Miracle-dz/UniFAR-FTUs huggingface dataset:
HIF-1α affects trophoblastic apoptosis involved in the onset of preeclampsia by regulating FOXO3a under hypoxic conditions

Preeclampsia (PE) is a pregnancy-specific syndrome that has severe implications on perinatal mortality and morbidity. Excessive apoptosis of trophoblasts induced by hypoxia may be associated with the development of PE, but the exact pathogenesis is unknown. Forkhead box O transcription factor 3a (FOXO3a) is activated under hypoxic conditions. Furthermore, hypoxia-inducible factor-1α (HIF-1α) is sensitive to variations in partial oxygen pressure. Thus, the aims of the present study were to investigate the expression levels of HIF-1α and FOXO3a in placental samples of early onset severe PE, and their effect on trophoblastic apoptosis under hypoxic conditions. Cobalt chloride was used to establish the hypoxic model. The present study examined the expression levels of HIF-1α and FOXO3a in the placental tissues and HTR8/SVneo cells under hypoxic conditions. It was found that HIF-1α and FOXO3a were highly expressed in placental tissues of patients with PE and in HTR8/SVneo cells under hypoxic conditions. Furthermore, knockdown of FOXO3a using a specific small interfering RNA (siRNA) decreased apoptosis in HTR8/SVneo cells. Moreover, it was found that after knockdown of HIF-1α using siRNA, FOXO3a expression and the apoptotic rate were reduced in HTR8/SVneo cells. Therefore, the present results indicated that the elevated expression of HIF-1α increased trophoblastic apoptosis by regulating FOXO3a, which may be involved in the pathogenesis of PE.
Fatal Fulminant Legionnaires' Disease in a Patient on Maintenance Hemodialysis

We herein report a case of fulminant Legionnaires' disease with autopsy findings in a patient on maintenance hemodialysis (HD). Chronic kidney disease is a strong risk factor for Legionnaires' disease, although there have been only a few reports in HD patients. Because most patients on HD are anuric, the use of rapid assay kits to detect antigens in urine samples for the diagnosis of Legionnaires' disease is not always feasible. We suggest the use of clinical predictive tools or the loop-mediated isothermal amplification (LAMP) method, which can be applied for anuric patients, such as those on HD, with pneumonia.
Consumption of the Artificial Sweetener Acesulfame Potassium throughout Pregnancy Induces Glucose Intolerance and Adipose Tissue Dysfunction in Mice.

BACKGROUND Sugar-sweetened beverage consumption is associated with metabolic dysfunction. Artificially sweetened beverages (ASBs) are often promoted as an alternative. However, evidence for the safety of ASB consumption during pregnancy is lacking. OBJECTIVES The effects of sugar-sweetened beverage and ASB consumption during pregnancy in mice were examined, and we hypothesized that both sugar-sweetened beverages and ASBs would impair maternal metabolic function. METHODS Pregnant female C57BL/6J mice received control drinking water (CD), high-fructose corn syrup (Fr; 20% kcal intake; 335 mM), or the artificial sweetener acesulfame potassium (AS; 12.5 mM) in their drinking water, from gestational day (GD) 0.5 (n = 8/group). Body weights and food and water intakes were assessed every second day, an oral-glucose-tolerance test (OGTT) was performed at GD 16.5, and mice were culled at GD 18.5. RT-PCR was carried out on adipose tissue, liver, and gut. Adipose tissue morphology was assessed using histological methods. In a separate cohort of animals, pregnancy length was assessed. Repeated-measures ANOVA was performed for the OGTT and weight gain data. All other data were analyzed by 1-way ANOVA. RESULTS Fr and AS significantly impaired glucose tolerance, as demonstrated by OGTT (21% and 24% increase in AUC, respectively; P = 0.0006). Fr and AS reduced expression of insulin receptor (39.5% and 33% reduction, respectively; P = 0.02) and peroxisome proliferator-activated receptor γ (45.2% and 47%, respectively; P = 0.039), whereas Fr alone reduced expression of protein kinase B (36.9% reduction; P = 0.048) and resulted in an increase in adipocyte size and leptin concentrations (40% increase; P = 0.03). AS, but not Fr, reduced male fetal weight (16.5% reduction; P = 0.04) and female fetal fasting blood glucose concentration at cull (20% reduction; P = 0.02) compared with CD. AS significantly reduced the length of pregnancy compared with the CD and Fr groups (1.25 d shorter; P = 0.02). CONCLUSIONS Fr and AS consumption were associated with maternal metabolic dysfunction in mice. AS was also associated with reduced fetal growth and fetal hypoglycemia. Therefore, ASBs may not be a beneficial alternative to sugar-sweetened beverages during pregnancy.
Neurological soft signs (NSS) and brain morphology in patients with chronic schizophrenia and healthy controls

