bluuebunny/crossref_metadata_2025_split huggingface dataset:
CLAVATA signalling shapes barley inflorescence architecture by controlling activity and determinacy of shoot apical and rachilla meristems
Authors: Vardanega Isaia , Maika Jan Eric , Demesa-Arevalo Edgar , Lan Tianyu , Kirschner Gwendolyn K. , Imani Jafargholi , Acosta Ivan F. , Makowska Katarzyna , Hensel Götz , Ranaweera Thilanka , Shiu Shin-Han , Schnurbusch Thorsten , von Korff Schmising Maria , Simon Rüdiger 
Published: May 2024

AbstractGrasses exhibit a large variety of diverse inflorescence architectures, from complex branched inflorescences inOryzeae(rice) to simple spike-type inflorescences inTriticeae(e.g. barley, wheat). Inflorescence architecture depends on shape, longevity and determinacy of meristems that direct growth of the main rachis and lateral branches, but how individual meristem activities are determined and integrated within complex inflorescences is not yet understood. We found that activity of distinct meristems in the barley inflorescence is coordinated by a signalling pathway comprising the receptor like kinaseHordeum vulgareCLAVATA1 (HvCLV1) and the secreted CLAVATA3/ENDOSPERM SURROUNDING REGION (CLE)-family peptide FON2- LIKE CLE PROTEIN1 (HvFCP1). HvFCP1 interacts with HvCLV1 to promote spikelet formation but restricts inflorescence meristem and rachilla meristem proliferation.Hvfcp1orHvclv1mutants generate branched inflorescences with additional rows of spikelets and supernumerary florets. Transcriptome analysis reveals thatHvFCP1/HvCLV1signalling controls inflorescence branching through the regulation of trehalose-6-phosphate synthesis and sugar transport. Our discoveries reveal the potential to engineer barley inflorescence architecture by manipulating regulation of distinct meristem activities.
Genetic background affects the strength of crossover interference in house mice
Authors: Morgan Andrew P , Payseur Bret A 
Published: May 2024

AbstractMeiotic recombination is required for faithful chromosome segregation in most sexually reproducing organisms and shapes the distribution of genetic variation in populations. Both the overall rate and the spatial distribution of crossovers vary within and between species. Adjacent crossovers on the same chromosome tend to be spaced more evenly than expected at random, a phenomenon known as crossover interference. Although interference has been observed in many taxa, the factors that influence the strength of interference are not well understood. We used house mice (Mus musculus), a well-established model system for understanding recombination, to study the effects of genetics and age on recombination rate and interference in the male germline. We analyzed crossover positions in 503 progeny from reciprocal F1 hybrids between inbred strains representing the three major subspecies of house mice. Consistent with previous studies, autosomal alleles fromM. m. musculustend to increase recombination rate, while inheriting aM. m. musculusX chromosome decreases recombination rate. Old males transmit an average of 0.6 more crossovers per meiosis (5.0%) than young males, though the effect varies across genetic backgrounds. We show that the strength of crossover interference depends on genotype, providing a rare demonstration that interference evolves over short timescales. Differences between reciprocal F1s suggest that X-linked factors modulate the strength of interference. Our findings motivate additional comparisons of interference among recently diverged species and further examination of the role of paternal age in determining the number and positioning of crossovers.
Direct lineage conversion of postnatal mouse cortical astrocytes to oligodendrocyte lineage cells
Authors: Bajohr Justine , Scott Erica Y. , Olfat Arman , Sadria Mehrshad , Lee Kevin , Fahim Maria , Taha Hiba T. , Lozano Casasbuenas Daniela , Derham Ann , Yuzwa Scott A. , Bader Gary D. , Faiz Maryam 
Published: May 2024

SUMMARYOligodendrocyte lineage cells (OLCs) are lost in many CNS diseases. Here, we investigate the generation of new OLCs via ectopic expression ofSox10,Olig2orNkx6.2in mouse postnatal astrocytes. Using stringent analyses including, Aldh1l1-astrocyte fate mapping and live cell imaging we confirm thatSox10andOlig2, but notNkx6.2, directly convert Aldh1l1posastrocytes to MBP+ and PDGFRα+ induced OLCs (iOLCs), respectively. With single cell RNA sequencing (scRNA-seq) we uncover the molecular signatures of iOLCs. Transcriptomic analysis ofSox10- and control cultures over time reveals a clear trajectory from astrocytes to iOLCs. Finally, perturbation models CellOracle and Fatecode support the idea thatSox10drives cells towards a terminal iOLC fate. Altogether, this multidimensional analysis shows bonafide conversion of astrocytes to iOLCs usingSox10orOlig2and provides a foundation for astrocyte DLR strategies to promote OLC repair.
Generative Artificial Intelligence Model for Simulating Brain Structural Changes in Schizophrenia
Authors: Yamaguchi Hiroyuki , Sugihara Genichi , Simizu Masaaki , Yamashita Yuichi 
Published: May 2024

