Miracle-dz/UniFAR-FTUs huggingface dataset:
Enhanced H3K4 Trimethylation in TNF-α Promoter Gene Locus with Cell Apoptosis in the Ventral-Medial Striatum following Opioid Withdrawal of Neonatal Rat Offspring from Morphine-Addicted Mothers

Prenatal opioid exposure might disturb epigenetic programming in the brain of neonatal offspring with various consequences for gene expressions and behaviors. This study determined whether altered trimethylation of histone 3 at lysine 4 (H3K4me3) in the promoter of the tumor necrosis factor-α (tnf-α) gene with neural cell apoptosis was involved in the ventral-medial striatum, an important brain region for withdrawal symptoms, of neonatal rat offspring from morphine-addicted mothers. Female adult rats were injected with morphine before gestation and until 14 days after giving birth. On postnatal day 14 (P14), rat offspring from morphine-addicted mothers were subjected to an opioid-withdrawal protocol and were analyzed 2 or 8 h after administration of that protocol. Expressions of the TNF-α protein, H3K4me3 in the tnf-α promoter gene, and neural cell apoptosis within the ventral-medial striatum of neonatal rat offspring were evaluated. In the absence of significant opioid withdrawal (2 h after initiation of the opioid-withdrawal protocol on P14), prenatal morphine exposure led to increased levels of H3K4me3 in the tnf-α promoter gene, of the TNF-α protein, and of neural cell apoptosis within the ventral-medial striatum of neonatal rat offspring. Following opioid withdrawal (8 h after initiation of the opioid-withdrawal protocol on P14), differential expression of H3K4me3 in the tnf-α promoter gene locus and upregulation of the level of TNF-α protein expression were further enhanced in these offspring. In addition, increased levels of caspase-3 and neural cell apoptosis were also observed. Taken together, this study revealed that prenatal opioid exposure can activate an epigenetic histone mechanism which regulates proinflammatory factor generation, which hence, led to cell apoptotic damage within the ventral-medial striatum of neonatal rat offspring from morphine-addicted mothers. More importantly, the opioid-withdrawal episode may provide augmented effects for the abovementioned alterations and could lead to deleterious effects in the neonatal brain of such offspring.
Synthesis of darusentan,an ET_A selective endothelin receptor antagonist

Objective: To synthesize darusentan, an ET_A selective endothelin receptor antagonist. Methods: Using diphenyl ketone as a starting material, the target compound was synthesized via several steps, involving in non-solvent Darzens condensation with ethyl chloroacetate, methanolysis catalyzed by p-toluene sulfonic acid, nucleophilic substitution with 2-chloro-4, 6-dimethoxypyrimidine catalyzed by sulfinate, and alkaline hydrolysis. Results: The chemical structure of the target compound was verified using IR, ~1H-NMR and MS. Conclusion: The easily controlled and low cost process for the synthesis of darusentan achieved a total yield of 53.5%.
Phytochemical composition and health properties of Sembung plant (Blumea balsamifera): A review

Indonesia’s mindset has been focusing on the use of natural medicines, food, and healing practices widely recognized by the nation’s culture. Traditional medicines and herbs used in traditional medicine can often lead to the discovery of drugs against certain diseases. The aim of this review was to study evidence-based data on the importance of Sembung plant, Blumea balsamifera, as a potential traditional medicine. The distribution, ethnopharmacology, secondary metabolites, and bioactivity against several diseases are focused in this review. Information and research related to Sembung plant were searched using the terms “B. balsamifera,” “phytochemicals,” and “pharmacological activity” on ResearchGate, Google Scholar, Science Direct, PubMed, and scientific information-based databases up to 2020. Several ethnomedical articles recommend B. balsamifera for the treatment of sinusitis, colic pain, cough, kidney stones, flu, or as a diuretic. This knowledge has already been applied in several countries in Southeast Asia. B. balsamifera has been reported to contain several phytochemicals both volatile (terpenoids, fatty acids, phenols, alcohol, aldehydes, ethers, ketones, pyridines, furans, and alkanes) and non-volatile (flavonoids, flavanones, and chalcones). Extracts and phytochemicals of B. balsamifera contain several biological capacities such as antioxidant, antimicrobial, antifungal, anti-inflammatory, hypolipidemic, anti-infertility, hepatoprotective activity, antidiabetic, gastroprotective, antitumor, anticancer, and immunomodulatory agent against Coronavirus disease-19 infection. This review provides essential data for the potential application of B. balsamifera as a nutraceutical or in future medicinal preparations.
Aberrant Mitochondrial Dynamics: An Emerging Pathogenic Driver of Abdominal Aortic Aneurysm

