Miracle-dz/UniFAR-FTUs huggingface dataset:
Oxygen Reductases in Alphaproteobacterial Genomes: Physiological Evolution From Low to High Oxygen Environments

Oxygen reducing terminal oxidases differ with respect to their subunit composition, heme groups, operon structure, and affinity for O2. Six families of terminal oxidases are currently recognized, all of which occur in alphaproteobacterial genomes, two of which are also present in mitochondria. Many alphaproteobacteria encode several different terminal oxidases, likely reflecting ecological versatility with respect to oxygen levels. Terminal oxidase evolution likely started with the advent of O2 roughly 2.4 billion years ago and terminal oxidases diversified in the Proterozoic, during which oxygen levels remained low, around the Pasteur point (ca. 2 μM O2). Among the alphaproteobacterial genomes surveyed, those from members of the Rhodospirillaceae reveal the greatest diversity in oxygen reductases. Some harbor all six terminal oxidase types, in addition to many soluble enzymes typical of anaerobic fermentations in mitochondria and hydrogenosomes of eukaryotes. Recent data have it that O2 levels increased to current values (21% v/v or ca. 250 μM) only about 430 million years ago. Ecological adaptation brought forth different lineages of alphaproteobacteria and different lineages of eukaryotes that have undergone evolutionary specialization to high oxygen, low oxygen, and anaerobic habitats. Some have remained facultative anaerobes that are able to generate ATP with or without the help of oxygen and represent physiological links to the ancient proteobacterial lineage at the origin of mitochondria and eukaryotes. Our analysis reveals that the genomes of alphaproteobacteria appear to retain signatures of ancient transitions in aerobic metabolism, findings that are relevant to mitochondrial evolution in eukaryotes as well.
Effect of Premedication on the Success of Inferior Alveolar Nerve Block in Patients with Irreversible Pulpitis: A Systematic Review of the Literature

Background Failure in the provision of inferior alveolar nerve block anesthesia (IANB) is a significant problem during endodontic treatment of irreversible pulpitis. Various methodologies have been advocated one of which is administration of premedication prior to anesthesia. Despite the considerable number of reports, the topic yet deserves more clarification. This systematic review was conducted to provide an oversight on the effectiveness of premedication prior to IANB in mandibular teeth. Methods A PubMed and Cochrane Database search was conducted by using MeSH terms inferior alveolar nerve block + pulpitis and mandibular anesthesia+pulpitis. Two reviewers independently performed the screening, selection of papers, and data extraction. Papers in English language that included randomized clinical studies on the impact of different medications on the success of inferior alveolar block anesthesia in irreversible pulpitis were included. Additionally, relevant supporting literature was also used where necessary. Results Initially, 118 papers were selected from PubMed and 68 were selected from Cochrane. Five additional articles were retrieved from Google Search. Following the elimination of duplicates and irrelevant articles, 35 studies were selected meeting the criteria. It was observed that there was moderate evidence to suggest that some premedications were partially effective for the enhancement of mandibular anesthetic effect in irreversible pulpitis. Conclusion Though some medications appear to be promising, further supporting research will help highlight this significant topic which requires further clarification.
Deciphering the Pharmacological Mechanism of the Herb Radix Ophiopogonis in the Treatment of Nasopharyngeal Carcinoma by Integrating iTRAQ-Coupled 2-D LC-MS/MS Analysis and Network Investigation

