Miracle-dz/UniFAR-FTUs huggingface dataset:
Neutrophil-to-lymphocyte ratio (NLR) at boundaries of Progressive Supranuclear Palsy Syndrome (PSPS) and Corticobasal Syndrome (CBS).

AIM OF THE STUDY To examine possible features of neuroinflammation in progressive supranuclear palsy - Richardson syndrome and corticobasal syndrome (CBS). CLINICAL RATIONALE FOR THE STUDY Neutrophil-to-lymphocyte ratio (NLR) is a parameter reflecting inflammation used in numerous branches of medicine. The search for pathogenesis of the diseases partly related to inflammatory processes confirms the need to obtain possible factors which could be relatively easily verified. NLR is a benchmark routinely evaluated in most hospitalised patients. MATERIALS AND METHODS 23 patients with a clinical diagnosis of PSP-RS, 18 patients with CBS, and 32 healthy controls, were included in the study. Blood samples were assessed in the context of neutrophil and lymphocyte rates. Subsequently, the results were transformed into neutrophil-to-lymphocyte ratio (NLR). The NLRs from each group were statistically assessed using a Kruskal-Wallis test and post-hoc analysis. RESULTS Statistical analysis confirmed significant differences in NLR between PSP-RS and control group. No other significant differences were observed. CLINICAL IMPLICATIONS The possible use of NLR in the additional examination of atypical parkinsonisms. CONCLUSIONS To the best of our knowledge, this is the first study comparing this aspect of neuroinflammation in PSP and CBS. It presents NLR as a promising non-specific parameter in neurodegenerative diseases.
Artesunate Impairs Growth in Cisplatin-Resistant Bladder Cancer Cells by Cell Cycle Arrest, Apoptosis and Autophagy Induction

Cisplatin, which induces DNA damage, is standard chemotherapy for advanced bladder cancer (BCa). However, efficacy is limited due to resistance development. Since artesunate (ART), a derivative of artemisinin originating from Traditional Chinese Medicine, has been shown to exhibit anti-tumor activity, and to inhibit DNA damage repair, the impact of artesunate on cisplatin-resistant BCa was evaluated. Cisplatin-sensitive (parental) and cisplatin-resistant BCa cells, RT4, RT112, T24, and TCCSup, were treated with ART (1–100 µM). Cell growth, proliferation, and cell cycle phases were investigated, as were apoptosis, necrosis, ferroptosis, autophagy, metabolic activity, and protein expression. Exposure to ART induced a time- and dose-dependent significant inhibition of tumor cell growth and proliferation of parental and cisplatin-resistant BCa cells. This inhibition was accompanied by a G0/G1 phase arrest and modulation of cell cycle regulating proteins. ART induced apoptos is by enhancing DNA damage, especially in the resistant cells. ART did not induce ferroptosis, but led to a disturbance of mitochondrial respiration and ATP generation. This impairment correlated with autophagy accompanied by a decrease in LC3B-I and an increase in LC3B-II. Since ART significantly inhibits proliferative and metabolic aspects of cisplatin-sensitive and cisplatin-resistant BCa cells, it may hold potential in treating advanced and therapy-resistant BCa.
Phenotypic sexual dimorphism in response to dietary fat manipulation in C57BL/6J mice.

BACKGROUND Obesity and the metabolic syndrome are increasingly prevalent in society and their complications and response to treatment exhibit sexual dimorphism. Mouse models of high fat diet-induced obesity are commonly used for both mechanistic and therapeutic studies of metabolic disease and diabetes. However, the inclusion of female mammals in obesity research has not been a common practice, and has resulted in a paucity of data regarding the effect of sex on metabolic parameters and its applicability to humans. METHODS Here we analyzed male and female C57BL/6 J mice beginning at 4 weeks of age that were placed on a low-fat diet (LFD, 10% calories from fat), a Western Diet (WD, 45% calories from fat), or a high fat diet (HFD, 60% calories from fat). Assessments of body composition, glucose homeostasis, insulin production, and energy metabolism, as well as histological analyses of pancreata were performed. RESULTS Both male and female C57BL/6 J mice had similar increases in total percent body weight gain with both WD and HFD compared to LFD, however, male mice gained weight earlier upon HFD or WD feeding compared to female mice. Male mice maintained their caloric food intake while reducing their locomotor activity with either WD or HFD compared to LFD, whereas female mice increased their caloric food intake with WD feeding. Locomotor activity of female mice did not significantly change upon WD or HFD feeding, yet female mice exhibited increased energy expenditure compared to WD or HFD fed male mice. Glucose tolerance tests performed at 4, 12 and 20 weeks of dietary intervention revealed impaired glucose tolerance that was worse in male mice compared to females. Furthermore, male mice exhibited an increase in pancreatic β cell area as well as reduced insulin sensitivity after HFD feeding compared to WD or LFD, whereas female mice did not. CONCLUSIONS Male and female C57BL/6 J mice exhibited strikingly different responses in weight, food consumption, locomotor activity, energy expenditure and β cell adaptation upon dietary manipulation, with the latter exhibiting less striking phenotypic changes. We conclude that the nature of these responses emphasizes the need to contextualize studies of obesity pathophysiology and treatment with respect to sex.
Contribution of Bowman layer to corneal biomechanics

