Miracle-dz/UniFAR-FTUs huggingface dataset:
The Merkel Cell Polyomavirus T Antigens Function as Tumor Promoters in Murine Skin

Simple Summary Merkel cell polyomavirus, a recently discovered human virus, is linked to the development of a rare form of skin cancer called Merkel cell carcinoma. The virus does not replicate in cancer cells, yet there is continued expression of viral proteins known as T antigens. The T antigens are believed to contribute to Merkel cell carcinoma development, yet how they do so remains an active area of research. In this study, we used transgenic mice expressing the viral T antigens in their skin to determine at which stage of skin cancer development these viral proteins function. We discovered that the Merkel cell polyomavirus T antigens function as tumor promoters, rather than tumor initiators, in the skin. These findings suggest that other tumor-initiating events may cooperate with the tumor-promoting activities of the viral T antigens, thus providing important insight into how Merkel cell polyomavirus can cause cancer in human skin. Abstract Merkel cell polyomavirus (MCPyV) causes the majority of human Merkel cell carcinomas (MCC), a rare but highly aggressive form of skin cancer. We recently reported that constitutive expression of MCC tumor-derived MCPyV tumor (T) antigens in the skin of transgenic mice leads to hyperplasia, increased proliferation, and spontaneous epithelial tumor development. We sought to evaluate how the MCPyV T antigens contribute to tumor formation in vivo using a classical, multi-stage model for squamous cell carcinoma development. In this model, two chemical carcinogens, DMBA and TPA, contribute to two distinct phases of carcinogenesis—initiation and promotion, respectively—that are required for tumors to develop. By treating the MCPyV transgenic mice with each chemical carcinogen, we determined how the viral oncogenes contributed to carcinogenesis. We observed that the MCPyV T antigens synergized with the tumor initiator DMBA, but not with the tumor promoter TPA, cause tumors. Therefore, the MCPyV tumor antigens function primarily as tumor promoters, similar to that seen with human papillomavirus (HPV) oncoproteins. These studies provide insight into the role of MCPyV T antigen expression in tumor formation in vivo and contribute to our understanding of how MCPyV may function as a human DNA tumor virus.
Soil organic matter and nutrient pools under long‐term non‐burning management of sugar cane

We employed CP/MAS 13C NMR spectroscopy and classical humus fractionation to evaluate the behaviour of soil organic matter (SOM) resulting from long‐term sugar cane production when harvested without burning. Soil samples were collected at two depths (0–0.2 and 0.2–0.4 m) from a tropical Entisol cropped with sugar cane for 55 years at Campos dos Goytacazes (Brazil), either with or without burning crop residues when harvesting. Continuous incorporation of sugar cane residues increased carbon (C) content and promoted changes in SOM, including increases in humins, humic acids and aromatic C moieties. Sequential extraction methods showed enhanced amounts of available forms of nitrogen (N), sulphur (S) and phosphorus (P). Moreover, 31P NMR analysis revealed an increase in organic P as diester phosphates of plant origin in the humic acids fraction. The increased macronutrient bioavailability of labile forms of N, P and S could be partially related to the more hydrophobic nature of SOM observed in soil samples collected from areas that were not burnt. These results show that the long‐term non‐burning management of sugar cane harvest promotes the hydrophobic character of SOM and a more conservative and sustainable management of soil fertility.
Total Antioxidant Capacity in HBV Carriers, a Promising Biomarker for Evaluating Hepatic Fibrosis: A Pilot Study

Oxidative stress plays a pivotal role in the progression of chronic hepatitis B; however, it is unclear whether the status of blood oxidative stress and antioxidant components differs depending on the degree of hepatic fibrosis. To explore the relationship between oxidative stress/antioxidant capacity and the extent of hepatic fibrosis, fifty-four subjects with liver fibrosis (5.5 ≤ liver stiffness measurement (LSM) score ≤ 16.0 kPa) by chronic hepatitis B virus (HBV) were analyzed. From the analysis of eight kinds of serum oxidative stress/antioxidant profiles and liver fibrosis degrees, the level of total antioxidant capacity (TAC) reflected a negative correlation with the severity of hepatic fibrosis (Pearson correlation, r = −0.35, p = 0.01). Moreover, TAC showed higher sensitivity (73.91%) than the aspartate transaminase (AST) to platelet ratio index (APRI, 56.52%) in the receiver operating characteristic (ROC) curves. Interestingly, the TAC level finely reflected the fibrosis degree in inactive carriers (HBV DNA < 2000 IU/mL), while the APRI did in active carriers (HBV DNA > 2000 IU/mL). In conclusion, TAC is a promising biomarker for evaluating the progression of liver fibrosis in patients with HBV, and this finding may indicate the involvement of TAC-composing factors in the pathogenesis of hepatic fibrosis in chronic HBV carriers.
Physico‐Chemical and Bacterial Characteristics of Water Quality in Three Villages West of Lake Nasser, Egypt

