Miracle-dz/UniFAR-FTUs huggingface dataset:
Abstract Memory Representations in the Ventromedial Prefrontal Cortex and Hippocampus Support Concept Generalization

Memory function involves both the ability to remember details of individual experiences and the ability to link information across events to create new knowledge. Prior research has identified the ventromedial prefrontal cortex (VMPFC) and the hippocampus as important for integrating across events in the service of generalization in episodic memory. The degree to which these memory integration mechanisms contribute to other forms of generalization, such as concept learning, is unclear. The present study used a concept-learning task in humans (both sexes) coupled with model-based fMRI to test whether VMPFC and hippocampus contribute to concept generalization, and whether they do so by maintaining specific category exemplars or abstract category representations. Two formal categorization models were fit to individual subject data: a prototype model that posits abstract category representations and an exemplar model that posits category representations based on individual category members. Latent variables from each of these models were entered into neuroimaging analyses to determine whether VMPFC and the hippocampus track prototype or exemplar information during concept generalization. Behavioral model fits indicated that almost three-quarters of the subjects relied on prototype information when making judgments about new category members. Paralleling prototype dominance in behavior, correlates of the prototype model were identified in VMPFC and the anterior hippocampus with no significant exemplar correlates. These results indicate that the VMPFC and portions of the hippocampus play a broad role in memory generalization and that they do so by representing abstract information integrated from multiple events. SIGNIFICANCE STATEMENT Whether people represent concepts as a set of individual category members or by deriving generalized concept representations abstracted across exemplars has been debated. In episodic memory, generalized memory representations have been shown to arise through integration across events supported by the ventromedial prefrontal cortex (VMPFC) and hippocampus. The current study combined formal categorization models with fMRI data analysis to show that the VMPFC and anterior hippocampus represent abstract prototype information during concept generalization, contributing novel evidence of generalized concept representations in the brain. Results indicate that VMPFC–hippocampal memory integration mechanisms contribute to knowledge generalization across multiple cognitive domains, with the degree of abstraction of memory representations varying along the long axis of the hippocampus.
Higher Heart-Rate Variability Is Associated with Ventromedial Prefrontal Cortex Activity and Increased Resistance to Temptation in Dietary Self-Control Challenges

Higher levels of self-control in decision making have been linked to better psychosocial and physical health. A similar link to health outcomes has been reported for heart-rate variability (HRV), a marker of physiological flexibility. Here, we sought to link these two, largely separate, research domains by testing the hypothesis that greater HRV would be associated with better dietary self-control in humans. Specifically, we examined whether total HRV at sedentary rest (measured as the SD of normal-to-normal intervals) can serve as a biomarker for the neurophysiological adaptability that putatively underlies self-controlled behavior. We found that HRV explained a significant portion of the individual variability in dietary self-control, with individuals having higher HRV being better able to downregulate their cravings in the face of taste temptations. Furthermore, HRV was associated with activity patterns in the ventromedial prefrontal cortex (vmPFC), a key node in the brain's valuation and decision circuitry. Specifically, individuals with higher HRV showed both higher overall vmPFC blood-oxygen-level-dependent activity and attenuated taste representations when presented with a dietary self-control challenge. Last, the behavioral and neural associations with HRV were consistent across both our stress induction and control experimental conditions. The stability of this association across experimental conditions suggests that HRV may serve as both a readily obtainable and robust biomarker for self-control ability across environmental contexts. SIGNIFICANCE STATEMENT Self-control is associated with better health, but behavioral and psychometric self-control measures allow only indirect associations with health outcomes and may be distorted by reporting bias. We tested whether resting heart-rate variability (HRV), a physiological indicator of psychological and physical health, can predict individual differences in dietary self-control in humans. We found that higher HRV was associated with better self-control and improved predictions of choice behavior. Specifically, higher HRV was associated with more effective downregulation of taste temptations, and with a diminished neural representation of taste temptations during self-control challenges. Our results suggest that HRV may serve as an easily acquired, noninvasive, and low-cost biomarker for self-control ability.
Diabetes Objective Control and Education (DOCE) Project Study: Continued education and multiprofessional care in type 1 diabetes contribute to long-term glycemic control?