Subtle abnormalities in sensory integration, motor coordination and sequencing of complex motor acts or neurological soft signs (NSS) are characteristic phenomena in patients with schizophrenia at any stage of the illness. Previous MRI studies in schizophrenia found NSS to be associated with cortical, thalamic and cerebellar changes. Since these studies mainly focused on first-episode or recent onset schizophrenia, the cerebral correlates of NSS in chronic schizophrenia remained rather unclear. 49 middle-aged patients with chronic schizophrenia with a mean duration of illness of 20.3 ± 14.0 years and 29 healthy subjects matched for age and sex were included. NSS were examined on the Heidelberg Scale and correlated to grey matter (GM) by using whole brain high resolution magnetic resonance imaging (3 Tesla) with SPM12/CAT12 analyses. As expected, NSS in patients were significantly (p≤0.001) elevated in contrast to healthy controls, a finding, which not only applied to NSS total score, but also to the respective subscales “motor coordination”, “sensory integration”, “complex motor tasks”, “right/left and spatial orientation” and “hard signs”. Within the patient group NSS total scores were significantly correlated to reduced GM in right lingual gyrus, left parahippocampal gyrus, left superior temporal gyrus, left thalamus (medial dorsal nucleus) and left posterior lobe of the cerebellum (declive). Respective negative associations could also be revealed for the subscales “motor coordination”, “complex motor tasks” and “right/left and spatial orientation”. These findings remained significant after FWE-correction for multiple comparisons and were confirmed when years of education, chlorpromazine-equivalents or variables indicating the severity of psychopathology were introduced as additional covariates. According to our results lingual, parahippocampal, superior temporal, inferior and middle frontal gyri, thalamus and cerebellum have to be considered as important sites of NSS in chronic schizophrenia. That these findings only applied for patients but not healthy controls may indicate a different pathogenesis of NSS.
Thermal stability analyses of human PERIOD-2 C-terminal domain using dynamic light scattering and circular dichroism

At the molecular level, the circadian clock is regulated by a time delayed transcriptional-translational feedback loop in which the core proteins interact with each other rhythmically to drive daily biological rhythms. The C-terminal domain of a key clock protein PER2 (PER2c) plays a critically important role in the loop, not only for its interaction with the binding partner CRY proteins but also for the CRY/PER complex’s translocation from the cytosol to the nucleus. Previous circular dichroism (CD) spectroscopic studies have shown that mouse PER2c (mPER2c) is less structured in solution by itself but folded into stable secondary structures upon interaction with mouse CRYs. To understand the stability and folding of human PER2c (hPER2c), we expressed and purified hPER2c. Three oligomerization forms of recombinant hPER2c were identified and thoroughly characterized through a combination of biochemical and biophysical techniques. Different to mPER2c, both thermal unfolding DLS and CD analyses suggested that all forms of hPER2c have very stable secondary structures in solution by themselves with melting temperatures higher than the physiological body temperature, indicating that hPER2c does not require CRY to fold. Furthermore, we examined the effects of EDTA, salt concentration, and a reducing agent on hPER2c folding and oligomerization. The ability of hPER2c forming oligomers reflects the potential role of hPER2c in the assembly of circadian rhythm core protein complexes.
The Effect of Carbazochrome Sodium Sulfonate in Patients with Colonic Diverticular Bleeding: Propensity Score Matching Analyses Using a Nationwide Inpatient Database

