Miracle-dz/UniFAR-FTUs huggingface dataset:
Mycoplasma pneumoniae Infections: Pathogenesis and Vaccine Development

Mycoplasma pneumoniae is a major causative agent of community-acquired pneumonia which can lead to both acute upper and lower respiratory tract inflammation, and extrapulmonary syndromes. Refractory pneumonia caused by M. pneumonia can be life-threatening, especially in infants and the elderly. Here, based on a comprehensive review of the scientific literature related to the respective area, we summarize the virulence factors of M. pneumoniae and the major pathogenic mechanisms mediated by the pathogen: adhesion to host cells, direct cytotoxicity against host cells, inflammatory response-induced immune injury, and immune evasion. The increasing rate of macrolide-resistant strains and the harmful side effects of other sensitive antibiotics (e.g., respiratory quinolones and tetracyclines) in young children make it difficult to treat, and increase the health risk or re-infections. Hence, there is an urgent need for development of an effective vaccine to prevent M. pneumoniae infections in children. Various types of M. pneumoniae vaccines have been reported, including whole-cell vaccines (inactivated and live-attenuated vaccines), subunit vaccines (involving M. pneumoniae protein P1, protein P30, protein P116 and CARDS toxin) and DNA vaccines. This narrative review summarizes the key pathogenic mechanisms underlying M. pneumoniae infection and highlights the relevant vaccines that have been developed and their reported effectiveness.
Pulmonary Barotrauma Resulting from Mechanical Ventilation in 2 Patients with a Diagnosis of COVID-19 Pneumonia

Case series Patients: Male, 71-year-old • Female, 58-year-old Final Diagnosis: Pulmonary barotrauma Symptoms: Pneumomediastinum Medication: — Clinical Procedure: Chest tube Specialty: Critical Care Medicine Objective: Unusual clinical course Background: Invasive mechanical ventilation can cause pulmonary barotrauma due to elevated transpulmonary pressure and alveolar rupture. A significant proportion of COVID-19 patients with acute respiratory distress syndrome (ARDS) will require mechanical ventilation. We present 2 interesting cases that demonstrate the possibility of COVID-19-associated ARDS manifesting with pulmonary barotrauma at acceptable ventilatory pressures. Case Reports: The first patient was a 71-year-old man who was intubated and placed on mechanical ventilation due to hypoxemic respiratory failure from SARS-CoV-2 infection. His partial pressure of O2 to fraction of inspired oxygen ratio (PaO2/FiO2) was 156. He developed subcutaneous emphysema (SE) and pneumomediastinum on day 5 of mechanical ventilation at ventilatory settings of positive end-expiratory pressure (PEEP) ≤15 cmH2O, plateau pressure (Pplat) ≤25 cmH2O and pulmonary inspiratory pressure (PIP) ≤30 cmH2O. He was managed with ‘blow-hole’ incisions, with subsequent clinical resolution of subcutaneous emphysema. The second patient was a 58-year-old woman who was also mechanically ventilated due to hypoxemic respiratory failure from COVID-19, with PaO2/FiO2 of 81. She developed extensive SE with pneumomediastinum and pneumothorax while on mechanical ventilation settings PEEP 13 cmH2O and PIP 28 cmH2O, Pplat 18 cmH2O, and FiO2 90%. SE was managed with blow-hole incisions and pneumothorax with chest tube. Conclusions: Clinicians should be aware of pulmonary barotrauma as a possible complication of COVID-19 pulmonary disease, even at low ventilatory pressures.
Interleukin-1β Induced Matrix Metalloproteinase Expression in Human Periodontal Ligament-Derived Mesenchymal Stromal Cells under In Vitro Simulated Static Orthodontic Forces