AbstractBackgroundRecent advancements in generative artificial intelligence (AI) for image generation have presented significant opportunities for medical imaging, offering a promising avenue for generating realistic virtual medical images while ensuring patient privacy. The generation of a large number of virtual medical images through AI has the potential to augment training datasets for discriminative AI models, particularly in fields with limited data availability, such as neuroimaging. Current studies on generative AI in neuroimaging have mainly focused on disease discrimination; however, its potential for simulating complex phenomena in psychiatric disorders remains unknown. In this study, as examples of a simulation, we aimed to present a novel generative AI model that transforms magnetic resonance imaging (MRI) images of healthy individuals into images that resemble those of patients with schizophrenia (SZ) and explore its application.MethodsWe used anonymized public datasets from the Center for Biomedical Research Excellence (SZ, 71 patients; healthy subjects [HSs], 71 patients) and the Autism Brain Imaging Data Exchange (autism spectrum disorder [ASD], 79 subjects; HSs, 105 subjects). We developed a model to transform MRI images of HSs into MRI images of SZ using cycle generative adversarial networks. The efficacy of the transformation was evaluated using voxel-based morphometry to assess the differences in brain region volume and the accuracy of age prediction pre- and post-transformation. In addition, the model was examined for its applicability in simulating disease comorbidities and disease progression.ResultsThe model successfully transformed HS images into SZ images and identified brain volume changes consistent with existing case-control studies. We also applied this model to ASD MRI images, where simulations comparing SZ with and without ASD backgrounds highlighted the differences in brain structures due to comorbidities. Furthermore, simulation of disease progression while preserving individual characteristics showcased the model’s ability to reflect realistic disease trajectories.DiscussionThe findings suggest that our generative AI model can capture subtle changes in brain structures associated with SZ and offers a novel tool for visualizing brain alterations across various conditions. The potential of this model extends beyond clinical diagnoses to advancements in the simulation of disease mechanisms, which may ultimately contribute to the refinement of therapeutic strategies.
Impact of Cerebrospinal Fluid Leukocyte Infiltration and Neuroimmmune Mediators on Survival with HIV-Associated Cryptococcal Meningitis
Authors: Okurut Samuel , Boulware David R. , Manabe Yukari C. , Tugume Lillian , Skipper Caleb P. , Ssebambulidde Kenneth , Rhein Joshua , Musubire Abdu K. , Akampurira Andrew , Okafor Elizabeth , Olobo Joseph O. , Janoff Edward N. , Meya David B. ,   ASTRO Trial Team
Published: May 2024

AbstractIntroductionCryptococcal meningitis remains a prominent cause of death in persons with advanced HIV disease. CSF leukocyte infiltration predicts survival at 18 weeks; however, how CSF immune response relates to CSF leukocyte infiltration is unknown.MethodsWe enrolled 401 adults with HIV-associated cryptococcal meningitis in Uganda who received amphotericin and fluconazole induction therapy. We assessed the association of CSF leukocytes, chemokine, and cytokine responses with 18-week survival.ResultsParticipants with CSF leukocytes ≥50/µL, had higher probability 68% (52/77) of 18-week survival compared with 52% (151/292) 18-week survival in those with ≤50 cells/µL (Hazard Ratio=1.63, 95% confidence intervals 1.14-2.23; p=0.008). Survival was also associated with higher expression of T helper (Th)-1, Th17 cytokines, and immune regulatory elements. CSF levels of Programmed Death-1 Ligand, CXCL10, and Interleukin (IL)-2 independently predicted survival. In multivariate analysis, CSF leukocytes were inversely associated with CSF fungal burden and positively associated with CSF protein, interferon-gamma (IFN-γ), IL-17A, tumor necrosis factor (TNF)-α, and peripheral blood CD4+and CD8+T cells expression.Conclusion18-week survival after diagnosis of cryptococcal meningitis was associated with higher CSF leukocytes at baseline with greater T helper 1 (IFN-γ, IL-2 and TNF-α cytokines), T helper 17 (IL-17A cytokine) and CXCR3+T cell (CXCL10 chemokine) responses. These results highlight the interdependent contribution of soluble and cellular immune responses in predicting survival with HIV-associated cryptococcal meningitis.
Sex and Marital-Status Differences in Delayed Initiation for Pharyngeal Cancer Treatment, Before and After Medicaid Expansion
Authors: Semprini Jason 
Published: May 2024

