Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic effects of diosgenin on alveolar bone loss and apoptosis in diabetic rats with experimental periodontitis

Objective(s): The present study aims to evaluate the efficacy of administered diosgenin (DG) which has anti-oxidant and anti-inflammatory effects, on alveolar bone loss (ABL) and apoptosis in diabetic rats with periodontitis. Materials and Methods: Forty male Wistar albino rats (n=40) were divided into five subgroups; control (non-ligated), periodontitis (P), diabetes mellitus (DM), P+DM, and P+DM+DG. To stimulate experimental periodontitis, a ligature was embedded at the gingival margin of the lower first molars for each rat, and diabetes was induced by streptozotocin (STZ) for DM groups. Then, DG (96 mg/kg daily) was performed on the P+DM+DG group by oral gavage for 29 days. At day 30, all animals were euthanized and the distance from the cement-enamel junction to the alveolar bone margin was measured using cone-beam computed tomography as ABL. In addition, immunohistochemical analyses were used to evaluate the expression levels of alkaline phosphatase (ALP), osteocalcin (OCN), bone morphogenetic protein 2 (BMP-2), receptor activator of NF-κB ligand (RANKL), collagen type I (Col-1), B-cell lymphoma-2 (Bcl-2), and Bcl-2-associated X protein (Bax). Results: Induction of periodontitis and diabetes significantly increased ABL (P<0.05). DG administration significantly reduced ABL, expression of RANKL and Bax, and enhanced the expression of ALP, OCN, BMP-2, Bcl-2, and Col-1 in the P+DM+DG group compared with the P+DM group (P<0.05). Conclusion: It is revealed that DG considerably enhanced bone formation and contributed to periodontal healing in this experimental study performed in diabetic rats.
Geometric stiffening and softening of an indented floating thin film

Thin sheets can exhibit geometric nonlinearities while remaining within the linear elastic response of the material. We uncover two distinct mechanisms for geometric nonlinearities by studying the normal-force response of an indented polymer film floating on a liquid bath, using experiments, simulations, and theory. The first nonlinearity is due to the appearance of wrinkles, which cause the system to become stiffer than the typical linear response for infinitesimal strain. When these wrinkles cover the sheet, the force is again linear with displacement, but with an effective spring constant that is independent of the elastic modulus of the film. A second nonlinearity occurs when the film reaches large slopes, causing the response to soften.
DNA structural properties of DNA binding sites for 21 transcription factors in the mycobacterial genome

Mycobacterium tuberculosis, the causative agent of tuberculosis, has evolved over time into a multidrug resistance strain that poses a serious global pandemic health threat. The ability to survive and remain dormant within the host macrophage relies on multiple transcription factors contributing to virulence. To date, very limited structural insights from crystallographic and NMR studies are available for TFs and TF–DNA binding events. Understanding the role of DNA structure in TF binding is critical to deciphering MTB pathogenicity and has yet to be resolved at the genome scale. In this work, we analyzed the compositional and conformational preference of 21 mycobacterial TFs, evident at their DNA binding sites, in local and global scales. Results suggest that most TFs prefer binding to genomic regions characterized by unique DNA structural signatures, namely, high electrostatic potential, narrow minor grooves, high propeller twist, helical twist, intrinsic curvature, and DNA rigidity compared to the flanking sequences. Additionally, preference for specific trinucleotide motifs, with clear periodic signals of tetranucleotide motifs, are observed in the vicinity of the TF–DNA interactions. Altogether, our study reports nuanced DNA shape and structural preferences of 21 TFs.
Magnetic Quincke rollers with tunable single-particle dynamics and collective states

Electrohydrodynamically driven active particles based on Quincke rotation have quickly become an important model system for emergent collective behavior in nonequilibrium colloidal systems. Like most active particles, Quincke rollers are intrinsically nonmagnetic, preventing the use of magnetic fields to control their complex dynamics on the fly. Here, we report on magnetic Quincke rollers based on silica particles doped with superparamagnetic iron oxide nanoparticles. We show that their magnetic nature enables the application of both externally controllable forces and torques at high spatial and temporal precision, leading to several versatile control mechanisms for their single-particle dynamics and collective states. These include tunable interparticle interactions, potential energy landscapes, and advanced programmable and teleoperated behaviors, allowing us to discover and probe active chaining, anisotropic active sedimentation-diffusion equilibria, and collective states in various geometries and dimensionalities.
Examining the long-term effects of traumatic brain injury on fear extinction in male rats

