Miracle-dz/UniFAR-FTUs huggingface dataset:
Rotavirus Diarrhoea in Children and Animals of Urban and Rural Nepal

Introduction Rotavirus, an etiologic agent of causing diarrhea, was identified in 25-40 percent of children with diarrhea in urban Kathmandu valley of Nepal, but the data in remote rural areas was inadequate. It was not clear whether domestic animals possessed Rotavirus and could become a source of infection in annual epidemic period. The current study described one-year prevalence of rotavirus in human beings and domestic animals in rural communities of Nepal. Objectives The purpose of this study was to reveal the association between domestic animal Rotavirus and child diarrhoea in the rural communities of Nepal. Methods Human faeces were collected from children under 5 years of age who developed diarrhoea and that from non-diarrhoeic children of equivalent ages. Animals' faecal samples were collected monthly from cows, buffaloes, pigs and dogs in the village. All samples were made 20 percent suspension in PBS and stored at -30 0 C. The study was undertaken from October 2001 to November 2002. Indirect sandwich ELISA with minor modification was applied for Rotavirus assay. Results A total of 714 stool samples from children and 772 from domestic animals were tested. Among children group, 116(16.2%) were found ELISA positive for Rotavirus whereas 8(1.03%) were positive among animal groups. The percentage of ELISA positive in hospital samples (30.6%) was significantly higher than in village (4.1%). The highest rate of rotavirus positive was also found in diarrhoeic stools (30.4%) compared to normal stools (0.87%) (P<0.05). The high incidence of diarrhea and Rotavirus was observed in winter. Rotavirus was found in 6 months to 2 years age groups more frequently than other groups while only three samples of normal feces contained Rotavirus. The incidence of Rotavirus in animals was 0.41 percent (1 of 242) of buffaloes, 2 of 254(0.78%) dogs and 3.62 percent (5 of 138) from diarrhoeal samples of pigs. Conclusion Rotavirus was found predominantly in winter and attacked 6 months to 2 years old children. The study indicated that the infected animals and hospitalized diarrhoeal children were possible source of Rotavirus infection in Nepal.
Discovery of small molecules that target the P-Rex1 PIP3-binding site and inhibit P-Rex1-dependent functions in neutrophils

Departments of Pharmacology and Biological Chemistry (J.N.C, P.V.S.), Life Sciences Institute, University of Michigan, Ann Arbor, Michigan Department of Pharmacology (N.R.C., A.V.S.), University of Michigan, Ann Arbor, Michigan Department of Biological Sciences (A.Y.H., Q.D., J.J.G.T.), Purdue University, West Lafayette, Indiana Department of Medicinal Chemistry and Molecular Pharmacology (J.J.G.T.), Purdue University, West Lafayette, Indiana This article has not been copyedited and formatted. The final version may differ from this version. Molecular Pharmacology Fast Forward. Published on January 3, 2020 as DOI: 10.1124/mol.119. 117556
The association between fasting blood glucose trajectory and cancer risk in Chinese population without diabetes

To examine the associations between fasting blood glucose (FBG) trajectories, the changes in FBG over time and the risk of cancer, particularly for gastrointestinal cancer, we enrolled 69,742 participants without diabetes from the Kailuan cohort. FBG trajectories (2006–2010) were modeled by group‐based trajectory modeling, and five trajectories were identified: low‐increasing (n = 6,275), moderate‐stable (n = 44,120), moderate‐increasing (n = 10,149), elevated‐decreasing (n = 5,244) and elevated‐stable (n = 3,954). A total of 1,364 cancer cases were accumulated between 2010 and 2015, including 472 gastrointestinal cancer cases. We used Cox proportional hazards regression models to evaluate the associations between FBG trajectory patterns and the risk of cancer. We further assessed the associations while carefully controlling for initial body mass index (BMI) in 2006 and for changes in BMI during 2006–2010. Relative to the moderate‐stable group, we found a higher hazard ratio (HR) for overall cancer in the low‐increasing group (HR = 1.26, 95% confidence interval (CI) 1.06–1.50); and for gastrointestinal cancer in the elevated‐stable group (HR = 1.66, 95% CI 1.22–2.26). Moreover, among participants with an initial BMI ≥25 kg/m2, a positive association with the low‐increasing group was observed for both overall cancer and gastrointestinal cancer (HR = 1.54, 95% CI 1.17–2.04; HR = 1.65, 95% CI 1.02–2.66; respectively); among participants with a stable BMI (4.40% loss–5.15% gain), a positive association with the elevated‐stable group was observed both for overall cancer and gastrointestinal cancer (HR = 1.43, 95% CI 1.10–1.87; HR = 1.95, 95% CI 1.33–2.86; respectively). Our study observed that FBG trajectories were associated with cancer risk among participants without diabetes, and BMI may modify the associations.
Trends of litter decomposition and soil organic matter stocks across forested swamp environments of the southeastern US