Abdominal aortic aneurysm (AAA) is defined as a progressive segmental dilation of the abdominal aorta and is associated with high mortality. The characterized features of AAA indicate several underlying mechanisms of AAA formation and progression, including reactive oxygen species production, inflammation, and atherosclerosis. Mitochondrial functions are critical for determining cell fate, and mitochondrial dynamics, especially selective mitochondrial autophagy, which is termed as mitophagy, has emerged as an important player in the pathogenesis of several cardiovascular diseases. The PARKIN/PARIS/PGC1α pathway is associated with AAA formation and has been proposed to play a role in mitochondrial dynamics mediated by the PINK/PARKIN pathway in the pathogenesis underlying AAA. This review is aimed at deepening our understanding of AAA formation and progression, which is vital for the development of potential medical therapies for AAA.
Intravenous versus inhalational anesthesia trial for outcome following intracranial aneurysm surgery: A prospective randomized controlled study

Background: For maintenance of anesthesia for intracranial aneurysmal neck clipping, both intravenous and inhalational anesthetics are in vogue. We aimed to evaluate the superiority of one agent over the other for long-term neurological outcomes in these patients. Methods: This prospective assessor-blind randomized study was conducted in 106 patients of 18–65 years of age with World Federation of Neurosurgeons Grade I-II of subarachnoid hemorrhage. After written informed consent, the patients were randomized into – intravenous group (Propofol) and inhalational group (Desflurane). The primary outcome was to study neurological outcome using Glasgow outcome scale (GOS) at 3 months following discharge while secondary outcomes included intraoperative brain condition, intraoperative hemodynamics, duration of hospital stay, Modified Rankin Score (MRS) at discharge, MRS, and Barthel’s index at 3 months following discharge and estimation of perioperative biomarkers of brain injury. Results: The GOS at 3 months was 5 (5.00–5.00) in the propofol group and 5 (4.00–5.00) in the desflurane group (P = 0.24). Both the anesthetics were similar in terms of intraoperative hemodynamics, brain relaxation, duration of hospital stay, MRS at discharge and 3 months, and Barthel Index at 3 months (P > 0.05). The perioperative serum interleukin-6 and S100B were comparable among the groups (P > 0.05). Conclusion: The long-term neurological outcome of good grade aneurysm patients undergoing craniotomy and clipping remains comparable with the use of either propofol or desflurane. The effect of the two anesthetic agents on the various clinical parameters and the biomarkers of brain injury is also similar.
Study of threshold voltage instability in E‐mode GaN MOS‐HEMTs

In this work, the threshold instability in E-mode GaN MOS-HEMTs was investigated. In particular, the shift of VTH as a function of the applied positive gate voltage during device characterization was monitored, resulting in positive VTH shifts up to 1 V. A complete VTH recovery required more than one day of unbiased storage, but a partial recovery of the observed VTH shift was observed after few seconds. These results could be related to different positions of trap states: fast states, localized at the dielectric/GaN interface and slow states, the traps inside the dielectric layer. Moreover, VTH shift of 0.2 and 0.8 V for fast and slow states, respectively, was obtained. To gain insight into the physical mechanism involved in the observed phenomena, numerical simulation were also carried out. A VTH shift was obtained adding the interface states. Moreover, three different distributions of traps were compared. In particular, the concentration of filled traps was monitored to understand the impact of the distribution on the electrical behaviour. An increment in filled trap concentration at the increasing of the applied VGS, which in turns correlates with experimentally evaluated device behaviour, was obtained if the distribution of traps states is also above the GaN conduction band energy. (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)
Diffusion Path and Conduction Mechanism of Protons in Hydroxyapatite

