Miracle-dz/UniFAR-FTUs huggingface dataset:
Prodromal Dementia With Lewy Bodies and Recurrent Panic Attacks as the First Symptom: A Case Report

Psychiatric-onset dementia with Lewy bodies (DLB) might include symptoms of depression, hallucinations, anxiety, and apathy. Here, we report a patient with DLB with recurrent panic attacks as her first symptom 5 years before a biological-based diagnosis of probable DLB. We provide an extended description of the clinical presentation and course from psychiatric-onset DLB to dementia in an 83-year-old woman. This case illustrates the common misdiagnosis of DLB and the delay of having a detailed clinical and biomarker assessment for structured diagnosis. With a detailed description of the clinical presentation of this case, the empirical treatment strategies, and the patient perspectives, we aim to make clinicians aware of panic attacks within the psychiatric-onset DLB.
Case Report: Hypercholesterolemia “Lean Mass Hyper-Responder” Phenotype Presents in the Context of a Low Saturated Fat Carbohydrate-Restricted Diet

Emerging evidence suggests that “leanness” and good metabolic health markers may predict larger increases in LDL cholesterol (LDL-C) in response to carbohydrate restriction. Specifically, a recent cohort study demonstrated an inverse association between BMI and LDL-C change among individuals on carbohydrate-restricted diets and identified a subgroup of “Lean Mass Hyper-Responders” (LMHR) who exhibit exceptional increases in LDL-C, in the context of low triglycerides and high HDL-C. We present the case of one subject, LM, who adopted a ketogenic diet for management of ulcerative colitis. He subsequently experienced an increase in LDL-C from 95 to 545 mg/dl, at peak, in association with HDL-C >100 mg/dl and triglycerides ~40 mg/dl, typical of the emergent LMHR phenotype. Assessments of LM’s dietary intake, lipid panels, and BMI are consistent with prior data and suggest that the LMHR phenomenon is not dependent on saturated fat intake but inversely associates with BMI changes. Finally, computed tomography angiography conducted on LM after over 2 years of hypercholesterolemia revealed no evidence of calcified or non-calcified plaque.
From Uterus to Brain: An Update on Epidemiology, Clinical Features, and Treatment of Brain Metastases From Gestational Trophoblastic Neoplasia

In this review, we provide the state of the art about brain metastases (BMs) from gestational trophoblastic neoplasia (GTN), a rare condition. Data concerning the epidemiology, clinical presentation, innovations in therapeutic modalities, and outcomes of GTN BMs are comprehensively presented with particular attention to the role of radiotherapy, neurosurgery, and the most recent chemotherapy regimens. Good response rates have been achieved thanks to multi-agent chemotherapy, but brain involvement by GTNs entails significant risks for patients’ health since sudden and extensive intracranial hemorrhages are possible. Moreover, despite the evolution of treatment protocols, a small proportion of these patients ultimately develops a resistant disease. To tackle this unmet clinical need, immunotherapy has been recently proposed. The role of this novel option for this subset of patients as well as the achieved results so far are also discussed.
Time-Frequency Representations of Brain Oscillations: Which One Is Better?

Brain oscillations are thought to subserve important functions by organizing the dynamical landscape of neural circuits. The expression of such oscillations in neural signals is usually evaluated using time-frequency representations (TFR), which resolve oscillatory processes in both time and frequency. While a vast number of methods exist to compute TFRs, there is often no objective criterion to decide which one is better. In feature-rich data, such as that recorded from the brain, sources of noise and unrelated processes abound and contaminate results. The impact of these distractor sources is especially problematic, such that TFRs that are more robust to contaminants are expected to provide more useful representations. In addition, the minutiae of the techniques themselves impart better or worse time and frequency resolutions, which also influence the usefulness of the TFRs. Here, we introduce a methodology to evaluate the “quality” of TFRs of neural signals by quantifying how much information they retain about the experimental condition during visual stimulation and recognition tasks, in mice and humans, respectively. We used machine learning to discriminate between various experimental conditions based on TFRs computed with different methods. We found that various methods provide more or less informative TFRs depending on the characteristics of the data. In general, however, more advanced techniques, such as the superlet transform, seem to provide better results for complex time-frequency landscapes, such as those extracted from electroencephalography signals. Finally, we introduce a method based on feature perturbation that is able to quantify how much time-frequency components contribute to the correct discrimination among experimental conditions. The methodology introduced in the present study may be extended to other analyses of neural data, enabling the discovery of data features that are modulated by the experimental manipulation.
Dose Escalation Trial of Desulfated Heparin (ODSH) in Septic Peritonitis

