bluuebunny/crossref_metadata_2025_split huggingface dataset:
Late-Term Findings of Pancreatitis on 68Ga-PSMA PET/CT in a Patient With Prostate Cancer
Authors: Tosunoğlu Zehranur , Erol Fenercioğlu Özge , Beyhan Ediz , Arslan Esra , Çermik Tevfik Fikret 
Published: August 2022

Abstract
The 68Ga-PSMA PET/CT imaging modality is used to evaluate biochemical recurrence, response to treatment, and staging in prostate cancer. Prostate-specific membrane antigen (PSMA) receptor activation can be seen in benign and malignant diseases as well as in many physiological tissues. Many pitfalls and artifacts have been reported when reporting 68Ga-PSMA PET/CT. In this case, diffuse moderate PSMA receptor activation in pancreatic tissue due to the previous pancreatitis is presented in 68Ga-PSMA PET/CT imaging modality that was performed for restaging of prostate cancer.
Potential Pitfall of Fluciclovine PET/CT in Castrate-Resistant Prostate Cancer With Adrenal Metastasis
Authors: Qi Jin , Nguyen Nghi C. 
Published: August 2022

Abstract
An 83-year-old man with castrate-resistant prostate cancer underwent an 18F-fluciclovine PET/CT scan, which was negative for local disease recurrence or locoregional lymphadenopathy, but there were multiple fluciclovine-avid bone metastases. In addition, mildly avid bilateral adrenal nodules were thought to be benign. However, on follow-up PET/CT 10 months later, while on additional therapy with enzalutamide, the bilateral nodules became mass lesions with interval decreased fluciclovine avidity. Adrenal metastases were suspected given their rapid growth, with subsequent CT-guided biopsy revealing metastatic prostate cancer without tumor necrosis. This false-negative case highlights the diagnostic challenge of fluciclovine PET in characterizing adrenal lesions.
Improving treatment outcomes for borderline personality disorder: what can we learn from biomarker studies of psychotherapy?
Authors: Marceau Ely M. , Ruocco Anthony C. , Grenyer Brin F.S. 
Published: August 2022

Purpose of review
Borderline personality disorder (BPD) is a severe and common psychiatric disorder and though evidence-based psychotherapies are effective, rates of treatment nonresponse are as high as 50%. Treatment studies may benefit from interdisciplinary approaches from neuroscience and genetics research that could generate novel insights into treatment mechanisms and tailoring interventions to the individual.

Recent findings
We provide a timely update to the small but growing body of literature investigating neurobiological and epigenetic changes and using biomarkers to predict outcomes from evidence-based psychotherapies for BPD. Using a rapid review methodology, we identified eight new studies, updating our earlier 2018 systematic review. Across all studies, neuroimaging (n = 18) and genetics studies (n = 4) provide data from 735 participants diagnosed with BPD (mean sample size across studies = 33.4, range 2–115).

Summary
We report further evidence for psychotherapy-related alterations of neural activation and connectivity in regions and networks relating to executive control, emotion regulation, and self/interpersonal functioning in BPD. Emerging evidence also shows epigenetic changes following treatment. Future large-scale multisite studies may help to delineate multilevel treatment targets to inform intervention design, selection, and monitoring for the individual patient via integration of knowledge generated through clinical, neuroscience, and genetics research.
Evaluation of Transfer Learning Methods for Detecting Alzheimer’s Disease with Brain MRI
Authors: Dhinagar Nikhil J. , Thomopoulos Sophia I. , Rajagopalan Priya , Stripelis Dimitris , Ambite Jose Luis , Ver Steeg Greg , Thompson Paul M. 
Published: August 2022