Calcium hydroxyapatite (HAp, Ca10(PO4)6(OH)2) is the principal inorganic component of bone and teeth, one of the most important bioceramics, and a proton (H+) conductor with potential for energy conversion devices. The proton diffusion pathway in the HAp lattice is a key to understand the proton conduction mechanism and chemical reaction. Previous neutron-diffraction studies of HAp visualized the short-range proton diffusion pathway. In this work, we report the successful visualization of the long-range proton diffusion pathway in stoichiometric HAp at 923, 673, and 298 K through a combined technique of high-temperature neutron diffraction and bond valence method. We have visualized (1) one-dimensional proton diffusional pathways along the c-axis in the hexagonal channel and (2) two-dimensional proton migration pathway network on the ab-planes at z = 0 and 1/2. The proton diffusion and reorientation of hydroxide ions (OH–) are a complex sinusoidal process in the hexagonal channel along the c-axis, which i.
Conception d'un biocapteur basé sur la photoluminescence du GAAS (001) pour la détection de micro-organismes

In the quest for the development of an all-optical biosensor for rapid detection and typing of viral pathogens, we have been investigating biosensing architectures that take advantage of strong PL emission from III-V quantum semiconductors (QS). One of the key elements in the development of such a biosensor is the ability to attach various analytes to GaAs a material of choice for capping III-V QS of our interest. We report on the study of biofunctionalization of GaAs (001) with polyethylene-glycol (PEG) thiols and the successful immobilization of Influenza A virus. A diluted solution of biotinylated PEG thiols in OH-terminated PEG thiols has been used to form a network of sites for the attachment of neutravidin. Biotinylated polyclonal Influenza A antibodies were applied to investigate the process of the immobilization of inactivated Influenza A virus. The successful immobilization has been demonstrated using atomic force microscopy and fluorescence microscopy measurements.
Relative sit‐to‐stand power: aging trajectories, functionally relevant cut‐off points, and normative data in a large European cohort

A validated, standardized, and feasible test to assess muscle power in older adults has recently been reported: the sit‐to‐stand (STS) muscle power test. This investigation aimed to assess the relationship between relative STS power and age and to provide normative data, cut‐off points, and minimal clinically important differences (MCID) for STS power measures in older women and men.
Reliability of the hyperaemic response to passive leg movement in young, healthy women

What is the central question of this study? This is the first study to assess the day‐to‐day reliability of passive leg movement‐induced hyperaemia (PLM‐H), an index of lower‐limb microvascular function, in young, healthy women. What is the main finding and its importance? Passive leg movement‐induced hyperaemia demonstrated good day‐to‐day reliability, comparable to other common indices of endothelial function, supporting the use of PLM‐H to assess lower‐limb microvascular function in women.
Diagnostic Performance and Clinical Impact of 68Ga-PSMA-11 PET/CT Imaging in Early Relapsed Prostate Cancer After Radical Therapy: A Prospective Multicenter Study (IAEA-PSMA Study)

Visual Abstract Biochemical recurrence (BCR) is a clinical challenge in prostate cancer (PCa) patients, as recurrence localization guides subsequent therapies. The use of PET with prostate-specific membrane antigen (PSMA) provides better accuracy than conventional imaging practice. This prospective, multicenter, international study was performed to evaluate the diagnostic performance and clinical impact of PSMA PET/CT for evaluating BCR in PCa patients in a worldwide scenario. Methods: Patients were recruited from 17 centers in 15 countries. Inclusion criteria were histopathologically proven prostate adenocarcinoma, previous primary treatment, clinically established BCR, and negative conventional imaging (CT plus bone scintigraphy) and MRI results for patients with PSA levels of 4–10 ng/mL. All patients underwent PET/CT scanning with 68Ga-PSMA-11. Images and data were centrally reviewed. Multivariate logistic regression analysis was applied to identify the independent predictors of PSMA-positive results. Variables were selected for this regression model on the basis of significant associations in the univariate analysis and previous clinical knowledge: Gleason score, the PSA level at the time of the PET scan, PSA doubling time, and primary treatment strategy. All patients were monitored for a minimum of 6 mo. Results: From a total of 1,004 patients, 77.7% were treated initially with radical prostatectomy and 22.3% were treated with radiotherapy. Overall, 65.1% had positive PSMA PET/CT results. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment (P < 0.001). Treatment was modified on the basis of PSMA PET/CT results in 56.8% of patients. PSMA PET/CT positivity rates were consistent and not statistically different among countries with different incomes. Conclusion: This multicenter, international, prospective trial of PSMA PET/CT confirmed its capability for detecting local and metastatic recurrence in most PCa patients in the setting of BCR. PSMA PET/CT positivity was correlated with the Gleason score, PSA level at the time of the PET scan, PSA doubling time, and radiotherapy as the primary treatment. PSMA PET/CT results led to changes in therapeutic management in more than half of the cohort. The study demonstrated the reliability and worldwide feasibility of PSMA PET/CT in the workup of PCa patients with BCR.
Which older emergency patients are at risk of intracranial bleeding after a fall? A protocol to derive a clinical decision rule for the emergency department