There is a strong association between traumatic brain injuries (TBIs) and the development of psychiatric disorders, including post-traumatic stress disorder (PTSD). Exposure-based therapy is a first-line intervention for individuals who suffer from PTSD and other anxiety-related disorders; however, up to 50% of individuals with PTSD do not respond well to this approach. Fear extinction, a core mechanism underlying exposure-based therapy, is a procedure in which a repeated presentation of a conditioned stimulus in the absence of an unconditioned stimulus leads to a decrease in fear expression, and is a useful tool to better understand exposure-based therapy. Identifying predictors of extinction would be useful in developing alternative treatments for the non-responders. We recently found that CO2 reactivity predicts extinction phenotypes in rats, likely through the activation of orexin receptors in the lateral hypothalamus. While studies have reported mixed results in extinction of fear after TBI, none have examined the long-term durability of this phenotype in the more chronically injured brain. Here we tested the hypothesis that TBI results in a long-term deficit in fear extinction, and that CO2 reactivity would be predictive of this extinction phenotype. Isoflurane-anesthetized adult male rats received TBI (n = 59) (produced by a controlled cortical impactor) or sham surgery (n = 29). One month post-injury or sham surgery, rats underwent a CO2 or air challenge, followed by fear conditioning, extinction, and fear expression testing. TBI rats exposed to CO2 (TBI-CO2) showed no difference during extinction or fear expression relative to shams exposed to CO2 (sham-CO2). However, TBI-CO2 rats, showed significantly better fear expression than TBI rats exposed to air (TBI-air). In contrast to previous findings, we observed no relationship between CO2 reactivity and post-extinction fear expression in either the sham or TBI rats. However, compared to the previously observed naïve sample, we observed more variability in post-extinction fear expression but a very similar distribution of CO2 reactivity in the current sample. Isoflurane anesthesia may lead to interoceptive threat habituation, possibly via action on orexin receptors in the lateral hypothalamus, and may interact with CO2 exposure, resulting in enhanced extinction. Future work will directly test this possibility.
Combination therapy is not associated with improved rates of clinical or endoscopic remission in patients with inflammatory bowel disease treated with ustekinumab or vedolizumab: a retrospective study

Background Management of inflammatory bowel disease (IBD) involves biological agents, often in combination with thiopurines or methotrexate. The aim of our study was to compare clinical and endoscopic outcomes in IBD patients treated with vedolizumab or ustekinumab, as monotherapy or in combination with thiopurines or methotrexate. Methods We conducted a retrospective cohort study of all patients aged ≥18 years with a diagnosis of ulcerative colitis or Crohn’s disease, commenced on vedolizumab or ustekinumab between October 2015 and March 2022. Primary outcome was clinical remission or response calculated by partial Mayo score (remission: <3; response: improvement >1) for ulcerative colitis or Harvey-Bradshaw index (<5, >2 respectively) for Crohn’s disease over 1 year. Secondary endpoints were treatment failure, relapse, endoscopic remission at 1 year. Statistical analysis was done using 2-sample Student’s t and chi-square tests. Results A total of 159 IBD patients were included in the study, 85 (53%) on vedolizumab and 74 (47%) on ustekinumab. For those on vedolizumab, 61 (72%) patients had ulcerative colitis, and 24 (28%) has Crohn’s disease. All patients on ustekinumab had Crohn’s disease. Mean disease duration in was 9.4 and 13.5 years respectively. There was no difference in clinical response or remission for vedolizumab or ustekinumab monotherapy compared to combination therapy at 1 year. There was also no difference in treatment failure, relapse or endoscopic remission. Conclusion Combining vedolizumab or ustekinumab with an immunomodulator is not superior to monotherapy in terms of clinical response or endoscopic remission up to 1 year in IBD.
The intestinal γδ T cells: functions in the gut and in the distant organs