Bowman layer does not enhance significantly the tensile elasticity of a thin corneal lamella, which may have implications in both refractive laser surgery and Bowman layer transplantation for keratoconus. Purpose: To compare the elastic modulus of thin corneal lamellas using 2D stress–strain extensometry in healthy ex vivo human corneal lamellas with or without the presence of Bowman layer. Setting: Center for Applied Biotechnology and Molecular Medicine, University of Zurich, Switzerland; ELZA Institute, Dietikon, Switzerland; Department of Ophthalmology, Philipps University of Marburg, Germany. Design: Prospective experimental laboratory study. Methods: Healthy human corneas were stripped of Descemet membrane and the endothelium for Descemet membrane endothelial keratoplasty. After epithelium removal, corneas were divided into 2 groups. In Group 1, Bowman layer was ablated with an excimer laser (20 μm thick, 10 mm). In Group 2, Bowman layer was left intact. Then, a lamella was cut from the anterior cornea with an automated microkeratome. Elastic and viscoelastic material properties were analyzed by 2D stress–strain extensometry between 0.03 and 0.70 N. Results: Twenty-six human corneas were analyzed. The mean lamella thickness was 160 ± 37 μm in corneas with Bowman layer and 155 ± 22 μm in corneas without. No statistically significant differences between flaps with and without Bowman layer were observed in the tangential elastic modulus between 5% and 20% strain (11.5 ± 2.9 kPa vs 10.8 ± 3.7 kPa, P > .278). Conclusions: The presence or absence of Bowman layer did not reveal a measurable difference in corneal stiffness. This may indicate that the removal of Bowman layer during photorefractive keratectomy does not represent a disadvantage to corneal biomechanics.
Resistive Switching in Electrodeposited Prussian Blue Layers

Prussian blue (PB) layers were electrodeposited for the fabrication of Au/PB/Ag stacks to study the resistive switching effect. The PB layers were characterized by different techniques to prove the homogeneity, composition, and structure. Electrical measurements confirmed the bipolar switching behavior with at least 3 orders of magnitude in current and the effect persisting for the 200 cycles tested. The low resistance state follows the ohmic conduction with an activation energy of 0.2 eV.
Effects of stern-layer conductance on electrokinetic transport properties of colloidal particles

The theory developed by O'Brien and White (R. W. O'Brien and L. R. White, J. Chem. Soc., Faraday Trans. 2, 1978, 77, 1607) to calculate the electrophoretic mobility of a solid, spherical colloidal particle, is reviewed and extended.The equations governing the ion distribution, electrostatic potential and hydrodynamic flow field around the particle, are modified to allow for the lateral movement of ions within the Stern layer. Two classes of Stern-layer adsorption isotherms are considered: (1) adsorption of ions onto available surface area; (2) adsorption of ions onto underlying surface charge (C. F. Zukoski IV and D. A. Saville, J. Colloid Interface Sci., 1986, 114, 32). The model equations are solved numerically for both adsorption isotherms, and the effects of varying individual Stern-layer parameters on the electrophoretic mobility and conductivity increment, are discussed and compared with the case when surface conductance is absent.Regardless of the adsorption model used, the presence of mobile Stern-layer ions causes the mobility to decrease and the conductivity to increase, in comparison with the case when surface conduction is absent. The magnitude of this effect is greater in model (2) owing to important contributions from both coion and counterion adsorption. Furthermore extra conditions on the surface charge density in model (2) can lead to negative site densities for some positive zeta potentials and ridiculously high site densities at large zeta or high salt concentrations. In contrast, model (1) shows negligible coion adsorption and modest charge densities throughout the range of zeta and salt concentration.A program for calculating electrokinetic transport properties, including these models of Stern-layer transport, is available from the authors.
Kinesiology Taping as an Innovative Measure against Post-Operative Complications after Third Molar Extraction—Systematic Review