Introduction Falling on level ground is now the most common cause of traumatic intracranial bleeding worldwide. Older adults frequently present to the emergency department (ED) after falling. It can be challenging for clinicians to determine who requires brain imaging to rule out traumatic intracranial bleeding, and often head injury decision rules do not apply to older adults who fall. The goal of our study is to derive a clinical decision rule, which will identify older adults who present to the ED after a fall who do not have clinically important intracranial bleeding. Methods and analysis This is a prospective cohort study enrolling patients aged 65 years or older, who present to the ED of 11 hospitals in Canada and the USA within 48 hours of having a fall. Patients are included if they fall on level ground, off a chair, toilet seat or out of bed. The primary outcome is the diagnosis of clinically important intracranial bleeding within 42 days of the index ED visit. An independent adjudication committee will determine the primary outcome, blinded to all other data. We are collecting data on 17 potential predictor variables. The treating physician completes a study data form at the time of initial assessment, prior to brain imaging. Data extraction is supplemented by an independent, structured electronic medical record review. We will perform binary recursive partitioning using Classification and Regression Trees to derive a clinical decision rule. Ethics and dissemination The study was initially approved by the Hamilton Integrated Research Ethics Committee and subsequently approved by the research ethics boards governing all participating sites. We will disseminate our results by journal publication, presentation at international meetings and social media. Trial registration number NCT03745755.
Anchoring the T6SS to the cell wall: Crystal structure of the peptidoglycan binding domain of the TagL accessory protein

The type VI secretion system (T6SS) is a widespread mechanism of protein delivery into target cells, present in more than a quarter of all sequenced Gram-negative bacteria. The T6SS constitutes an important virulence factor, as it is responsible for targeting effectors in both prokaryotic and eukaryotic cells. The T6SS comprises a tail structure tethered to the cell envelope via a trans-envelope complex. In most T6SS, the membrane complex is anchored to the cell wall by the TagL accessory protein. In this study, we report the first crystal structure of a peptidoglycan-binding domain of TagL. The fold is conserved with members of the OmpA/Pal/MotB family, and more importantly, the peptidoglycan binding site is conserved. This structure further exemplifies how proteins involved in anchoring to the cell wall for different cellular functions rely on an interaction network with peptidoglycan strictly conserved.
Seeding of Au on CdSe/CdS nanoplates using Langmuir–Blodgett technique

Oleyl amine capped CdSe/CdS nanoplates were synthesized by hot injection technique which formed a stable monolayer over both a water subphase and an aqueous HAuCl4 subphase using a Langmuir–Blodgett trough. Au islands were generated at the edge as well as on one specific surface of the flat nanoplates by exploiting the reducing capacity of oleyl amine to form Au nanoseeds from AuCl4− ions. The initial Au nanoseeds changed to a shell surrounding these nanoplates on prolonged exposure to the subphase containing the Au precursor. Monolayer of the hybrid structures was deposited onto suitable substrates for characterization by a number of different techniques and to study the photocatalytic activity. The same substrate with the monolayers could be re-used in several cycles of photocatalysis.
The Lab4P Consortium of Probiotics Attenuates Atherosclerosis in LDL Receptor Deficient Mice Fed a High Fat Diet and Causes Plaque Stabilization by Inhibiting Inflammation and Several Pro‐Atherogenic Processes

