Miracle-dz/UniFAR-FTUs huggingface dataset:
The AST-120 Recovers Uremic Toxin-Induced Cognitive Deficit via NLRP3 Inflammasome Pathway in Astrocytes and Microglia

Chronic kidney disease (CKD) is characterized by the progressive loss of renal function; moreover, CKD progression commonly leads to multiple comorbidities, including neurological dysfunction and immune disorders. CKD-triggered neuroinflammation significantly contributes to cognitive impairment. This study aimed to investigate the contribution of uremic toxins to cognitive impairment. Serum creatinine, blood urea nitrogen (BUN), indoxyl sulfate (IS), and p-cresol sulfate (PCS) levels were measured using an enzyme-linked immunosorbent assay and high-performance liquid chromatography. The creatinine, BUN, IS, and PCS levels were increased from 4 weeks after 5/6-nephrectomy in mice, which suggested that 5/6-nephrectomy could yield a CKD animal model. Further, CKD mice showed significantly increased brain and serum indoxyl sulfate levels. Immunohistochemistry analysis revealed hippocampal inflammation and NLRP3-inflammasomes in astrocytes. Further, the Y-maze and Morris water maze tests revealed learning and memory defects in CKD mice. AST-120, which is also an IS absorbent, effectively reduced serum and hippocampal IS levels as well as reversed the cognitive impairment in CKD mice. Additionally, NLRP3-knockout mice that underwent 5/6-nephrectomy showed no change in cognitive function. These findings suggested that IS is an important uremic toxin that induces NLRP3 inflammasome-mediated not only in microglia, but it also occurred in astrocytic inflammation, which subsequently causes cognitive impairment.
Ultrasound Elastography in the Assessment of the Intestinal Changes in Inflammatory Bowel Disease—Systematic Review

Inflammatory bowel disease (IBD) is a chronic condition affecting primarily the gastrointestinal tract and characterized by growing incidence worldwide. Complex diagnostic process of IBD as well as evaluation of disease activity and intestinal complications that are crucial for the therapeutic decisions, require repetitive, invasive, expensive, time-consuming and poorly tolerated tests. In contrast to endoscopy and computed tomography, ultrasound elastography (UE) is non-invasive, non-radiating and non-contrasting dependent tool which might be utilized in IBD patients for the assessment of the intestinal changes. Therefore, we performed the systematic review to evaluate the possible application of the ultrasound elastography for assessment of the intestinal changes in IBD. After the search of three databases: PubMed, World of Knowledge and Scopus, we identified 12 papers which were included in the final analysis. The majority of the studies were focused on the evaluation of the symptomatic ileal/ileocolonic strictures in Crohn’s disease patients that required surgical resection. Only one study concerned ulcerative colitis. The authors evaluated different UE techniques: strain elastography (SE), acoustic radiation force impulse (ARFI) and shear wave elastography (SWE). Results were expressed with semi-quantitative color mapping and strain measurement. Histological scores of inflammation and fibrosis in Crohn’s disease were used as a reference test in the majority of studies. Ultrasound elastography seems to be a promising novel imaging technique supporting evaluation of the intestinal strictures in Crohn’s disease patients in respect to fibrosis detection as well as differentiation between fibrosis and inflammation. However, further research is needed to establish the position of ultrasound elastography in IBD management.
Study of the Lipolysis Effect of Nanoliposome-Encapsulated Ganoderma lucidum Protein Hydrolysates on Adipocyte Cells Using Proteomics Approach

Excessive lipid accumulation is a serious condition. Therefore, we aimed at developing safe strategies using natural hypolipidemic products. Lingzhi is an edible fungus and potential lipid suppression stimulant. To use Lingzhi as a functional hyperlipidemic ingredient, response surface methodology (RSM) was conducted to optimize the time (X1) and enzyme usage (X2) for the hydrolysate preparation with the highest degree of hydrolysis (DH) and % yield. We encapsulated the hydrolysates using nanoscale liposomes and used proteomics to study how these nano-liposomal hydrolysates could affect lipid accumulation in adipocyte cells. RSM analysis revealed X1 at 8.63 h and X2 at 0.93% provided the highest values of DH and % yields were 33.99% and 5.70%. The hydrolysates were loaded into liposome particles that were monodispersed. The loaded nano-liposomal particles did not significantly affect cell survival rates. The triglyceride (TG) breakdown in adipocytes showed a higher TG increase compared to the control. Lipid staining level upon the liposome treatment was lower than that of the control. Proteomics revealed 3425 proteins affected by the liposome treatment, the main proteins being TSSK5, SMU1, GRM7, and KLC4, associated with various biological functions besides lipolysis. The nano-liposomal Linzghi hydrolysate might serve as novel functional ingredients in the treatment and prevention of obesity
Direct Oral Anticoagulants in Patients with Obesity and Atrial Fibrillation: Position Paper of Italian National Association of Hospital Cardiologists (ANMCO)

