Miracle-dz/UniFAR-FTUs huggingface dataset:
Best management of irritable bowel syndrome

Irritable bowel syndrome (IBS) is a common disorder of gut-brain interaction which can have a considerable impact on quality of life. Following diagnosis, timely and evidence-based management is vital to the care of patients with IBS, aiming to improve outcomes, and enhance patient satisfaction. Good communication is paramount, and clinicians should provide a clear explanation about the disorder, with a focus on exploring the patient’s own beliefs about IBS, and a discussion of any concerns they may have. It should be emphasised that symptoms are often chronic, and that treatment, while aiming to improve symptoms, may not relieve them completely. Initial management should include simple lifestyle and dietary advice, discussion of the possible benefit of some probiotics, and, if this is unsuccessful, patients can be referred to a dietician for consideration of a low FODMAP (fermentable oligosaccharides, disaccharides, monosaccharides and polyols) diet. Antispasmodics and peppermint oil can be used first-line for the treatment of abdominal pain. If patients fail to respond, central neuromodulators can be used second-line; tricyclic antidepressants should be preferred. Loperamide and laxatives can be used first-line for treating diarrhoea and constipation, respectively. Patients with constipation who fail to respond to laxatives should be offered a trial of linaclotide. For patients with diarrhoea, the 5-hydroxytryptamine-3 receptor agonists alosetron and ramosetron appear to be the most effective second-line drugs. Where these are unavailable, ondansetron is a reasonable alternative. If medical treatment is unsuccessful, patients should be referred for psychological therapy, where available, if they are amenable to this. Cognitive behavioural therapy and gut-directed hypnotherapy are the psychological therapies with the largest evidence base.
Environmental and Sensor Integration Influences on Temperature Measurements by Rotary-Wing Unmanned Aircraft Systems

Obtaining thermodynamic measurements using rotary-wing unmanned aircraft systems (rwUAS) requires several considerations for mitigating biases from the aircraft and its environment. In this study, we focus on how the method of temperature sensor integration can impact the quality of its measurements. To minimize non-environmental heat sources and prevent any contamination coming from the rwUAS body, two configurations with different sensor placements are proposed for comparison. The first configuration consists of a custom quadcopter with temperature and humidity sensors placed below the propellers for aspiration. The second configuration incorporates the same quadcopter design with sensors instead shielded inside of an L-duct and aspirated by a ducted fan. Additionally, an autopilot algorithm was developed for these platforms to face them into the wind during flight for kinematic wind estimations. This study will utilize in situ rwUAS observations validated against tower-mounted reference instruments to examine how measurements are influenced both by the different configurations as well as the ambient environment. Results indicate that both methods of integration are valid but the below-propeller configuration is more susceptible to errors from solar radiation and heat from the body of the rwUAS.
Staying awake to stay alive: A circuit controlling starvation-induced waking

The balance of sleep and wake is plastic and changes to meet environmental demands. Mechanisms that allow an animal to suppress sleep and maintain waking in potentially adverse situations could serve adaptive functions in evolution. The fruit fly, Drosophila melanogaster, is well poised as a system in which to explore these questions. The environment changes sleep and wake in flies, e.g., starvation induces waking in Drosophila as it does in many animals. Further, the sophisticated neurobiological toolkit available to Drosophila researchers gives the fly a great advantage as a system to investigate the precise neurobiological mechanisms underlying these adaptive changes. In a paper in this issue of PLOS Biology, Yurgel and colleagues elegantly exploit the advantages of the Drosophila model to map starvation-induced wakefulness to a single pair of peptidergic neurons and their partners.
A continuously changing selective context on microbial communities associated with fish, from egg to fork