Located in the frontline against the largest population of microbiota, the intestinal mucosa of mammals has evolved to become an effective immune system. γδ T cells, a unique T cell subpopulation, are rare in circulation blood and lymphoid tissues, but rich in the intestinal mucosa, particularly in the epithelium. Via rapid production of cytokines and growth factors, intestinal γδ T cells are key contributors to epithelial homeostasis and immune surveillance of infection. Intriguingly, recent studies have revealed that the intestinal γδ T cells may play novel exciting functions ranging from epithelial plasticity and remodeling in response to carbohydrate diets to the recovery of ischemic stroke. In this review article, we update regulatory molecules newly defined in lymphopoiesis of the intestinal γδ T cells and their novel functions locally in the intestinal mucosa, such as epithelial remodeling, and distantly in pathological setting, e.g., ischemic brain injury repair, psychosocial stress responses, and fracture repair. The challenges and potential revenues in intestinal γδ T cell studies are discussed.
High expression of the circadian clock gene NPAS2 is associated with progression and poor prognosis of gastric cancer: A single-center study

BACKGROUND The prognostic assessment of patients after surgical resection of gastric cancer (GC) patients is critical. However, the role of the circadian clock gene NPAS2 expression in GC remains unknown. AIM To explore the relationship between NPAS2 and the survival prognosis of GC patients and clarify its role in evaluating GC prognosis. METHODS The tumor tissues and clinical data of 101 patients with GC were collected retrospectively. Immunohistochemical staining (IHC) was used to detect the expression of NPAS2 protein in GC and adjacent tissues. Univariate and multivariate Cox regression analysis was used to determine the independent prognostic factors of GC, and a nomogram prediction model was established. The receiver operating characteristic (ROC) curve, the ROC area under the curve, the calibration curve, and C-index were used to evaluate the predictive effectiveness of the model. Kaplan Meier analysis was used to compare the risk stratification of subgroups according to the median score in the nomogram model of each patient. RESULTS Microarray IHC analysis showed that the positive rate of NPAS2 protein expression in GC tissues was 65.35%, which was significantly higher than 30.69% in adjacent tissues. The high expression of NPAS2 was correlated with tumor-node-metastasis (TNM) stage (P < 0.05), pN stage (P < 0.05), metastasis (P < 0.05), venous invasion (P < 0.05), lymphatic invasion (P < 0.05), and lymph node positive (P < 0.05) of GC. Kaplan Meier survival analysis showed that the 3-year overall survival (OS) of patients with high NPAS2 expression was significantly shortened (P < 0.0001). Univariate and multivariate COX regression analysis showed that TNM stage (P = 0.009), metastasis (P = 0.009), and NPAS2 expression (P = 0.020) were independent prognostic factors of OS in GC patients for 3 years. The nomogram prediction model based on independent prognostic factors has a C-Index of 0.740 (95%CI: 0.713-0.767). Furthermore, subgroup analysis showed that the 3-year OS time of the high-risk group was significantly lower than that of the low-risk group (P < 0.0001). CONCLUSION NPAS2 is highly expressed in GC tissues and is closely related to worse OS in patients. Therefore, the evaluation of NPAS2 expression may be a potential marker for GC prognosis evaluation. Notably, the nomogram model based on NPAS2 can improve the accuracy of GC prognosis prediction and assist clinicians in postoperative patient management and decision-making.
PIF1 Promotes Autophagy to Inhibit Chronic Hypoxia Induced Apoptosis of Pulmonary Artery Endothelial Cells

Purpose Pulmonary artery hypertension (PAH) is a common complication of chronic obstructive pulmonary disease and obstructive sleep apnea/hypopnea syndrome worldwide. Pulmonary vascular alterations associated with PAH have multifactorial causes, in which endothelial cells play an important role. Autophagy is closely related to endothelial cell injury and the development of PAH. PIF1 is a multifunctional helicase crucial for cell survival. The present study investigated the effect of PIF1 on autophagy and apoptosis in human pulmonary artery endothelial cells (HPAECs) under chronic hypoxia stress. Methods Chronic hypoxia Gene expression profiling chip-assays identified the PIF1 gene as differentially expressed, which was verified by RT-qPCR analysis. Electron microscopy, immunofluorescence, and Western blotting were used to analyze autophagy and the expression of LC3 and P62. Apoptosis was analyzed using flow cytometry. Results Our study found that chronic hypoxia induces autophagy in HPAECs, and apoptosis was exacerbated by inhibiting autophagy. Levels of the DNA helicase PIF1 were increased in HPAECs after chronic hypoxia. PIF1 knockdown inhibited autophagy and promoted the apoptosis of HPAECs under chronic hypoxia stress. Conclusion Based on these findings, we conclude that PIF1 inhibits the apoptosis of HPAECs by accelerating the autophagy pathway. Therefore, PIF1 plays a crucial role in HPAEC dysfunction in chronic hypoxia-induced PAH and may be a potential target for the treatment of PAH.
Use of a new non-contrast-enhanced BOOST cardiac MR sequence before electrical cardioversion or ablation of atrial fibrillation—a pilot study