The use of the direct oral anticoagulants dabigatran, rivaroxaban, apixaban and edoxaban (DOACs) offers some major advantages over warfarin and other vitamin K antagonists (VKAs). One advantage is the possibility to use a fixed dose in normal-weight patients, overweight patients and patients with obesity. However, the “one size fits all” strategy raised a concern regarding the possibility to undertreat patients with a high body mass index. No randomized controlled trials (RCTs) have ever compared VKAs and DOACs in this population. We analyzed data from the literature on DOAC pharmacokinetics and pharmacodynamics, results from the four pivotal phase III trials on non-valvular atrial fibrillation, retrospective observational studies and metanalyses. While we are aware of the limitation imposed by the absence of specific RCTs, we propose the position of the Italian Association of Hospital Cardiologists (ANMCO) on the use of DOACs in patients with obesity based on the existing evidence.
Advanced Photocatalysts Based on Conducting Polymer/Metal Oxide Composites for Environmental Applications

Photocatalysts provide a sustainable method of treating organic pollutants in wastewater and converting greenhouse gases. Many studies have been published on this topic in recent years, which signifies the great interest and attention that this topic inspires in the community, as well as in scientists. Composite photocatalysts based on conducting polymers and metal oxides have emerged as novel and promising photoactive materials. It has been demonstrated that conducting polymers can substantially improve the photocatalytic efficiency of metal oxides owing to their superior photocatalytic activities, high conductivities, and unique electrochemical and optical properties. Consequently, conducting polymer/metal oxide composites exhibit a high photoresponse and possess a higher surface area allowing for visible light absorption, low recombination of charge carriers, and high photocatalytic performance. Herein, we provide an overview of recent advances in the development of conducting polymer/metal oxide composite photocatalysts for organic pollutant degradation and CO2 conversion through photocatalytic processes.
Serous Borderline Ovarian Tumor Diagnosis, Management and Fertility Preservation in Young Women

Borderline ovarian tumors (BOT) represent about 10 to 20 percent of all epithelial tumors of the ovary. They constitute intermediate lesions between benign ovarian cysts and invasive carcinomas. They often occur in young women of reproductive age, and, albeit with a favorable prognosis, it may recur on the ipsilateral or contralateral ovary. Controversies surround the diagnostic criteria used for their assessment, and the optimal management to minimize their risk of recurrence and/or transformation into malignant carcinoma. Fertility preservation (FP) is considered a priority in the management of these patients, and studies aim at finding the safest and most effective way to help women with BOT history conceive with minimal risk. We present the experience of a single institution in managing three cases of serous BOT in young nulliparous women, followed by a thorough review of the existing literature, highlighting controversies and exploring the possible FP techniques for these women.
Trial Design of a Prospective Multicenter Diagnostic Accuracy Study of a Point-of-Care Test for the Detection of Taenia solium Taeniosis and Neurocysticercosis in Hospital-Based Settings in Tanzania

Taenia solium diagnosis is challenging as trained personnel, good diagnostic tools, and infrastructure is lacking in resource-poor areas. This paper aims to describe the study trial design adopted to evaluate a newly developed rapid point-of-care test that simultaneously detects taeniosis and neurocysticercosis (TS POC) in three district hospitals in Tanzania. The two-stage design included three types of patients: patients with specific neurological signs and symptoms (group 1); patients with complaints compatible with intestinal worm infections (group 2); patients with other symptom(s) (group 3). For group 1, all patients were tested using the TS POC test (stage 1), after which all positive, and a subset of negative, patients were selected for laboratory reference tests, clinical examination, and a brain computed tomography (CT) scan (stage 2). For groups 2 and 3, a similar design was adopted, but clinical examination and a brain CT scan (stage 2) were only performed in patients who were TS POC test-positive for cysticercosis. Due to the lack of a gold standard, a Bayesian approach was used to determine test accuracy for taeniosis and cysticercosis. For neurocysticercosis, a composite case definition was used as the reference standard. If successful, this study will help the future developments (commercialization and implementation) of the rapid test and improve patient management and disease prevention.
The Effect of the Climatic Housing Environment on the Growth of Dairy-Bred Calves in the First Month of Life on a Scottish Farm