Objective Carbazochrome sodium sulfonate (CSS) has been routinely used to treat bleeding; however, no study has examined the effect of CSS for gastrointestinal bleeding. Therefore, we aimed to investigate the effect of CSS for colonic diverticular bleeding. Methods We performed a nationwide observational study using the Japanese Diagnosis Procedure Combination inpatient database. We identified patients who were admitted for diverticular bleeding from July 2010 to March 2018. Patients who received CSS on the day of admission were defined as the CSS group, and those not receiving CSS were defined as the control group. The primary outcome was in-hospital mortality. Secondary outcomes were length of stay, total costs, and blood transfusion within 7 days of admission. Propensity score matching analyses were performed to compare outcomes between the two groups. Results A total of 59,965 patients met our eligibility criteria. Of these, 14,437 (24%) patients received CSS on the day of admission. One-to-one propensity score matching created 14,379 matched pairs. There was no significant difference in the in-hospital mortality between the CSS and control groups (0.6% vs. 0.5%, respectively; odds ratio: 0.96; 95% confidence interval: 0.72-1.29). The length of stay was longer in the CSS group than in the control group (11.4 vs. 11.0 days, respectively; difference: 0.44; 95% confidence interval: 0.14-0.73). There were no significant differences in the total costs or the proportion of patients receiving blood transfusion between the groups. Conclusions CSS may not reduce in-hospital mortality, length of stay, total costs, or the need for blood transfusion in patients with colonic diverticular bleeding.
Dopamine D2-Like Receptors Modulate Intrinsic Properties and Synaptic Transmission of Parvalbumin Interneurons in the Mouse Primary Motor Cortex

Abstract Dopamine (DA) plays a crucial role in the control of motor and higher cognitive functions such as learning, working memory, and decision making. The primary motor cortex (M1), which is essential for motor control and the acquisition of motor skills, receives dopaminergic inputs in its superficial and deep layers from the midbrain. However, the precise action of DA and DA receptor subtypes on the cortical microcircuits of M1 remains poorly understood. The aim of this work was to investigate in mice how DA, through the activation of D2-like receptors (D2Rs), modulates the cellular and synaptic activity of M1 parvalbumin-expressing interneurons (PVINs) which are crucial to regulate the spike output of pyramidal neurons (PNs). By combining immunofluorescence, ex vivo electrophysiology, pharmacology and optogenetics approaches, we show that D2R activation increases neuronal excitability of PVINs and GABAergic synaptic transmission between PVINs and PNs in Layer V of M1. Our data reveal how cortical DA modulates M1 microcircuitry, which could be important in the acquisition of motor skills.
Impairment of wound healing by reactive skin decontamination lotion (RSDL®) in a Göttingen minipig® model

Abstract Reactive Skin Decontamination Lotion (RSDL®) is an FDA-approved skin decontamination kit carried by service members for removal and neutralisation of vesicants and nerve agents. The RSDL kit, comprised of a lotion-impregnated sponge, was shown to be the superior medical decontamination device for chemical warfare agent (CWA) exposure on intact skin. In the event of a chemical exposure situation (i.e. terrorism, battlefield) physical injuries are probable, and preservation of life will outweigh the risk associated with application of RSDL to compromised skin. The purpose of this study was to quantify the rate and quality of wound healing in epidermal skin wounds treated with RSDL in a porcine model. Degree of wound healing was assessed using bioengineering methods to include ballistometry, colorimetry, evaporimetry, and high-frequency ultrasonography. Clinical observation, histopathology and immunohistochemistry were also utilised. All pigs received four bilateral superficial abdominal wounds via a pneumatic dermatome on their ventral abdomen, then were treated with the following dressings over a seven-day period: RSDL sponge, petroleum based Xeroform® gauze, 3 M™ Tegaderm™ Film, and 3 M™ Tegaderm™ Foam. Two additional non-wounded sites on the flank were used as controls. Two groups of pigs were then evaluated for a 21- or 56-day time period, representing short- and long-term wound-healing progression. Our findings indicated RSDL had a negative impact on wound-healing progression at both 21 and 56 days post-injury. Wounds receiving RSDL demonstrated a decreased skin elasticity, significant transepidermal water loss, and altered skin colouration and thickness. In addition, the rate of wound healing was delayed, and return to a functional skin barrier was altered when compared to non-RSDL-treated wounds. In conclusion, wound management care and clinical therapeutic intervention plans should be established to account for a prolonged duration of healing in patients with RSDL-contaminated wounds.
Using Natural Language Processing Techniques to Provide Personalized Educational Materials for Chronic Disease Patients in China: Development and Assessment of a Knowledge-Based Health Recommender System