Fast increase of fish aquaculture production to meet consumer demands is accompanied by important ecological concerns such as disease outbreaks. Meanwhile, food waste is an important concern with fish products since they are highly perishable. Recent aquaculture and fish product microbiology, and more recently, microbiota research, paved the way to a highly integrated approach to understand complex relationships between host fish, product and their associated microbial communities at health/disease and preservation/spoilage frontiers. Microbial manipulation strategies are increasingly validated as promising tools either to replace or to complement traditional veterinary and preservation methods. In this review, we consider evolutionary forces driving fish microbiota assembly, in particular the changes in the selective context along the production chain. We summarize the current knowledge concerning factors governing assembly and dynamics of fish hosts and food microbial communities. Then, we discuss the current microbial community manipulation strategies from an evolutionary standpoint to provide a perspective on the potential for risks, conflict and opportunities. Finally, we conclude that to harness evolutionary forces in the development of sustainable microbiota manipulation applications in the fish industry, an integrated knowledge of the controlling abiotic and especially biotic factors is required.
Protective Effect of the Hexanic Extract of Eryngium carlinae Inflorescences In Vitro, in Yeast, and in Streptozotocin-Induced Diabetic Male Rats

In the present study, we investigated the composition and antioxidant activity of the hexanic extract of Eryngium carlinae inflorescences by employing in vitro assays to measure antioxidant capacity and 2,2-diphenyl-1-picrylhydrazyl scavenging activity. We also applied the hexanic extract to Saccharomyces cerevisiae, under hydrogen peroxide-induced stress. Finally, we tested the extract in male Wistar rats with and without streptozotocin-induced diabetes. The compounds in the hexanic extract were analyzed by gas-chromatography-mass spectrometry, which revealed mainly terpenes and sesquiterpenes, including (Z)β-farnesene (38.79%), β-pinene (17.53%), calamene (13.3%), and α-farnesene (10.38%). In vitro and in S. cerevisiae, the extract possessed antioxidant activity at different concentrations, compared to ascorbic acid (positive control). In normoglycemic and hyperglycemic rats, oral administration of 30 mg/kg of the extract reduced blood glucose levels; lipid peroxidation in liver, kidney and brain; protein carbonylation; and reactive oxygen species (ROS) production. It also increased catalase activity in the brain, kidneys and liver. These findings show that this hexanic extract of E. carlinae inflorescences possessed antioxidant properties.
Pan-European Economic Analysis to Identify Cost Savings for the Health Care Systems as a Result of Integrating Glucose Monitoring Based Telemedical Approaches Into Diabetes Management

Background: Self-monitoring of blood glucose supported by the diabetes-app OneTouch Reveal® has demonstrated to improve HbA1c. We aimed at analyzing costs savings related the integration of telemedical features into diabetes management. Methods: Data from a randomized controlled trial were used to assess the 10-year risk of patients for fatal myocardial infarction (MI). On the basis of this risk assessments—also related to a 5% or 10% reduction of hypoglycemic episodes—cost savings for the health care systems of five European countries—France, Germany, Italy, Spain, and the United Kingdom—were modeled. Results: HbA1c reduction of 0.92% in insulin-treated type 2 diabetes patients (T2DM) was associated with a 2.3% decreased 10-year risk for fatal MI. In combination with a 10% reduction of hypoglycemic events this risk reduction led to cost savings of €16.1 million (France), €57.8 million (Germany), €30.9 million (Italy), €23.8 million (Spain), and €5.8 million (UK), considering all insulin-treated T2DM patients in the respective countries. Conclusion: Improving metabolic control and thus risk for comorbidities like MI by combining the glucose meter with CRI with telemedical features has the potential to reduce costs for European health care systems.
Vulnerability of the agricultural sector to climate change: The development of a pan-tropical Climate Risk Vulnerability Assessment to inform sub-national decision making