The purpose of this study was to assess the effectiveness of continued education and multiprofessional care for type 1 diabetes mellitus patients as a strategy for long-term glycemic control evaluated by glycosylated hemoglobin (A1C) levels. This study is a retrospective, observational study of the Diabetes Objective Control and Education (DOCE) Project. A group of 74 patients accompanied by family member attended multiprofessional appointments and an epidemiologic profile of the group was created. The analyzed variables were age, body mass index (BMI), height, duration of disease, age at diagnosis, duration of follow-up, current and baseline A1C, and the relationship between the period of follow-up and the variation in A1C. Mean age at diagnosis was 10.4±7.3 years, and duration of disease was 5.6±6.3 years. Mean age was 16±9.3 years, while mean BMI was 20.3±5.3. Mean duration of follow-up was 27.5±15.6 months. Baseline and current A1C were 10.5±1.8 and 8.2±1.7, respectively. A significant reduction in A1C was observed with the follow-up by the DOCE Project (p=0.00436). Other significant correlations were found between duration of treatment and reduction of current A1C (p=0.00000001) and duration follow-up and A1C reduction (p=0.00000003). Continued education and multiprofessional care for type 1 diabetes mellitus patients is an effective method for long-term glycemic control. Key words: Diabetes mellitus, glycosylated hemoglobin (A1C), education, glycemic control.
Electrical and Network Neuronal Properties Are Preferentially Disrupted in Dorsal, But Not Ventral, Medial Entorhinal Cortex in a Mouse Model of Tauopathy

The entorhinal cortex (EC) is one of the first areas to be disrupted in neurodegenerative diseases such as Alzheimer's disease and frontotemporal dementia. The responsiveness of individual neurons to electrical and environmental stimuli varies along the dorsal–ventral axis of the medial EC (mEC) in a manner that suggests this topographical organization plays a key role in neural encoding of geometric space. We examined the cellular properties of layer II mEC stellate neurons (mEC-SCs) in rTg4510 mice, a rodent model of neurodegeneration. Dorsoventral gradients in certain intrinsic membrane properties, such as membrane capacitance and afterhyperpolarizations, were flattened in rTg4510 mEC-SCs, while other cellular gradients [e.g., input resistance (Ri), action potential properties] remained intact. Specifically, the intrinsic properties of rTg4510 mEC-SCs in dorsal aspects of the mEC were preferentially affected, such that action potential firing patterns in dorsal mEC-SCs were altered, while those in ventral mEC-SCs were unaffected. We also found that neuronal oscillations in the gamma frequency band (30–80 Hz) were preferentially disrupted in the dorsal mEC of rTg4510 slices, while those in ventral regions were comparatively preserved. These alterations corresponded to a flattened dorsoventral gradient in theta-gamma cross-frequency coupling of local field potentials recorded from the mEC of freely moving rTg4510 mice. These differences were not paralleled by changes to the dorsoventral gradient in parvalbumin staining or neurodegeneration. We propose that the selective disruption to dorsal mECs, and the resultant flattening of certain dorsoventral gradients, may contribute to disturbances in spatial information processing observed in this model of dementia. SIGNIFICANCE STATEMENT The medial entorhinal cortex (mEC) plays a key role in spatial memory and is one of the first areas to express the pathological features of dementia. Neurons of the mEC are anatomically arranged to express functional dorsoventral gradients in a variety of neuronal properties, including grid cell firing field spacing, which is thought to encode geometric scale. We have investigated the effects of tau pathology on functional dorsoventral gradients in the mEC. Using electrophysiological approaches, we have shown that, in a transgenic mouse model of dementia, the functional properties of the dorsal mEC are preferentially disrupted, resulting in a flattening of some dorsoventral gradients. Our data suggest that neural signals arising in the mEC will have a reduced spatial content in dementia.
Mapping the Subcellular Distribution of α-Synuclein in Neurons using Genetically Encoded Probes for Correlated Light and Electron Microscopy: Implications for Parkinson's Disease Pathogenesis