The present study aims to investigate physico-chemical and bacterial characteristics of Nasser Lake water and houses drinking water, as well as fish cultures and its wastewater, in three villages west of Lake Nasser, Egypt. Fifteen representative water samples (Nasser Lake, different drinking water, fish cultures, and wastewater sources) were collected from three villages (Garf Hussein, Bashaier, and Kalabsha) in the west of Lake Nasser. Physico-chemical, total viable counts, and bacterial qualification of water were achieved. The obtained results indicated that the produced water, supposed to be for domestic use in the three villages, contained all the tested organisms. The investigated water samples of the lake and drinking water in the selected three villages are supposed to be chemically safe according to World Health Organization and to Egyptian standards for drinking water. Water pollution index (WPI) was used in this study and the result concluded that for irrigation canals from the lake to the agriculture site, fish cultures (both concrete and earth pond systems), and drainage canal of fish ponds need to be treated before it is discharged to the lake. It is better to reuse it after treatment for agricultural purposes or recycled it to the fish cultures.
Impact of Sample Preparation on Dissolution Testing: Drug Binding and Extractable Impurities and Their Effect on Dissolution Data

Dissolution testing is a key pharmaceutical QC test required for release of oral dosage forms. It is also commonly used to predict in vivo behavior of the formulation. Filtration is a key sample preparation step that follows the drug dissolution test before sample analysis. Because of the simplicity of the filtration process, the choice of filtration devices is often ignored, leading to inaccurate and irreproducible results. This paper discusses the effects of drug binding and extractable impurities from syringe filters on dissolution data. The data presented here demonstrate that various basic and acidic drugs bind strongly to nylon membrane filters, thereby reducing drug recovery and giving an incorrect dissolution profile. On the other hand, various drugs with different physicochemical properties do not bind to hydrophilic polytetrafluoroethylene (PTFE) syringe filters, thereby leading to quantitative drug recovery. In combination with its very low extractable profile, hydrophilic PTFE is an ideal filtration choice for dissolution testing.
Observational cohort study of IP-10’s potential as a biomarker to aid in inflammation regulation within a clinical decision support protocol for patients with severe COVID-19

Background Treatment of severely ill COVID-19 patients requires simultaneous management of oxygenation and inflammation without compromising viral clearance. While multiple tools are available to aid oxygenation, data supporting immune biomarkers for monitoring the host-pathogen interaction across disease stages and for titrating immunomodulatory therapy is lacking. Methods In this single-center cohort study, we used an immunoassay platform that enables rapid and quantitative measurement of interferon γ-induced protein 10 (IP-10), a host protein involved in lung injury from virus-induced hyperinflammation. A dynamic clinical decision support protocol was followed to manage patients infected with severe acute respiratory syndrome coronavirus 2 and examine the potential utility of timely and serial measurements of IP-10 as tool in regulating inflammation. Results Overall, 502 IP-10 measurements were performed on 52 patients between 7 April and 10 May 2020, with 12 patients admitted to the intensive care unit. IP-10 levels correlated with COVID-19 severity scores and admission to the intensive care unit. Among patients in the intensive care unit, the number of days with IP-10 levels exceeding 1,000 pg/mL was associated with mortality. Administration of corticosteroid immunomodulatory therapy decreased IP-10 levels significantly. Only two patients presented with subsequent IP-10 flare-ups exceeding 1,000 pg/mL and died of COVID-19-related complications. Conclusions Serial and readily available IP-10 measurements potentially represent an actionable aid in managing inflammation in COVID-19 patients and therapeutic decision-making. Trial registration Clinicaltrials.gov, NCT04389645, retrospectively registered on May 15, 2020.
Significance of fucose in intestinal health and disease