The herb Radix Ophiopogonis (RO) has been used effectively to treat nasopharyngeal carcinoma (NPC) as an adjunctive therapy. Due to the complexity of the traditional Chinese herbs, the pharmacological mechanism of RO’s action on NPC remains unclear. To address this problem, an integrative approach bridging proteome experiments with bioinformatics prediction was employed. First, differentially expressed protein profile from NPC serum samples was established using isobaric tag for relative and absolute quantification (iTRAQ) coupled 2-D liquid chromatography (LC)-MS/MS analysis. Second, the RO putative targets were predicted using Traditional Chinese Medicines Integrated Database and known therapeutic targets of NPC were collected from Drugbank and OMIM databases. Then, a network between RO putative targets and NPC known therapeutic targets was constructed. Third, based on pathways enrichment analysis, an integrative network was constructed using DAVID and STRING database in order to identify potential candidate targets of RO against NPC. As a result, we identified 13 differentially expressed proteins from clinical experiments compared with the healthy control. And by bioinformatics investigation, 12 putative targets of RO were selected. Upon interactions between experimental and predicted candidate targets, we identified three key candidate targets of RO against NPC: VEGFA, TP53, and HSPA8, by calculating the nodes’ topological features. In conclusion, this integrative pharmacology-based analysis revealed the anti-NPC effects of RO might be related to its regulatory impact via the PI3K-AKT signaling pathway, the Wnt signaling pathway, and the cAMP signaling pathway by targeting VEGFA, TP53, and HSPA8. The findings of potential key targets may provide new clues for NPC’s treatments with the RO adjunctive therapy.
Magnitude of Biofilm Formation and Antimicrobial Resistance Pattern of Bacteria Isolated from Urinary Catheterized Inpatients of Jimma University Medical Center, Southwest Ethiopia

Biofilm formation is one of the features of most bacteria. Catheterization in medicine is a source of highly resistant bacterial infections, and those bacteria respond poorly to antimicrobial therapy. Bacterial biofilm features were not described from catheterized inpatients in Ethiopia as its formation is known to afford antimicrobial resistance and challenge patient management. The aim of this study was to isolate catheter-associated urinary bacterial pathogens, their biofilm formation, and antimicrobial susceptibility pattern among inpatients of Jimma University Medical Center (JUMC) in Southwest Ethiopia. A prospective cross-sectional study was conducted among urinary catheterized inpatients of JUMC from February to August 2016. A total of 143 study participants were enrolled consecutively in this study. Urine samples were collected from catheterized patients and processed using a standard bacteriological protocol for isolation and identification. Evaluation of in vitro biofilm formation and antimicrobial susceptibility pattern of uropathogenic bacteria was done using microtiter plates and disk diffusion method, respectively. Data were cleaned, coded, and entered into SPSS version 20 for analysis. All statistical test values of p < 0.05 were considered statistically significant. From all study participants, mean age was 44 years. Sixty bacterial strains were recovered from 57 urinary catheterized inpatients among which 54 of them were monomicrobial (94.7%). The remaining six bacterial strains were recovered from three study participants each with two bacterial isolates. The predominant bacterial isolates were Gram-negative bacteria with E. coli turning out first. About 80% of bacterial isolates were biofilm formers. The majority of the bacteria were resistant to commonly prescribed antimicrobial agents. In conclusion, the majority of bacterial uropathogen isolates were Gram-negative, biofilm formers, and resistant to commonly prescribed antimicrobial agents. Relatively ciprofloxacin, nitrofurantoin, and amikacin were highly effective against most isolated bacteria.
The Capsule Depolymerase Dpo48 Rescues Galleria mellonella and Mice From Acinetobacter baumannii Systemic Infections