There are many randomized clinical trials suggesting a positive effect of kinesiotaping on postoperative swelling. In dentistry, however, the use of kinesiotaping still seems to be innovative, since not many articles on kinesiotaping within the craniofacial area have been published. This study aimed to systematically review and synthesize available controlled trials examining the use of kinesiotaping to reduce morbidity after third molar extraction. Literature searches for free text and MeSH terms were performed using five search engines, and used to find studies which focused on kinesiotaping as a form of rehabilitation after third molar extraction. The keywords used in the search were: “((“molar, third”[MeSH Terms] OR (“molar”[All Fields] AND “third”[All Fields]) OR “third molar”[All Fields] OR (“third”[All Fields] AND “molar”[All Fields])) AND extraction [All Fields]) AND “kinesiology”[All Fields]”. For the assessment of the risk of bias, the Jadad and Maastricht scales were applied. The search strategy identified 317 potential articles. After analysis, 10 papers were included in the final evaluation. Despite the fact that most of the included articles adhered to methodological standards, the fact that there are only a few of them points to a further need for scientific development of physiotherapy in this regard. Kinesiology taping is useful against post-operative morbidity of the third molar extraction site. The present studies show a low level of the risk of bias, but they are limited in number; therefore, it seems that more research is needed.
Immediate fat and nanofat-enriched fat grafting in breast reduction for scar management

Abstract Background Reduction mammoplasty can be successful but surgical scars may continue to be a most undesirable and unavoidable outcome. Various medical and non-invasive methods are available to minimize scar formation but as yet no methods have been discovered to eliminate them. We hypothesize that immediate fat and nanofat-enriched fat graft transfer may improve the scar quality and optimize results. Materials and methods This prospective study comprised 45 superomedial pedicle wise-pattern breast reduction patients divided into three groups of 15 in a randomized fashion. The control group had no additional injections whereas the other two groups received injections of fat and nanofat-enriched fat grafts immediately under their surgery scars, respectively. Surgical scar formation was evaluated at six months and scars were scored using the Vancouver scar scale and a visual analogue scale. Results Fat and nanofat-enriched fat graft-injected groups scored significantly better on all items of the Vancouver scar scale, except for scar height, compared to the control group (p < 0.05). Visual analogue scores were significantly lower in the fat and nanofat-enriched fat graft-injected groups compared to the control group (p < 0.05). Conclusions In breast reduction patients, simultaneous fat and nanofat-enriched fat grafting appears to be a safe and promising strategy for scar management.
Polygenic Selection within a Single Generation Leads to Subtle Divergence among Ecological Niches

Abstract Selection on standing genetic variation may be effective enough to allow for adaptation to distinct niche environments within a single generation. Minor allele frequency changes at multiple, redundant loci of small effect can produce remarkable phenotypic shifts. Yet, demonstrating rapid adaptation via polygenic selection in the wild remains challenging. Here we harness natural replicate populations that experience similar selection pressures and harbor high within-, yet negligible among-population genetic variation. Such populations can be found among the teleost Fundulus heteroclitus that inhabits marine estuaries characterized by high environmental heterogeneity. We identify 10,861 single nucleotide polymorphisms in F. heteroclitus that belong to a single, panmictic population yet reside in environmentally distinct niches (one coastal basin and three replicate tidal ponds). By sampling at two time points within a single generation, we quantify both allele frequency change within as well as spatial divergence among niche subpopulations. We observe few individually significant allele frequency changes yet find that the “number” of moderate changes exceeds the neutral expectation by 10–100%. We find allele frequency changes to be significantly concordant in both direction and magnitude among all niche subpopulations, suggestive of parallel selection. In addition, within-generation allele frequency changes generate subtle but significant divergence among niches, indicative of local adaptation. Although we cannot distinguish between selection and genotype-dependent migration as drivers of within-generation allele frequency changes, the trait/s determining fitness and/or migration likelihood appear to be polygenic. In heterogeneous environments, polygenic selection and polygenic, genotype-dependent migration offer conceivable mechanisms for within-generation, local adaptation to distinct niches.
Prevalence of nocturia after brain injury: a cross-sectional study in a single rehabilitation center