As climate change continues to exert increasing pressure upon the livelihoods and agricultural sector of many developing and developed nations, a need exists to understand and prioritise at the sub national scale which areas and communities are most vulnerable. The purpose of this study is to develop a robust, rigorous and replicable methodology that is flexible to data limitations and spatially prioritizes the vulnerability of agriculture and rural livelihoods to climate change. We have applied the methodology in Vietnam, Uganda and Nicaragua, three contrasting developing countries that are particularly threatened by climate change. We conceptualize vulnerability to climate change following the widely adopted combination of sensitivity, exposure and adaptive capacity. We used Ecocrop and Maxent ecological models under a high emission climate scenario to assess the sensitivity of the main food security and cash crops to climate change. Using a participatory approach, we identified exposure to natural hazards and the main indicators of adaptive capacity, which were modelled and analysed using geographic information systems. We finally combined the components of vulnerability using equal-weighting to produce a crop specific vulnerability index and a final accumulative score. We have mapped the hotspots of climate change vulnerability and identified the underlying driving indicators. For example, in Vietnam we found the Mekong delta to be one of the vulnerable regions due to a decline in the climatic suitability of rice and maize, combined with high exposure to flooding, sea level rise and drought. However, the region is marked by a relatively high adaptive capacity due to developed infrastructure and comparatively high levels of education. The approach and information derived from the study informs public climate change policies and actions, as vulnerability assessments are the bases of any National Adaptation Plans (NAP), National Determined Contributions (NDC) and for accessing climate finance.
Pharmacology Update: Low-Dose Naltrexone as a Possible Nonopioid Modality for Some Chronic, Nonmalignant Pain Syndromes

Pain can have a devastating effect on the quality of life of patients in palliative medicine. Thus far, majority of research has been centered on opioid-based pain management, with a limited empirical evidence for the use of nonopioid medications in palliative care. However, opioid and nonopioid medications such as nonsteroidal anti-inflammatory drugs have their limitations in the clinical use due to risk of adverse effects, therefore, there is a need for more research to be directed to finding an alternative approach to pain management in comfort care setting. The purpose of this article is to discuss a potential new drug that would adequately alleviate pain and enhance quality of life without significant risks of adverse effects that would limit its use. Naltrexone is a reversible competitive antagonist at μ-opioid and κ-opioid receptors, which when used at standard doses of 50 to 150 mg was initially intended for use in opioid and alcohol use disorders. However, it was discovered that its use in low doses follows alternate pharmacodynamic pathways with various effects. When used in doses of 1 to 5 mg it acts as a glial modulator with a neuroprotective effect via inhibition of microglial activation. It binds to Toll-like receptor 4 and acts as an antagonist, therefore inhibiting the downstream cellular signaling pathways that ultimately lead to pro-inflammatory cytokines, therefore reducing inflammatory response. Its other mode of action involves transient opioid receptor blockade ensuing from low-dose use which upregulates opioid signaling resulting in increased levels of endogenous opioid production, known as opioid rebound effect. Low dose naltrexone has gained popularity as an off-label treatment of several autoimmune diseases including multiple sclerosis and inflammatory bowel disease, as well as chronic pain disorders including fibromyalgia, complex regional pain syndrome, and diabetic neuropathy. Low-dose naltrexone (LDN) may also have utility in improving mood disorders and the potential to enhance the quality of life. This article will therefore propose the potential off-label use of LDN in management of nonmalignant pain in the palliative medicine setting.
Modeling neural circuit, blood–brain barrier, and myelination on a microfluidic 96 well plate

Microfluidics have enabled a wide range of experimental possibilities in the field of neuroscience. Unfortunately, the wider scale adoption of polydimethylsiloxane (PDMS) based microfluidic devices faces challenges due to inherent material compatibility issues and lack of standardized manufacturable devices. In this work, we present an injection molded plastic array three-dimensional (3D) neuron culture platform (Neuro-IMPACT) made of polystyrene (PS) with a standard 96-well plate form factor that can recapitulate elements of both the central and peripheral nervous systems. A standardized in vitro platform for neuron culture will facilitate the development of new therapies for neurodegenerative diseases, as they would enable quantitative analysis based on imaging as well as biochemical analysis. To demonstrate the versatility of Neuro-IMPACT, we modeled physiologically relevant complex co-culture models such as a 3D neuronal network, blood–brain barrier, and myelination. The Neuro-IMPACT offers a high-throughput screening compatible platform with the ability to engineer the neuronal microenvironment to aid both basic and applied neuroscience research.
Mapping neuronal inputs to Kiss1 neurons in the arcuate nucleus of the mouse