Objective Septic peritonitis is associated with significant morbidity and mortality. As a potential therapeutic agent in the treatment of sepsis, 2-O, 3-O desulfated heparin (ODSH) reduces histones and platelet factor 4 (PF4) in mouse sepsis models. This pilot clinical trial evaluated the safety and effect of ODSH in client-owned dogs with septic peritonitis. Interventions In an IACUC-approved, open-label, prospective, dose-escalation clinical trial in 6 dogs with spontaneous septic peritonitis, ODSH administration was initiated following surgical explore to achieve source control. Acute patient physiology and laboratory evaluation (APPLEfast and APPLEfull) scores on admission, source of septic peritonitis, requirement for vasopressors, the administration of blood products, and survival to discharge were recorded. Platelet count, cell free DNA (cfDNA) concentration, and platelet factor 4 (PF4) concentrations were measured at the time of each ODSH dosage. A dose of ODSH was administered every 8 hs for a total of 4 doses (maximum total dosage 75 mg/kg) based on a pre-determined escalation protocol. Patients were monitored in the ICU following administration for evidence of clinical hemorrhage. Main Results The mean APPLEfast and APPLEfull scores on admission were 22 +/- 6 and 32 +/-10, respectively. Four dogs received 4 total dosages of ODSH and 2 dogs received 3 total dosages of ODSH intravenously. The mean total dosage of ODSH administered during the study period was 48.3 +/- 21.6 mg/kg. No dog required dose de-escalation or had any evidence of bleeding. Four dogs survived to discharge. Conclusions No adverse effects of ODSH administration were documented in dogs with septic peritonitis. A randomized controlled trial is necessary to evaluate ODSH as a novel therapeutic in the treatment of septic peritonitis.
Longitudinal Influences of DRD4 Polymorphism and Early Maternal Caregiving on Personality Development and Problem Behavior in Middle Childhood and Adolescence

Most studies examining gene-environment effects on self-regulation focus on outcomes early childhood or adulthood. However, only a few studies investigate longitudinal effects during middle childhood and adolescence and compare two domains of early caregiving. In a longitudinal follow-up with a sample of N = 87, we studied the effects of differences in the DRD4 tandem repeat polymorphisms and two domains of early maternal caregiving quality on children’s personality development using Block’s California Child Q-Set (CCQ) at age six and age 12 and on problem behavior at ages six and seven. Early maternal regulation quality predicted later ego-resiliency and aggressiveness. In addition, significant gene-environment interactions revealed that children with the 7+ DRD4 tandem repeat polymorphism and poor maternal regulation quality in infancy showed lower scores in ego-resiliency and higher scores in ego-undercontrol and CCQ aggressiveness. In contrast, children who had experienced effective maternal regulation in infancy showed a comparable level in personality traits and problem behavior as the DRD4 7- group independent of the levels of maternal regulatory behavior. Similarly, longitudinal caregiving × DRD4 interactions were found for behavior problems in middle childhood, especially for oppositional-aggression, inattentive-hyperactivity, and social competence. Early caregiving effects were only found for maternal regulation quality, but not for maternal responsiveness. Effective early maternal regulation in infancy can moderate the negative effect of DRD4 7+ on children’s self-regulation in middle childhood and adolescence. However, maternal responsiveness has no comparable effects. It seems relevant to consider several dimensions of early caregiving and to also measure the environment in more detail in gene-environment studies.
Study of Geometric Illusory Visual Perception – A New Perspective in the Functional Evaluation of Children With Strabismus

