Miracle-dz/UniFAR-FTUs huggingface dataset:
Changes in Physical Fitness and Body Composition Associated with Physical Exercise in Patients with Myasthenia Gravis: A Longitudinal Prospective Study

There is a lack of guidelines for physical exercise in patients with myasthenia gravis (MG). A few pilot studies have shown that exercise can be safely applied to patients with MG. However, how physical exercise affects body composition, disease function, and disease severity remains unknown. In this prospective study, we enrolled 34 patients with MG with stable condition and evaluated the disease severity, physical fitness parameters, and body composition (measured using whole-body dual-energy X-ray absorptiometry (DXA)), before and after conducting a 24-week physical exercise regimen of aerobic and resistance strength training. The outcomes were measured by DXA, quantitative MG (QMG) score, quality of life score, handgrip strength and walking speed. During the training regimen, participants were free to decide how many exercise sessions per week and regularly reported their weekly exercise time. The physical exercise program was well tolerated by the participants, the parameters of the QMG score and handgrip strength improved, and participants’ body composition did not change significantly. The high exercise group experienced greater deterioration in muscle mass in the arms, but exhibited a greater improvement in forced vital capacity, walking speed, and symptom severity. The group with low QMG scores improved more in terms of physical fitness, including walking speed. These findings indicate that physical exercise is well tolerated by patients with MG, and is accompanied by improved muscular and physical functions. We propose that physical exercise is safe, effective, and appropriate for patients with well-regulated MG.
Chrysosplenol D Triggers Apoptosis through Heme Oxygenase-1 and Mitogen-Activated Protein Kinase Signaling in Oral Squamous Cell Carcinoma

Simple Summary Oral squamous cell carcinoma (OSCC) accounts for the most malignancies. A GLO-BOCAN 2020 report estimated 377,713 new cases of oral cancer and 177,757 deaths due to oral cancer in 2020. Chrysosplenol D, a flavonol isolated from Artemisia annua L. , can exert an-ticancer effects. This study investigated the anticancer property of chrysosplenol D and its un-derlying mechanism in oral squamous cell carcinoma. We observed that chrysosplenol D reduced cell viability, cell cycle arrest, apoptosis and autophagy in OSCC. Moreover, the upregulation of heme oxygenase-1 (HO-1) was found to be critical for chrysosplenol D-induced apoptotic cell death that patients with head and neck cancer had lower HO-1 expression. The findings of the present study indicated that chrysosplenol D exerts anticancer effects on OSCC by suppressing the MAPK pathway and activating HO-1 expression. Suggest that chrysosplenol D might be a potential anticancer agent for treating OSCC. Abstract Chrysosplenol D, a flavonol isolated from Artemisia annua L. , can exert anticancer effects. This study investigated the anticancer property of chrysosplenol D and its underlying mechanism in oral squamous cell carcinoma (OSCC). We observed that chrysosplenol D reduced cell viability and caused cell cycle arrest in the G2/M phase. The findings of annexin V/propidium iodide staining, chromatin condensation, and apoptotic-related protein expression revealed that chrysosplenol D regulated apoptosis in OSCC. Furthermore, chrysosplenol D altered the expression of the autophagy marker LC3 and other autophagy-related proteins. Phosphatidylinositol 3-kinase/protein kinase B, extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase (MAPK) were downregulated by chrysosplenol D, and the inhibition of these pathways significantly enhanced chrysosplenol D-induced cleaved poly (ADP-ribose) polymerase activation. Moreover, the upregulation of heme oxygenase-1 (HO-1) was found to be critical for chrysosplenol D-induced apoptotic cell death. The analysis of clinical data from The Cancer Genome Atlas and Gene Expression Omnibus datasets revealed that patients with head and neck cancer had lower HO-1 expression than did those with no head and neck cancer. The findings of the present study indicated that chrysosplenol D exerts anticancer effects on OSCC by suppressing the MAPK pathway and activating HO-1 expression.
Deletion of Cdk5 in Macrophages Ameliorates Anti-Inflammatory Response during Endotoxemia through Induction of C-Maf and Il-10

