bluuebunny/crossref_metadata_2025_split huggingface dataset:
The LPP Indexes Baseline and Treatment-Related Changes in Anxiety Sensitivity
Authors: Butler Devin , Pavuluri Asha , Fix Spencer , Schmidt Norman B. , Bernat Edward 
Published: October 2024

AbstractDevelopment of neurophysiological treatment targets has been an important way to validate and advance treatment implementations. Anxiety Sensitivity (AS), described as a fear of fear, is one of the most well-researched transdiagnostic risk factors for psychopathology and has been demonstrated to be associated with a number of different INT symptoms and disorders, making it an ideal intervention target for treatment of anxiety and mood pathology. Currently, there exists a gap in terms of understanding underlying neural mechanisms of AS and treatment-related change in AS. The current study sought to examine the impact of 2 brief computerized interventions on AS in order to assess the P300 and late positive potential (LPP) event-related potential (ERP) components as an index of both baseline and treatment change in the transdiagnostic anxiety sensitivity construct. Participants received one of the following, with a 1-month follow-up: an anxiety reduction intervention of cognitive anxiety sensitivity treatment (CAST) alone, a mood intervention of cognitive bias modification interpretation (CBM-I), a combined CAST and CBM-I intervention, or a repeated contact control group. Baseline AS was significantly related to baseline P3/LPP, such that higher P3/LPP amplitude (heightened emotional reactivity) is associated with higher AS at intake. Further, treatment-related reductions in AS were associated with higher baseline reactivity: greater AS reductions at month one were associated with higher P3/LPP activity. Heightened emotional response was predictive of better treatment outcomes. Analyses also showed evidence for different mechanisms associated with CAST and CBM-I groups. Specifically, the CAST group evidenced predictions of treatment outcome in parietal areas, where the CBM-I group evidenced predictions in frontal areas. The Combined group evidenced both frontal and parietal activations, consistent with combining the effects from the CAST and CBM-I groups. These findings suggest that the P3/LPP is an index of cognitive-affective processes underlying AS at baseline and has predictive ability in assessing AS treatment outcome in that our observed treatment types engage different neural mechanisms.
Immunohistochemical profiles of dermatofibroma and dermatofibrosarcoma protuberans: A scoping review
Authors: Hardy Céline S. C. , Razavi Ali , Nunez Natalie , Fitzmaurice William , Dave Loma , Slutzky Amy R. , Vanderbeck Kaitlin , Farah Ramsay 
Published: October 2024

ABSTRACTThis review summarizes the immunohistochemical profiles of dermatofibroma (DF) and dermatofibrosarcoma protuberans (DFSP) as reported by primary literature in the past 10 years. 63 studies were included in the review, with staining information for a total of 99 unique IHC markers reported. The most commonly reported stains were CD34, SMA, S100, and FXIIIa. Most studies applied IHC either to explore descriptive features of DF or DFSP or to determine their utility in diagnostic identification of the lesions. A number of studies applied novel biomarkers which may hold promise for distinguishing DF and DFSP, namely WT1, Cx43, LSP-1, and PHH3, which demonstrated considerable expression differences between the two lesions. This review highlights the need for validation of existing and emerging IHC markers for the diagnosis of DF and DFSP.
LUNAR: A Deep Learning Model to Predict Glioma Recurrence Using Integrated Genomic and Clinical Data
Authors: Patricoski-Chavez Jessica A. , Nagpal Seema , Singh Ritambhara , Warner Jeremy L. , Gamsiz Uzun Ece D. 
Published: October 2024