ABSTRACTDeep neural networks show great promise for classifying brain diseases and making prognostic assessments based on neuroimaging data, but large, labeled training datasets are often required to achieve high predictive accuracy. Here we evaluated a range oftransfer learningor pre-training strategies to create useful MRI representations for downstream tasks that lack large amounts of training data, such as Alzheimer’s disease (AD) classification. To test our proposed pre-training strategies, we analyzed 4,098 3D T1-weighted brain MRI scans from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort and independently validated with an out-of-distribution test set of 600 scans from the Open Access Series of Imaging Studies (OASIS3) cohort for detecting AD. First, we trained 3D and 2D convolutional neural network (CNN) architectures. We tested combinations of multiple pre-training strategies based on (1) supervised, (2) contrastive learning, and (3) self-supervised learning - using pre-training data within versus outside the MRI domain. In our experiments, the 3D CNN pre-trained with contrastive learning provided the best overall results - when fine-tuned on T1-weighted scans for AD classification - outperformed the baseline by 2.8% when trained with all of the training data from ADNI. We also show test performance as a function of the training dataset size and the chosen pre-training method. Transfer learning offered significant benefits in low data regimes, with a performance boost of 7.7%. When the pre-trained model was used for AD classification, we were able to visualize an improved clustering of test subjects’ diagnostic groups, as illustrated via a uniform manifold approximation (UMAP) projection of the high-dimensional model embedding space. Further, saliency maps indicate the additional activation regions in the brain scan using pre-training, that then maximally contributed towards the final prediction score.
The kinesin motor KIF1C is a putative transporter of the exon junction complex in neuronal cells
Authors: Nagel Maike , Noß Marvin , Xu Jishu , Horn Nicola , Ueffing Marius , Boldt Karsten , Schüle Rebecca 
Published: August 2022

AbstractNeurons critically depend on regulated RNA localization and tight control of spatio-temporal gene expression to maintain their morphological and functional integrity. Mutations in the kinesin motor protein gene KIF1C cause Hereditary Spastic Paraplegia, an autosomal recessive disease leading to predominant degeneration of the long axons of central motoneurons. In this study we aimed to gain insight into the molecular function of KIF1C and understand how KIF1C dysfunction contributes to motoneuron degeneration.We used affinity proteomics in neuronally differentiated neuroblastoma cells (SH-SY5Y) to identify the protein complex associated with KIF1C in neuronal cells; candidate interactions were then validated by immunoprecipitation and mislocalization of putative KIF1C cargoes was studied by immunostainings.We found KIF1C to interact with all core components of the exon junction complex (EJC); expression of mutant KIF1C in neuronal cells leads to loss of the typical localization distally in neurites. Instead, EJC core components accumulate in the pericentrosomal region, here co-localizing with mutant KIF1C. These findings suggest KIF1C as a neuronal transporter of the EJC. Interestingly, the binding of KIF1C to the EJC is RNA-mediated, as treatment with RNAse prior to immunoprecipitation almost completely abolishes the interaction. Silica-based solid-phase extraction of UV-crosslinked RNA-protein complexes furthermore supports direct interaction of KIF1C with RNA, as recently also demonstrated for kinesin heavy chain. Taken together, our findings are consistent with a model where KIF1C transports mRNA in an EJC-bound and therefore transcriptionally silenced state along neurites, thus providing the missing link between the EJC and mRNA localization in neurons.
MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells
Authors: Zelceski Anabel , Francica Paola , Lingg Lea , Mutlu Merve , Stok Colin , Liptay Martin , Alexander John , Baxter Joseph S. , Brough Rachel , Gulati Aditi , Haider Syed , Raghunandan Maya , Song Feifei , Sridhar Sandhya , Forment Josep V. , O’Connor Mark J. , Davies Barry R. , van Vugt Marcel A.T.M. , Krastev Dragomir B. , Pettitt Stephen J. , Tutt Andrew N. J. , Rottenberg Sven , Lord Christopher J. 
Published: August 2022

AbstractThe PSMC3IP-MND1 heterodimer promotes RAD51 and DMC1-dependent D-loop formation during meiosis in yeast and mammalian organisms. For this purpose, it catalyzes the DNA strand exchange activities of the recombinases. Interestingly, in a panel of genome-scale CRISPR-Cas9 mutagenesis and interference screens in mitotic cells, we found that depletion of either PSMC3IP or MND1 caused sensitivity to clinical Poly (ADP-Ribose) Polymerase inhibitors (PARPi). A retroviral mutagenesis screen in mitotic cells also identified PSMC3IP and MND1 as genetic determinants of ionizing radiation sensitivity. The role PSMC3IP and MND1 play in preventing PARPi sensitivity in mitotic cells appears to be independent of a previously described role in alternative lengthening of telomeres (ALT). PSMC3IP or MND1 depleted cells accumulate toxic RAD51 foci in response to DNA damage, show impaired homology-directed DNA repair, and become PARPi sensitive, even in cells lacking both BRCA1 and TP53BP1. Although replication fork reversal is also affected, the epistatic relationship between PSMC3IP-MND1 and BRCA1/BRCA2 suggests that the abrogated D-loop formation is the major cause of PARPi sensitivity. This is corroborated by the fact that a PSMC3IP p.Glu201del D-loop formation mutant associated with ovarian dysgenesis fails to reverse PARPi sensitivity. These observations suggest that meiotic proteins such as MND1 and PSMC3IP could have a greater role in mitotic cells in determining the response to therapeutic DNA damage.
Early midbrain sensorimotor pathway is involved in the timely initiation and direction of swimming in the hatchling Xenopus laevis tadpole
Authors: Larbi Michelle Christine , Messa Giulia , Jalal Helin , Koutsikou Stella 
Published: August 2022