Immune response control is critical as excessive cytokine production can be detrimental and damage the host. Interleukin-10 (Il-10), an anti-inflammatory cytokine produced primarily by macrophages, is a key regulator that counteracts and controls excessive inflammatory response. Il-10 expression is regulated through the transcription factor c-Maf. Another regulator of Il-10 production is p35, an activator of the cyclin-dependent kinase 5 (Cdk5), which decreases Il-10 production in macrophages, thus increasing inflammation. However, Cdk5 regulation of c-Maf and the involvement of Il-10 production in macrophages has not yet been investigated. We used in vitro primary bone marrow-derived macrophages (BMDMs) lacking Cdk5, stimulated them with lipopolysaccharid (LPS) and observed increased levels of c-Maf and Il-10. In an in vivo mouse model of LPS-induced endotoxemia, mice lacking Cdk5 in macrophages showed increased levels of c-Maf and elevated levels of Il-10 in lungs as well as in plasma, resulting in ameliorated survival. Taken together, we identified Cdk5 as a potential novel regulator of Il-10 production through c-Maf in macrophages under inflammatory conditions. Our results suggest that inhibition of Cdk5 enhances the c-Maf-Il-10 axis and thus potentiates improvement of anti-inflammatory therapy.
The Role of the α Cell in the Pathogenesis of Diabetes: A World beyond the Mirror

Type 2 Diabetes Mellitus (T2DM) is one of the most prevalent chronic metabolic disorders, and insulin has been placed at the epicentre of its pathophysiological basis. However, the involvement of impaired alpha (α) cell function has been recognized as playing an essential role in several diseases, since hyperglucagonemia has been evidenced in both Type 1 and T2DM. This phenomenon has been attributed to intra-islet defects, like modifications in pancreatic α cell mass or dysfunction in glucagon’s secretion. Emerging evidence has shown that chronic hyperglycaemia provokes changes in the Langerhans’ islets cytoarchitecture, including α cell hyperplasia, pancreatic beta (β) cell dedifferentiation into glucagon-positive producing cells, and loss of paracrine and endocrine regulation due to β cell mass loss. Other abnormalities like α cell insulin resistance, sensor machinery dysfunction, or paradoxical ATP-sensitive potassium channels (KATP) opening have also been linked to glucagon hypersecretion. Recent clinical trials in phases 1 or 2 have shown new molecules with glucagon-antagonist properties with considerable effectiveness and acceptable safety profiles. Glucagon-like peptide-1 (GLP-1) agonists and Dipeptidyl Peptidase-4 inhibitors (DPP-4 inhibitors) have been shown to decrease glucagon secretion in T2DM, and their possible therapeutic role in T1DM means they are attractive as an insulin-adjuvant therapy.
Modification of the Forms of Self-Determined Regulation and Quality of Life after a Cardiac Rehabilitation Programme: Tennis-Based vs. Bicycle Ergometer-Based

Background: The objective is to analyse and compare the effects of an adapted tennis cardiac rehabilitation programme and a classical bicycle ergometer-based programme on the type of motivation towards sports practice and quality of life in patients classified as low risk after suffering acute coronary syndrome. Methods: The Behavioural Regulation in Exercise Questionnaire (BREQ-2) and Velasco’s Qualityof Life Test were applied. The sample comprised 110 individuals (age = 55.05 ± 9.27) divided into two experimental groups (tennis and bicycle ergometer) and a control group. Results: The intra-group analysis showed a significant increase between pre- and post-test results in intrinsic regulation in the tennis group and in the control group. In identified regulation, the bicycle ergometer group presented significant differences from the control group. On the other hand, in the external regulation variable, only the tennis group showed significant differences, which decreased. Significant improvements in all quality-of-life factors when comparing the pre-test period with the post-test period were only found in the experimental groups. As per the inter-group analysis, significant differences were observed in favour of the tennis group with respect to the control group in the variables of health, social relations and leisure, and work time as well as in favour of the bicycle ergometer group compared with the control group in the variables of health, sleep and rest, future projects and mobility. No significant differences were found in any of the variables between the tennis group and the bicycle ergometer group. Conclusion: It is relevant to enhance the practice of physical exercise in infarcted patients classified as low risk as it improves the forms of more self-determined regulation towards sporting practice and their quality of life.
On the Effect of Bimodal Rehabilitation in Asymmetric Hearing Loss