A common idea in the discussion of soil carbon processes is that litter decomposition rates and soil carbon stocks are inversely related. To test this overall hypothesis, simultaneous studies were conducted of the relationship of environmental gradients to leaf and wood decomposition, buried cloth decomposition and percent soil organic matter in Taxodium distichum swamps across the Mississippi River Alluvial Valley (MRAV) and northern Gulf of Mexico (GOM) of the US. Decomposition of leaf tissue was 6.2 to 10.9 times faster than wood tissue. Both precipitation and flooding gradients were negatively related to leaf and wood litter decomposition rates based on models developed using Stepwise General Model Selection (MRAV vs. GOM, respectively). Cotton cloth should not be used as a proxy for plant litter without prior testing because cloth responded differently than plant litter to regional environmental gradients in T. distichum swamps. The overall hypothesis was supported in the MRAV because environments with higher precipitation (climate normal) had lower rates of decomposition and higher percent soil organic matter. In the MRAV, higher levels of percent soil organic matter were related to increased 30-year climate normals (30 year averages of precipitation and air temperature comprising southward increasing PrinComp1). Soil organic carbon % in inland vs. coastal T. distichum forests of the MRAV were comparable (range = 1.5% to 26.9% vs. 9.8 to 31.5%, respectively). GOM swamps had lower rates of litter decomposition in more flooded environments. Woody T. distichum detritus had a half-life of up to 300 years in the MRAV, which points to its likely role in the maintenance of inland “teal” soil organic carbon. This unique study can contribute to the discussion of approaches to maintain environments conducive to soil carbon stock maximization.
Cerebral metabolism, oxidation and inflammation in severe passive hyperthermia with and without respiratory alkalosis

It was unknown whether respiratory alkalosis impacts the global cerebral metabolic response as well as the cerebral pro‐oxidation and inflammatory response in passive hyperthermia. This study demonstrated that the cerebral metabolic rate was increased by ∼20% with passive hyperthermia of up to +2°C oesophageal temperature, and this response was unaffected by respiratory alkalosis. Additionally, the increase in cerebral metabolism did not significantly impact the net cerebral release of oxidative and inflammatory markers. These data indicate that passive heating of up to +2°C core temperature in healthy young men is not enough to confer a major oxidative and inflammatory burden on the brain, but it does markedly increase the cerebral metabolic rate, independently of PaCO2 .
Research Report:A training needs analysis to support mobile learning and information and communication technology teacher training in MLEARN partner countries

This report has been produced by the Department of Educational Research at Lancaster University for the MLEARN project, to support the development of a training programme for in-service teachers focusing on mobile learning through appropriate pedagogic uses of mobile or handheld technologies. The MLEARN project, a European Union (EU)-funded project, will explore and promote teacher development of mobile learning practices in four member states – The Netherlands, the UK (England), Greece and Italy. To support this development, a training needs analysis has been conducted and completed by the Department of Educational Research at Lancaster University. For this training needs analysis, two target groups were involved: 1) trainers and partners in each country; and 2) teachers to be involved in the training. Four countries were involved, where there were known to be substantial differences in terms of handheld devices’ acceptance within teaching practices, and resources in place to implement mobile learning initiatives and other activities. The survey was devised, using findings from the previous background report (Passey & Zozimo, 2014).
Data From the World Health Organization's Pharmacovigilance Database Supports the Prominent Role of Pneumonia in Mortality Associated With Clozapine Adverse Drug Reactions.