The periodontal ligament (PDL) responds to applied orthodontic forces by extracellular matrix (ECM) remodeling, in which human periodontal ligament-derived mesenchymal stromal cells (hPDL-MSCs) are largely involved by producing matrix metalloproteinases (MMPs) and their local inhibitors (TIMPs). Apart from orthodontic forces, the synthesis of MMPs and TIMPs is influenced by the aseptic inflammation occurring during orthodontic treatment. Interleukin (IL)-1β is one of the most abundant inflammatory mediators in this process and crucially affects the expression of MMPs and TIMPs in the presence of cyclic low-magnitude orthodontic tensile forces. In this study we aimed to investigate, for the first time, how IL-1β induced expression of MMPs, TIMPs and how IL-1β in hPDL-MSCs was changed after applying in vitro low-magnitude orthodontic tensile strains in a static application mode. Hence, primary hPDL-MSCs were stimulated with IL-1β in combination with static tensile strains (STS) with 6% elongation. After 6- and 24 h, MMP-1, MMP-2, TIMP-1 and IL-1β expression levels were measured. STS alone had no influence on the basal expression of investigated target genes, whereas IL-1β caused increased expression of these genes. In combination, they increased the gene and protein expression of MMP-1 and the gene expression of MMP-2 after 24 h. After 6 h, STS reduced IL-1β-induced MMP-1 synthesis and MMP-2 gene expression. IL-1β-induced TIMP-1 gene expression was decreased by STS after 6- and 24-h. At both time points, the IL-1β-induced gene expression of IL-1β was increased. Additionally, this study showed that fetal bovine serum (FBS) caused an overall suppression of IL-1β-induced expression of MMP-1, MMP-2 and TIMP-1. Further, it caused lower or opposite effects of STS on IL-1β-induced expression. These observations suggest that low-magnitude orthodontic tensile strains may favor a more inflammatory and destructive response of hPDL-MSCs when using a static application form and that this response is highly influenced by the presence of FBS in vitro.
Istradefylline – a first generation adenosine A2A antagonist for the treatment of Parkinson’s disease

ABSTRACT Introduction It is now accepted that Parkinson’s disease (PD) is not simply due to dopaminergic dysfunction, and there is interest in developing non-dopaminergic approaches to disease management. Adenosine A2A receptor antagonists represent a new way forward in the symptomatic treatment of PD. Areas covered In this narrative review, we summarize the literature supporting the utility of adenosine A2A antagonists in PD with a specific focus on istradefylline, the most studied and only adenosine A2A antagonist currently in clinical use. Expert opinion: At this time, the use of istradefylline in the treatment of PD is limited to the management of motor fluctuations as supported by the results of randomized clinical trials and evaluation by Japanese and USA regulatory authorities. The relatively complicated clinical development of istradefylline was based on classically designed studies conducted in PD patients with motor fluctuations on an optimized regimen of levodopa plus adjunctive dopaminergic medications. In animal models, there is consensus that a more robust effect of istradefylline in improving motor function is produced when combined with low or threshold doses of levodopa rather than with high doses that produce maximal dopaminergic improvement. Exploration of istradefylline as a ‘levodopa sparing’ strategy in earlier PD would seem warranted.
Forensic analysis of anabolic steroids tablets composition using attenuated total reflection Fourier transform infrared microspectroscopy (µATR‐FTIR) mapping

The use of falsified and unregistered drugs is a worldwide public health problem. Because these global market products usually do not follow the Good Manufacturing Practices required by health legislation, its composition may be completely different from the original or may contain relevant concentrations of impurities and toxic contaminants. Since anabolic steroids are among the main irregular therapeutic classes seized in Brazil, here we propose a new methodology for analyzing these products, in tablets form, using Attenuated Total Reflection Fourier Transform Infrared Microspectroscopy (µATR‐FTIR) mapping. Spectra were acquired from solid tablets by attenuated total reflection, through point mapping methodology. In data processing, a characteristic absorption band for each Active Pharmaceutical Ingredient (API) was integrated and plotted to create its distribution map. This technique was applied in an unprecedented way for the forensic analysis of anabolic steroids and proved to be effective in distinguishing falsified products based on the detection of their APIs. It was possible to detect APIs in 26 out of 30 samples, five of which were classified as falsified only through µATR‐FTIR analysis. We were able to create distribution maps of the detected substances associating the microspectroscopic results with characteristic band integration method, which can be used to detect substances and to study samples’ homogeneity. We concluded that this methodology is promising for the analysis of anabolic steroid tablets, and can be used in a complementary way with techniques already consolidated in forensic laboratory routine for a better classification of questioned samples between authentic and falsified ones.
Trends in Outbreak-Associated Cases of COVID-19 — Wisconsin, March–November 2020