Background: Bone conductive implants (BCI) have been reported to provide greater beneficial effects for the auditory and perceptual functions of the contralateral ear in patients presenting with asymmetric hearing loss (AHL) compared to those with single-sided deafness (SSD). The aim of the study was to assess the effects of wearing a conventional hearing aid in the contralateral ear on BCI in terms of an improved overall auditory performance. Methods: eleven AHL subjects wearing a BCI in their worse hearing ear underwent an auditory evaluation by pure tone and speech audiometry in free field. This study group was obtained by adding to the AHL patients those SSD subjects that, during the follow-up, showed deterioration of the hearing threshold of the contralateral ear, thus presenting with the features of AHL. Four different conditions were tested and compared: unaided, with BCI only, with contralateral hearing aid (CHA) only and with BCI combined with CHA. Results: all of the prosthetic conditions caused a significant improvement with respect to the unaided condition. When a CHA was adopted, its combination with the BCI showed significantly better auditory performances than those achieved with the BCI only. Conclusions: the present study suggests the beneficial role of a CHA in BCI-implanted AHL subjects in terms of overall auditory performance.
Foamed Geopolymer Composites with the Addition of Glass Wool Waste

This study examines foamed geopolymer composites based on fly ash from the Skawina coal-fired power plant in Poland. The paper presents the effect of adding 3% and 5% by weight of glass wool waste on selected properties of foamed geopolymers. The scope of the tests carried out included density measurements, compressive and bending strength tests, measurements of the heat conduction coefficient, and the results of measurements of changes in thermal radiation in samples subjected to a temperature of 800 °C. The obtained results indicate that glass wool waste can be successfully used to lower the density and heat conduction coefficient of foamed geopolymer composites with a fly ash matrix. In addition, the results of changes in thermal radiation in the samples subjected to the temperature of 800 °C showed a positive effect of the addition of glass wool waste. Moreover, the introduction of the addition of glass wool waste made it possible to increase the compressive strength of the examined foamed geopolymers. For the material modified with 3% by weight of mineral wool, the increase in compressive strength was about 10%, and the increase in fibers in the amount of 5% by weight resulted in an increase of 20% concerning the base material. The obtained results seem promising for future applications. Such materials can be used in technical constructions as thermal insulation materials.
Pattern of Prostate Cancer Recurrence Assessed by 68Ga-PSMA-11 PET/CT in Men Treated with Primary Local Therapy

Imaging plays a vital role in detecting the recurrence of prostate cancer (PCa) to guide the choice of salvage therapy. Gallium-68 prostate-specific membrane antigen positron-emission tomography/computed tomography (68Ga-PSMA-11 PET/CT) is useful for detecting PCa recurrence. We assessed the pattern of PCa recurrence stratified by serum prostate-specific antigen level and type of primary local treatment in men with biochemical recurrence (BCR) after primary local therapy with radical prostatectomy or external beam radiotherapy (EBRT) using 68Ga-PSMA-11 PET/CT. We reviewed patients imaged with 68Ga-PSMA-11 PET/CT for the localization of the site of PCa recurrence. We determined the site and number of lesions due to PCa recurrence at different PSA levels. A total of 247 men (mean age of 65.72 ± 7.51 years and median PSA of 2.70 ng/mL (IQR = 0.78–5.80)) were included. 68Ga-PSMA-11 PET/CT detected the site of recurrence in 81.4% of patients with a median number of lesions per patient of 1 (range = 1–5). 68Ga-PSMA-11 PET/CT positivity was 43.6%, 75.7%, 83.3%, 90.0%, and 95.8% at PSA levels of <0.5, 0.5–1.0. , 1.1–2.0, 2.1–5.0, and 5.0–10.0, respectively. The most common site of recurrence was in the prostate gland/bed at all PSA levels. Pelvic, extra-pelvic, and combined pelvic and extra-pelvic sites of recurrence were seen in 118, 50, and 33 patients, respectively. The risk of extra-pelvic recurrence increases with rising PSA levels. 68Ga-PSMA-11 PET/CT has a high lesion detection rate for biochemical recurrence of PCa in patients previously treated with primary local therapy.
Experimental Investigations on Electric-Field-Induced Crystallization in Erythritol