The deoxyhexose sugar L‐fucose is important for many biological processes within the human body and the associated microbiota. This carbohydrate is abundant in host gut mucosal surfaces, numerous microbial cell surface structures, and some dietary carbohydrates. Fucosylated oligosaccharides facilitate the establishment of a healthy microbiota and provide protection from infection. However, there are instances where pathogens can also exploit these fucosylated structures to cause infection. Furthermore, deficiencies in host fucosylation are associated with specific disease outcomes. This review focuses on our current understanding of the impact of fucosylation within the mucosal environment of the gastrointestinal tract with a specific emphasis on the mediatory effects in host–microbe interactions.
Hyperoxia‐induced miR‐342‐5p down‐regulation exacerbates neonatal bronchopulmonary dysplasia via the Raf1 regulator Spred3

Bronchopulmonary dysplasia (BPD) is the most prevalent chronic paediatric lung disease and is linked to the development of chronic obstructive pulmonary disease. MicroRNA‐based regulation of type II alveolar epithelial cell (T2AEC) proliferation and apoptosis is an important factor in the pathogenesis of BPD and warrants further investigation.
Modeling Brain Pathology of Niemann‐Pick Disease Type C Using Patient‐Derived Neurons

Niemann‐Pick disease type C (NPC) is a rare autosomal‐recessive lysosomal storage disease that is also associated with progressive neurodegeneration. NPC shares many pathological features with Alzheimer's disease, including neurofibrillary tangles, axonal spheroids, β‐amyloid deposition, and dystrophic neurites. Here, we examined if these pathological features could be detected in induced pluripotent stem cell (iPSC)‐derived neurons from NPC patients.
Chemistry, Chemotaxonomy and Biological Activity of the Latrunculid Sponges (Order Poecilosclerida, Family Latrunculiidae)

Marine sponges are exceptionally prolific sources of natural products for the discovery and development of new drugs. Until now, sponges have contributed around 30% of all natural metabolites isolated from the marine environment. Family Latrunculiidae Topsent, 1922 (class Demospongiae Sollas, 1885, order Poecilosclerida Topsent, 1928) is a small sponge family comprising seven genera. Latrunculid sponges are recognized as the major reservoirs of diverse types of pyrroloiminoquinone-type alkaloids, with a myriad of biological activities, in particular, cytotoxicity, fuelling their exploration for anticancer drug discovery. Almost 100 pyrroloiminoquinone alkaloids and their structurally related compounds have been reported from the family Latrunculiidae. The systematics of latrunculid sponges has had a complex history, however it is now well understood. The pyrroloiminoquinone alkaloids have provided important chemotaxonomic characters for this sponge family. Latrunculid sponges have been reported to contain other types of metabolites, such as peptides (callipeltins), norditerpenes and norsesterpenes (trunculins) and macrolides (latrunculins), however, the sponges containing latrunculins and trunculins have been transferred to other sponge families. This review highlights a comprehensive literature survey spanning from the first chemical investigation of a New Zealand Latrunculia sp. in 1986 until August 2020, focusing on the chemical diversity and biological activities of secondary metabolites reported from the family Latrunculiidae. The biosynthetic (microbial) origin and the taxonomic significance of pyrroloiminoquinone related alkaloids are also discussed.
Mechanisms of Bone Fragility: From Osteogenesis Imperfecta to Secondary Osteoporosis

Bone material strength is determined by several factors, such as bone mass, matrix composition, mineralization, architecture and shape. From a clinical perspective, bone fragility is classified as primary (i.e., genetic and rare) or secondary (i.e., acquired and common) osteoporosis. Understanding the mechanism of rare genetic bone fragility disorders not only advances medical knowledge on rare diseases, it may open doors for drug development for more common disorders (i.e., postmenopausal osteoporosis). In this review, we highlight the main disease mechanisms underlying the development of human bone fragility associated with low bone mass known to date. The pathways we focus on are type I collagen processing, WNT-signaling, TGF-ß signaling, the RANKL-RANK system and the osteocyte mechanosensing pathway. We demonstrate how the discovery of most of these pathways has led to targeted, pathway-specific treatments.
Making the Case for Proactive Strategies to Alleviate Homelessness: A Systems Approach

