Miracle-dz/UniFAR-FTUs huggingface dataset:
A Paper-Based Colorimetric Aptasensor for the Detection of Gentamicin

Antibiotics are classes of antimicrobial substances that are administered widely in the field of veterinary science to promote animal health and feed efficiency. Cattle-administered antibiotics hold a risk of passing active residues to milk, during the milking process. This becomes a public health concern as these residues can cause severe allergic reactions to sensitive groups and considerable economic losses to the farmer. Hence, to ensure that the produced milk is safe to consume and adheres to permissible limits, an on-farm quick and reliable test is essential. This study illustrates the design and development of a microfluidic paper biosensor as a proof-of-concept detection system for gentamicin in milk. Localized surface plasmon resonance (LSPR) properties of gold nanoparticles have been explored to provide the user a visual feedback on the test, which was also corroborated by RGB analysis performed using Image J. The assay involves the use of a short stretch of single stranded DNA, called aptamer, which is very specific to the gentamicin present in the milk sample. The camera-based LOD for the fabricated paper device for milk samples spiked with gentamicin was calculated to be 300 nM, with a reaction time of 2 min.
Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers

Objective To measure the effects of faecal immunochemical test (FIT) for colorectal cancer (CRC) screening on overall and site-specific long-term effectiveness of population-based organised service screening. Design A prospective cohort study of Taiwanese nationwide biennial FIT screening was performed. A total of 5 417 699 eligible subjects were invited to attend screening from 2004 through 2009 and were followed up until 2014. We estimated the adjusted relative rates (aRRs) on the effectiveness of reducing advanced-stage CRC (stage II+) and CRC death by Bayesian Poisson regression models with the full adjustment for a cascade of self-selection factors (including the screening rate and the colonoscopy rate) and the completeness of colonoscopy together with demographic features. Results FIT screening (exposed vs unexposed) reduced the incidence of advanced-stage CRC (48.4 vs 75.7 per 100 000) and mortality (20.3 vs 41.3 per 100 000). Statistically significant reductions of both incidence of advanced-stage CRCs (aRR=0.66, 95% CI 0.63 to 0.70) and deaths from CRC (aRR=0.60, 95% CI 0.57 to 0.64) were noted. FIT screening was more effective in reducing distal advanced-stage CRCs (aRR=0.61, 95% CI 0.58 to 0.64) and CRC mortality (aRR=0.56, 95% CI 0.53 to 0.69) than proximal advanced CRCs (aRR=0.84, 95% CI 0.77 to 0.92) and CRC mortality (aRR=0.72, 95% CI 0.66 to 0.80). Conclusion A large-scale population-based biennial FIT screening demonstrates 34% significant reduction of advanced-stage CRCs and 40% reduction of death from CRC with larger long-term effectiveness in the distal colon than the proximal colon. Our findings provide a strong and consistent evidence-based policy for supporting a sustainable population-based FIT organised service screening worldwide. The disparity of site-specific long-term effectiveness also provides an insight into the remedy for lower effectiveness of FIT screening in the proximal colon.
Deep Brain Stimulation of the Lateral Hypothalamus Facilitates Extinction and Prevents Reinstatement of Morphine Place Preference in Rats

We have previously shown that high‐frequency (HF) deep brain stimulation (DBS) of the lateral hypothalamus (LH) during the acquisition phase of morphine‐induced conditioned place preference (CPP) abolished the development of morphine reward. In the present study, we investigated the effect of DBS in the LH during the extinction phase of morphine CPP.
Catalase deficiency induces reactive oxygen species mediated pexophagy and cell death in the liver during prolonged fasting