ABSTRACT Aim: to analyze the prevalence of nocturia and its possible neuro-urological correlations in patients with a history of acquired brain injury (ABI). Methods: a single-centre population-based prospective study involving outpatients who were previously admitted to our Rehabilitation Hospital for acute ABI ≥ 18 months and ≤2 years prior. Impact of nocturia on QoL was evaluated by the standardized International Consultation on Incotinence Nocturia Quality of Life (ICIQ N-QoL). All participants were given a three-day frequency chart. Probability value <0.05 was statistically significant. Results: 48/138 subjects (35%) showed nocturia at 2-year follow-up visit. No, significant differences in age, gender, duration of coma, state of consciousness, disability, cognitive impairment and stroke severity were found in patients with or without nocturia. Subarachnoid haemorrhage (ESA) was the main reason for ABI in subjects showing nocturia (p = .037). The overall ICIQ N-QOL score ranged from 12 to 50 (mean 30.12 ± 8.87). Of them, 75% showed a total score >26. Increased diurnal frequency and small bladder capacity was statistically significantly associated with nocturia (p < .05). Conclusions: the rate of nocturia 2 years following ABI was lower compared to other neurological populations, although it was significantly associated with other storage urinary symptoms.
The Antinociceptive, Antioxidant and Anti-Inflammatory Effects of 5-Fluoro-2-Oxindole during Inflammatory Pain

Recent studies demonstrate that 5-fluoro-2-oxindole inhibits neuropathic pain but the antinociceptive actions of this drug and its effects on the plasticity, oxidative and inflammatory changes induced by peripheral inflammation as well as on the effects and expression of µ-opioid receptors (MOR) have not been evaluated. In C57BL/6 male mice with inflammatory pain provoked by the subplantar administration of complete Freund’s adjuvant (CFA), we evaluated: (1) the antinociceptive actions of 5-fluoro-2-oxindole and its reversion with the HO-1 inhibitor, tin protoporphyrin IX (SnPP); (2) the effects of 5-fluoro-2-oxindole in the protein levels of mitogen-activated protein kinase (MAPK), Nrf2, NADPH quinone oxidoreductase1 (NQO1), heme oxygenase 1 (HO-1), oxidative stress marker (4-hydroxy-2-nonenal; 4-HNE), inducible nitric oxide synthase (NOS2), microglial markers (CD11b/c and IBA-1), and MOR in the spinal cord and/or paw of animals with inflammatory pain; (3) the antinociceptive effects of morphine in 5-fluoro-2-oxindole pre-treated animals. Treatment with 5 and 10 mg/kg of 5-fluoro-2-oxindole inhibited the allodynia and hyperalgesia induced by CFA in a different, time-dependent manner. These effects were reversed by SnPP. Treatment with 5-fluoro-2-oxindole increased the expression of NQO1, HO-1 and MOR and inhibited the CFA-induced upregulation of phosphorylated MAPK, 4-HNE, NOS2, CD11b/c and IBA-1 in spinal cords and/or paws. The local effects of morphine were improved with 5-fluoro-2-oxindole. This work reveals that 5-fluoro-2-oxindole inhibits the plasticity, oxidative and inflammatory responses provoked by peripheral inflammation and potentiates the antinociceptive effects of morphine. Thus, treatment with 5-fluoro-2-oxindole alone and/or combined with morphine are two remarkable new procedures for chronic inflammatory pain management.
Particulate Matter-Induced Inflammation/Oxidative Stress in Macrophages: Fucosterol from Padina boryana as a Potent Protector, Activated via NF-κB/MAPK Pathways and Nrf2/HO-1 Involvement