The emergence of multidrug- and extensively drug-resistant Acinetobacter baumannii has made it difficult to treat and control infections caused by this bacterium. Thus, alternatives to conventional antibiotics for management of severe A. baumannii infections is urgently needed. In our previous study, we found that a capsule depolymerase Dpo48 could strip bacterial capsules, and the non-capsuled A. baumannii were significantly decreased in the presence of serum complement in vitro. Here, we further explored its potential as a therapeutic agent for controlling systemic infections caused by extensively drug-resistant A. baumannii. Prior to mammalian studies, the anti-virulence efficacy of Dpo48 was first tested in a Galleria mellonella infection model. Survival rate of Dpo48-pretreated bacteria or Dpo48 treatment group was significantly increased compared to the infective G. mellonella without treatment. Furthermore, the safety and therapeutic efficacy of Dpo48 to mice were evaluated. The mice treated with Dpo48 displayed normal serum levels of TBIL, AST, ALT, ALP, Cr, BUN and LDH, while no significant histopathology changes were observed in tissues of liver, spleen, lung, and kidney. Treatment with Dpo48 could rescue normal and immunocompromised mice from lethal peritoneal sepsis, with the bacterial counts in blood, liver, spleen, lung, and kidney significantly reduced by 1.4–3.3 log colony-forming units at 4 h posttreatment. Besides, the hemolysis and cytotoxicity assays showed that Dpo48 was non-homolytic to human red blood cells and non-toxic to human lung, liver and kidney cell lines. Overall, the present study demonstrated the promising potential of capsule depolymerases as therapeutic agents to prevent antibiotic-resistant A. baumannii infections.
Monthly Intramuscular Neridronate for the Treatment of Postmenopausal Osteoporosis: Results of a 6-Year Prospective Italian Study

Purpose Oral bisphosphonates (BPs) are the most commonly used medications for osteoporosis (OP), but their poor gastrointestinal (GI) absorption and tolerance hamper compliance. Intramuscular (IM) neridronate (NE), an amino-BP, is an easy-to-administer, effective, and safe alternative to oral BPs. We assessed the 6-year effects of monthly IM NE on bone mineral density (BMD) and bone turnover biomarkers (BMs) in postmenopausal OP. Methods This single-center, prospective study enrolled postmenopausal osteoporotic outpatients with gastric intolerance to BPs (based on Tuscany Region's law GRT n. 836 20/10/2008). They received 25 mg IM NE once a month (with vitamin D and calcium if necessary) for 6 years. BMD was evaluated at lumbar spine (L1-L4), femoral neck (FN), and total femur (TF) at baseline (BL) and every 12 months afterwards. At BL, month 3, and every 12 months after BL, total and ionized calcium, vitamin D, parathyroid hormone 1-84, bone alkaline phosphatase (BALP), osteocalcin, and N- and C-terminal telopeptides were assayed. Results Overall, 60 women (mean age: 62.3 ± 7.5 years) received monthly IM NE for 6 years, with vitamin D and calcium supplementation in 81.3% of cases. Compared to BL, BMD increased significantly already after 1 year at all sites (4.5 ± 0.9% for L1-L4, 4.5 ± 0.8% for TF, and 2.1 ± 0.6% for FN, P ≤ 0.05), and the changes were maintained over time, whereas FN further improved up to year 3 and remained stable afterwards (P ≤ 0.05). All BMs, except for total calcium and BALP, progressively decreased over time (P ≤ 0.05). No fractures and significant adverse events were reported. Conclusion The monthly administration of IM NE represents a manageable and effective option, in terms of BMD and bone BM improvement, for the long-term treatment of postmenopausal OP women with gastric intolerance to BPs. This trial is registered with ClinicalTrials.gov Identifier: NCT03699150.
Predicting Known Sentences: Neural Basis of Proverb Reading Using Non-parametric Statistical Testing and Mixed-Effects Models

Predictions of future events play an important role in daily activities, such as visual search, listening, or reading. They allow us to plan future actions and to anticipate their outcomes. Reading, a natural, commonly studied behavior, could shed light over the brain processes that underlie those prediction mechanisms. We hypothesized that different mechanisms must lead predictions along common sentences and proverbs. The former ones are more based on semantic and syntactic cues, and the last ones are almost purely based on long-term memory. Here we show that the modulation of the N400 by Cloze-Task Predictability is strongly present in common sentences, but not in proverbs. Moreover, we present a novel combination of linear mixed models to account for multiple variables, and a cluster-based permutation procedure to control for multiple comparisons. Our results suggest that different prediction mechanisms are present during reading.
Comparative Immunopathology of Cetacean morbillivirus Infection in Free-Ranging Dolphins From Western Mediterranean, Northeast-Central, and Southwestern Atlantic