Homelessness is a complex public health issue that affects some of the most vulnerable populations in the United States. This study takes a holistic approach to better understand and analyze the multiple factors and their interconnections that contribute to the complexity of this problem. A systems analysis was conducted by utilizing the system dynamics method, which allows analyzing and comparing trends and behavior of system outcomes for different “what if” scenarios, interventions, and policy implications. Three leverage points were identified in this study to increase the effectiveness and efficiency of the current strategies to address homelessness: (1) increasing the number of affordable permanent housing units, (2) increasing the utilization of transitional housing units or shelters by the individuals experiencing homelessness, and (3) providing preventative services to at-risk populations before the onset of homelessness. Our results demonstrate that the most effective strategy is an amalgam of the solutions identified by these three leverage points. In addition, a policy analysis was conducted to study and estimate the effectiveness of various potential scenarios. This research provides data-driven and model-based insights into how decision-makers can utilize a systems approach to analyze new policy implications and create effective solutions to homelessness.
Expert consensus for the diagnosis and treatment of patient with hyperuricemia and high cardiovascular risk: 2021 update

Department of Medical and Surgical Sciences, University of Bologna, Italy Department of Internal Medicine and Cardiology with the Center for Diagnosis and Treatment of Venous Thromboembolism, Medical University of Warsaw, Poland Club 30, Polish Cardiac Society, Poland Department of Hypertension, Angiology and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland Department of Hypertension and Internal Medicine, Pomeranian Medical University, Szczecin, Poland First Department of Cardiology, Medical University of Warsaw, Poland First Department of Cardiology, Medical University of Gdansk, Poland Department of Hypertension and Diabetology, Medical University of Gdansk, Poland Università Milano-Bicocca, Milan, Italy
Outcome challenges for cataract surgery employing the New Zealand Cataract Risk Stratification criteria

bedside test. However, the CGT could be useful in patients who give a history of jaw pain on chewing, with a positive test after 2 minutes increasing the likelihood that the patient has GCA. From a practical perspective, there are some limitations to CGT as a clinical test. First, 5 minutes are required to confirm a negative test. Second, chewing gum may not be readily accessible. Finally, there may be reluctance from older patients to chew gum due to poor dentition; two patients were not included in this study for this reason. In conclusion, the CGT is no better than a clinical history of jaw claudication for the diagnosis of GCA. However, if there is onset of pain after 2 minutes of chewing, specificity increases, which may assist clinicians to distinguish GCA-related jaw claudication from other causes of jaw pain.
Preparation and characterization of [Mn11O10Cl2(OAc)11(bpy)2(MeCN)2(H2O)2](ClO4)2·8MeCN, a mixed-valence manganese(III/IV) aggregate with rare undecanuclearity (bpy = 2,2′-bipyridyl)

Treatment of [Mn4O2(OAc)7(bpy)2](ClO4)·3H2O (bpy = 2,2′-bipyridyl)1 with Me3SiCl in MeCN leads to a disproportionation and nuclearity change to give [Mn11O10Cl2(OAc)11(bpy)2(MeCN)2(H2O)2](ClO4)2·8MeCN 2; the crystal structure shows the core of this aggregate to comprise two [Mn4O3Cl]6+ cubane units ‘bridged’ by a nearly linear [Mn3O4]+ moiety.
Nanog maintains stemness of Lkb1‐deficient lung adenocarcinoma and prevents gastric differentiation

Growing evidence supports that LKB1‐deficient KRAS‐driven lung tumors represent a unique therapeutic challenge, displaying strong cancer plasticity that promotes lineage conversion and drug resistance. Here we find that murine lung tumors from the KrasLSL‐G12D/+; Lkb1flox/flox (KL) model show strong plasticity, which associates with up‐regulation of stem cell pluripotency genes such as Nanog. Deletion of Nanog in KL model initiates a gastric differentiation program and promotes mucinous lung tumor growth. We find that NANOG is not expressed at a meaningful level in human lung adenocarcinoma (ADC), as well as in human lung invasive mucinous adenocarcinoma (IMA). Gastric differentiation involves activation of Notch signaling, and perturbation of Notch pathway by the γ‐secretase inhibitor LY‐411575 remarkably impairs mucinous tumor formation. In contrast to non‐mucinous tumors, mucinous tumors are resistant to phenformin treatment. Such therapeutic resistance could be overcome through combined treatments with LY‐411575 and phenformin. Overall, we uncover a previously unappreciated plasticity of LKB1‐deficient tumors and identify the Nanog‐Notch axis in regulating gastric differentiation, which holds important therapeutic implication for the treatment of mucinous lung cancer.
Analyzing the Magnitude of Interlimb Asymmetries in Young Female Soccer Players: A Preliminary Study