Although clozapine is underprescribed in many countries, it may be the most efficacious antipsychotic and the best for treatment-refractory schizophrenia. Moreover, a meta-analysis1 reported significantly lower deaths in patients continuously treated with clozapine compared to other antipsychotics. This editorial proposes that clozapine mortality may be further decreased by paying more attention to pneumonia. The prominent role of pneumonia in clozapine mortality is supported by an update of a review article2 and by the new data from a global database of adverse drug reactions (ADRs) for comparing the mortality associated with pneumonia and other clozapine ADRs.
EPIGENETIC TARGETING OF TERT-ASSOCIATED GENE EXPRESSION SIGNATURE IN HUMAN NEUROBLASTOMA WITH TERT OVEREXPRESSION.

Neuroblastoma is a deadly pediatric solid tumor with infrequent recurrent somatic mutations. Particularly, the pathophysiology of tumors without MYCN amplification remains poorly defined. Utilizing an unbiased approach, we performed gene set enrichment analysis of RNA-seq data from 498 neuroblastoma patients and revealed a differentially overexpressed gene signature in MYCN non-amplified neuroblastomas with telomerase reverse transcriptase (TERT) gene overexpression and coordinated activation of oncogenic signaling pathways, including E2Fs, Wnt, Myc, and the DNA repair pathway. Promoter rearrangement of the TERT gene juxtaposes the coding sequence to strong enhancer elements, leading to TERT overexpression and poor prognosis in neuroblastoma, but TERT-associated oncogenic signaling remains unclear. ChIP-seq analysis of the human CLB-GA neuroblastoma cells harboring TERT rearrangement uncovered genome-wide chromatin co-occupancy of Brd4 and H3K27Ac and robust enrichment of H3K36me3 in TERT and multiple TERT-associated genes. Brd4 and cyclin-dependent kinases (CDKs) had critical regulatory roles in the expression and chromatin activation of TERT and multiple TERT-associated genes. Epigenetically targeting Brd4 or CDKs with their respective inhibitors suppressed the expression of TERT and multiple TERT-associated genes in neuroblastoma with TERT overexpression or MYCN amplification. ChIP-seq and ChIP-qPCR provided evidence that the CDK inhibitor directly inhibited Brd4 recruitment to activate chromatin globally. Therefore, inhibiting Brd4 and CDK concurrently with AZD5153 and dinaciclib would be most effective in tumor growth suppression, which we demonstrated in neuroblastoma cell lines, primary human cells, and xenografts. In summary, we describe a unique mechanism in neuroblastoma with TERT overexpression and an epigenetically targeted novel therapeutic strategy.
Vitamin K and bone metabolism: the myth and the truth

ABSTRACT Several natural/syntheticproducts, containing different metabolites of vitamin K, are freely available and their use is suggested for non-specific ‘bone health’. It is therefore necessary and useful to address this specific aspect of their use, describing the state of the art in basic, translational, and clinical studies, reported in the literature. In fact, we do not have any certainty about a real effectiveness of vitamin K in preventing fragility fractures. To date, published clinical trials have been conducted on different ethnicities, with different dietary habits, different supplementations and doses of vitamin K, and with different fracture risk factors. This review aims to provide basic cultural tools to improve the knowledge of readers concerning the use of vitamin K for bone health, helping them to develop an independent critical spirit.
Characterization of the EPS from a thermophilic corrosive consortium

Abstract Biofilm forming microorganisms are known to contribute to the corrosion of metallic materials, as they can attach to surfaces and influence the electrochemical behavior. Extracellular polymeric substances (EPS) produced by these microorganisms play a major role in adhesion and resistance of the biofilm, thus also contributing to corrosion. A better understanding of the composition of EPS could help mitigate the impact of bacterial mediated corrosion. Here, a preliminary characterization of the EPS from a thermophilic consortium isolated from a corroded airplane engine is presented. Analysis revealed five different monosaccharides, with predominance of glucose and manose, but also a significant amount of rhamnose. Glycosyl linkage analysis was also performed. On the lipid fraction, three types of fatty acids were found. The predominant protein found by peptide finger printing was S-Layer protein, related to bacterial adhesion. Morphological characterization of the biofilm forming consortium was carried using confocal and scanning electron microscopy.
Long noncoding RNA DRAIC inhibits prostate cancer progression by interacting with IKK to inhibit NF-κB activation.