Cetacean morbillivirus (CeMV; Paramyxoviridae) causes epizootic and interepizootic fatalities in odontocetes and mysticetes worldwide. Studies suggest there is different species-specific susceptibility to CeMV infection, with striped dolphins (Stenella coeruleoalba), bottlenose dolphins (Tursiops truncatus), and Guiana dolphins (Sotalia guianensis) ranking among the most susceptible cetacean hosts. The pathogenesis of CeMV infection is not fully resolved. Since no previous studies have evaluated the organ-specific immunopathogenetic features of CeMV infection in tissues from infected dolphins, this study was aimed at characterizing and comparing immunophenotypic profiles of local immune responses in lymphoid organs (lymph nodes, spleen), lung and CNS in CeMV-molecularly (RT-PCR)-positive cetaceans from Western Mediterranean, Northeast-Central, and Southwestern Atlantic. Immunohistochemical (IHC) analyses targeted molecules of immunologic interest: caspase 3, CD3, CD20, CD57, CD68, FoxP3, MHCII, Iba1, IFNγ, IgG, IL4, IL10, lysozyme, TGFβ, and PAX5. We detected consistent CeMV-associated inflammatory response patterns. Within CNS, inflammation was dominated by CD3+ (T cells), and CD20+ and PAX5+ (B cells) lymphocytes, accompanied by fewer Iba1+, CD68+, and lysozyme+ histiocytes, mainly in striped dolphins and bottlenose dolphins. Multicentric lymphoid depletion was characterized by reduced numbers of T cells and B cells, more pronounced in Guiana dolphins. Striped dolphins and bottlenose dolphins often had hyperplastic (regenerative) phenomena involving the aforementioned cell populations, particularly chronically infected animals. In the lung, there was mild to moderate increase in T cells, B cells, and histiocytes. Additionally, there was a generalized increased expression of caspase 3 in lymphoid, lung, and CNS tissues. Apoptosis, therefore, is believed to play a major role in generalized lymphoid depletion and likely overt immunosuppression during CeMV infection. No differences were detected regarding cytokine immunoreactivity in lymph nodes, spleen, and lung from infected and non-infected dolphins by semiquantitative analysis; however, there was striking immunoreactivity for IFNγ in the CNS of infected dolphins. These novel results set the basis for tissue-specific immunophenotypic responses during CeMV infection in three highly susceptible delphinid species. They also suggest a complex interplay between viral and host's immune factors, thereby contributing to gain valuable insights into similarities, and differences of CeMV infection's immunopathogenesis in relation to body tissues, CeMV strains, and cetacean hosts.
Glucocorticoid Receptor-Deficient Foxp3+ Regulatory T Cells Fail to Control Experimental Inflammatory Bowel Disease

Activation of the immune system increases systemic adrenal-derived glucocorticoid (GC) levels which downregulate the immune response as part of a negative feedback loop. While CD4+ T cells are essential target cells affected by GC, it is not known whether these hormones exert their major effects on CD4+ helper T cells, CD4+Foxp3+ regulatory T cells (Treg cells), or both. Here, we generated mice with a specific deletion of the glucocorticoid receptor (GR) in Foxp3+ Treg cells. Remarkably, while basal Treg cell characteristics and in vitro suppression capacity were unchanged, Treg cells lacking the GR did not prevent the induction of inflammatory bowel disease in an in vivo mouse model. Under inflammatory conditions, GR-deficient Treg cells acquired Th1-like characteristics and expressed IFN-gamma, but not IL-17, and failed to inhibit pro-inflammatory CD4+ T cell expansion in situ. These findings reveal that the GR is critical for Foxp3+ Treg cell function and suggest that endogenous GC prevent Treg cell plasticity toward a Th1-like Treg cell phenotype in experimental colitis. When equally active in humans, a rationale is provided to develop GC-mimicking therapeutic strategies which specifically target Foxp3+ Treg cells for the treatment of inflammatory bowel disease.
The Use of Titanium Mesh in Guided Bone Regeneration: A Systematic Review