AbstractGliomas account for approximately 25.5% of all primary brain and central nervous system tumors, with a striking 80.8% of these being malignant. The prognosis varies significantly; low-grade gliomas (LGGs) can exhibit 5-year survival rates of up to 80%, while higher-grade gliomas (HGGs) often see rates below 5%. Recurrence is a common challenge, occurring in 52%-62% of LGGs and 90% of HGGs, complicating clinical management and treatment planning. Currently, no widely available models exist for predicting glioma recurrence, which is critical for optimizing patient outcomes. Machine learning (ML) and deep learning (DL) techniques have shown promise in predicting recurrence for various cancers, most using Electronic Health Records (EHR). This study introduces gLioma recUrreNceAttention-based classifieR(LUNAR), a DL-based model to predict early versus late glioma recurrence by integrating clinical, genomic, and mRNA expression data from patients with primary grade II-IV gliomas. The data was obtained from The Cancer Genome Atlas and the Glioma Longitudinal Analysis Consortium (GLASS).
Psilocybin Reduces Grooming in the SAPAP3 Knockout Mouse Model of Compulsive Behaviour
Authors: Gattuso James J , Wilson Carey , Hannan Anthony J , Renoir Thibault 
Published: October 2024

AbstractPsilocybin is a serotonergic psychedelic compound which shows promise for treating compulsive behaviours. This is particularly pertinent as compulsive disorders require research into new pharmacological treatment options as the current frontline treatments such as selective serotonin reuptake inhibitors, require chronic administration, have significant side effects, and leave almost half of the clinical population refractory to treatment.In this study, we investigated psilocybin administration in male and female SAPAP3 knockout (KO) mice, a well-validated mouse model of obsessive compulsive and related disorders. We assessed the effects of acute psilocybin (1 mg/kg, intraperitoneal) administration on head twitch and locomotor behaviour as well as anxiety- and compulsive-like behaviours at multiple time-points (1-, 3- and 8-days post-injection).While psilocybin did not have any effect on anxiety-like behaviours, we revealed for the first time that acute psilocybin administration led to enduring reductions in compulsive behaviour in male SAPAP3 KO mice and reduced grooming behaviour in female WT and SAPAP3 KO mice. We also found that psilocybin increased locomotion in wild-type littermates but not in SAPAP3 KO mice, suggestingin vivoserotonergic dysfunctions in KO animals. On the other hand, the typical head-twitch response following acute psilocybin (confirming its hallucinogenic-like effect at this dose) was observed in both genotypes.Our novel findings suggest that acute psilocybin may have potential to reduce compulsive-like behaviours (up to 1 week after a single injection). Our study can inform future research directions as well as supporting the utility of psilocybin as a novel treatment option for compulsive disorders.
Distinct optimization of motor control and learning: Self-paced motor learning achieves different motor patterns from overtrained
Authors: Hayashi Takuji , Takiyama Ken 
Published: October 2024

AbstractSelf-paced movement, resulting from extensive training and optimization, serves as an ideal model for investigating internal objectives without external constraints within the sensorimotor system. Previous studies have shown that the self-paced movement is consistent within individuals but inconsistent across individuals, highlighting a robust, unique optimization in motor control. Although motor learning is similarly an optimization process, it is unknown whether the internal objectives are shared with motor control and learning, i.e., whether it replicates the motor patterns identified by self-paced motor control. As the optimality principles typically address redundancy, a human behavioral experiment was designed to equate movement distance for motor control and learning, comparing redundant motion parameters, movement velocity, and duration, through detailed analysis that accommodates their nonlinear interaction and significant inter-individual baseline differences. Participants, instructed to use their preferred velocities and duration, exhibited minimal intra-individual variability in motion parameters. Notably, visuomotor shift perturbations exclusively affected velocity, while changes in target distances affected both velocity and duration. These findings suggest that the sensorimotor system employs distinct optimization mechanisms for motor control and learning to resolve redundancy.Significance statementOur natural behaviors are thought to be well-optimized. Self-paced movements, a major form of the behaviors, demonstrate significant stability within individuals but vary across individuals, suggesting that the sensorimotor system in the central nervous system operates a unique and robust optimization involved in self-paced motor control. Self-paced motor control is further refined during the motor learning process. However, it is unknown whether motor control and learning share a common objective function. We demonstrated that laboratory-based motor learning never resulted in identical motor patterns from the overtrained movements with natural instruction. Thus, the sensorimotor system would employ distinct optimization mechanisms for motor control and learning, suggesting that these processes are not contiguous.
Preemptive minocycline decreases allodynia and depressive-like behaviors in a peripheral neuropathy rat model: a preliminary study
Authors: Le Anh Cong Tuan , Sousa Ângela , Alves Nuno Dinis , Leite-Almeida Hugo 
Published: October 2024

