Miracle-dz/UniFAR-FTUs huggingface dataset:
Anaerobic degradation of paraffins by thermophilic Actinobacteria under methanogenic conditions.

Microbial anaerobic alkane degradation is a key process in subsurface oil reservoirs and anoxic environments contaminated with petroleum, with a major impact on global carbon cycling. However, the thermophiles capable of water-insoluble paraffins (>C17) degradation under methanogenic conditions has remained understudied. Here, we established thermophilic (55 °C) n-paraffins-degrading (C21-C30) cultures from an oil reservoir. After over 900 days of incubation, the even-numbered n-paraffins were biodegraded to methane. The bacterial communities are dominated by a novel class-level lineage of Actinobacteria, 'Candidatus Syntraliphaticia'. These 'Ca. Syntraliphaticia'-like metagenome-assembled genomes (MAGs) encode a complete alkylsuccinate synthases (ASS) gene operon, as well as hydrogenases and formate dehydrogenase, and several enzymes potentially involved in alkyl-CoA oxidation and the Wood-Ljungdahl pathway. Metatranscriptomic analysis suggests that n-paraffins are activated via fumarate addition reaction, and oxidized into carbon dioxide, hydrogen/formate and acetate by 'Ca. Syntraliphaticia', that could be further converted to methane by the abundant hydrogenotrophic and acetoclastic methanogens. We also found a divergent methyl-CoM reductase-like complex (MCR) and a canonical MCR in two MAGs representing 'Ca. Methanosuratus' (within candidate phylum Verstraetearchaeota), indicating the capability of methane and short-chain alkane metabolism in the oil reservoir. Ultimately, this result offers new insights into the degradability and the mechanisms of n-paraffins under methanogenic conditions at high temperatures.
The Cleft Nurse Specialist: A Key Building Block in the Cleft Multidisciplinary Team

Introduction: The cleft nurse specialist (CNS) plays a key role in counselling and supporting parents from the diagnosis onward. The CNS started in 2012 and we aimed to perform a qualitative study to determine the benefits this brought to the cleft community from the parents’ perspective. Methods: The cleft database was used to locate babies born in 2010/2011 and 2013/2014. Parents were contacted by phone by 2 authors and completed a questionnaire on the care and support they received following the diagnosis, in the early days and around the time of surgery. Results: Parents of 38 babies completed the survey. In 2010/2011, only 21% had an antenatal diagnosis compared to 47% in 2013/2014. 2011/2012: 3 unilateral cleft lip and palate (UCLP), 3 bilateral cleft lip and palate (BCLP), 4 CLO, 9 cleft palate only (CPO). 2013/2014: 5 UCLP, 7 BCLP, 7 CPO. 2011/2012: 68% were counselled by a surgeon, 42% were seen >1 week after birth, with some over a month. 2013/2014: 84% were counselled by the CNS, 53% were seen within 48 hours, and 100% within 7 days. Parents in 2013/2014 felt more supported by the cleft team throughout pregnancy and the early days, with home visits being particularly advantageous. Conclusion: The introduction of the CNS to the cleft multidisciplinary team has significantly improved the pathway for parents and is a key link with the wider cleft team. With the improvement in antenatal diagnosis, counselling occurs at an earlier stage and prepares parents for the difficulties commonly experienced in the early days. Key themes included; home visits and direct contact with the CNS.
Assessment of Anxiety in Long-Term Care Residents: Issues and Strategies

The experience of clinically significant anxiety and anxiety disorders represent significant and often debilitating problems for many residents in long-term care (LTC) settings. However, anxiety problems often go undetected and untreated in this growing population. The purposes of this paper are to examine the prevalence and impact of anxiety problems among residents in LTC facilities, describe the efficacy of the current instruments that are used to detect anxiety in these settings, and provide clinical guidance for the thorough assessment of anxiety. Regarding measurement tools, the GAI, GAI-SF, GAS-LTC, and the BADS are the only self-report measures designed for older adults that have been successfully validated for use with older adults living in LTC settings. Clinicians should focus on ways to educate LTC directors and staff to emphasize the importance of screening and assessing for anxiety, using validated measures, to improve the assessment and treatment of anxiety in their residents.
Thrombolysis in acute stroke under dual antiplatelet therapy: perspectives arising from translational studies