Modifications to the gene encoding human α-synuclein have been linked to the development of Parkinson's disease. The highly conserved structure of α-synuclein suggests a functional interaction with membranes, and several lines of evidence point to a role in vesicle-related processes within nerve terminals. Using recombinant fusions of human α-synuclein, including new genetic tags developed for correlated light microscopy and electron microscopy (the tetracysteine-biarsenical labeling system or the new fluorescent protein for electron microscopy, MiniSOG), we determined the distribution of α-synuclein when overexpressed in primary neurons at supramolecular and cellular scales in three dimensions (3D). We observed specific association of α-synuclein with a large and otherwise poorly characterized membranous organelle system of the presynaptic terminal, as well as with smaller vesicular structures within these boutons. Furthermore, α-synuclein was localized to multiple elements of the protein degradation pathway, including multivesicular bodies in the axons and lysosomes within neuronal cell bodies. Examination of synapses in brains of transgenic mice overexpressing human α-synuclein revealed alterations of the presynaptic endomembrane systems similar to our findings in cell culture. Three-dimensional electron tomographic analysis of enlarged presynaptic terminals in several brain areas revealed that these terminals were filled with membrane-bounded organelles, including tubulovesicular structures similar to what we observed in vitro. We propose that α-synuclein overexpression is associated with hypertrophy of membrane systems of the presynaptic terminal previously shown to have a role in vesicle recycling. Our data support the conclusion that α-synuclein is involved in processes associated with the sorting, channeling, packaging, and transport of synaptic material destined for degradation.
Succinobucol: review of the metabolic, antiplatelet and cardiovascular effects

Background: Succinobucol (AGI-1067) was developed as a probucol derivative with anti-inflammatory and antioxidant properties. It has undergone Phase III clinical trials to determine its place in the treatment of atherosclerotic disease. Objective: This paper reviews the available history, pharmacology and preclinical and clinical trial data of succinobucol. Methods: Data were compiled following review of publications indexed in Medline and International Pharmaceutical Abstracts, industry media releases and relevant bibliographies. Results/conclusion: In preclinical studies, succinobucol exhibited antioxidant, anti-inflammatory, antihyperglycemic and antiplatelet properties; however, these effects have not resulted in a reduction in cardiovascular clinical end points in clinical trials. Although proposed antihyperglycemic effects are being investigated, safety concerns and lack of clear cardiovascular benefit may limit its clinical use as an antihyperglycemic agent.
Heading Tuning in Macaque Area V6

Cortical areas, such as the dorsal subdivision of the medial superior temporal area (MSTd) and the ventral intraparietal area (VIP), have been shown to integrate visual and vestibular self-motion signals. Area V6 is interconnected with areas MSTd and VIP, allowing for the possibility that V6 also integrates visual and vestibular self-motion cues. An alternative hypothesis in the literature is that V6 does not use these sensory signals to compute heading but instead discounts self-motion signals to represent object motion. However, the responses of V6 neurons to visual and vestibular self-motion cues have never been studied, thus leaving the functional roles of V6 unclear. We used a virtual reality system to examine the 3D heading tuning of macaque V6 neurons in response to optic flow and inertial motion stimuli. We found that the majority of V6 neurons are selective for heading defined by optic flow. However, unlike areas MSTd and VIP, V6 neurons are almost universally unresponsive to inertial motion in the absence of optic flow. We also explored the spatial reference frames of heading signals in V6 by measuring heading tuning for different eye positions, and we found that the visual heading tuning of most V6 cells was eye-centered. Similar to areas MSTd and VIP, the population of V6 neurons was best able to discriminate small variations in heading around forward and backward headings. Our findings support the idea that V6 is involved primarily in processing visual motion signals and does not appear to play a role in visual–vestibular integration for self-motion perception. SIGNIFICANCE STATEMENT To understand how we successfully navigate our world, it is important to understand which parts of the brain process cues used to perceive our direction of self-motion (i.e., heading). Cortical area V6 has been implicated in heading computations based on human neuroimaging data, but direct measurements of heading selectivity in individual V6 neurons have been lacking. We provide the first demonstration that V6 neurons carry 3D visual heading signals, which are represented in an eye-centered reference frame. In contrast, we found almost no evidence for vestibular heading signals in V6, indicating that V6 is unlikely to contribute to multisensory integration of heading signals, unlike other cortical areas. These findings provide important constraints on the roles of V6 in self-motion perception.
Sexual Dimorphism in a Reciprocal Interaction of Ryanodine and IP3 Receptors in the Induction of Hyperalgesic Priming