BackgroundIn the United States, pharyngeal cancer has become the most common type of head and neck cancer, with 80% of cases found in males. Although disparities in treatment delays have been observed in pharyngeal patients, less is known about how policies facilitate timely care. This study aimed to estimate the association between Medicaid expansion and delaying initiation of pharyngeal cancer treatment.MethodologyWe extracted Surveillance, Epidemiological, End Results (SEER) case data to analyze pharyngeal cancers diagnosed between 2000-2018. The outcome of interest was a binary variable indicating if the patient initiated treatment two or more months after diagnosis. We conducted subgroup analyses by sex, marital status, and type of treatment received (surgery, radiation, chemotherapy, post-operative radiation, systemic therapy). We implement the Matrix Completion algorithm to account for staggered rollout of Medicaid expansion within our difference-in-differences design.ResultsOur sample included 79,433 patients diagnosed with pharynx cancer. Delayed treatment was lowest among married females receiving systemic therapy (5%), and highest among married males and females not recommended to receive surgery (43%). Generally, there was no association between Medicaid expansion and changes in delayed treatment. Subgroup analyses show that Medicaid expansion was associated with reduced treatment delays in unmarried females receiving systemic therapy (-4.5%-points), and married males receiving chemotherapy (Est. = -2.6%-points), radiotherapy (Est. = -3.1%-points), and married males not recommended to receive surgery (Est. = -4.6%-points).ConclusionsGiven the importance of timely pharyngeal cancer treatment, health systems must identify and address the drivers of treatment delays to advance cancer equity.
What Factors are Important to the Success of Resubmitted Grant Applications in Health Research? A Retrospective Study of Over 20,000 Applications to the Canadian Institutes of Health Research
Authors: Wrightson J.G , Lasinsky A. , Snell R.R. , Hogel M. , Mota A. , Khan K.M. , Ardern C.L. 
Published: May 2024

AbstractBackgroundIn this retrospective study, we investigated the outcomes (funded/not funded) and factors related to the funding of resubmitted applications to the Canadian Institutes of Health Research (CIHR) Open Operating Grants Competition and Project Grant Competition between 2000 and 2022.Method and FindingsThe primary outcome was the proportion of resubmissions and new applications that were funded. Using a random forest model, we explored the importance of variables related to the success of resubmissions. A higher proportion of resubmissions (∼23%) were funded compared to new submissions (∼12%). The most important variables related to resubmission success were the rank (%) and score (/5) given to the preceding (initial) application and the number of the number of CIHR-funded grants where the PI was a named team member.ConclusionResubmitting applications to the CIHR Project Grant Competition was beneficial, particularly for projects that were previously highly ranked and received high scores. These results may offer guidance for researchers who are deciding whether to resubmit rejected applications.
Is Wear Still a Concern in TKA With Contemporary Conventional and Highly Crosslinked Polyethylene Tibial Inserts in the Mid- to Long-Term?
Authors: Asher Devin P. , Wright Jennifer L. , Hall Deborah J. , Lundberg Hannah J. , Van Citters Douglas W. , Jacobs Joshua J. , Levine Brett R. , Pourzal Robin 
Published: May 2024