We have recently established a mouse model of focal stroke under dual antiplatelet therapy (DAPT) to study tissue plasminogen activator (tPA)-associated hemorrhagic transformation. The purpose of this short perspective is to discuss the rationale for establishing the model, highlighting its relevance for addressing unresolved clinical questions. Hemorrhagic conversion of the ischemic stroke remains one of the major liabilities of thrombolytic therapy with tPA, contributing to unfavorable outcomes and failed regeneration. This was recognized early on, and the resulting restrictions on tPA usage have led to only a minor percentage of stroke patients receiving any kind of drug treatment to limit ischemic injury. Broadening the patient population eligible for thrombolytic therapy is a major goal, and thus efforts are being directed at optimally defining inclusion criteria based on prior drug treatment status, among other factors. DAPT with aspirin and clopidogrel (ASA + CPG) is commonly given to patients at high risk for atherothrombotic events. However, clinical data to date has not been entirely clear as to whether the increased likelihood of bleeding following thrombolysis in patients on DAPT is indeed detrimental to patient outcome, and many see this potential downside outweighed by the benefits of recanalization of the blocked vessel. Accordingly, current guidelines allow for tPA thrombolysis in patients under DAPT. Nonetheless, doubts remain if on balance tPA is actually beneficial in these patients, and these doubts may lead to undertreatment. Final clarity might be achieved with a prospective, randomized clinical trial, but it appears unlikely that this will ever occur. In this situation, modeling the process in animals subjected to experimental ischemic stroke under DAPT can provide insights into mechanisms of hemorrhagic transformation (HT). Even more importantly, e s t a b l i s h i n g s u c h a m o d e l e n a b l e s researchers to test possible strategies to mitigate the bleeding risk in patients on DAPT. If the safety of tPA thrombolysis can be increased by reducing hemorrhage, this could clearly tilt the balance towards favoring tPA treatment, and thus improve long-term outcomes of ischemic strokes. Testing such an approach in the animal model is the best first step in evaluating the utility of such an adjuvant.
Metabolism of Gallic Acid and Its Distributions in Tea (Camellia sinensis) Plants at the Tissue and Subcellular Levels

In tea (Camellia sinensis) plants, polyphenols are the representative metabolites and play important roles during their growth. Among tea polyphenols, catechins are extensively studied, while very little attention has been paid to other polyphenols such as gallic acid (GA) that occur in tea leaves with relatively high content. In this study, GA was able to be transformed into methyl gallate (MG), suggesting that GA is not only a precursor of catechins, but also can be transformed into other metabolites in tea plants. GA content in tea leaves was higher than MG content—regardless of the cultivar, plucking month or leaf position. These two metabolites occurred with higher amounts in tender leaves. Using nonaqueous fractionation techniques, it was found that GA and MG were abundantly accumulated in peroxisome. In addition, GA and MG were found to have strong antifungal activity against two main tea plant diseases, Colletotrichum camelliae and Pseudopestalotiopsis camelliae-sinensis. The information will advance our understanding on formation and biologic functions of polyphenols in tea plants and also provide a good reference for studying in vivo occurrence of specialized metabolites in economic plants.
The cellular origins of cancer with particular reference to the gastrointestinal tract