AbstractVertebrate locomotion is heavily dependent on descending control originating in the midbrain and subsequently influencing central pattern generators in the spinal cord. However, the midbrain neuronal circuitry and its connections with other brainstem and spinal motor circuits has not been fully elucidated. Basal vertebrates with very simple nervous system, like the hatchling Xenopus laevis tadpole, have been instrumental in unravelling fundamental principles of locomotion and its suspraspinal control. Here, we use behavioral and electrophysiological approaches in combination with lesions of the midbrain to investigate its contribution to the initiation and control of the tadpole swimming in response to trunk skin stimulation. None of the midbrain lesions studied here blocked the tadpole’s sustained swim behavior following trunk skin stimulation. However, we identified that distinct midbrain lesions led to significant changes in the latency and trajectory of swimming. These changes could partly be explained by the increase in synchronous muscle contractions on the opposite sides of the tadpole’s body and permanent deflection of the tail from its normal position, respectively. Furthermore, the midbrain lesions led to significant changes in the tadpole’s ability to stop swimming when it bumps head on to solid objects. We conclude that the tadpole’s embryonic trunk skin sensorimotor pathway involves the midbrain, which harbors essential neuronal circuitry to significantly contribute to the appropriate, timely and coordinated selection and execution of locomotion, imperative to the animal’s survival.
Aspirin reprogrammes colorectal cancer cell metabolism and sensitises to glutaminase inhibition
Authors: Holt Amy K. , Najumudeen Arafath K. , Hoskin Ashley J. , Legge Danny N. , Mortensson Eleanor M.H. , Flanagan Dustin J. , Jones Nicholas , Kollareddy Madhu , Collard Tracey J. , Timms Penny , Sansom Owen J. , Williams Ann C. , Vincent Emma E. 
Published: August 2022

AbstractTo support proliferation and survival within a challenging microenvironment, cancer cells must reprogramme their metabolism. As such, targeting cancer cell metabolism is a promising therapeutic avenue. However, identifying tractable nodes of metabolic vulnerability in cancer cells is challenging due to their metabolic plasticity. Identification of effective treatment combinations to counter this is an active area of research. Aspirin has a well-established role in cancer prevention, particularly in colorectal cancer (CRC), although the mechanisms are not fully understood. Here, we comprehensively characterise the metabolic impact of long-term aspirin exposure (2-4mM for 52 weeks) on CRC cells. We show that aspirin regulates several enzymes and transporters of central carbon metabolism and results in a reduction in glutaminolysis and a concomitant increase in glucose metabolism, demonstrating reprogramming of nutrient utilisation. We show that aspirin causes likely compensatory changes that renders the cells sensitive to the glutaminase 1 (GLS1) inhibitor - CB-839. Of note given the clinical interest, treatment with CB-839 alone had little effect on CRC cell growth or survival. However, in combination with aspirin, CB-839 inhibited CRC cell proliferation and induced apoptosis in vitro, and importantly, reduced crypt proliferation in Apcfl/fl mice in vivo. Together, these results show that aspirin leads to significant metabolic reprogramming in colorectal cancer cells and raises the possibility that aspirin could significantly increase the efficacy of metabolic cancer therapies in CRC.
Disrupted Cerebral Peri-Microvascular Glycogen Promotes Capillary Constrictions and Aggravates Ischemia in Mice
Authors: Uruk Gokhan , Yilmaz-Ozcan Sinem , Cakir-Aktas Canan , Taskiran-Sag Aslihan , Donmez-Demir Buket , Duran Jordi , Guinovart Joan J. , Karatas-Kurşun Hulya , Dalkara Turgay , Yemisci Muge 
Published: August 2022