Peroxisomes are dynamic organelles that participate in a diverse array of cellular processes, including β‐oxidation, which produces a considerable amount of reactive oxygen species (ROS). Although we showed that catalase depletion induces ROS‐mediated pexophagy in cells, the effect of catalase deficiency during conditions that favor ROS generation remains elusive in mice. In this study, we reported that prolonged fasting in catalase‐knockout (KO) mice drastically increased ROS production, which induced liver‐specific pexophagy, an autophagic degradation of peroxisomes. In addition, increased ROS generation induced the production of pro‐inflammatory cytokines in the liver tissues of catalase‐KO mice. Furthermore, there was a significant increase in the levels of aspartate transaminase and alanine transaminase as well as apparent cell death in the liver of catalase‐KO mice during prolonged fasting. However, an intra‐peritoneal injection of the antioxidant N‐acetyl‐l‐cysteine (NAC) and autophagy inhibitor chloroquine inhibited the inflammatory response, liver damage, and pexophagy in the liver of catalase‐KO mice during prolonged fasting. Consistently, genetic ablation of autophagy, Atg5 led to suppression of pexophagy during catalase inhibition by 3‐aminotriazole (3AT). Moreover, treatment with chloroquine also ameliorated the inflammatory response and cell death in embryonic fibroblast cells from catalase‐KO mice. Taken together, our data suggest that ROS‐mediated liver‐specific pexophagy observed during prolonged fasting in catalase‐KO mice may be responsible for the process associated with hepatic cell death.
Decomposing fecundity and evaluating demographic influence of multiple broods in a migratory bird.

1. Relevance of breeding season fecundity as a driver of population dynamics has been highlighted by many studies. Despite that, knowledge about how brood type specific (i.e. first, second or replacement) fecundity affects demography of multiple-brooded species is limited. In fact, estimation of brood type specific fecundity is often challenging due to imperfect detection of nesting attempts. 2. We examined the demographic contribution and the feedback on population density of different components of fecundity, along with other vital rates, in a facultative multiple-brooded migratory bird. 3. We used a novel formulation of a fecundity model that allows incorporating reproductive data for which information on the type of brood was unknown in some cases, and embedded it into an integrated population model (IPM) to obtain consensual estimates of all demographic rates, including brood type specific fecundities, reproductive success probabilities, and proportion of breeding pairs that performed a second or replacement brood. We then conducted transient life table response experiments on IPM estimates to account for non-stationary environments. We applied the model to two twenty-year data sets collected in a Swiss and a German local population of wrynecks (Jynx torquilla). 4. Brood type specific fecundities and temporal patterns of brood type specific probabilities of success, number of successful and unsuccessful first broods, probability of starting a second or a replacement brood, and proportion of pairs that performed a second or a replacement brood differed between the two populations. However, changes in immigration rate and apparent survival were the dominant contributors to temporal variation and large sequential changes in realized population growth rates in both populations. In the Swiss population we also found that second brood fecundity declined when population size increased. 5. Our study provides insight into the reproductive processes that affect population dynamics and mediate density-dependent fecundity in a migratory bird. In addition, the analytical approach proposed can be used in other studies of multiple-brooded species to maximize the use of available fecundity data through the estimation of unknown brood types, thus favouring a better understanding of the demographic contribution of brood type specific fecundity.
Closed-loop EEG study on visual recognition during driving

Objective. In contrast to the classical visual brain–computer interface (BCI) paradigms, which adhere to a rigid trial structure and restricted user behavior, electroencephalogram (EEG)-based visual recognition decoding during our daily activities remains challenging. The objective of this study is to explore the feasibility of decoding the EEG signature of visual recognition in experimental conditions promoting our natural ocular behavior when interacting with our dynamic environment. Approach. In our experiment, subjects visually search for a target object among suddenly appearing objects in the environment while driving a car-simulator. Given that subjects exhibit an unconstrained overt visual behavior, we based our study on eye fixation-related potentials (EFRPs). We report on gaze behavior and single-trial EFRP decoding performance (fixations on visually similar target vs. non-target objects). In addition, we demonstrate the application of our approach in a closed-loop BCI setup. Main results. To identify the target out of four symbol types along a road segment, the BCI system integrated decoding probabilities of multiple EFRP and achieved the average online accuracy of 0.37 ± 0.06 (12 subjects), statistically significantly above the chance level. Using the acquired data, we performed a comparative study of classification algorithms (discriminating target vs. non-target) and feature spaces in a simulated online scenario. The EEG approaches yielded similar moderate performances of at most 0.6 AUC, yet statistically significantly above the chance level. In addition, the gaze duration (dwell time) appears to be an additional informative feature in this context. Significance. These results show that visual recognition of sudden events can be decoded during active driving. Therefore, this study lays a foundation for assistive and recommender systems based on the driver’s brain signals.
Introduction to Artificial Intelligence and Machine Learning for Pathology.