Despite the various perceptual-motor deficits documented in strabismus, there is a paucity of studies evaluating visual illusions in patients with strabismus. The aim of this study was to examine how the illusionary perception occurs in children/adolescents (10–15 years old) with strabismus with referral for surgery to correct ocular deviations. A controlled cross-sectional study was carried out in which 45 participants with strabismus and 62 healthy volunteers aged 10–15 years were evaluated. The behavioral response to three geometric illusions [Vertical-Horizontal illusion, Müller-Lyer illusion (Bretano version) and Ponzo illusion] and respective neutral stimuli (non-illusory images) regarding the estimation of image size and response time were measured using the Method of Adjustment. To analyze the influence of secondary factors: type of ocular deviation (convergent, divergent or associated with vertical deviation); amount of eye deviation; presence of amblyopia and stereopsis, a one-way ANOVA was performed. Among the tested illusions, children with strabismus showed greater susceptibility (p = 0.006) and response time (p = 0.004) to Ponzo’s illusory images. Children with strabismus and preserved stereopsis, on the other hand, showed similar susceptibility and response time to control group patients to the Ponzo illusion (p < 0.005). Patients with amblyopia showed overcorrection in the estimate of non-illusory Ponzo images (p = 0.046). Children with horizontal ocular deviation (esotropia or exotropia) associated with vertical deviation (hypertropia, DVD and/or alphabetical anisotropy) showed higher susceptibility to vertical adjustment images for the Müller-Lyer illusion (Brentano version) (p = 0.017). Individuals with strabismus tended to overcorrect the length of the straight-line segment adjusted for non-illusory images when testing non-illusory images in the Müller-Lyer test (Brentano version) (p = 0.009), as well as for the neutral images in the Vertical-Horizontal test (p = 0.000). The findings indicated impairment in the perception of geometric illusions and neutral figures, especially for the Ponzo illusion test by children with strabismus. As the behavioral response to illusory images may indirectly reflect the visual and morphofunctional alterations present in these individuals, we suggest that the investigation of visual illusory perception can be used as a new research strategy in the field of investigating the visual function in strabismus.
Investigation of Beraprost Sodium on Cardiac Function and Hemodynamics in Canine Models of Chronic Pulmonary Hypertension

Pulmonary hypertension (PH) is a life-threatening disease in dogs characterized by increased pulmonary arterial pressure (PAP) and/or pulmonary vascular resistance. No study has evaluated the utility of Beraprost sodium (BPS) in dogs with PH. This study aimed to evaluate the effect of BPS on cardiac function and hemodynamics and examine the optimal dose of BPS in canine models of chronic embolic PH. In this prospective crossover study, three doses of BPS (5, 15, and 25 μg/kg, twice a day) were examined in eight canine models of chronic embolic PH. All model dogs underwent invasive PAP measurement, echocardiography, and non-invasive systemic blood pressure measurement before and after continuous administration of oral BPS for 1 week. No side effects of BPS were observed in any dog during the study. All doses of BPS significantly decreased systolic PAP and pulmonary vascular impedance. Additionally, systemic vascular impedance significantly decreased with 15 and 25 μg/kg of BPS. The right ventricular stroke volume and longitudinal strain significantly decreased with all doses of BPS. The left ventricular stroke volume and circumferential strain decreased with 15 μg/kg BPS. BPS was well-tolerated in this study. A dose-dependent vasodilating effect on pulmonary vessels was observed in canine models of chronic PH. Additionally, 15 μg/kg BPS showed a balanced vasodilating effect on systemic and pulmonary vessels. Furthermore, with a decrease in systemic and pulmonary vascular impedance, the left and right ventricular functions were significantly improved. Our results suggest that BPS may be useful in the treatment of canine PH.
Changes in Large Lake Water Level Dynamics in Response to Climate Change