ABSTRACTIschemic stroke results in sudden blood flow cessation, thus, unmet energy requirements. Although the clotted artery can be recanalized and blood flow is restored, brain perfusion may not be fully attained due to microvascular constrictions. Under glucose deprived and hypoxic conditions, glucose derived from the glycogen stored around peri-microvascular astrocyte end-feet may serve as an emergency fuel to meet the metabolic demand during acute period of ischemic stroke. To elucidate the impact of glycogen utilization on brain microcirculation, we administered glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-d-arabinitol (DAB) intracerebroventricularly. Transgenic mice in which glycogen synthase-1 expression was selectively knocked out in central nervous system (GYS1Nestin-KO) were also used. Both approaches caused microvascular constrictions mediated by CD13-positive pericyte contractions. When mice with disrupted glycogen utilization were subjected to MCA ischemia, pericyte-mediated microvascular constrictions and the infarct volumes were further increased compared to untreated controls or wild type littermates. Perimicrovascular glycogen depletions were highly correlated with microvascular constrictions as shown by Periodic acid Schiff (PAS) staining and immunolabeling with anti-glycogen antibodies. Imaging of regional cortical blood flow changes during ischemia disclosed severely compromised blood flow dynamics in mice with disrupted glycogen metabolism. In conclusion, disrupting glycogen utilization causes ischemic-like microvascular constrictions under non-ischemic circumstances and increases susceptibility to brain ischemia. Understanding the role of glycogen at neurogliovascular level in brain may provide novel insight to the pathophysiology of ischemic stroke and therapeutic opportunities.Graphical Abstract
Dynamics of bacterial recombination in the human gut microbiome
Authors: Liu Zhiru , Good Benjamin H 
Published: August 2022

AbstractHorizontal gene transfer is a ubiquitous force in microbial evolution. Previous studies have shown that the human gut is a hot spot for gene transfer between species, but the more subtle exchange of variation within species – collectively known as recombination – remains poorly characterized in this ecosystem. Here, we show how the genetic structure of the human gut microbiome provides a unique opportunity to measure individual recombination events from sequenced fecal samples, enabling quantitative comparisons of recombination across a diverse range of species that inhabit a common environment. By analyzing a large collection of recent recombination events in the core genomes of 29 gut commensals, we uncovered systematic heterogeneities in the rates and lengths of transferred segments, which are difficult to explain by existing models of ecological isolation or homology-dependent recombination rates. We also find that natural selection plays a role in facilitating the spread of genetic variants onto different strain backgrounds, both within individual hosts and across the broader global population. These results shed light on the dynamics ofin siturecombination, which place important constraints on the adaptability of gut microbial communities.
1,000 ancient genomes uncover 10,000 years of natural selection in Europe
Authors: Le Megan K. , Smith Olivia S. , Akbari Ali , Harpak Arbel , Reich David , Narasimhan Vagheesh M. 
Published: August 2022

AbstractAncient DNA has revolutionized our understanding of human population history. However, its potential to examine how rapid cultural evolution to new lifestyles may have driven biological adaptation has not been met, largely due to limited sample sizes. We assembled genome-wide data from 1,291 individuals from Europe over 10,000 years, providing a dataset that is large enough to resolve the timing of selection into the Neolithic, Bronze Age, and Historical periods. We identified 25 genetic loci with rapid changes in frequency during these periods, a majority of which were previously undetected. Signals specific to the Neolithic transition are associated with body weight, diet, and lipid metabolism-related phenotypes. They also include immune phenotypes, most notably a locus that confers immunity to Salmonella infection at a time when ancient Salmonella genomes have been shown to adapt to human hosts, thus providing a possible example of human-pathogen co-evolution. In the Bronze Age, selection signals are enriched near genes involved in pigmentation and immune-related traits, including at a key human protein interactor of SARS-CoV-2. Only in the Historical period do the selection candidates we detect largely mirror previously-reported signals, highlighting how the statistical power of previous studies was limited to the last few millennia. The Historical period also has multiple signals associated with vitamin D binding, providing evidence that lactase persistence may have been part of an oligogenic adaptation for efficient calcium uptake and challenging the theory that its adaptive value lies only in facilitating caloric supplementation during times of scarcity. Finally, we detect selection on complex traits in all three periods, including selection favoring variants that reduce body weight in the Neolithic. In the Historical period, we detect selection favoring variants that increase risk for cardiovascular disease plausibly reflecting selection for a more active inflammatory response that would have been adaptive in the face of increased infectious disease exposure. Our results provide an evolutionary rationale for the high prevalence of these deadly diseases in modern societies today and highlight the unique power of ancient DNA in elucidating biological change that accompanied the profound cultural transformations of recent human history.
A model predictive control strategy to regulate movements and interactions
Authors: Takagi A. , Gomi H. , Burdet E. , Koike Y. 
Published: August 2022