Fucosterol is a phytosterol that is abundant in marine brown algae and is a renowned secondary metabolite. However, its ability to protect macrophages against particulate matter (PM) has not been clarified with regard to inflammation; thus, this study aimed to illustrate the above. Padina boryana, a brown algae that is widespread in Indo–Pacific waters, was applied in the isolation of fucosterol. Isolation was conducted using silica open columns, while identification was assisted with gas chromatography-mass spectroscopy (GC-MS) and NMR. Elevated levels of PM led the research objectives toward the implementation of it as a stimulant. Both inflammation and oxidative stress were caused due the fact of its effect. RAW 264.7 macrophages were used as a model system to evaluate the process. It was apparent that the increased NO production levels, due to the PM, were mediated through the inflammatory mediators, such as inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and pro-inflammatory cytokines (i.e., interleukin-6 (IL-6), interleukin-1 (IL-1β) and tumor necrosis factor-α (TNF-α), including prostaglandin E2 (PGE2)). Further, investigations provided solid evidence regarding the involvement of NF-κB and mitogen-activated protein kinases (MAPKs) in the process. Oxidative stress/inflammation which are inseparable components of the cellular homeostasis were intersected through the Nrf2/HO-1 pathway. Conclusively, fucosterol is a potent protector against PM-induced inflammation in macrophages and hence be utilized as natural product secondary metabolite in a sustainable manner.
Response to Shao Et Al.

Alexander H Seeto, Bo Abrahamsen, Peter R Ebeling,5,6† and Alexander J Rodríguez2,5† School of Medicine, Griffith University, Gold Coast, Australia OPEN-Odense Patient Data Explorative Network, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark Musculoskeletal Pharmacoand Device Epidemiology, Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Sciences, University of Oxford, Oxford, UK Department of Medicine, Holbæk Hospital, Holbæk, Denmark Bone andMuscle Health Research Group, Department of Medicine, School of Clinical Sciences, Faculty of Medicine, Nursing and Health Sciences, Monash University, Monash Medical Centre, Clayton, Australia Australian Institute for Musculoskeletal Science, St. Albans, Australia
Influence of HLA-DQ2.5 Dose on Clinical Picture of Unrelated Celiac Disease Patients

The clinical phenotype of celiac disease varies considerably among patients and the dosage of HLA-DQ2.5 alleles has been suggested to be a contributing factor. We investigated whether HLA-DQ2.5 allele dosage is associated with distinct clinical parameters at the time of diagnosis and with patients’ response to a gluten-free diet. The final cohort included 605 carefully phenotyped non-related Finnish celiac disease patients grouped as having 0, 1 or 2 copies of HLA-DQ2.5. Clinical data at the time of diagnosis and during gluten-free diet were collected systematically from medical records and supplementary interviews. An increasing HLA-DQ2.5 dose effect was detected for celiac disease antibody positivity at diagnosis (p = 0.021) and for the presence of any first-degree relatives with celiac disease (p = 0.011 and p = 0.031, respectively). Instead, DQ2.5-negative patients were suffering most often from classical symptoms at diagnosis (p = 0.007 between HLA groups). In addition, during follow-up they were most often symptomatic despite a gluten-free diet (p = 0.002 between groups). Our results thus suggest that increasing HLA-DQ2.5 dose only has a minor effect on the clinical picture of celiac disease. However, HLA-DQ2.5-negative patients should not be overlooked in clinical practice and particular attention should be paid to this patient group during gluten-free diet.
Coagulation dysfunction in ICU patients with coronavirus disease 2019 in Wuhan, China: a retrospective observational study of 75 fatal cases

Coagulation dysfunction in critically ill patients with coronavirus disease 2019 (COVID-19) has not been well described, and the efficacy of anticoagulant therapy is unclear. In this study, we retrospectively reviewed 75 fatal COVID-19 cases who were admitted to the intensive care unit at Jinyintan Hospital (Wuhan, China). The median age of the cases was 67 (62–74) years, and 47 (62.7%) were male. Fifty patients (66.7%) were diagnosed with disseminated intra-vascular coagulation. Approximately 90% of patients had elevated D-dimer and fibrinogen degradation products, which decreased continuously after anticoagulant treatment and was accompanied by elevated albumin (all P<0.05). The median survival time of patients treated with anticoagulant was 9.0 (6.0–14.0) days compared with 7.0 (3.0–10.0) days in patients without anticoagulant therapy (P=0.008). After anticoagulation treatment, C-reactive protein levels decreased (P=0.004), as did high-sensitivity troponin (P=0.018), lactate dehydrogenase (P<0.001), and hydroxybutyrate dehydrogenase (P<0.001). In conclusion, coagulation disorders were widespread among fatal COVID-19 cases. Anticoagulant treatment partially improved hypercoagulability, prolonged median survival time, and may have postponed inflammatory processes and cardiac injury.