Stem cells or their closely related committed progenitor cells are the likely founder cells of most neoplasms. In the continually renewing and hierarchically organized epithelia of the oesophagus, stomach and intestine, homeostatic stem cells are located at the beginning of the cell flux, in the basal layer of the oesophagus, the isthmic region of gastric oxyntic glands and at the bottom of gastric pyloric‐antral glands and colonic crypts. The introduction of mutant oncogenes such as KrasG12D or loss of Tp53 or Apc to specific cell types expressing the likes of Lgr5 and Mist1 can be readily accomplished in genetically engineered mouse models to initiate tumorigenesis. Other origins of cancer are discussed including ‘reserve’ stem cells that may be activated by damage or through disruption of morphogen gradients along the crypt axis. In the liver and pancreas, with little cell turnover and no obvious stem cell markers, the importance of regenerative hyperplasia associated with chronic inflammation to tumour initiation is vividly apparent, though inflammatory conditions in the renewing populations are also permissive for tumour induction. In the liver, hepatocytes, biliary epithelial cells and hepatic progenitor cells are embryologically related, and all can give rise to hepatocellular carcinoma and cholangiocarcinoma. In the exocrine pancreas, both acinar and ductal cells can give rise to pancreatic ductal adenocarcinoma (PDAC), although the preceding preneoplastic states are quite different: acinar‐ductal metaplasia gives rise to pancreatic intraepithelial neoplasia culminating in PDAC, while ducts give rise to PDAC via. mucinous cell metaplasia that may have a polyclonal origin.
Freshwater aquatic and aquaphile vertebrates from Black Crow (Ypresian/Lutetian, Namibia) and their palaeoenvironmental significance

The freshwater limestone deposits at Black Crow, Namibia, have yielded a low diversity of aquatic and aquaphile vertebrates comprising three sp cies of fishes, one frog and a crocodile. As a fauna these vertebrates suggest that, at the time o f d p sition during the Late Ypresian or Early-Midd le Lutetian, the area lay within a tropical to sub-tro pical climatic regime, and that the water bodies we re fresh, clear and well-oxygenated, contrasting with the hyper-arid conditions that prevail in the area today. One of the fishes, Hydrocynus, is exclusively African. Its Palaeogene distributi on was wider than it’s extant range, the five localities where it has been recorded occurring well outside its present-d ay range. The Black Crow occurrence of this genus is p otentially the oldest known (if the deposits are La te Ypresian).
DNA Methylation as a Therapeutic Target for Bladder Cancer

Bladder cancer (BC) is the tenth most frequent cancer worldwide and is associated with high mortality when diagnosed in its most aggressive form, which is not reverted by the current treatment options. Thus, the development of new therapeutic strategies, either alternative or complementary to the current ones, is of major importance. The disruption of normal epigenetic mechanisms, namely, DNA methylation, is a known early event in cancer development. Consequently, DNA methyltransferase (DNMT) inhibitors constitute a promising therapeutic target for the treatment of BC. Although these inhibitors, mainly nucleoside analogues such as 5-azacytidine (5-aza) and decitabine (DAC), cause re-expression of tumor suppressor genes, inhibition of tumor cell growth, and increased apoptosis in BC experimental models and clinical trials, they also show important drawbacks that prevent their use as a valuable option for the treatment of BC. However, their combination with chemotherapy and/or immune-checkpoint inhibitors could aid in their implementation in the clinical practice. Here, we provide a comprehensive review of the studies exploring the effects of DNA methylation inhibition using DNMTs inhibitors in BC, from in vitro and in vivo studies to clinical trials.
Real-Time Stress Assessment Using Sliding Window Based Convolutional Neural Network

Mental stress has been identified as a significant cause of several bodily disorders, such as depression, hypertension, neural and cardiovascular abnormalities. Conventional stress assessment methods are highly subjective and tedious and tend to lack accuracy. Machine-learning (ML)-based computer-aided diagnosis systems can be used to assess the mental state with reasonable accuracy, but they require offline processing and feature extraction, rendering them unsuitable for real-time applications. This paper presents a real-time mental stress assessment approach based on convolutional neural networks (CNNs). The CNN-based approach afforded real-time mental stress assessment with an accuracy as high as 96%, the sensitivity of 95%, and specificity of 97%. The proposed approach is compared with state-of-the-art ML techniques in terms of accuracy, time utilisation, and quality of features.
Early IL‐2 treatment of mice with Pseudomonas aeruginosa pneumonia induced PMN‐dominating response and reduced lung pathology