During September 3-November 16, 2020, daily confirmed cases of coronavirus disease 2019 (COVID-19) reported to the Wisconsin Department of Health Services (WDHS) increased at a rate of 24% per week, from a 7-day average of 674 (August 28-September 3) to 6,426 (November 10-16) (1). The growth rate during this interval was the highest to date in Wisconsin and among the highest in the United States during that time (1). To characterize potential sources of this increase, the investigation examined reported outbreaks in Wisconsin that occurred during March 4-November 16, 2020, with respect to their setting and number of associated COVID-19 cases.
Spatial–Temporal Distribution Variation of Ground-Level Ozone in China’s Pearl River Delta Metropolitan Region

Long-term exposure to ozone pollution will cause severe threats to residents’ physical and mental health. Ground-level ozone is the most severe air pollutant in China’s Pearl River Delta Metropolitan Region (PRD). It is of great significance to accurately reveal the spatial–temporal distribution characteristics of ozone pollution exposure patterns. We used the daily maximum 8-h ozone concentration data from PRD’s 55 air quality monitoring stations in 2015 as input data. We used six models of STK and ordinary kriging (OK) for the simulation of ozone concentration. Then we chose a better ozone pollution prediction model to reveal the ozone exposure characteristics of the PRD in 2015. The results show that the Bilonick model (BM) model had the highest simulation precision for ozone in the six models for spatial–temporal kriging (STK) interpolation, and the STK model’s simulation prediction results are significantly better than the OK model. The annual average ozone concentrations in the PRD during 2015 showed a high spatial variation in the north and east and low in the south and west. Ozone concentrations were relatively high in summer and autumn and low in winter and spring. The center of gravity of ozone concentrations tended to migrate to the north and west before moving to the south and then finally migrating to the east. The ozone’s spatial autocorrelation was significant and showed a significant positive correlation, mainly showing high-high clustering and low-low clustering. The type of clustering undergoes temporal migration and conversion over the four seasons, with spatial autocorrelation during winter the most significant.
Baseline T cell immune phenotypes predict virologic and disease control upon SARS-CoV infection in Collaborative Cross mice

The COVID-19 pandemic has revealed that infection with SARS-CoV-2 can result in a wide range of clinical outcomes in humans. An incomplete understanding of immune correlates of protection represents a major barrier to the design of vaccines and therapeutic approaches to prevent infection or limit disease. This deficit is largely due to the lack of prospectively collected, pre-infection samples from individuals that go on to become infected with SARS-CoV-2. Here, we utilized data from genetically diverse Collaborative Cross (CC) mice infected with SARS-CoV to determine whether baseline T cell signatures are associated with a lack of viral control and severe disease upon infection. SARS-CoV infection of CC mice results in a variety of viral load trajectories and disease outcomes. Overall, a dysregulated, pro-inflammatory signature of circulating T cells at baseline was associated with severe disease upon infection. Our study serves as proof of concept that circulating T cell signatures at baseline can predict clinical and virologic outcomes upon SARS-CoV infection. Identification of basal immune predictors in humans could allow for identification of individuals at highest risk of severe clinical and virologic outcomes upon infection, who may thus most benefit from available clinical interventions to restrict infection and disease.
Hedgehog Signaling in Colorectal Cancer: All in the Stroma?

Hedgehog (Hh) signaling regulates intestinal development and homeostasis. The role of Hh signaling in cancer has been studied for many years; however, its role in colorectal cancer (CRC) remains controversial. It has become increasingly clear that the “canonical” Hh pathway, in which ligand binding to the receptor PTCH1 initiates a signaling cascade that culminates in the activation of the GLI transcription factors, is mainly organized in a paracrine manner, both in the healthy colon and in CRC. Such canonical Hh signals largely act as tumor suppressors. In addition, stromal Hh signaling has complex immunomodulatory effects in the intestine with a potential impact on carcinogenesis. In contrast, non-canonical Hh activation may have tumor-promoting roles in a subset of CRC tumor cells. In this review, we attempt to summarize the current knowledge of the Hh pathway in CRC, with a focus on the tumor-suppressive role of canonical Hh signaling in the stroma. Despite discouraging results from clinical trials using Hh inhibitors in CRC and other solid cancers, we argue that a more granular understanding of Hh signaling might allow the exploitation of this key morphogenic pathway for cancer therapy in the future.
Effect of Mn Doping on the Dielectric and Electrical Conductivity of CaBi4Ti4O15 Ceramics