ABSTRACTBackground and ObjectiveThe neuroimmune system plays a critical role at all phases of chronic pain including at its onset. We therefore hypothesized that preemptive immunomodulation could decrease susceptibility and/or offer protection to pain.Materials and MethodsSix days before the spared nerve injury (SNI), Wistar Han rats were treated with either the immunomodulator minocycline (MIN) or vehicle (VEH). After that, half of the animals from each group switch treatments for additional 7 days, resulting in 4 groups: continuous treatment (MIN/MIN), pretreatment (MIN/VEH), early treatment (VEH/MIN) and the control (VEH/VEH). Mechanical allodynia was recorded using Von Frey test until 4 weeks after SNI where depressive-like behaviors of the animals were also assessed using sucrose preference test.ResultsThe continuous treatment provided sustained protection against mechanical allodynia, with rats in this group showing a significantly higher threshold to pain sensitivity compared to those in VEH/VEH. In contrast, pain relief effects were not observed with MIN/VEH and VEH/MIN. Additionally, animals in MIN/MIN, and VEH/MIN exhibited decreased anhedonic-like behavior at 30 days after SNI, relative to the control.ConclusionsThe exposure to an anti-inflammatory drug circa the installation of a neuropathic lesion had a positive impact on allodynia and on anhedonic behavior for a relatively long period after treatment cessation. The results support the assertions that pain trajectories can be altered at pain early stages by targeting the neuroimmune system. This proof-of-concept has the potential to be broadened to other drugs and/or therapeutical schemes.HighlightsChronic pain susceptibility varies across individuals.(endo)phenotypes of susceptibility manifest prior/circa pain onset.Preemptive minocycline treatment transiently decreases allodynia.Preemptive minocycline treatment provides sustained reduction of depressive-like behavior.Immune system modulation prior to pain onset or at early stages have beneficial outcomes.
Sex-biased effect of sodium leak channel NALCN deletion in striatalDrd2spiny projection neurons
Authors: Castell Laia , Naon Claire , Rogliardo Angelina , Makrini Leila , Avrillon Maëlle , Mignon Audrey , Bernat Claire , Lory Philippe , Bertaso Federica , Monteil Arnaud , Bosch-Bouju Clémentine , Valjent Emmanuel 
Published: October 2024

ABSTRACTThe sodium leak channel NALCN is an important modulator of neuronal excitability, yet its specific role in striatal medium-sized spiny neurons remains largely unexplored. In this study, considering thatNalcntranscripts are enriched in the dorsal and ventral striatum ofDrd2-SPNs, we investigated the functional impact of NALCN deletion inDrd2-expressing SPNs in both male and female mice. Electrophysiological recordings revealed significant sex differences, with male SPNs exhibiting altered membrane properties and increased excitability, while females showed more subtle changes. Interestingly, eticlopride-induced intracellular signaling was selectively enhanced in female SPNs lacking NALCN. Behaviorally, male mice exhibited reduced motivation in food-seeking tasks and impaired discrimination of threat cues. Our findings uncover an important, sex-specific role for NALCN in regulating striatal function and behavior and underscore its significance in maintaining normal striatal function.
Twelve phosphomimetic mutations induce the assembly of recombinant full-length human tau into paired helical filaments
Authors: Lövestam Sofia , Wagstaff Jane L. , Katsinelos Taxiarchis , Freund Stefan M.V. , Goedert Michel , Scheres Sjors H.W. 
Published: October 2024