Introduction Left atrial appendage (LAA) thrombus is the most common source of embolization in atrial fibrillation (AF). Transesophageal echocardiography (TEE) is the gold standard method for LAA thrombus exclusion. Our pilot study aimed to compare the efficacy of a new non-contrast-enhanced cardiac magnetic resonance (CMR) sequence (BOOST) with TEE for the detection of LAA thrombus and to evaluate the usefulness of BOOST images for planning radiofrequency catheter ablation (RFCA) compared with left atrial (LA) contrast-enhanced computed tomography (CT). We also attempted to assess the patients' subjective experiences with TEE and CMR. Methods Patients with AF undergoing either electrical cardioversion or RFCA were enrolled. Participants underwent pre-procedural TEE and CMR scans to evaluate LAA thrombus status and pulmonary vein anatomy. Patient experiences with TEE and CMR were assessed using a questionnaire developed by our team. Some patients scheduled for RFCA also had pre-procedural LA contrast-enhanced CT. In such cases, the operating physician was asked to subjectively define the quality of the CT and CMR scan on a scale of 1–10 (1 = worst, 10 = best) and comment on CMR's usefulness in RFCA planning. Results Seventy-one patients were enrolled. In 94.4%, both TEE and CMR excluded, and in 1 patient, both modalities reported the presence of LAA thrombus. In 1 patient, TEE was inconclusive, but CMR excluded LAA thrombus. In 2 patients, CMR could not exclude the presence of thrombus, but in 1 of those cases, TEE was also indecisive. During TEE, 67%, during CMR, only 1.9% of patients reported pain (p < 0.0001), and 89% would prefer CMR in case of a repeat examination. The quality of the left atrial contrast-enhanced CT scans was better compared with the image quality of the CMR BOOST sequence [8 (7–9) vs. 6 (5–7), p < 0.0001]. Still, the CMR images were useful for procedural planning in 91% of cases. Conclusion The new CMR BOOST sequence provides appropriate image quality for ablation planning. The sequence might be useful for excluding larger LAA thrombi; however, its accuracy in detecting smaller thrombi is limited. Most patients preferred CMR over TEE in this indication.
Upper-body isometric horizontal strength in game sport athletes

Imagine blocking the opposing defense linemen in American football to protect your quarterback or creating gaps in the opponents' defense by setting blocks as a pivot player in handball. Such movements require a pushing action away from the body with the arms and stabilizing the whole body in different postural positions. Upper-body strength obviously plays an important role during American football and handball as well as in other game sports with opponent contact such as basketball. Yet, the availability of appropriate tests to measure upper-body strength serving sport-specific requirements seems limited. Therefore, a whole-body setup to measure isometric horizontal strength in game sport athletes was developed. The purpose of the study was to verify validity and reliability of this setup and present empirical data from game sport athletes. In 119 athletes, isometric horizontal strength was measured in three game-like standing positions (upright, slightly leaning forward and clearly leaning forward), each in three weight-shift conditions (80% of body weight on the left leg, 50/50% on both legs, 80% on the right leg). Also, handgrip strength on both sides was measured in all athletes using a dynamometer. Linear regression indicated that handgrip strength is a significant predictor of upper-body horizontal strength in female (β = 0.70, p = 0.043) but not in male athletes (β = 0.31, p = 0.117). As an expertise-related factor, linear regression indicated that the number of years played at the top level is a predictor of the upper-body horizontal relative strength measure (β = 0.05, p = 0.03). Reliability analyses showed high levels of within-test reliability (ICC > 0.90) as well as test-retest reliability between two separate measurements (r > 0.77). The results indicate that the setup used in this study could be a valid tool for measuring performance-relevant upper-body horizontal strength in different game-like positions in professional game sport athletes.
Alzheimer-type cerebral amyloidosis in the context of HIV infection: implications for a proposed new treatment approach