Background Health education emerged as an important intervention for improving the awareness and self-management abilities of chronic disease patients. The development of information technologies has changed the form of patient educational materials from traditional paper materials to electronic materials. To date, the amount of patient educational materials on the internet is tremendous, with variable quality, which makes it hard to identify the most valuable materials by individuals lacking medical backgrounds. Objective The aim of this study was to develop a health recommender system to provide appropriate educational materials for chronic disease patients in China and evaluate the effect of this system. Methods A knowledge-based recommender system was implemented using ontology and several natural language processing (NLP) techniques. The development process was divided into 3 stages. In stage 1, an ontology was constructed to describe patient characteristics contained in the data. In stage 2, an algorithm was designed and implemented to generate recommendations based on the ontology. Patient data and educational materials were mapped to the ontology and converted into vectors of the same length, and then recommendations were generated according to similarity between these vectors. In stage 3, the ontology and algorithm were incorporated into an mHealth system for practical use. Keyword extraction algorithms and pretrained word embeddings were used to preprocess educational materials. Three strategies were proposed to improve the performance of keyword extraction. System evaluation was based on a manually assembled test collection for 50 patients and 100 educational documents. Recommendation performance was assessed using the macro precision of top-ranked documents and the overall mean average precision (MAP). Results The constructed ontology contained 40 classes, 31 object properties, 67 data properties, and 32 individuals. A total of 80 SWRL rules were defined to implement the semantic logic of mapping patient original data to the ontology vector space. The recommender system was implemented as a separate Web service connected with patients' smartphones. According to the evaluation results, our system can achieve a macro precision up to 0.970 for the top 1 recommendation and an overall MAP score up to 0.628. Conclusions This study demonstrated that a knowledge-based health recommender system has the potential to accurately recommend educational materials to chronic disease patients. Traditional NLP techniques combined with improvement strategies for specific language and domain proved to be effective for improving system performance. One direction for future work is to explore the effect of such systems from the perspective of patients in a practical setting.
Proactive interference apraxic agraphia: a writing and drawing disorder associated with corticobasal syndrome

ABSTRACT Proactive interference is when a previously performed task impairs performance on a current task. It is often associated with memory tasks and has not been reported to interfere with writing or drawing. We evaluated a left-handed man diagnosed with corticobasal syndrome who had a two-year history of progressive agraphia. On the sentence writing and clock drawing tasks, he initially wrote letters and numbers correctly but revealed an increase of movement errors as the tasks progressed. We propose the term “proactive interference apraxic agraphia” for this novel disorder. Prefrontal dysfunction may cause an impairment in disengaging from previously activated motor programs.
Anticipatory emotion regulation of a highly arousing stressor in adulthood and old age

Abstract Objectives Most studies of emotion regulation across the lifespan have focused on how individuals manage their emotions during or after emotional events. However the current study examined how anticipatory emotion regulation behavior, a process that occurs before an emotional event has been experienced, influenced young (Mage = 19.66) and older (Mage = 70.02) adults’ affective experience, physiological reactivity, and task performance. Method Participants were first provided with a detailed description of an upcoming evaluative stress task, but were able to regulate their affective state by selecting one video to watch from a selection of 8 videos labelled by valence and arousal before completing the stressful task. Results Participants across age groups were more likely to select a positive video, and participants who made positive selections initially felt better than those who selected negative content, though they experienced sharper mood declines than those who selected a negative video. Negative selections were linked to better performance on the speech task across age groups. Conclusions These findings suggest that, when anticipating a negative situation, participants preemptively increase positive emotions. However, while positive selections served to temporarily improve mood, the effects did not last throughout the stress task. These results provide more evidence for age similarity than age differences in anticipatory emotion regulation effects and behaviors.
The relationship between executive functions and fluid intelligence in multiple sclerosis