AbstractBackgroundModern literature has brought into question if wear of tibial inserts made from conventional or highly-crosslinked polyethylene (HXL PE) is still a factor limiting longevity of total knee arthroplasty (TKA) in the mid- to long-term. It is the objective of this study to determine: 1) most common causes of mid- to long-term TKA failure, 2) the prevalence of delamination, and 3) the medial/lateral linear wear rates of conventional and HXL PE tibial inserts retrieved in the mid- to long-term.MethodsA tibial insert retrieval cohort of 107 inserts (79 conventional, 28 HXL PE) with a minimum timein situof 6.5 years (mean 11.7±4) was studied. Failure causes were determined from chart-review, delamination presence was assessed microscopically, and medial/lateral linear wear was determined by minimal thickness changes measured with a dial-indicator.ResultsThe most common mid-to long-term etiologies for failure were instability (44.9%), PE wear 15%), aseptic loosening (14%) and infection (13.1%). Delamination occurred in 70% of inserts (72.1% conventional, 64.3% HXLPE). Gross material loss due to delamination appeared to be the underlying reason for at least 33.3% of cases exhibiting instability. Of the cases removed for infection, 75% exhibited no histopathological hallmarks of acute infection. The medial/lateral wear rates were 0.054/0.051 (conventional) and 0.014/0.011 (HXL) mm/year, respectively.ConclusionsPolyethylene wear still appears to be a major primary and secondary cause for TKA revision in the mid- to long-term. Wear may manifest as destabilizing delamination or as continuous release of fine wear particles potentially resulting in inflammatory responses and subsequent failure.
Large-scale integration of omics and electronic health records to identify potential risk protein biomarkers and therapeutic drugs for cancer prevention and intervention
Authors: Li Qing , Song Qingyuan , Chen Zhishan , Choi Jungyoon , Moreno Victor , Ping Jie , Wen Wanqing , Li Chao , Shu Xiang , Yan Jun , Shu Xiao-ou , Cai Qiuyin , Long Jirong , Huyghe Jeroen R , Pai Rish , Gruber Stephen B , Casey Graham , Wang Xusheng , Toriola Adetunji T. , Li Li , Singh Bhuminder , Lau Ken S , Zhou Li , Wu Chong , Peters Ulrike , Zheng Wei , Long Quan , Yin Zhijun , Guo Xingyi 
Published: May 2024

AbstractIdentifying risk protein targets and their therapeutic drugs is crucial for effective cancer prevention. Here, we conduct integrative and fine-mapping analyses of large genome-wide association studies data for breast, colorectal, lung, ovarian, pancreatic, and prostate cancers, and characterize 710 lead variants independently associated with cancer risk. Through mapping protein quantitative trait loci (pQTL) for these variants using plasma proteomics data from over 75,000 participants, we identify 365 proteins associated with cancer risk. Subsequent colocalization analysis identifies 101 proteins, including 74 not reported in previous studies. We further characterize 36 potential druggable proteins for cancers or other disease indications. Analyzing >3.5 million electronic health records, we uncover five drugs (Haloperidol, Trazodone, Tranexamic Acid, Haloperidol, and Captopril) associated with increased cancer risk and two drugs (Caffeine and Acetazolamide) linked to reduced colorectal cancer risk. This study offers novel insights into therapeutic drugs targeting risk proteins for cancer prevention and intervention.
Abscisic acid and GIGANTEA signalling converge to regulate the recruitment of CONSTANS to theFTpromoter and activate floral transition
Authors: Test Alice Robustelli , Perrella Giorgio , Colanero Sara , Landoni Beatrice , Sutti Aldo , Krukowski Paolo Korwin , Vellutini Elisa , Castorina Giulia , Galbiati Massimo , Martignago Damiano , Kaiserli Eirini , Tonelli Chiara , Conti Lucio 
Published: May 2024

AbstractPlants align flowering with optimal seasonal conditions to increase reproductive success. This process depends on modulating signalling pathways that respond to diverse environmental and hormonal inputs, thereby regulating the transition to flowering at the shoot apical meristem. InArabidopsis, long-day photoperiods (LDs) stimulate the transcription ofFLOWERING LOCUS T(FT), encoding the main florigenic signal.FTactivation is mediated by the transcriptional regulator CONSTANS (CO), which binds to the CO responsive elements (COREs) located in the proximalFTpromoter region. The phytohormone abscisic acid also (ABA) contributes toFTactivation together with GIGANTEA (GI) to regulate drought escape (DE). Whether CO is a target of ABA and GI actions for the regulation ofFTis, however, unknown. Here we report that ABA and its signalling components promote CO recruitment to the COREs, without causing clear effects on the diel pattern of CO protein accumulation. We also found that GI promotes CO recruitment to the COREs region, and that CO recruitment is required for the accumulation of RNAPol II at theTRANSCRIPTION START SITEofFT. Finally, we show that GI and ABA signalling pathways are largely epistatic in the control of flowering time, suggesting their involvement in the same molecular process. Taken together, these observations suggest that varying water deficit conditions modulate CO recruitment andFTexpression, thus dictating DE strategies inArabidopsis.HighlightABA and GIGANTEA signalling promoteFLOWERING LOCUS T(FT) transcriptional activation by regulating the binding of the transcription factor CONSTANS to the proximalFTpromoter.
mTOR inhibition in Q175 Huntington’s disease model mice facilitates neuronal autophagy and mutant huntingtin clearance
Authors: Stavrides Philip , Goulbourne Chris N. , Peddy James , Huo Chunfeng , Rao Mala , Khetarpal Vinod , Marchionini Deanna M. , Nixon Ralph A. , Yang Dun-Sheng 
Published: May 2024