DRAIC is a 1.7 kb spliced long noncoding RNA downregulated in castration-resistant advanced prostate cancer. Decreased DRAIC expression predicts poor patient outcome in prostate and seven other cancers, while increased DRAIC represses growth of xenografted tumors. Here we show that cancers with decreased DRAIC expression have increased NF-κB target gene expression. DRAIC downregulation increased cell invasion and soft agar colony formation; this was dependent on NF-κB activation. DRAIC interacted with subunits of the IκB kinase (IKK) complex to inhibit their interaction with each other, the phosphorylation of IκBα and the activation of NF-κB. These functions of DRAIC mapped to the same fragment containing bases 701-905. Thus, DRAIC lncRNA inhibits prostate cancer progression through suppression of NF-κB activation by interfering with IKK activity.
Long‐term risk of postthrombotic syndrome after symptomatic distal deep vein thrombosis: The CACTUS‐PTS study

After a proximal lower limb deep vein thrombosis (DVT; involving popliteal veins or above), up to 40% of patients develop postthrombotic syndrome (PTS) as assessed by the Villalta scale (VS). Poor initial anticoagulant treatment is a known risk factor for PTS. The risk of developing PTS after isolated distal DVT (infra‐popliteal DVT without pulmonary embolism), and the impact of anticoagulant treatment on this risk, are uncertain.
Therapeutic Targeting of Vasculature in the Premetastatic and Metastatic Niches Reduces Lung Metastasis

Key Points Angiogenesis contributes to the lung premetastatic niche in a model of breast cancer. This angiogenesis is initiated by C5a/C5aR1-regulated MDSC. Inhibition of C5aR1 combined with antiangiogenic vaccines reduces lung metastasis. In the metastasis-targeted organs, angiogenesis is essential for the progression of dormant micrometastases to rapidly growing and clinically overt lesions. However, we observed changes suggesting angiogenic switching in the mouse lungs prior to arrival of tumor cells (i.e., in the premetastatic niche) in the models of breast carcinoma. This angiogenic switching appears to be caused by myeloid-derived suppressor cells recruited to the premetastatic lungs through complement C5a receptor 1 signaling. These myeloid cells are known to secrete several proangiogenic factors in tumors, including IL-1β and matrix metalloproteinase-9, and we found upregulation of these genes in the premetastatic lungs. Blockade of C5a receptor 1 synergized with antiangiogenic Listeria monocytogenes–based vaccines to decrease the lung metastatic burden by reducing vascular density and improving antitumor immunity in the lungs. This was mediated even when growth of primary breast tumors was not affected by these treatments. This work provides initial evidence that angiogenesis contributes to the premetastatic niche in rapidly progressing cancers and that inhibiting this process through immunotherapy is beneficial for reducing or even preventing metastasis.
Potentially inappropriate prescribing in dementia: a state-of-the-art review since 2007

Objectives Dementia frequently occurs alongside comorbidities. Coexisting conditions are often managed with multiple medications, leading to increased risk of potentially inappropriate medication and adverse drug reactions. We aimed to estimate prevalence of, and identify factors reported to be associated with, potentially inappropriate prescribing (PIP) for older individuals diagnosed with dementia. Design We used a state-of-the-art review approach, selecting papers written in English and published from 2007 to January 2018. Publications were retrieved from Scopus and Web of Science databases. Inclusion criteria included a formal diagnosis of dementia, a formal classification of PIP and reported prevalence of PIP as an outcome. Random effects models were used to provide a pooled estimate of prevalence of PIP. The Appraisal tool for Cross-Sectional Studies (AXIS tool) was used to assess bias in the included studies. Results The bibliographic search yielded 221 citations, with 12 studies meeting the inclusion criteria. The estimates of PIP prevalence for people living with dementia ranged from 14% to 64%. Prevalence was 31% (95% CI 9 to 52) in the community, and 42% (95% CI 30 to 55) in nursing/care homes. PIP included prescribing likely related to dementia (eg, hypnotics and sedative and cholinesterase inhibitors) and prescribing related to treatment of comorbidities (eg, cardiovascular drugs and non-steroidal anti-inflammatory medication). Higher levels of comorbidity were associated with increased risk of PIP; however, only one study investigated associations with specific comorbidities of dementia. Conclusion PIP remains a significant issue in healthcare management for people living with dementia. Higher levels of comorbidity are associated with increased prevalence of PIP, but the specific conditions driving this increase remain unknown. Further work is necessary to investigate PIP related to the presence of common comorbidities in patients living with dementia.
A Randomized Controlled Trial of Three Noninvasive Analgesic Techniques for the Prevention of Pain During Facial Injections.