Hyperalgesic priming, a model of pain chronification in the rat, is mediated by ryanodine receptor-dependent calcium release. Although ryanodine induces priming in both sexes, females are 5 orders of magnitude more sensitive, by an estrogen receptor α (EsRα)-dependent mechanism. An inositol 1,4,5-triphosphate (IP3) receptor inhibitor prevented the induction of priming by ryanodine. For IP3 induced priming, females were also more sensitive. IP3-induced priming was prevented by pretreatment with inhibitors of the sarcoendoplasmic reticulum calcium ATPase and ryanodine receptor. Antisense to EsRα prevented the induction of priming by low-dose IP3 in females. The induction of priming by an EsRα agonist was ryanodine receptor-dependent and prevented by the IP3 antagonist. Thus, an EsRα-dependent bidirectional interaction between endoplasmic reticulum IP3 and ryanodine receptor-mediated calcium signaling is present in the induction of hyperalgesic priming, in females. In cultured male DRG neurons, IP3 (100 μm) potentiated depolarization-induced transients produced by extracellular application of high-potassium solution (20 mm, K20), in nociceptors incubated with β-estradiol. This potentiation of depolarization-induced calcium transients was blocked by the IP3 antagonist, and not observed in the absence of IP3. IP3 potentiation was also blocked by ryanodine receptor antagonist. The application of ryanodine (2 nm), instead of IP3, also potentiated K20-induced calcium transients in the presence of β-estradiol, in an IP3 receptor-dependent manner. Our results point to an EsRα-dependent, reciprocal interaction between IP3 and ryanodine receptors that contributes to sex differences in hyperalgesic priming. SIGNIFICANCE STATEMENT The present study demonstrates a mechanism that plays a role in the marked sexual dimorphism observed in a model of the transition to chronic pain, hyperalgesic priming. This mechanism involves a reciprocal interaction between the endoplasmic reticulum receptors, IP3 and ryanodine, in the induction of priming, regulated by estrogen receptor α in the nociceptor of female rats. The presence of this signaling pathway modulating the susceptibility of nociceptors to develop plasticity may contribute to our understanding of sex differences observed clinically in chronic pain syndromes.
Polymodal TRPC signaling

TRPC proteins have been implicated in a large array of Ca2+ signaling processes and are considered as pore-forming subunits of unique polymodal channel sensors. The mechanisms of TRPC activation are so far incompletely understood but appear to involve a concert of signals that are generated typically downstream of receptor-mediated activation of phospholipase C. Specifically for the TRPC1/4/5 subfamily the activating scenario is ill-defined and appears enigmatic due to the observation of multiple modes of activation. TRPC4 was initially described as a store-operated cation channel and was repeatedly proposed as a pivotal element of the store-operated signaling pathways of various tissues. However, classical reconstitution of TRPC4 complexes in expression systems as well as recent knock-down strategies provided evidence against store-dependent regulation of this channel and raised considerable doubt in its proposed prominent role agonist-induced Ca2+ signaling. Recent analysis of the function of TRPC4 in vascular endothelial cells of divergent phenotype revealed a novel aspect of TRPC signaling, extending the current concept of TRPC regulation by a phenotype-dependent switch between Ca2+ transport and a potential intracellular scaffold function of the TRPC protein.
Serodiagnosis of Tuberculosis in Children Using A60 Antigen