Ca1-xMnxBi4Ti4O15 (CMBT) ceramics were prepared using solid state reaction method with x = 0 to 0.3. X-ray diffraction confirms the orthorhombic structure of CMBT ceramics. FTIR and Raman spectroscopy study indicates the formation of single phase layered perovskite material. Thermo-gravimetric studies shows that the thermal decomposition of carbonates was completed at 700°C for Mn doped samples whereas was 950°C for CaBi4Ti4O15 ceramic. DC conductivity exhibits non-Arrhenius behaviour and the activation energy decrease from 1.35 to 1.0eV with increase in x from 0 to 0.3. The room temperature dielectric constant decreases from 160 to 140 at 1MHz with the increase in Mn concentration (x = 0–0.3). Curie's temperature (790°C) was found to be independent of Mn incorporation at Ca site.
Oral Human Papillomavirus Infection in Children during the First 6 Years of Life, Finland

Human papillomavirus (HPV) infections are found in children, but transmission modes and outcomes are incompletely understood. We evaluated oral samples from 331 children in Finland who participated in the Finnish Family HPV Study from birth during 9 follow-up visits (mean time 51.9 months). We tested samples for 24 HPV genotypes. Oral HPV prevalence for children varied from 8.7% (at a 36-month visit) to 22.8% (at birth), and 18 HPV genotypes were identified. HPV16 was the most prevalent type to persist, followed by HPV18, HPV33, and HPV6. Persistent, oral, high-risk HPV infection for children was associated with oral HPV carriage of the mother at birth and seroconversion of the mother to high-risk HPV during follow-up (odds ratio 1.60–1.92, 95% CI 1.02–2.74). Children acquire their first oral HPV infection at an early age. The HPV status of the mother has a major impact on the outcome of oral HPV persistence for her offspring.
Microbial metabolic response to winter warming stabilizes soil carbon

Current consensus on global climate change predicts warming trends with more pronounced temperature changes in winter than summer in the Northern Hemisphere at high latitudes. Moderate increases in soil temperature are generally related to faster rates of soil organic carbon (SOC) decomposition in Northern ecosystems, but there is evidence that SOC stocks have remained remarkably stable or even increased on the Tibetan Plateau under these conditions. This intriguing observation points to altered soil microbial mediation of carbon‐cycling feedbacks in this region that might be related to seasonal warming. This study investigated the unexplained SOC stabilization observed on the Tibetan Plateau by quantifying microbial responses to experimental seasonal warming in a typical alpine meadow. Ecosystem respiration was reduced by 17%–38% under winter warming compared with year‐round warming or no warming and coincided with decreased abundances of fungi and functional genes that control labile and stable organic carbon decomposition. Compared with year‐round warming, winter warming slowed macroaggregate turnover rates by 1.6 times, increased fine intra‐aggregate particulate organic matter content by 75%, and increased carbon stabilized in microaggregates within stable macroaggregates by 56%. Larger bacterial “necromass” (amino sugars) concentrations in soil under winter warming coincided with a 12% increase in carboxyl‐C. These results indicate the enhanced physical preservation of SOC under winter warming and emphasize the role of soil microorganisms in aggregate life cycles. In summary, the divergent responses of SOC persistence in soils exposed to winter warming compared to year‐round warming are explained by the slowing of microbial decomposition but increasing physical protection of microbially derived organic compounds. Consequently, the soil microbial response to winter warming on the Tibetan Plateau may cause negative feedbacks to global climate change and should be considered in Earth system models.
The diagnostic value of p63, p16, and p53 immunohistochemistry in distinguishing seborrheic keratosis, actinic keratosis, and Bowen's disease