AbstractThe assembly of tau into amyloid filaments is associated with more than twenty neurodegenerative diseases, collectively termed tauopathies. Cryo-EM structures of brain-derived tau filaments revealed that specific structures define different diseases, triggering a quest for the development of experimental model systems that replicate the structures of disease. Here, we describe twelve phosphomimetic, serine/threonine to aspartate, mutations in tau, which we termed PAD12, that collectively induce thein vitroassembly of full-length tau into filaments with the same structure as that of paired helical filaments extracted from the brains of individuals with Alzheimer’s disease. Solution-state nuclear magnetic resonance spectroscopy suggests that phosphomimetic mutations in the carboxy-terminal domain of tau may facilitate filament formation by disrupting an intramolecular interaction between two IVYK motifs. PAD12 tau can be used for both nucleation-dependent and multiple rounds of seeded assemblyin vitro, as well as for the seeding of tau biosensor cells. PAD12 tau can be assembled into paired helical filaments under various shaking conditions, with the resulting filaments being stable for extended periods of time. They can be labelled with fluorophores and biotin. Tau filaments extracted from the brains of individuals with Alzheimer’s disease brains have been known to be made of hyperphosphorylated and abnormally phosphorylated full-length tau, but it was not known if the presence of this post-translational modification is more than a mere correlation. Our findings suggest that hyperphosphorylation of tau may be sufficient for the formation of the Alzheimer tau fold. PAD12 tau will be a useful tool for the study of molecular mechanisms of neurodegeneration.
Pre-existing H1N1 immunity reduces severe disease with bovine H5N1 influenza virus
Authors: Le Sage Valerie , Werner Bailee D. , Merrbach Grace A. , Petnuch Sarah E. , O’Connell Aoife K , Simmons Holly C. , McCarthy Kevin R. , Reed Douglas S. , Moncla Louise H. , Bhavsar Disha , Krammer Florian , Crossland Nicholas A. , McElroy Anita K. , Duprex W. Paul , Lakdawala Seema S. 
Published: October 2024

AbstractThe emergence of highly pathogenic H5N1 avian influenza in dairy cattle herds across the United States has caused multiple mild human infections. There is an urgent need to understand the risk of spillover into humans. Here, we show that pre-existing immunity from the 2009 H1N1 pandemic influenza virus provided protection from mortality and severe clinical disease to ferrets intranasally infected with bovine H5N1. H1N1 immune ferrets exhibited a differential tissue tropism with little bovine H5N1 viral dissemination to organs outside the respiratory tract and significantly less H5N1 virus found in nasal secretions and the respiratory tract. Additionally, ferrets with H1N1 prior immunity produced antibodies that cross-reacted with H5N1 neuraminidase protein. Taken together, these results suggest that mild disease in humans may be linked to prior immunity to human seasonal influenza viruses.
Over supplementation of folic acid reduces survival 24 hours after hypoxia in male and femaleDrosophila melanogaster
Authors: Gunnala Siddarth , Harrison Alisha , Juba Amber , Ashcraft Paula , Bottiglieri Teodoro , Buhlman Lori M , Jadavji Nafisa M. 
Published: October 2024

AbstractHypoxia is a major component of ischemic stroke. Nutrition has been established as a modifiable risk factor for ischemic stroke. Over-supplementation of folic acid (FA) has become an increasing problem in the U.S and other countries as more people are consuming at or above the recommended daily amount of FA. The impact of over-supplementation of FA on hypoxia is not well understood. This study aimed to investigate how FA over-supplementation impacts hypoxia outcomes usingDrosophila melanogasteras a model. Adultw1118Drosophila melanogasterwere placed on control and 100 µM folic acid supplemented diets (FASD). Progeny 5 to 6 days old were exposed to hypoxia for two hours prior to returning to normoxic conditions to model reperfusion. Using liquid chromatography-tandem mass spectrometry, elevated FA levels were observed in FASD flies. Escape behavior was also demonstrated in hypoxia larvae, and increased hypoxia-induced mortality was exacerbated in FASD flies; however, diet did not influence hypoxia-medicated reductions in climbing motivation and ability. Data obtained suggests that hypoxia has a negative effect on survival and climbing behavior in the flies, and that FA over-supplementation has selected negative health outcomes after hypoxia.
Interplay of Virulence Factors and Signaling Molecules: Albumin and Calcium-Mediated Biofilm Regulation inBordetella bronchiseptica
Authors: Mugni Sabrina Laura , Ambrosis Nicolás , O’Toole George A. , Sisti Federico , Fernández Julieta 
Published: October 2024