Scope Previous studies show that Lab4 probiotic consortium plus Lactobacillus plantarum CUL66 (Lab4P) reduces diet‐induced weight gain and plasma cholesterol levels in C57BL/6J mice fed a high fat diet (HFD). The effect of Lab4P on atherosclerosis is not known and is therefore investigated. Methods and Results Atherosclerosis‐associated parameters are analyzed in LDL receptor deficient mice fed HFD for 12 weeks alone or supplemented with Lab4P. Lab4P increases plasma HDL and triglyceride levels and decreases LDL/VLDL levels. Lab4P also reduces plaque burden and content of lipids and macrophages, indicative of dampened inflammation, and increases smooth muscle cell content, a marker of plaque stabilization. Atherosclerosis arrays show that Lab4P alters the liver expression of 19 key disease‐associated genes. Lab4P also decreases the frequency of macrophages and T‐cells in the bone marrow. In vitro assays using conditioned media from probiotic bacteria demonstrates attenuation of several atherosclerosis‐associated processes in vitro such as chemokine‐driven monocytic migration, proliferation of monocytes and macrophages, foam cell formation and associated changes in expression of key genes, and proliferation and migration of vascular smooth muscle cells. Conclusion This study provides new insights into the anti‐atherogenic actions of Lab4P together with the underlying mechanisms and supports further assessments in human trials.
Perforant path inputs to hippocampal subfields predict heterogeneous AMPA receptor subunit expression following rapid new spatial learning in a novel context

The hippocampus plays a critical role in spatial learning and memory. Its contribution to support these kinds of learning and memory functions relies on synaptic plasticity and related molecular mechanisms, well documented in the long‐term potentiation (LTP) literature. The present experiment measures AMPA subunit expression, in a ratio of GluA2:GluA1 as an indicator of plasticity across the hippocampus, in rats that underwent new spatial learning in either a familiar or novel context. Statistically significant effects in this plasticity indicator were observed of context condition, time after task and hippocampal subfield. Based on the strong inputs of entorhinal cortex to hippocampus, we also identified differences in GluA2:GluA1 expression trends between time points and room conditions that mirror trends in medial and lateral entorhinal cortex connectivity between new room and same room context learning, respectively. Across the transverse axis in infrapyramidal dentate gyrus, CA3 and CA1, plasticity followed entorhinal cortex projection patterns. Along the transverse axis in the suprapyramidal blade of the dentate gyrus, and along the long axis in dentate gyrus and CA3, results did not follow entorhinal cortex subregion projection patterns. These latter results may be indicative of pattern separation in the dentate gyrus and emotional triage functions of the ventral hippocampus.
Leptin and advanced glycation end products receptor (RAGE) in tuberculosis patients

Introduction The pathogenesis of consumptive syndrome of tuberculosis (TB) is largely unknown. Leptin concentrations may be high because of the host’s inflammatory response, contributing to weight loss in patients with TB. The receptor for advanced glycation end products (RAGE) is also associated with weight loss in patients with TB and is related to enhanced mortality. The objective of this study was to evaluate the association between leptin and AGE/RAGE. Methods Case-control study. Leptin, AGE (carboxymethyl lysine, CML) and soluble RAGE (sRAGE) were measured from blood samples by ELISA. Results We included in the study 34 patients with TB and 34 controls. We found an inverse correlation between serum leptin levels and sRAGE, only in cases (r = -0.609, p < 0.0001). sRAGE levels were lower in patients with TB who died as compared with patients who survive (21.90 ± 4.24 pg/mL vs 66.14 ± 29.49 pg/mL; p = 0.045). Leptin levels were higher in patients with TB who died as compared with patients who survive (14.11 [7.48–14.11] ng/mL vs 3.08 [0.54–6.34] ng/mL; p = 0.028). Conclusions We identified lower sRAGE levels and higher leptin levels in patients with TB who died as compared with patients who survive. In addition, an inverse and significant correlation between serum leptin and sRAGE levels was demonstrated. Future studies, with a larger sample size and in different settings, including not only hospitalized patients, are needed to confirm these findings.