Simple Summary The climatic environment within calf housing can have an effect on calf health, but also on growth and performance. Calves have a lower threshold environmental temperature (lower critical temperature, LCT), below which can impact on the calf’s ability to maintain its core body temperature. This can cause the calf to partition more of its available energy into heat production and less into growth. The LCT decreases as the calf gets older. This year-long study followed 299 dairy-bred calves on one farm in Scotland from birth until approximately 28 days of age, and looked at the proportion of time for which the temperature was below the LCT for the individual calf, as well as the daily liveweight gain (DLWG; kg/d) of the calves during this time. For their first 6–14 days of life the calves were individually housed, and then subsequently group housed. Air temperature (°C), relative humidity (%), and wind speed (m/s) were recorded every hour of every day throughout the study, and calves were weighed regularly so that DLWG could be calculated. The study demonstrated that calves that spent a high proportion of their time below their LCT had a lower DLWG compared to calves that spent a low proportion of their time below their LCT. Abstract Calf housing is naturally thermodynamic, with interactions between various elements such as wind speed, air temperature, and humidity. This study investigated the effect of the proportion of time for which calves were exposed to effective environmental temperatures below their lower critical temperature (LCT) on their daily liveweight gain (DLWG) within their first month of life. This study used the naturally occurring climatic environment, whereas other such studies have been conducted under climatically controlled conditions. Air temperature (°C), relative humidity (%), and wind speed (m/s) were recorded within the calf housing from birth until approximately 28 days of age, with calves being health-scored and weighed at regular intervals. Calves were housed from birth until 6–14 days old in individual hutches, and then moved into group housing igloo pens. Whilst individually housed, calves that spent less than 32% of their time below their LCT had a DLWG of 0.06 ± 0.34 kg/d (mean ± SE) compared to calves that spent more than 97% of their time below their LCT, which had a DLWG of −0.19 ± 0.045 kg/d. When group housed, calves that spent less than 1% of their time below their LCT had a DLWG of 0.59 ± 0.18 kg/d, whereas calves that spent more than 28% of their time below their LCT had a DLWG of 0.53 ± 0.23 kg/d. The proportion of time for which calves were exposed to effective environmental temperatures below their LCT had a significant effect on DLWG when calves were individually housed. Therefore, exposure to effective environmental temperatures below the LCT can be detrimental to the growth of the calf in the early stages of its life.
Molecular-Morphological Relationships of the Scaffold Protein FKBP51 and Inflammatory Processes in Knee Osteoarthritis

Knee osteoarthritis (OA) is one of the most prevalent chronic conditions affecting the adult population. OA is no longer thought to come from a purely biomechanical origin but rather one that has been increasingly recognized to include a persistent low-grade inflammatory component. Intra-articular corticosteroid injections (IACSI) have become a widely used method for treating pain in patients with OA as an effective symptomatic treatment. However, as the disease progresses, IACSI become ineffective. FKBP51 is a regulatory protein of the glucocorticoid receptor function and have been shown to be dysregulated in several pathological scenario’s including chronic inflammation. Despite of these facts, to our knowledge, there are no previous studies of the expression and possible role of FKBP51 in OA. We investigated by double and triple immunofluorescence confocal microscopy the cellular and subcellular expression of FKBP51 and its relations with inflammation factors in osteoarthritic knee joint tissues: specifically, in the tibial plateau knee cartilage, Hoffa’s fat pad and suprapatellar synovial tissue of the knee. Our results show co-expression of FKBP51 with TNF-α, IL-6, CD31 and CD34 in OA chondrocytes, synovial membrane cells and adipocytes in Hoffa’s fat pad. FKBP51 is also abundant in nerve fibers within the fat pad. Co-expression of FKBP51 protein with these markers may be indicative of its contribution to inflammatory processes and associated chronic pain in OA.
Goals and Challenges of Stem Cell-Based Therapy for Corneal Blindness Due to Limbal Deficiency