AbstractBordetella bronchiseptica, a respiratory pathogen capable of infecting various mammals, including humans, is associated with chronic infections, contrasting with the acute infections caused byBordetella pertussis. Both pathogens can form biofilm-like structuresin vivo, providing tolerance against environmental stresses. Biofilm formation byB. bronchisepticais regulated by the BvgAS two-component system, with intermediate concentrations of certain modulators inducing a phase favoring biofilm formation. Recent studies have highlighted the role of cyclic diguanylate monophosphate (c-di-GMP) in this process: elevated c-di-GMP levels stimulate biofilm formation, whereas phosphodiesterase (PDE) activation reduces biofilms. Respiratory secretions, which contain albumin and calcium at higher concentrations than standard growth media, promote an increase in the amount and extracellular localization of the adenylate cyclase toxin (ACT), an importantBordetella spp. virulence factor. Secreted ACT present in the extracellular media or attached to the outer membrane inhibits biofilm formation. Based on these observations, we hypothesized that serum albumin and calcium together inhibit biofilm formation and explored the potential role of c-di-GMP in this process. Our findings demonstrate that serum albumin and calcium inhibitB. bronchisepticabiofilm formation by two apparently independent mechanisms, increasing AC secretion and inducing c-di-GMP degradation. This study contributes to the understanding of the mechanisms governingB. bronchisepticabiofilm formation and its modulation by host factors.
Variable Presence of an Evolutionarily New Brain Structure is Related to Trait Impulsivity
Authors: Willbrand Ethan H. , Maboudian Samira A. , Elliott Matthew V. , Kellerman Gabby M. , Johnson Sheri L. , Weiner Kevin S. 
Published: October 2024

AbstractBackgroundImpulsivity is a multidimensional construct reflecting poor constraint over one’s behaviors. Clinical psychology research identifies separable impulsivity dimensions that are each unique transdiagnostic indicators for psychopathology. Yet, despite this apparent clinical importance, the shared and unique neuroanatomical correlates of these factors remain largely unknown. Concomitantly, neuroimaging research identifies variably present human brain structures implicated in cognition and disorder: the folds (sulci) of the cerebral cortex located in the latest developing and most evolutionarily expanded hominoid-specific association cortices.MethodsWe tethered these two fields to test whether variability in one such structure in anterior cingulate cortex (ACC)—the paracingulate sulcus (PCGS)—was related to individual differences in trait impulsivity. 120 adult participants with internalizing or externalizing psychopathology completed a magnetic resonance imaging scan and the Three-Factor Impulsivity Index. Using precision imaging techniques, we manually identified the PCGS, when present, and acquired quantitative folding metrics (PCGS length and ACC local gyrification index).ResultsNeuroanatomical-behavioral analyses revealed that participants with leftward or symmetrical PCGS patterns had greater severity of Lack of Follow Through (LFT)—which captures inattention and lack of perseverance—than those with rightward asymmetry. Neuroanatomical-functional analyses identified that the PCGS co-localized with a focal locus found in a neuroimaging meta-analysis on a feature underlying LFT. Both quantitative folding metrics did not relate to any impulsivity dimension.ConclusionsThis study advances understanding of the neuroanatomical correlates of impulsivity and establishes the notion that the topographical organization of distinct, hominoid-specific cortical expanses underlie separable impulsivity dimensions with robust, transdiagnostic implications for psychopathology.