The objective of this experimental study was to develop a method to induce crystallization of sugar alcohols using an electric field for its future implementation in latent heat thermal energy storage systems. To better understand the mechanisms behind this approach, the first step of this work was dedicated to the replication, continuation, and consolidation of promising results on erythritol reported by another research group. In the second step, a second experimental configuration, previously used to electrically control the supercooling of other phase change materials, was tested with the same sugar alcohol. For both configurations, the influence of the type of current (DC and AC at different frequencies), its amplitude, and time of exposure were studied. However, none of these tests allowed influencing the crystallization of erythritol. Even if surprising at first glance, the difficulty in reproducing experiments and interpreting the results is not new in the field of electric-field-induced crystallization, as shown in particular by the abundant literature reviews concerning water. Currently, to the best of our knowledge, we consider that electric fields could be an attractive option to initiate and accelerate the crystallization of erythritol, but this solution must be considered with caution.
Analyses of the Mode of Action of an Alpha-Adrenoceptor Blocker in Substantia Gelatinosa Neurons in Rats

To elucidate why naftopidil increases the frequency of spontaneous synaptic currents in only some substantia gelatinosa (SG) neurons, post-hoc analyses were performed. Blind patch-clamp recording was performed using slice preparations of SG neurons from the spinal cords of adult rats. Spontaneous inhibitory and excitatory postsynaptic currents (sIPSCs and sEPSCs, respectively) were recorded. The ratios of the frequency and amplitude of the sIPSCs and sEPSCs following the introduction of naftopidil compared with baseline, and after the application of naftopidil, serotonin (5-HT), and prazosin, compared with noradrenaline (NA) were evaluated. First, the sIPSC analysis indicated that SG neurons reached their full response ratio for NA at 50 μM. Second, they responded to 5-HT (50 μM) with a response ratio similar to that for NA, but prazosin (10 μM) did not change the sEPSCs and sIPSCs. Third, the highest concentration of naftopidil (100 μM) led to two types of response in the SG neurons, which corresponded with the reactions to 5-HT and prazosin. These results indicate that not all neurons were necessarily activated by naftopidil, and that the micturition reflex may be regulated in a sophisticated manner by inhibitory mechanisms in these interneurons.
Nature versus Number: Monocytes in Cardiovascular Disease

Monocytes play a key role in cardiovascular disease (CVD) as their influx into the vessel wall is necessary for the development of an atherosclerotic plaque. Monocytes are, however, heterogeneous differentiating from classical monocytes through the intermediate subset to the nonclassical subset. While it is recognized that the percentage of intermediate and nonclassical monocytes are higher in individuals with CVD, accompanying changes in inflammatory markers suggest a functional impact on disease development that goes beyond the increased proportion of these ‘inflammatory’ monocyte subsets. Furthermore, emerging evidence indicates that changes in monocyte proportion and function arise in dyslipidemia, with lipid lowering medication having some effect on reversing these changes. This review explores the nature and number of monocyte subsets in CVD addressing what they are, when they arise, the effect of lipid lowering treatment, and the possible implications for plaque development. Understanding these associations will deepen our understanding of the clinical significance of monocytes in CVD.
Neoantigen-Specific T-Cell Immune Responses: The Paradigm of NPM1-Mutated Acute Myeloid Leukemia

The C-terminal aminoacidic sequence from NPM1-mutated protein, absent in normal human tissues, may serve as a leukemia-specific antigen and can be considered an ideal target for NPM1-mutated acute myeloid leukemia (AML) immunotherapy. Different in silico instruments and in vitro/ex vivo immunological platforms have identified the most immunogenic epitopes from NPM1-mutated protein. Spontaneous development of endogenous NPM1-mutated-specific cytotoxic T cells has been observed in patients, potentially contributing to remission maintenance and prolonged survival. Genetically engineered T cells, namely CAR-T or TCR-transduced T cells, directed against NPM1-mutated peptides bound to HLA could prospectively represent a promising therapeutic approach. Although either adoptive or vaccine-based immunotherapies are unlikely to be highly effective in patients with full-blown leukemia, these strategies, potentially in combination with immune-checkpoint inhibitors, could be promising in maintaining remission or preemptively eradicating persistent measurable residual disease, mainly in patients ineligible for allogeneic hematopoietic stem cell transplant (HSCT). Alternatively, neoantigen-specific donor lymphocyte infusion derived from healthy donors and targeting NPM1-mutated protein to selectively elicit graft-versus-leukemia effect may represent an attractive option in subjects experiencing post-HSCT relapse. Future studies are warranted to further investigate dynamics of NPM1-mutated-specific immunity and explore whether novel individualized immunotherapies may have potential clinical utility in NPM1-mutated AML patients.
The ClearSight System for Postoperative Arterial Blood Pressure Monitoring After Carotid Endarterectomy: A Validation Study