BACKGROUND Injections are associated with a certain amount of pain, the tolerance of which can vary between individuals. With regard to noninvasive pain control techniques in subcutaneous injections, few studies with adequate levels of evidence and design quality exist to support any specific analgesic method. OBJECTIVES In this study, we evaluated the efficacy of 3 noninvasive analgesic techniques (cold, anesthetic cream, and vibration) during subcutaneous forehead injections in 100 healthy volunteers. METHODS This randomized, single-blind, controlled trial comprised 100 healthy volunteers. Every subject received 4 forehead injections of 0.1 ml physiological saline through 29G needles, after 1 of 3 noninvasive analgesic techniques (cold, vibration, or anesthetic cream) or control treatment was applied to each injection site. The results were evaluated through a survey that included a visual analog scale for pain measurements. RESULTS All analgesic methods demonstrated better pain control than the no-treatment arm (p<0.001), of which vibration performed better than the other analgesic techniques (p<0.015 vs cold and p<0.015 vs anesthetic cream). No differences were observed between cold and anesthetic cream. The average amount of pain per injection in males was higher compared with females (p<0.014). CONCLUSIONS Vibration analgesia effected significantly better pain control than cold and anesthetic cream. Nevertheless, the choice of anesthetic method should be adapted to the preferences and experiences of each patient to optimize pain control in procedures that involve subcutaneous injections.
Deceptive and Non-deceptive Placebos to Reduce Pain - An Experimental Study in Healthy People.

OBJECTIVES Recent research has shown that placebos are effective even if they are openly prescribed to participants. However, it is unclear how such "open-label placebos" (OLPs) compare to deceptive placebo (DP) and what the mechanisms of actions are. In this study, we therefore compared two versions of OLP to DP and no treatment (NT). METHODS Using a standard heat pain paradigm, 117 healthy volunteers underwent a baseline and post-treatment pain assessment. With the exception of NT, all groups received an inert placebo cream after the first assessment. OLP was administered by either evoking positive expectancies or by raising hope for placebo analgesia, thus distinguishing for the first time conceptually between expectancy and hope in experimental pain research. The primary outcome was pre-post change in pain tolerance. RESULTS Increase in pain tolerance was larger in the three treatment groups compared to NT, while the treatment groups did not differ from each other. Further results showed that participants receiving DP reported a large reduction of subjective pain intensity and unpleasantness, while no such reduction was found for the two OLP groups. The two OLP versions did not differ in terms of their analgesic effects. DISCUSSION The study provided evidence for traditional placebo analgesia based on deception. For OLP, we found that OLP indeed increased pain tolerance; however, participants receiving OLP were reluctant to report any subjective analgesic effects. Combined with previous studies, the present findings suggest that the effects of OLP are weaker in healthy volunteers than in clinical samples.
Palliative chemotherapy in head and neck cancer: balancing between beneficial and adverse effects

ABSTRACT Introduction: Head and neck squamous cell cancer (HNSCC) is the sixth most common cancer in the world. Almost 2/3rds of patients have recurrent or metastatic (R/M) HNSCC. Treatment options for R/M HNSCC have evolved, with relatively little change in survival. Thus, it is imperative that management decisions must balance efficacy with toxicity and emphasize the importance of maintaining the patient’s quality of life (QOL). Areas covered: We cover the various chemotherapeutic options available for R/M HNSCC including single agent chemotherapy, platinum-based doublets and triplet options. The role of cetuximab, immunotherapy and oral metronomic chemotherapy (OMCT) is also reviewed. We discuss the management of patients with platinum-refractory disease. Expert opinion: In all patients with R/M HNSCC, we recommend assessment of extent of disease, patient symptomatology, performance status, affordability and availability of logistic and social support. In patients with PD-L1 CPS =/> 20, pembrolizumab is an option. In patients with PD-L1 CPS < 20, pembrolizumab/cisplatin/5FU or cisplatin/5FU/cetuximab (EXTREME) may be considered based on affordability and availability. Options available that have a lower toxicity and can help to maintain the patient’s QOL include; single agent chemotherapy, carboplatin/paclitaxel combination chemotherapy, sequential combination chemotherapy followed by cetuximab, replacing 5FU with docetaxel (TPEx regime) and OMCT.