The normal function of the mammalian reproductive axis is strongly influenced by physiological, metabolic and environmental factors. Kisspeptin neuropeptides, encoded by the Kiss1 gene, are potent regulators of the mammalian reproductive axis by stimulating gonadodropin releasing hormone secretion from the hypothalamus. To understand how the reproductive axis is modulated by higher order neuronal inputs we have mapped the afferent circuits into arcuate (ARC) Kiss1 neurons. We used a transgenic mouse that expresses the CRE recombinase in Kiss1 neurons for conditional viral tracing with genetically modified viruses. CRE-mediated activation of these viruses in Kiss1 neurons allows the virus to move transynaptically to label neurons with primary or secondary afferent inputs into the Kiss1 neurons. Several regions of the brain showed synaptic connectivity to arcuate Kiss1 neurons including proopiomelanocortin neurons in the ARC itself, kisspeptin neurons in the anteroventral periventricular nucleus, vasopressin neurons in the supraoptic and suprachiasmatic nuclei, thyrotropin releasing neurons in the paraventricular nucleus and unidentified neurons in other regions including the subfornical organ, amygdala, interpeduncular nucleus, ventral premammilary nucleus, basal nucleus of stria terminalis and the visual, somatosensory and piriform regions of the cortex. These data provide an insight into how the activity of Kiss1 neurons may be regulated by metabolic signals and provide a detailed neuroanatomical map for future functional studies.
Functionalized chitosan-modified defect-related luminescent mesoporous silica nanoparticles as new inhibitors for hIAPP aggregation

Human islet amyloid polypeptide (hIAPP or amylin) forms the amyloid deposits that is an important factor in the induction of type II diabetes. Accordingly, it is essential to efficiently and accurately inhibit the aggregation of hIAPP for the treatment and prevention of the disease. Here, defect mesoporous silica (DLMSN), with blue fluorescence, can perfectly achieve the accurate positioning in cells or organisms. DL@CS@NF cannot only specifically bind to a hIAPP monomer, but also effectively inhibit hIAPP aggregation, reduce cytotoxicity and overcome the instability and inefficiency of NF(N-Me)GA(N-Me)IL (NF). Furthermore, DL@CS@NF nanoparticles can significantly improve the survival rate of islet cells, stabilize the mitochondrial membrane potential, reduce the content of intracellular reactive oxygen species. In summary, DL@CS@NF nanoparticles may have broader implications in inhibiting the aggregation of hIAPP and reducing cytotoxicity.
A Methodology Study of Hydrophosphonylation of Aldehydes Derivatives with H6P2W18O62•14H2O as a Catalyst

A catalytic process for hydrophosphonylation of aldehydes with H6P2W18O62·14H2O has been developed in this paper. Various aldehydes were reacted with diethylphosphite in the presence of 1 % of heteropolyacids (HPAs) as a catalyst to generate the α-hydroxyphosphonates. All the synthesized compounds were sys tematically characterized by IR, H NMR, C NMR, and P NMR. Simple and mild method, short reaction time, solvent-free conditions, availability and reusability of the catalyst are the main advantages of this procedure.
Emerging Cellular Therapies: T Cells and Beyond

Cellular therapies, including those based on T cells, are becoming approved options for clinicians treating a range of diseases. Cytotoxic T lymphocytes (CTLs) can be modified ex vivo to express receptors such as chimeric antigen receptors (CARs) or T cell receptors, allowing them to target tumour cells when infused back into patients with particular cancers. CTLs specific for viruses can be purified ex vivo and reinfused into patients transplanted with haematopoietic stem cells to help combat viral reactivation. Regulatory T cells (Tregs) can be expanded ex vivo for infusion into patients with autoimmunity or allergy, or into those at risk of rejecting transplanted cells or tissues, or suffering graft versus host disease. Effector and regulatory T cells can also be generated by infusion of patient-derived dendritic cells (DCs) conditioned in ways to elicit anti-tumour immunity (CTLs) or Tregs. All such therapies are resource-heavy (particularly in process regulation) and so must be initially targeted to patients that have limited treatment options, but also where they have a chance of being effective.
Oral DhHP-6 for the Treatment of Type 2 Diabetes Mellitus