Although asymmetries in lower limbs have been linked with players’ performance in male soccer players, literature that has been published addressing female soccer is scarce. Thus, the aim of this study was twofold: (i) describe the asymmetries of women soccer players during jumping, change-of-direction and range-of-motion tests; and (ii) test possible relationships between asymmetries and injury risk in female soccer players. Sixteen female players (15.5 ± 1.5 years) performed a battery of fitness tests (i.e., jump ability, change-of-direction ability and passive range-of-motion) and muscle mass analysis via dual-energy X-ray absorptiometry, through which the specific asymmetry index and the related injury risk were calculated. Significant (p < 0.05) lower asymmetries in the change-of-direction test were observed in comparison to those observed in jumping and range-of-motion tests; significant (p < 0.05) lower asymmetries in muscle mass were also reported compared to those found in the change-of-direction and countermovement jump tests. Additionally, increased injury risk for countermovement jump and hip flexion with extended knee range-of-motion (relating to asymmetry values) and for ankle flexion with flexed knee range-of-motion in both legs (relating to reference range-of-motion values), as well as increased individual injury risk values, were observed across all tests. These findings suggest the necessity to implement individual approaches for asymmetry and injury risk analyses.
Bio-inspired mechanically-adaptive nanocomposites derived from cotton cellulose whiskers

A new series of biomimetic, stimuli-responsive nanocomposites, which change their mechanical properties upon exposure to physiological conditions, was investigated. The materials were produced by introducing percolating networks of cellulose whiskers isolated from cotton into poly(vinyl acetate). Below the glass-transition temperature (Tg ∼ 63 °C), the tensile storage moduli (E′) of the dry nanocomposites increased two fold, from 2 GPa for the neat polymer to 4 GPa for a nanocomposite with 16.5% v/v whiskers. The relative reinforcement was more significant above Tg, where E′ was increased nearly 40 fold, from ∼1.2 MPa to ∼45 MPa. Upon exposure to emulated physiological conditions (immersion in artificial cerebrospinal fluid at 37 °C) all nanocomposites showed a pronounced decrease in E′, for example to 5 MPa for the 16.5% v/v whisker nanocomposites with only about 28% w/w swelling. This is a significant reduction in the amount of swelling required to decrease the E′, compared to earlier material versions based on cellulose whiskers with higher surface charge density; the decreased swelling may be a considerable advantage for the intended use of these materials as adaptive substrates for intracortical electrodes and other biomedical applications.
Relationship between cognitive emotion regulation strategies and coronary heart disease: an empirical examination of heart rate variability and coronary stenosis

Abstract Objective Despite longstanding interest in emotion regulation and cardiovascular health, limited studies have investigated the relationship between cognitive emotion regulation (CER) strategies and coronary heart disease (CHD) using objective measures of heart rate variability (HRV) and coronary stenosis. This study aimed to objectively explore the associations between CER strategies and both HRV and coronary stenosis and provide empirical evidence for the relationship between emotion regulation and CHD. Methods Questionnaires on CER strategies were distributed to 251 CHD patients and 250 healthy persons. HRV and coronary stenosis were measured for CHD respondents using the 24-h dynamic electrocardiogram and coronary angiography, respectively. Results CHD patients with low HRV/severe stenosis used maladaptive emotion regulation more frequently and adaptive emotion regulation less frequently. Various maladaptive emotion regulation strategies (e.g. acceptance, rumination, putting into perspective) were positively associated with lower HRV and coronary stenosis severity, while adaptive emotion regulation strategies (e.g. positive refocusing, refocusing on planning) were negatively associated with lower HRV and coronary stenosis severity. Conclusions Patients with more serious diseases exhibited increased maladaptive emotion regulation, which was associated with lower HRV and severe coronary stenosis. Further, adaptive emotion regulation was associated with higher HRV and moderate coronary stenosis.