Background: Measurement of antimycobacterial antibody may be used as an accurate diagnostic tool in childhood tuberculosis. Materials and Methods: This study was conducted to evaluate the value of IgG, IgA, and IgM levels against A60 antigen by using ELISA method for diagnosis of tuberculosis. 238 children aged from 6 months to 18 years old, divided into 4 groups; group A(n=51),patients with documented diagnosis of tuberculosis ;group B (n=75), patients who had close contact with TB patients; group C (n=51), patients with lung diseases other than tuberculosis; group D(n=40), healthy children . Serums of 4 different groups of patients were studied. Results: Group A consisted of 22 smear positive, 24 smear negative, and 5 extrapulmonary tuberculosis patients. Sensitivity for bacteriologic study in smear positive cases was 51.2%. The mean levels of IgG, IgA, and IgM were significantly high in group A compared to other groups. IgM anti-A60 antibody had 70.6% sensitivity and 62% specificity for tuberculosis. Among the smear negative tuberculosis patients IgM anti-A60 had a sensitivity of 62.1%. Sensitivity of IgM anti-A60 in group B was 53.3% . The sensitivity of combined use of IgG and IgM was 70.6% in group A. Conclusion: The sensitivity of serologic diagnosis of A60 antigen is higher than bacteriologic findings (77.3% vs. 51.2%). A60-ELISA test is a simple and rapid diagnostic method, which can facilitate the diagnosis of tuberculosis. (Tanaffos
Hand‐held turbine spirometer: Agreement with the conventional spirometer at baseline and after exercise

Portable hand‐held spirometers are widely used in outpatient clinics and in field surveys when examining children for asthma. However, the validity of the results obtained from the hand‐held spirometers has not been assessed in population‐based studies. We evaluated the agreement between the forced expiratory volume (FEV1) values got by the conventional flow volume spirometer (FVS) and the pocket‐sized turbine spirometer (TS) at baseline and after exercise, among the 212 children screened for asthma and asthma‐like symptoms from a population of 1633 school‐aged children. The comparison was made between and within three diagnostic groups: clinical asthma (n = 34), possible asthma (n = 31), and controls (n = 147). In general, the differences in FEV1 between the FVS and the TS were small. For all children, the mean difference in FEV1 and the limits of agreement (difference ±2 s.d.) was 0.05 l (0.23 to −0.13) at baseline and 0.06 l (0.24 to −0.12) after exercise. No significant differences were observed in the agreement between the diagnostic groups. In conclusion, although FEV1 results obtained by the hand‐held spirometer are not interchangeable with those by the conventional spirometer, they are in reasonable agreement. The agreement is similar both at baseline and after exercise, and is not influenced by the presence of asthma.
Nurse-controlled analgesia for postoperative pain in pediatric patients: effects on nurses’ attitudes and patient care

Background: Because of the limited number of patient-controlled analgesia (PCA) pumps in our developing country, we proposed a technique of modified nurse-controlled analgesia (NCA) to relieve postoperative painin pediatric patients. Objective: We assessed efficacy, safety, compliance by nurses, and satisfaction including parent satisfaction of a modified NCA protocol compared with fixed-dose analgesia conventionally used for postoperative pain relief in pediatric patients. Methods: A prospective study design was conducted in pediatric patients who underwent major surgery in a university hospital. In the pre-NCA phase, patients received a conventional fixed-dose opioid after surgery. Inthe NCA phase, nurses could initiate two additional small doses autonomously, as prescribed, if the initial bolus was inadequate. Outcome measures were the number of moderate to severe pain scores, respiratory depression, compliance by nurses, and parent satisfaction. Results: There were 117 and 113 patients in the pre-NCA and NCA phases, respectively. Detection of moderate to severe pain ? 2 episodes in 24 h after surgery was significantly higher in the NCA phase especially in moderate to severe pain procedures. Respiratory depression was not found in either phase. The majority of nurses showed positive attitudes to routine use of a modified NCA protocol. Parent satisfaction was high in both groups. Conclusion: The attitude of nurses toward the modified NCA protocol was positive and it significantly increased detection of episodes of moderate to severe postoperative pain, which accordingly increased patient care andpain relief without severe untoward effects. Keywords: Nurse-controlled analgesia, nurse attitude, pediatrics, postoperative pain