Corneal failure is a highly prevalent cause of blindness. One special cause of corneal failure occurs due to malfunction or destruction of the limbal stem cell niche, upon which the superficial cornea depends for homeostatic maintenance and wound healing. Failure of the limbal niche is referred to as limbal stem cell deficiency. As the corneal epithelial stem cell niche is easily accessible, limbal stem cell-based therapy and regenerative medicine applied to the ocular surface are among the most highly advanced forms of this novel approach to disease therapy. However, the challenges are still great, including the development of cell-based products and understanding how they work in the patient’s eye. Advances are being made at the molecular, cellular, and tissue levels to alter disease processes and to reduce or eliminate blindness. Efforts must be coordinated from the most basic research to the most clinically oriented projects so that cell-based therapies can become an integrated part of the therapeutic armamentarium to fight corneal blindness. We undoubtedly are progressing along the right path because cell-based therapy for eye diseases is one of the most successful examples of global regenerative medicine.
Selective Serotonin Reuptake Inhibitors for the Treatment of Depression in Adults with Down Syndrome: A Preliminary Retrospective Chart Review Study

Background: Depression is a common psychiatric comorbidity in individuals with Down syndrome (DS), particularly adults, with an estimated lifetime prevalence of at least 10%. The current literature on the treatment of depression in adults with DS is limited to case series published more than two decades ago, prior to the widespread use of modern antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs). The purpose of this retrospective chart review study was to examine the effectiveness, tolerability, and safety of SSRIs for depression in adults with DS. Methods: Medical records of 11 adults with DS and depression were reviewed. Assignment of scores for severity (S) of symptoms of depression and improvement (I) of symptoms with treatment with an SSRI was made retrospectively using the Clinical Global Impression Scale (CGI). Demographic and clinical characteristics of the study population, SSRI name, dose, and duration of treatment; and adverse effects were also recorded. Results: All 11 patients (7 male, 4 female; mean age = 27.2 years, range 18–46 years) completed a 12-week treatment course with an SSRI. The median duration of time after initiation of the SSRI covered by record review was 2.1 years, with a range of 24 weeks to 6.7 years. Nine of the 11 patients (82%; 95% CI 52%, 95%) were judged responders to SSRIs based on a rating of “much improved” or “very much improved” on the CGI-I after 12 weeks of treatment (median time of follow-up was 14.4 weeks, with a range of 12.0–33.0 weeks). Adverse effects occurred in four patients (36%). The most common adverse effects were daytime sedation and anger. Conclusions: In this preliminary retrospective study, the majority of patients responded to a 12-week course of SSRI treatment and some tolerated long-term use. Controlled studies are needed to further assess the efficacy, tolerability, and safety of SSRIs for the treatment of depression in adults with DS.
MicroRNA-Based Risk Score for Predicting Tumor Progression Following Radioactive Iodine Ablation in Well-Differentiated Thyroid Cancer Patients: A Propensity-Score Matched Analysis