AbstractHuntington’s disease (HD) is caused by expansion of the polyglutamine stretch in huntingtin protein (HTT) resulting in hallmark aggresomes/inclusion bodies (IBs) composed of mutant huntingtin protein (mHTT) and its fragments. Stimulating autophagy to enhance mHTT clearance is considered a potential therapeutic strategy for HD. Our recent evaluation of the autophagic-lysosomal pathway (ALP) in human HD brain reveals upregulated lysosomal biogenesis and relatively normal autophagy flux in early Vonsattel grade brains, but impaired autolysosome clearance in late grade brains, suggesting that autophagy stimulation could have therapeutic benefits as an earlier clinical intervention. Here, we tested this hypothesis by crossing the Q175 HD knock-in model with our autophagy reporter mouse TRGL (Thy-1-RFP-GFP-LC3) to investigatein vivoneuronal ALP dynamics. In the Q175 and/or TRGL/Q175 mice, mHTT was detected in autophagic vacuoles and also exhibited high level colocalization with autophagy receptors p62/SQSTM1 and ubiquitin in the IBs. Compared to the robust lysosomal pathology in late-stage human HD striatum, ALP alterations in Q175 models are also late-onset but milder that included a lowered phospho-p70S6K level, lysosome depletion and autolysosome elevation including more poorly acidified autolysosomes and larger-sized lipofuscin granules, reflecting impaired autophagic flux. Administration of a mTOR inhibitor to 6-mo-old TRGL/Q175 normalized lysosome number, ameliorated aggresome pathology while reducing mHTT-, p62- and ubiquitin-immunoreactivities, suggesting beneficial potential of autophagy modulation at early stages of disease progression.
Not so griddy: Internal representations of RNNs path integrating more than one agent
Authors: Redman William T. , Acosta Francisco , Acosta–Mendoza Santiago , Miolane Nina 
Published: May 2024

AbstractSuccess in collaborative and competitive environments, where agents must work with or against each other, requires individuals to encode the position and trajectory of themselves and others. Decades of neurophysiological experiments have shed light on how brain regions [e.g., medial entorhinal cortex (MEC), hippocampus] encode the self’s position and trajectory. However, it has only recently been discovered that MEC and hippocampus are modulated by the positions and trajectories of others. To understand how encoding spatial information of multiple agents shapes neural representations, we train a recurrent neural network (RNN) model that captures properties of MEC to path integrate trajectories of two agents simultaneously navigating the same environment. We find significant differences between these RNNs and those trained to path integrate only a single agent. At the individual unit level, RNNs trained to path integrate more than one agent develop weaker grid responses, stronger border responses, and tuning for therelativeposition of the two agents. At the population level, they develop more distributed and robust representations, with changes in network dynamics and manifold topology. Our results provide testable predictions and open new directions with which to study the neural computations supporting spatial navigation.
Healthy human induced pluripotent stem cell-derived cardiomyocytes exhibit sex dimorphism even without the addition of hormones
Authors: Givens Sophie E. , Andebrhan Abygail A. , Schmuck Eric G. , Renaud Aimee , Abrahante Juan E. , Stanis Noah , Dutton James R. , Ogle Brenda M. 
Published: May 2024

AbstractHuman induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CM) are a valuable cell type for studying human cardiac health and diseasein vitro. However, it is not known whether hiPSC-CM display sex dimorphism and therefore whether sex should be incorporated as a biological variable inin vitrostudies that include this cell type. To date, the vast majority of studies that utilize hiPSC-CM do not include both male and female sex nor stratify results based on sex because it is challenging to amass such a cohort of cells. Here we generated three female and three male hiPSC-lines from adult left ventricular cardiac fibroblasts as a resource for studying sex differences inin vitrocardiac models. We used this resource to generate hiPSC-CM and maintained them in basal media without exogenous hormones. Functional assessment of CM showed enhanced calcium handling in female-derived hiPSC-CM relative to male. Bulk RNA sequencing revealed over 300 differentially expressed genes (DEG) between male and female hiPSC-CM. Some of the DEG are X and Y-linked genes and many are implicated in cardiac health and disease including potassium channels which could account for net differences in calcium handling shown here. Gene ontology analysis of DEG showed distinct differences in pathways related to cardiac pathology including cell-cell adhesion, metabolic processes, and response to ischemic stress. These findings highlight the importance of considering sex as a variable when conducting studies to evaluate aspects of human cardiac health and disease related to cardiomyocyte function.