CONTEXT. — Recent developments in machine learning have stimulated intense interest in software that may augment or replace human experts. Machine learning may impact pathology practice by offering new capabilities in analysis, interpretation, and outcomes prediction using images and other data. The principles of operation and management of machine learning systems are unfamiliar to pathologists, who anticipate a need for additional education to be effective as expert users and managers of the new tools. OBJECTIVE. — To provide a background on machine learning for practicing pathologists, including an overview of algorithms, model development, and performance evaluation; to examine the current status of machine learning in pathology and consider possible roles and requirements for pathologists in local deployment and management of machine learning systems; and to highlight existing challenges and gaps in deployment methodology and regulation. DATA SOURCES. — Sources include the biomedical and engineering literature, white papers from professional organizations, government reports, electronic resources, and authors' experience in machine learning. References were chosen when possible for accessibility to practicing pathologists without specialized training in mathematics, statistics, or software development. CONCLUSIONS. — Machine learning offers an array of techniques that in recent published results show substantial promise. Data suggest that human experts working with machine learning tools outperform humans or machines separately, but the optimal form for this combination in pathology has not been established. Significant questions related to the generalizability of machine learning systems, local site verification, and performance monitoring remain to be resolved before a consensus on best practices and a regulatory environment can be established.
A hypothesis for the role of axon demyelination in seizure generation

Loss of myelin and altered oligodendrocyte distribution in the cerebral cortex are commonly observed both in postsurgical tissue derived from different focal epilepsies (such as focal cortical dysplasias and tuberous sclerosis) and in animal models of focal epilepsy. Moreover, seizures are a frequent symptom in demyelinating diseases, such as multiple sclerosis, and in animal models of demyelination and oligodendrocyte dysfunction. Finally, the excessive activity reported in demyelinated axons may promote hyperexcitability. We hypothesize that the extracellular potassium rise generated during epileptiform activity may be amplified by the presence of axons without appropriate myelin coating and by alterations in oligodendrocyte function. This process could facilitate the triggering of recurrent spontaneous seizures in areas of altered myelination and could result in further demyelination, thus promoting epileptogenesis.
Synergistic Effects of Milk-Derived Exosomes and Galactose on α-Synuclein Pathology in Parkinson’s Disease and Type 2 Diabetes Mellitus

Epidemiological studies associate milk consumption with an increased risk of Parkinson’s disease (PD) and type 2 diabetes mellitus (T2D). PD is an α-synucleinopathy associated with mitochondrial dysfunction, oxidative stress, deficient lysosomal clearance of α-synuclein (α-syn) and aggregation of misfolded α-syn. In T2D, α-syn promotes co-aggregation with islet amyloid polypeptide in pancreatic β-cells. Prion-like vagal nerve-mediated propagation of exosomal α-syn from the gut to the brain and pancreatic islets apparently link both pathologies. Exosomes are critical transmitters of α-syn from cell to cell especially under conditions of compromised autophagy. This review provides translational evidence that milk exosomes (MEX) disturb α-syn homeostasis. MEX are taken up by intestinal epithelial cells and accumulate in the brain after oral administration to mice. The potential uptake of MEX miRNA-148a and miRNA-21 by enteroendocrine cells in the gut, dopaminergic neurons in substantia nigra and pancreatic β-cells may enhance miRNA-148a/DNMT1-dependent overexpression of α-syn and impair miRNA-148a/PPARGC1A- and miRNA-21/LAMP2A-dependent autophagy driving both diseases. MiRNA-148a- and galactose-induced mitochondrial oxidative stress activate c-Abl-mediated aggregation of α-syn which is exported by exosome release. Via the vagal nerve and/or systemic exosomes, toxic α-syn may spread to dopaminergic neurons and pancreatic β-cells linking the pathogenesis of PD and T2D.
Development and implementation of a stroke rehabilitation integrated care pathway in an Italian no profit institution: an observational study.