Understanding impacts of climate change on water level fluctuations across Earth's large lakes has critical implications for commercial and recreational boating and navigation, coastal planning, and ecological function and management. A common approach to advancing this understanding is the propagation of climate change scenarios (often from global circulation models) through regional hydrological models. We find, however, that this approach does not always fully capture water supply spatiotemporal features evolving from complex relationships between hydrologic variables. Here, we present a statistical approach for projecting plausible climate-related regional water supply scenarios into localized net basin supply sequences utilizing a parametric vine copula. This approach preserves spatial and temporal correlations between hydrologic components and allows for explicit representation and manipulation of component marginal and conditional probability distributions. We demonstrate the capabilities of our new modeling framework on the Laurentian Great Lakes by coupling our copula-derived net basin supply simulations with a newly-formulated monthly lake-to-lake routing model. This coupled system projects monthly average water levels on Lake Superior, Michigan-Huron, and Erie (we omit Lake Ontario from our study due to complications associated with simulating strict regulatory controls on its outflow). We find that our new method faithfully replicates marginal and conditional probability distributions, as well as serial autocorrelation, within and among historical net basin supply sequences. We find that our new method also reproduces seasonal and interannual water level dynamics. Using readily-available climate change simulations for the Great Lakes region, we then identified two plausible, transient, water supply scenarios and propagated them through our model to understand potential impacts on future water levels. Both scenarios result in an average water level increase of <10 cm on Lake Superior and Erie, with slightly larger increases on Michigan-Huron, as well as elevated variability of monthly water levels and a shift in seasonal water level modality. Our study contributes new insights into plausible impacts of future climate change on Great Lakes water levels, and supports the application and advancement of statistical modeling tools to forecast water supplies and water levels on not just the Great Lakes, but on other large lakes around the world as well.
CD154 Expression Indicates T Cell Activation Following Tetanus Toxoid Vaccination of Horses

Despite the relevance of adaptive immunity against equine pathogens antigen-specific T cell responses of horses are not well characterized and the lack of insight into T cell responses hampers the understanding of the pathogeneses of important diseases. In this study we used tetanus toxoid (TT) as a well-defined antigen to characterize antigen-reactive T cells. Six healthy adult horses received a routine booster against tetanus with an immune stimulating complex (ISCOM)-based vaccine and were followed for 28 days. TT-specific serum antibodies were quantified by ELISA and increased in all horses by day 7 after vaccination. CD154 is an established indicator of antigen-reactive T helper cells in other species, but has not been characterized in horses. CD154 detection in equine PBMC by an anti-human CD154 antibody (clone 5C8) was confirmed by Western blots and then applied for flow cytometry. As a common indicator of equine T cell activation, cytokine induction was studied in parallel. T cells were analyzed by multicolor flow cytometry of PBMC after re-stimulation with TT in vitro. Reactive T helper (Th) cells were characterized by increased frequencies of CD4+CD154+ lymphocytes in in vitro TT-re-stimulated PBMC on day 14 after vaccination of the horses compared to pre-vaccination. The majority of all CD154+ cells after TT re-stimulation were CD4+ Th cells, but CD154 was also induced on CD4- cells albeit in lower frequencies. CD154+CD4+ Th cells were enriched in cytokine-expressing cells compared to CD154-CD4+ Th cells. Similar to the CD4+CD154+ frequencies, CD4+IL-4+, CD4+IFN-γ+ and CD4+TNF-α+ were increased after vaccination, but IL-4+ increased later than IFN-γ+ and CD4+TNF-α+, which already exceeded pre-vaccination frequencies on day 7. CD4+CD154+ frequencies correlated positively with those of CD4+IL-4+ (Th2) on day 14, and negatively with CD4+IFN-γ+ induction on day 7, but did not correlate with CD4+TNF-α+ frequencies or TT-specific antibody concentrations. CD154 appears to be a useful marker of antigen-reactive equine Th cells in combination with cytokine expression. The T cell analyses established here with TT can be applied to other antigens relevant for infections or allergies of horses and in horse models for translational research.
A Complement-Related Gene Signature for Predicting Overall Survival and Immunotherapy Efficacy in Sarcoma Patients