IL‐2 is a pro‐inflammatory and a Th1 inducing cytokine, which is important for activation of the cell‐mediated immunity. IL‐2 in serum and sputum has been observed to be reduced in cystic fibrosis (CF) patients. The present IL‐2 treatment study of Pseudomonas aeruginosa (PA) lung infected mice was performed in order to evaluate the effect of IL‐2 supplement. One hundred‐and‐twenty female BALB/c mice were divided into three groups: 1) IL‐2 treatment/infection (TIG), 2) non‐treatment/infection (NTIG), and 3) IL‐2 treatment/non‐infection (TNIG). The mice were challenged intra‐tracheally with PA (PAO579) embedded in seaweed alginate to resemble the biofilm mode of growth. At day 0 and 1, the treatment groups received IL‐2 s.c. Mice were killed on day 1 or 2, and cytokine production, lung pathology, and quantitative lung bacteriology were estimated. IL‐2 treatment of infected mice reduced the number of mice with signs of macroscopic lung pathology at day 2 (p < 0.05). The reduced macroscopic pathology was paralleled by a reduced IL‐1β and TNF‐α. In contrast, an increased PMN response at day 2 was observed in the IL‐2 treated mice (p < 0.01). This was preceded by a significantly higher degree of microscopic inflammation at day 1 (p < 0.02). The IL‐12 levels decreased in both groups of infected mice at day 2 (p < 0.01), however, significantly more in the IL‐2 treated mice (p < 0.02). In accordance, but surprisingly, IFN‐γ was significantly reduced in the IL‐2 treated PA infected group at day 2 (p < 0.05). The present results indicate that early IL‐2 treatment prolongs the PMN response but also reduces pro‐inflammatory IL‐1β and TNF‐α and macroscopic signs of pathology.
Nordihydroguaiaretic acid reduces secondary organ injury in septic rats after cecal ligation and puncture

Background Nordihydroguaiaretic acid (NDGA) is a plant extract that has been shown to act as a free radical scavenger and pluripotent inhibitor of pro-inflammatory cytokines, two major cellular processes involved in the pathophysiology of sepsis. We investigated whether NDGA would improve markers of organ injury as well as survival in a rodent model of sepsis. Methods Abdominal sepsis was induced by cecal ligation and double puncture (CLP) in male Sprague-Dawley rats. NDGA was administered either at the time of injury (pre-) or 6 hours later (post-treatment). A sham surgery group and a vehicle only group were also followed as controls. Blood and lung tissue were collected 24 h after CLP. Lung tissue was used for histopathologic analysis and to measure pulmonary edema. Arterial oxygenation was measured directly to generate PaO2/FiO2, and markers of renal injury (blood urea nitrogen), liver injury (alanine aminotransferase), and tissue hypoxia (lactate) were measured. In a separate set of animals consisting of the same treatment groups, animals were followed for up to 36 hours for survival. Results NDGA pre-treatment resulted in improved oxygenation, less lung edema, lower lactate, lower BUN, and reduced histologic lung injury. NDGA post-treatment resulted in less lung edema, lower lactate, lower BUN, and less histologic lung injury, but did not significantly change oxygenation. None of the NDGA treatment groups statistically affected ALT or creatinine. NDGA pre-treatment showed improved survival compared with control CLP animals at 36 hours, while post-treatment did not. Conclusions NDGA represents a novel pleiotropic anti-inflammatory agent with potential clinical utility for modulation of organ injury secondary to sepsis.
Near-Infrared Photo-Switched MicroRNA Amplifier for Precise Photodynamic Therapy of Early-Stage Cancers.

Stimuli responsive photodynamic therapy (PDT) is a hot topic in precise medicine. However the low abundance of responsive trigger molecules in early-stage diseases limits its application. Here we designed an amplifier with multiple upconversion luminances to achieve near-infrared photo-switched cascade reaction triggered by specific microRNA and precise PDT of early-stage cancers. This amplifier was composed of photo-caged DNA nanocombs and an upconversion nanoparticle (UCNP) sensitized with IRDye® 800CW. The nanocomb was prepared by assembling a "photozipper"-protected hairpin and two kinds of hybridizable hairpin probes on a DNA skeleton. Upon 808-nm light irradiation, the produced UV light cleaved off the "photozipper" to induce microRNA-responsive cascade hybridization reaction, which activated the photosensitizers linked to different hairpins to generate reactive oxygen species (ROS) under the simultaneously emitted blue light for efficient PDT. The in vitro and in vivo results demonstrated the high amplification efficiency and promising application of the photo-switched amplifier in early-stage cancer treatment.
Efficient and effective control of confounding in eQTL mapping studies through joint differential expression and Mendelian randomization analyses