AbstractHumans are adept at moving the arm to interact with objects and surfaces. The brain is thought to regulate motion and interactions using two different controllers, one specialized for movements and the other for force regulation. However, it remains unclear whether different control mechanisms are necessary. Here we show that the brain can employ a single high-level control strategy for both movement and interaction control. The Model Predictive Control (MPC) strategy introduced in this paper uses an internal model of the environment to plan the arm’s muscle activity whilst updating its predictions using periodic feedback. Computer simulations demonstrate MPC’s ability to produce human-like movements and after-effects in free and force field environments. It can simultaneously regulate both force and stiffness during interactions, and can accomplish motor tasks demanding transitions between motion and interaction control. Model Predictive Control promises to be an important tool to test ideas of motor control as it can handle nonlinear dynamics with changing environments and goals without having to specify the movement duration.
PrioriTree: a utility for improving phylodynamic analyses in BEAST
Authors: Gao Jiansi , May Michael R. , Rannala Bruce , Moore Brian R. 
Published: August 2022

AbstractSummaryPhylodynamic methods are central to studies of the geographic and demographic history of disease outbreaks. Inference under discrete-geographic phylodynamic models—which involve many parameters that must be inferred from minimal information—is inherently sensitive to our prior beliefs about the model parameters. We present an interactive utility, PrioriTree, to help researchers identify and accommodate prior sensitivity in discrete-geographic inferences. Specifically, PrioriTree provides a suite of functions to generate input files for—and summarize output from—BEAST analyses for performing robust Bayesian inference, data-cloning analyses, and assessing the relative and absolute fit of candidate discrete-geographic (prior) models to empirical datasets.Availability and ImplementationPrioriTree is distributed as an R package available at https://github.com/jsigao/prioritree, with a comprehensive user manual provided at https://bookdown.org/jsigao/prioritree_manual/.Contactjsigao@ucdavis.edu
A putative xanthine dehydrogenase protects Borrelia burgdorferi from reactive oxygen species and promotes virulence
Authors: Phelan James P. , Bourgeois Jeffrey S. , McCarthy Julie E , Hu Linden T. 
Published: August 2022

AbstractBorrelia burgdorferi is a pathogenic bacterium and the causative agent of Lyme Disease. It is exposed to reactive oxygen species (ROS) in both the vertebrate and tick hosts. While some mechanisms by which B. burgdorferi ameliorates the effects of ROS exposure have been studied, there are likely many other unknown mechanisms of ROS neutralization that contribute to virulence. Here, we follow up on a three gene cluster of unknown function, BB_0554, BB_0555, and BB_0556, that our prior unbiased transposon insertional sequencing studies implicated in both ROS survival and survival in Ixodes scapularis. We confirmed these findings through genetic knockout and provide evidence that these genes are co-transcribed as an operon to produce a xanthine dehydrogenase. In agreement with these results, we found that B. burgdorferi exposure to either uric acid (a downstream product of xanthine dehydrogenase) or allopurinol (an inhibitor of xanthine dehydrogenase) could modulate sensitivity to ROS in a BB_0554-BB_0556 dependent manner. Together, this study identifies a previously uncharacterized three gene operon in B. burgdorferi as a putative xanthine dehydrogenase critical for virulence.ImportanceBorrelia burgdorferi, the causative agent of Lyme disease, is highly successful at evading host immune defenses such as reactive oxygen species, despite minimal identified defenses against oxidative stress. We identified a putative xanthine dehydrogenase that is important in survival of the organism when exposed to oxidative stress and in both its tick and murine hosts. The mechanism appears based on a previously unrecognized role of uric acid in neutralizing reactive oxygen species and highlights how B. burgdorferi can utilize its very limited metabolic capabilities in unique ways.