The prognoses of sarcomas are poor and the responses of them to systemic therapies are limited and controversial. Thus, there is an urgent need to stratify the risk factors and identify the patients who may benefit from systemic therapies. Here, we developed a reliable, complement-based gene signature to predict the prognosis of sarcoma patients. Survival-related complement genes were identified by univariate Cox analyses and were used to build a gene signature, which was further selected using the least absolute shrinkage and selection operator model, and determined using a stepwise Cox proportional hazards regression model. The whole sarcoma cohort of TCGA was randomly divided into a training set and a test set. The signature was constructed using the training set and validated subsequently in the test set, the whole TCGA sarcoma cohort, and another two independent cohorts from the TARGET and GEO databases, respectively. Furthermore, the prognostic value of the signature was also validated in an independent cohort from our center. This model effectively predicted prognoses across the training set, different validation cohorts, and different clinical subgroups. Next, immune cell infiltration analysis, GO and KEGG analysis, and gene set enrichment analysis were performed to explore possible underlying mechanisms of this signature. Moreover, this signature may predict the response to immunotherapy. Collectively, the current complement-related gene signature can predict overall survival and possible immunotherapy response of sarcoma patients; it may serve as a powerful prognostic tool to further optimize clinical treatment and prognosis management for sarcoma patients.
Aging Affects Subcortical Pitch Information Encoding Differently in Humans With Different Language Backgrounds

Aging and language background have been shown to affect pitch information encoding at the subcortical level. To study the individual and compounded effects on subcortical pitch information encoding, Frequency Following Responses were recorded from subjects across various ages and language backgrounds. Differences were found in pitch information encoding strength and accuracy among the groups, indicating that language experience and aging affect accuracy and magnitude of pitch information encoding ability at the subcortical level. Moreover, stronger effects of aging were seen in the magnitude of phase-locking in the native language speaker groups, while language background appears to have more impact on the accuracy of pitch tracking in older adult groups.
CCN2/CTGF—A Modulator of the Optic Nerve Head Astrocyte

In primary open-angle glaucoma (POAG), a neurodegenerative disease of the optic nerve (ON) and leading cause of blindness, the optic nerve head (ONH) undergoes marked structural extracellular matrix (ECM) changes, which contribute to its permanent deformation and to degeneration of ON axons. The remodeling process of the ECM causes changes in the biomechanical properties of the ONH and the peripapillary sclera, which is accompanied by an increased reactivity of the resident astrocytes. The molecular factors involved in the remodeling process belong to the Transforming growth factor (TGF)-β superfamily, especially TGF-β2. In previous publications we showed that TGF-β2 induced ECM alterations are mediated by Cellular Communication Network Factor (CCN)2/Connective Tissue Growth Factor (CTGF) and recently we showed that CCN2/CTGF is expressed by astrocytes of the ON under normal conditions. In this study we wanted to get a better understanding of the function of CCN2/CTGF under normal and pathologic conditions. To this end, we analyzed the glial lamina and peripapillary sclera of CCN2/CTGF overexpressing mice and studied the effect of CCN2/CTGF and increasing substratum stiffness on murine ON astrocytes in vitro. We observed enhanced astrocyte reactivity in the ONH, increased ECM protein synthesis in the peripapillary sclera and increased Ccn2/Ctgf expression in the ONH during the pathologic development in situ. CCN2/CTGF treatment of primary murine ON astrocytes induced a higher migration rate, and increase of ECM proteins including fibronectin, elastin and collagen type III. Furthermore, the astrocytes responded to stiffer substratum with increased glial fibrillary acidic protein, vimentin, actin and CCN2/CTGF synthesis. Finally, we observed the reinforced appearance of CCN2/CTGF in the lamina cribrosa of glaucomatous patients. We conclude that reactive changes in ONH astrocytes, induced by the altered biomechanical characteristics of the region, give rise to a self-amplifying process that includes increased TGF-β2/CCN2/CTGF signaling and leads to the synthesis of ECM molecules and cytoskeleton proteins, a process that in turn augments the stiffness at the ONH. Such a scenario may finally result in a vicious circle in the pathogenesis of POAG. The transgenic CTGF-overexpressing mouse model might be an optimal model to study the chronic pathological POAG changes in the ONH.