Background & objective Deficits in cognitive functions dependent upon the integrity of the prefrontal cortex have been described in Multiple Sclerosis (MS). In a series of studies we have shown that fluid intelligence (g) is a substantial contributor to frontal deficits and that, for some classical “executive” tasks, frontal deficits were entirely explained by g. However, for another group of frontal tasks deficits remained once g was introduced as a covariate. This second set of tests included multitasking and theory of mind tasks. In the present study, we aimed at determining the role of fluid intelligence in frontal deficits seen in patients with MS. Methods A group of patients with Relapsing Remitting MS (n = 36) and a group of control subjects (n = 42) were assessed with a battery of classical executive tests (which included the Wisconsin Card Sorting Test, Verbal Fluency, and Trail Making Test B), a multitasking test, a theory of mind test and a fluid intelligence test. Results MS patients showed significant deficits in the fluid intelligence task. We found differences between patients and control subjects in all tests except for the multitasking test. The differences in the classical executive tests became non-significant once fluid intelligence was introduced as a covariate, but differences in theory of mind remained. Conclusions The present results suggest that fluid intelligence can be affected in MS and that this impairment can play a role in the executive deficits described in MS.
The role of larval fat cells in starvation resistance and reproduction in adult Drosophila melanogaster

The Role of Larval Fat Cells in Starvation Resistance and Reproduction in Adult Drosophila melanogaster by Jerell Roland Aguila Dr. Deborah K. Hoshizaki, Examination Committee Chair Associate Professor of Life Sciences University of Nevada, Las Vegas The intricate life cycle of holometabolous insects includes well-defined larval and adult stages associated with feeding and non-feeding periods. The larval stage is distinguished by prevalent feeding and is necessary for supporting the animal as it quickly grows. The larval stage also serves as the period for the animal to obtain adequate energy stores, primarily in the larval fat body, to fuel the animal through the non-feeding pupal and immature adult stages. Acquiring sufficient energy stores is paramount for the success of the adult animal. In fact, certain insects, such as silkworms and mayflies, do not feed as adults and must obtain all their lifetime nutrients during the larval stage. In Drosophila melanogaster, the larval fat body is preserved during the pupal stage as individual dissociated cells, enabling the animal access to the energy stores. These larval fat cells do not undergo early pupal autophagic cell death that eliminates most of the larval cells during metamorphosis. Instead, these larval fat cells persist into the adult stage and have a nutritional role in the young adult. By utilizing cell markers, I show that the larval fat cells remain in the young adult and are ultimately removed in the adult by a
Fr-PPIChem: An academic compound library dedicated to protein-protein interactions.

Protein-protein interactions (PPIs) mediate nearly every cellular process and represent attractive targets for modulating disease states but are challenging to target with small molecules. Despite this, several PPI inhibitors (iPPIs) have entered clinical trials, and a growing number of PPIs have become validated drug targets. However, high-throughput screening efforts still endure low hit rates mainly because of the use of unsuitable screening libraries. Here, we describe the collective effort of a French consortium to build, select and store in plates a unique chemical library dedicated to the inhibition of PPIs. Using two independent predictive models and two updated databases of experimentally confirmed PPI inhibitors developed by members of the consortium, we built models based on different training sets, molecular descriptors and machine learning methods. Independent statistical models were used to select putative PPI inhibitors from large commercial compound collections showing great complementarity. Medicinal chemistry filters were applied to remove undesirable structures from this set (such as PAINS, frequent hitters and toxic compounds) and to improve drug likeness. The remaining compounds were subjected to a clustering procedure to reduce the final size of the library while maintaining its chemical diversity. In practice, the library showed a 46-fold activity rate enhancement when compared to a non-iPPI-enriched diversity library in high-throughput screening against the CD47-SIRPα PPI. The Fr-PPIChem library is plated in 384-well plates and will be distributed on demand to the scientific community as a powerful tool for discovering new chemical probes and early hits for the development of potential therapeutic drugs.