed that VHL, but not Cereblon, is able to induce WDR5 degradation - a finding previously made by PROTACs, demonstrating its predictive power. By optimizing the steric arrangement of all components and fusing the target protein with a minimal luciferase, RiPA can identify the ideal E3 for any target protein of interest in living cells, significantly reducing and focusing the chemical effort in the early stages of PROTAC development.
Exploring transient states of PAmKate to enable improved cryogenic single-molecule imaging
Authors: Perez Davis , Dowlatshahi Dara P. , Azaldegui Christopher A. , Ansell T. Bertie , Dahlberg Peter D. , Moerner W. E. 
Published: April 2024

AbstractSuper-resolved cryogenic correlative light and electron microscopy is a powerful approach which combines the single-molecule specificity and sensitivity of fluorescence imaging with the nano-scale resolution of cryogenic electron tomography. Key to this method is active control over the emissive state of fluorescent labels to ensure sufficient sparsity to localize individual emitters. Recent work has identified fluorescent proteins (FPs) which photoactivate or photoswitch efficiently at cryogenic temperatures, but long on-times due to reduced quantum yield of photobleaching remains a challenge for imaging structures with a high density of localizations. In this work, we explore the photophysical properties of the red photoactivatable FP PAmKate and identify a 2-color process leading to enhanced turn-off of active emitters, improving localization rate. Specifically, after excitation of ground state molecules, we find a transient state forms with a lifetime of ∼2 ms under cryogenic conditions which can be bleached by exposure to a second wavelength. We measure the response of the transient state to different wavelengths, demonstrate how this mechanism can be used to improve imaging, and provide a blueprint for study of other FPs at cryogenic temperatures.
Biochemical and structural insights into a 5’ to 3’ RNA ligase reveal a potential role in tRNA ligation
Authors: Hu Yingjie , Lopez Victor A. , Xu Hengyi , Pfister James P. , Song Bing , Servage Kelly A. , Sakurai Masahiro , Jones Benjamin T. , Mendell Joshua T. , Wang Tao , Wu Jun , Lambowitz Alan M. , Tomchick Diana R. , Pawłowski Krzysztof , Tagliabracci Vincent S. 
Published: April 2024

AbstractATP-grasp superfamily enzymes contain a hand-like ATP-binding fold and catalyze a variety of reactions using a similar catalytic mechanism. More than 30 protein families are categorized in this superfamily, and they are involved in a plethora of cellular processes and human diseases. Here we identify C12orf29 as an atypical ATP-grasp enzyme that ligates RNA. Human C12orf29 and its homologs auto-adenylate on an active site Lys residue as part of a reaction intermediate that specifically ligates RNA halves containing a 5’-phosphate and a 3’-hydroxyl. C12orf29 binds tRNA in cells and can ligate tRNA within the anticodon loopin vitro. Genetic depletion ofc12orf29in female mice alters global tRNA levels in brain. Furthermore, crystal structures of a C12orf29 homolog fromYasminevirusbound to nucleotides reveal a minimal and atypical RNA ligase fold with a unique active site architecture that participates in catalysis. Collectively, our results identify C12orf29 as an RNA ligase and suggest its involvement in tRNA biology.Significance StatementATP-grasp enzymes share an atypical ATP-binding fold and catalyze a diverse set of reactions involved in many essential cellular processes. We identified C12orf29 as an atypical ATP-grasp enzyme. Our biochemical and structural characterizations reveal this enzyme to be a 5’ to 3’ RNA ligase, structurally and functionally similar to the phage T4 RNA ligase. C12orf29 can ligate tRNAsin vitroand C12orf29 knockout female mice have altered tRNA levels in brain. We also report structures of C12orf29, which have revealed critical insights into the mode of ATP binding and catalysis. Our work suggests that C12orf29 may be a new player in the regulation of tRNAs.
Intelligent soaring and path planning for solar-powered unmanned aerial vehicles
Authors: Wu Yansen , Wen Dongsheng , Zhao Anmin , Liu Haobo , Li Ke 
Published: April 2024

Purpose
This study aims to study the thermal identification issue by harvesting both solar energy and atmospheric thermal updraft for a solar-powered unmanned aerial vehicle (SUAV) and its electric energy performance under continuous soaring conditions.

Design/methodology/approach
The authors develop a specific dynamic model for SUAVs in both soaring and cruise modes. The support vector machine regression (SVMR) is adopted to estimate the thermal position, and it is combined with feedback control to implement the SUAV soaring in the updraft. Then, the optimal path model is built based on the graph theory considering the existence of several thermals distributed in the environment. The procedure is proposed to estimate the electricity cost of SUAV during flight as well as soaring, and making use of dynamic programming to maximize electric energy.

Findings
The simulation results present the integrated control method could allow SUAV to soar with the updraft. In addition, the proposed approach allows the SUAV to fly to the destination using distributed thermals while reducing the electric energy use.

Originality/value
Two simplified dynamic models are constructed for simulation considering there are different flight mode. Besides, the data-driven-based SVMR method is proposed to support SUAV soaring. Furthermore, instead of using length, the energy cost coefficient in optimization problem is set as electric power, which is more suitable for SUAV because its advantage is to transfer the three-dimensional path planning problem into the two-dimensional.