Seborrheic keratosis (SK), actinic keratosis (AK), and Bowen's disease (BD) are squamoproliferative disorders of the skin. Histologically, they may mimic each other and therefore, they might be misinterpreted, especially in small samples. The aim of this study is to clarify the expression of p63, p16, and p53 proteins in SK, AK, and BD and evaluate the efficacy of these markers in order to distinguish between the aforementioned lesions. A total of 46 cases were collected (15 SK, 16 AK, and 15 BD) and stained for p63, p16, and p53. The stain intensity and the cell distribution labeling were scored and then analyzed by SPSS software. All cases of BD which became positive for p53 revealed basal keratinocytes sparing. Instead, all or nearly all basal keratinocytes in AK cases were positive for this marker. These were also seen in p16 staining results and they were between AK and BD (P = .024). Our study demonstrates p16 and p53 are useful markers in separating AK and BD according to basal keratinocytes involvement and sparing, respectively.
Lentiviral transduction facilitates RNA interference in the nematode parasite Nippostrongylus brasiliensis

Animal-parasitic nematodes have thus far been largely refractory to genetic manipulation, and methods employed to effect RNA interference (RNAi) have been ineffective or inconsistent in most cases. We describe here a new approach for genetic manipulation of Nippostrongylus brasiliensis, a widely used laboratory model of gastrointestinal nematode infection. N. brasiliensis was successfully transduced with Vesicular Stomatitis Virus glycoprotein G (VSV-G)-pseudotyped lentivirus. The virus was taken up via the nematode intestine, RNA reverse transcribed into proviral DNA, and transgene transcripts produced stably in infective larvae, which resulted in expression of the reporter protein mCherry. Improved transgene expression was achieved by incorporating the C. elegans hlh11 promoter and the tbb2 3´-UTR into viral constructs. MicroRNA-adapted short hairpin RNAs delivered in this manner were processed correctly and resulted in partial knockdown of β-tubulin isotype-1 (tbb-iso-1) and secreted acetylcholinesterase B (ache-B). The system was further refined by lentiviral delivery of double stranded RNAs, which acted as a trigger for RNAi following processing and generation of 22G-RNAs. Virus-encoded sequences were detectable in F1 eggs and third stage larvae, demonstrating that proviral DNA entered the germline and was heritable. Lentiviral transduction thus provides a new means for genetic manipulation of parasitic nematodes, including gene silencing and expression of exogenous genes.
Mind Your Goals, Mind Your Emotions: Mechanisms Explaining the Relation Between Dispositional Mindfulness and Action Crises

Action crises describe the intra-psychic conflicts people face when deliberating whether to continue pursuing or to give up a goal for which difficulties keep accumulating. Action crises lead to negative consequences such as elevated distress and depression. Less is known about their predictors. We propose mindfulness as a negative predictor of action crises because mindful people should set more autonomous goals and better regulate their emotions. Three prospective studies examined the relation between mindfulness and action crises and explored goal motivation and emotion regulation as mediators (Study 1, N = 137 students, mean age 22; Study 2, N = 79 students, mean age 24.27; Study 3, N = 236 workers, mean age 40.71). Results showed that mindfulness predicts action crises over time and that this relation is mediated by goal motivation and emotion regulation. We discuss how mindfulness can affect action crises in the phases of the Rubicon Model of goal pursuit.
Mechanistic Studies of the Antiallergic Activity of Phyllanthus amarus Schum. & Thonn. and Its Compounds

Phyllanthus amarus Schum. & Thonn. (Phyllanthaceae) is a medicinal plant that is commonly used to treat diseases such as asthma, diabetes, and anemia. This study aimed to examine the antiallergic activity of P. amarus extract and its compounds. The antiallergic activity was determined by measuring the concentration of allergy markers release from rat basophilic leukemia (RBL-2H3) cells with ketotifen fumarate as the positive control. As a result, P. amarus did not stabilize mast cell degranulation but exhibited antihistamine activity. The antihistamine activity was evaluated by conducting a competition radioligand binding assay on the histamine 1 receptor (H1R). Four compounds were identified from the high performance liquid chromatography (HPLC) analysis which were phyllanthin (1), hypophyllanthin (2), niranthin (3), and corilagin (4). To gain insights into the binding interactions of the most active compound hypophyllanthin (2), molecular docking was conducted and found that hypophyllanthin (2) exhibited favorable binding in the H1R binding site. In conclusion, P. amarus and hypophyllanthin (2) could potentially exhibit antiallergic activity by preventing the activation of the H1 receptor.