BACKGROUND To standardize assessment and coordinate processes in stroke rehabilitation, an integrated care pathway (ICP) was developed in an Italian Rehabilitation and Research Institution by a knowledge-translation interdisciplinary process, from evidence-based guidelines to rehabilitation practice. The ICP was implemented in two pilot Tuscan rehabilitation Centers. AIM The purpose of this study was to describe ICP development and assess the ICP effects on postacute stroke inpatient rehabilitation outcomes. DESIGN Prospective observational study, before and after comparison. SETTING Two Tuscan inpatient rehabilitation centers. POPULATION Patients accessing either centers for intensive rehabilitation after acute stroke. METHODS Two cohorts were prospectively recruited before (2015-2017) and after (2018) implementation of the pathway. The primary outcome was change in activities of daily living disability, assessed by the modified Barthel Index (mBI) from admission to discharge. Secondary outcomes included length of stay (LOS), adverse outcomes, and changes in communication ability, trunk control, pain, ambulation, bladder catheter (Y/N), bedsores (Y/N). RESULTS In 2015-2017, 443 postacute stroke patients (mean age 77±11 years, 47% women), while in 2018, 84 patients (mean age 76±13 years, 61% women) were admitted to the two facilities. Comparing the 2018 vs. the 2015-17 cohort, the mean mBI increase was not substantially different (26 vs. 24 points), nor were LOS (37±18 vs. 36±16 days), adverse outcomes, discharge destination, and improvement of ambulation, pain, and communication (P>0.05). Instead, a significantly higher improvement of trunk control (trunk control test: 69.6±33.2 vs. 79.0±31.3, P=0.019), and a higher percentage of bedsore resolution (13% vs. 5%, P=0.033), and bladder catheter removal (37% vs. 17% P<0.001) were observed in 2018 vs. 2015-2017. CONCLUSIONS Compared to prior practice, ICP was associated to improvement of trunk control recovery, bladder catheter removal, and bedsores resolution. Further ICP implementation on a larger scale is needed to verify improvements of stroke inpatient rehabilitation outcomes. CLINICAL REHABILITATION IMPACT An evidence-based stroke rehabilitation ICP was interdisciplinary developed and implemented in two rehabilitation centers of a multicenter Italian health group. ICP implementation as to inpatient intensive postacute stroke rehabilitation was associated to improved trunk control recovery, bladder catheter removal, and bedsore resolution. Further ICP implementation will allow multicenter studies and quality benchmarking.
Health-related quality of life among rural adults with type 2 diabetes mellitus: a cross-sectional study.

BACKGROUND Previous reports about health-related quality of life (HRQoL) of type 2 diabetes mellitus (T2DM) concentrated on general patients rather than patients in rural areas with poor infrastructure and limited resources. Thus, the aims of this study were to evaluate the HRQoL of diabetics in the countryside and explore its influencing factors. METHODS A total of 23 053 participants aged from 18 to 79 years were drawn from the Henan Rural Cohort Study for this cross-sectional study. The HRQoL of participants were assessed by utility index and VAS-score of European Quality of Life Five Dimension Five Level Scale (EQ-5D-5L) instrument. Binary logistic regression, generalized linear and tobit regression models were used to estimate the potential influencing factors on HRQoL. RESULTS This study (23 053 participants) included 2231 T2DM patients with a crude prevalence of 9.68%. The utility index and VAS-score in health group were 0.96 ± 0.10 and 78.85 ± 14.53, while in T2DM group were 0.93 ± 0.15 and 74.09 ± 16.09, respectively. In total, most diabetics reported problem about pain/discomfort dimension. Being old, poverty, low physical activity, and with comorbidities was negatively related to HRQoL of diabetics, while high educational level was positively related to HRQoL. CONCLUSION HRQoL of rural T2DM patients depended on several sociodemographic factors. More attention should be paid to diabetics with poor socioeconomic status in rural areas. CLINICAL TRIAL REGISTRATION The Henan Rural Cohort Study has been registered at Chinese Clinical Trial Register (Registration number: ChiCTR-OOC-15006699) http://www.chictr. org.cn/showproj.aspx? proj=11375.
Development of a loop-mediated isothermal amplification (LAMP) method for specific detection of Mycobacterium bovis