Reverse transcriptase inhibitors (RTIs) are currently broadly prescribed for the treatment of HIV infection but are also thought to prevent Alzheimer’s Disease (AD) progression by protecting against amyloidosis. Our study evaluates the hypothesis that reverse transcriptase inhibitors protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection. We compiled a case series of participants from a prospective study of the neurological consequences of HIV infection at the HIV Neurobehavioral Research Program (HNRP) who had serial neuropsychological and neurological assessments and were on RTIs. Two participants had gross and microscopic examination and immunohistochemistry of the brain at autopsy; one was assessed clinically for Alzheimer’s Disease by cerebrospinal fluid (CSF) analysis of phosphorylated-Tau, Total-Tau and Aβ42. Additionally, a larger cohort of autopsied individuals was evaluated for presence of amyloid plaques, Tau, and related pathologies. Three older, virally suppressed individuals with HIV who had long-term treatment with RTIs were included in analyses. Two cases demonstrated substantial cerebral amyloid deposition at autopsy. The third case met clinical criteria for AD based on a typical clinical course and CSF biomarker profile. In the larger cohort of autopsied individuals, the prevalence of cerebral amyloidosis among people with HIV (PWH) was greater for those on RTIs. Our study showed that long-term RTI therapy did not protect against Alzheimer-type brain amyloidogenesis in the context of HIV infection in these patients. Given the known toxicities of RTIs, it is premature to recommend them to individuals at risk or with Alzheimer’s disease who do not have HIV infection.
On a Q–Curvature Equation on Complete Riemannian Manifolds

Abstract We proceed by variational method to prove the existence of solution of a fourth order partial differential equation on complete non compact manifolds. Sufficient conditions, including the geometry of the manifold, are given to make a minimizing sequence converge to a non trivial solution belonging to Cloc4,α (M) for some α ∈ (0, 1).
Protein Kinase A Is Responsible for the Presynaptic Inhibition of Glycinergic and Glutamatergic Transmissions by Xenon in Rat Spinal Cord and Hippocampal CA3 Neurons

The effects of a general anesthetic xenon (Xe) on spontaneous, miniature, electrically evoked synaptic transmissions were examined using the “synapse bouton preparation,” with which we can clearly evaluate pure synaptic responses and accurately quantify pre- and postsynaptic transmissions. Glycinergic and glutamatergic transmissions were investigated in rat spinal sacral dorsal commissural nucleus and hippocampal CA3 neurons, respectively. Xe presynaptically inhibited spontaneous glycinergic transmission, the effect of which was resistant to tetrodotoxin, Cd2+, extracellular Ca2+, thapsigargin (a selective sarcoplasmic/endoplasmic reticulum Ca2+-ATPase inhibitor), SQ22536 (an adenylate cyclase inhibitor), 8-Br-cAMP (membrane-permeable cAMP analog), ZD7288 (an hyperpolarization-activated cyclic nucleotide-gated channel blocker), chelerythrine (a PKC inhibitor), and KN-93 (a CaMKII inhibitor) while being sensitive to PKA inhibitors (H-89, KT5720, and Rp-cAMPS). Moreover, Xe inhibited evoked glycinergic transmission, which was canceled by KT5720. Like glycinergic transmission, spontaneous and evoked glutamatergic transmissions were also inhibited by Xe in a KT5720-sensitive manner. Our results suggest that Xe decreases glycinergic and glutamatergic spontaneous and evoked transmissions at the presynaptic level in a PKA-dependent manner. These presynaptic responses are independent of Ca2+ dynamics. We conclude that PKA can be the main molecular target of Xe in the inhibitory effects on both inhibitory and excitatory neurotransmitter release. SIGNIFICANCE STATEMENT Spontaneous and evoked glycinergic and glutamatergic transmissions were investigated using the whole-cell patch clamp technique in rat spinal sacral dorsal commissural nucleus and hippocampal CA3 neurons, respectively. Xenon (Xe) significantly inhibited glycinergic and glutamatergic transmission presynaptically. As a signaling mechanism, protein kinase A was responsible for the inhibitory effects of Xe on both glycine and glutamate release. These results may help understand how Xe modulates neurotransmitter release and exerts its excellent anesthetic properties.