Several techniques have been proposed for bone regeneration in patients with atrophic ridges. Nowadays, GBR represents the gold standard, and it allows obtaining sufficient bone volumes for a correct implant-prosthetic rehabilitation. Our goal is to perform a systematic review of the literature on the use of titanium meshes in GBR in order to evaluate the reliability of the procedure, the regeneration obtained, and the failures. Furthermore, we will evaluate the success and survival rate of the inserted implants. The selected articles concern vertical and/or horizontal regeneration of the alveolar ridge using titanium grids, in association or not with biomaterials, before and simultaneously with implant placement. Six articles were selected for the present review, including a total of 139 patients, 156 sites, and 303 implants. Titanium grids in combination with autogenous bone were used in 2 cases, 5 in combination with a mixture of autogenous bone and bone substitutes. The overall survival and success rates of implants were 98.3% and 85.25%, respectively. In conclusion, our review shows how the use of titanium mesh represented a predictable method for the rehabilitation of complex atrophic sites.
Electromagnetic Brain Stimulation in Patients With Disorders of Consciousness

Severe brain injury is a common cause of coma. In some cases, despite vigilance improvement, disorders of consciousness (DoC) persist. Several states of impaired consciousness have been defined, according to whether the patient exhibits only reflexive behaviors as in the vegetative state/unresponsive wakefulness syndrome (VS/UWS) or purposeful behaviors distinct from reflexes as in the minimally conscious state (MCS). Recently, this clinical distinction has been enriched by electrophysiological and neuroimaging data resulting from a better understanding of the physiopathology of DoC. However, therapeutic options, especially pharmacological ones, remain very limited. In this context, electroceuticals, a new category of therapeutic agents which act by targeting the neural circuits with electromagnetic stimulations, started to develop in the field of DoC. We performed a systematic review of the studies evaluating therapeutics relying on the direct or indirect electro-magnetic stimulation of the brain in DoC patients. Current evidence seems to support the efficacy of deep brain stimulation (DBS) and non-invasive brain stimulation (NIBS) on consciousness in some of these patients. However, while the latter is non-invasive and well tolerated, the former is associated with potential major side effects. We propose that all chronic DoC patients should be given the possibility to benefit from NIBS, and that transcranial direct current stimulation (tDCS) should be preferred over repetitive transcranial magnetic stimulation (rTMS), based on the literature and its simple use. Surgical techniques less invasive than DBS, such as vagus nerve stimulation (VNS) might represent a good compromise between efficacy and invasiveness but still need to be further investigated.
Microbiological study of vendor and packed fruit juices locally available in Dhaka city, Bangladesh

Present investigation attempted to resolve the microbiological attributes of the fruit juices collected from different areas around Dhaka city. Twenty six vendor fruit juices and 15 packed juices were examined for the presence of total bacterial load, coliforms and staphylococci. Samples were found to harbor viable bacteria within the range between 10 2 -10 7 cfu/ml. Thirty samples exhibited the presence of staphylococci. Total coliforms were detected in 31 samples within the range of 10 2 -10 6 cfu/ml which were further detected as Escherichia coli and Klebsiella spp. Fecal coliforms were found in 4 vendor fruit juice samples (10 2 cfu/ ml), while in the industrially packed samples, they were completely absent. Drug resistance among the isolates was found against ampicillin, ciprofloxacin, amoxicillin, erythromycin, chloramphenicol, ceftriaxone, piperaciline, trimethoprime-sulfomethoxazole, nalidixic acid and vancomycin. Overall, the study demonstrates that the quality of the both packed and fresh juices was unsatisfactory and hence the products need to be microbiologically controlled in order to ensure the overall health safety.