Type 2 diabetes mellitus (T2DM) is associated with pancreatic β-cell dysfunction which can be induced by oxidative stress. Deuterohemin-βAla-His-Thr-Val-Glu-Lys (DhHP-6) is a microperoxidase mimetic that can scavenge reactive oxygen species (ROS) in vivo. In our previous studies, we demonstrated an increased stability of linear peptides upon their covalent attachment to porphyrins. In this study, we assessed the utility of DhHP-6 as an oral anti-diabetic drug in vitro and in vivo. DhHP-6 showed high resistance to proteolytic degradation in vitro and in vivo. The degraded DhHP-6 product in gastrointestinal (GI) fluid retained the enzymatic activity of DhHP-6, but displayed a higher permeability coefficient. DhHP-6 protected against the cell damage induced by H2O2 and promoted insulin secretion in INS-1 cells. In the T2DM model, DhHP-6 reduced blood glucose levels and facilitated the recovery of blood lipid disorders. DhHP-6 also mitigated both insulin resistance and glucose tolerance. Most importantly, DhHP-6 promoted the recovery of damaged pancreas islets. These findings suggest that DhHP-6 in physiological environments has high stability against enzymatic degradation and maintains enzymatic activity. As DhHP-6 lowered the fasting blood glucose levels of T2DM mice, it thus represents a promising candidate for oral administration and clinical therapy.
Mutational Signatures in Mandibular Ameloblastoma Correlate with Smoking

Ameloblastoma is a rare tumor of odontogenic epithelium, the low incidence rate of which precludes statistical determination of its molecular characterizations. Despite recent genomic and transcriptomic profiling, the etiology of ameloblastomas remains poorly understood. Risk factors of ameloblastoma development are also largely unknown. Whole exome sequencing was performed on 11 mandibular ameloblastoma samples. We identified 2 convergent mutational signatures in ameloblastoma: 1) a signature found in multiple types of lung cancers with probable etiology of tobacco carcinogens (COSMIC signature 4) and 2) a signature present in gingivobuccal oral squamous cell carcinoma and correlated with tobacco-chewing habits (COSMIC signature 29). These mutational signatures highlight tobacco usage or related mutagens as one possible risk factor of ameloblastoma, since the association of BRAF mutations and smoking was demonstrated in multiple studies. In addition to BRAF hotspot mutations (V600E), we observed clear inter- and intratumor heterogeneities. Interestingly, prior to BRAF mutation, important genes regulating odontogenesis mutated (e.g., corepressor BCOR), possibly playing important roles in tumorigenesis. Furthermore, recurrent mutations in the CDC73 gene, the germline mutations of which predispose patients to the development of jaw tumors, were found in 2 patients, which may lead to recurrence if not targeted by therapeutic drugs. Our unbiased profiling of coding regions of ameloblastoma genomes provides insights to the possible etiology of mandibular ameloblastoma and highlights potential disease risk factors for screening and prevention, especially for Asian patients. Because of the limited sample size and incomplete habitual, dietary, and occupational data, a causal link between tobacco usage and ameloblastoma still requires further investigations.
Inspection procedures in manufacturing processes: recent studies and research perspectives

Quality inspections are performed in almost every production system to prevent nonconforming products from reaching final customers or end users. Quality inspections are typically performed referring to specific inspection procedures, depending on the production process. Two general inspection paradigms may be identified: online inspection and offline inspection. These are differentiated by the way in which inspections are made. The paper presents a recent survey on new studies on inspection procedures for both paradigms. The main novelty of the study is the identification of new research perspectives in such a highly explored field. New schemes of analysis allow highlighting the research areas which are not adequately covered by the literature. A brief examination of some bibliometric aspects is also proposed.