Simple Summary The three-tiered American Thyroid Association (ATA) risk stratification helps clinicians tailor decisions regarding follow-up modalities and the need for postoperative radioactive iodine (RAI) ablation and radiotherapy. However, a significant number of well-differentiated thyroid cancers (DTC) progress after treatment. Current follow-up modalities have also been proposed to detect disease relapse and recurrence but have failed to be sufficiently sensitive or specific to detect, monitor, or determine progression. Therefore, we assessed the predictive accuracy of the microRNA-based risk score in DTC with and without postoperative RAI. We confirm the prognostic role of triad biomarkers (miR-2f04, miR-221, and miR-222) with higher sensitivity and specificity for predicting disease progression than the ATA risk score. Compared to indolent tumors, a higher risk score was found in progressive samples and was associated with shorter survival. Consequently, our prognostic microRNA signature and nomogram provide a clinically practical and reliable ancillary measure to determine the prognosis of DTC patients. Abstract To identify molecular markers that can accurately predict aggressive tumor behavior at the time of surgery, a propensity-matching score analysis of archived specimens yielded two similar datasets of DTC patients (with and without RAI). Bioinformatically selected microRNAs were quantified by qRT-PCR. The risk score was generated using Cox regression and assessed using ROC, C-statistic, and Brier-score. A predictive Bayesian nomogram was established. External validation was performed, and causal network analysis was generated. Within the eight-year follow-up period, progression was reported in 51.5% of cases; of these, 48.6% had the T1a/b stage. Analysis showed upregulation of miR-221-3p and miR-222-3p and downregulation of miR-204-5p in 68 paired cancer tissues (p < 0.001). These three miRNAs were not differentially expressed in RAI and non-RAI groups. The ATA risk score showed poor discriminative ability (AUC = 0.518, p = 0.80). In contrast, the microRNA-based risk score showed high accuracy in predicting tumor progression in the whole cohorts (median = 1.87 vs. 0.39, AUC = 0.944) and RAI group (2.23 vs. 0.37, AUC = 0.979) at the cutoff >0.86 (92.6% accuracy, 88.6% sensitivity, 97% specificity) in the whole cohorts (C-statistics = 0.943/Brier = 0.083) and RAI subgroup (C-statistic = 0.978/Brier = 0.049). The high-score group had a three-fold increased progression risk (hazard ratio = 2.71, 95%CI = 1.86–3.96, p < 0.001) and shorter survival times (17.3 vs. 70.79 months, p < 0.001). Our prognostic microRNA signature and nomogram showed excellent predictive accuracy for progression-free survival in DTC.
Tasting the Italian Terroir through Craft Beer: Quality and Sensory Assessment of Cascade Hops Grown in Central Italy and Derived Monovarietal Beers

The present study aimed to chemically and sensorially characterize hop samples, cv Cascade, grown in two different Italian regions (Latium and Tuscany) as well as their derived beers by a multi analytical approach. Significant differences in bitter acid, oil and polyphenol content were observed for hop samples according to their origin. Gas chromatography-olfactometry analysis pointed out floral notes for Tuscany samples, where hops from Latium were characterized by spicy and resinous notes, correlated to the presence of sesquiterpenes. Differences in the molecular fingerprinting were also highlighted by Fourier–Transform Infrared Spectroscopy. The differences found in the hops were reflected in the beers, which were clearly recognized as distinct by a sensory panel. Both beer samples were mainly characterized by six aroma compounds (linalool, geraniol and β-damascenone, citronellol, 2-phenylethyl acetate, and 2-phenylethanol), three of which were potentially responsible for the geographic origin of the hops given their significantly different concentrations.
Participation of the ABC Transporter CDR1 in Azole Resistance of Candida lusitaniae

Candida lusitaniae is an opportunistic pathogen in humans that causes infrequent but difficult-to-treat diseases. Antifungal drugs are used in the clinic to treat C. lusitaniae infections, however, this fungus can rapidly acquire antifungal resistance to all known antifungal drugs (multidrug resistance). C. lusitaniae acquires azole resistance by gain-of-function (GOF) mutations in the transcriptional regulator MRR1. MRR1 controls the expression of a major facilitator transporter (MFS7) that is important for fluconazole resistance. Here, we addressed the role of the ATP Binding Cassette (ABC) transporter CDR1 as additional mediator of azole resistance in C. lusitaniae. CDR1 expression in isolates with GOF MRR1 mutations was higher compared to wild types, which suggests that CDR1 is an additional (direct or indirect) target of MRR1. CDR1 deletion in the azole-resistant isolate P3 (V688G GOF) revealed that MICs of long-tailed azoles, itraconazole and posaconazole, were decreased compared to P3, which is consistent with the role of this ABC transporter in the efflux of these azoles. Fluconazole MIC was only decreased when CDR1 was deleted in the background of an mfs7Δ mutant from P3, which underpins the dominant role of MFS7 in the resistance of the short-tailed azole fluconazole. With R6G efflux readout as Cdr1 efflux capacity, our data showed that R6G efflux was increased in P3 compared to an azole-susceptible wild type parent, and diminished to background levels in mutant strains lacking CDR1. Milbemycin oxim A3, a known inhibitor of fungal ABC transporters, mimicked efflux phenotypes of cdr1Δ mutants. We therefore provided evidence that CDR1 is an additional mediator of azole resistance in C. lusitaniae, and that CDR1 regulation is dependent on MRR1 and associated GOF mutations.