Abstract BACKGROUND The majority of postoperative events in patients undergoing carotid endarterectomy (CEA) are of hemodynamic origin, requiring preventive strict postoperative arterial blood pressure (BP) control. This study aimed to assess whether BP monitoring with noninvasive beat-to-beat ClearSight finger BP (BPCS) can replace invasive beat-to-beat radial artery BP (BPRAD) in the postoperative phase. METHODS This study was a single-center clinical validation study using a prespecified study protocol. In 48 patients with symptomatic carotid artery stenosis, BPCS and BPRAD were monitored ipsilateral in a simultaneous manner during a 6-hour period on the recovery unit following CEA. Primary endpoints were accuracy and precision of BP derived by ClearSight (Edward Lifesciences, Irvine, CA) vs. the reference standard (Arbocath 20 G, Hospira, Lake Forest, IL) to investigate if BPCS is a reliable noninvasive alternative for BP monitoring postoperatively in CEA patients. Validation was guided by the standard set by the Association for Advancement of Medical Instrumentation (AAMI), considering a BP-monitor adequate when bias (precision) is <5 (8) mm Hg. Secondary endpoint was percentage under- and overtreatment, defined as exceedance of individual postoperative systolic BP threshold by BPRAD or BPCS in contrast to BPCS or BPRAD, respectively. RESULTS The bias (precision) of BPCS compared to BPRAD was −10 (13.6), 8 (7.2) and 4 (7.8) mm Hg for systolic, diastolic and mean arterial pressure (MAP), respectively. Based on BPCS, undertreatment was 5.6% and overtreatment was 2.4%; however, percentages of undertreatment quadrupled for lower systolic BP thresholds. CONCLUSIONS Noninvasive MAP, but not systolic and diastolic BP, was similar to invasive BPRAD during postoperative observation following CEA, based on AAMI criteria. However, as systolic BP is currently leading in postoperative monitoring to adjust BP therapy on, BPCS is not a reliable alternative for BPRAD.
Apigenin Ameliorates Scopolamine-Induced Cognitive Dysfunction and Neuronal Damage in Mice

We investigated the protective effect and mechanisms of apigenin against cognitive impairments in a scopolamine-injected mouse model. Our results showed that intraperitoneal (i.p.) injection of scopolamine leads to learning and memory dysfunction, whereas the administration of apigenin (synthetic compound, 100 and 200 mg/kg/day) improved cognitive ability, which was confirmed by behavioral tests such as the T-maze test, novel objective recognition test, and Morris water maze test in mice. In addition, scopolamine-induced lipid peroxidation in the brain was attenuated by administration of apigenin. To further evaluate the protective mechanisms of apigenin on cognitive and memory function, Western blot analysis was carried out. Administration of apigenin decreased the B-cell lymphoma 2-associated X/B-cell lymphoma 2 (Bax/Bcl-2) ratio and suppressed caspase-3 and poly ADP ribose polymerase cleavage. Furthermore, apigenin down-regulated the β-site amyloid precursor protein-cleaving enzyme, along with presenilin 1 (PS1) and PS2 protein levels. Apigenin-administered mice showed lower protein levels of a receptor for advanced glycation end-products, whereas insulin-degrading enzyme, brain-derived neurotrophic factor (BDNF), and tropomyosin receptor kinase B (TrkB) expression were promoted by treatment with apigenin. Therefore, this study demonstrated that apigenin is an active substance that can improve cognitive and memory functions by regulating apoptosis, amyloidogenesis, and BDNF/TrkB signaling pathways.