Bovine tuberculosis (TB) caused by Mycobacterium bovis is a significant health threat to cattle and a zoonotic threat for humans in many developing countries. Rapid and accurate detection of M. bovis is fundamental for controlling the disease in animals and humans, and for the proper treatment of patients as one of the first-line anti-TB drug, pyrazinamide, is ineffective against M. bovis. Currently, there are no rapid, simplified and low-cost diagnostic methods that can be easily integrated for use in many developing countries. Here, we report the development of a loop-mediated isothermal amplification (LAMP) assay for specific identification of M. bovis by targeting the region of difference 4 (RD4), a 12.7 kb genomic region that is deleted solely in M. bovis. The assay's specificity was evaluated using 139 isolates comprising 65 M. bovis isolates, 40 M. tuberculosis isolates, seven M. tuberculosis complex reference strains, 22 non-tuberculous mycobacteria and five other bacteria. The established LAMP detected only M. bovis isolates as positive and no false positives were observed using the other mycobacteria and non-mycobacteria tested. Our LAMP assay detected as low as 10 copies of M. bovis genomic DNA within 40 minutes. The procedure of LAMP is simple with an incubation at a constant temperature. Results are observed with the naked eye by a color change, and there is no need for expensive equipment. The established LAMP can be used for the detection of M. bovis infections in cattle and humans in resource-limited areas.
Influence of the dental implant macrogeometry and threads design on primary stability: an in vitro simulation on artificial bone blocks

Abstract The implant macrogeometry and thread profile represent one of the most important factors for a successful achievement of primary stability during the positioning procedure. The aim of the present investigation was to evaluate the insertion torque (IT), removal torque (RT) and Implant stability Quotient (ISQ) of two different implant macrogeometry and thread profile on solid rigid polyurethane model. Two different implants macrogeometries were tested: K2 (Group I) with 11° angle, 1.17 mm pitch and self-cutting V thread profile and K3 (Group II) implants with 30° angle, 0.71 mm pitch and spyral thread profile. A total of 120 specimens (n = 60 for each group) were positioned into different conditions of solid rigid polyurethane blocks. The insertion torque (IT), removal torque (RT) and ISQ were measured for each specimen. All specimens achieved the positioning into solid rigid polyurethane blocks for both of groups with no loss of stability. A significantly higher IT, RT and ISQ were detected in Group II (p < 0.05). In both groups the mean values for IT, RT and ISQ appeared promising from a clinical point of view. In spite of different macrogeometry and thread profile, both implant types achieved high primary stability on solid rigid polyurethane block to support the functional loading for a clinical application.
Oxygen-Sensitivity and Pulmonary Selectivity of Vasodilators as Potential Drugs for Pulmonary Hypertension

Current approved therapies for pulmonary hypertension (PH) aim to restore the balance between endothelial mediators in the pulmonary circulation. These drugs may exert vasodilator effects on poorly oxygenated vessels. This may lead to the derivation of blood perfusion towards low ventilated alveoli, i.e., producing ventilation-perfusion mismatch, with detrimental effects on gas exchange. The aim of this study is to analyze the oxygen-sensitivity in vitro of 25 drugs currently used or potentially useful for PH. Additionally, the study analyses the effectiveness of these vasodilators in the pulmonary vs. the systemic vessels. Vasodilator responses were recorded in pulmonary arteries (PA) and mesenteric arteries (MA) from rats and in human PA in a wire myograph under different oxygen concentrations. None of the studied drugs showed oxygen selectivity, being equally or more effective as vasodilators under conditions of low oxygen as compared to high oxygen levels. The drugs studied showed low pulmonary selectivity, being equally or more effective as vasodilators in systemic than in PA. A similar behavior was observed for the members within each drug family. In conclusion, none of the drugs showed optimal vasodilator profile, which may limit their therapeutic efficacy in PH.