MOTIVATION Identifying cis-acting genetic variants associated with gene expression levels - an analysis commonly referred to as expression quantitative trait loci (eQTLs) mapping - is an important first step towards understanding the genetic determinant of gene expression variation. Successful eQTL mapping requires effective control of confounding factors. A common method for confounding effects control in eQTL mapping studies is the probabilistic estimation of expression residual (PEER) analysis. PEER analysis extracts PEER factors to serve as surrogates for confounding factors, which is further included in the subsequent eQTL mapping analysis. However, it is computationally challenging to determine the optimal number of PEER factors used for eQTL mapping. In particular, the standard approach to determine the optimal number of PEER factors examines one number at a time and chooses a number that optimizes eQTLs discovery. Unfortunately, this standard approach involves multiple repetitive eQTL mapping procedures that are computationally expensive, restricting its use in large-scale eQTL mapping studies that being collected today. RESULTS Here, we present a simple and computationally scalable alternative, ECCO, to determine the optimal number of PEER factors used for eQTL mapping studies. Instead of performing repetitive eQTL mapping, ECCO jointly applies differential expression analysis and Mendelian randomization (MR) analysis, leading to substantial computational savings. In simulations and real data applications, we show that ECCO identifies a similar number of PEER factors required for eQTL mapping analysis as the standard approach but is two orders of magnitude faster. The computational scalability of ECCO allows for optimized eQTL discovery across 48 GTEx tissues for the first time, yielding an overall 5.89% power gain on the number of eQTL harboring genes (eGenes) discovered as compared to the previous GTEx recommendation that does not attempt to determine tissue-specific optimal number of PEER factors. AVAILABILITY Our method is implemented in the ECCO software, which, along with its GTEx mapping results, is freely available at www.xzlab. org/software.html. All R scripts used in this study are also available at this site. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Diversity and structure of prokaryotic communities within organic and conventional farming systems in central highlands of Kenya

Management practices such as tillage, crop rotation, irrigation, organic and inorganic inputs application are known to influence diversity and function of soil microbial populations. In this study, we investigated the effect of conventional versus organic farming systems at low and high input levels on structure and diversity of prokaryotic microbial communities. Soil samples were collected from the ongoing long-term farming system comparison trials established in 2007 at Chuka and Thika in Kenya. Physicochemical parameters for each sample were analyzed. Total DNA and RNA amplicons of variable region (V4—V7) of the 16S rRNA gene were generated on an Illumina platform using the manufacturer’s instructions. Diversity indices and statistical analysis were done using QIIME2 and R packages, respectively. A total of 29,778,886 high quality reads were obtained and assigned to 16,176 OTUs at 97% genetic distance across both 16S rDNA and 16S rRNA cDNA datasets. The results pointed out a histrionic difference in OTUs based on 16S rDNA and 16S rRNA cDNA. Precisely, while 16S rDNA clustered by site, 16S rRNA cDNA clustered by farming systems. In both sites and systems, dominant phylotypes were affiliated to phylum Actinobacteria, Proteobacteria and Acidobacteria. Conventional farming systems showed a higher species richness and diversity compared to organic farming systems, whilst 16S rRNA cDNA datasets were similar. Physiochemical factors were associated differently depending on rRNA and rDNA. Soil pH, electrical conductivity, organic carbon, nitrogen, potassium, aluminium, zinc, iron, boron and micro-aggregates showed a significant influence on the observed microbial diversity. The observed higher species diversity in the conventional farming systems can be attributed to the integration of synthetic and organic agricultural inputs. These results show that the type of inputs used in a farming system not only affect the soil chemistry but also the microbial population dynamics and eventually the functional roles of these microbes.